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ID PMID Title PublicationDate abstract
19024275 [Cardiovascular disorders in rheumatoid arthritis]. 2008 Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Traditional cardiovascular risk factors (including male sex, family history for cardiovascular disease, age, dyslipidaemia, arterial hypertension, diabetes mellitus, smoking and obesity) do not adequately account for the extent of cardiovascular disease in RA. The pathogenesis of accelerated atherosclerosis in RA is not clear. Increasing evidence suggests a key role of inflammation in the onset and progression of atherosclerosis. Endothelial dysfunction represents the earliest manifestation of atherosclerosis. Hypertension prevalence in patients with RA is higher than that in the general population, It is attributable risk to the development of future cardiovascular events. Despite its serious complications, control of hypertension is far from adequate in the general population and even more so in rheumatoid arthritis patients.
17665451 Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthri 2007 Aug OBJECTIVE: Modification of antigens represents a trigger for the generation of autoantibodies. In the pathogenesis of rheumatoid arthritis (RA), citrullination of proteins has been shown to be a critical process, and the determination of antibodies against citrullinated antigens has been a diagnostic milestone. We undertook this study to determine whether antibodies to mutated and citrullinated vimentin (MCV) could serve as a diagnostic and prognostic marker for RA. METHODS: We identified novel isoforms of human MCV in the synovial fluid of RA patients. The significance of these disease-related modifications was investigated by the analysis of autoantibody reactivities. In a group of 1,151 RA patients, the diagnostic significance and the prognostic value of an anti-MCV enzyme-linked immunosorbent assay (ELISA) were compared with that of an anti-cyclic citrullinated peptide (anti-CCP) ELISA. RESULTS: In RA, sensitivities of 82% and 72% were calculated for the anti-MCV and anti-CCP assays, respectively. The specificity of both assays was comparable (98% and 96%, respectively). In followup analyses of 16 RA patients with moderate disease activity (mean Disease Activity Score in 28 joints [DAS28] of 2.72) and 26 RA patients with active disease (mean DAS28 of 5.07), disease stratification of RA was possible using the anti-MCV assay (P = 0.0084). A significant correlation of anti-MCV antibodies with the DAS28 was documented (r = 0.5334, P = 0.0003), in 42 RA patients (n = 427 antibody determinations at different time points). CONCLUSION: Antigenic properties of vimentin were determined by mutation and citrullination. Anti-MCV antibodies are a novel diagnostic marker for RA. Furthermore, they may allow monitoring and-if confirmed in even larger series of patients-stratification of disease.
18390589 Rheumatoid arthritis patients who smoke have a higher need for DMARDs and feel worse, but 2008 Jun OBJECTIVES: To investigate the influence of smoking on disease activity, drug need and radiographic joint damage in RF-positive and -negative patients with early RA. METHODS: Baseline and 3-yr follow-up data of 896 patients of an early RA cohort comprised clinical and radiographic parameters (Ratingen Score). Information about disease severity, treatment and smoking were obtained by questionnaires. Univariate and multivariate analyses were used to show the influence of smoking on drug use, ACR improvement and joint damage. Smokers and non-smokers were compared according to RF serology. RESULTS: Fifty per cent of the patients were never, 23% past and 27% current smokers. Current smokers were significantly more often RF-positive (71%) than past (66%) or never smokers (53%), but neither the RF-positive nor the RF-negative current smokers had higher 28-joint disease activity score (DAS28) or radiographic scores than never or past smokers. Within 3 yrs, current smokers had taken significantly more DMARD combinations or biologics. Non-smokers and those with <20 pack-years (PYs) had a 2-fold higher probability to reach ACR improvement than heavy smokers (>20 PYs). However, smokers did not differ in radiographic joint damage when compared with non-smokers of the same serological group. CONCLUSIONS: The higher use of DMARDs may indicate that smoking weakens the potency of anti-rheumatic drugs and/or is needed to control an otherwise higher disease activity. Since the risk of adverse events increases with the amount of drugs taken, this is another reason to persuade RA patients to quit smoking.
18818228 A functional Ser(413)/Ser(413) PAI-2 polymorphism is associated with susceptibility and da 2009 Mar Systemic lupus erythematosus in some cases is characterized for development of thrombotic events with a significantly increased risk of mortality. The frequencies and clinical associations of Ser(413)/Cys(413) PAI-2 polymorphism in 40 systemic lupus erythematosus, 50 rheumatoid arthritis patients, and 100 healthy subjects were investigated. The Ser(413)/Ser(413) genotype frequency was 53% (lupus), 36% (rheumatoid arthritis), and 35% (healthy subjects). The Ser(413) allele was associated with systemic lupus erythematosus (P = .04, odds ratio = 1.76, 95% confidence interval = 1.01-3.06). In all, 4 patient carriers of Ser(413)/Ser(413) genotype, developed thrombotic events. The lupus patients identified with Ser( 413)/Ser(413) genotype showed an increased damage (57%), compared with Ser(413)/Cys(413) and Cys(413)/Cys(413) genotypes, with significant difference (P = .03). These findings suggest an association of Ser( 413) /Ser( 413) genotype with greater damage index score and Ser( 413) allele with systemic lupus erythematosus. Besides, PAI-2 polymorphism could be related with thrombotic phenomena in systemic lupus erythematosus.
18634162 Patients with rheumatoid arthritis treated with methotrexate (MTX): concentrations of stea 2008 Sep OBJECTIVE: To investigate the accumulation of methotrexate (MTX) in circulating erythrocytes and the association with pharmacokinetic variables, weekly dose, and clinical efficacy in 2 cohorts of patients with chronic active rheumatoid arthritis (RA) undergoing MTX monotherapy. METHODS: Seventy-six patients with RA were included in this open prospective study: 40 were included before initiation of MTX therapy. Laboratory analyses, intracellular MTX concentrations in erythrocytes (Ery-MTX), and clinical examinations including toxicity data were performed prospectively for 52 weeks. Plasma concentrations of MTX were measured and area under the plasma concentration versus time curve (AUC) was estimated along with other pharmacokinetic variables in a population based software model. RESULTS: Ery-MTX rose after initiation of therapy and reached a steady state after 6-8 weeks. The correlation between steady-state Ery-MTX and dose was poor (r(2) = 0.16), whereas steady-state Ery-MTX levels correlated strongly with the estimated AUC (r(2) = 0.51, log-transformed variables). Both steady-state Ery-MTX levels and estimated AUC were significantly higher in patients responding to MTX therapy than in patients classified as nonresponders according to American College of Rheumatology core criteria and were similar to patients on longterm MTX therapy. CONCLUSION: Our results indicate that clinical efficacy and Ery-MTX may have a causal relation and that measurement of Ery-MTX or estimation of AUC in a software model provides useful guidelines to the clinician when starting MTX therapy in patients with RA. The latter can be performed immediately after initiation of therapy.
17712000 Increased concentrations of antibody-bound circulatory cell-free DNA in rheumatoid arthrit 2007 Sep BACKGROUND: Increased concentrations of cell-free DNA have been found in several disorders and have been interpreted as evidence of increased rates of cell death or turnover. Evidence from in vitro and animal experiments suggests that DNA may play a role in the pathogenesis of rheumatoid arthritis (RA). METHODS: We measured cell-free DNA in plasma and serum from patients with RA and healthy controls by use of quantitative PCR for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA. We used protein G Sepharosetrade mark bead adsorption of plasma and elution to isolate antibody-bound DNA. RESULTS: In paired plasma and serum samples of 16 healthy controls the median GAPDH copies were 4500 genome equivalents (GE)/mL plasma (range 319-21 000) and in 26 RA patients 17 000 GE/mL plasma (2100-2 375 000, P = 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700-239 000) and from RA patients 222 000 GE/mL (21 000-2 375 000, P = 0.004). A median of 81% of the cell-free DNA in RA was associated with antibody compared with 9% in healthy controls (P = 0.001). The concentrations of DNA did not vary with the type of therapy patients received. CONCLUSIONS: These results provide new evidence for a role of cell-free DNA-antibody complexes in the etiology of RA, suggest new avenues for basic research, and may prove to be relevant to diagnosis and assessment of therapy.
16469113 Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patien 2006 Peptidylarginine deiminase type 4 (PADI4) genotypes were shown to influence susceptibility to rheumatoid arthritis (RA) in the Japanese population. Such an association could not previously be confirmed in different European populations. In the present study, we analysed exons 2-4 of PADI4 in 102 German RA patients and 102 healthy individuals to study the influence of PADI4 variability on RA susceptibility by means of haplotype-specific DNA sequencing. Analyses of the influence of PADI4 and HLA-DRB1 genotypes on disease activity and on levels of anti-cyclic citrullinated peptide antibodies were performed. Comparing the frequencies of PADI4 haplotype 4 (padi4_89*G, padi4_90*T, padi4_92*G, padi4_94*T, padi4_104*C, padi4_95*G, padi4_96*T) (patients, 14.7%; controls, 7.8%; odds ratio = 2.0, 95% confidence interval = 1.1-3.8) and carriers of this haplotype (patients, 27.5%; controls, 13.7%; odds ratio = 2.4, 95% confidence interval = 1.2-4.8), a significant positive association of PADI4 haplotype 4 with RA could be demonstrated. Other PADI4 haplotypes did not differ significantly between patients and controls. Regarding the individual PADI4 variants, padi4_89 (A-->G), padi4_90 (C-->T), and padi4_94 (C-->T) were significantly associated with RA (patients, 49.5%; controls, 38.7%; odds ratio = 1.6, 95% confidence interval = 1.1-2.3). Considering novel PADI4 variants located in or near to exons 2, 3, and 4, no quantitative or qualitative differences between RA patients (8.8%) and healthy controls (10.8%) could be demonstrated. While the PADI4 genotype did not influence disease activity and the anti-cyclic citrullinated peptide antibody level, the presence of the HLA-DRB1 shared epitope was significantly associated with higher anti-cyclic citrullinated peptide antibody levels (P = 0.033). The results of this small case-control study support the hypothesis that variability of the PADI4 gene may influence susceptibility to RA in the German population. Quantitative or qualitative differences in previously undefined PADI4 variants between patients and controls could not be demonstrated.
18448480 Rheumatoid cachexia: a clinical perspective. 2008 Aug Rheumatoid cachexia is under-recognized in clinical practice. The loss of lean body tissue, which characterizes cachexia, is often compensated for by gain in body fat-so called 'cachectic obesity'-so that 85% or more RA patients have a normal BMI. Severe cachexia with loss of weight leads to increased morbidity and premature mortality but loss of muscle bulk with a normal BMI also associates with poor clinical outcomes. Increasing BMI, even into the obese range, is associated with less joint damage and reduced mortality. Measurement of body composition using DXA and other techniques is feasible but the results must be interpreted with care. Newer techniques such as whole-body MRI will help define with more confidence the mass and distribution of fat and muscle and help elucidate the relationships between body composition and outcomes. Cachexia shows little response to diet alone but progressive resistance training and anti-TNF therapies show promise in tackling this potentially disabling extra-articular feature of RA.
18817643 Tumor necrosis factor inhibitors and infection complications. 2008 Oct Rheumatoid arthritis patients are at heightened risk for infections because of intrinsic disease severity with associated inflammation, comorbid illnesses, and use of glucocorticoids and various immunosuppressives. Although several studies have reported up to a twofold increase in risk of serious infections in RA patients treated with anti-tumor necrosis factor-alpha agents, results from other studies have been conflicting. Comparing results from different studies is challenging because of differences in patient populations, heterogeneous prevalence of comorbidities, and differing patterns of concomitant medication use. Based on available evidence, an excess risk for infection occurs early after initiation of tumor necrosis factor-alpha inhibitor therapy. Additionally, special circumstances such as surgical procedures may increase infection risk. The appropriate use of biologics in the perioperative setting remains empiric at best.
18232281 [Effects of therapy on functional ability of patients with rheumatoid arthritis]. 2007 Rheumatoid arthritis (RA) is a diseases which causes great suffering of patients, and it demands a complex medicamentosus therapy (including diseases modifying antirheumatic drugs DMARD) and physical therapy. Disease often progresses, in spite of therapy and leads to severe functional disability. That is why it is often discussed whether the usage of expensive therapy such as DMARD is justified. This question is often asked in countries with poor socio economic standard where health funds cannot cover all expenses of the treatment for RA, and patients themselves cannot afford expensive therapy. In order to assess the real potential of DMARD therapy it is necessary to compare results of treatment of patients which do not take those medications. This cannot be done in a country where DMARDs are available to all patients because it would be unethical to take them off drugs. In Bosnia and Herzegovina, a country with a recent war history, there are many RA patients who could not afford those expensive medications and could be examined as a control group in this research. Effects of treatment could be evaluated by analysis of functional ability of patients, because its loss is the first thing that is noticed by patients, right after pain. It is a key factor in the strategy development of examination, treatment and analysis of patients with RA. The aim of this research was to evaluate the efficacy of the DMARD and physical therapy on the functional ability of patient with rheumatoid arthritis (RA). METHODS: The research was conducted on 40 RA patients who were under the control of the rheumatologist, were taking DMARD and were hospitalized at the rehabilitation clinic for physical therapy once in a year, and later conducted exercises at home. Control group had 70 RA patients, who were not under the control of rheumatologists and did not take drugs from the DMARD group, nor did they use physical therapy. Groups were comparable according to age, duration of their disease, sex and presence of RF. Functional ability was assessed with Health Assessment Questionnaire (HAQ). Walking quality and need for prostheses were also evaluated. RESULTS: According to HAQ mild functional disability was found in 69% of the examined group and in 9% of the control group, moderate functional disability was found in 30% of the examined group and in 29% of the control group. Severe functional disability and dependency of other people's help was found in 2% of the examined group and in 26% of the control group. Complete disability was not found in the examined group and was found in 14% of the control group. 65% of patients in the examined group did have problems with walking while 25% did not. Remaining 10% had to use one stick while walking. In control group 3% did not have any problems with walking, 42% did, 31% used stick, 13 % used crunches, and wheel chairs were necessary for 7% of patients. DISCUSSION: This research showed that functional disability progresses in patients who are treated and the ones that are not. There is a significant difference in the severity of functional disability among examined groups (p < 0.00001). Among patients that are using DMARD and physical therapy there are no patients that are completely dependent, using crutches or wheel chair. That is justified reason for finding the means for quality treatment of patients with RA. CONCLUSION: Out of this research one can conclude that drugs can slow the progression of the disease, but with the usage of the contemporary therapy with DMARD and regular physical therapy one could modify the course of the disease and significantly reduce the functional disability of RA patients.
16826106 Periapatite may not improve micromotion of knee prostheses in rheumatoid arthritis. 2006 Jul Prosthesis migration in bone inevitably occurs in cemented and uncemented total knee arthroplasty tibial components. Cemented designs as the gold standard give immediate fixation whereas cementless designs need a period of bone ingrowth onto the surface irregularities of the implants. The addition of bioactive coatings may enhance this process of ingrowth. A controlled randomized prospective RSA study was carried out on 26 Duracon implants in a rheumatoid arthritis patient group to evaluate the effect of a periapatite coating on the fixation of the tibial tray. The coated and the noncoated groups were matched for sex, age, body mass index, and HSS Knee Score. Stage of preoperative joint destruction and preoperative and postoperative mechanical leg axis showed no differences. We saw no differences in migration between the two groups, but a trend for lesser translations along and rotations about all three axes in the periapatite group. The periapatite-coated components showed a lower variance in subsidence than did the uncoated components. Both groups also showed a high variance in anterior tilting of the components. The cementless PA-coated Duracon prosthesis used in patients with RA may provide improved fixation of tibial components although we could not demonstrate improvement in this small controlled series. LEVEL OF EVIDENCE: Therapeutic Level II. See the Guidelines for Authors for a complete description of levels of evidence.
18534002 Therapeutic effects of antibodies to tumor necrosis factor-alpha, interleukin-6 and cytoto 2008 INTRODUCTION: Immunization with glucose-6-phosphate isomerase (GPI) induces severe arthritis in DBA/1 mice. The present study was designed to identify the cytokines and co-stimulatory molecules involved in the development of GPI-induced arthritis. METHODS: Arthritis was induced in DBA/1 mice with 300 microg human recombinant GPI. CD4+ T cells and antigen-presenting cells from splenocytes of arthritic mice were cultured in the presence of GPI. Tumor necrosis factor (TNF)-alpha, IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-12 levels were assessed using cytometric bead array. Monoclonal antibodies to TNF-alpha, IFN-gamma, IL-12, CD40L, inducible co-stimulator (ICOS), and cytotoxic T-lymphocyte antigen 4 immunoglobulin (CTLA-4Ig) were used to block TNF-alpha and IFN-gamma production, examine clinical index in mice with GPI-induced arthritis, and determine anti-GPI antibody production. RESULTS: Large amounts of TNF-alpha and IFN-gamma and small amounts of IL-2 and IL-6 were produced by splenocytes from mice with GPI-induced arthritis. Anti-TNF-alpha mAbs and CTLA-4Ig suppressed TNF-alpha production, whereas anti-IFN-gamma mAbs, anti-IL-12 mAbs, and CTLA-4 Ig inhibited IFN-gamma production. A single injection of anti-TNF-alpha and anti-IL-6 mAbs and two injections of CTLA-4Ig reduced the severity of arthritis in mice, whereas injections of anti-IFN-gamma and anti-IL-12 mAbs tended to exacerbate arthritis. Therapeutic efficacy tended to correlate with reduction in anti-GPI antibodies. CONCLUSION: TNF-alpha and IL-6 play an important role in GPI-induced arthritis, whereas IFN-gamma appears to function as a regulator of arthritis. Because the therapeutic effects of the tested molecules used in this study are similar to those in patients with rheumatoid arthritis, GPI-induced arthritis appears to be a suitable tool with which to examine the effect of various therapies on rheumatoid arthritis.
19019893 Monitoring anti-TNFalpha treatment in rheumatoid arthritis: responsiveness of magnetic res 2009 Oct OBJECTIVES: To evaluate the responsiveness of magnetic resonance imaging (MRI) and ultrasonography (US) compared with conventional measures of disease activity and structural damage in patients with rheumatoid arthritis (RA) during the first year of treatment with anti-tumour necrosis factor alpha (TNFalpha). METHODS: A cohort of patients with RA (N = 36, median age 53 years, disease duration 7.6 years and disease activity score (DAS28) 5.7) was evaluated by core measures of disease activity, US (one wrist), MRI (one wrist) and conventional radiography (CR, both hands and wrists) at initiation of treatment with anti-TNFalpha agents and after 3, 6 and 12 months. Responsiveness was assessed by standardised response means (SRM). Accepted thresholds were applied to classify responsiveness as trivial, low, moderate or good. RESULTS: MRI synovitis (SRM between -0.79 and -0.92) and the MRI total inflammation score comprising synovitis, tenosynovitis and bone marrow oedema (SRM between -1.05 and -1.24) were highly responsive. Moderate to high responsiveness was found for MRI tenosynovitis and bone marrow oedema, all the composite indices (DAS28, simplified disease activity index (SDAI) and clinical disease activity index (CDAI)) and the 28-swollen joint count. US displayed low to moderate responsiveness. The MRI erosion score displayed low responsiveness but was more responsive than CR measures at 3 and 6 months follow-up. MRI and CR measures of annual progression rates of damage performed similarly and were highly responsive. CONCLUSIONS: The most responsive measure of inflammation when evaluating anti-TNFalpha medication was a composite measure comprising MRI synovitis, tenosynovitis and bone marrow oedema, and this may be a promising outcome measure in clinical studies.
16798995 Arthrodesis versus Mayo resection: the management of the first metatarsophalangeal joint i 2006 Jul In a prospective randomised study 31 patients were allocated to either arthrodesis or Mayo resection of the first metatarsophalangeal joint as part of a total reconstruction of the rheumatoid forefoot. Of these, 29 were re-examined after a mean of 72 months (57 to 80), the Foot Function Index was scored and any deformity measured. Load distribution was analysed using a Fscan mat in 14 cases, and time and distance were measured in 12 of these patients using a 3D Motion system. We found excellent patient satisfaction and a significant, lasting reduction of the Foot Function Index, with no statistically significant differences between the groups. There were no significant differences in recurrence of the deformity, the need for special shoes, gait velocity, step length, plantar moment, mean pressure or the position of the centre of force under the forefoot. The cadence was higher and the stance phase shorter in the fusion group. These results suggest that a Mayo resection may be an equally good option for managing the first metatarsophalangeal joint in reconstruction of the rheumatoid forefoot.
17850677 Tumour necrosis factor blockade and the risk of osteoporosis: back to the future. 2007 Osteoporosis is a common clinical problem, especially in patients with rheumatoid arthritis (RA). A reduction in bone mineral density (BMD) of the axial and appendicular skeleton ranging from 7% to 15% has been reported in RA in studies employing a variety of densitometric techniques. Reports consistent with a beneficial effect of tumour necrosis factor blockade on BMD have begun to emerge in recent years, and in Arthritis Research and Therapy, a case control study reports that patients treated with infliximab for RA had preservation of BMD in the lumbar spine and femoral neck compared to those treated with methotrexate.
17869648 Macrophage migration inhibitory factor gene: influence on rheumatoid arthritis susceptibil 2007 Sep The macrophage inhibitory factor (MIF) is a cytokine that has been implicated in several inflammatory and autoimmune diseases, including rheumatoid arthritis, systemic lupus, glomerulonephritis, and multiple sclerosis. In rheumatoid arthritis (RA), results ranging from lack of association of MIF polymorphisms with RA, to involvement in either severity or susceptibility to the disease have been reported in the past. We aimed at investigating the role of this gene in RA in the Spanish population. Two well-known MIF promoter polymorphisms were tested in 606 adult RA patients and 886 healthy controls: a single nucleotide polymorphism at -173G/C and a tetranucleotide repeat (CATT)(5-8) located at -794. We found a significant association of the allele -173C with RA (p = 0.01; odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.06-1.62). The -173C risk allele, previously reported to be transmitted in excess in patients with juvenile idiopathic arthritis, was significantly more frequent in early-onset adult RA patients than in healthy controls (p = 0.003; OR = 1.57; 95% CI = 1.14-2.15), whereas late-onset patients were not significantly different to controls (p = 0.6; OR = 1.09; 95% CI = 0.77-1.55). In conclusion, the -173C allele in the MIF promoter region is associated with increased RA predisposition, mainly in early-onset patients.
18467931 Evaluation of disability in patients with degenerative and inflammatory arthritis. 2008 Jun Both degenerative and inflammatory arthritis cause disability that has deteriorative effect on patients' daily activities. The aim of this study was to determine the disability level of patients with chronic degenerative and inflammatory arthritis and evaluate the relationship of different activities with disability. Sixty-three rheumatoid arthritis (RA) and 39 osteoarthritis (OA) patients who were hospitalized in our clinics to receive physical therapy and rehabilitation were included in this study. The patients were evaluated for severity of pain (Likert), functional stage (Steinbrocker), and physical disability (Stanford Health Assessment Questionnaire). The severity of pain was higher and functional stage was more advanced in the RA group (P<0.05). Disability levels were mild in 38%, moderate in 44.5%, and severe in 16% of RA patients. In contrast, disability levels of OA patients were mild in 84.5% and moderate in 13%. The total disability score and the disability scores of activities, such as dressing, eating, hygiene, reaching for an object, and gripping an object were significantly higher in the RA group than in the OA group (P<0.05). Disability in walking and rising were not different between the two groups (P>0.05). Although the parameters that strongly correlated with general disability were gripping, hygiene/grooming, running errands, and shopping in the RA group, they were walking, running errands, and shopping in the OA group. Degenerative arthritis can cause as much disability as inflammatory arthritis regarding activities related with lower extremity functions. Thus, while planning treatment these factors must be determined and an appropriate multidisciplinary rehabilitation process should be initiated.
17654306 Platelet P-selectin is significantly involved in leukocyte-endothelial cell interaction in 2007 Aug There is growing evidence that platelets play an important role in the development and maintenance of rheumatoid arthritis. Activation and adherence of platelets in the synovial microcirculation might be in part responsible for endothelial damage and activation of leukocytes. Recent findings show a direct influence of P-selectin on platelet- and leukocyte-endothelial cell interaction in mice with Antigen-induced Arthritis (AiA). P-selectin is only expressed by platelets and endothelial cells, not by leukocytes. Therefore, the aim of the present study was to investigate the differential influence of platelet and endothelial P-selectin on the extent of inflammation in AiA. AiA was induced in wild-type mice and in P-selectin-deficient mice from the same genetic background (four groups: each n = 7). Intravital fluorescence microscopy (IVM) was used to visualize platelets and leukocytes in the synovial microcirculation at day 8 after AiA. Platelets from either strain were fluorescence-labelled ex vivo and transferred into either strain. We were able to demonstrate a significant decrease of platelet- and leukocyte-endothelial cell interaction in P-selectin-deficient mice with AiA in comparison to wild-type mice with AiA. When wild-type platelets were donated into P-selectin-deficient AiA recipients, the leukocyte-endothelial cell interaction was significantly increased compared to the group consisting of P-selectin-deficient recipient and donor mice. These are the first in vivo results showing that the P-selectin stored in platelets is at least partly responsible for the leukocyte-endothelial cell interaction and the resulting tissue damage in AiA. In the future, a suppression of platelet P-selectin could potentially become a treatment option for reducing the effects of rheumatoid arthritis.
18283523 Retrospective clinical study on the notable efficacy and related factors of infliximab the 2008 Biologics targeting TNF have brought about a paradigm shift in the treatment of rheumatoid arthritis (RA) and infliximab, anti-TNF-alpha chimeric monoclonal antibody, was marketed in 2003 in Japan. We previously reported on the RECONFIRM study, a retrospective clinical study on the efficacy of infliximab therapy in a RA management group in Japan, where we evaluated the clinical response after 22 weeks of the therapy in 258 patients. The study reported here was aimed at reconfirming the clinical efficacy of the infliximab therapy and demographic factors related to the efficacy over a 54-week study period in 410 RA patients in the same study group. Infliximab was infused according to the domestically approved method, and the clinical response was evaluated following 54 weeks of infliximab therapy using the European League Against Rheumatism (EULAR) response criteria. Disease activity was assessed by DAS28-CRP (Disease Activity Score including a 28-joint count/C-reactive protein). Infliximab was discontinued in 24.4% of the 410 patients at 54 weeks and 9.3% and 8.1% discontinued the therapy due to adverse events and inefficiency, respectively. Average DAS28-CRP decreased from 5.5 at week 0 to 3.1 at week 54 after the therapy. Patients in remission and those showing low-, moderate-, and high-disease activity changed from 0.0, 1.0, 9.0 and 90.0%, respectively, at the start of the study to 27.6, 11.7, 34.4 and 26.3%, respectively, at week 54. Younger age, RF-negativity and low scores of DAS28-CRP showed significant correlations with remission at week 54. EULAR response criteria -- good, moderate, and no response to infliximab -- were 37.0, 41.7 and 21.2%, respectively. In conclusion, we reconfirmed the clinical efficacy of infliximab and demographic factors related to the efficacy over a 54-week study period in 410 Japanese patients with RA using DAS28-CRP and EULAR response criteria.
16626489 Do visual analogue scale (VAS) derived standard gamble (SG) utilities agree with Health Ut 2006 Apr 20 BACKGROUND: Assessment of Health Related Quality of Life (HRQL) has become increasingly important and various direct and indirect methods and instruments have been devised to measure it. In direct methods such as Visual Analog Scale (VAS) and Standard Gamble (SG), respondent both assesses and values health states therefore the final score reflects patient's preferences. In indirect methods such as multi-attribute health status classification systems, the patient provides the assessment of a health state and then a multi-attribute utility function is used for evaluation of the health state. Because these functions have been estimated using valuations of general population, the final score reflects community's preferences. The objective of this study is to assess the agreement between community preferences derived from the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) systems, and patient preferences. METHODS: Visual analog scale (VAS) and HUI scores were obtained from a sample of 320 rheumatoid arthritis patients. VAS scores were adjusted for end-aversion bias and transformed to standard gamble (SG) utility scores using 8 different power conversion formulas reported in other studies. Individual level agreement between SG utilities and HUI2 and HUI3 utilities was assessed using the intraclass correlation coefficient (ICC). Group level agreement was assessed by comparing group means using the paired t-test. RESULTS: After examining all 8 different SG estimates, the ICC (95% confidence interval) between SG and HUI2 utilities ranged from 0.45 (0.36 to 0.54) to 0.55 (0.47 to 0.62). The ICC between SG and HUI3 utilities ranged from 0.45 (0.35 to 0.53) to 0.57 (0.49 to 0.64). The mean differences between SG and HUI2 utilities ranged from 0.10 (0.08 to 0.12) to 0.22 (0.20 to 0.24). The mean differences between SG and HUI3 utilities ranged from 0.18 (0.16 to 0.2) to 0.28 (0.26 to 0.3). CONCLUSION: At the individual level, patient and community preferences show moderate to strong agreement, but at the group level they have clinically important and statistically significant differences. Using different sources of preference might alter clinical and policy decisions that are based on methods that incorporate HRQL assessment. VAS-derived utility scores are not good substitutes for HUI scores.