11 research outputs found

    What are the important components of the clinical assessment of hand problems in older adults in primary care? Results of a Delphi study

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    <p>Abstract</p> <p>Background</p> <p>To identify clinical questions and assessments regarded by health care practitioners as important when assessing undifferentiated hand pain or problems in adults aged 50 years and over presenting to primary care.</p> <p>Methods</p> <p>A purposively selected panel of 26 UK-based Health Care Practitioners comprising occupational therapists, physiotherapists, rheumatologists and general practitioners, were invited to take part in a consensus study involving three postal rounds of a Delphi questionnaire with accompanying case scenarios. Participants were asked to generate questions and assessments (round 1), rate their importance (round 2), and vote on which items were most important (round 3).</p> <p>Results</p> <p>Sixteen Health Care Practitioners agreed to participate with 11 completing all three rounds. The first round of the Delphi study generated 156 questions and 143 assessments. After three rounds agreement was reached on the importance of 25 questions and 19 assessments. Questions were weighted towards current symptoms, but also included the history of previous hand problems, self-reported hand function, co-morbidity and general health. Observation and palpation of features predominated in the choice of assessment, but specific tests, grip strength, evaluation of sensation and hand function were also included.</p> <p>Conclusions</p> <p>A pool of clinical questions and assessments were generated by Health Care Practitioners, and those considered most important for assessing older adults presenting with undifferentiated hand pain and hand problems in primary care were identified. Further evaluation is required to establish the reliability and feasibility of using these questions and assessments in primary care. In particular, the relative contribution of these questions and assessments in evaluating the nature and severity of hand problems, assisting diagnosis, indicating appropriate management, and predicting future course requires further investigation.</p

    Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

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    Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
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