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ID PMID Title PublicationDate abstract
21078625 Long-term effectiveness and safety of TNF-blocking agents in daily clinical practice: resu 2011 Jan OBJECTIVES: Experience with anti-TNF agents for a decade can be used to research the safety and effectiveness of anti-TNF agents in the long term. The objective of this article is to describe drug survival, disease activity, daily functioning, quality of life and adverse events of TNF-blocking agents in daily clinical practice after 5 years of follow-up. METHODS: Data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) register of 1560 RA patients were used for analyses (5-year follow-up, n=174). Drug survival and time to first serious infection or malignancy were analysed by Kaplan-Meier analysis. Several outcome measures at several follow-up moments were analysed per intention to treat and per protocol. RESULTS: The 5-year drug survival of the first anti-TNF was 45%, and 60% for total use of TNF-blocking agents. Baseline 28-joint DAS (DAS-28) was 5.1 (s.d. 1.3). After 5 years, the mean DAS-28 was 3.2 (s.d. 1.3) in all patients who had started with TNF-blocking agents and 2.9 (s.d. 1.1) in patients who were still on TNF-blocking agents. In the latter group, the HAQ score was 0.88 (s.d. 0.7) and the EuroQol five dimensions (EQ-5D) utility score was 0.7 (s.d. 0.2). Incidence rates of serious infections and malignancies were 2.9 and 0.6 per 100 patient-years, respectively. CONCLUSION: Five-year follow-up of RA patients treated with TNF-blocking agents showed a 60% drug survival accompanied by sustained low disease activity, normalized function and quality of life similar to that in the general population. The benefit to risk ratio for long-term TNF-blocking therapy remains favourable.
20080922 Abatacept for rheumatoid arthritis: a Cochrane systematic review. 2010 Feb OBJECTIVE: To perform a systematic review of efficacy and safety of abatacept in patients with rheumatoid arthritis (RA). METHODS: We searched the Cochrane Library, MEDLINE, EMBASE, ACP Journal Club, and Biosis Previews for randomized controlled trials (RCT) comparing abatacept alone or in combination with disease modifying antirheumatic drugs (DMARD)/biologics to placebo or other DMARD/biologics in patients with RA. Two reviewers independently assessed search results, risk of bias, and extracted data. RESULTS: Seven trials with 2908 patients were included. Compared with placebo, patients with RA treated with abatacept were 2.2 times more likely to achieve an American College of Rheumatology 50% response (ACR50) at one year (relative risk 2.21, 95% CI 1.73, 2.82) with a 21% (95% CI 16%, 27%) absolute risk difference between groups. The number needed to treat to achieve an ACR50 response was 5 (95% CI 4, 7). Significantly greater improvements in physical function, disease activity, pain, and radiographic progression were noted in abatacept-treated patients compared to placebo. Total adverse events (AE) were greater in the abatacept group (RR 1.05, 95% CI 1.01, 1.08). Other harm outcomes were not significant, with the exception of serious infections at 12 months, which were more common in the abatacept group versus control group (Peto odds ratio 1.91, 95% CI 1.07, 3.42). Serious AE were more numerous in the abatacept + etanercept group versus the placebo + etanercept group (RR 2.30, 95% CI 1.15, 4.62). CONCLUSION: Abatacept seems to be efficacious and safe in the treatment of RA. Abatacept should not be used in combination with other biologics to treat RA. Further longterm studies and postmarketing surveillance are required to assess for longer-term harms and sustained efficacy.
19333993 Choice of second-line disease-modifying antirheumatic drugs after failure of methotrexate 2009 Apr 15 OBJECTIVE: To survey rheumatologists' preferences for the choice of a second-line disease-modifying antirheumatic drug (DMARD) after inadequate response with methotrexate (MTX) therapy in rheumatoid arthritis (RA). METHODS: Thirty-six rheumatologists stated their preferences for RA treatment after inadequate response with MTX therapy (optimal dose at least 6 months). From the initial scenario, we derived 54 vignettes varying by rheumatoid factor or anti-cyclic citrullinated peptide antibody presence, swollen joint count, Disease Activity Score in 28 joints, and structural damage. Respondents stated their preference among 5 therapeutic options: MTX continuation, switch to another conventional DMARD, addition of another conventional DMARD, addition of anakinra, or addition of a tumor necrosis factor (TNF) blocker. Presentation by pairs yielded 10 combinations of strategies for each variant, totaling 540 vignettes; participants evaluated a random sample of 180 vignettes. Determinants of each top-ranked option were analyzed by logistic regression. The compilation of these data served to define a therapeutic algorithm. RESULTS: The responses of 33 rheumatologists were analyzable. Therapeutic preferences corresponded to the top-ranked options. For patients with mild or moderately active RA, either a switch or step-up strategy to another conventional DMARD was top ranked. TNF blockers were preferred for RA patients with high disease activity or progressive structural damage. On the basis of these preferences, we developed a simple decision tree for use in daily clinical practice. CONCLUSION: Our simple, easy-to-use decision tree developed from rheumatologists' preferences for therapy after failure of MTX therapy in RA treatment may guide rheumatologists in daily practice to choose a second-line DMARD.
18772191 Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis 2009 Jul OBJECTIVES: Abatacept is the only agent currently approved to treat rheumatoid arthritis (RA) that targets the co-stimulatory signal required for full T-cell activation. No studies have been conducted on its effect on the synovium, the primary site of pathology. The aim of this study was to determine the synovial effect of abatacept in patients with RA and an inadequate response to tumour necrosis factor alpha (TNFalpha) blocking therapy. METHODS: This first mechanistic study incorporated both dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and arthroscopy-acquired synovial biopsies before and 16 weeks after therapy, providing tissue for immunohistochemistry and quantitative real-time PCR analyses. RESULTS: Sixteen patients (13 women) were studied; all had previously failed TNFalpha-blocking therapy. Fifteen patients completed the study. Synovial biopsies showed a small reduction in cellular content, which was significant only for B cells. The quantitative PCR showed a reduction in expression for most inflammatory genes (Wald statistic of p<0.01 indicating a significant treatment effect), with particular reduction in IFNgamma of -52% (95% CI -73 to -15, p<0.05); this correlated well with MRI improvements. In addition, favourable changes in the osteoprotegerin and receptor activator of nuclear factor kappa B levels were noted. DCE-MRI showed a reduction of 15-40% in MRI parameters. CONCLUSION: These results indicate that abatacept reduces the inflammatory status of the synovium without disrupting cellular homeostasis. The reductions in gene expression influence bone positively and suggest a basis for the recently demonstrated radiological improvements that have been seen with abatacept treatment in patients with RA.
20472597 Blood pressure changes in patients with recent-onset rheumatoid arthritis treated with fou 2010 Jul OBJECTIVE: To evaluate the effect of disease activity and antirheumatic treatment on blood pressure (BP) in patients with recent-onset rheumatoid arthritis (RA). METHODS: 508 patients with RA were randomised to receive (1) sequential monotherapy, (2) step-up combination therapy, (3) initial combination with prednisone or (4) with infliximab. Systolic and diastolic BP (SBP, DBP), disease activity score (DAS) and body mass index (BMI) were evaluated every 3 months. A linear mixed model was used to model SBP and DBP in each treatment group during year 1, adjusting for baseline BP, changes in BMI, DAS and cardiovascular medication. RESULTS: In all groups, mean SBP and DBP were lower for patients with DAS < or =2.4 than for patients with DAS >2.4. In addition, patients initially treated with infliximab (group 4) had a larger decrease in SBP and DBP over time than patients in groups 1-3. The decrease in BP was also observed in patients treated with infliximab after failure on conventional disease-modifying antirheumatic drugs in groups 1-3. The decrease in BP associated with treatment with infliximab occurred irrespective of the DAS response. CONCLUSION: A lower DAS is associated with lower BP. An additional decrease in BP was observed in patients treated with infliximab. Further research is needed to confirm the effect of infliximab on BP.
19801788 Serum levels of TNF-alpha, TNF-alphaRI, TNF-alphaRII and IL-12 in treated rheumatoid arthr 2009 Sep BACKGROUND: Rheumatoid arthritis (RA) is a chronic multisystem autoimmune disease common in all races and ethnics. Cytokines and cytokines receptors play an important role in RA pathogenesis and clinical presentation. OBJECTIVE: To investigate the serum levels of TNF-alpha, TNF-alpha RI, TNF-alpha RII and IL-12 in RA patients and healthy control group. METHODS: In this study 43 patients fulfilling the revised criteria of American College of Rheumatology (ACR) for RA and 13 healthy cases as a control group were selected for TNF-alpha, TNF-alphaRI, TNF-alphaRII and IL-12 serum level analysis. The patients' age was 42.2 +/- 22 and the age of healthy group was 40.1 +/- 19.2 years (p=0.1). The patients had an active disease with at least six swollen and ten tender joints. Minimum ESR was 28 mm at first hours of the morning. Early morning stiffness in patients lasted longer than 45 minutes. RESULTS: Our study showed that IL-12 serum level of the patients (91.69 +/- 43.07 rhog/ml) and control (61.79 +/- 40.08 rhog/ml) group was significantly different (p<0.001). The serum level of TNF-alphaRI was 2.36 +/- 0.77 ng/ml in the patient and 1.73 +/- 0.37 ng/ml in the control group (p<0.01). TNF-alphaRII serum concentration in patients was 8.89 +/- 2.3 ng/ml, while that of control group was 7.06+/-1.30 ng/ml (p=0.03). The serum level of TNF-alpha in patients was 32.90 +/- 19.27 rhog/ml and that of the control group was 24.27+/- 8.28 rhog/ml (p=0.08) with no significant difference between the two. CONCLUSIONS: It is concluded that IL-12, TNF-alphaRI and TNF- alphaRII serum concentrations are more important and better predictive factors than TNF-alpha in RA course and in the active forms of the disease.
19137355 Expression of multidrug resistance-1 protein correlates with disease activity rather than 2009 Apr Disease-modifying antirheumatic drugs (DMARDs) improve the disability and slow the progression of the joint damage in rheumatoid arthritis (RA). However, a large proportion of patients experience inefficacy by the end of 2 years. This loss of efficacy may be due to expression of multidrug resistance (MDR) proteins on lymphocytes. The objective is to study the expression of MDR protein on the peripheral blood lymphocytes in patients with RA and correlate it with the disease status and response to treatment. Twenty-eight patients were enrolled. Expression of MDR-1 by flow cytometry was carried out on lymphocytes at baseline and after 4 months of therapy. This expression was correlated with disease activity scores (DAS 28). There were 25 females with mean age of 48.13 years and median disease duration of 48 months. Eighteen patients were DMARD naive and ten were refractory to DMARD (methotrexate). The percentage of cells expressing MDR-1 in the DMARD-naive (p<0.O5) and DMARD-refractory (p<0.05) groups were significantly higher than the healthy controls at the baseline. The relative fluorescence intensity was significantly higher in the DMARD-refractory group (p<0.05) as compared to the DMARD-naive group. After 4 months of therapy, there was significant improvement in the D value (p<0.01) in the DMARD-naive group (treated with methotrexate only) and DMARD-refractory group (p<0.05). A significant correlation (r=0.563) between the DAS 28 scores and the D value (p=0.003) was observed. Expression of MDR-1 in RA correlated with disease activity status and improved with DMARD therapy. It is not related to the refractoriness to therapy with methotrexate.
20535785 Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheum 2010 Jun OBJECTIVE: To explore the influence of anti-tumor necrosis factor (anti-TNF) therapy upon the incidence of cancer in patients with rheumatoid arthritis (RA) and prior malignancy. METHODS: Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study established in 2001, we identified 293 patients with a prior malignancy from over 14,000 patients with RA. We compared rates of incident malignancy in 177 anti-TNF-treated patients and 117 patients with active RA treated with traditional disease-modifying antirheumatic drugs (DMARDs), all with prior malignancy. One patient switched therapy and contributed to both cohorts. RESULTS: The rates of incident malignancy were 25.3 events/1,000 person-years in the anti-TNF cohort and 38.3/1,000 person-years in the DMARD cohort, generating an age- and sex-adjusted incidence rate ratio of 0.58 (95% confidence interval 0.23-1.43) for the anti-TNF-treated cohort compared with the DMARD cohort. Of the patients with prior melanomas, 3 (18%) of 17 in the anti-TNF cohort developed an incident malignancy, compared with 0 of 10 in the DMARD cohort. CONCLUSION: The way in which UK rheumatologists are selecting patients with RA and prior malignancy to receive anti-TNF therapy is not leading to an increased risk of incident malignancy. Although reassuring, these results should not be interpreted as indicating that it is safe to treat all RA patients with prior malignancy with anti-TNF therapy.
18848428 The relationship between increased hip range of motion, wear, and locking mechanism failur 2009 Sep We performed both clinical and radiographic evaluations of 178 patients (190 hips) who had undergone cementless total hip arthroplasties using Harris-Galante I/II porous cups after an average 12-year follow-up period (range, 8-18 years). We revised 15 Harris-Galante I/II porous cups (7.8%), and the locking mechanism was broken in 10 revised cups (67%). There was a significant association between locking mechanism failure and linear polyethylene wear. We observed a significant positive correlation between linear polyethylene wear and increased ranges of motion such as flexion, adduction, and external rotation at the last follow-up visit after the primary operation. Increased ranges of motion seen in Asians induced higher linear polyethylene wear and locking mechanism failure due to impingement of the neck and cup.
19684150 Plasma adiponectin in patients with active, early, and chronic rheumatoid arthritis who ar 2009 Sep OBJECTIVE: Rheumatoid arthritis (RA) is a systemic chronic inflammatory joint disease, whereas osteoarthritis (OA) is a local joint disease with low-level inflammatory activity. The pathogenic role of the adipocytokine adiponectin is largely unknown in these diseases. We hypothesized (1) that plasma adiponectin concentrations differ in healthy controls and patients with early disease-modifying antirheumatic drug (DMARD)-naive RA, chronic RA, and OA; (2) that changes in adiponectin are observed during methotrexate (MTX) treatment of chronic RA; and (3) that adiponectin correlates to disease activity measures in RA. METHODS: Plasma adiponectin was analyzed with a validated in-house immunoassay. We measured adiponectin in healthy controls (n = 45) and patients with early DMARD-naive RA (n = 40), chronic RA (n = 74), and OA (n = 35). In a subgroup of patients with chronic RA (n = 31), the longitudinal effect of MTX treatment on adiponectin (Week 0 vs Week 28) was investigated. RESULTS: Adiponectin differed significantly between healthy controls (mean 4.8 +/- SD 2.7 mg/l) and the 3 groups, with 8.9 +/- 4.8 mg/l in early RA, 11.6 +/- 5.6 mg/l in chronic RA, and 14.1 +/- 6.4 mg/l in OA. Longitudinally, MTX treatment increased adiponectin significantly from 9.7 +/- 4.5 mg/l at Week 0 to 11.0 +/- 4.5 mg/l at Week 28 in chronic RA. No correlations to disease activity measures were found. CONCLUSION: Both early DMARD-naive and chronic RA were associated with higher plasma adiponectin compared to healthy controls, but lower plasma adiponectin than OA. Adiponectin increased 13% during MTX treatment. In patients with RA and OA body mass index, age, sex, and disease activity measures failed to explain the findings.
20337855 Whole blood cytokine attenuation by cholinergic agonists ex vivo and relationship to vagus 2010 Jul OBJECTIVE: The central nervous system regulates innate immunity in part via the cholinergic anti-inflammatory pathway, a neural circuit that transmits signals in the vagus nerve that suppress pro-inflammatory cytokine production by an alpha-7 nicotinic acetylcholine receptors (alpha7nAChR) dependent mechanism. Vagus nerve activity is significantly suppressed in patients with autoimmune diseases, including rheumatoid arthritis (RA). It has been suggested that stimulating the cholinergic anti-inflammatory pathway may be beneficial to patients, but it remains theoretically possible that chronic deficiencies in this pathway will render these approaches ineffective. METHODS: Here we addressed the hypothesis that inflammatory cells from RA patients can respond to cholinergic agonists with reduced cytokine production in the setting of reduced vagus nerve activity. RESULTS: Measurement of RR interval variability (heart rate variability, HRV), in RA patients (n = 13) and healthy controls (n = 10) revealed that vagus nerve activity was significantly depressed in patients. Whole blood cultures stimulated by exposure to endotoxin produced significantly less tumour necrosis factor in samples from RA patients as compared to healthy controls. Addition of cholinergic agonists (nicotine and GTS-21) to the stimulated whole blood cultures however significantly suppressed cytokine production to a similar extent in patients and healthy controls. CONCLUSION: These findings suggest that it is possible to pharmacologically target the alpha7nAChR dependent control of cytokine release in RA patients with suppressed vagus nerve activity. As alpha7nAChR agonists ameliorate the clinical course of collagen induced arthritis in animals, it may be possible in the future to explore whether alpha7nAChR agonists can improve clinical activity in RA patients.
19852912 [Coronary calcification and subclinical myocardial dysfuncion in rheumatoid arthritis]. 2009 Oct Rheumatoid arthritis (RA) is characterized by high cardiovascular (CV) mortality, which has been related to systemic inflammation. Our aim was to analyze coronary calcification by computed tomography and subclinical myocardial dysfunction evaluated by brain natriuretic peptide (BNP) levels and an electrocardiogram in RA patients and its relationship with disease characteristics. Seventy-three RA patients and same number of controls formed by osteoarthritis patients were studied, all without a background of cardiovascular clinical events. RA patients had a higher calcium score than the control group (19.2% vs. 11%; p=0.17)), this being associated with disease duration. BNP levels (90.0 vs. 45.4; p=0.003), corrected QT length, large QT frequency and silent myocardial infarct were higher in the RA group. In conclusion, RA patients showed more coronary calcification frequency than in general population and more biochemical and electrocardiogram myocardial subclinical dysfunction signs.
21205460 Smokers and non smokers with rheumatoid arthritis have similar clinical status: data from 2010 Nov OBJECTIVES: To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. METHODS: The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. RESULTS: Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). CONCLUSIONS: RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).
21205464 Differences in pain and fatigue perception among a group of rheumatoid arthritis patients 2010 Nov OBJECTIVES: The concordance of patient reported outcomes in rheumatoid arthritis (RA) among different countries has not been studied in detail. We tried to determine the differences in pain and fatigue perception among a group of RA patients in the US and in Turkey who had similar disease activity and functional score in multidimensional health assessment questionnaire (MDHAQ FN). METHODS: One hundred and thirty seven RA patients from Turkey and 129 from the US were studied. An MDHAQ was obtained and a DAS28 was calculated for each patient. Pain and fatigue perception was compared between the two groups after adjusting for age, sex, MDHAQ FN and DAS 28. RESULTS: Turkish patients had less pain than their US counterparts when adjusted for MDHAQ FN, DAS 28, age and sex (3.56 (2.24) vs. 4.35 (2.23), p=0.005) whereas there was no difference in fatigue between the two groups (3.85 (2.44) vs. 4.25 (2.45), p=0.194). When the patients with a DAS28 score of above 5.1 and below 2.6 were compared in both groups, Turkish patients had again less pain albeit less in the high disease activity group. CONCLUSIONS: This study suggests that Turkish patients have less pain than the US patients when controlled for age, gender and MDHAQFN and DAS28 scores. This is at odds to the conventional wisdom that pain perception is increased among the non-Western cultures.
19435719 Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study. 2010 May OBJECTIVE: A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. METHODS: A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the chi(2) test using Stata. RESULTS: Association to the CD40 gene was robustly replicated (p=2 x 10(-4), OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8 x 10(-8), OR 0.87 (95% CI 0.83 to 0.92). CONCLUSION: In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus.
21517638 Aggressive treatment of early rheumatoid arthritis: recognizing the window of opportunity 2010 Nov Evidence supports the use of aggressive therapy for patients with early rheumatoid arthritis (RA). Clinical outcomes in patients with early RA can improve with a treat-to-target approach that sets the goal at disease remission. The current selection of antirheumatic therapies, including conventional and biologic disease-modifying antirheumatic drugs (DMARDs), has made disease remission a realistic target for patients with early RA. The challenge is selecting the optimal antirheumatic drug or combination of drugs for initial and subsequent therapy to balance the clinical benefits, risks, and economic considerations. In some cases, the use of biologic agents as part of the treatment regimen has shown superior results compared with conventional DMARDs alone in halting the progression of disease, especially in reducing radiographic damage. However, the use of biologic agents as initial therapy is challenged by cost-effectiveness analyses, which favor the use of conventional DMARDs. The use of biologic agents may be justified in certain patients with poor prognostic factors or those who experience an inadequate response to conventional DMARDs as a means to slow or halt disease progression and its associated disability. In these cases, the higher cost of treatment with biologic agents may be offset by decreased societal costs, such as lost work productivity, and increased health-related quality of life. Further research is needed to understand optimal strategies for balancing costs, benefits, and risks of antirheumatic drugs. Some key questions are (1) when biologic agents are appropriate for initial therapy, and (2) when to conclude that response to conventional DMARDs is inadequate and biologic agents should be initiated.
19562403 Patients' perceptions of health-related quality of life in rheumatoid arthritis. 2009 Oct The purpose of this study is to determine how health-related quality of life (HRQL) is perceived by patients with rheumatoid arthritis using textual analysis and to identify associations between sociodemographic and clinical variables and patients' perceptions. Multicentre, cross-sectional study, including 781 patients (78.8% females, mean age 60.65 years, standard deviation 14.22). Sociodemographic and clinical variables were collected. A questionnaire was used which included an open question, "What does HRQL mean to you?" Cluster analysis was used, and answers to the open question were analysed using textual analysis. Cluster analysis showed three typologies differentiated by gender, age, and socioeconomic level and by the terms used to describe perceptions of HRQL with no marked clinical differences. Characteristic phrases were "to be totally independent, to have no pain, and to do things without thinking about the negative effects" (typology 1); "to have no pain and control my moods and my illness has made me a little excitable" (typology 2); and "to feel well enough to do things for myself" (typology 3). Three representative typologies of patients were identified who differed clearly in their perceptions of HRQL. Textual analysis may be considered as a valid tool for the analysis of complex issues such as quality of life.
20192993 Role of HLA class II genes in susceptibility/resistance to inflammatory arthritis: studies 2010 Jan Predisposition to develop rheumatoid arthritis (RA) has been associated with certain human leukocyte antigen (HLA) class II molecules, although the mechanism is still unknown. Various experimental animal models of inflammatory arthritis have been studied to address the role of major histocompatibility complex (MHC) genes in pathogenesis. We have generated transgenic mice expressing HLA class II molecules (DR and DQ) lacking complete endogenous class II molecules to study the interactions involved between class II molecules (DQ and DR) and to define the immunologic mechanisms in inflammatory arthritis. The HLA transgene can positively select CD4(+) T cells expressing various V beta T-cell receptors, and a peripheral tolerance is maintained to transgenic HLA molecules. The expression of HLA molecules on various cells in these mice is similar to that known in humans. In this review, we describe collagen-induced arthritis as a model for human inflammatory arthritis using these transgenic mice. The transgenic mice carrying RA-susceptible haplotype develop gender-biased inflammatory arthritis with clinical and histopathological similarities to RA. Our studies show that polymorphism of HLA class II genes determine the predisposition to rheumatoid/inflammatory arthritis and the epistatic interactions between HLA-DQ and HLA-DR molecules dictate the severity, progression, and modulation of the disease.
19327237 Positive treatment response improves the health-related quality of life of patients with e 2009 Jan OBJECTIVE: To examine treatment induced changes in health-related quality of life (HR-QoL) in patients with early rheumatoid arthritis (RA). METHODS: Changes in HR-QoL were assessed by the Nottingham Health Profile (NHP) instrument in 62 consecutive working age patients with recent onset RA with duration of symptoms of less than two years and naive with regard to disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids. Treatment-response was assessed by the criteria of the European League against Rheumatism (EULAR; 28-joint score; DAS28) at 6 months. RESULTS: NHP mean scores for pain (p=0.029) and emotional reaction (p=0.035) at baseline were related to EULAR response at 6 months, i.e. non-responders had the poorest baseline HR-QoL scores. When the patients were grouped according to EULAR response at 6 months there was a statistically significant mean linear change to better HR-QoL in NHP energy (p=0.0023), pain (p<0.001) and mobility (p=0.0085) from baseline to 6 months from the lowest to highest treatment-response level. CONCLUSION: Our results show that good treatment-response as measured by the EULAR response criteria translates into improved HR-QoL dimensions for energy, pain and mobility.
20536603 Miliary tuberculosis and necrotizing tuberculous fasciitis--an unusual coexistence in a rh 2010 May We report a case of a 65-year-old Korean female patient with rheumatoid arthritis, who presented with extensive necrotizing fasciitis of the gluteus muscles, as an unusual initial manifestation of miliary tuberculosis. The patient had been previously treated with conventional disease-modifying antirheumatic drugs and low-dose steroids for 7 years. However, she recently developed fever, warmth and painful swelling in her right buttock. Magnetic resonance imaging indicated necrotizing fasciitis of the gluteus muscles and a fasciectomy specimen revealed a Mycobacterium tuberculosis infection. Two weeks after a fasciectomy, miliary tuberculosis of the lung was diagnosed by high resolution chest computed tomography. Soft tissue infection due to M. tuberculosis should be included as a differential diagnosis in the immunocompromised host. Clinicians should be alert to the possibility of miliary tuberculosis even in the absence of respiratory symptoms and normal chest radiograph.