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ID PMID Title PublicationDate abstract
15794200 Marital and sexual satisfaction in patients with RA and their spouses. 2004 This study sets out to determine predictors of marital and sexual satisfaction in patients with rheumatoid arthritis (RA) and their spouses. Fifty-nine patients and their spouses completed questionnaires independent from each other. Multiple correlations with marital and sexual satisfaction were computed for demographic variables, disease status, psychological distress, and social support. The results indicate that psychological distress and social support are more important than objectively assessed disease status in determining marital and sexual satisfaction in patients with RA.
12186261 Eculizumab (Alexion). 2002 Jul Eculizumab (5G1.1), a humanized monoclonal antibody that prevents the cleavage of human complement component C5 into its pro-inflammatory components, is under development by Alexion as a potential treatment for several chronic inflammatory diseases, including rheumatoid arthritis (RA) and nephritis [190673], [292328]. In January 2002, a phase IIb trial was initiated for RA [437814]. This trial was ongoing in April 2002, at which time, eculizumab was also in phase II trials for the treatment of membranous nephritis and lupus nephritis, and in earlier stage clinical trials for dermatomyositis and pemphigoid [446377]. The company is also developing a single-chain version of this antibody, pexelizumab, for use in acute cardiovascular indications [188760]. In October 2000, eculizumab was granted Orphan Drug status by the FDA for the treatment of dermatomyositis [385057]. In February 2002, the product received Orphan Drug designation for its use in patients with membranous nephritis [440583]. In September 2001, analysts at US Bancorp Piper Jaffray predicted eculizumab's launch for dermatomyositis and pemphigus in 2003, RA and nephritis in 2004, and chronic heart failure (CHF) after 2006 [426537]. In March 2002, analysts at US Bancorp Piper Jaffray predicted that the product would have peak worldwide sales in RA of US $175 million and US $400 million for nephritis. Sales for the RA indication are predicted to reach US $35 million in 2006, rising to US $110 million in 2008, and US $10 million in 2006, rising to US $50 million in 2008, in the US and the rest of the world, respectively. For the nephritis/other indication(s), sales are pegged at US $50 million in 2006, rising to US $200 million in 2008, and US $15 million in 2006, rising to US $100 million in 2008, again in the US and the rest of the world, respectively [446992].
14971085 Mortality in rheumatoid arthritis patients treated with or without methotrexate. 2003 BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease associated with excess mortality. In 1974 a registry of RA patients was established at the Wichita Arthritis Center. It has been directed by its founder, Dr. Frederick Wolfe, ever since. The database for RA patients provided results for the present study and 1 of the 4 series reported previously. RESULTS: These are based on a consecutive series (after specific exclusions) of RA patients, 18 years of age and older, treated at the Wichita Arthritis Center, 1981 through 1999. During this period, 588 of the total 1240 RA patients were treated with methotrexate, and 652 patients did not receive any methotrexate. Total exposure amounted to 7584 patient-years, and total deaths numbered 191. An elaborate statistical method was developed by Wolfe and a team of Harvard epidemiologists to adjust for prognostic risk factors, which were higher in the methotrexate than in the non-methotrexate group. Detailed descriptive data were included in the database. Overall excess mortality in comparison with population rates was higher in the methotrexate than in the non-methotrexate group, but the unadjusted difference was not significant. Results for the 1981-1999 total Wichita cohort were compared with those of the 1974-1990 cohort and the 1983 Impairment Study (both before and after adjustment to the older age distribution of the Wichita patients). CONCLUSION: Mortality improved somewhat in the RA patients at the Wichita Center from 1974-1990 to 1980-1999. In the later period, mortality was lower in patients treated with methotrexate than in those not so treated. After the authors of the source article made adjustments for the increased RA severity in the patients treated with methotrexate, mortality was significantly lower in the methotrexate-treated group, with a mortality hazard ratio of 0.4 (95% confidence interval 0.2-0.8).
15286005 Association between baseline radiographic damage and improvement in physical function afte 2005 Jan OBJECTIVES: To identify factors associated with poor physical function in rheumatoid arthritis and to assess whether baseline joint damage has an impact on improvement in physical function during infliximab treatment. METHODS: 428 patients with active rheumatoid arthritis despite methotrexate treatment received methotrexate alone or with infliximab (3 mg/kg or 10 mg/kg every four or eight weeks) for 54 weeks (the ATTRACT trial). Data on clinical outcomes and physical function (assessed by the health assessment questionnaire (HAQ)) were collected. Structural damage was assessed using the van der Heijde modification of the Sharp score. Odds ratios (OR) for factors associated with severe functional disability (HAQ > or =2.0) at baseline were estimated using multiple logistic regression analyses, and baseline factors related to the change in physical function after treatment at week 54 were determined. RESULTS: Baseline radiographic scores were correlated with baseline HAQ scores. After adjustment for demographic characteristics in the logistic regression model, baseline disease activity scores, radiological joint damage, fatigue, and morning stiffness were found to be associated with severe functional disability (HAQ >2.0), with OR values of 2.00 (1.53 to 2.63), 1.82 (1.15 to 2.87), 1.19 (1.05 to 1.34), and 1.07 (1.01 to 1.13), respectively. In multiple linear regression analysis, physical disability, joint damage, and fatigue at baseline were correlated with less improvement in physical function after treatment. Infliximab treatment was associated with greater improvement in physical function. CONCLUSIONS: Greater joint damage at baseline was associated with poorer physical function at baseline and less improvement in physical function after treatment, underlining the importance of early intervention to slow the progression of joint destruction.
12623520 Time trends in disability pensioning for rheumatoid arthritis, osteoarthritis and soft tis 2003 AIMS: Disability pensioning with musculoskeletal diagnoses increased more than general disability pensioning in Norway during 1968-97. Incidences of disability pensioning for three main musculoskeletal diseases - rheumatoid arthritis, osteoarthritis and soft tissue rheumatism - during the period 1968-97 were assessed. Changes in incidence were related to changes in Norwegian society with respect to prevalence of these diseases, the number of individuals having high probability of disability pensioning for these diseases, the labour market and legal amendments that may have changed the probability of being granted a disability pension among these patients. METHODS: Data on all new disability pensioners aged 50-66 years registered by the National Insurance Administration during 1968-97 and the total population of Norway excluding disability pensioners were used to calculate annual incidence rates of disability pension for the selected musculoskeletal diagnoses. RESULTS: The incidence of disability pension for soft tissue rheumatism and osteoarthritis increased during the study period, and both increased more than the incidence of disability pension in general. The incidence of disability pension for rheumatoid arthritis decreased when compared with disability pensioning in general. The year an upward or downward trend started is similar for osteoarthritis and soft tissue rheumatism for men and women in the age groups studied. CONCLUSION: Changes in prevalence of a disease seem to be an important factor in explaining differences in time trends of disability pensioning with different diagnoses. Changes in unemployment, female employment, number of manual workers or the legal system do not appear to be related to the increases in incidence of disability pensioning with musculoskeletal diseases.
12484691 Diagnostic and therapeutic injection of the elbow region. 2002 Dec 1 Joint injection of the elbow is a useful diagnostic and therapeutic tool for the family physician. In this article, the injection procedures for the elbow joint, medial and lateral epicondylitis, and olecranon bursitis are reviewed. Persistent pain related to inflammatory conditions responds well to injection in the region. Indications for elbow joint injection include osteoarthritis and rheumatoid arthritis. Corticosteroid injection is an accepted treatment option for medial and lateral epicondylitis. Olecranon bursa aspiration and injection are useful when that bursa is inflamed. The proper techniques, choice and quantity of pharmaceuticals, and appropriate follow-up essential for effective outcomes are discussed.
15246026 Endothelial dysfunction in rheumatoid arthritis: influence of HLA-DRB1 alleles. 2004 Jun Cardiovascular disease is the commonest cause of premature mortality in rheumatoid arthritis (RA) patients. Vascular endothelial injury is the primary event in atherosclerosis. It has been associated with endothelial dysfunction. We have recently observed that actively treated RA patients had endothelial dysfunction. HLA-DRB1 shared epitope alleles, in particular HLA-DRB1*0404, seem to be implicated in the development of endothelial dysfunction. These results underline the influence of genetic factors in the risk of atherosclerosis in RA patients.
12598804 Complementary medicine. 2003 Mar Complementary medicine has become an important subject for rheumatologists, not least because many patients try complementary treatments. Recent clinical trials yield promising results. In particular, evidence suggests that several herbal medicines and dietary supplements can alleviate the pain of osteoarthritis and rheumatoid arthritis. Clearly, rigorous testing of complementary treatments is possible, and considering their popularity, should be encouraged.
12120910 Posterior tibial tendon dysfunction and MR imaging in rheumatoid arthritis. 2002 May We present the case of a patient with long-standing rheumatoid arthritis and an acute onset of total dysfunction of the posterior tibial tendon. On MRI, a rupture of the tendon was apparent. Intraoperatively, however, massive tenosynovitis with stricture of the tendon was identified as the cause of posterior tibial tendon dysfunction. This case illustrates a pitfall in MRI imaging with potential diagnostic and therapeutic consequences.
15375655 [Surgical aspects of the cervical spine in rheumatoid arthritis]. 2004 Oct Approximately 20% percent of the patients with rheumatoid arthritis show pathology in the cervical spine. The translational instability between axis and atlas might be painful and leads in the long term to myelopathic changes due to chronic traumatization of the myelon. Ongoing osseous resorption of the lateral masses of the atlas cause upward migration of the dens into the foramen magnum. In the subaxial cervical spine, the inflammatory process causes instability and deformity. Neck pain is the most common indication for surgery, but neurological symptoms with myelopathy or radicular deficits might be the primary cause for surgery. Neurophysiological investigation is suitable to obtain objective results. Stabilization of the atlantoaxial segment is the most common procedure for treatment of atlantoaxial instability. It is performed by screw fixation technique from a posterior approach. In case of severe occipitocervical dislocation, the fixation has to be extended to the occiput. Persistent dislocation or compression by the dislocated dens has to be treated by transoral decompression. In the subaxial spine, instabilities may be treated by posterior plate fixation with lateral mass screws or pedicle screws. Concomitant nar-rowing of the spinal canal should be approached by anterior decompression with corpectomy and/or posterior laminectomy. The timing of surgery in rheumatoid patients is crucial to obtain satisfactory clinical results.
14969067 Databases of patients with early rheumatoid arthritis in the USA. 2003 Sep Several databases of patients with early rheumatoid arthritis (RA) have been established in the USA. The University of Tennessee at Memphis Cohort was organized in 1967-1971 to enroll 50 young adults (16-44 years) with symptom onset of < or = 6 months who met the 1958 American Rheumatism Association (ARA) criteria for at least probable RA. Two important observations from this database were that many patients seen within the first 6 months of meeting the criteria for probable RA have a self-limited rather than progressive disease, and that progressive disease is predicted by a high number of baseline swollen and tender joints. The National Institutes of Health (NIH) cohort of patients with peripheral synovitis for > or = 6 weeks but < 12 months in at least one peripheral joint was established in 1994. At the one-year follow-up, 45% of the patients met the RA criteria, 9% had reactive arthritis, 6% had psoriatic arthritis, 5% had other rheumatic diseases, and 35% had undifferentiated arthritis. The number of active joints, rather than meeting the criteria for RA, was the primary determinant of function and performance after one year. The Western Consortium of Practicing Rheumatologists (CPR) was established in 1993 to enroll patients with an RA duration < 1 year, positive rheumatoid factor, > or = 6 swollen and > or = 9 tender joints, and no previous treatment with disease modifying anti-rheumatic drugs (DMARDs). Data from this cohort indicated the validity of self-report joint counts. American College of Rheumatology 20% improvement (ACR20) responses were seen in 50% of patients at 6 months and in 57% of patients at 24 months, while antinuclear antibodies (ANA) were seen in 69% of patients prior to the availability of biologic agents. The North American Cohort of Patients with Early RA (SONORA), which included patients with symptoms for > 3 but < 12 months, indicated that methotrexate (MTX) was the most frequently prescribed DMARD, being taken by more than half the patients. The Consortium for the Longitudinal Evaluation of African-Americans with RA (CLEAR) registry and DNA repository has enrolled 123 African-American patients with early RA of less than 2 years' duration to analyze genetic and non-genetic factors associated with disease severity. The Early RA Treatment Evaluation Registry (ERATER) of patients with early RA (< 3 years) was established in 2001. In this registry, MTX was the first DMARD used in 83% of patients, and most patients would not meet the criteria for inclusion in recent clinical trials of biological agents. Further observation of recent cohorts of patients with early RA over the next decade should be informative regarding whether aggressive intervention strategies and new DMARDs and biologic agents lead to improved long-term outcomes.
12635863 Prevalence of C282Y mutation in patients with rheumatoid arthritis and spondylarthritis. 2002 Rheumatoid arthritis is an inflammatory joint and systemic disease believed to be of autoimmune origin. Predisposing factors also include genetic factors, such as the presence of alleles HLA-DRB1 *04, (HLA-DRB1 *0401, *0404, *0405 and *0408) and, in other ethnic groups, of subtypes DRB1 *0101, *0102 and DRB1 *1001. These genetic factors are believed to raise the risk of developing the disease. In rheumatoid arthritis, as in other chronic inflammatory diseases, iron metabolism dysfunction has been observed and attributed to inflammation. In hereditary hemochromatosis, tissue sideropexia is associated with a peculiar form of arthropathy. C282Y is a point mutation involving the replacement of a cysteine with a tyrosine at position 282 of the HFE protein. When found in homozygosis, there is a close association with hereditary hemochromatosis, accounting for one of the causes of iron metabolism dysfunction observed in this disease. The aim of this study was to compare the frequency of C282Y in patients with rheumatoid arthritis with that in patients with different forms of spondylarthritis and to correlate these findings with iron metabolism parameters. In the group of patients with rheumatoid arthritis, 2/24 (8.34%) were found to be positive for the C282Y mutation in the case of heterozygosis compared with 3/24 (12.5%) of patients with spondylarthritis. In patients with the C282Y mutation, ferritin levels were significantly higher than those in controls; conversely, serum iron levels were higher in patients with spondylarthritis. Serum transferrin levels, although slightly higher in rheumatoid arthritis patients, showed no statistically significant differences.
14969077 Role of adalimumab in the treatment of early rheumatoid arthritis. 2003 Sep Adalimumab, a recent addition to the therapeutic armamentarium in rheumatoid arthritis (RA), has been evaluated in patients with early RA. The DE019 study, a double blind randomized placebo controlled trial of adalimumab given 20 mg once a week or 40 mg every other week demonstrated both clinical and radiographic efficacy. A subset analysis of patients with early disease revealed that early treatment with adalimumab may be more efficacious than therapy later in the course of disease, particularly with regard to radiographic progression. The findings support early aggressive intervention in RA.
12020477 Small-molecule inhibitors of NF-kappaB for the treatment of inflammatory joint disease. 2002 Jun Recent advances in our understanding of the role of cytokine networks in inflammatory processes have led to the development of novel biological agents for the treatment of chronic inflammatory diseases. At the present time, significant efforts are focused on characterizing the complex signal transduction cascades that are activated by these cytokines and, in turn, regulate their expression. The transcription factor NF-kappaB is a pivotal regulator of the inducible expression of key proinflammatory mediators, and activated NF-kappaB has been observed in several debilitating inflammatory disorders, including rheumatoid arthritis and osteoarthritis. In light of its central role in inflammation, the identification of inhibitors of NF-kappaB should provide novel therapeutics for the treatment of chronic joint disease.
12817089 The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. 2003 May The role of the cytokine network in mediating inflammation and joint destruction in rheumatoid arthritis (RA) has been investigated extensively in recent years. Interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha) are two pivotal proinflammatory cytokines that have been shown to contribute to the clinical manifestations of RA. The ability of IL-1 to drive inflammation and joint erosion and to inhibit tissue repair processes has been clearly established in in vitro systems and animal models. Under physiological conditions, the activity of IL-1 is balanced by IL-1 receptor antagonist (IL-1R alpha). Understanding of the respective roles of IL-1 and IL-1R alpha in conditions of health and disease has led to the development of a recombinant IL-1ra, anakinra (Kineret; Amgen Inc., Thousand Oaks, CA), which offers a new therapeutic modality for RA.
15579209 The value of the qualitative method for adaptation of a disease-specific quality of life a 2004 Dec 4 BACKGROUND: Due to differences in current socio-economical situation and historically shaped values, different societies have their own concepts of high-quality life. This diversity of concepts interferes with quality of life (Qol) research in health sciences. Before deciding to apply a Qol assessment tool designed in and for another society, a researcher should answer the question: how will this instrument work under the specific circumstances of my research. Our study represents an example of the utilization of qualitative research methods to investigate the appropriateness of the Rheumatoid Arthritis Quality of Life Scale (RAQol) for the assessment of Qol in Estonian patients. METHODS: Semi-structured interviews were conducted with the rheumatoid arthritis (RA) patients of Tartu University Hospital and these were analyzed using the principles of the grounded theory. RESULTS: We described the significance of the questionnaire's items for our patients and also identified topics that were important for the Qol of Estonian RA patients, but that were not assessed by the RAQol. We concluded that the RAQol can be successfully adapted for Estonia; the aspects of Qol not captured by the questionnaire but revealed during our study should be taken into account in future research. CONCLUSIONS: Our results show that qualitative research can successfully be used for pre-adaptation assessment of a Qol instrument's appropriateness.
12073116 Pathophysiology and imaging in inflammatory and blastomatous synovial diseases. 2002 Jun Variable pathologies are subsumed under the term "synovial disease", including common pathologies such as rheumatoid arthritis. While formerly radiologists had to rely on conventional radiographs and bone scintigraphy with their inherent problems in visualizing soft tissue, noninvasive imaging of the synovium has recently improved substantially with the technical development of MRI and (Doppler) ultrasound. These imaging modalities allow differentiation of characteristic pathologic features based on a profound knowledge of normal anatomy and pathophysiology.
15561738 The inhibition of antithrombin by peptidylarginine deiminase 4 may contribute to pathogene 2005 Mar OBJECTIVE: The gene for peptidylarginine deiminase 4 (PADI4) has been found to be closely associated with rheumatoid arthritis (RA). Peptidylarginine deiminase (PADI) catalyses the post-translational modification of peptidylarginine to citrulline, a reaction known as citrullination. PADI extracted from rabbit muscle has been reported to citrullinate antithrombin, a principal plasma inhibitor of thrombin. Thrombin is known to induce angiogenesis, fibrin formation and inflammation, the primary events of the RA joint. Here, we investigate whether human PADI4 can inhibit antithrombin by catalysing antithrombin citrullination and how the enzyme is involved in RA pathogenesis. METHODS: Antithrombin was incubated with recombinant PADI4 protein, and the inactivation of antithrombin was determined by reduction of its thrombin-inhibiting activity. Citrullination of antithrombin was detected by western blotting and enzyme-linked immunosorbent assay (ELISA). In addition, the citrullination level, activity and concentration of antithrombin in RA plasma were investigated by sandwich ELISA. RESULTS: Incubation of antithrombin with PADI4 resulted in loss of thrombin-inhibitory activity and in citrullination of antithrombin. RA plasma showed higher levels of citrullinated antithrombin than controls with non-arthritis disease and healthy individuals. CONCLUSION: The results indicate that PADI4 could inactivate antithrombin through citrullination. The abnormal expression or activation of PADI4 in RA synovium is suggested to be responsible for the high level of citrullinated antithrombin in RA plasma. Local inhibition of antithrombin activity in RA synovium might lead to the excessive angiogenesis, fibrin deposition and inflammation of the tissue.
12767265 Imbalance of peripheral B lymphocytes and NK cells in rheumatoid arthritis. 2003 Jan The study was focused on several cellular immune disorders correlated with the imbalance between peripheral blood B lymphocytes and NK cells in severe rheumatoid arthritis. By flow cytometry we calculated the proportions of T, T helper, T cytotoxic/suppressor, B lymphocytes and natural killer cells in peripheral blood. The mitogen-induced proliferation of peripheral lymphocytes was measured by tritium-labeled uridine incorporation. Experimental data highlight a connection between annomal values of the B to natural killer cells ratio and disorders of the peripheral mononuclear cells concentration. We also showed that the polyclonal proliferation capacity of peripheral lymphocytes in rheumatoid arthritis is solely related to the B to natural killer cells ratio or to the natural killer cells proportion. The study reveals a potential role of the imbalance between proportions of peripheral B lymphocytes and natural killer cells in the immune pathogenesis of rheumatoid arthritis, thus pointing out an interrelation between the adaptive and innate immune systems.
14757997 Calorie restricted diet and urinary pentosidine in patients with rheumatoid arthritis. 2004 Jan Low-energy diets and fasting have suppressive effects on rheumatoid arthritis. It was reported recently that urine levels of pentosidine (i.e., an advanced glycation end product formed by glycosylation) is associated with the activity of rheumatoid arthritis. We conducted a regimen of caloric restriction combined with fasting in patients with rheumatoid arthritis, and then evaluated urinary pentosidine levels. Ten patients with rheumatoid arthritis underwent a 54-day caloric restriction program. Urinary pentosidine levels were measured and the Lansbury Index were determined by examining the clinical features, blood biochemistry and the inflammation activity of rheumatoid arthritis on days 0, 25 and 54. On day 0, the mean urinary pentosidine level of patients with rheumatoid arthritis was significantly higher than that of the control subjects. On day 54, the mean body weight had reduced due to caloric restriction. The mean values of the erythrocyte sedimentation rate and the Lansbury Index of patients both significantly decreased during the study. In addition, although the urinary pentosidine levels showed no significant difference between day 0 and 25, it was significantly decreased at the end of the study (day 54). The study showed that under a low energy diet a reduction of disease activity in rheumatoid arthritis was accompanied with a reduction of the urinary pentosidine.