Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696]

BACKGROUND: Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndrome (ACS). Elevated levels of serum inflammatory markers such as C-reactive protein (CRP) represent independent risk factors for further cardiovascular events. Recent evidence indicates that in addition to lowering cholesterol levels, statins also decrease levels of inflammatory markers. Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were designed for very early secondary prevention. To our knowledge, no controlled trials have evaluated the potential benefits of statin therapy, beginning immediately at the time of hospital admission. A previous pilot study performed by our group focused on early initiation of cerivastatin therapy. We demonstrated a highly significant reduction in levels of inflammatory markers (CRP and interleukin-6). Based on these preliminary findings, we are conducting a clinical trial to evaluate the efficacy of another statin, fluvastatin, as an early intervention in patients with ACS. METHODS: The FACS-trial (Fluvastatin in the therapy of Acute Coronary Syndrome) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission. The study will enroll 1,000 participants admitted to hospital for ACS (both with and without ST elevation). The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers (CRP and interleukin-6) and on pregnancy associated plasma protein A (PAPP-A). A combined secondary endpoint is 30-day and one-year occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest. CONCLUSION: The primary objective of the FACS trial is to demonstrate that statin therapy, when started immediately after hospital admission for ACS, results in reduction of inflammation and improvement of prognosis. This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins

Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial)

<p>Abstract</p> <p>Background</p> <p>Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS.</p> <p>Methods</p> <p>The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy.</p> <p>Results</p> <p>We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037).</p> <p>Conclusions</p> <p>This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS.</p> <p>Trial registration</p> <p>NCT00171275</p

RELATION BETWEEN LEFT VENTRICULAR UNLOADING DURING ECMO AND DRAINAGE CATHETER SIZE ASSESSED BY MATHEMATICAL MODELING

The flow-dependent left ventricle overload is a well-known complication of the veno-arterial extracorporeal membrane oxygenation in a severe cardiogenic shock, which leads to a distension of the left ventricle and, frequently, to a severe pulmonary edema. Recently, an unloading of the left ventricle using a catheter inserted to the left ventricle and connected to the extracorporeal membrane oxygenation circuit has been proposed. The computational method was used to simulate the blood flow in the extracorporeal membrane oxygenation system with a drainage catheter incorporated to the left ventricle and connected to the inflow part of the extracorporeal membrane oxygenation circuit by a Y-shaped connector. The whole system was modelled in Modelica modelling language. The impact of various catheter sizes (from 5 Fr to 10 Fr) and extracorporeal blood flow values (from 1L/min to 5 L/min) were investigated. In our simulation model, the extracorporeal blood flow only modestly affected the value of volume that was withdrawn from the left ventricle by a catheter. Conversely, the size of the drainage catheter was the principal factor responsible for the achievement of the adequate left ventricle decompression. A 10 Fr drainage catheter, inserted into the left ventricle and connected to the venous part of the ECMO system, presents a promising solution to the unloading of the left ventricle during a extracorporeal membrane oxygenation

Crowdsourced Security Reconstitution for Wireless Sensor Networks: Secrecy Amplification

Research in the area of security for Wireless Sensor Networks over the past two decades has yielded many interesting findings. We focus on the topic of (re-)securing link keys between sensor nodes through so-called secrecy amplification (SA) protocols. Crowdsourcing is at the very heart of these SA protocols. Not only do SA protocols work wonders even for low-level constrained nodes with no tamper resistance, they exhibit astonishing performance in networks under significant attacker control. Our work shows that even when 50% of all network links are compromised, SA protocols can re-secure over 90% of the link keys through an intriguingly simple crowdsourcing mechanism. These protocols allow us to re-take control without any broadly coordinated cooperation, without knowledge of the compromised links, with only very limited knowledge of each particular network node and independently of decisions made by other nodes. Our article first outlines the principles of and presents existing approaches to SA, introducing most of the important related concepts, then presents novel conclusive results for a realistic attacker model parametrised by attacker behaviour and capabilities. We undertook this work using two very different simulators, and we present here the results of analyses and detailed comparisons that have not previously been available. Finally, we report the first real, non-simulated network test results for the most attractive SA protocol, our implementations of which are available as open-source code for two platforms: Arduino and TinyOS. This work demonstrates the practical usability (and the attractive performance) of SA, serving as a ripe technology enabler for (among others) networks with many potentially compromised low-level devices

Association of neuron-specific enolase values with outcomes in cardiac arrest survivors is dependent on the time of sample collection

Abstract Background Despite marked advances in intensive cardiology care, current options for outcome prediction in cardiac arrest survivors remain significantly limited. The aim of our study was, therefore, to compare the day-specific association of neuron-specific enolase (NSE) with outcomes in out-of-hospital cardiac arrest (OHCA) survivors treated with hypothermia. Methods Eligible patients were OHCA survivors treated with targeted temperature management at 33 °C for 24 h using an endovascular device. Blood samples for NSE levels measurement were drawn on days 1, 2, 3, and 4 after hospital admission. Thirty-day neurological outcomes according to the Cerebral Performance Category (CPC) scale and 12-month mortality were evaluated as clinical end points. Results A total of 153 cardiac arrest survivors (mean age 64.2 years) were enrolled in the present study. Using ROC analysis, optimal cutoff values of NSE for prediction of CPC 3–5 score on specific days were determined as: day 1 > 20.4 mcg/L (sensitivity 63.3%; specificity 82.1%; P = 0.002); day 2 > 29.0 mcg/L (72.5%; 94.4%; P  20.7 mcg/L (94.4%; 86.7%; P  19.4 mcg/L (93.5%; 91.0%; P 50.2 mcg/L at day 4 was associated with poor outcome with 100% specificity and 42% sensitivity. Moreover, NSE levels measured on all individual days also predicted 12-month mortality (P  18.1 mcg/L (85.3%; 72.0%; P  20.0 mcg/L, together with a change > 0.0 mcg/L from day 3 to day 4, predicted poor outcome (CPC 3–5) with 100% specificity and 73% sensitivity. Conclusions Our results suggest that NSE levels are a useful tool for predicting 30-day neurological outcome and long-term mortality in OHCA survivors treated with targeted temperature management at 33 °C. The highest associations of NSE with outcomes were observed on day 4 and day 3 after cardiac arrest

Evaluating Dynamic Approaches to Key (Re-)Establishment in Wireless Sensor Networks

Wireless sensor networks with a large number of cheap low-power interconnected devices bring up challenging tasks when considering the security of their communications. In our previous work, we presented two approaches for the design of dynamic protocols for link key (re-)establishment in ad hoc networks, using two elements studied earlier&#8212;secrecy amplification and key extraction from radio channel fading. The goal of this article is to provide a unified approach to the design of these protocols, together with their experimental verification, in a real network with various settings. The overall results of our experiments show that our dynamic combination of secrecy amplification and key extraction from radio channel fading saves a significant portion of messages with corresponding energy expenditure and can adapt to a much wider scale of environments when compared to previous solutions based on the exploitation of the individual elements of secrecy amplification and key extraction from radio channel fading