Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
24804270 Anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti 2014 We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P = 0.40 and P = 0.91, resp.). Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF); (P = 0.01), anti-CCP (P = 0.048), and anti-MCV (P = 0.02). Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di) (r = 0.154, P = 0.03), erythrocyte sedimentation rate (ESR); (r = 0.155, P = 0.03), and RF (P = 0.254, P < 0.001), whereas anti-MCV titres only correlated with RF (r = 0.169, P = 0.02). On adjusted analysis, ExRA was associated with longer age (P = 0.015), longer disease duration (P = 0.007), higher DAS-28 score (P = 0.002), and higher HAQ-DI score (P = 0.007), but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation.
25043000 Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis. 2014 Aug 7 Rheumatoid arthritis is a chronic autoinflammatory disease that affects 1-2% of the world's population and is characterized by widespread joint inflammation. Interleukin-1 is an important mediator of cartilage destruction in rheumatic diseases, but our understanding of the upstream mechanisms leading to production of interleukin-1β in rheumatoid arthritis is limited by the absence of suitable mouse models of the disease in which inflammasomes contribute to pathology. Myeloid-cell-specific deletion of the rheumatoid arthritis susceptibility gene A20/Tnfaip3 in mice (A20(myel-KO) mice) triggers a spontaneous erosive polyarthritis that resembles rheumatoid arthritis in patients. Rheumatoid arthritis in A20(myel-KO) mice is not rescued by deletion of tumour necrosis factor receptor 1 (ref. 2). Here we show, however, that it crucially relies on the Nlrp3 inflammasome and interleukin-1 receptor signalling. Macrophages lacking A20 have increased basal and lipopolysaccharide-induced expression levels of the inflammasome adaptor Nlrp3 and proIL-1β. As a result, A20-deficiency in macrophages significantly enhances Nlrp3 inflammasome-mediated caspase-1 activation, pyroptosis and interleukin-1β secretion by soluble and crystalline Nlrp3 stimuli. In contrast, activation of the Nlrc4 and AIM2 inflammasomes is not altered. Importantly, increased Nlrp3 inflammasome activation contributes to the pathology of rheumatoid arthritis in vivo, because deletion of Nlrp3, caspase-1 and the interleukin-1 receptor markedly protects against rheumatoid-arthritis-associated inflammation and cartilage destruction in A20(myel-KO) mice. These results reveal A20 as a novel negative regulator of Nlrp3 inflammasome activation, and describe A20(myel-KO) mice as the first experimental model to study the role of inflammasomes in the pathology of rheumatoid arthritis.
23601129 The combined use of disease activity and infliximab serum trough concentrations for early 2013 Dec AIM: Early prediction of (non-)response to infliximab therapy can improve therapeutic benefit by avoiding unnecessary periods of high disease activity during ineffective therapy. This prospective cohort study therefore aimed to study the predictive value of (1) disease activity alone and (2) infliximab serum trough concentrations in addition to disease activity 6 weeks after start of treatment for achieving low disease activity after 6 months. METHODS: Disease activity and infliximab serum trough concentrations were assessed in all rheumatoid arthritis (RA) patients at 2, 6 and 26 weeks after initiation of infliximab therapy. Receiver operating characteristic (ROC) curves and Youden indices were used to calculate specificity for prediction of good response after 6 months while aiming for maximum sensitivity. RESULTS: Fifty-seven consecutive RA patients starting with infliximab therapy were included. After 6 months, 15 (26%, 95 % CI 15, 38%) patients reached good European League against Rheumatism (EULAR) response. A disease activity score <4.2 at 6 weeks after initiation of therapy was a moderate predictor for reaching EULAR response after 6 months (sensitivity 100%, specificity 49%). Infliximab serum trough concentrations (>2.5 mg l(-1)) as predictor complimentary to disease activity (<4.2) slightly increased the specificity from 49% to 54% without changing the sensitivity (100%). As 39% of the patients did not fulfill at least one of these criteria at week 6, these patients could already be switched to another therapy after 6 weeks. CONCLUSIONS: The combination of disease activity and infliximab serum trough concentrations could be a fair predictor to identify early (after 6 weeks) patients who have insufficient response after 6 months of therapy.
24265411 Personalised treatment using serum drug levels of adalimumab in patients with rheumatoid a 2015 Feb OBJECTIVE: To evaluate the cost-effectiveness of personalised treatment for rheumatoid arthritis (RA) using clinical response and serum adalimumab levels. METHODS: A personalised treatment algorithm defined, based on clinical (European League Against Rheumatism) response and drug levels at 6 months, whether adalimumab treatment should be continued in a specific dose or discontinued and/or switched to a next biological. Outcomes were simulated using a patient level Markov model, with 3 months cycles, based on a cohort of 272 adalimumab-treated patients with RA for 3 years and data of patients from the Utrecht Rheumatoid Arthritis Cohort. Costs, clinical effectiveness and quality adjusted life years (QALYs) were compared with outcomes as observed in usual care and incremental cost-effectiveness ratios were calculated. Analyses were performed probabilistically. RESULTS: Clinical effectiveness was higher for the cohort simulated to receive personalised care compared with usual care; the average difference in QALYs was 3.84 (95 percentile range -8.39 to 16.20). Costs were saved on drugs: €2 314 354. Testing costs amounted to €10 872. Mean total savings were €2 561 648 (95 percentile range -3 252 529 to -1 898 087), resulting in an incremental cost-effectiveness ratio of €666 500 or €646 266 saved per QALY gained from a societal or healthcare perspective, respectively. In 72% of simulations personalised care saved costs and resulted in more QALYs, in 28% it was cost saving with lower QALYs. Scenario analyses showed cost saving along with QALYs gain or limited loss. CONCLUSIONS: Tailoring biological treatment to individual patients with RA starting adalimumab using drug levels and short-term outcome is cost-effective. Results underscore the potential merit of personalised biological treatment in RA.
23399828 Periarticular osteoporosis is a prominent feature in early rheumatoid arthritis: estimatio 2013 Feb We aimed to quantify periarticular osteoporosis and investigate its significance in 45 patients with rheumatoid arthritis (RA) and 106 controls. Dual-energy X-ray absorptiometry (DXA) was used to determine the ratio of shaft to periarticular bone mineral density (BMD) as an index of periarticular demineralization. Periarticular osteoporosis was measured by conventional radiography. The BMDs of shaft and periarticular regions in eight designated areas on proximal phalanges were quantified. Clinical variables were examined to identify risk factors for periarticular osteoporosis. The assessment of periarticular osteoporosis on X-ray images reached a moderate degree of interobserver agreement among four physicians (ĸ = 0.47). For BMD quantification, we designed three types of mathematical formulae: the ratio of shaft to periarticular BMD, the mean of the ratios, and the ratio of the sums. These ratios were significantly higher in the patients with early RA (disease duration ≤ 3 yr) than in controls (P < 0.01). The findings were not as distinctive in patients with established RA. Body mass index, cumulative dose of corticosteroid, and C-terminal telopeptide were correlated with BMD ratios. Conclusively, DXA-assisted localized quantification and BMD ratio calculations are feasible for assessing periarticular demineralization. Periarticular osteoporosis is a relatively distinctive feature of early RA.
23695990 Using actigraphy to measure sleep patterns in rheumatoid arthritis: a pilot study in patie 2013 Sep OBJECTIVE: Poor sleep quality is a commonly reported but under-investigated consequence of rheumatoid arthritis (RA). Actigraphy is a non-invasive way of measuring sleep, estimated from the frequency and intensity of physical movement at the wrist. We used actigraphy to measure sleep parameters compared with sleep questionnaire data, and assessed the practicality of actigraph use in patients with RA. METHODS: In a pilot study of actigraphy conducted within an investigation of night-time prednisone treatment and circadian interleukin-6 concentrations in ten patients with active RA, we compared actigraphy with the St Mary's Hospital Sleep Questionnaire and assessed whether night-time administration of prednisone resulted in increased sleep disturbance. RESULTS: The actigraph watch was well tolerated by our patients, producing adequate data for analysis for 128 out of 133 test days (96.2%). The results indicated reasonable concordance between actigraph and sleep questionnaire data in the present sample. Patient satisfaction with sleep (question 11) strongly correlated with sleep efficiency measured by the actigraph (r = 0.71, p = 0.22) and showed a trend for inverse correlation with the fragmentation index (r = -0.60, p = 0.067). Quality of sleep (question 9) correlated non-significantly with the fragmentation index (r = -0.59, p = 0.072). We were unable to identify any significant correlations between clinical measures of disease and sleep parameters in this sample. There were no apparent detrimental consequences of the night-time dose of prednisone on the measures of sleep quality and quantity. CONCLUSION: In spite of the physical disability imposed by RA, the actigraph was well tolerated and gave a useful measure of sleep in patients with active disease. It has the potential for use in larger controlled trials.
24618272 Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracel 2016 Apr AIM: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. METHODS: Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. RESULTS: Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). CONCLUSION: Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy.
23553228 Toxoplasma gondii: bystander or cofactor in rheumatoid arthritis. 2013 Jul Parasitic infections may induce variable immunomodulatory effects and control of autoimmune disease. Toxoplasma gondii (T. gondii) is a ubiquitous intracellular protozoan that was recently associated with autoimmunity. This study was undertaken to investigate the seroprevalence and clinical correlation of anti-T. gondii antibodies in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We evaluated sera from European patients with RA (n = 125) and SLE (n = 164) for the prevalence of anti-T. gondii IgG antibodies (ATXAb), as well as other common infections such as Cytomegalovirus, Epstein-Barr, and Rubella virus. The rates of seropositivity were determined utilizing the LIAISON chemiluminescent immunoassays (DiaSorin, Italy). Our results showed a higher seroprevalence of ATXAb in RA patients, as compared with SLE patients [63 vs. 36 %, respectively (p = 0.01)]. The rates of seropositivity of IgG against other infectious agents were comparable between RA and SLE patients. ATXAb-seropositivity was associated with older age of RA patients, although it did not correlate with RA disease activity and other manifestations of the disease. In conclusion, our data suggest a possible link between exposure to T. gondii infection and RA.
24956925 An administrative data validation study of the accuracy of algorithms for identifying rheu 2014 Jun 23 BACKGROUND: We have previously validated administrative data algorithms to identify patients with rheumatoid arthritis (RA) using rheumatology clinic records as the reference standard. Here we reassessed the accuracy of the algorithms using primary care records as the reference standard. METHODS: We performed a retrospective chart abstraction study using a random sample of 7500 adult patients under the care of 83 family physicians contributing to the Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Using physician-reported diagnoses as the reference standard, we computed and compared the sensitivity, specificity, and predictive values for over 100 administrative data algorithms for RA case ascertainment. RESULTS: We identified 69 patients with RA for a lifetime RA prevalence of 0.9%. All algorithms had excellent specificity (>97%). However, sensitivity varied (75-90%) among physician billing algorithms. Despite the low prevalence of RA, most algorithms had adequate positive predictive value (PPV; 51-83%). The algorithm of "[1 hospitalization RA diagnosis code] or [3 physician RA diagnosis codes with ≥1 by a specialist over 2 years]" had a sensitivity of 78% (95% CI 69-88), specificity of 100% (95% CI 100-100), PPV of 78% (95% CI 69-88) and NPV of 100% (95% CI 100-100). CONCLUSIONS: Administrative data algorithms for detecting RA patients achieved a high degree of accuracy amongst the general population. However, results varied slightly from our previous report, which can be attributed to differences in the reference standards with respect to disease prevalence, spectrum of disease, and type of comparator group.
23560463 Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: histology, 2013 Jul OBJECTIVES: Patients with rheumatoid arthritis (RA) may develop lymphoproliferative disorders (RA-LPD). Immunosuppressive states due to methotrexate (MTX) and Epstein-Barr virus (EBV) reactivation have been regarded as causes. Sometimes spontaneous regression occurs after withdrawal of MTX. The objective of this study was to identify factors predictive of relapse and survival in patients with RA-LPD, and spontaneous regression in patients with RA-LPD treated with MTX (MTX-LPD). METHODS: We evaluated the clinicopathological features, clinical characteristics, and treatment outcomes in 102 cases of RA-LPD. In addition, EBV infection and clonality of immunoglobulin heavy chain gene (IGH) were analyzed by in situ hybridization and polymerase chain reaction, respectively. RESULTS: The 102 cases included patients with diffuse large B-cell lymphoma (DLBCL; n = 53), Hodgkin lymphoma (n = 9), polymorphic B-cell LPD (n = 20), reactive lymphadenitis (n = 11), peripheral T-cell lymphoma (PTCL; n = 4), composite lymphoma (n = 2), and follicular lymphoma (n = 3). EBV was detected in 60% (56/93) of patients. Spontaneous regression occurred in 59% (28/47) of patients in whom MTX was withdrawn. Regression was associated with EBV positivity (P = 0.007) and non-DLBCL (P = 0.006), but not with MTX amount and other clinical features. Monoclonal bands of IGH were observed in 31 of 74 cases. In patients with DLBCL, poor disease-free survival (P = 0.05) was associated with clonality of IGH. In all patients, factors predictive of shorter survival were age (>70 yr) and histological type of DLBCL. CONCLUSIONS: Histology, EBV positivity, and monoclonality of IGH are useful for predicting clinical outcomes in patients with RA-LPD.
23908443 Prevalence of anti-peptidylarginine deiminase type 4 antibodies in rheumatoid arthritis an 2013 Sep OBJECTIVE: To determine whether anti-peptidylarginine deiminase type 4 (PAD4) antibodies were present in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA) in 2 indigenous North American populations with high prevalence of RA. METHODS: Participants were recruited from 2 indigenous populations in Canada and the United States, including patients with RA (probands), their unaffected FDR, and healthy unrelated controls. Sera were tested for the presence of anti-PAD4 antibodies, anticyclic citrullinated peptide (anti-CCP) antibodies, and rheumatoid factor (RF). HLA-DRB1 subtyping was performed and participants were classified according to number of shared-epitope alleles present. RESULTS: Antibodies to PAD4 were detected in 24 of 82 (29.3%) probands; 2 of 147 (1.4%) relatives; and no controls (p < 0.0001). Anti-CCP was present in 39/144 (27.1%) of the relatives, and there was no overlap between positivity for anti-CCP and PAD4 in the relatives. In RA patients, anti-PAD4 antibodies were associated with disease duration (p = 0.0082) and anti-CCP antibodies (p = 0.008), but not smoking or shared-epitope alleles. CONCLUSION: Despite a significant prevalence of anti-CCP in FDR, anti-PAD4 antibodies were almost exclusively found in established RA. The prevalence of anti-PAD4 antibodies in RA is similar to the prevalence described in other populations and these autoantibodies are associated with disease duration and anti-CCP in RA.
24016323 The potential of stem cell therapy for osteoarthritis and rheumatoid arthritis. 2013 Nov Joint diseases are a major cause of disability and are a significant financial burden on health care systems. Regenerative medicine offers exciting possibilities for treating osteoarthritis and rheumatoid arthritis. As well as possessing the ability to differentiate into other tissue lineages, some stem cells such as mesenchymal stem cells possess immmunomodulatory properties that make them useful in the search for alternative treatments for rheumatoid arthritis specifically. Various studies have been carried out using animal models to evaluate the role of stem cells in the treatment of arthritis, with some research being translated into clinical studies. However, the number of patients used in some studies has left questions on the ability of stem cell therapy to treat arthritic conditions unanswered. This article reviews the innovative studies that have been carried out to treat arthritis using stem cells and also highlights the key challenges associated with these techniques.
24568534 Examining the effects of perceived social support on momentary mood and symptom reports in 2014 OBJECTIVE: Social support has been linked to beneficial effects on health directly (main effect) and as a buffer to stress. Most research, however, has examined these relationships using global and retrospective assessments of health and stress, which may be subject to recall biases. This study used ambulatory ecological momentary assessment (EMA) methods to test the main and stress-buffering effects of social support on the daily health and well-being of asthma and rheumatoid arthritis (RA) patients. DESIGN: Community volunteers with asthma (n = 97) or RA (n = 31) responded to EMA prompts five times daily for one week. MAIN OUTCOMES: Baseline perceived social support was obtained, and then, participants reported mood, stress and symptoms using EMA. Multilevel mixed-modelling examined whether social support predicted mood and symptoms directly or via stress-reducing effects. RESULTS: Supporting a main effect, more perceived social support predicted decreased negative mood and stress severity. Supporting a stress-buffering effect, more perceived social support resulted in fewer reported symptoms when stress was present. CONCLUSION: Results suggest perceived social support directly relates to better ambulatory status and dynamically buffers individuals against the negative effects of stressors, and highlight the importance of studying social support across different temporal and contextual levels.
24884454 Safety of infusing rituximab at a more rapid rate in patients with rheumatoid arthritis: r 2014 May 24 BACKGROUND: As recommended in the current prescribing information, rituximab infusions in patients with rheumatoid arthritis (RA) take 4.25 hours for the first infusion and 3.25 hours for subsequent infusions, which is a burden on patients and the health care system. We therefore evaluated the safety of infusing rituximab at a faster rate for an infusion period of 2 hours in patients with RA. METHODS: Patients with an inadequate response to anti-TNF who were rituximab-naive or -experienced received 2 courses of rituximab: Infusion 1 (Day 1) was administered over the standard 4.25 hours, and Infusions 2 (Day 15), 3 (Day 168) and 4 (Day 182) were administered over a faster 2-hour period. The primary endpoint was incidence of infusion-related reactions (IRRs) associated with Infusion 2. RESULTS: Of the 351 patients enrolled, 87% and 13% were rituximab-naive and -experienced, respectively. The incidence (95% CI) of IRRs associated with Infusion 1 was 16.2% (12.5%, 20.5%) and consistent with weighted historical incidence of 20.7% (19.4%, 22.1%). The incidence (95% CI) of IRRs associated with Infusions 2, 3, and 4 compared with respective weighted historical incidences at the standard infusion rate was 6.5% (4.1%, 9.7%) vs 8.1% (7.2%, 9.1%); 5.9% (3.5%, 9.3%) vs 11.5% (10.3%, 12.8%); and 0.7 (0.1%, 2.6%) vs 5.0% (4.2%, 6.0%), respectively. All IRRs were grade 1 or 2, except for 3 grade 3 IRRs associated with Infusion 1 and 2 grade 3 IRRs associated with Infusion 2. Four patients experienced a total of 5 grade 3 IRRs; 3 of these patients continued on to received subsequent infusions at the faster rate. There were no serious IRRs. CONCLUSION: This study demonstrated that rituximab can be administered at the faster infusion rate at the second and subsequent infusions without increasing the rate or severity of IRRs.
24219764 Rituximab-induced interleukin-15 reduction associated with clinical improvement in rheumat 2014 Jul Rituximab therapy alters all aspects of B-cell participation in the disturbed immune response of rheumatoid arthritis patients. To determine the impact of B-cell depletion on other immune compartments, we analysed levels of soluble and surface interleukin-15 (IL-15) along with the frequency of IL-15-related subsets after rituximab treatment. We then studied the correlation of observed changes with clinical activity. Heparinized blood samples from 33 rheumatoid arthritis patients were collected on days 0, 30, 90 and 180 after each of three rituximab cycles. Serum cytokine levels were determined by ELISA. Interleukin-15 trans-presentation was analysed by cytometry. Flow cytometry with monoclonal antibodies was performed to analyse circulating cell subsets. Interleukin-15 was detected in the serum of 25 patients before initiating the treatment. Rituximab then progressively reduced serum IL-15 (138 ± 21 pg/ml at baseline, 48 ± 18 pg/ml after third cycle, P = 0·03) along with IL-17 (1197 ± 203 pg/ml at baseline, 623 ± 213 pg/ml after third cycle, P = 0·03) and tended to increase the frequency of circulating regulatory T cells (3·1 ± 1 cells/μl at baseline, 7·7 ± 2 cells/μl after third cycle). Rituximab also significantly decreased IL-15 trans-presentation on surface monocytes of patients negative for IL-15 serum (mean fluorescence intensity: 4·82 ± 1·30 at baseline, 1·42 ± 0·69 after third cycle P = 0·05). Reduction of serum IL-15 was associated with decrease in CD8(+)  CD45RO(+) /RA(+) ratio (1·17 ± 0·21 at baseline, 0·36 ± 0·06 at third cycle, P = 0·02). DAS28, erythrocyte sedimentation rate and C-reactive protein correlated significantly with CD8(+)  CD45RO(+) /RA(+) ratio (R = 0·323, R = 0·357, R = 0·369 respectively, P < 0·001). Our results suggest that sustained clinical improvement after rituximab treatment is associated with IL-15/memory T-cell-related mechanisms beyond circulating B cells.
24677768 DTB Select: 4 | April 2014. 2014 Apr Every month, DTB scans sources of information on treatments, disease management and other healthcare topics for key items to bring to our readers' attention and help them keep up to date. To do this, we produce succinct, contextualised summaries of the information concerned. We also include comments on, for example, the strengths of the information, whether it contains anomalies, ambiguities, apparent error or omissions, or whether or how it affects current practice.
23179262 Impact of modified-release prednisone on functional ability in patients with rheumatoid ar 2013 Jun This observational study assessed functional ability in patients treated with modified-release prednisone under conditions of normal clinical practice. Patients treated with modified-release prednisone were observed over 9 months. The primary outcome measure was the change from baseline total score using the Questionnaire on Activity Status (QAS); total QAS score ranges from 0 (severely impaired) to 100 (completely unimpaired). Other measures included Visual Analogue Scale (VAS) from 0 to 10 (where 10 = full daily performance) and Health Assessment Questionnaire Disability Index (HAQ-DI). There were no restrictions on dose of modified-release prednisone or use of concomitant therapy. A total of 1,733 patients were included in the study, with valid observations at baseline and study end for 1,185 patients (thereof 74 % female, median age 59 years, median disease duration 5 years). Mean total QAS score improved significantly after 9 months of treatment with modified-release prednisone from 54.3 to 70.2 (p < 0.001). There were also significant (p < 0.001) improvements in all three QAS dimensions (occupational performance: 66.6-78.9; household duties: 55.6-70.9; leisure activities: 51.6-69.4), daily performance (mean VAS 5.1-7.0; p < 0.001) and mean HAQ-DI score (1.35-1.00; p < 0.001). Dose of modified-release prednisone was significantly reduced (from 5.0 to 4.4 mg/day, p < 0.001) and fewer patients required biological rheumatoid arthritis (RA) treatments, analgesia and gastroprotectants. Functional ability in patients with RA improved significantly from baseline after 9 months of treatment with modified-release prednisone. This observational study, conducted under daily-practice conditions, confirms the beneficial effects of modified-release prednisone shown previously in randomised controlled trials.
23743624 Do impaired memory, cognitive dysfunction and distress play a role in methotrexate-related 2013 Oct We evaluated the roles of sociocultural status, distress and cognitive functions in rheumatoid arthritis (RA) patients who developed methotrexate (MTX)-related neutropenia. The data of 37 RA patients with MTX-related neutropenia who were being followed up at 3 centers were evaluated. The control group included 74 RA patients. The clinical features, biochemical tests and treatment modalities of the patients were obtained from hospital files. The mini-mental state examination (MMSE) test and the Hospital Anxiety and Depression Scale (HADS) were administered for all RA patients with neutropenia as well as the control group. The frequencies of male patients, illiterate patients, patients living alone, patients with serious visual impairment, those with low income, and patients with high creatinine were significantly higher among RA patients with MTX-related neutropenia than in controls (p values <0.05). The RA patients with MTX-related neutropenia had significantly lower MMSE scores, and significantly higher HADS-A and HADS-D scores than controls (p values <0.05). In addition, the proportion of patients with probable dementia was significantly higher in RA patients with MTX-related neutropenia than in controls (p < 0.001). Twenty-six of the 37 patients (70.3 %) developed neutropenia with daily dosing. Patients who used MTX daily were more likely to be living alone than those using weekly dosing (p = 0.011). Multivariate analysis showed that having probable dementia on the MMSE test (OR 52.6), low income level (OR 56.8) and age (OR 1.12) were independent risk factors for the development of MTX-related neutropenia. The presence of probable dementia on MMSE, low socioeconomical status and older age are associated with serious toxicity in RA patients using MTX. Measures should be taken to prevent wrong MTX dosing by the patients. Compliance and patient education is of major importance, in particular, in the patients presented in this study.
23581251 Change in Gait Deviation Index after anti-tumour necrosis factor-α treatment in individua 2013 OBJECTIVES: Anti-tumour necrosis factor-alpha (TNF-α) inhibitors provide fast, effective resolution of rheumatoid arthritis (RA) inflammation. In this study we aimed to quantify the impact of TNF-α treatment on gait dynamics. METHOD: The sample comprised 16 subjects [11 female, median age 56 (range 48-66) years, median disease duration 9.5 (range 4.6-20.6) years] with RA who met the American College of Rheumatology (ACR) criteria, had lower extremity involvement, did not use walking aids, and had started TNF-α treatment within 1 week of baseline gait analysis. Gait analysis focused on three-dimensional (3D) lower extremity joint kinematics, kinetics, time and distance parameters. The Gait Deviation Index (GDI) and GDI-Kinetic were calculated. Data on gait, disease activity, and physical disability were collected at baseline and at 3.5 months. RESULTS: Following treatment with TNF-α, statistically significant improvements were found in disease activity [using the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP); median difference (m(d)) = 2.3, p < 0.01], physical disability [Health Assessment Questionnaire (HAQ) m(d) = 0.4, p < 0.01], and pain during walking [visual analogue scale (VAS) m(d) = 11.0, p < 0.05]. Reductions in gait deviations were noted (GDI m(d) = 3.7, p = 0.04; GDI-Kinetic m(d) = 4.1, p = 0.05) along with reductions in dimensionless time and distance parameters. A moderate to good negative correlation existed between baseline GDI and GDI change scores (r(s) = -0.7, p < 0.01). CONCLUSIONS: Treatment with TNF-α improved gait dynamics in adults with RA. Significant gait deviations were, however, still present after treatment. In this study, GDI and GDI-Kinetic scores appeared to be useful outcome measures to quantify changes in gait deviations after this intervention.
25437122 Approach to the diagnosis of unusual carpal ankylosis from ancient Egypt. 2015 Jan OBJECTIVES: Carpal fusion is not an uncommon finding in archaeological bones. The majority of cases are due to inflammatory or infectious diseases and those are usually associated with other major alterations in the skeleton. METHODS: Two distinct individual cases, both adult females recovered from the Necropolis of Sharuna in the Middle Egypt from the Ptolemaic Period (IV to I BC) are presented in this study. Specimen 4323/1 shows a fusion of the scaphoid, lunate and triquetral bones in the right wrist. Specimen 4323/2 is a very rare fusion of a dysplastic lunate bone with the radius in the left wrist. In the proximal end of that left wrist, two possible remains of the flattened scaphoid and triquetral bones are also present. RESULTS: A differential diagnosis of both abnormalities as well as broad research into similar paleopathological cases were carried out: the most probable diagnosis for the specimen 4323/1 is an uncommon carpal coalition of three bones from the same row; the diagnosis of the specimen 4323/2 is more dubious with both rheumatoid arthritis and septic arthritis being strong candidates. CONCLUSIONS: In archaeological remains, carpal fusion should be thoroughly studied in order to ensure an accurate differential diagnosis.