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ID PMID Title PublicationDate abstract
16701130 Rheumatoid arthritis: silicone metacarpophalangeal joint arthroplasty indications, techniq 2006 May Silicone implant arthroplasty has been used for more than 40 years for severe rheumatoid disease at the metacarpophalangeal (MCP) joint. Multiple investigations have shown that silicone arthroplasty places the MCP joint in a more extended posture, with some improvement in the total arc of motion. Ulnar drift is also improved, but strength and other objective measures have not demonstrated marked changes postoperatively. The lack of prospective data and more complete outcome assessment has been, at least in part, responsible for the marked difference in opinions between rheumatologists and hand surgeons on the effectiveness of MCP arthroplasty. Recent reports using patient-centered outcome measures have shown that early outcome is favorable, with improvements in appearance, pain, and function.
15711231 Outcomes of patients with rheumatoid arthritis receiving rehabilitation. 2005 Mar PURPOSE OF REVIEW: Rehabilitation, including physical therapy and occupational therapy, complements drug therapy in the management of symptoms in patients with rheumatoid arthritis. Approximately 26% of patients with rheumatoid arthritis receive a referral for rehabilitation by rheumatologists. This review summarizes findings on the effectiveness and economic outcomes of physical therapy and occupational therapy in managing rheumatoid arthritis. RECENT FINDINGS: Studies evaluating the outcomes of various service delivery models for physical therapy and occupational therapy demonstrate improvements, especially in physical function, among people with rheumatoid arthritis. A recent pilot study examining the primary therapist model also suggests that the primary therapist model may be a viable option for delivering rheumatoid arthritis rehabilitation services. However, the evidence on other alternative models such as the physical therapy/occupational therapy practitioner model is limited. Only a few economic evaluations have been performed, and among those, none examine the cost-effectiveness of different service models. SUMMARY: Systematically interpreting the findings of service delivery models in rehabilitation is challenging because of the wide range of interventions and outcome measures used. A thorough understanding of the value of different rehabilitation models will require the guidance of a sound evaluation framework. Future clinical trials should consider including a component for evaluating cost-effectiveness. Such knowledge can contribute to evidence-informed resource allocation.
16283676 Rheumatoid arthritis, a complex multifactorial disease: on the way toward individualized m 2006 Jan With the availability of the human genome sequence and those of related species like chimpanzee, mouse, and rat, data driven research for tackling the molecular grounds of rheumatoid arthritis (RA), a multifactorial polygenic disease, can be considered a realistic challenge to the scientific community. A comprehensive research strategy is presented enabling the integration of multiple research efforts on studying autoimmunity by so called systems biology approaches. An integrative scientific concept is discussed of how to unravel molecular mechanisms of complex diseases by making use of state-of-the-art methodologies in functional and comparative genomics. A continuous interchange of data-driven and hypothesis-driven research is adjoined to determine the nature of rheumatic diseases with autoimmune background. Instead of studying single genes and proteins, RNA and protein microarray profiles are currently obtained in numerous research projects producing read-outs termed gene signatures rather than DNA and/or protein markers. A comprehensive study of the RNA, protein, and metabolite regimes is undertaken that eventually will lead to a "holistic" view of how all respective molecules, pathways and cells themselves interact with each other. Some of the above mentioned research aspects have already been studied by the authors, hopefully leading to new diagnostics and therapeutics in the future.
15884771 Rodent models of rheumatoid arthritis. 2005 Apr The study of rheumatoid arthritis is greatly facilitated by animal models that enable investigation of a complex system involving inflammation, immunological tolerance, and autoimmunity. Although the models cover several species and pathogenetic mechanisms and can be classified as induced or spontaneous, all converge on arthritis. However, because each model features a different mechanism driving disease expression, the merits of each should be evaluated carefully in making the appropriate choice for the scientific question to be addressed. In addition, because the incidence and kinetics of disease vary by model, careful thought should be given to protocol design to minimize animal use.
16583201 [Systemic manifestations of rheumatoid arthritis]. 2006 May Extra-articular manifestations of rheumatoid arthritis are gaining in importance both in rheumatology and other specialities. This report provides information on various organ manifestations and interactions between mere disease-related symptoms and therapeutic effects. Diagnostic radiology plays a crucial role in finding the diagnosis, planning and monitoring of treatment, early detection of complications and drug-related adverse events.
16245956 Management issues with elderly-onset rheumatoid arthritis: an update. 2005 Elderly-onset rheumatoid arthritis (EORA) is defined as rheumatoid arthritis (RA) starting at >60 years of age. EORA is characterised by a lower female/male ratio compared with RA in younger patients and it more frequently has an acute onset accompanied by constitutional symptoms. Two incompletely overlapping subsets of RA have been recognised: one exhibits the classical RA clinical picture while the other has a polymyalgia rheumatica-like appearance, characterised by shoulder involvement, absence of rheumatoid factor and, usually, by a nonerosive course. Identification of anti-cyclic citrullinated peptide antibodies is useful for distinguishing the latter subset from true polymyalgia rheumatica. Elderly-onset spondyloarthritis, crystal-related arthritis, remitting seronegative symmetrical synovitis with pitting oedema syndrome and hepatitis C virus-related arthritis must also be considered in the differential diagnosis. EORA treatment requires prudence because of the increase in age-related risks pertaining principally to the renal, cardiovascular and gastrointestinal systems. No groups of molecules usually employed for RA therapy in younger subjects (analgesics, NSAIDs, corticosteroids, disease-modifying antirheumatic drugs, anticytokine drugs) can be excluded a priori from the treatment of EORA patients. Nevertheless, the risk/benefit ratio relating to their use must be accurately evaluated for every single patient. Recently marketed compounds such as leflunomide and tumour necrosis factor-alpha antagonists have also increased the therapeutic opportunities for aged RA patients.
15705634 Wnt signalling in rheumatoid arthritis. 2005 Jun Rheumatoid arthritis (RA) is a symmetrical polyarticular disease of unknown aetiology that affects primarily the diarthrodial joints. Characteristic features of RA pathogenesis are synovial hyperplasia and inflammation accompanied by cartilage loss and joint destruction. Synovial hyperplasia and inflammation are a consequence of an increase in the macrophage-like and fibroblast-like synoviocytes of the synovial intimal lining associated with infiltration of leucocytes into the subintimal space. Although therapeutic interventions are available, the disease persists despite therapy in a significant fraction of patients. Several lines of evidence have substantiated a crucial role of activated fibroblast-like synoviocytes (FLS) during RA pathogenesis. The hyperplastic FLS population potentially promotes leucocyte infiltration and retention. The rheumatoid synovium eventually transforms into a pannus that destroys articular cartilage and bone. There are no approved drugs that are known to target the FLS in RA, and the underlying mechanisms driving FLS activation remain unresolved. In this review, the importance of Wnt-frizzled (Fz)-mediated signalling in the autonomous activation of FLS is discussed. Anti-Wnt/anti-Fz antibodies, Fz receptor antagonists or small-molecule inhibitors of Wnt-Fz signalling might be useful for therapeutic interventions in refractory RA.
15688916 The management of osteoarthritis and rheumatoid arthritis. 2005 Jan 11 The scale of arthritis is often underestimated as the term covers about 200 different diseases. The two most common conditions are osteoarthritis and rheumatoid arthritis. Nurses' pivotal role in the care of patients with arthritis requires a combination of knowledge, understanding and expertise.
15588974 What are the consequences of early rheumatoid arthritis for the individual? 2005 Feb Rheumatoid arthritis (RA) has important impacts on health that can be related to the World Health Organization's new International Classification of Functioning, Disability and Health (ICF framework). The physical consequences of RA for the individual relate to body functions and structures in the ICF framework. The functional consequences of RA are related to activity in the ICF framework, and the impact of RA on society relates to participation in the ICF framework. Despite conventional treatment, early RA continues to result in significant physical consequences for most patients. From the patients' perspective, this primarily results from persistent pain, although symptoms such as fatigue and depression are also relevant. This is confirmed from the clinician's perspective by the infrequency of remission, persistence of disease activity and unrelenting radiographic progression in early RA. Patients with early RA often progress, within only a few years, to significant disability. This has mainly been shown in studies using the Health Assessment Questionnaire as the disability measure, although a small number of studies using generic health measures such as Short Form-36 have reached similar conclusions. RA patients and their friends and families incur the majority of costs associated with early RA. Many patients are not able to continue to work at the same level as they would have anticipated had they not developed RA. Later on, society bears an increased load, especially in patients with higher levels of disability; this results from major social care costs and interventions such as surgery. However, the evidence favouring expensive biological therapies, even in early RA, is likely to turn this analysis on its head in the near future.
16287595 Biologics in early rheumatoid arthritis. 2005 Nov Treatment of patients with rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs is started immediately after diagnosis, resulting in more effective suppression of disease activity and substantial reduction of joint damage. The development of biologic agents has enabled remission as a realistic therapeutic goal in a greater proportion of patients. The tumor necrosis factor-alpha inhibitors, infliximab, etanercept, and adalimumab, have been studied in numerous randomized clinical trials. These agents can suppress disease activity directly, slow or stop progression of radiologic damage, and prevent further loss of quality of life. Patients treated with tumor necrosis factor-alpha inhibitors show few adverse events, which together with the high clinical effectiveness is favorable for treatment compliance. The exact role of these agents in the treatment of early-stage RA is unknown.
15945217 [Management of patients with rheumatoid arthritis]. 2005 May Recent years have shown considerable advances in the understanding of pathophysiology and clinical course of patients with rheumatoid arthritis. We now know that there is preclinical disease. Autoantibodies precede clinical symptoms and erosive disease can be seen in patients as early as at the beginning of the symptoms. Clinical progress has come from a better recognition of the natural history of disease. Outcome measures were developed and validated, allowing innovative trial design. Therapy must aim at achieving clinical remission, reversal from destructive to nondestructive arthritis and even healing of erosions. Such aim necessitates early diagnosis of disease and aggressive treatment. Regular assessment of the disease state should be performed. For disease assessment validated tools should be used. The search for new therapies is ongoing. Studies indicate there is a considerable window of opportunity in very early rheumatoid arthritis. If we can use this window of opportunity with an efficient therapeutic strategy we should be able to change the course of disease or even achieve long term remission.
16174489 Chemokines: their role in rheumatoid arthritis. 2005 Oct Chemokines are small proteins that can act on cells that express matching receptors. They are best known for their role in migration of cells, especially immune cells. Chemokine/chemokine-receptor pairs are often functionally categorized into three groups: inflammatory, homeostatic, and angiogenic/angiostatic, although functions sometimes overlap. Interfering with the interaction between chemokines and their receptors is currently under investigation as a therapeutic strategy in rheumatoid arthritis.
16616575 Bisphosphonate therapy in rheumatoid arthritis. 2006 Jul Focal bone damage and generalized bone loss are features of rheumatoid arthritis (RA). The introduction of TNFalpha antagonists has radically improved the management of RA by providing a means of slowing or preventing the occurrence of focal bone damage. However, some patients with severe RA have contraindications to TNFalpha antagonist therapy and others either fail to respond or fail to tolerate TNFalpha antagonists. In addition, whether TNFalpha antagonists effectively combat generalized bone loss remains unknown. Bisphosphonates can prevent generalized bone loss. Their main target is the osteoclast, which has been identified as the culprit in focal bone damage caused by inflammatory diseases. As a result, the potential effects of bisphosphonates on focal bone damage related to RA are generating strong interest. Although results from the few studies in humans have been disappointing, new insights into the mechanisms of action of amino-bisphosphonates and recent data obtained in animals, most notably with new-generation bisphosphonates, have rekindled the hope that bisphosphonates may be beneficial in RA. We review herein the main studies of the effects of bisphosphonate therapy on focal bone damage and generalized bone loss in patients with RA.
16548834 Reducing the cardiovascular disease burden in rheumatoid arthritis. 2006 Mar 20 Rheumatoid arthritis is associated with an increase in cardiovascular mortality and morbidity; this increase is independent of traditional cardiovascular risk factors. Effective treatment of rheumatoid arthritis with disease-modifying antirheumatic drugs appears to reduce cardiovascular mortality. The optimal approach to prevention of cardiovascular disease in rheumatoid arthritis is evolving, but will include a combination of: cardiovascular risk factor screening and management; effective and sustained control of joint and systemic inflammation; and a high index of suspicion for silent cardiac disease.
16932686 T-cell-targeted therapies in rheumatoid arthritis. 2006 Apr T cells regulate the disease process in rheumatoid arthritis (RA) on multiple levels and represent a logical choice for anti-inflammatory therapy. In the inflamed joint they promote neoangiogenesis and lymphoid organogenesis, and stimulate synoviocyte proliferation and development of bone-eroding osteoclasts. The design of T-cell-targeted therapies for RA needs to take into account the uniqueness of T-cell generation, turnover and differentiation in affected patients. Patients accumulate 'old' T cells that respond to alternate regulatory signals because of an accelerated immune aging process; any therapeutic interventions that increase the replicative stress of T cells should, therefore, be avoided. Instead, therapeutic approaches that raise the threshold for T-cell activation are more promising. As a rule, antigen-derived signals synergize with co-stimulatory signals to stimulate T cells; such co-stimulatory signals are now targeted in novel immunosuppressive therapies. An example is abatacept (soluble cytotoxic-T-lymphocyte-associated protein 4-immunoglobulin), which binds with high affinity to CD80/CD86 and effectively suppresses inflammatory activity in RA. The therapeutic benefits gained by disrupting T-cell co-stimulation indicate that the pathogenesis of RA is driven by a more generalized abnormality in T-cell activation thresholds rather than a highly selective action of arthritogenic antigens.
15782541 Immunotherapy of rheumatoid arthritis: past, present and future. 2005 Mar Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by inflammation of the synovial lining of joints, and the destruction of cartilage and bone. Seminal studies demonstrating that pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFalpha), are expressed in RA, has resulted in the approval of anti-TNFalpha biological therapies for its treatment. Although groundbreaking in themselves, these studies have also paved the way for further research to determine whether the targeting of other cytokines and immune pathways might aid in development of the next generation of drugs for the treatment of RA.
16226478 Gene therapy for patients with rheumatoid arthritis. 2006 Mar Gene therapy seeks either to supply a missing or dysfunctional gene or to ensure continuous long-lasting production of a therapeutic protein. Rheumatoid arthritis is a candidate for gene therapy, as the mechanisms leading to joint inflammation and destruction have been partly elucidated. Nevertheless, several crucial questions need to be addressed. Knowledge of the underlying pathophysiological mechanisms is needed to guide selection of the candidate gene. In the light of current data, TNF and IL-1 antagonists are generating interest. A choice must be made between a viral vector (adenovirus, retrovirus, adeno-associated virus) and a nonviral vector (naked DNA, administered by electrotransfer or in liposomes). Finally, the relative merits of intraarticular and systemic administration need to be considered. Safety is a primary concern. The transgene and/or vector may induce adverse effects. For instance, a transgene inserted within the host genome (when a retroviral vector is used) may induce a mutation. A number of vectors and transgenes induce immune responses. Numerous studies are ongoing to investigate the safety and efficacy of gene therapy strategies in experimental models of rheumatoid arthritis. These studies will have to be completed before further clinical trials of gene therapy in rheumatoid arthritis are considered.
15798057 Rheumatoid arthritis: a practical guide to state-of-the-art imaging, image interpretation, 2005 Mar Rheumatoid arthritis (RA) is a chronic systemic disease of unknown origin that predominantly involves synovial tissue. RA affects 0.5%-1.0% of the global population, with females affected more frequently than males. Early diagnosis and initiation of proper therapy help modify the course of the disease and reduce the degree of severe late sequelae. Radiology plays a key role in diagnosis and management of RA. Currently, magnetic resonance imaging is the best imaging modality because it depicts soft-tissue changes and damage to cartilage and bone even better and at an earlier stage than does computed tomography. Ultrasound and conventional radiography are more readily available but cannot show the entire spectrum of the disease. Diagnosis and differential diagnosis are achieved by identifying certain radiologic parameters, which are also used for grading purposes. The disease does not follow a linear course, especially with the early initiation of potent therapy. Knowledge of the imaging findings enables the radiologist to accurately select the most helpful imaging technique. Familiarity with the pathophysiologic mechanisms of RA, the imaging findings, and the grading systems and a basic knowledge of therapeutic regimens are prerequisites for a tailored diagnostic approach by the radiologist.
16234180 Quality of life in rheumatoid arthritis. 2005 Sep Assessment of health-related quality of life (HRQoL) is relevant for the patients and is important in both clinical research and daily clinical practice. Generic and disease-specific instruments for assessment of HRQoL are reviewed. Changes in HRQoL provide important information on randomized controlled clinical trials as well as on observational studies. The floor effect is a limitation of many of the scales, especially in patients with less severe disease. Feasibility and low test-retest reproducibility limit the use of many of the instruments in clinical practice, especially when they are used for individual treatment decisions. Electronic transferral of data from patients to the health professionals by, for example, internet or a personal digital assistant (PDA), opens up new opportunities for frequent patient reports and improved access to the data.
15720276 The role of macrophages in rheumatoid arthritis. 2005 Rheumatoid arthritis (RA) is a common autoimmune chronic inflammatory joint disease, characterized by macrophage and lymphocyte infiltration, proliferation of synovial fibroblasts, and joint destruction. Macrophages are critically involved in the pathogenesis of RA. Not only do they produce a variety of pro-inflammatory cytokines and chemokines, but they also contribute to the cartilage and bone destruction in RA through multiple mechanisms. Macrophage activation by several distinct mechanisms is crucial for their function. This review will discuss several aspects of macrophage function in RA, including the mechanisms for macrophage activation, the signaling pathways in activated macrophages, and the mechanisms that inhibit apoptosis in macrophages in the rheumatoid joints.