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

ID PMID Title PublicationDate abstract
19924705 Inclusion of a priori information in genome-wide association analysis. 2009 Genome-wide association studies (GWAS) continue to gain in popularity. To utilize the wealth of data created more effectively, a variety of methods have recently been proposed to include a priori information (e.g., biologically interpretable sets of genes, candidate gene information, or gene expression) in GWAS analysis. Six contributions to Genetic Analysis Workshop 16 Group 11 applied novel or recently proposed methods to GWAS of rheumatoid arthritis and heart disease related phenotypes. The results of these analyses were a variety of novel candidate genes and sets of genes, in addition to the validation of well-known genotype-phenotype associations. However, because many methods are relatively new, they would benefit from further methodological research to ensure that they maintain type I error rates while increasing power to find additional associations. When methods have been adapted from other study types (e.g., gene expression data analysis or linkage analysis), the lessons learned there should be used to guide implementation of techniques. Lastly, many open research questions exist concerning the logistic details of the origin of the a priori information and the way to incorporate it. Overall, our group has demonstrated a strong potential for identifying novel genotype-phenotype relationships by including a priori data in the analysis of GWAS, while also uncovering a series of questions requiring further research.
20383728 Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to developmen 2010 Dec This study was intended to evaluate HLA-DRB1 alleles and antibodies against anti-cyclic citrullinated peptides (anti-CCP Abs) for their value in predicting patient responses to treatment with disease-modifying antirheumatic drugs (DMARDs) in early rheumatoid arthritis (RA). The subjects were 124 Japanese patients who had received their first treatment with DMARDs, usually methotrexate, within 1 year of disease onset and who had been followed-up for 2 years subsequently. Approximately 40% of patients developed DMARD resistance and accordingly required anti-tumor necrosis factor α (TNFα) therapy during the 2-year period. DMARD resistance was strongly associated with the carriage of SE-positive HLA-DRB1*04 alleles, especially the *0405 allele (OR, 3.92; 95%CI, 1.83-8.41; p = 0.0003). In contrast, the SE-positive allele HLA-DRB1*0101 was less potent in contributing to DMARD resistance. The rate of anti-CCP Ab-positive patients was significantly higher in the DMARD-resistant group (OR, 6.62; 95%CI, 1.45-30.24; p = 0.008). Multivariate logistic regression analysis confirmed the strong association of DMARD resistance with the presence of SE-positive *04 alleles (OR, 2.89; 95%CI, 1.28-6.53; p = 0.011) and anti-CCP Abs (OR, 6.31; 95%CI, 1.23-32.34; p = 0.027), yielding an area under the receiver operating characteristic curve of 0.76 (95% CI, 0.68-0.84; p = 0.000). After stratification, the highest rate of DMARD resistance was observed in patients having both SE-positive *04 alleles and anti-CCP Abs. These observations show that the presence of SE-positive *04 alleles in combination with anti-CCP Abs is the strongest predictor for development of DMARD resistance and eventual need of anti-TNFα agents in patients with early RA.
19509327 Comparative overview of safety of the biologics in rheumatoid arthritis. 2009 Jun Six biologic agents are currently available in Canada for the treatment of rheumatoid arthritis (RA): abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab. Although they are generally considered to be safe and well tolerated, concerns have been raised regarding the use of biologic therapies in the treatment of RA. The new biologic agents abatacept and rituximab have novel mechanisms of action, and may therefore offer different safety profiles. The most important safety concerns with the biologic therapies remain the increased risk of infection. An increased risk of malignancies, including lymphoma and skin cancer, has been noted in RA trials, but the extent to which each of the biologic therapies contributes to the risk of malignancy has not been clearly defined.
19470527 Patients with rheumatoid arthritis treated with tumour necrosis factor antagonists increas 2010 Jan OBJECTIVE: To investigate the effect of tumour necrosis factor (TNF) antagonist treatment on workforce participation in patients with rheumatoid arthritis (RA). METHODS: Data from the Stockholm anti-TNFalpha follow-up registry (STURE) were used in this observational study. Patients with RA (n = 594) aged 18-55 years, (mean (SD) 40 (9) years) followed for up to 5 years were included with hours worked/week as the main outcome measure. Analyses were performed unadjusted and adjusted for baseline age, disease duration, Health Assessment Questionnaire (HAQ), 28-joint Disease Activity Score (DAS28) and pain score. RESULTS: At baseline patients worked a mean 20 h/week (SD 18). In unadjusted analyses, significant improvements in hours worked/week could already be observed in patients at 6 months (mean, 95% CI) +2.4 h (1.3 to 3.5), with further increases compared to baseline at 1-year (+4.0 h, 2.4 to 5.6) and 2-year follow-up (+6.3 h, 4.2 to 8.4). The trajectory appeared to stabilise at the 3-year (+6.3 h, 3.6 to 8.9), 4-year (+5.3 h, 2.3 to 8.4) and 5-year follow-up (+6.6 h, 3.3 to 10.0). In a mixed piecewise linear regression model, adjusted for age, sex, baseline disease activity, function and pain, an improvement of +4.2 h/week was estimated for the first year followed by an added improvement of +0.5 h/week annually during the years thereafter. Over 5 years of treatment, the expected indirect cost gain corresponded to 40% of the annual anti-TNF drug cost in patients continuing treatment. CONCLUSION: Data from this population-based registry indicate that biological therapy is associated with increases in workforce participation in a group typically expected to experience progressively deteriorating ability to work. This could result in significant indirect cost benefits to society.
19280937 [Targeted therapies including monoclonal antibodies for connective tissue diseases]. 2009 Mar Recent advance of targeted therapies including monoclonal antibodies and fusion proteins has allowed effective strategies in the treatment of rheumatoid arthritis. And now, TNF inhibitors are broadly used for rheumatoid arthritis and prevent the disease progression. Meanwhile, B cell targeted therapies and anti-interleukin-6 receptor antibody treatment are not only used for second line biological agents for rheumatoid arthritis, but also expected for the treatments of various autoimmune diseases. Recent year, some of novel small molecules, which inhibit the signal transduction of various surface receptors of immune cells, are in clinical trials. These drugs will be a breakthrough for the treatment of some autoimmune disorders.
19333936 Opposing effects of HLA-DRB1*13 alleles on the risk of developing anti-citrullinated prote 2009 Apr OBJECTIVE: The effect of non-shared epitope HLA-DRB1 alleles on rheumatoid arthritis (RA) is poorly understood. This study was undertaken to investigate the effects of several HLA-DRB1 alleles, independent of the shared epitope, on the risk of developing anti-citrullinated protein antibody (ACPA)-positive or ACPA-negative RA in a large case-control study. METHODS: HLA typing for the DRB1 gene was performed in 1,352 patients with RA and 922 controls from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: DRB1*13 was found to protect against ACPA-positive RA when stratifying for the shared epitope and using a dominant genetic model (RR 0.41 [95% CI 0.26-0.64]). Furthermore, DRB1*13 neutralized the effect of the shared epitope in ACPA-positive RA (RR 3.91 [95% CI 3.04-5.02] in patients who had the shared epitope but not DRB1*13, and RR 1.22 [95% CI 0.81-1.83] in patients with both the shared epitope and DRB1*13, as compared with patients negative for both the shared epitope and DRB1*13). However, we did not replicate the previous published risk of ACPA-negative RA conferred by DRB1*03 when a dominant genetic model was used (RR 1.29 [95% CI 0.91-1.82]). Similarly, no significant effect of DRB1*03 on RR for ACPA-negative RA was seen using the recessive genetic model (RR 1.18 [95% CI 0.6-2.4]). In contrast, the combination of DRB1*03 and DRB1*13 was significantly associated with increased risk of developing ACPA-negative RA (RR 2.07 [95% CI 1.17-3.67]). CONCLUSION: Our findings indicate that the DRB1*13 allele plays a dual role in the development of RA, by protecting against ACPA-positive RA but, in combination with DRB1*03, increasing the risk of ACPA-negative RA.
19701638 A systematic review of the effects of dynamic exercise in rheumatoid arthritis. 2009 Dec Exercise is commonly used in the management of patients with rheumatoid arthritis (RA); however, there is little consensus in the literature to support its use. This systemic review aimed to determine the effects of dynamic exercise on patients with RA. A systematic search of Medline (1949–2007), Cinahl (1982–2007), Embase (1974–2007) and Cochrane library was performed for randomised-controlled trials using the keywords “rheumatoid arthritis” and “exercise” or “training” or “sport”. The methodological quality of studies was assessed using a ten-point scale. Eighteen papers relating to 12 different studies met inclusion criteria. The mean methodological quality score was 6.9/10. Studies using aerobic training, strength training and combinations of both were included. Patients with early, stable, and active RA were studied. A number of studies reported improvement in muscle strength, physical function and aerobic capacity with dynamic exercise. Some studies also reported improvements in disease activity measures, and small improvements in hip bone mineral density. One study reported significantly less progression of small joint radiographic damage of the feet in the dynamic exercise group. However, one study also reported worse large joint radiographic damage in patients using dynamic exercise who had pre-existing large joint damage, though this was a retrospective analysis. No studies reported worse outcomes for function, disease activity or aerobic capacity with dynamic exercise. Cardiovascular outcomes were not reported in any study, and no data were presented to assess the effect of exercise on patients with significant underlying cardiovascular disease. This systematic review suggests that the majority of patients with RA should be encouraged to undertake aerobic and/or strength training exercise. Exercise programmes should be carefully tailored to the individual, particularly for patients with underlying large joint damage or pre-existing cardiovascular disease.
19663200 [Rituximab treatment of rheumatoid arthritis: new evidence]. 2009 New evidence is reviewed on efficacy and safety of chimeric monoclonal antibodies to B-cell CD20 molecule (rituximab) in the treatment of rheumatoid arthritis.
19922015 Costs and outcomes for patients with rheumatoid arthritis treated with biological drugs in 2009 Nov OBJECTIVE: To design an economic model describing the costs and outcomes for patients treated with tumour necrosis factor alpha (TNFalpha) inhibitors for rheumatoid arthritis (RA) in current clinical practice in Sweden, to be used as a tool to estimate cost-effectiveness of the next generation of treatments. METHODS: The model was constructed as a discrete event simulation (DES) model analysed at patient level. It contains treatment and outcome data for 1903 patients followed in the RA registry for biological drugs in southern Sweden between 1999 and 2007 [the Southern Swedish Arthritis Treatment Group (SSATG) Register]. Resource consumption was based on a survey of 1027 patients in the same region. Costs and quality-adjusted life years (QALYs) are presented for 10(5) years, for patients with the mean characteristics at treatment start in SSATG [Health Assessment Questionnaire (HAQ) score 1.33, disease duration 12.1 years, age 55 years], but also for patients with more or less severe disease. Cost and outcomes (QALYs) are discounted with 3%. RESULTS: The 10-year costs in the base case amount to USD 336,000 (SD USD 64,000) or EUR 223 000, with a total of 4.4 QALYs. Over 5 years, the costs amount to USD 208,000 or EUR 138,000 and QALYs to 2.5. The results were most sensitive to HAQ level at treatment start, but also to underlying disease progression, age, and disease duration. Starting treatment at a lower HAQ level (0.85) reduces costs by 10% and increase QALYs by 20%. CONCLUSION: This analysis is based on the longest available follow-up for patients treated with TNFalpha inhibitors and provides an opportunity to explore treatment strategies when new therapies become available using actual clinical practice data.
20665252 Epstein-Barr virus-infected subcutaneous panniculitis-like T-cell lymphoma associated with 2010 Sep Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a lymphoid proliferation or lymphoma in patients treated with MTX. We report a case of Epstein-Barr virus (EBV)-positive subcutaneous panniculitis-like T-cell lymphoma (SPTCL) in a 60-year-old Japanese man treated with MTX for rheumatoid arthritis (RA). SPTCL is a rare cytotoxic T-cell lymphoma characterized by involvement of subcutaneous fat mimicking panniculitis. The patient, who had been on MTX therapy for RA, manifested high fever and lumbago. Physical examination showed multiple subcutaneous nodules on the trunk including axillary and inguinal regions. Biopsy of the inguinal nodule showed profuse infiltration of CD8(+) T-cell lymphoma cells in the subcutaneous adipose tissues. A diagnosis of SPTCL was made according to the diagnostic criteria of World Health Organization classification. EBV-encoded small RNA in situ hybridization revealed that the lymphoma cells contained EBV genome. The cells were positive for EBV latent membrane protein 1, but not for EBNA2. After discontinuation of MTX, the nodules regressed spontaneously. Studies have reported that most MTX-LPDs are B-cell type lymphomas and Hodgkin lymphoma. To the best of our knowledge, EBV-positive SPTCL has not been reported in patients receiving MTX. Our case emphasizes the importance of clinical and virological characterization of MTX-associated SPTCL.
19254920 Belgian rheumatologists' perception on eligibility of RA patients for anti-TNF treatment m 2009 May OBJECTIVES: To assess discrepancies between perception of Belgian rheumatologists on eligibility of RA patients for anti-TNF treatment and Belgian reimbursement criteria and to compare Belgian with Dutch criteria and UK guidelines. METHODS: Consecutive MTX-experienced patients with active RA were recruited from 25 private and academic rheumatology practices. Discrepancies between eligibility for anti-TNF treatment according to the rheumatologist and fulfillment of Belgian reimbursement criteria [HAQ > or =25%, tender joint count (TJC) and swollen joint count (SJC) > or =8; > or =1 erosion; failure of > or =2 DMARDs including MTX; no tuberculosis] were recorded. Reasons for failing the Belgian criteria and results of applying Dutch reimbursement criteria and UK guidelines on the dataset were analysed. RESULTS: Of 492 patients, rheumatologists considered 135 (27.4%) as eligible, whereas Belgian criteria were fulfilled for only 34 (6.9%). Positive predictive value (PPV) of rheumatologists' perception on eligibility for fulfillment of Belgian criteria was 22.9%, whereas negative predictive value (NPV) was 99.1%. The 104 patients (21.1%) considered eligible despite criteria not being fulfilled had significantly greater TJCs, SJCs, disease activity score (DAS28) and Rheumatoid Arthritis Disease Activity Index scores than the 385 patients (78.2%) in the no-discrepancy group. Number of swollen joints, HAQ and erosions mainly accounted for discrepancies. Of 492 patients, 263 (53.4%) qualified for Dutch criteria and 41 (8.3%) for UK guidelines. PPV of Belgian rheumatologists' perception was 72.6% for fulfilling Dutch criteria (NPV 49.6%) and 23.4% for UK guidelines (NPV 96.7%). CONCLUSIONS: Rheumatologists consider more RA patients eligible for anti-TNF treatment than would be reimbursed according to Belgian criteria. Dutch guidelines, based on DAS28, match more closely eligibility according to Belgian rheumatologists.
19657582 Modification of Wright's technique for C2 translaminar screw fixation: technical note. 2009 Nov PURPOSE: To describe a modification of Wright's technique for C2 translaminar screw fixation. METHODS: Bilateral crossing C2 laminar screws have recently become popular as an alternative technique for C2 fixation. This technique is particularly useful in patients with anomalous anatomy, as a salvage technique where other modes of fixation have failed or as a primary procedure. However, reported disadvantages of this technique include breach of the dorsal lamina and spinal canal, early hardware failure and difficulty in bone graft placement due to the position of the polyaxial screw heads. To address some of these issues, a modified technique was used in six patients. In this technique, the upper part of the spinous process of C2 was removed and the entry point of the screw was in the base of this removed spinous process. RESULTS: The screw position was satisfactory in all patients. There were no intraoperative or early postoperative complications. CONCLUSIONS: Our modification enables placement of a bone graft on the C2 lamina and is also less likely to cause inadvertent cortical breach. Because of these advantages, it is especially suitable for patients with advanced rheumatoid arthritis with destruction of the lateral masses of C2 or as part of a hybrid construct in patients with a unilateral high-riding vertebral artery. This technique is not suitable for bilateral translaminar screw placement.
20036936 Chemokines and chemokine receptors in arthritis. 2010 Jan 1 Chemokines are involved in leukocyte recruitment to inflammatory sites, such as the synovial tissue in rheumatoid arthritis (RA). There is a structural and a functional classification of chemokines. The former includes four groups: CXC, CC, C and CX3C chemokines. Chemokines may also be either inflammatory or homeostatic, however, these functions often overlap. Anti-chemokine and anti-chemokine receptor targeting may be therapeutically used in the future biological therapy of arthritis. Most data in this field have been obtained from animal models of arthritis as only very few human RA trials have been completed. However, it is very likely that various specific chemokine and chemokine receptor antagonists will be developed and administered to RA patients.
18945584 A systematic review of the effectiveness of contrast baths. 2009 Jan STUDY DESIGN: Systematic review. INTRODUCTION: Contrast baths are used as an intervention in hand therapy, yet it is unclear which patients, if any, benefit from this intervention. PURPOSE OF THE STUDY: To examine the nature and quality of the evidence regarding the use of contrast baths using a systematic review process. METHODS: Of a total of 28 clinical research articles on contrast baths, from 1938 forward, ten met the inclusion criteria set by the authors. RESULTS: These studies addressed the physiological changes of hot and cold on blood flow, intramuscular temperature, subcutaneous temperature, and the influence of room temperature and age. The subjects included normal/healthy volunteers and patients with a diagnosis of rheumatoid arthritis, diabetes, or foot/ankle injuries. The diversity of conditions, protocols, and outcomes limited the ability to make definitive conclusions on efficacy. CONCLUSIONS: The contrast bath procedure may increase superficial blood flow and skin temperature, though the evidence on the impact on edema is conflicting. No relationship between physiologic effects and functional outcomes has been established. LEVEL OF EVIDENCE: 2A.
20883636 Rituximab in the treatment of rheumatoid arthritis patients in Italy: a budget impact anal 2010 Sep OBJECTIVES: The objective of this Budget Impact Analysis is to evaluate the financial implications of a rituximab-based sequencing strategy in the treatment of rheumatoid arthritis in the perspective of the Italian National Health Service. METHODS: Yearly patients who were eligible for a second-line biological DMARD in Italy were entered into a 5-year model. A Markov chain reproduced the course of this cohort under a number of alternative strategies, including anti-TNF-α cycling and rituximab or abatacept as second and third line agents. The dynamic of the simulation was given by first biological drug failure data, mortality rates, and survival-on-treatment data from published literature. Drug acquisition, administration and monitoring costs were assessed. RESULTS: Italian patients refractory to a first anti-TNF-α therapy resulted to be about 650 per year, giving a cumulative number of treated patients in five years of 3,240. The anti-TNF-α cycling had a total direct cost which rose from €8.2 million in the first year to €33.8 million in the fifth. The cost per patient of rituximab was lower than the average cost of the anti-TNF-α therapies; the annual difference was around € 4,300. The savings gained from lower individual costs with rituximab were partially offset by the increasing number of patients receiving active medication, resulting in a substantial cost equivalence between third line rituximab and anti-TNF-α cycling scenarios; rituximab, as a second line therapy, produced a savings in total costs of -31.8%. Strategies including abatacept shared the same dynamics, but with higher costs. CONCLUSIONS: The introduction of rituximab in clinical practice could allow an increase in the number of patients receiving an active rheumatoid arthritis treatment without inflating therapy costs.
19019887 Erosive progression is minimal, but erosion healing rare, in patients with rheumatoid arth 2009 Oct OBJECTIVE: With computed tomography (CT) and radiography, to investigate if repair of bone erosions, defined as regression of erosion scores, occurs during adalimumab treatment of patients with rheumatoid arthritis (RA). METHODS: Fifty-two patients with RA, naïve to biological agents, with at least two low-grade radiographic erosions in the wrist or metacarpophalangeal (MCP) joints in the same (index) hand, initiated adalimumab 40 mg subcutaneously every other week. Thirty-five patients completed the study (median age 61 years (interquartile range 46-68), disease duration 8 years (3-15)). CT of the index wrist and MCP joints 2-5 and radiographs of hands and forefeet were obtained at baseline, 6 and 12 months. Images were evaluated by investigators blinded to chronology and clinical data, and assessed according to Sharp/van der Heijde (radiographs) and OMERACT RA MRI scoring (CT) methods. RESULTS: Disease activity score, C-reactive protein, tender and swollen joints count and Health Assessment Questionnaire score had all decreased at 6 and 12 months (wilcoxon signed-ranks test p<0.001). No significant change in any imaging parameters of joint destruction was observed at 6 and 12 months. High intrareader agreements were reached (mean intraobserver intraclass coefficients: 0.96 (CT) and 0.97 (radiography)). The number of patients with change scores exceeding the smallest detectable change (SDC) was comparable on CT and radiography, as were the proportions of patients progressing/regressing. Decreased erosion scores at 12 months were registered in 1.6% and 1.8% of sites assessed on CT and radiography, respectively. CONCLUSION: Repair of erosions in adalimumab-treated patients with RA is rare, but erosive regression, exceeding the SDC, on CT and radiography occurred. The very limited overall erosive progression supports the view that joint destruction is minimal during adalimumab treatment of patients with RA.
18593759 Radiographic changes in rheumatoid arthritis patients attaining different disease activity 2009 Jun OBJECTIVE: To examine the association of radiographic progression and disease activity states in patients with rheumatoid arthritis (RA) treated with methotrexate with or without infliximab. METHODS: Patients (n = 1049) with active RA for 3 years or less and no previous methotrexate treatment were randomly assigned (4 : 5 : 5) to receive methotrexate plus placebo or methotrexate plus infliximab 3 or 6 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter to week 46. Disease activity was classified by the simplified disease activity index as remission (< or =3.3), low (>3.3 to < or =11), moderate (>11 to < or =26), high (>26). Radiographic progression was measured as a change from baseline to week 54 in total Sharp score. RESULTS: At weeks 14 and 54, more patients receiving methotrexate plus infliximab than methotrexate plus placebo were in remission (10.7% versus 2.8% week 14; 21.3% versus 12.3% week 54; p<0.001 for both). Methotrexate plus placebo halted radiographic progression only if patients achieved remission within 3 months, whereas methotrexate plus infliximab also halted or minimised progression in patients with low or moderate activity, respectively. Patients with persistently high disease activity levels had much less progression of joint damage if treated with methotrexate plus infliximab versus methotrexate monotherapy. Even with infliximab plus methotrexate there was a direct relationship between disease activity and radiographic changes, although the slope was deflected when compared with methotrexate monotherapy. CONCLUSION: With methotrexate, joint damage progresses even at low and moderate disease activity levels, whereas methotrexate plus infliximab inhibits radiographic progression across all disease activity states.
19877103 Anti-citrullinated peptide antibody assays and their role in the diagnosis of rheumatoid a 2009 Nov 15 Increasingly, assays for the detection of anti-citrullinated peptide antibodies (ACPA) are used in RA diagnosis. This review summarizes the biologic basis and development of ACPA assays, available ACPA assays and their performance characteristics, and diagnostic properties of ACPA alone and compared to rheumatoid factor (RF) in early RA. We also review correlations, precision, costs and cost-effectiveness, availability, stability and reproducibility of the available assays. Taken together, data indicate that ACPA has a higher specificity than RF for early RA, good predictive validity, high sensitivity, apparent cost-effectiveness and good stability and reproducibility. Given its superior performance characteristics and increasing availability, ACPA is emerging as the most useful single assay for the diagnosis of RA.
20193858 A cost-utility analysis of nonsurgical management, total wrist arthroplasty, and total wri 2010 Mar PURPOSE: Management of end-stage rheumatoid wrist disease remains controversial. Total wrist arthrodesis provides reliable pain relief and stability and is the most commonly applied management strategy. Total wrist arthroplasty is a motion-preserving alternative that is gaining popularity. The purpose of this study was to perform a cost-utility analysis comparing nonsurgical management, total wrist arthroplasty, and total wrist arthrodesis for the rheumatoid wrist. METHODS: A time trade-off utility survey was developed to investigate patient and physician preferences for the potential outcomes of total wrist arthroplasty and total wrist arthrodesis. The study sample consisted of rheumatoid patients (N = 49) recruited as part of an ongoing prospective study and a national random sample of hand surgeons and rheumatologists (N = 109). A decision tree was created using utility values derived from the survey, and the expected quality-adjusted life-years (QALYs) for each procedure were determined. Using the societal perspective, costs were based on the Medicare fee schedules for the Current Procedural Terminology codes associated with total wrist arthroplasty and total wrist arthrodesis and their potential complications. Costs per QALY were calculated and compared. RESULTS: Patients and physicians both showed a preference for surgical management over nonsurgical management. Application of cost data indicated that the incremental cost per additional QALY gained for total wrist arthroplasty over nonsurgical management was $2,281 and the incremental cost per QALY gained with total wrist arthroplasty over total wrist arthrodesis was $2,328, which is substantially less than the national standard of $50,000/QALY deemed acceptable for adoption. CONCLUSIONS: In the absence of rigorous outcome data, cost-utility analysis is a useful tool to guide treatment decisions. Total wrist arthroplasty and total wrist arthrodesis are both extremely cost-effective procedures. This study incorporated patient and physician utilities to demonstrate that total wrist arthroplasty has only a small incremental cost over the traditional total wrist arthrodesis procedure. Based on this economic model, total wrist arthroplasty may be worthy of further consideration, and cost should not be considered prohibitive. TYPE OF STUDY/LEVEL OF EVIDENCE: Decision Analysis II.
20203421 Comparison of hyaluronan effects among normal, osteoarthritis, and rheumatoid arthritis ca 2010 Feb High molecular weight hyaluronan (HA) is widely used in the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA) by intra-articular injection. However, comparative studies of HA actions on catalytically activated cartilages in different pathologic conditions have rarely been investigated. This study was aimed to compare the inhibitory effects of HA on nitric oxide (NO) production by COOH-terminal heparin-binding fibronectin fragment (HBFN-f) between normal and diseased cartilages. When articular cartilage explants from normal, OA, or RA joints were incubated with HBFN-f, the RA and OA cartilages produced higher levels of NO compared with normal cartilage. Pretreatment with 2700 kDa HA resulted in significant suppression of HBFN-f-stimulated NO production in OA and RA cartilages. While CD44 was up-regulated in OA and RA cartilages, anti-CD44 antibody reversed HA inhibition of HBFN-f action in those cartilages. The present results clearly demonstrated that HA blocked HBFN-f actions in OA and RA cartilages through interaction with CD44. HA, which targets CD44 highly expressed on OA and RA chondrocytes, could suppress catabolic actions by fibronectin fragments like HBFN-f in diseased cartilage.