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24095940 Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: re 2014 Jan BACKGROUND: PATIENTS with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions. OBJECTIVES: To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide. STUDY DESIGN: international, cross-sectional. PATIENTS: consecutive RA patients. DATA COLLECTED: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric disorders). RESULTS: Of 4586 patients recruited in 17 participating countries, 3920 were analysed (age, 56±13 years; disease duration, 10±9 years (mean±SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)-erythrocyte sedimentation rate, 3.7±1.6 (mean±SD); Health Assessment Questionnaire, 1.0±0.7 (mean±SD); past or current methotrexate use, 89%; past or current use of biological agents, 39%. The most frequently associated diseases (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry variability was observed for both the prevalence of comorbidities and the proportion of subjects complying with recommendations for preventing and managing comorbidities. The systematic evaluation of comorbidities in this study detected abnormalities in vital signs, such as elevated blood pressure in 11.2%, and identified conditions that manifest as laboratory test abnormalities, such as hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%. CONCLUSIONS: Among RA patients, there is a high prevalence of comorbidities and their risk factors. In this multinational sample, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities. Systematic measurement of vital signs and laboratory testing detects otherwise unrecognised comorbid conditions.
23954014 Pulmonary cryptococcosis in rheumatoid arthritis (RA) patients: comparison of imaging char 2013 Nov PURPOSE: The imaging characteristics of cryptococcosis in rheumatoid arthritis (RA) patients were analyzed by comparing them with those of acquired immunodeficiency syndrome (AIDS) and immunocompetent patients, and the imaging findings were correlated with pathological findings. METHODS: Two radiologists retrospectively compared the computed tomographic (CT) findings of 35 episodes of pulmonary cryptococcosis in 31 patients with 3 kinds of underlying states (10 RA, 12 AIDS, 13 immunocompetent), focusing on the nature, number, and distribution of lesions. The pathological findings of 18 patients (8 RA, 2 AIDS, 8 immunocompetent) were analyzed by two pathologists, and then correlated with imaging findings. RESULTS: The frequencies of consolidation and ground glass attenuation (GGA) were significantly higher, and the frequency of peripheral distribution was significantly lower in the RA group than in the immunocompetent group. Peripheral distribution was less common and generalized distribution was more frequent in the RA group than in the AIDS group. The pathological findings of the AIDS and immunocompetent groups reflected their immune status: There was lack of a granuloma reaction in the AIDS group, and a complete granuloma reaction in the immunocompetent group, while the findings of the RA group varied, including a complete granuloma reaction, a loose granuloma reaction and a hyper-immune reaction. Cases with the last two pathologic findings were symptomatic and showed generalized or central distribution on CT. CONCLUSION: Cryptococcosis in the RA group showed characteristic radiological and pathological findings compared with the other 2 groups.
24643396 Preclinical rheumatoid arthritis (autoantibodies): an updated review. 2014 May Multiple studies demonstrate that there is a period of development of rheumatoid arthritis (RA) during which there are elevations of disease-related biomarkers, including autoantibodies, in the absence of and prior to the development of RA; this period can be termed 'preclinical RA'. These 'preclinical' autoantibodies including rheumatoid factor and antibodies to citrullinated protein antigens, and more recent studies have also identified additional autoantibodies and a wide range of inflammatory biomarkers. These findings in conjunction with established and emerging data about genetic and environmental risk factors for RA support a model of disease development where certain factors lead to an initial triggering of RA-related autoimmunity that expands over time to the point where symptomatic arthritis classifiable as RA develops. Herein will be reviewed updates in the field, as well as a discussion of current limitations of our understanding of preclinical RA, and potential future directions for study.
24023053 Tumor necrosis factor α inhibitor use and decreased risk for incident coronary events in 2014 Mar OBJECTIVE: To determine the association of tumor necrosis factor α (TNFα) inhibitors with risk for cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients. METHODS: A retrospective cohort of 2,101 incident RA patients was established. Medication exposure was categorized into the following groups: TNFα inhibitors alone or in combination with methotrexate (MTX; aTNF group); MTX alone or in combination with other nonbiologic disease-modifying antirheumatic drugs (DMARDs; MTX group); and no MTX, nonbiologic DMARDs (reference group). Primary outcome was adjudicated incident coronary artery disease (CAD), defined as myocardial infarction, unstable angina, or coronary revascularization procedure. Secondary outcome was adjudicated incident CVD, defined as a composite of CAD, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure. Cox regression models were used to calculate the hazard ratio for CAD and CVD for the aTNF and MTX groups compared to the reference group. RESULTS: There were 46 incident CAD and 82 incident CVD events. Adjusting for covariates associated with CAD and CVD, the hazard ratio for incident CAD was 0.45 (95% confidence interval [95% CI] 0.21-0.96) for the aTNF group and 0.54 (95% CI 0.27-1.09) for the MTX group compared to the reference group. Use of TNFα inhibitors for >16.1 months was associated with a relative risk for CAD of 0.18 (95% CI 0.06-0.50) and for CVD of 0.31 (95% CI 0.15-0.65) compared to the reference group. A similar, although not significant, trend was seen with the MTX group. CONCLUSION: Use of TNFα inhibitors is associated with a decreased risk for CAD in RA; the risk decreases further with long-term use. This should be considered when weighing the risks versus benefits of these medications.
25399388 Does socioeconomic status affect outcomes in early inflammatory arthritis? Data from a can 2015 Jan OBJECTIVE: To assess the effect of socioeconomic status (SES) on outcomes in patients with early inflammatory arthritis, using data from the Canadian Early Arthritis Cohort (CATCH) study. METHODS: In an incident cohort, 2023 patients were recruited, and allocated to low SES or high SES groups based on education and income. Outcomes at baseline and 12 months were analyzed in relation to SES including the 28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI), pain, patient's global assessment scale (PtGA), the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the SF12-v2 Health Survey, using the ANOVA, chi-squared test, and regression analyses. RESULTS: The CATCH population had 43% with high school education or less and 37% in the low-income group (< 50,000 Can$ per annum household income). The low-education group had higher DAS28 at baseline (p = 0.045), becoming nonsignificant at 12 months and lower physical component score on SF12-v2 at baseline (p = 0.022). Patients in the low-income group presented with higher HAQ-DI (p = 0.017), pain (p = 0.035), PtGA (p = 0.004), and SDAI (p = 0.022). Low-income versus high-income groups were associated with an OR above the median for HAQ-DI (1.20; 95% CI 1.00-1.45), PtGA (1.27; 95% CI 1.06-1.53), and SDAI (1.25; 95% CI 1.02-1.52) at baseline. The association with low income persisted at 12 months for HAQ-DI (OR 1.30; 95% CI 1.02-1.67), but not for other variables. CONCLUSION: Low SES was initially associated with higher disease activity, pain, and PtGA, and poorer function. At 1 year, outcomes were similar to those with high SES, with the exception of HAQ-DI.
24131910 A seroimmunological profile of erosive hand osteoarthritis. 2013 Jan OBJECTIVES: erosive hand osteoarthritis (EHOA) is an inflammatory disorder involving joints of the hands, which may be accompanied by acute phase reactants. The relationship between EHOA and classical osteoarthritis (OA) is still controversial, since some authors consider EHOA as a distinct disease, other as a subset of OA, and some as a border entity between OA and rheumatoid arthritis (RA). Scarce data are available about the seroimmunological profile of the disease, which could aid to identify a possible role of the immune system in EHOA pathogenesis, and could also allow to better differentiate EHOA both from OA and RA. MATERIAL AND METHODS: blood was drawn from the following patients: 37 with EHOA, 35 with OA and 45 with RA. All sera were tested for rheumatoid factor, anti-cyclic citrullinated peptide antibodies (anti-CCP), antinuclear antibodies (ANA), anti-extractable nuclear antigens (anti-ENA) and anti-neutrophil cytoplasmic antibodies (ANCA). RESULTS: ANCA were never detected in OA, whereas they were found in 7 (19%) EHOA and 8 (18%) RA patients; the difference between EHOA and OA was statistically significant (p<0.01). Anti-CCP antibodies, which were consistently negative in OA, were positive in 2 EHOA (5%) at a low titre and in 23 (51%) RA patients, usually at a very high titre. The difference between EHOA and OA was not statistically significant, while the number of RA positive patients was significantly higher (p<0.001). CONCLUSIONS: our findings suggest that the seroimmunological profile of EHOA is different from that of OA. In EHOA patients ANCA and anti-CCP antibodies might be either markers of inflammation involving neutrophils and/or markers of an underlying autoimmune process.
24642038 Biologics, cardiovascular effects and cancer. 2014 Mar 18 Rheumatoid arthritis (RA) is associated with increased cardiovascular risk. Treatment with tumor necrosis factor (TNF)-inhibitors leads to about a 50% reduction in the first cardiovascular event. TNF-inhibitors could transiently improve flow-mediated vasodilation and improve carotid intima-media thickness (ccIMT) during the treatment of RA. Treatment with TNF-inhibitors is associated with an increased total cholesterol (TC) and HDL-cholesterol (HDLc) level, without sustained change of the atherogenic index. The overall cancer risk in RA patients is comparable to that of the general population, but patients with RA slightly more often have lymphomas and lung tumors, and less often have colorectal and breast tumors in comparison to the general population. In randomized controlled trials (RCT) TNF-inhibitors did not increase the risk of solid malignancies, except for non-melanoma skin cancer (risk doubled compared to control treatment). Meta-analysis of registries and long-term extension studies showed no increased risk for total malignancies as well as for non-melanoma skin cancer when comparing TNF-inhibitors and the classical disease modifying anti-rheumatic drugs (DMARDs) treatment.
23982963 Local synovial engagement of angiogenic TIE-2 is associated with the development of persis 2013 Dec OBJECTIVE: To examine the role of vascular endothelial growth factor (VEGF) and angiopoietin signaling in the diagnosis and disease outcome of patients with early arthritis. METHODS: Fifty patients with early arthritis (disease duration <1 year) who had not been treated with disease-modifying antirheumatic drugs (DMARDs) were monitored prospectively and were classified at baseline and after 2 years as having undifferentiated arthritis (UA), rheumatoid arthritis (RA), or spondyloarthritis (SpA). All patients underwent arthroscopic synovial biopsy at baseline. Synovial expression of VEGF, VEGF receptor, angiopoietin 1 (Ang-1), Ang-2, TIE-2, and activated p-TIE-2 was evaluated by immunohistochemistry. Serum levels of VEGF, Ang-1, and Ang-2 were measured by enzyme-linked immunosorbent assay. Secreted products of macrophages stimulated with Ang-1 and Ang-2 were measured using a multiplex system. RESULTS: Expression of Ang-1 was comparable between the patients with RA at baseline and patients with UA who fulfilled the criteria for RA over time (UA/RA), and it was significantly higher in patients with RA (P < 0.05) or UA/RA (P < 0.005) than in patients with SpA. TIE-2 and p-TIE-2 were more highly expressed in patients with RA (P < 0.005) or UA/RA (P < 0.05) than in patients with SpA. Ang-1 significantly enhanced the tumor necrosis factor-dependent macrophage production of cytokines and chemokines that are known to be elevated in the synovial fluid of patients with early RA. In RA, relative TIE-2 activation predicted the development of erosive disease (R(2) = 0.35, P < 0.05). CONCLUSION: Local engagement of synovial TIE-2 is observed during the earliest phases of RA, suggesting that TIE-2 signaling may contribute to disease development and progression or may indicate an attempt to protect against these processes. Early therapeutic targeting of TIE-2 signaling may be useful in improving outcome in arthritis.
24010810 The association between functional and morphological assessments of endothelial function i 2013 INTRODUCTION: Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD). One of the earliest manifestations of CVD is endothelial dysfunction (ED), which can lead to functional and morphological vascular abnormalities. Several non-invasive assessments of vascular function and morphology can be utilised to assess vascular health, but little is known about the association between each of these assessments in patients with RA, and they tend to be used interchangeably in the literature. The objective of the present study was to examine associations between measures of vascular function and morphology in patients with RA. METHODS: A total of 201 RA patients (155 females, median (25th to 75th percentile) age: 67 (59 to 73)) underwent assessments of microvascular endothelium-dependent and endothelium-independent function (laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside respectively), macrovascular endothelium-dependent and endothelium-independent function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilation respectively), and vascular morphology (pulse wave analysis, carotid intima-media thickness (cIMT), and carotid plaque). RESULTS: Spearman's correlations revealed that from the functional parameters, only macrovascular endothelium-independent function was inversely associated with cIMT (-0.294 (P < 0.001)) after applying the Bonferroni correction for multiple comparisons. For carotid plaque, t tests showed that macrovascular endothelium-independent function was lower in patients with plaque than without (15.5 ± 8.3 vs. 23.1 ± 9.1%, P = 0.002, respectively). CONCLUSIONS: With the exception of macrovascular endothelium-independent function, all other measures of vascular function were not associated with vascular morphology. This suggests that different assessments of vascular function and morphology in patients with RA reflect quite distinct mechanisms and phases of the atherosclerotic process and should not be used interchangeably.
23538163 Inhibitory effects of the root extract of Litsea cubeba (lour.) pers. on adjuvant arthriti 2013 May 20 ETHNOPHARMACOLOGICAL RELEVANCE: The dried root of Litsea cubeba (Lour.) Pers. (Family Lauraceae) has long been used as a folk remedy in Traditional Chinese Medicine (TCM) and Dai Ethnopharmacy for the treatment of rheumatic diseases in southwestern China. AIM OF THE STUDY: This study investigated the preventive efficacy of Litsea cubeba root in treating rheumatoid arthritis using Freund's complete adjuvant (CFA) induced arthritis (AA) in rat model. MATERIALS AND METHODS: Arthritis was induced in male Wistar rats by immunization with CFA. Ethanol extract (EELC) and water extract (WELC) of Litsea cubeba root both at 50mg/kg and 200mg/kg were orally administered from a day after the induction of arthritis. Paw swelling, arthritic score, body weight growth rate, index of thymus and spleen were observed, and the production of TNF-α, IL-1β, IL-6 and IL-10 in serum were measured by enzyme-linked immunosorbent assay. The expression levels of inflammatory enzymes like cyclooxygenase and lipoxygenase were also measured by enzyme-linked immunosorbent assay. Moreover, histological changes in the ankle joint were analyzed in AA rats. RESULTS: Both EELC and WELC significantly suppressed paw swelling and arthritic score, increased the loss in body weight and decreased the index of thymus. Histopathological improvement in joint architecture was also observed in EELC, WELC-treated AA rats. The expression levels of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) were decreased on treatment with EELC and WELC. Furthermore, the overproduction of TNF-α, IL-1β and IL-6 were remarkably attenuated in serum of all Litsea cubeba-treated rats, however, IL-10 was markedly increased at doses of 50mg/kg of EELC and WELC. CONCLUSIONS: These results indicate that extract of Litsea cubeba root significantly attenuates adjuvant arthritis in rats by decreasing the levels of TNF-α, IL-1β and IL-6 and increasing of IL-10 in serum as well as down-regulate the levels of inflammatory enzymes such as COX-2 and 5-LOX. This suggests that Litsea cubeba root might be used as a therapeutic agent for the treatment of human arthritis.
24729685 Tocilizumab in the treatment of rheumatoid arthritis and beyond. 2014 Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases.
23754243 Test-retest reliability of the disease activity score 28 CRP (DAS28-CRP), the simplified d 2013 Oct Composite disease activity scores are frequently used in daily practice as tools for treatment decisions in patients with rheumatoid arthritis (RA). If reliable, patient-reported disease activity may be time saving in the busy clinic. The objective was to examine the test-retest reliability of the Disease Activity Score 28 CRP (DAS28-CRP) with four variables (4v) and three variables (3v), the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) when based on patient self-assessment of tender and swollen joints and to examine the agreement between these scores and physician-derived scores. Thirty out-clinic RA patients with stable disease were included. A joint count was performed two times 1 week apart by the patient and by an experienced physician. Test-retest reliability was expressed as the least significant difference (LSD), as the LSD in percent of the mean score (%LSD) and as intra-individual coefficients of variation (CVi). Mean scores based on physician vs. patient joint counts (visit 1) were: DAS28-CRP(4v) 3.5 ± 1.0 vs. 3.6 ± 1.1 (not significant (NS)), DAS28-CRP(3v) 3.4 ± 0.9 vs. 3.5 ± 0.9 (NS), SDAI 14.2 ± 9.4 vs.14.1 ± 9.4 (NS) and CDAI 13.4 ± 9.3 vs. 13.3 ± 9.4 (NS). The LSDs (%LSD) for duplicate assessments of patient-derived scores (visit 2 vs. 1) were: DAS28-CRP(4v) 0.8 (23.2), DAS28-CRP(3v) 0.9 (25.2), SDAI 8.3 (59.9) and CDAI 8.4 (63.8). Similar LSDs were found for differences between duplicate assessments of physician-derived scores and for differences between physician and patient-derived scores. CVis for SDAI and CDAI were significantly higher than for DAS28-CRP(4v) and DAS28-CRP(3v) (p < 0.005). Patient- and physician-derived scores agreed closely on group level. On the individual level, the LSDs between patient- and physician-derived scores were considerable but corresponded to both patient and physician intra-observer LSDs. Thus, scores based on patient-performed joint counts may be an alternative to traditional physician-derived scores in patients with stable disease.
24574211 Ultrasound assessment of synovial pathologic features in rheumatoid arthritis using compre 2014 Mar OBJECTIVE: The aim of this pilot study was to provide groundwork that could be utilized to optimize the global ultrasound (US) assessment of the whole joint for synovial pathologic features in patients with rheumatoid arthritis (RA). METHODS: US images of the second metacarpophalangeal joint in 8 predefined imaging planes, comprising regions that comprehensively capture the synovial pathologic features of the whole joint, were obtained from 30 patients with RA. Twelve experienced sonographers evaluated these images at the level of both the individual image and the whole joint, using a visual analog scale (VAS) to assess pathologic severity. Interrater reproducibility of the VAS scores was evaluated with intraclass correlation coefficients (ICCs), and factors that independently influenced the global assessment of the whole joint were identified using multiple linear regression analysis. RESULTS: A total of 14,276 VAS scores were analyzed. Interrater reproducibility of any eligible VAS assessment of synovial pathologic features was good (ICC 0.65). US assessment of synovial pathologic features in joints with mild inflammation was less reproducible than that in joints with severe inflammation. Although the most severely affected region in a joint did not always represent the average pathologic severity among the 8 regions, global assessment of the whole joint strongly correlated with assessment of the most severely affected region (P < 0.001). Importantly, the standard, midline imaging plane was not the most influential plane on the global assessment of the whole joint. Assessment of synovial fluid accumulation was not reproducible (ICCs 0.20-0.42) and did not substantially influence the global assessment of synovial inflammation (β = 0.06). CONCLUSION: The results of this study provide a unique data set that could be utilized to optimize the global US assessment of synovial pathologic features of the whole joint in patients with RA.
23384668 Advances in the discovery of selective JAK inhibitors. 2013 In this review, we describe the current knowledge of the biology of the JAKs. The JAK family comprises the four nonreceptor tyrosine kinases JAK1, JAK2, JAK3, and Tyk2, all key players in the signal transduction from cytokine receptors to transcription factor activation. We also review the progresses made towards the optimization of JAK inhibitors and the importance of their selectivity profile. Indeed, the full array of many medicinal chemistry enabling tools (HTS, X-ray crystallography, scaffold morphing, etc.) has been deployed to successfully design molecules that discriminate among JAK family and other kinases. While the first JAK inhibitor was launched in 2011, this review also summarizes the status of several other small-molecule JAK inhibitors currently in development to treat arthritis, psoriasis, organ rejection, and multiple cancer types.
24728031 Functional FCGR3A 158 V/F and IL-6 -174 C/G polymorphisms predict response to biologic the 2014 Oct The aim of this study was to investigate whether the Fc gamma receptor 3A (FCGR3A) 158 V/F and interleukin-6 (IL-6) promoter -174 G/C polymorphisms can predict the response to biologic-based therapy in patients with rheumatoid arthritis (RA). We conducted a meta-analysis of studies on the association between the FCGR3A V/F polymorphism or the IL-6 -174 C/G polymorphism and non-responsiveness to biologic therapy in RA patients. A total of 10 studies involving 1,427 patients were considered. These studies consisted of seven studies on the FCGR3A polymorphism and three studies on the IL-6 polymorphism. Meta-analysis showed no association between the FCGR3A VV+VF genotype and non-responders to biologic therapy [odds ratio (OR) 0.881, 95 % confidence interval (CI) 0.505-1.537, p = 0.655]. However, stratification by biologic type indicated an association between the FCGR3A VV+VF genotype and non-responders to rituximab (OR 0.566, 95 % CI 0.373-0.857, p = 0.007), but no association was found in non-responders to tumor necrosis factor (TNF)-blockers (OR 1.337, 95 % CI 0.869-2.056, p = 0.186). Meta-analysis revealed no association between the IL-6 CC+CG genotype and non-responders to the biologics (OR 3.233, 95 % CI 0.766-13.64, p = 0.110). However, an association was found between the IL-6 CC+CG genotype and non-responders to anti-TNF therapy (OR 8.030, 95 % CI 1.807-33.68, p = 0.006). This meta-analysis demonstrates that FCGR3A V allele carriers show a better response to rituximab, and individuals carrying the IL-6 -174 C allele show a poorer response to anti-TNF therapy for RA. Genotyping for these polymorphisms may be a useful tool for predicting the response to biologics with respect to personalized medicine.
25954396 First-order logic theory for manipulating clinical practice guidelines applied to comorbid 2014 Clinical practice guidelines (CPGs) implement evidence-based medicine designed to help generate a therapy for a patient suffering from a single disease. When applied to a comorbid patient, the concurrent combination of treatment steps from multiple CPGs is susceptible to adverse interactions in the resulting combined therapy (i.e., a therapy established according to all considered CPGs). This inability to concurrently apply CPGs has been shown to be one of the key shortcomings of CPG uptake in a clinical setting1. Several research efforts are underway to address this issue such as the K4CARE2 and GuideLine INteraction Detection Assistant (GLINDA)3 projects and our previous research on applying constraint logic programming to developing a consistent combined therapy for a comorbid patient4. However, there is no generalized framework for mitigation that effectively captures general characteristics of the problem while handling nuances such as time and ordering requirements imposed by specific CPGs. In this paper we propose a first-order logic-based (FOL) approach for developing a generalized framework of mitigation. This approach uses a meta-algorithm and entailment properties to mitigate (i.e., identify and address) adverse interactions introduced by concurrently applied CPGs. We use an illustrative case study of a patient suffering from type 2 diabetes being treated for an onset of severe rheumatoid arthritis to show the expressiveness and robustness of our proposed FOL-based approach, and we discuss its appropriateness as the basis for the generalized theory.
22289054 How many life years are lost in patients with rheumatoid arthritis? Secular cause-specific 2013 Jan BACKGROUND: There is an excess of mortality in patients with rheumatoid arthritis (RA) but no long-term Australian cohort data. AIMS: To determine median life years lost, all-cause standardised mortality ratio (SMR) and cause-specific SMR, their predictors and secular change in Australian patients with RA. METHODS: Study population was all patients seen by a rheumatologist between 1990 and 1994. Record linkage with Australian National Death Index was performed to determine fact and cause of death up to 2004. All-cause and cause-specific SMR, and median life years lost were determined. RESULTS: There were 35 (31%) deaths in the early 1990s cohort (n = 113), SMR 1.31 (95% 0.93, 1.80). There were 216 (44%) deaths in the pre-1990s established cohort (n = 495), SMR 1.73 (1.49, 1.95). Median life years lost in the early cohort was 6 years for males and 7 years for females compared with 8 and 10 years, respectively, in the established cohort. Patients with low disease activity score at baseline (DAS < 3.2), SMR was 0.8 (0.3, 2.2) and 1.5 (1.1, 2.2) for the early and established cohorts, and if DAS ≥3.2, SMR was 1.4 (1.02, 1.98) and 1.8 (1.5, 2.1) respectively. Primary cause of death was cardiovascular disease (SMR 1.43 (1.17, 1.74). Patients at most risk were those age 45-54 years. RA was listed as a comorbid condition on the death certificate in only 16% of patients. CONCLUSIONS: Within a period of 14 years, median life expectancy of patients with RA with disease onset in the early 1990s is reduced by 6-7 years. However, our results also suggest a secular reduction in excess mortality.
23268368 The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis syn 2013 Sep 1 BACKGROUND: Interleukin (IL)-36α is a recently described member of the IL-1 cytokine family with pro-inflammatory and clearly pathogenic properties in psoriasis. OBJECTIVE: To determine the IL-36α expression in psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial tissues obtained from arthritis patients were stained for IL-36α, IL-36 receptor (IL-36R) and IL-36R antagonist (IL-36Ra) by immunohistochemistry and immunofluorescence. Lysates were examined for IL-36α by western blot analysis. Synovial fibroblasts (FLS) cultured in the presence of IL-36α were assayed for cytokine expression by quantitative real time PCR and multiplex assay. IL-36α-induced signal transduction in FLS was analysed by immunoblotting. RESULTS: Expression of IL-36R and its ligands IL-36α and IL-36Ra was detected in the synovial lining layer and cellular infiltrates of patients with inflammatory arthritis. IL-36α was expressed significantly higher in PsA and RA than in OA synovium. CD138-positive plasma cells were identified as the main cellular source of IL-36α. No differences were observed for the expression of IL-36R and IL-36Ra between PsA, RA and OA. Functionally, IL-36α induced the expression of IL-6 and IL-8 in FLS through p38/NFkB activation. CONCLUSIONS: IL-36α is up-regulated in PsA and RA synovium, expressed by tissue plasma cells and leads to IL-6 and IL-8 production by synovial fibroblasts. Hence, IL-36α links plasma cells to inflammatory cytokine production by FLS and may represent a key link between autoimmunity and the induction of synovitis.
23514404 Cardiovascular risk management in rheumatoid arthritis: are we still waiting for the first 2013 Mar 19 Rheumatoid arthritis (RA) is associated with a similar cardiovascular risk to that in diabetes, and therefore cardiovascular risk management (CV-RM) - that is, identification and treatment of cardiovascular risk factors (CRFs) - is mandatory. However, whether and to what extent this is done in daily clinical practice is unknown. In a retrospective cohort investigation, CV-RM was therefore compared between rheumatologists and primary care physicians (PCPs). Remarkably, CRFs in RA were less frequently identified and managed by rheumatologists in comparison with PCPs. In addition, PCPs assessed CRFs less frequently in RA than in diabetes. Obviously, there is a clear need for improvement of CV-RM in RA and this should be a joint effort from the rheumatologist and the PCP.
23463543 Changes in use of disease-modifying antirheumatic drugs for rheumatoid arthritis in the Un 2013 Sep OBJECTIVE: Use of nonbiologic disease-modifying antirheumatic drugs (DMARDs) and/or biologic DMARDs is generally recommended to improve the prognosis of patients with rheumatoid arthritis (RA). The objective of this study was to describe the changing trends in DMARD use for RA over the past 2 decades. METHODS: We analyzed data from an open longitudinal cohort of RA patients recruited from rheumatologists' practices in northern California. We examined baseline demographic and clinical characteristics of the participants and their long-term DMARD use through annual comprehensive structured telephone interviews. RESULTS: A total of 1,507 established RA patients were recruited through 5 enrollment periods between 1983 and 2009. Between 1983 and 2009, the use of any DMARD increased from 71% of all patients to 83% (P for trend < 0.0001). In 2009, 43% received a biologic DMARD, 34% were on both nonbiologic and biologic DMARDs, and 40% were treated with only nonbiologic DMARDs. The 4 most commonly used nonbiologic DMARDs in 2009 were methotrexate (49%), hydroxychloroquine (30%), leflunomide (13%), and sulfasalazine (7%). Etanercept (20%) was the most commonly used biologic DMARD in 2009, followed by infliximab (10%), adalimumab (9%), and abatacept (6%). Use of oral steroids was common (40-50%) and remained similar throughout the study period. CONCLUSION: There has been a significant increase in the use of DMARDs for RA over the past 2 decades. However, 15% of the individuals with a clinical diagnosis of RA were not receiving DMARDs in 2009. Future research should focus on sociodemographic and clinical factors associated with DMARD use for RA.