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ID PMID Title PublicationDate abstract
19210873 Analysis of peripheral blood lymphocytes using flow cytometry in polymyalgia rheumatica, R 2008 Nov OBJECTIVE: Clinical pictures of poly-myalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) are often indistinguishable from those of early rheumatoid arthritis (RA). To investigate whether there is a difference in immunological aspects among these 3 disorders, we performed a phenotypic analysis of peripheral blood lymphocytes. PATIENTS AND METHODS: Eleven patients with early RA, 14 with PMR and 11 with RS3PE were enrolled in this study. After separation of mononuclear cells from peripheral blood using the Ficoll-Hypaque method, surface markers and intracellular cytokines of lymphocytes were analyzed by 2- or 3-color flow cytometry. RESULTS: Both PMR and RS3PE showed a significant decrease in CD8+CD25+ cells (p<0.05), and significant increases in CD4+IFN-gamma+IL-4- (p<0.05), CD8+IFN-gamma+IL-4- (p<0.05 and p<0.01, respectively) and CD4+TNF-alpha+ cells (p<0.05) compared with early RA. CD3+CD4+ cells were higher in PMR than in RS3PE (p<0.01), but there were no significant differences in any other phenotypes between these disorders. CONCLUSION: A decrease in activated cytotoxic/suppressor T cells and increases in circulating Th1 and Tc1 cells may be common characteristics of PMR and RS3PE in comparison with early RA. Both disorders are clearly different from early RA, and probably belong to the same disease entity with regard to phenotypes of peripheral blood lymphocytes.
18260177 Anemia in early rheumatoid arthritis is associated with interleukin 6-mediated bone marrow 2008 Mar OBJECTIVE: Anemia of chronic disease (ACD) is the most common extraarticular manifestation of rheumatoid arthritis (RA), but there is limited information on the cause and consequences of ACD. We investigated the prevalence, relation with proinflammatory cytokines, and effect on disease outcome of ACD in patients with RA. METHODS: The presence of anemia was analyzed in a cohort of 111 consecutive patients with early RA. Anemia was related to markers of erythropoiesis and inflammation [clinically and by levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum interleukin 1beta (IL-1beta), IL-2, IL-6, IL-8, and tumor necrosis factor-alpha]. The frequency of various disease outcomes during the mean followup of 74 months was compared between ACD and nonanemic patients. RESULTS: ACD was present in 25% during the first year of disease. ACD was associated with higher CRP (45 vs 22 g/l; p = 0.04) and ESR levels (54 vs 33 mm/h; p = 0.002). Hemoglobin levels were inversely correlated with serum erythropoietin (p = 0.003) in univariate analysis, but in multivariate analysis only ESR (p = 0.005) and IL-6 (p = 0.056) remained as independent predictors of hemoglobin levels. Presence of ACD was not associated with later development of disease manifestations or mortality. CONCLUSION: While ACD affected 25% of patients with RA early in the disease course, this had no influence on disease outcome including mortality during the following 6 years. The association between IL-6 and ACD suggests that IL-6-mediated bone marrow suppression is the main mechanism for development of ACD in RA.
18046554 Patient demographics and disease variables correlate with distinct cytokine patterns in mi 2008 Apr There is paucity of literature on the association of peripheral blood cytokine patterns with patient demographics and disease variables in rheumatoid arthritis (RA). We test the hypothesis that there may be differences in peripheral blood levels of inflammatory cytokines in RA subjects according to various disease variables. In this case, we could identify peripheral blood cytokine markers that correlate with different disease variables. Forty-two seropositive RA patients were characterized according to the age at onset, gender, disease duration, severity, activity and ACR functional class. The production levels in mitogen-stimulated PBMCs of five pro-inflammatory cytokines (IFNgamma, TNFalpha, TNFbeta, IL-8, IL-18) and three anti-inflammatory cytokines (IL-4, IL-10, IL-13) were evaluated in these patients and in healthy controls. Several new findings emerge: (1) higher levels of IL-4 correlate with female gender, milder disease, non-erosive disease, and earlier age at onset; (2) higher levels of IL-10 correlate with the requirement of < or =2 DMARDs; (3) higher levels of IL-18 correlate with non-erosive disease and younger age at onset; (4) higher TNFbeta levels correlate with older present age of patients; and (5) higher IL-8 levels correlate with established/late disease. There are several interesting differences in cytokine patterns with respect to age at onset, current age, disease severity, and the number of DMARDs the patients require.
17102944 Durability of treatment with methotrexate in Venezuelan patients with rheumatoid arthritis 2007 Apr A multicenter, national, retrospective, and cross-sectional study of 219 hospital-based Venezuelan patients with rheumatoid arthritis (RA) was aimed to evaluate the probability of continuity of treatment with oral methotrexate (MTX). Treatment survival decreased from 92% at 12 months to 42% at 180 months, as assessed by life table analysis and the Kaplan-Meier method. Forty-seven patients stopped treatment and adverse effects (29.7%) and lack of continuous access to medication (19.1%) were the most common causes for withdrawal. MTX survival was decreased in the group with combined MTX plus leflunomide therapy, as shown by the log-rank test. Venezuelan patients with RA have a probability of continuing treatment with oral MTX comparable to non-Hispanic patient populations. However, concomitant use of leflunomide may increase the risk of interruption of MTX treatment in this RA population.
17369281 Disease Activity Score 28 (DAS28) using C-reactive protein underestimates disease activity 2007 Sep OBJECTIVES: To compare disease activity and the improvement of disease activity evaluated between by Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) and by DAS28 using C-reactive protein (DAS28-CRP) in Japanese patients with rheumatoid arthritis (RA). METHODS: Data from 3073 RA patients registered in the large cohort database (NinJa: National Database of Rheumatic Diseases by iR-net in Japan) of 2003 was used to calculate DAS28-ESR and DAS28-CRP and disease activities were evaluated. Improvements in disease activities were also evaluated according to the European League Against Rheumatism (EULAR) response criteria in 1482 RA patients whose DAS28-ESR and DAS28-CRP could be calculated from data for both 2002 and 2003. RESULTS: The mean value of DAS28-CRP (3.59, SD 1.25) was significantly smaller than that of mean DAS28-ESR (4.31, SD 1.32) (p < 0.0001). The number of patients who satisfied the criteria of remission was 297 (9.7%) in DAS28-ESR versus 705 (22.9%) in DAS28-CRP and the number of patients with high disease activity was 842 (27.4%) versus 357 (11.6%) for DAS28-ESR and DAS28-CRP, respectively; there was a significant difference between the two (p < 0.0001). Change of respective DAS28 was significantly correlated (DeltaDAS28-ESR -0.05, SD 1.14 versus DeltaDAS28-CRP -0.10, SD 1.10) (p < 0.0001); however, the number of "good response" patients was significantly different (p < 0.03) between DAS28-ESR (97 patients, 6.5%) and DAS28-CRP (136 patients, 9.2%). CONCLUSIONS: DAS28-CRP significantly underestimated disease activity and overestimated the improvement in disease activity compared with DAS28-ESR. DAS28-CRP should be evaluated using different criteria from that for DAS28-ESR.
19104753 Radiographic progression in weight-bearing joints of patients with rheumatoid arthritis af 2009 Apr The aim of the present study was to assess the influence of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis. Changes in clinical variables and radiological findings in 213 weight-bearing joints (69 hip joints, 63 knee joints, and 81 ankle joints) of 42 consecutive patients were investigated at baseline and at 1 year of TNF-blocking therapies. Structural damage to the weight-bearing joints was assessed using the Larsen scoring method. Detailed comparisons of the sizes and locations of erosions were performed for each set of radiographs of the respective joints. Assessment of radiographs of the 213 weight-bearing joints indicated progression of the Larsen grade in eight joints. Another five joints without Larsen grade progression showed apparent radiographic progression of joint damage based on increases in bony erosions. Overall, 13 joints (6%) of eight patients (19%) showed progression of joint damage after 1 year of TNF-blocking therapies. Analysis of each baseline grade indicated that radiographic progression of joint damage was inhibited in most grade 0-II joints. On the other hand, all hip and knee joints with pre-existing damage of grade III/IV showed apparent progression even in patients with good response. The results further suggested that radiographic progression may occur in less damaged joints when the patients were non-responders to the therapy. Among the weight-bearing joints, ankle joints showed different radiographic behavior and four ankle joints displayed improvement of radiographic damage. Early initiation of anti-TNF therapy should be necessary especially when the patients are starting to show early structural damage in weight-bearing joints.
17307765 Step-up combination versus switching of non-biological disease-modifying antirheumatic dru 2007 Aug BACKGROUND: In rheumatoid arthritis (RA), treatment with disease-modifying antirheumatic drugs (DMARDs) frequently needs to be changed because of insufficient effectiveness. AIM: To compare the clinical outcomes of two potential strategies for patients experiencing DMARD discontinuations related to ineffectiveness: switching to another DMARD or step-up combination therapy of the present DMARD with a new one. METHODS: In a large observational database of 4585 DMARD courses in 1214 patients with RA, all patients who had experienced a change in treatment regimen were identified, and retention, effectiveness and safety of these subsequent treatment courses between the two strategies (switching vs step-up combination). All analyses were stratified according to the type of the new DMARD into methotrexate (MTX), sulphasalazine (SSZ) or leflunomide (LEF); all other DMARDs were excluded. RESULTS: Kaplan-Meier analysis for MTX courses showed no significant difference in overall retention rates between the strategies of adding MTX and switching to MTX (p = 0.49 by log rank test). Likewise, switching or adding did not result in significantly different retention rates for SSZ and LEF (p = 0.61 and 0.74, respectively). This similarity between strategies remained after adjusting for several confounding variables. The frequencies of treatment terminations related to ineffectiveness or toxicity were likewise similar between the two strategies for the MTX, SSZ and LEF groups. This was also confirmed by the similarity of erythrocyte sedimentation rates that were reached at the end of the two therapeutic strategies for all three drugs, in adjusted analysis. CONCLUSION: Given all limitations of observational studies, the present data indicate that in situations of ineffective DMARD treatments, step-up combination therapy using traditional DMARDs, such as MTX, SSZ or LEF, bears no clear clinical advantage over switching to the new DMARD. Our results do not implicate any predication about step-up design including biologicals, where the benefit of combination therapy has been suggested convincingly.
18270866 Should rituximab be considered as the first-choice treatment for severe autoimmune rheumat 2008 Feb The present study aimed to assess the tolerance and efficacy of rituximab (RTX), a chimeric IgG1 monoclonal antibody directed against the CD20 receptor present in B lymphocytes, in patients with autoimmune rheumatic diseases (AIRD). For this purpose, patients treated with RTX and their respective clinical charts were comprehensively examined. Indications for treatment were a refractory character of the disease, inefficacy or intolerance of other immunosuppressors. Activity indexes (SLEDAI, DAS28, and specific clinical manifestations) were used to evaluate efficacy. Serious side effects were also recorded. Seventy-four patients were included. Forty-three patients had systemic lupus erythematosus (SLE), 21 had rheumatoid arthritis (RA), 8 had Sjögren's syndrome (SS), and 2 had Takayasu's arteritis (TA). RTX was well-tolerated in 66 (89%) patients. In 8 patients (SLE=3, SS=3, RA=2), serious side effects lead to discontinuation. The mean follow-up period was 12+/-7.8 (2-35) months. The efficacy of RTX was registered in 58/66 (87%) patients, of whom 36 (83%) had SLE, 18/21 (85%) had RA, 3/8 (37%) had SS, and 1 had TA. The mean time of efficacy was 6.3+/-5.1 weeks. A significant steroid-sparing effect was noticed in half of the patients. These results add further evidence for the use of RTX in AIRD. Based on its risk-benefit ratio, RTX might be used as the first-choice treatment for patients with severe AIRD.
17435844 [Synoviocyte cultures from synovial fluid]. 2007 Jan The study of the pathogenetic mechanisms of rheumatic diseases is in general carried out through "in vitro" systems based on cellular cultures models. The difficulties to achieve fresh human tissue prompted us to develop a simpler method to obtain fibroblast-like synovial cells from synovial fluid (SF). METHODS: SF was collected from the knees of 5 patients with rheumatoid arthritis (RA), 4 with osteoarthritis (OA) and 5 with psoriatic arthritis (PsA). The pellet obtained after centrifugation was resuspended in DMEM/HamF12 containing 10% foetal calf serum, 1% peni-streptomycin, 4 ng/ml of fibroblast grow factor and incubated at 37 degrees C in T25 culture flasks. Synoviocytes were also obtained from fresh synovial membranes (SM) by explants technique. Both types of cells were characterized by immunocytochemistry and their inflammatory response to synthetic monosodium urate crystals was studied through the measurement of nitric oxide (NO). RESULTS: Adherent synoviocytes were obtained from the culture of 2/5 SF from RA, 4/4 SF from OA and 5/5 SF from PsA. Synoviocytes isolated from both SF and SM expressed surface antigens CD90, CD55, and the intracellular prolyl-4-hydroxylase. Morphologically, the cells showed the typical spindle-shape fibroblast-like appearance. NO levels induced by UMS crystals in SF synoviocytes were similar to those obtained in SM synoviocytes. CONCLUSION: Adherent cells obtained from SF showed the phenotype and the reactivity of tissue synoviocytes. Due to the easy accessibility of SF, this method may represents an useful alternative when synovial tissues is not promptly available.
17951669 Analysis of leukocyte recruitment in synovial microcirculation by intravital microscopy. 2007 A complete pattern of adhesion molecules and chemokines involved in leukocyte migration in different tissues and in homeostatic vs inflammatory conditions is still lacking. This chapter describes how to characterize the mechanisms of leukocyte recruitment in synovial vessels in vivo by using epifluorescence videomicroscopy. It has been proposed that inflamed endothelium expresses a combination of adhesion ligands and activating factor(s) for Gi-linked receptors that together orchestrate leukocyte recruitment in vivo. Thus, the combination of molecules involved in the adhesion cascade in synovial vessels may favor the arrest of specific leukocyte subpopulations during different phases of joint inflammation. The approach presented here may provide a useful tool for further investigations of physiologic and pathologic events that occur in normal synovial microcirculation as well as during arthritis.
17011587 Monotonicity of interleukin-1 receptor-ligand binding with respect to antagonist in the pr 2007 Feb 7 We consider the interaction between interleukin-1 IL-1, its receptor IL-1RI, the receptor antagonist IL-1Ra and a decoy receptor (or trap) that binds both with the ligand and the antagonist. We study how the interaction between IL-1Ra and the decoy receptor influences the effect of either reagent on reducing the equilibrium concentration of the receptor-ligand complex. We obtain that, given a certain relationship among the equilibrium constants and the total concentrations of solutes, IL-1Ra can reverse the effect of the decoy receptor of decreasing the equilibrium concentration of the receptor-ligand complex. This finding derives from a mathematical result applicable to any reversible chemical reaction system comprising four species arranged in a square such that each species binds its two immediate neighbors. The result gives the monotonicity of the equilibrium concentrations of the complex species as functions of the total concentrations of the simple species.
18037627 Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-m 2008 Aug OBJECTIVES: Everolimus, a proliferation signal inhibitor with disease-modifying properties, may be useful in treating rheumatoid arthritis (RA). This proof-of-concept study assessed efficacy and safety of everolimus in combination with methotrexate (MTX) in patients with refractory RA. METHODS: A multi-centre, randomised, double-blind, placebo-controlled trial was performed in 121 patients with active RA receiving MTX. Patients were randomised to receive everolimus (6 mg/day) or placebo. The primary endpoint was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR20) at 12 weeks. RESULTS: There was a rapid onset of action and at 12 weeks the ACR20 response rate was significantly higher in the everolimus group (36.1%) than in the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and swollen joint counts, patient's assessment of pain, and patient's and physician's global assessment of disease activity were significantly greater after treatment with everolimus. The most common adverse events (AEs) in the everolimus group were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs 8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment discontinuation were reported for 16.4% and 10.0% of patients, respectively. Changes in haematological parameters, liver function tests, and lipid levels occurred more frequently with everolimus compared to placebo, but were mild and reversible. CONCLUSIONS: The study indicates that everolimus plus MTX provides clinical benefit with an acceptable safety and tolerability profile. It may offer a new treatment option in RA patients with inadequate response to MTX.
19210874 Lack of linkage and association of adrenomedullin and its receptor genes in French Caucasi 2008 Nov OBJECTIVE: Rheumatoid arthritis (RA) is characterized by hyperplasia of fibro-blast-like synoviocytes (FLSs), in part due to apoptosis resistance. Adrenomedullin, an anti-apoptotic peptide, is secreted more by RA than osteoarthritis FLSs. Adrenomedullin binds to a heterodimeric functional receptor, of calcitonin receptor-like receptor (CRLR) coupled with a receptor activity-modifying protein-2 (RAMP-2), which is also overexpressed by rheumatoid synoviocytes. Since adrenomedullin decreases RA FLS apoptosis, possibly contributing to the development of pannus, study of adrenomedullin and its receptor genes might reveal a linkage and association in French Caucasian RA trio families. METHODS: Within each of 100 families, one RA-affected patient and both parents underwent genotyping for polymorphisms of adrenomedullin, CRLR and RAMP-2, by PCR-restricted fragment-length polymorphism (RFLP) or Taqman 5' allelic discrimination assay. Statistical analysis relied on the transmission disequilibrium test, the affected family-based controls and the genotype relative risk. Haplotypes of CRLR were inferred, and linkage and association studies were performed. RESULTS: No significant transmission disequilibrium or association between the three genes and RA was observed. CRLR haplotypes revealed two major haplotypes, but no significant linkage with RA. CONCLUSION: Our findings provided no significant linkage or association of adrenomedullin and CRLR-RAMP-2 genes with RA in the studied trio families. The two CRLR polymorphisms rs3771076 and rs3771084 should be investigated in larger samples.
18289792 The effects of anxiety and depression on weekly pain in women with arthritis. 2008 Aug 31 This study examined the effects of anxiety and depression on pain in women with rheumatoid arthritis (RA; n=82) or osteoarthritis (OA; n=88). Anxiety and depression symptoms were assessed at the beginning of the study. Arthritis pain, interpersonal stress, negative affect, and positive affect were assessed weekly for 11 consecutive weeks. Multilevel analyses were conducted to investigate direct, indirect, and interactive effects of anxiety and depression on weekly changes in pain. When entered separately into the prediction equations, anxiety and depression were both related to elevations in current and next week pain, although the effects were nearly twice as large for anxiety. In addition, both anxiety and depression were indirectly related to current pain through negative and positive affect and depression interacted with stress to predict current pain in the RA group. When entered together into the prediction equations, anxiety alone was still related to elevations in current and next week pain. In addition, anxiety alone was indirectly related to current pain through negative affect and depression alone was indirectly related to current pain through positive affect. These results highlight the need for careful study of the differential effects of anxiety and depression and treatments that target their unique mechanisms.
18185905 Treatment adherence in patients with rheumatoid arthritis and systemic lupus erythematosus 2008 Jul This study assessed self-reported adherence in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) from underserved healthcare settings. We conducted a cross-sectional survey of 102 ethnically diverse patients--70 with RA and 32 with SLE--attending rheumatology clinics at publicly funded hospitals in Houston, Texas; 43% were Hispanic, 32% African-American, and 25% White. Treatment adherence was evaluated using the compliance questionnaire rheumatology (CQR; 0, low adherence and 100, high adherence) and the questionnaire of the Adult AIDS Clinical Trials Group (AACTG). The patients were also asked how often they forgot to take their prescribed medications or discontinued them on their own. Mean patient age was 48.5 years; 75% were female, 32% were African-American, 43% Hispanic, and 25% White. Only one third reported never forgetting to take their medications; 40% reported having stopped their medications on their own because of side effects, and 20% because of lack of efficacy. Mean CQR score was 69.1 +/- 10.5, suggesting moderate adherence overall. Differences were also observed across ethnic groups: 23% of ethnic minority patients had problems taking their medications at specified times compared to 11% of Whites (p = 0.03). Lower education and side effects were associated with lower adherence. No differences were observed between RA and SLE patients. Many patients with RA and SLE report problems with treatment adherence. These appear to be more prevalent in African Americans and Hispanics than Whites; the impact of decreased adherence on outcomes could be significant and should be considered when treating patients with RA and SLE.
16776632 Increased fructosamine in non-diabetic rheumatoid arthritis patients: role of lipid peroxi 2006 Modification of proteins by non-enzymatic glycation is one of the underlying factors known to play a major role in the pathogenesis of many clinical disorders. Glycation of plasma proteins is enhanced by elevated glucose concentrations. However, increased fructosamine has been documented in rheumatoid arthritis patients without any history of diabetes. Collective evidence reveals that malondialdehyde and reduced glutathione can modulate the glycation process. This study was undertaken to unravel the possible association of malondialdehyde and glutathione with fructosamine in rheumatoid arthritis patients. A case-control study was performed on 15 rheumatoid arthritis patients and 15 control subjects. Whole blood glutathione, plasma malondialdehyde, fructosamine and fasting glucose were analyzed in both groups. Partial correlation analysis was performed to predict the independent association of malondialdehyde, glutathione and fasting glucose on fructosamine. In rheumatoid arthritis patients, while fructosamine and malondialdehyde levels were significantly increased, glutathione levels were significantly decreased compared with controls. With partial correlation analysis, fructosamine was found to have a significant positive correlation with malondialdehyde and a negative correlation with glutathione. These data suggest that plasma fructosamine levels are closely associated with malondialdehyde and glutathione in rheumatoid arthritis patients, warranting extra precaution in interpreting fructosamine as a measure of glycemic control in these patients.
16755805 Handling safety for patients with inflammatory arthritis. 2006 May 23 Moving and handling in the healthcare setting is heavily focused on the safety of healthcare workers and the importance of ensuring training in techniques is up to date. However, careful risk assessment should focus on reduction of injury to patients as much as to healthcare workers. Patients with inflammatory arthritis can be particularly challenging due to the condition and its symptoms.
19010354 A possible role of Fas-ligand-mediated "reverse signaling" in pathogenesis of rheumatoid a 2009 Jan 29 Fas/FasL system is involved in pathogenesis of a variety of autoimmune diseases. In overwhelming majority of situations alterations in Fas and FasL expression are viewed in frames of Fas-mediated apoptosis. In the present work we tested a possible involvement of Fas-ligand-mediated "reverse signaling" in pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We show that high level of sFas in RA patient blood correlates with a high activity of disease; in SLE patients with elevated sFas level there was a correlation between sFas concentration and leucopenia, and tissue and organ damage. We showed for the first time that at high concentrations in serum sFas is present in oligomeric form. Oligomeric sFas demonstrated cytotoxicity in lymphocyte primary culture and in transformed cells, while non-toxic recombinant Fas-ligand partially blocked this effect. Besides, immunohistochemical analysis of PBLs and injured synovia of RA patients revealed the high expression of Fas-ligand. All this together allow assuming the involvement of cytotoxic "reversed signaling" in the pathogenesis of autoimmune diseases.
18410226 Significance of serum TRACP in rheumatoid arthritis. 2008 Aug Human serum contains two related isoforms of TRACP: TRACP 5a and TRACP 5b. Serum TRACP 5a protein is increased in about one third of rheumatoid arthritis (RA) sera. This study was undertaken to examine the significance of serum TRACP isoforms 5a and 5b as disease markers of inflammation and bone destruction in RA. One hundred eighteen patients were recruited including 50 with RA (25 with nodules), 26 with osteoarthritis (OA), and 42 with other rheumatic diseases. Twenty-six healthy adults served as controls. Serum TRACP 5a activity, TRACP 5a protein, and TRACP 5b activity were determined by in-house immunoassays. C-reactive protein (CRP) was determined by in-house immunoassay using commercial antibodies and CRP. Other commercial markers included bone-specific alkaline phosphatase (BALP), C-telopeptides of type-I collagen (ICTP), cartilage glycoprotein-39 (YKL-40), and IgM rheumatoid factors (IgM-RF). Mean TRACP 5a protein was significantly elevated only in RA compared with healthy controls and other disease groups. TRACP 5a protein correlated significantly only with IgM-RF in RA. Among RA patients, mean TRACP 5a protein and IgM RF were significantly higher in nodule formers. In contrast, TRACP 5b activity was slightly elevated in RA and correlated with BALP, ICTP, and YKL-40 but not with IgM-RF or CRP. Mean TRACP 5b activity was no different in RA patients with or without nodules. TRACP isoforms could be useful disease markers in RA; TRACP 5a protein may be a measure of systemic inflammatory macrophage burden and disease severity. TRACP 5b activity is a marker for osteoclast number and perhaps local or systemic bone destruction.
16583428 What factors account for referral delays for patients with suspected rheumatoid arthritis? 2006 Apr 15 OBJECTIVE: Rheumatoid arthritis (RA) is a common, costly, and disabling disease. Early referral and treatment reduce long-term joint damage and improve functional outcomes. Despite efforts to improve referral, half of patients with RA are not referred in a timely manner. Our objective was to explore the factors influencing the decision of a primary care physician (PCP) to refer or not refer a patient with suspected RA, and to identify modifiable factors influencing timely referral. METHODS: Using qualitative methods and in-depth, face-to-face interviews, we asked Connecticut PCPs to describe the last patient encounter where they suspected RA and the factors influencing referral and nonreferral. Participants represented a range of clinical experience, access to rheumatologists, and practice settings. Sample size was determined by thematic saturation. Transcripts were coded and analyzed using the constant comparative method of qualitative data analysis. RESULTS: We interviewed 19 PCPs, 9 of whom were women. Our analysis identified clinical characteristics, patient preferences, access issues, clinical and administrative leadership, physician confidence and expectations, and interpersonal relationships as important domains influencing the referral decision. These domains interacted to impact timely referral and quality of care. Previously underappreciated factors, such as the magnitude of the effect of physician rapport, appeared to be critical in determining whether or not patients are promptly referred. CONCLUSION: Issues such as physician rapport, as well as clinical and system issues, influence referral for suspected RA. To improve referral for RA, clinical guidelines, medical education, and quality improvement efforts should address all domains influencing the referral decision.