Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Subtle Europeanisers: Czech and Slovak advocacy and assistance strategy in the Western Balkans

Two and half decades after the fall of the Berlin Wall, Europe has made signifi cant headway in unifi cation “despite its diversity”. In unprecedented “big bang” rounds of EU enlargement, eight Central and East European (CEE) countries joined the European Union in 2004; two Eastern Balkan countries, Bulgaria and Romania, in 2007; and the fi rst Western Balkan country, Croatia, became the EU’s 28th member state in July 2013. As of early 2015, the rest of the Western Balkans (WB) 2 has obtained either a candidate status (Albania, the Former Yugoslav Republic of Macedonia-FYROM, Montenegro and Serbia) or a potential candidate status (Bosnia and Herzegovina and Kosovo).</p

Commodity risk assessment of ash logs from the US treated with sulfuryl fluoride to prevent the entry of the emerald ash borer Agrilus planipennis

The European Commission submitted to the EFSA Panel on Plant Health a dossier by USDA proposing to use sulfuryl fluoride on ash log shipments to treat Agrilus planipennis for phytosanitary certification. After collecting additional evidence from USDA APHIS, external experts and literature, the Panel performed a quantitative assessment on the likelihood of pest freedom from A. planipennis, at the point of entry in the EU, of two different commodities fumigated with sulfuryl fluoride: (a) ash logs with bark; and (b) debarked ash logs. An expert judgement is given on the likelihood of pest freedom taking into consideration the measures acting on the pest, including uncertainties associated with the assessment. The likelihood of pest freedom from A. planipennis is lower for ash logs with bark compared with debarked ash logs. With 95% certainty, the Panel concludes that between 9,740 and 10,000 containers of ash logs with bark per 10,000 and between 9,989 and 10,000 containers of debarked ash logs per 10,000 will be free from A. planipennis, when fumigated with sulfuryl fluoride at the specific treatment regime proposed by the USDA APHIS