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ID PMID Title PublicationDate abstract
17101049 T-cell contact-dependent regulation of CC and CXC chemokine production in monocytes throug 2006 We and others have reported that rheumatoid arthritis (RA) synovial T cells can activate human monocytes/macrophages in a contact-dependent manner to induce the expression of inflammatory cytokines, including tumour necrosis factor alpha (TNFalpha). In the present study we demonstrate that RA synovial T cells without further activation can also induce monocyte CC and CXC chemokine production in a contact-dependent manner. The transcription factor NFkappaB is differentially involved in this process as CXC chemokines but not CC chemokines are inhibited after overexpression of IkappaBalpha, the natural inhibitor of NFkappaB. This effector function of RA synovial T cells is also shared by T cells activated with a cytokine cocktail containing IL-2, IL-6 and TNFalpha, but not T cells activated by anti-CD3 cross-linking that mimics TCR engagement. This study demonstrates for the first time that RA synovial T cells as well as cytokine-activated T cells are able to induce monocyte chemokine production in a contact-dependent manner and through NFkappaB-dependent and NFkappaB-independent mechanisms, in a process influenced by the phosphatidyl-inositol-3-kinase pathway. Moreover, this study provides further evidence that cytokine-activated T cells share aspects of their effector function with RA synovial T cells and that their targeting in the clinic has therapeutic potential.
18496696 Epigallocatechin-3-gallate suppresses TNF-alpha -induced production of MMP-1 and -3 in rhe 2008 Nov Rheumatoid arthritis (RA) synovial fibroblasts produce matrix metaloproteinases (MMPs), which destroy cartilage and bone in RA joint. Tumor necrosis factor-alpha (TNF-alpha) is one of the most important mediator leading to MMP production in RA synovial fibroblasts. Here we show that epigallocatechin-3-Gallate (EGCG) suppresses TNF-alpha-induced production of MMP-1 and MMP-3 in RA synovial fibroblasts, which was accompanied by inhibition of mitogen activated protein kinase (MAPK) and activator protein-1 (AP-1) pathways. EGCG treatment resulted in dose-dependent inhibition of TNF-alpha-induced production of MMP-1 and MMP-3 at the protein and mRNA levels in RA synovial fibroblast. EGCG treatment also inhibited TNF-alpha-induced phosphorylation of MAPKs, such as ERK1/2, p38, JNK. Electrophoretic mobility shift assay revealed that EGCG inhibits binding of AP-1 proteins to its response elements in synovial fibroblast treated. Thus, EGCG may play a role in regulating inflammation and bone destruction in RA patients.
18415766 Increased levels of autoantibodies against catalase and superoxide dismutase associated wi 2008 Mar OBJECTIVE: To evaluate the level of autoantibodies against superoxide dismutase (SOD) and catalase (CAT) in the sera of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) Tunisian patients, to study the oxidative profile among the same patients and to establish a correlation between the two parameters in order to understand the role of each one in the genesis of the two diseases. METHOD: Using a standard enzyme-linked immunosorbent assay (ELISA), the levels of immunoglobulin G (IgG) and IgM directed against CAT and SOD in the sera of 39 RA patients, 40 SLE patients, and 50 control healthy individuals were evaluated. The oxidative/antioxidative profile was tested by measuring serum malondialdehyde (MDA), conjugated dienes (CD), CAT activity, and SOD activity. RESULTS: Our data showed increased levels of IgG antibodies (Ab) against CAT in both groups of patients (p<0.05) compared to control subjects. However, the SLE patients displayed an increased level of anti-SOD IgG (p<0.05). In all patients the lipid peroxidation was confirmed by high levels of MDA and conjugated dienes (p<0.05). RA patients exhibited an increasing CAT and SOD activity in their sera (p<0.05) with a positive correlation observed between CAT and IgG anti-CAT (p<0.05). The same results were observed for SLE patients. In addition, a positive correlation was observed between anti-CAT Ab and anti-SOD Ab in SLE patients (p<0.05). CONCLUSION: Collectively, these results suggested that the primary factor causing the oxidative stress observed in RA and SLE is excessive free radical production rather than impaired CAT or SOD activity due to autoantibody inhibition.
17534091 Coccidioidomycosis pneumonia in a nonendemic area associated with infliximab. 2007 May Tumor necrosis factor (TNF) inhibitors, such as infliximab, are highly effective in the management of rheumatoid arthritis; however, these agents are associated with an increased risk of infectious complications. Individuals developing coccidiomycosis pneumonia frequently acquire this while residing in endemic regions. We present a patient with rheumatoid arthritis treated with infliximab who developed acute respiratory distress syndrome (ARDS) from coccidiomycosis pneumonia while residing in a non-endemic region near the Texas-Louisiana border and was successfully treated with antifungal therapy. The source for coccidiomycosis was suspected to be from inhalation of pulverized rock dust imported from Arizona. Patients treated with TNF inhibitors may acquire coccidiomycosis infection through fomite dust exposure.
18438842 Association of interferon regulatory factor 5 haplotypes, similar to that found in systemi 2008 May OBJECTIVE: Previous studies have shown either a lack of effect of IRF5 polymorphisms or an association of the IRF5 gene in only a minor subset of rheumatoid arthritis (RA) patients in whom anti-citrullinated protein antibodies (ACPAs) are absent. The present study was undertaken to investigate the role of genetic variation in IRF5 in susceptibility to RA. METHODS: Nine IRF5 single-nucleotide polymorphisms (SNPs) were studied in 1,338 patients with RA and 1,342 control subjects in analyses of exploratory and replication sample collections, with stratification according to sex and by the presence or absence of ACPAs, rheumatoid factor, the shared epitope, the 620W PTPN22 allele, and erosions. A meta-analysis that included results from previous studies was also carried out. RESULTS: Our findings together with those from previous studies, in a total of 4,620 RA patients and 3,741 controls, showed a significant association of the rs2004640 IRF5 SNP in RA patients as a whole (odds ratio [OR] 0.88, 95% confidence interval [95% CI] 0.83-0.94; P = 6.5 x 10(-5) versus controls). This association was stronger in ACPA- patients, but was also present in ACPA+ patients (from 3 sample collections). Further analysis of our exploratory sample collection showed that only patients in the ACPA+ and SE- group lacked an association with IRF5 SNPs. All of the remaining RA patients (ACPA- or SE+) showed a strong association with IRF5 SNPs, which followed a complex pattern of opposing effects mediated by independent haplotypes. The susceptibility haplotype showed an OR of 1.8 (95% CI 1.4-2.3; P = 1.2 x 10(-6) versus controls), whereas the protective haplotype showed an OR of 0.76 (95% CI 0.6-0.98; P = 0.046 versus controls). CONCLUSION: IRF5 polymorphisms seem to influence RA susceptibility in a large subgroup of patients, following a pattern of association very similar to that described in patients with systemic lupus erythematosus.
17521223 Etanercept: a review of its use in the management of rheumatoid arthritis. 2007 Etanercept (Enbrel), a soluble fusion protein that binds specifically to the cytokine human tumour necrosis factor (TNF), is approved for subcutaneous use in the treatment of patients with moderate to severe active rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing arthritis and plaque psoriasis in the US, Italy, the rest of the EU and other countries worldwide. Subcutaneous etanercept was efficacious and generally well tolerated in several large, well designed, clinical trials and in the clinical-practice setting in adult patients with rheumatoid arthritis, including methotrexate-naive patients with early disease and those with long-standing, treatment-resistant active disease. Etanercept plus methotrexate combination therapy was generally superior to either monotherapy in reducing disease activity and structural joint damage, as well as improving health-related quality of life (HR-QOL). Furthermore, etanercept monotherapy was superior to placebo and at least as effective as methotrexate therapy in reducing disease activity and improving HR-QOL in patients with early or refractory disease. The beneficial effects of etanercept monotherapy or combination therapy were sustained in the long term (< or =9 years). Some pharmaco-economic analyses suggest that etanercept is a cost-effective option in the treatment of patients with rheumatoid arthritis. Direct head-to-head comparisons with other biological agents would help to definitively position etanercept with respect to these agents. Nevertheless, extensive clinical experience indicates that etanercept is a valuable treatment option in adult patients with long-standing moderate to severe active rheumatoid arthritis and an emerging option in those with early disease.
18757951 Birmingham hip resurfacing arthroplasty: a series of 110 consecutive hips with a minimum f 2008 Sep We report the outcome at a minimum of five years of 110 consecutive metal-on-metal Birmingham Hip Resurfacing arthroplasties in 98 patients. The procedures were performed between October 1999 and June 2002 by one surgeon. All patients were followed up clinically and radiologically. The mean follow-up was 71 months (60 to 93). Revision of either component was defined as failure. The mean Harris Hip score at follow-up was 96.4 (53 to 100). The mean Oxford hip score was 41.9 (16 to 57) pre-operatively and 15.4 (12 to 49) post-operatively (p < 0.001). The mean University of California Los Angeles activity score was 3.91 (1 to 10) pre-operatively and 7.5 (4 to 10) post-operatively (p < 0.001). There were four failures giving a survival at five years of 96.3% (95% confidence interval 92.8 to 99.8). When applying a new method to estimate narrowing of the femoral neck we identified a 10% thinning of the femoral neck in 16 hips (14.5%), but the relevance of this finding to the long-term outcome remains unclear. These good medium-term results from an independent centre confirm the original data from Birmingham.
17142384 Arthritis of the large joints - in particular, the knee - at first presentation is predict 2007 May OBJECTIVE: To investigate the predictive value of the distribution of inflamed joints at first presentation for the severity of the disease course in rheumatoid arthritis (RA). METHODS: Of the 1009 consecutive patients included in the Leiden Early Arthritis Clinic (Leiden, The Netherlands), 285 patients fulfilled the American College of Rheumatology criteria for RA within 1 year of follow-up. Of these, 28 patients achieved remission. Radiographs of hands and feet were scored according to the Sharp-van der Heijde method, and the 28 patients with the most destructive disease were selected. The distribution of inflamed joints of the patients with the extreme disease courses was compared. The association between the distribution of inflamed joints and the level of destruction of the joints of hands and feet in the whole group of patients with RA was assessed using regression analysis. RESULTS: Comparison of patients with extreme disease courses using univariate and logistic regression analyses showed that arthritis of the large joints - in particular, the knee - was associated with severe RA. In the whole group of patients with RA, the total number of swollen joints and the presence of knee arthritis were associated independently with the level of destruction of the small joints. Patients with RA with knee arthritis had higher C reactive protein (CRP) levels than patients without knee arthritis, and investigating the distribution of inflamed joints together with other variables yielded the number of swollen joints, CRP, presence of anti-cyclic citrullinated peptide antibodies and symptom duration as predictors for severity of RA. CONCLUSION: Arthritis of large joints - in particular, the knee - at first presentation is associated with a destructive course of RA.
19054823 Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy wit 2009 Jul OBJECTIVE: To evaluate the efficacy and toxicity of methotrexate (MTX) monotherapy compared with MTX combination with non-biological disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis. METHOD: A systematic review of randomised trials comparing MTX alone and in combination with other non-biological DMARDs was carried out. Trials were identified in Medline, EMBASE, the Cochrane Library and ACR/EULAR meeting abstracts. Primary outcomes were withdrawals for adverse events or lack of efficacy. RESULTS: A total of 19 trials (2025 patients) from 6938 citations were grouped by the type of patients randomised. Trials in DMARD naive patients showed no significant advantage of the MTX combination versus monotherapy; withdrawals for lack of efficacy or toxicity were similar in both groups (relative risk (RR) = 1.16; 95% CI 0.70 to 1.93). Trials in MTX or non-MTX DMARD inadequate responder patients also showed no difference in withdrawal rates between the MTX combo versus mono groups (RR = 0.86; 95% CI 0.49 to 1.51 and RR = 0.75; 95% CI 0.41 to 1.35), but in one study the specific combination of MTX with sulfasalazine and hydroxychloroquine showed a better efficacy/toxicity ratio than MTX alone with RR = 0.3 (95% CI 0.14 to 0.65). Adding leflunomide to MTX non-responders improved efficacy but increased the risk of gastrointestinal side effects and liver toxicity. Withdrawals for toxicity were most significant with ciclosporin and azathioprine combinations. CONCLUSION: In DMARD naive patients the balance of efficacy/toxicity favours MTX monotherapy. In DMARD inadequate responders the evidence is inconclusive. Trials are needed that compare currently used MTX doses and combination therapies.
18250472 A plant-derived ligand favoring monomeric glucocorticoid receptor conformation with impair 2008 Feb 15 The glucocorticoid receptor (GR) is a transcription factor regulating its target genes either positively, through direct binding to the promoter of target genes, or negatively by the interference with the activity of transcription factors involved in proinflammatory gene expression. The well-known adverse effects of glucocorticoids are believed to be mainly caused by their GR-mediated gene-activating properties. Although dimerization of GR is thought to be essential for gene-activating properties, no compound has yet been described which selectively imposes GR monomer formation and interference with other transcription factors. In the present study, we report on a GR-binding, plant-derived compound with marked dissociative properties in rheumatoid arthritis fibroblast-like synoviocytes, which are important effector cells in inflammation and matrix degradation in rheumatoid arthritis. In addition, these findings could be extended in vivo in murine collagen-induced arthritis, in which joint inflammation was markedly inhibited without inducing hyperinsulinemia. Therefore, we conclude that GR monomers are sufficient for inhibition of inflammation in vivo.
18506884 Mutual antagonistic relationship between prostaglandin E(2) and IFN-gamma: Implications fo 2008 Jul Prostaglandin E(2) (PGE(2)) is a major mediator of inflammation and is present at high concentrations in the synovial fluid of rheumatoid arthritis (RA) patients. PGE(2), acting through the EP4 receptor, has both pro- and anti-inflammatory roles in vivo. To shed light on this dual role of PGE(2), we investigated its effects in whole blood and in primary human fibroblast-like synoviocytes (FLS). Gene expression analysis in human leukocytes, confirmed at the protein level, revealed an EP4-dependent inhibition of the expression of genes involved in the IFN-gamma-activation pathway, including IFN-gamma itself. This effect of the PGE(2)/EP4 axis on IFN-gamma is a reciprocal phenomenon since IFN-gamma blocks PGE(2) release and blocks EP receptor expression. The mutually antagonistic relationship between IFN-gamma and PGE(2) extends to downstream cytokine and chemokine release; PGE(2) counters the effects of IFN-gamma, on the release of IP-10, IL-8, TNF-alpha and IL-1beta. To gain further insight into IFN-gamma-mediated cellular events in RA, we assessed the effects of IFN-gamma on gene expression in FLS. We observed an IFN-gamma-dependent up-regulation of macrophage-attracting chemokines, and down-regulation of metalloprotease expression. These results suggest the existence of a mutually antagonistic relationship between PGE(2) and IFN-gamma, which may represent a fundamental mechanism of immune control in diseases such as RA.
18438829 Progression of joint damage in early rheumatoid arthritis: association with HLA-DRB1, rheu 2008 May OBJECTIVE: To determine the association of HLA-DRB1, rheumatoid factor (RF), and anti-citrullinated protein antibody (ACPA) status with progression of joint damage in early rheumatoid arthritis (RA) treated according to different treatment strategies. METHODS: The present study was conducted using data from the BeSt study (Behandelstrategieën voor Reumatoide Artritis [treatment strategies for rheumatoid arthritis]), a randomized trial comparing 4 targeted (toward achievement of a Disease Activity Score [DAS] of < or =2.4) treatment strategies: sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with methotrexate, sulfasalazine, and prednisone (group 3), and initial combination therapy with methotrexate and infliximab (group 4), in 508 patients with early RA. Multivariate logistic regression analysis was used to predict progressive disease (increase of Sharp/van der Heijde score over 2 years beyond the smallest detectable change [4.6]) according to the presence or absence of the shared epitope (SE), DERAA, RF, and ACPA, with correction for other baseline characteristics. RESULTS: Progressive disease could not be predicted by presence of the SE: the odds ratio in groups 1, 2, 3, and 4, respectively, was 1.4, 2.6, 1.9, and 3.0. DERAA carriership did not protect against progressive disease (odds ratio 0.4, 1.4, 0.9, and 0.9 in groups 1, 2, 3, and 4, respectively). RF positivity and ACPA positivity predicted progressive disease in group 1 (odds ratio 4.7 [95% confidence interval 1.5-14.5] for RF and 12.6 [95% confidence interval 3.0-51.9] for ACPA), but not in groups 2-4 (for RF, odds ratio [95% confidence interval] 1.5 [0.5-4.9], 1.0 [0.3-3.3], and 1.4 [0.4-4.8] in group 2, group 3, and group 4, respectively; for ACPA, odds ratio [95% confidence interval] 3.4 [0.8-14.2], 1.7 [0.5-5.4], and 1.8 [0.5-6.8] in group 2, group 3, and group 4). CONCLUSION: In patients with early RA treated with the goal of tight control of the DAS, no significant association between HLA-DRB1 status and radiographic progression was found. RF and ACPA were predictive of progressive disease only in patients treated with sequential monotherapy. These observations suggest that effective treatment can prevent radiographic progression, even in patients with risk factors for severe damage.
19050823 Serum levels of tissue inhibitor of metalloproteinase-1 and periarticular bone loss in ear 2009 Mar We investigated the relationship between disease activity, serum biological mediators of joint damage, and periarticular bone loss in inflammatory arthritis. Patients with early inflammatory arthritis were recruited from a dedicated early arthritis clinic. At the time of recruitment, all had clinical evidence of synovitis. Patients were assessed at baseline and at 1-year follow-up. Periarticular and axial bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Serum levels of matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by enzyme-linked immunosorbent assay. A total 38 patients were included in the study. Twenty had rheumatoid arthritis (RA) and 18 had a seronegative spondylarthropathy (SpA). At baseline, periarticular hand BMD measurements were similar in RA and SpA. At 1 year, the mean periarticular hand BMD was significantly lower in RA (p < 0.05). Significant inverse correlations between both the Ritchie articular index and C-reactive protein levels and the change in periarticular hand BMD at 1 year were observed in RA (r = -0.792, p < 0.001 and r = -0.478, p = 0.045, respectively). Baseline TIMP-1 levels correlated with the change in periarticular hand BMD at 1 year in RA (r = 0.519, p = 0.02). At 1 year, radiographic measures of joint damage were highest in RA. Inverse correlations between the change in periarticular hand BMD and the changes in erosion score (r = -0.90, p = 0.04) were observed in patients demonstrating significant periarticular bone loss. Persistent disease activity was associated with increased periarticular bone loss in the hands in patients with RA, consistent with synovitis-mediated periarticular bone loss. The correlation between baseline TIMP-1 levels and periarticular bone loss over 1 year suggests that TIMP-1 may have utility as a biomarker of periarticular bone loss in early RA.
17141021 Sex differences in autoimmune disease. 2006 Oct Many, but not all, autoimmune diseases primarily affect women. In humans, severity of illness does not differ between men and women. Men and women respond similarly to infection and vaccination, which suggests that the intrinsic differences in immune response between the sexes do not account for differences in disease frequency. In autoimmune-like illnesses caused by recognized environmental agents, sex discrepancy is usually explained by differences in exposure. Endogenous hormones are not a likely explanation for sex discrepancy; hormones could have an effect if the effect is a threshold rather than quantitative. X and Y chromosomal differences have not been studied in depth. Other possibilities to explain sex discrepancy include chronobiologic difference and various other biologies, such and pregnancy and menstruation, in which men differ from women.
17314120 Changes in lipid profile during infliximab and corticosteroid treatment in rheumatoid arth 2007 Jul OBJECTIVE: To evaluate the effects of infliximab and corticosteroid treatment on the lipid profile in patients with active rheumatoid arthritis (RA). METHODS: Infliximab infusions were given at weeks 0, 2, 6 and then every 8 weeks. Before each infusion, disease activity parameters (Disease Activity Index 28-Joint Score (DAS28)) C reactive protein (CRP) and lipid levels (total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein A1 (apo A1) and apolipoprotein B) were measured in 80 consecutive patients with RA, who completed the study period of 48 weeks. Longitudinal analyses were used to investigate (1) the course of lipid levels over a period of time and (2) the relationship between lipids, prednisone dose and disease activity. RESULTS: Infliximab treatment causes a significant reduction in disease activity and a concomitant decrease in prednisone dose. Although they initially improved significantly, all lipid levels had returned to baseline levels after 48 weeks, except for apo A1. Longitudinal analyses revealed significant yet opposite associations between lipid levels and disease activity and between lipid levels and prednisone dose. DAS28 improvement by 1 point was associated with an increase of 0.016 mmol/l (0.618 mg/dl) total cholesterol and 0.045 mmol/l (1.737 mg/dl) HDL-cholesterol. Reduction of 10 mg prednisone was associated with a decrease of 0.04 mmol/l (1.544 mg/dl) total cholesterol and 0.16 mmol/l (6.177 mg/dl) HDL-cholesterol. CONCLUSION: Overall, no changes in serum lipid levels were observed after 48 weeks of infliximab treatment. The initial beneficial effects of infliximab on the lipid profile, by means of a reduction of disease activity, are attenuated by a concomitant decrease in prednisone dose.
18227853 Receptors for complement C5a. The importance of C5aR and the enigmatic role of C5L2. 2008 Feb Complement component C5a is one of the most potent inflammatory chemoattractants and has been implicated in the pathogenesis of numerous inflammatory diseases. C5a binds two receptors, C5aR and C5L2. Most of the C5a functional effects occur through C5aR, and the pharmaceutical industry has focused on this receptor for the development of new anti-inflammatory therapies. We used a novel approach to generate and test therapeutics that target C5aR. We created human C5aR knock-in mice, and used neutrophils from these to immunize wild-type mice. This yielded high-affinity blocking mAbs to human C5aR. We tested these anti-human C5aR mAbs in mouse models of inflammation, using the human C5aR knock-in mice. These antibodies completely prevented disease onset and were also able to reverse established disease in the K/B x N arthritis model. The physiological role of the other C5a receptor, C5L2 is still unclear, and our studies with blocking mAbs to human C5L2 have failed to demonstrate a clear functional role in signaling to C5a. The development of effective mAbs to human C5aR is an alternative approach to drug development, for this highly attractive target.
18697778 The sensitivity to change for lower disease activity is greater than for higher disease ac 2009 Aug OBJECTIVE: To test whether rheumatoid arthritis (RA) trials treatment efficacy versus control is better detected for patients with lower tender joint counts (TJC) or swollen joint counts (SJC) than for higher counts. METHODS: Using data from six large multicentre trials (N = 2002) and an intent-to-treat approach at 6 months, two subtrials were created within each trial, the lower disease activity group (defined by TJC less than overall median) and the higher disease activity group. The same approach was used for SJC. Active treatment was tested for treatment control differences using several RA trial outcome measures: ACR20, EULAR response, ACRHybrid. Sample sizes needed for higher TJC and SJC RA trials versus lower TJC and SJC trials were compared. RESULTS: Subtrials of subjects with lower TJC were found to have much higher sensitivity to change than those of subjects with higher TJC across all trials and outcome measures. A trial with lower TJC patients would require a smaller sample size than those with higher TJC patients. Results were not consistent for SJC subgroups. Three reasons were found for sensitivity to change of lower TJC: compared with higher TJC, those with lower TJC showed greater response to active treatment. SUBJECTS: with higher TJC on control treatment had greater percentage improvement and more variable responses than those in the lower TJC group. CONCLUSIONS: In RA trials, patients with lower disease activity within the range of current trial eligibility are more likely to show treatment efficacy than patients with higher disease activity. Lowering thresholds especially for TJC in trials may make it easier to detect treatment effects in RA.
18443391 Effects of a multifaceted psychiatric intervention targeted for the complex medically ill: 2008 BACKGROUND: This study evaluated a multifaceted psychiatric intervention targeted at the complex medically ill identified by means of the INTERMED, an instrument to assess case complexity. METHODS: Of 885 rheumatology inpatients and diabetes outpatients who were assessed for eligibility, 247 were identified as complex (INTERMED score >20) and randomized to the intervention (n = 125, 84 rheumatology and 41 diabetes patients) or care as usual (n = 122, 78 rheumatology and 44 diabetes patients). For the majority of the cases the multifaceted intervention consisted of an intervention conducted by a psychiatric liaison nurse and/or of referral to a liaison psychiatrist, followed by advice to the treating physician or organization of a multidisciplinary case conference. Baseline and follow-up at months 3, 6, 9 and 12 measured prevalence of major depression (Mini-International Neuropsychiatric Interview), depressive symptoms (Center for Epidemiological Studies Depression Rating Scale), physical and mental health (SF-36), quality of life (EuroQol), health care utilization and HbA(1c) levels (diabetic patients). RESULTS: Prevalence of major depression was reduced from 61% (T0) to 28% (T4) in the intervention group and remained stable in care as usual (57% at T0 to 50% at T4). Compared to care as usual, significant improvement over time was observed in the intervention group with regard to depressive symptoms (F = 11.9; p = 0.001), perception of physical (F = 5.7; p = 0.018) and mental health (F = 3.9; p = 0.047) and quality of life (F = 21.8; p < 0.001). Effects tended to be stronger in diabetes patients, in patients with baseline major depression and in patients with moderate INTERMED scores. Finally, hospital admissions occurred less often in the intervention group, reaching statistical significance for the period between 6 and 9 months of follow-up (p = 0.02). CONCLUSIONS: The results suggest that a psychiatric intervention targeted for complex medical patients can improve health outcomes.
17564781 Primary cervical epidural malignant lymphoma with rheumatoid arthritis: a case report. 2007 We report a case of primary cervical epidural malignant lymphoma with rheumatoid arthritis. Because of the acute progression of paralysis in both legs, surgical decompression and stabilization of the cervical spine were performed. The resected specimen showed proliferation of lymphoblastic cells diagnosed as malignant lymphoma. Four series of chemotherapy were administered after surgery, and the patient recovered from paralysis.
18383356 Biologic drugs for rheumatoid arthritis in the Medicare program: a cost-effectiveness anal 2008 Apr OBJECTIVE: Since the introduction of the Medicare Prescription Drug Improvement and Modernization Act and its associated demonstration project, coverage of selected biologic drugs has been expanded for Medicare beneficiaries. For rheumatoid arthritis, coverage was extended to etanercept, adalimumab, and anakinra in addition to the previously covered infliximab. We undertook to develop a model to compare the costs and quality-adjusted life years (QALYs) generated by each of the 4 biologic agents. METHODS: Data were drawn from meta-analysis of randomized controlled trials and from a large longitudinal outcomes databank. Uncertainty was addressed using probabilistic and one-way sensitivity analyses. A lifetime horizon and Medicare viewpoint were adopted. RESULTS: In the base case analysis, anakinra was the least effective and least costly strategy. Etanercept, adalimumab, and infliximab were similar in terms of effectiveness, but infliximab was more costly. If decision makers are willing to pay a maximum of $50,000/QALY, the probability that infliximab is cost-effective is <1%. Findings were robust to a range of sensitivity analyses. Only if the dose of infliximab remains constant over time is this likely to be a cost-effective strategy. CONCLUSION: Infliximab is unlikely to be cost-effective in the Medicare population compared with either etanercept or adalimumab. Anakinra is substantially less costly but is also less effective than the 3 tumor necrosis factor alpha inhibitors.