Effect of statins on venous thromboembolic events: a meta-analysis of published and unpublished evidence from randomised controlled trials

Background - It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins. Methods and Findings - We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78–1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72–1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76–1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82–1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80–1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Please see later in the article for the Editors' Summary. Conclusions - The findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more moderate reduction in risk up to about one-fifth cannot be ruled out

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

Monitoring recombinant factor VIIa treatment: efficacy depends on high levels of fibrinogen in a model of severe dilutional coagulopathy

OBJECTIVES: Recombinant activated factor VII (rFVIIa) is increasingly being given to treat massive bleeding. However, there is no clear guidance on which patients are suitable for treatment and how the effects of treatment should be monitored. The aim of this in vitro study was to assess the coagulation status of severely hemodiluted blood samples before and after treatment with therapeutic doses of rFVIIa and/or fibrinogen with 2 viscoelastic point-of-care coagulation analyzers: ROTEM (Pentapharm GmbH, Munich, Germany) and Sonoclot (Sienco Inc, Arvada, CO). DESIGN: Laboratory study. SETTING: Research coagulation laboratory. PARTICIPANTS: Ten healthy male volunteers without hereditary or acquired coagulation disorders. INTERVENTIONS: Blood samples were obtained. After severe hemodilution with albumin 5%, therapeutic doses of rFVIIa and/or fibrinogen were added, and the coagulation status was assessed with new 1:1,000 diluted tissue factor-activated tests from ROTEM and Sonoclot. MEASUREMENTS AND MAIN RESULTS: The administration of therapeutic doses of rFVIIa to hemodiluted samples shortened the initiation phase of coagulation only. Isolated fibrinogen administration to physiologic levels improved both the initiation of coagulation as well as clot formation and strength. Combined fibrinogen and rFVIIa administration further improved both effects. CONCLUSIONS: ROTEM and Sonoclot were able to monitor the effects of rFVIIa and fibrinogen administration with 1:1,000 diluted tissue factor-activated tests. The efficacy of rFVIIa was largely dependent on the presence of high levels of fibrinogen in reversing this severe dilutional coagulopathy