Raltitrexed (Tomudex) administration in patients with relapsed metastatic colorectal cancer after weekly irinotecan/5-Fluorouracil/Leucovorin chemotherapy

PURPOSE: The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC) in relapse (>8 weeks) after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU)+Leucovorin (LV). METHODS: Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47–70), median Karnovsky PS: 80 (70–90), and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m(2) i.v. every 21 days. RESULTS: Three patients (12%) achieved a partial response (PR), 8 (32%) had stable disease (SD), and the remaining 14 (56%) developed progressive disease (PD). Median time-to-progression (TTP) was 5.5 months (range, 2–8.5), and median overall survival (OS) 8 months (range, 4.0–12.5). Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1–2: 52%-grade 3: 28%, and anemia grade 1–2 only: 36%. Mild mucositis grade 1–2 occured in 13.5% of patients and was the principal non-hematologic toxicity. CONCLUSION: Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study

43 REDUCED KIDNEY FUNCTION IS ASSOCIATED WITH POORER GLOBAL AND DOMAIN-SPECIFIC COGNITIVE PERFORMANCE IN COMMUNITY-DWELLING OLDER ADULTS

Abstract Background Chronic Kidney Disease (CKD) is an important risk factor in the development of cognitive impairment. However, the association between reduced estimated Glomerular Filtration Rate (eGFR) and performance on domain-specific cognitive and neuropsychological assessments is less clear and may represent an important target in the promotion of optimal brain health in older adults. Methods Participants from the Trinity, Ulster and Department of Agriculture cohort study underwent detailed assessment of cognitive and neuropsychological function using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Mixed-effects Poisson and linear regression was used to assess the relationship between eGFR strata and cognitive/neuropsychological test performance. Results 4,887 participants were included (73.94 ± 8.25 years; 67.7% female). Reduced eGFR was associated with poorer performance on all three cognitive assessments, most pronounced in those with eGFR &amp;lt;45 mL/mL/1.73m2 (IRR: 1.19; 95% CI: 1.09, 1.29; p &amp;lt; 0.001 for MMSE/IRR: 1.14; 95% CI 1.04, 1.24; p &amp;lt; 0.001 for the FAB/β: -3.23; 95% CI -5.18, −1.30; p = 0.001 for RBANS, fully adjusted). Reduced eGFR was associated with poorer performance on immediate memory, visual–spatial and attention RBANS domains. Associations were strongest in the youngest old (&amp;lt;70 years) with no association observed in those aged &amp;gt;80 years. Conclusion Reduced kidney function was associated with poorer global and domain-specific function in community-dwelling older adults. Associations were strongest for those with eGFR &amp;lt;45 mL/min/1.73m2 and the youngest-old, suggesting that this group may be most at risk and may benefit from potential preventative interventions. </jats:sec

The Days to Pay Accounts Payable Determinants - Financing, Pricing Motives and Financial Substitution Effect - A Panel Data GMM Estimation from European Western Countries

Documento de Trabajo 03/10 perteneciente a la colección de documentos de trabajo "Nuevas Tendencias en Dirección de Empresas", dentro del Máster en Investigación en Economía y Empresa.[ES]En este trabajo se propone elegir a los días para pagar las cuentas por pagar y los factores determinantes de nuestra resultados apoyan firmemente que las cuentas por pagar problemática está estrechamente relacionado con el corto plazo decisiones financieras con una influencia positiva y significativa de la rentabilidad empresarial y el tamaño factores. La existencia de capital de trabajo negativo de la empresa se confirma a influir fuertemente en la reducción del crédito comercial obtenido de los proveedores en países de Europa Occidental en paralelo con una contribución conjunta de la financiación bancaria a corto y largo plazo como un sustituto de la deuda comercial.[EN]This paper proposes to elect the days to pay accounts payable determinants and our findings strongly support that the accounts payable problematic is closely related to short term financial decisions with a positive and significative influence of firm’s profitability and size factors. The existence of a firm’s negative working capital is confirmed to influence strongly the reduction of the trade credit obtained from suppliers in Western Europe countries in parallel with a joint contribution of short and long term bank financing as a substitute from trade debt. Firm characteristics related to negative working capital and fixed assets level, jointly or alone, give more importance to the role of short term bank financing on substituting or reducing the volume of trade credit obtained from suppliers. Negative working capital reinforces the role of long term bank financing. It seems to induce the presence of a corporate cost reduction strategy to preserve or increment the firm’s market reputation and competition. The firm’s return on assets implies an enlargement of the days to pay accounts payable in line with a rising creditworthiness. All interacted variables are responsible for the reduction of the days to pay accounts payable and the confirmation of the financial substitution effect introduces more financing discipline compatible with firm’s cost reduction strategy and pricing motives included in a price discrimination strategy. Signs of future unbalanced capital structure and financial distress may appear due also to the more banking financing justified by firm’s investment and negative working capital under finance motives point of view. The more firm’s growth the less trade credit obtained and, on the contrary, profitability and size contribute to facilitate the trade credit obtained from suppliers under finance and pricing motives point of view, more over the stability on terms trade credit. As important as the days to pay accounts and/or days sales outstanding determinants are future investigations related to trade credit duration gap as a synthesis of the prior trade credit issues, to country and economic sector or union analysis, as well