Search

Background: Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder associated with abnormal angiogenesis and disabling epistaxis. Tranexamic acid (TA) has been widely used in the treatment of these severe bleeds but with no properly designed trial., Objectives: To demonstrate the efficacy of TA in epistaxis in HHT patients and to explore its safety of use., Patients/methods: A randomized, placebo-controlled, double-blind, cross-over trial was conducted. Participants were randomized to receive TA (3 g a day) then placebo or the opposite sequence. The main analysis compared intra-individual mean duration of epistaxis under TA vs. placebo on a log scale. The primary outcome was the mean duration of epistaxis per month, assessed with specific grids to be completed by participants. The number of epistaxis episodes was recorded as a secondary outcome., Results: A total of 118 randomized patients contributed to the statistical analysis. The mean duration of epistaxis per month was significantly shorter with TA than placebo (0.19 on the log scale; SD = 0.07; P = 0.005), corresponding to a decrease of 17.3% (15.7 min) in the duration of epistaxis per month (CI 95%, 5.5-27.6). The median number of epistaxis episodes per month was 22.1 episodes in the placebo arm vs. 23.3 episodes in the TA arm. No thrombophlebitis was observed., Conclusions: In the ATERO study, we demonstrated a significant decrease in the duration of epistaxis in HHT patients taking TA. No safety issues were recorded in our cohort of patients., (© 2014 International Society on Thrombosis and Haemostasis.)

Background: The use of Clinical Data Management Systems (CDMS) has become essential in clinical trials to handle the increasing amount of data that must be collected and analyzed. With a CDMS trial data are captured at investigator sites with "electronic Case Report Forms". Although more and more of these electronic data management systems are used in academic research centres an overview of CDMS products and of available data management and quality management resources for academic clinical trials in Europe is missing., Methods: The ECRIN (European Clinical Research Infrastructure Network) data management working group conducted a two-part standardized survey on data management, software tools, and quality management for clinical trials. The questionnaires were answered by nearly 80 centres/units (with an overall response rate of 47% and 43%) from 12 European countries and EORTC., Results: Our survey shows that about 90% of centres have a CDMS in routine use. Of these CDMS nearly 50% are commercial systems; Open Source solutions don't play a major role. In general, solutions used for clinical data management are very heterogeneous: 20 different commercial CDMS products (7 Open Source solutions) in addition to 17/18 proprietary systems are in use. The most widely employed CDMS products are MACRO and Capture System, followed by solutions that are used in at least 3 centres: eResearch Network, CleanWeb, GCP Base and SAS. Although quality management systems for data management are in place in most centres/units, there exist some deficits in the area of system validation., Conclusions: Because the considerable heterogeneity of data management software solutions may be a hindrance to cooperation based on trial data exchange, standards like CDISC (Clinical Data Interchange Standard Consortium) should be implemented more widely. In a heterogeneous environment the use of data standards can simplify data exchange, increase the quality of data and prepare centres for new developments (e.g. the use of EHR for clinical research). Because data management and the use of electronic data capture systems in clinical trials are characterized by the impact of regulations and guidelines, ethical concerns are discussed. In this context quality management becomes an important part of compliant data management. To address these issues ECRIN will establish certified data centres to support electronic data management and associated compliance needs of clinical trial centres in Europe.

Objective: Although current guidelines rest exclusively on the measurement of systolic and diastolic blood pressures, the arterial pressure wave is more precisely described as consisting of a pulsatile (pulse pressure) and a steady (mean pressure) component. This study explored the independent roles of pulse pressure and mean pressure as predictors of mortality in a wide range of patients with hypertension., Design and Methods: This meta-analysis, based on individual patient data, has combined results from the control groups of seven randomized clinical trials conducted in patients with systolo-diastolic or isolated systolic hypertension. The relative hazard rates associated with pulse pressure and mean pressure were calculated using Cox's proportional hazard regression models with stratification for the seven trials and with adjustment for sex, age, smoking and the other pressure., Results: A 10 mmHg wider pulse pressure at baseline, which corresponds to approximately one-half of its standard deviation, was independently associated with an increase in risk by 6% for total mortality (P = 0.001), 7% for cardiovascular mortality (P = 0.01), and 7% for fatal coronary accidents (P = 0.03). The corresponding increase in risk of fatal stroke was similar (+6%, P = 0.27) but there were too few strokes to reach statistical significance. In similar analyses, mean pressure was not identified as an independent predictor of these outcomes. Significant interactions of pulse pressure or mean pressure with age suggested that the prognostic power of pulse pressure for fatal stroke was more important at higher age (P = 0.04), whereas the prognostic power of mean pressure for coronary mortality was greatest in the young (P = 0.01)., Conclusions: In hypertensive patients pulse pressure, not mean pressure, is associated with an increased risk of fatal events. This appears to be true in a broad range of patients with hypertension.