Fluid challenges in intensive care: the FENICE study A global inception cohort study

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account

Safety of Recombinant Activated Factor VII in Randomized Clinical Trials

Background: The use of recombinant activated factor VII (rFVIIa) on an off-label basis to treat life-threatening bleeding has been associated with a perceived increased risk of thromboembolic complications. However, data from placebo-controlled trials are needed to properly assess the thromboembolic risk. To address this issue, we evaluated the rate of thromboembolic events in all published randomized, placebo-controlled trials of rFVIIa used on an off-label basis. Methods: We analyzed data from 35 randomized clinical trials (26 studies involving patients and 9 studies involving healthy volunteers) to determine the frequency of thromboembolic events. The data were pooled with the use of random-effects models to calculate the odds ratios and 95% confidence intervals. Results: Among 4468 subjects (4119 patients and 349 healthy volunteers), 498 had thromboembolic events (11.1%). Rates of arterial thromboembolic events among all 4468 subjects were higher among those who received rFVIIa than among those who received placebo (5.5% vs. 3.2%, P=0.003). Rates of venous thromboembolic events were similar among subjects who received rFVIIa and those who received placebo (5.3% vs. 5.7%). Among subjects who received rFVIIa, 2.9% had coronary arterial thromboembolic events, as compared with 1.1% of those who received placebo (P=0.002). Rates of arterial thromboembolic events were highest among subjects older than 65 years of age, as compared with those who were 65 years of age or younger (9.0% vs. 3.8%, P=0.003); the rates were especially high among subjects 75 years of age or older, as compared with those who were younger than 75 years of age (10.8% vs. 4.1%, P=0.02). Conclusions: In a large and comprehensive cohort of persons in placebo-controlled trials of rFVIIa, treatment with high doses of rFVIIa on an off-label basis significantly increased the risk of arterial but not venous thromboembolic events, especially among the elderly. (Funded by Novo Nordisk.) N Engl J Med 2010;363:1791-80

Usefulness of Cochrane Reviews in Clinical Guideline Development—A Survey of 585 Recommendations

The Danish Health Authority develops clinical practice guidelines to support clinical decision-making based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and prioritizes using Cochrane reviews. The objective of this study was to explore the usefulness of Cochrane reviews as a source of evidence in the development of clinical recommendations. Evidence-based recommendations in guidelines published by the Danish Health Authority between 2014 and 2021 were reviewed. For each recommendation, it was noted if and how Cochrane reviews were utilized. In total, 374 evidence-based recommendations and 211 expert consensus recommendations were published between 2014 and 2021. Of the 374 evidence-based recommendations, 106 included evidence from Cochrane reviews. In 28 recommendations, all critical and important outcomes included evidence from Cochrane reviews. In 36 recommendations, a minimum of all critical outcomes included evidence from Cochrane reviews, but not all important outcomes. In 33 recommendations, some but not all critical outcomes included evidence from Cochrane reviews. Finally, in nine recommendations, some of the important outcomes included evidence from Cochrane reviews. In almost one-third of the evidence-based recommendations, Cochrane reviews were used to inform clinical recommendations. This evaluation should inform future evaluations of Cochrane review uptake in clinical practice guidelines concerning outcomes important for clinical decision-making

Safety and Preliminary Efficacy of Recombinant Activated FVII Analog (NN1731) In the Treatment of Joint Bleeds In Congenital Hemophilia Patients with Inhibitors

52nd Annual Meeting of the American-Society-of-Hematology (ASH) -- DEC 04-07, 2010 -- Orlando, FLWOS: 000289662200720Amer Soc Hemato

Effects of Co, Fe, and Al doping on the oxygen disordering and superconducting transition temperature of YBa₂Cu₃O₆₊_x

Using computer simulation on a model of oxygen ordering in the basal Cu1−yMyOx plane of the high-temperature superconductor YBa2Cu3−yMyO6+x, we show that the effect of substituting Cu with M = Co, Fe, or Al is a diminishing of the oxygen-ordered orthorhombic domain sizes and eventually a breakdown of the orthorhombic structure. The model accounts for experimental structural data. By use of a previously established minimal model, which connects the superconducting transition temperature, Tc, to the formation of specific ordered orthorhombic domains in the undoped material, we show that the detrimental effect on Tc by metal-ion doping as well as oxygen depletion becomes manifest in a unified way as a result of oxygen disorderin