Home About us Contact
|
Home About us Contact | ||
|
|
||
Major Endpoint (major + endpoint)
Selected AbstractsCentral nervous system dissemination in immunocompetent patients with aggressive lymphomas: incidence, risk factors and therapeutic optionsHEMATOLOGICAL ONCOLOGY, Issue 2 2009Andrés J. M. Ferreri Abstract Central nervous system (CNS) dissemination is a rare (4,5%) but usually fatal complication of aggressive lymphomas. Prophylaxis modalities to prevent CNS dissemination in aggressive lymphomas cannot be widely applied to every lymphoma patient since it is associated with increased risk of neurotoxicity. Therefore, identification of high-risk patients as the best candidates to receive CNS prophylaxis constitutes a major endpoint in the management of these malignancies. Various risk factors and models for CNS recurrence have been described. Parameters reflecting the extent and proliferation of the disease, like elevated serum lactate dehydrogenase levels, involvement of multiple extranodal sites, advanced stage and high age-adjusted International Prognostic Index (IPI) score, as well as the involvement of specific anatomic sites, like testes, orbit, paranasal sinuses, have been identified and confirmed as important to predict CNS dissemination. Management of this complication in aggressive lymphomas with conventional-dose chemotherapy is associated with disappointing results, while some preliminary but encouraging experiences suggest a potential role of high-dose chemotherapy and stem cell transplantation. The analysis of recent clinical studies could lead to advancement in the prognosis of aggressive lymphomas, but several questions regarding the optimum chemotherapy combination, the best conditioning regimen and the role of radiation therapy and intrathecal chemotherapy remain still unanswered. The purposes of the present review are to critically analyse current data on the risk of CNS dissemination in aggressive lymphomas, the clinical presentation of secondary CNS lymphomas and the efficacy of CNS prophylaxis as well as to discuss the available therapeutic options for this devastating event. Copyright © 2009 John Wiley & Sons, Ltd. [source] Postnatal corticosteroids in preterm infants: Systematic review of effects on mortality and motor functionJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2000LW Doyle Background: Postnatal corticosteroid therapy has been proved in randomized controlled trials to reduce ventilator dependence and the rate of chronic lung disease in preterm infants with few serious short-term side effects. However, there are other consequences that might follow postnatal corticosteroid therapy that are more important, including mortality or cerebral palsy. Objectives: To review the evidence from reported randomized controlled trials on the effects of postnatal corticosteroid on long-term mortality and motor dysfunction, including cerebral palsy. Methods: The methods involved a meta-analysis of reported randomized controlled trials, following guidelines of the Cochrane Collaboration, including calculation of event rate differences (ERD) and 95% confidence intervals (CI). Results: The mortality rate difference was non-significant both statistically and clinically (ERD , 0.1% favouring corticosteroids, 95% CI ,2.9% to 2.8%). There were no subgroups in which a beneficial effect of postnatal corticosteroids on survival could be demonstrated. The rate of motor dysfunction in survivors was significantly higher in survivors from the postnatal corticosteroid group (ERD 11.9% favouring controls, 95% CI 4.6% to 19.2%). The rate of survival, free of motor dysfunction, was significantly lower in the postnatal corticosteroid group (ERD 7.8% favouring controls, 95% CI 0.5% to 15.1%). Conclusions: Although postnatal corticosteroids have short-term benefits, they do not increase the survival rate, and they may cause motor dysfunction in survivors. A large-scale, placebo-controlled randomized trial, with survival free of sensorineural impairments and disabilities as the major endpoint, is urgently needed. [source] Determinants of Mortality in Patients Undergoing Cardiac Resynchronization Therapy: Baseline Clinical, Echocardiographic, and Angioscintigraphic Evaluation Prior to ResynchronizationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 12 2005ANTONIO DE SISTI Background: In dilated cardiomyopathy (DCM) patients (pts) with cardiac resynchronization therapy (CRT) for ventricular dyssynchrony, long-term predictors of mortality and morbidity remain poorly investigated. Method and Results: We reviewed data of 102 pts, 68 ± 10 years, NYHA Class II,IV (14 Class II, 67 Class III, 21 Class IV), who benefited from CRT (69 CRT, 33 CRT-ICD). Fifty-two patients had an ischemic DCM, 36 a previously implanted conventional PM/ICD, 29 a permanent atrial fibrillation, and 19 needed dobutamine in the month preceding implant. QRS duration was 187 ± 35 ms, left ventricular end-diastolic diameter 72 ± 10 mm, mitral regurgitation severity 1.9 ± 0.8, echographic aorto-pulmonary electromechanical delay 61.5 ± 25 ms and septo-lateral left intraventricular delay 86 ± 56 ms, pulmonary artery pressure (PAP) 43 ± 11 mmHg, angioscintigraphic left ventricular ejection fraction (EF) 20 ± 9%, and right ventricular EF 30.5 ± 14%. Over a mean follow-up of 23 ± 20 months, 26 pts died (18 heart failures (HFs), 1 arrhythmic storm, 7 noncardiac deaths). Positive univariate predictors of death from any cause were NYHA Class IV (P < 0.001), and need for dobutamine the month preceding CRT (P < 0.008), while use of ,-blocking agents (P < 0.08) and left ventricular EF (P < 0.09) were negative ones. NYHA Class IV was the only independent predictor at multivariate analysis (P < 0.01). Survival at 24 months was 85% in Class II, 80% in Class III, and 37% in Class IV (II vs III, P = ns; III vs IV, P < 0.001). When using a composite endpoint of death from any cause and unplanned rehospitalization for a major cardiovascular event, there were 48 events (14 HF deaths, 3 noncardiac deaths, 26 HF rehospitalizations, 2 paroxysmal atrial fibrillation, 2 sustained ventricular tachycardia, 1 nonfatal pulmonary embolism). Predictors of death from any cause/unplanned rehospitalization for a major cardiovascular event in the follow-up were NYHA Class IV (P < 0.001), need for dobutamine during the month preceding CRT (P < 0.002), and PAP (<0.02). NYHA Class IV was the only independent predictor at multivariate analysis (P < 0.05). Event-free proportion at 24 months was 70% in Class II, 64% in Class III, and 37% in Class IV (II vs III, P = ns; III vs IV, P < 0.01). When considering determinants of mortality only in NYHA Class IV patients, no variable was significantly correlated to mortality. Need for dobutamine during the last month preceding CRT did not add an adjunctive mortality risk. Conclusion: Baseline NYHA Class IV at implantation appears as the most important determinant of a poor clinical outcome in terms of both mortality and morbidity. No predictive criteria seem available for NYHA Class IV patients, in order to discriminate who will die after CRT and who will not. NYHA Class IV strongly influences the clinical outcome, suggesting that, in future studies planned on mortality and rehospitalization as major endpoints, baseline NYHA Class IV should be separately taken into account. [source] Electrical stimulation as an adjunct to spinal fusion: A meta-analysis of controlled clinical trialsBIOELECTROMAGNETICS, Issue 7 2002Masami Akai Abstract This study was a meta-analysis to examine whether electrical stimulation has a specific effect on spinal fusion. Little evidence exists on the efficacy of electrical stimulation for improving fusion rate of spinal fusion surgery. Using MEDLINE (1966,2000) and EMBASE (1985,1999), a search for articles was carried out using the Medical Subject Headings: (1) electric stimulation or electromagnetic fields, (2) spinal fusion, (3) controlled or clinical trial, and (4) human. Data were extracted from all the hit articles and additionally collected from appropriate journal lists. A total of five randomized controlled trials (RCT) on bones assessing healing of spinal fusion were identified and scored on methodological quality. All the identified studies reported positive findings, but the quality score of each trial showed wide flaws. Because of relatively homogenous subjects who had spine fusion and radiographic assessment from these studies, pooling of the data was able to be performed. Excluding one trial with the lowest score, the combined results of four trials, whose major endpoints were the success rate of the fusion, revealed a statistically significant effect of electrical stimulation with various techniques, but the selected trials still showed wide variation in view of stimulation modalities and treatment protocol. The pooled result of the studies in this review revealed the efficacy of electrical stimulation based on proved methodological quality. As problems on therapeutic modality and protocol remain, there is a further need for improvement in design to constitute acceptable proof and to establish treatment programs that better demonstrate electrical stimulation effects on spinal fusion. Bioelectromagnetics 23:496,504, 2002. © 2002 Wiley-Liss, Inc. [source] | ||||||||||