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Ravani P.,University of Calgary | Parfrey P.,Memorial University of Newfoundland | MacRae J.,University of Calgary | James M.,University of Calgary | And 8 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2010

Background and objectives: Comparing outcomes of arteriovenous grafts and fistulas is challenging because the pathophysiology of access dysfunction and failure rate profiles differ by access type. Studying how risks vary over time may be important. Design, setting, participants, & measurements: Longitudinal data from 535 incident hemodialysis patients were used to study the relationship between access type and access survival, without (semiparametric Cox modeling) and with specification of the underlying hazard function (parametric Weibull modeling). Results: The hazard for failure of fistulas and grafts declined over time, becoming proportional only after 3 months from surgery, with a graft versus fistula hazard ratio of 3.2 (95% confidence interval 1.9 to 5.3; Cox and Weibull estimation) and time ratio of 0.11 (i.e., the estimated access survival time was approximately one tenth shorter in grafts; 95% confidence interval 0.04 to 0.28; Weibull estimation only). Considering the entire observation period, grafts had slower hazard decline (P < 0.001) with shorter median survival times than fistulas (8.4 versus 38.3 months; Weibull regression only). Conclusions: Parametric models of arteriovenous access survival may provide relevant information about temporal risk profiles and predicted survival times. Copyright © 2010 by the American Society of Nephrology.

Miceli R.,Unit of Medical Statistics | Tomasello G.,Azienda Istituti Ospitalieri di Cremona | Bregni G.,Fondazione Istituto Nazionale Tumori | Di Bartolomeo M.,Fondazione Istituto Nazionale Tumori | Pietrantonio F.,Fondazione Istituto Nazionale Tumori
World Journal of Gastroenterology | Year: 2014

Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that diseasefree survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Eurlings L.W.M.,Maastricht University | Bettencourt P.,University of Porto | Pimenta J.M.,University of Porto | Metra M.,University of Brescia | And 4 more authors.
European Journal of Heart Failure | Year: 2015

Aims NT-proBNP is a strong predictor for readmissions and mortality in acute decompensated heart failure (ADHF) patients. We assessed whether absolute or relative NT-proBNP levels should be used as pre discharge treatment target. Methods and results Our study population was assembled from seven ADHF cohorts. We defined absolute (<1500, <3000, <5000, and <15 000 ng/L) and relative NT-proBNP targets (>30, >50, and >70%). Population attributable risk fraction (PARF) is the proportion of all-cause 6-month mortality in the population that would be reduced if all patients attain the NT-proBNP target. PARF was determined for each target as well as the percentage of patients attaining the NT-proBNP target. Attainability was investigated by logistic regression analysis. A total of 1266 patients [age 74 (64-80), 60% male] was studied. For every absolute NT-proBNP level, a corresponding percentage reduction was found that resulted in similar PARFs. The highest PARF (?60-70%) was observed for <1500 or >70%, but attainability was low (27% and 22%, respectively). The strongest predictor for not attaining these targets was admission NT-proBNP. In admission NT-proBNP tertiles, PARFs were significantly different for absolute, but not for relative targets. Conclusion In an ADHF population, pre-discharge absolute or relative NT-proBNP targets may both be useful as they have similar effects on PARF. However, depending on admission NT-proBNP, absolute targets show varying PARFs, while PARFs for relative targets were similar. A relative target is predicted to reduce mortality consistently across the whole spectrum of ADHF patients, while this is not the case using a single absolute target. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Rutgers E.,Netherlands Cancer Institute | Piccart-Gebhart M.J.,Institute Jules Bordet | Bogaerts J.,European Organisation for Research and Treatment of Cancer | Delaloge S.,Institute Gustave Roussy | And 12 more authors.
European Journal of Cancer | Year: 2011

Background: The MINDACT (Microarray In Node-negative and 1-3 node positive Disease may Avoid ChemoTherapy) trial investigates the clinical utility of the 70-gene profile (MammaPrint) for the selection of breast cancer patients for adjuvant chemotherapy (CT) together with standard clinicopathological criteria. We present the results of the pilot phase consisting of first 800 patients included. Methods: MINDACT has enrolled 6600 patients, classified into high or low risk by MammaPrint and clinicopathological risk through Adjuvant! Online. Patients with both clinical (C) and genomic (G) high risks are offered adjuvant CT; those with both C and G low risks do not receive CT; patients with discordant risk are randomised for the decision of adjuvant CT based on C or G risk. CT randomisation of anthracycline-based versus docetaxel/capecitabine and endocrine therapy randomisation between letrozole and tamoxifen → letrozole are offered. Results: During the pilot phase 46% of screened patients were enrolled. Main reasons for non-enrolment were node positivity before trial amendment, sample quality problems and failure to meet logistic settings. Among the 800 patients, 386 (48%) were C-low/G-low, 198 (24.8%) as C-high/G-high, 75 (9.4%) as C-low/G-high and 141 (17.6%) as C-high/G-low. In total 216 (27%) cases were discordant. The difference between patients with C-high (42%) and G-high risk (34%) is 8.25% (95% confidence interval (CI), 4.7-11.8%; P <.0001). Compliance with the treatment decision was high (>92%). Conclusions: The logistically complex MINDACT trial is feasible in a multinational setting. The proportion of discordant patients, the potential reduction in CT by using the genomic signature and compliance to treatment assignment are in accordance with the trial hypotheses. © 2011 Elsevier Ltd. All rights reserved.

Masini C.,University of Modena and Reggio Emilia | Sabbatini R.,University of Modena and Reggio Emilia | Porta C.,University of Pavia | Procopio G.,Unit 2 | And 13 more authors.
BJU International | Year: 2012

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Sunitinib and sorafenib are orally administered multikinase inhibitors approved for the treatment of advanced RCC. The limited pharmacokinetics data on sunitinib and sorafenib suggest that haemodialysis does not significantly alter plasma concentrations. In this retrospective study we define the safety and efficacy of tyrosine kinase inhibitors in patients with metastatic RCC (mRCC) and end-stage renal disease requiring haemodialysis. Even though the retrospective nature of this survey and the relatively small sample size represent major limitations, these data indicate that treatment with sunitinib and sorafenib in this cohort of patients is feasible with no unexpected toxicity and good efficacy, results similar to those in the general population of patients with mRCC. Objective To investigate the safety and efficacy of tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease requiring haemodialysis (HD). Patients and methods Between July 2006 and December 2010, 24 patients undergoing HD were treated with sunitinib and/or sorafenib for mRCC in 14 Italian institutions. We retrospectively reviewed the medical records of these patients to evaluate the administered doses of TKIs, treatment-related toxicities and the clinical response to therapy. Results Sunitinib was administered at 50 mg daily for 4-6 weeks in six patients, 37.5 mg daily for 4-6 weeks in seven patients (one patient subsequently increased the dose to 50 mg daily), 25 mg daily for 4-6 weeks in two patients and 12.5 mg daily for 4-6 weeks in one patient. Among the eight patients treated with sorafenib, four patients received 800 mg daily (400 mg every 12 h), three patients 400 mg daily and one patient 200 mg daily with a continuous schedule. The estimated median progression-free and overall survival periods of this cohort of patients were 10.3 months and 22.6 months, respectively. With regard to tolerability and safety, no unexpected adverse events were registered and no grade 4 haematological or non-haematological toxicities were reported. Conclusions Sunitinib and sorafenib treatment is not contraindicated in patients with mRCC undergoing HD. The outcome of this patient population is similar to that observed in patients with normal renal function treated with TKIs. These results merit further confirmation by a larger prospective trial. © 2012 BJU INTERNATIONAL.

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