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ID PMID Title PublicationDate abstract
16842163 Angiogenesis as a therapeutic target in arthritis: lessons from oncology. 2006 Rheumatoid arthritis (RA) is a chronic disabling autoimmune inflammatory disease of unknown aetiology with a prevalence of about 1% in most parts of the world. As a result of the debilitating nature of the disease, sufferers struggle with the simple activities of daily living and frequently fail to remain in full time employment. Furthermore, the mortality associated with the disease is equivalent to that seen in triple vessel coronary artery disease. Over the 10-15 years, advances in understanding the mechanisms of RA pathogenesis based on studies of human cells and animal models of arthritis have led to the identification of new targets for therapeutic intervention. Despite these advances, a significant proportion of patients continue to exhibit disease which is refractory to such therapy. As an alternative to anti-cytokine therapy, formation of new blood vessels ('angiogenesis') represents a potentially attractive target for therapy in RA. Angiogenesis has been a putative target in cancer since it was first linked to tumour growth and metastases in the 1970s. A number of significant advances have been made in the development of anti-cancer therapy using such an approach. This review focuses on the potential for targeting angiogenesis in RA, building upon the experience of angiogenesis inhibition in the oncological setting. Through this we hope to emphasise the potential value of anti-angiogenic therapy in RA and identify future directions for optimising treatment of this disabling disease.
17090982 The effectiveness of occupational therapy in restoring the functional state of hands in rh 2006 The aim of the study was to evaluate the effectiveness of occupational therapy in rheumatoid arthritis patients with impaired hand function. Standardized Functional Independence Measure was employed in order to evaluate the functional status of the patients and impaired activities. A dynamometer was used for the measurements of muscular strength of hands and a goniometer, for the range of motion of the wrist. Totally, we have examined 120 rheumatoid arthritis patients. They were divided into two groups: 60 patients in each. Occupational therapy was applied only to the patients of the first group. The mean age of Group 1 patients was 53.4+/-1.8 years, the mean age of Group 2 patients was 52.0+/-1.9 years. The mean duration of the disease was 11.5+/-2.6 years and 12.1+/-2.4 years, respectively. The effectiveness of therapy was considered ineffective if, after the completion of the course of occupational therapy, no increase in Functional Independence Measure score for patients with rheumatoid arthritis was observed. When the score increased from 1 to 3, we considered this as moderate effectiveness; when the score increased to 4-6, we evaluated the effectiveness of occupational therapy as good, and when the score of 7 was attained, effectiveness of occupational therapy was considered as very good. In Group 1, the moderate effectiveness of occupational therapy was determined in 31.7% of patients; good effectiveness, in 61.7%; and very good effectiveness, in 3.3% of rheumatoid arthritis patients. In Group 2, the moderate effectiveness of treatment was determined in 48.3% of patients and good effectiveness, in 5% of rheumatoid arthritis patients. CONCLUSIONS. Hand function (the strength of fingers and hands, the range of motion of the wrist) significantly improved in patients with rheumatoid arthritis after completion of a course of occupational therapy (p<0.05). The improvement of hand functions in patients with rheumatoid arthritis led to increased ability to take food and drink, to wash themselves, to put the clothes on the upper and lower parts of the body and take them off, to use the toilet, a bathtub or a shower, to walk, to manage a wheelchair, and to do personal hygiene (p<0.05).
16247721 MR imaging appearance of rheumatoid arthritis in the foot. 2005 Sep Although conventional radiographs remain the initial mainstay for imaging of the foot in patients with rheumatoid arthritis (RA), magnetic resonance (MR) imaging has afforded the ability to detect early signs of the disease (i.e., synovitis, tenosynovitis, bone lesions, and bursitis), especially at the forefoot. In addition, the relatively symmetric distribution of the imaging abnormalities depicted in the metatarsophalangeal joints and the frequent involvement of the retro-calcaneal bursitis are almost specific for RA. In more advanced stages of the disease, MR imaging is well suited to evaluation of the hindfoot joints and tendons as well as the musculoskeletal complications of RA (e.g., tendon disruption, rheumatoid nodules, sinus tarsi syndrome).
15934121 Effect of a high-intensity weight-bearing exercise program on radiologic damage progressio 2005 Jun 15 OBJECTIVE: To investigate whether a high-intensity exercise program accelerates the rate of radiologic damage of the large joints in predefined subgroups of patients with rheumatoid arthritis. METHODS: The data of 277 participants in a 2-year randomized controlled trial, comparing the effects of high-intensity exercises with usual care, were used. Linear regression analysis was used to test which predefined variables at baseline (age, disease duration, disease activity, physical capacity, functional ability, joint damage) modified the effect of high-intensity exercise on the progression of radiologic damage of the large joints over 24 months. RESULTS: Baseline radiologic joint damage was the only variable associated with the effect of high-intensity exercise on joint damage progression in large joints. In a subgroup of 218 patients with no or little joint damage (defined as Larsen score < or = 5; 80% of our study population) the proportions of patients with an increase in joint damage were similar for the exercise and usual-care group (35% versus 36%, risk ratio [RR] 1.0 [0.7-1.4]; P = not significant), whereas, in a subgroup of 59 patients who already had extensive damage of large joints (defined as Larsen score >5) the proportion was significantly higher in the exercise group (85% versus 48%, RR 1.8 [1.2-2.6]; P < 0.05). CONCLUSION: High-intensity weight-bearing exercises appear to accelerate joint damage progression in patients with preexisting extensive damage. Patients with extensive large joint damage should, therefore, be advised to refrain from activities excessively loading the damaged joints.
16333645 [Health economic research in rheumatic diseases]. 2006 Jan Thorough health economic research of budget-relevant diseases should be one of the major tasks in the German health care system. Up to now cost studies were only performed for special research questions and/or with very limited focuses, e.g. the patients' view. Hence, federal programmes, like competence networks for certain diseases, which were introduced by the German Ministry for Research and Education in the late 1990s, should give a broader focus on health services research. With such an approach health politicians may obtain a deeper insight into areas of the health care sector which are likely to be more efficient after reorganisation. The process of a structured analysis of certain diseases will be demonstrated using the example of rheumatoid arthritis (RA). To this end, the results of a research programme sponsored within the Competence Network for Musculoskeletal Diseases will be presented. Direct costs, indirect costs as well as values for health-related quality of life of German RA patients in routine care by generalists and specialists will be discussed.
16050144 Anti-CCP: history and its usefulness. 2005 Jun Antibodies directed to cyclic citrullinated peptides (anti-CCP) are highly specific for rheumatoid arthritis (RA) and can easily be detected in sera by using commercially available immunoassays. The second version of the anti-CCP test (anti-CCP2) demonstrated high specificity (89-98%) and good sensitivity (41-88%) for RA. Commercially available ELISA methods from three different companies are on the market. All three CCP2 assays show similar results as all CCP2 assays use the same antigen-coated plates. This study was an evaluation of a new automated method for the determination of anti-CCP2 in a routine laboratory setting. Five hundred and forty three serum samples were tested for anti-CCP2 within normal routine diagnostic using a commercially available ELISA and retested with a prelaunch version of a new and fully-automated method (EliA). The results were comparable. The new automated assay is easy to use and demonstrated a diagnostic sensitivity of 80% and specificity of 97%.
15972910 Results after 24 years of prophylactic surgery for rheumatoid atlantoaxial subluxation. 2005 Jul We evaluated the use of surgical stabilisation for atlantoaxial subluxation after a follow-up of 24 years in 50 rheumatoid patients who had some degree of pain but no major neurological deficit. The mortality of patients treated by atlantoaxial fusion was significantly lower than for those who received conservative treatment. The deaths resulted from infection or comorbid conditions. The significantly high relative risks of mortality from conservative treatment compared with surgical treatment were mutilating disease and susceptible factors on both of the HLA-DRB1 alleles. Relief from pain and neurological and functional recovery were better, and the radiological degree of atlantoaxial translocation was less in those who were surgically treated compared with those who were not. Two patients had superficial local infections after surgery. We conclude that prophylactic atlantoaxial fusion is better than conservative treatment in these patients.
16870104 Effect of Avemar--a fermented wheat germ extract--on rheumatoid arthritis. Preliminary dat 2006 May OBJECTIVE: To investigate the effect of the fermented wheat germ extract (Avemar)in patients with severe rheumatoid arthritis (RA). METHODS: Fifteen female RA (Steinbrocker II-III) patients, who had unsuccessfully tried two different DMARD treatments, were enrolled in an open-label, 1-year long, pilot clinical study. DMARD and steroid therapies were recorded and continued. All patients received Avemar as additional therapy. For measurement of efficacy the Ritchie Index, the Health Assessment Questionnaire (HAQ) and the assessment of morning stiffness were applied. Patients were evaluated at baseline, 6 and 12 months. For statistical analyses the Wilcoxon test was used. RESULTS: At both 6 and 12 months, Ritchie index, HAQ and morning stiffness showed significant improvements compared with the baseline values. Dosages of steroids could be reduced in about half of the patients. No side effects of Avemar were observed. CONCLUSION: Supplementation of standard therapies with a continuous administration of Avemar is beneficial for RA patients.
15696556 Comprehensive assessment of clinical outcome and quality of life after total elbow arthrop 2005 Feb 15 OBJECTIVE: To assess quantitatively the outcome and to explore the physiometric and psychometric properties of clinical, generic, and condition-specific instruments after total elbow arthroplasty. METHODS: Seventy-nine patients were assessed in a 6-19-year cross-sectional catamnesis by means of 6 widely used questionnaires, clinical examinations, and radiographic examinations. RESULTS: With regard to pain, general physical health, and all the mental health dimensions of the Short Form 36 (SF-36), the patients showed scores comparable to normative values. Elbow joint stability and satisfaction were both good. Significant functional limitation was evidenced by the low mean scores of the SF-36 physical functioning measure (48.7, normative 69.9) and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) function measure (51.1, normative 89.3). The SF-36 physical component summary and the DASH correlated highly (r = 0.76) and, in factor analysis, loaded on the factor "physical unspecific." The patient and clinical modified American Shoulder and Elbow Surgeons questionnaire (mASES) correlated with the Patient Related Elbow Evaluation form (r = 0.92 with the patient mASES) and loaded on "physical specific." The SF-36 mental component summary loaded on "mental quality of life." CONCLUSION: The patients' self-rated health, quality of life, and clinical outcome were good and were not affected by impairment in some specific functional abilities. A questionnaire set comprising the SF-36 and the patient and clinical mASES is proposed for the comprehensive and specific assessment of outcome after elbow arthroplasty.
16891219 The expression of collagenase 3 (MMP-13) mRNA in the synovial tissue is associated with hi 2006 Jun The histopathologic analysis of the synovial tissue is important to distinguish rheumatoid arthritis (RA) from other forms of synovitis and to provide information about prognosis and therapeutic strategies at early stages of the disease. In this context, the present study was performed to investigate the correlation between immunohistopathological and morphological features of synovitis and the expression of collagenase 3 (MMP-13) known to contribute significantly to cartilage degradation in RA. In the histopathologic scoring system used in this study, type I synovitis is characterized by B lymphocyte infiltration and an intact lining, and is only mild destructive to cartilage and bone. Type II shows marked diffuse infiltrations of macrophages and T lymphocytes, an ulcerated lining, fibrin exudation, and invasive growth into cartilage and bone tissue. Investigating 36 patients with RA, 21 patients (58%) were positive for the expression of collagenase 3 mRNA in the synovial tissue. Among these patients, 19 showed a histopathologic type II synovitis and only 2 patients had undifferentiated synovitis. In contrast, synovial tissue samples from patients without collagenase 3 mRNA expression were characterized in 6 cases by type I, in 5 cases by type II and in 4 cases by undifferentiated synovitis. The analysis of the clinical data revealed that RA patients with a histopathologic type II synovitis and synovial tissue collagenase 3 mRNA expression had elevated levels of systemic markers of inflammation and received stronger therapies. The data suggest, that collagenase 3 expression and the histopathologic type II synovitis are associated with a severe and destructive course of RA.
16296568 Change in and predictors of leisure activities among patients with rheumatoid arthritis: a 2005 Sep OBJECTIVE: To describe factors associated with leisure activities, changes in leisure activities over time, and predictors of such changes among persons with rheumatoid arthritis (RA). METHODS: A prospective study was conducted of 80 consecutive persons with RA, recruited while participating in a 3-week, rehabilitation day-care programme. The number of leisure activities was assessed through a structured interview. Sociodemographic variables, measures of disease activity [pain, patient's global assessment, C-reactive protein (CRP)], disability [Health Assessment Questionnaire (HAQ), Signals of Functional Impairment (SOFI), grip strength], quality of life at baseline, as well as disease activity [mean erythrocyte sedimentation rate (ESR)] and treatment (proportion of follow-up time on anti-rheumatic drugs during follow-up) were evaluated as possible predictors of change in leisure activities. RESULTS: Active leisure activities increased, while 'not obviously active or passive' leisure activities were unchanged during the follow-up period. The change in active leisure activities did not correlate with the predictors evaluated. CONCLUSION: The increase in active leisure activities was not predicted to a substantial degree by disease activity, disability, or medication. The results suggest that factors other than those evaluated influence changes in leisure activities.
17139662 Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A 2006 Dec 15 OBJECTIVE: Although early initiation of disease-modifying antirheumatic drugs (DMARDs) is effective in controlling short-term joint damage in individuals with rheumatoid arthritis (RA), the long-term benefit in disease progression is still controversial. We examined the long-term benefit of early DMARD initiation on radiographic progression in early RA. METHODS: We identified published and unpublished clinical trials and observational studies from 1966 to September 2004 examining the association between delay to treatment initiation and progressive radiographic joint damage. We included studies of persons with RA disease duration <2 years and DMARD therapy of similar efficacy during followup. The differences in annual rates of radiographic progression between early and delayed therapy were pooled as standardized mean differences (SMDs). RESULTS: A total of 12 studies met the inclusion criteria. The pooled estimate of effects from these studies demonstrated a significant reduction of radiographic progression in patients treated early (-0.19 SMD, 95% confidence interval [95% CI] -0.34, -0.04), which corresponded to a -33% reduction (95% CI -50, -16) in long-term progression rates compared with patients treated later. Patients with more aggressive disease seemed to benefit most from early DMARD initiation (P = 0.04). CONCLUSION: These results support the existence of a critical period to initiate antirheumatic therapy, a therapeutic window of opportunity early in the course of RA associated with sustained benefit in radiographic progression for up to 5 years. Prompt initiation of antirheumatic therapy in persons with RA may alter the long-term course of the disease.
16396695 Quality of life in rheumatoid arthritis: impact of disability and lifetime depressive spec 2005 Nov OBJECTIVE: The aim of this study was to investigate the impact of disability and lifetime subthreshold depressive symptoms on Health-Related Quality of Life (HRQoL) among patients with rheumatoid arthritis (RA). METHODS: Ninety-two subjects with a diagnosis of RA according to the American College of Rheumatology (ACR) criteria were recruited at the Department of Rheumatology of the University Hospital, Pisa, Italy. Participants who met DSM-IV-TR diagnostic criteria for current or previous Axis I disorders were excluded. Assessments of functional status and disability was conducted using both the ACR classification and the Stanford Health Assessment Questionnaire (HAQ). Health-related Quality of Life was assessed using the Medical Outcomes Study Short Form 36 health survey questionnaire (MOS-SF36) and lifetime depressive spectrum symptomatology using the Mood Spectrum Questionnaire, Self-Report version (MOODS-SR). RESULTS: Comparison with MOS-SF36 Italian normative values indicated that RA patients were significantly impaired on mental and physical HRQoL areas. Correlations between MOODS-SR depressive scores and ACR severity (Spearman rho = 0.15, p = 0.07) and HAQ score (Spearman rho = 0.20, p = 0.05) were modest in absolute value and borderline significant. Lifetime mood depressive spectrum was related with impaired HRQoL levels, both in physical (except for bodily pain) and mental (except for social functioning) domains. Associations of mood depressive spectrum and general health, vitality, role emotional and mental health continued to be significant after controlling for functional status, duration of illness, age and gender. CONCLUSIONS: Because lifetime mood depressive symptoms significantly contribute to impairment in HRQoL in RA patients without a past psychiatric history, even after controlling for functional status, duration of illness and demographic characteristics, these symptoms should be assessed for an accurate clinical evaluation and appropriate clinical management of RA patients.
16095151 [Progressive physical disability, pain and quality of life of patients with rheumatoid inf 2005 WHO pronounced years 2000-2010 the Decade of Bones and Joints--the main purpose of which is the improvement of the quality of life of patients suffering from inflammatory movement organ condition. A chronic disease leading to disability, handicap and even premature death is progressive rheumatoid arthritis (RA). Irreversible changes in the joints develop during the first years of RA. For the patient it results in certain ailments, physical disorders, lowering of the level of health and the quality of life. The purpose of the thesis was: specifying health problems of patients suffering from RA; evaluation of the level of physical disability along with patient's quality of life; defining both educational and caring tasks contributing to the improvement of the quality of life of the patient and preparation of the patient and their family to self-care. Patient suffering from RA demands professional manifold care and complex therapeutic actions. It is the patient themselves, however, who decides to what extent they allow the disease to control their lives or how much they control the disease themselves. Patient and their family need advice and support in the first stage of illness but also throughout the disease, in order to adapt to patient's changing health conditions--disorganizing and disordering physical, psychological and social functioning of the patient. Ascertaining the factors determining attitudes and aspirations of the patient may lead to achieving conditions influencing the improvement of the quality of their lives.
16255011 Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression 2005 Nov OBJECTIVE: To assess the effect of 5 mg/day prednisolone on disease progression in patients with early rheumatoid arthritis (RA) receiving standardized disease-modifying antirheumatic drug (DMARD) therapy. METHODS: Patients with active RA of <2 years' duration were randomly assigned in a double-blinded manner to receive prednisolone or placebo while starting concomitant DMARD therapy (gold sodium thiomalate or methotrexate). Hand and foot radiographs were taken at baseline and at 6, 12, and 24 months and were evaluated according to the Ratingen score and the total modified Sharp/van der Heijde score (SHS). RESULTS: Of 192 included patients, 166 were available for the intent-to-treat analysis (ITT). Seventy-six patients completed the study per protocol (PP). Radiographic progression (increase in the Ratingen score) was significantly less with prednisolone than with placebo. The difference in the progression rate between the groups was greatest in the first 6 months. At 24 months in the ITT population, the least squares (LS) mean difference was 3.14 (95% confidence interval [95% CI] 0.94, 5.34), P = 0.006. The results were confirmed by the total SHS in the ITT population (LS mean difference 7.20 [95% CI 0.93, 13.47], P = 0.022) and with the PP population. Clinical and functional outcomes tended to be better and the rate of remissions was higher in the prednisolone group. Side effects were observed more frequently in the prednisolone group than in the control group: weight gain (4 versus 0 patients), hypertension (6 versus 2 patients), glaucoma (3 versus 0 patients), Cushing's syndrome (5 versus 0 patients), gastric distress (9 versus 4 patients), and gastric ulcers (only with concomitant nonsteroidal antiinflammatory drug therapy; 3 versus 0 patients). No new lumbar fractures were found in either group. CONCLUSION: The very low daily dose of 5 mg prednisolone given over 2 years in combination with background DMARD therapy substantially decreased radiographic progression in early RA at low risk.
17133543 Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying 2006 Dec OBJECTIVE: More timely and effective therapy for rheumatoid arthritis (RA) has contributed to increasing rates of clinical remission. However, progression of structural damage may still occur in patients who have satisfied remission criteria, which suggests that there is ongoing disease activity. This questions the validity of current methods of assessing remission in RA. The purpose of this study was to test the hypothesis that modern joint imaging improves the accuracy of remission measurement in RA. METHODS: We studied 107 RA patients receiving disease-modifying antirheumatic drug therapy who were judged by their consultant rheumatologist to be in remission and 17 normal control subjects. Patients underwent clinical, laboratory, functional, and quality of life assessments. The Disease Activity Score 28-joint assessment and the American College of Rheumatology remission criteria, together with strict clinical definitions of remission, were applied. Imaging of the hands and wrists using standardized acquisition and scoring techniques with conventional 1.5T magnetic resonance imaging (MRI) and ultrasonography (US) were performed. RESULTS: Irrespective of which clinical criteria were applied to determine remission, the majority of patients continued to have evidence of active inflammation, as shown by findings on the imaging assessments. Even in asymptomatic patients with clinically normal joints, MRI showed that 96% had synovitis and 46% had bone marrow edema, and US showed that 73% had gray-scale synovial hypertrophy and 43% had increased power Doppler signal. Only mild synovial thickening was seen in 3 of the control subjects (18%), but no bone marrow edema. CONCLUSION: Most RA patients who satisfied the remission criteria with normal findings on clinical and laboratory studies had imaging-detected synovitis. This subclinical inflammation may explain the observed discrepancy between disease activity and outcome in RA. Imaging assessment may be necessary for the accurate evaluation of disease status and, in particular, for the definition of true remission.
16978395 Four-year follow-up of infliximab therapy in rheumatoid arthritis patients with long-stand 2006 Although there is strong evidence supporting the short-term efficacy and safety of anti-tumour necrosis factor-alpha agents, few studies have examined the long-term effects. We evaluated 511 patients with long-standing refractory rheumatoid arthritis treated with intravenous infusions of infliximab 3 mg/kg at weeks 0, 2, 6, and 14 and every 8 weeks thereafter for 4 years. Among the initial 511 patients included in the study, 479 could be evaluated; of these, 295 (61.6%) were still receiving infliximab treatment at year 4 of follow-up. The most common reasons for treatment discontinuation were lack of efficacy (65 patients, 13.6%), safety (81 patients, 16.9%), and elective change (38 patients, 7.9%). Analysis of disease activity scores (DAS28 [disease activity score based on the 28-joint count]) over time showed that, after the initial rapid improvement during the first 6 to 22 weeks of therapy, a further decrease in disease activity of 0.2 units in the DAS28 score per year was observed. DAS28 scores, measured at week 14 or 22, were found to predict subsequent discontinuation due to lack of efficacy. In conclusion, long-term maintenance therapy with infliximab 3 mg/kg is effective in producing further reductions in disease activity. Disease activity measured by the DAS28 at week 14 or 22 of infliximab therapy was the best predictor of long-term attrition.
17160372 Aspects of the biology of hyaluronan, a largely neglected but extremely versatile molecule 2006 Nov HA takes part in a surprisingly large number of biological processes such as embryogenesis, angiogenesis, cell motility, wound healing and cell adhesion. While substantial progress in HA research has indeed been made over the last years, many important questions have not yet been answered. One of the most pertinent questions awaiting an answer is the quest for functional differences of HA synthesized by the three HAS genes. Of similar importance would be investigations into intracellular signaling pathways involved in the activation of this gene family, a field in which to date very little is known. A better understanding of functional differences between the HAS encoding genes not only holds the promise for a better understanding of a series of biological processes but also the opportunity for selective intervention in a number of maladies characterized by abnormalities of HA levels.
16331787 Magnetic resonance imaging in rheumatoid arthritis advances and research priorities. 2005 Dec This article updates the work and results of the OMERACT MRI in RA Working Group as presented at the OMERACT 7 meeting in May 2004, focusing on the development of the EULAR-OMERACT rheumatoid arthritis magnetic resonance imaging reference image atlas, and on areas for future research.
16783859 Psychosocial variables and fatigue: a longitudinal study comparing individuals with rheuma 2006 Aug OBJECTIVE: In individuals with rheumatoid arthritis (RA) and healthy controls, at enrollment and one year later, we evaluated relationships between diverse psychosocial characteristics and fatigue in multivariate analyses. METHODS: Participants with RA and controls completed the Fatigue Severity Scale (FSS) at enrollment and again after one year. All participants also completed measures of depressive symptoms, anxiety, role satisfaction, social support, social stress, disability, physical activity, and sleep quality at enrollment. RESULTS: A total of 122 individuals with RA and 122 controls of similar age, sex, education, employment, and marital status were enrolled. Those with RA had more fatigue compared to controls (FSS scores 4.2 +/- 1.2 vs 3.4 +/- 1.1; p < 0.0001) (possible range 1-7, higher score = more fatigue). In cross-sectional multivariate regression analysis for the RA group, more fatigue was associated with more anxiety, more disability, less social support, and more social stress (p