Seminars in arthritis and rheumatism
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Semin. Arthritis Rheum. · Feb 2021
ReviewStatins and lower mortality in rheumatic diseases: An effect of immortal time bias?
Randomized controlled trials of the effectiveness of statins on rheumatic disease outcomes have shown limited or no benefit. On the other hand, observational studies have reported remarkable effectiveness of statins at reducing mortality in patients with rheumatic diseases. We evaluated these observational studies for the presence of immortal time bias, which tends to exaggerate the effectiveness of drugs by creating a survival advantage for exposed patients. ⋯ Bias in observational studies may explain the discrepancy in findings with randomized controlled trials on the effectiveness of statins in patients with rheumatic diseases. Future observational studies will need to rely on incident and prevalent new-user designs that emulate randomized trials and avoid immortal time bias.
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Semin. Arthritis Rheum. · Aug 2020
Review Meta AnalysisThe experience of a gout flare: a meta-synthesis of qualitative studies.
Gout flares are an important concern for people with gout and an understanding of patients' experiences with gout flares is central in developing meaningful outcome measures for clinical trials. This study aimed to systematically review and thematically synthesize the qualitative literature reporting the patient experience of gout flares, to inform the development of flare-specific outcome measures. ⋯ Gout flares impact many aspects of patients' lives, including physical and psychological and social and family life. The patient experience of gout flares goes beyond what is routinely measured in research settings. Measurement and reporting methods that capture these aspects of patients' experiences with gout flares would provide more meaningful outcome measures in clinical trials of flare prevention.
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Urate is the end-product of the purine metabolism in humans. The dominant source of urate is endogenous purines and the remainder comes through diet. Approximately two thirds of urate is eliminated via the kidney with the rest excreted in the feces. ⋯ Hyperuricemia can result in the formation of monosodium urate (MSU) crystals that may be recognized as danger signals by the immune system. This immune response results in the activation of the NLRP3 inflammasome and ultimately in the production and release of interleukin-1β, and IL-18, that mediate both inflammation, pyroptotic cell death, and necroinflammation. It has also been demonstrated that soluble urate mediates effects on the kidney to induce hypertension and can induce long term epigenetic reprogramming in myeloid cells to induce "trained immunity." Together, these sequelae of urate are thought to mediate most of the physiological effects of hyperuricemia and gout, illustrating this biologically active molecule is more than just an "end-product" of purine metabolism.
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Musculoskeletal (MSK) involvement of the hands is a significant source of morbidity, impacting on quality of life in patients with systemic sclerosis (SSc). MSK complications are common in SSc and can affect the whole of the MSK system. MSK hand involvement can occur early in the course of the disease. ⋯ Other important manifestations include (but are not limited to) calcinosis, acro-osteolysis and carpal tunnel syndrome. MSK imaging is an important tool that allows insight into both disease pathogenesis and to inform the clinical management of MSK complications. The purpose of this review is to provide an overview of the MSK hand complications in patients with SSc, highlighting the breadth and burden of pathology relevant to clinical practice.
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Semin. Arthritis Rheum. · Aug 2019
Review Case ReportsSecondary thrombotic microangiopathy in systemic lupus erythematosus and antiphospholipid syndrome, the role of complement and use of eculizumab: Case series and review of literature.
Thrombotic microangiopathy (TMA) is a life-threatening, albeit infrequent, complication of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). Recommendations for the treatment of SLE- and APS-related secondary TMA are currently based solely on case reports and expert opinion. Unfortunately, interventions may not yield timely results or effectively halt the progression of TMA. Since complement activation plays a key role in the pathogenesis of secondary TMA due to SLE, APS, a therapy that targets the complement pathway is an attractive intervention. Eculizumab, a recombinant, fully humanized IgG2/IgG4 monoclonal antibody inhibits C5 activation and is FDA-approved for PNH and atypical HUS (aHUS). However, limited case reports are available on its use in treatment of secondary TMA. ⋯ Based on these observations, we suggest that eculizumab may be a potential treatment option for acutely ill patients with secondary TMA due to SLE and/or APS who have failed standard of care. A collective approach is needed to better elucidate the role and optimal timing of eculizumab use in the management of TMA complicating SLE and/or APS.