116 research outputs found
Prescribing anti-rheumatic drugs in pregnancy and breastfeeding—the British Society for Rheumatology guideline scope
Malignancy in scleroderma patients from south west England: a population-based cohort study
The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate
Purpose: Gastrointestinal stromal tumours (GIST) are mesenchymal neoplasms of the gastrointestinal tract that are unresponsive to standard sarcoma chemotherapy. Imaging of GIST patients is done with structural and functional methods such as contrast-enhanced helical computed tomography (ceCT) and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG). The aim of this study was to compare the prognostic power of PET and ceCT and to evaluate the clinical role of PET/CT imaging. Methods: All patients with GIST undergoing PET or PET/CT examinations were prospectively included in this study, and the median overall survival, time to progression and treatment duration were documented. The prognostic significance of PET and ceCT criteria of treatment response was assessed and PET/CT was compared with PET and ceCT imaging. Data for 34 patients (19 male, 15 female, 21-76 years) undergoing PET or PET/CT for staging or restaging were analysed. Results: In 28 patients, PET/CT and ceCT were available after introduction of treatment with the tyrosine kinase inhibitor imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). Patients without FDG uptake after the start of treatment had a better prognosis than patients with residual activity. In contrast, ceCT criteria provided insufficient prognostic power. However, more lesions were found on ceCT images than on PET images, and FDG uptake was sometimes very variable. PET/CT delineated active lesions better than did the combination of PET and ceCT imaging. Conclusion: Both PET and PET/CT provide important prognostic information and have an impact on clinical decision-making in GIST patients. PET/CT precisely delineates lesions and thus allows for the correct planning of surgical intervention
The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults
Valuing Health Gain from Composite Response Endpoints for Multisystem Diseases
Objectives: This study aimed to demonstrate how to estimate the value of health gain after patients with a multisystem disease achieve a condition-specific composite response endpoint. Methods: Data from patients treated in routine practice with an exemplar multisystem disease (systemic lupus erythematosus) were extracted from a national register (British Isles Lupus Assessment Group Biologics Register). Two bespoke composite response endpoints (Major Clinical Response and Improvement) were developed in advance of this study. Difference-in-differences regression compared health utility values (3-level version of EQ-5D; UK tariff) over 6 months for responders and nonresponders. Bootstrapped regression estimated the incremental quality-adjusted life-years (QALYs), probability of QALY gain after achieving the response criteria, and population monetary benefit of response. Results: Within the sample (n = 171), 18.2% achieved Major Clinical Response and 49.1% achieved Improvement at 6 months. Incremental health utility values were 0.0923 for Major Clinical Response and 0.0454 for Improvement. Expected incremental QALY gain at 6 months was 0.020 for Major Clinical Response and 0.012 for Improvement. Probability of QALY gain after achieving the response criteria was 77.6% for Major Clinical Response and 72.7% for Improvement. Population monetary benefit of response was £1 106 458 for Major Clinical Response and £649 134 for Improvement. Conclusions: Bespoke composite response endpoints are becoming more common to measure treatment response for multisystem diseases in trials and observational studies. Health technology assessment agencies face a growing challenge to establish whether these endpoints correspond with improved health gain. Health utility values can generate this evidence to enhance the usefulness of composite response endpoints for health technology assessment, decision making, and economic evaluation
A randomized study of the effect of patient positioning on setup reproducibility and dose distribution to organs at risk in radiotherapy of rectal cancer patients
Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function
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
Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation
In 1997, the first consensus guidelines for haematopoietic SCT (HSCT) in autoimmune diseases (ADs) were published, while an international coordinated clinical programme was launched. These guidelines provided broad principles for the field over the following decade and were accompanied by comprehensive data collection in the European Group for Blood and Marrow Transplantation (EBMT) AD Registry. Subsequently, retrospective analyses and prospective phase I/II studies generated evidence to support the feasibility, safety and efficacy of HSCT in several types of severe, treatment-resistant ADs, which became the basis for larger-scale phase II and III studies. In parallel, there has also been an era of immense progress in biological therapy in ADs. The aim of this document is to provide revised and updated guidelines for both the current application and future development of HSCT in ADs in relation to the benefits, risks and health economic considerations of other modern treatments. Patient safety considerations are central to guidance on patient selection and HSCT procedural aspects within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and EBMT accredited centres. A need for prospective interventional and non-interventional studies, where feasible, along with systematic data reporting, in accordance with EBMT policies and procedures, is emphasized
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