Is rheumatoid factor useful in primary care? A retrospective cross-sectional study.

Rheumatoid factor (RF) is frequently tested in general practice where its utility as a diagnostic test for rheumatoid arthritis (RA) is not known. We undertook a retrospective cross-sectioal study to determine the utility and cost of RF in a primary care population. We compared RF with recorded clinical features based on the American College of Rheumatology (ACR) criteria as a diagnostic test for RA in 235 patients in general practice using receiver operating characteristic curves and calculated the cost of testing per case of RA. We analysed 36,191 RF requests made to one laboratory from 2003-2009 at a mean annual cost of £58,164 and the variation and annual cost of RF testing between 77 practices. The sensitivity and specificity of RF at the optimal cut-off value of 20 U/ml were 0.6 and 0.96 and that of two documented clinical ACR criteria were 0.9 and 0.92, respectively. No ACR criteria were documented in 150 (63.8%) patients who had RF tested. The overall cost of RF testing per case of seropositive RA was £708.75. Of all RF requests, 66.6% was made by GPs, 7.0% by rheumatologists and 26.4% by other hospital departments. The proportion of positive tests was 5.8% in primary care and 17.7% in rheumatology. The mean number of tests performed annually in primary care was 4.65 (SD 2.7) per 1,000 patients. RF is less sensitive for RA than clinical features in primary care and is frequently requested in cases without clinical evidence of the disease, adding to the overall cost.

Phase I study of copper-binding agent ATN-224 in patients with advanced solid tumors.

PURPOSE: Copper chelation reduces the secretion of many angiogenic factors and reduces tumor growth and microvascular density in animal models. ATN-224 is a second-generation analogue of ammonium tetrathiomolybdate. The aim of our phase I study was to reduce serum copper levels, as measured by ceruloplasmin, to 5 to 15 mg/dL (normal 16-60) in 14 to 21 days, to determine the pharmacokinetic profile of ATN-224 and to evaluate dose-limiting toxicities. PATIENTS AND METHODS: Cohorts of patients were treated with escalating oral doses of ATN-224 until copper depletion followed by a titrated maintenance dose. RESULTS: Eighteen patients received 78 cycles of ATN-224. Mean baseline ceruloplasmin was 39.6 mg/dL. The maximum administered dose was 330 mg/d where grade 3 fatigue was dose-limiting. At the maximum tolerated dose of 300 mg/d, the median time to achieve target ceruloplasmin was 21 days, and toxicities included grade 3 anemia, grade 3 neutropenia, fatigue, and sulfur eructation. ATN-224 treatment caused a significant reduction (> 90%) in RBC superoxide dismutase 1 activity and circulating endothelial cells. Pharmacokinetic data indicate greater absorption of ATN-224 and more rapid ceruloplasmin reduction when administered with a proton pump inhibitor. Stable disease of > 6 months was observed in 2 patients. CONCLUSIONS: Oral ATN-224 is a well-tolerated therapy and at a loading dose of 300 mg/d leads to a reduction of serum ceruloplasmin levels in 80% patients within 21 days. A loading dose of 300 mg/d for 2 weeks followed by a titrated maintenance dose will be the recommended starting dose for phase II study.