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.

Post-war reconstruction in the Balkans

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Sleep and Circadian Rhythm During a Short Space Mission

An experiment was conducted to assess sleep and circadian regulation in an orbiting spacecraft. In orbit, the weakened influence of 24-h zeitgebers could result in delayed circadian phases with the possibility of a transition to fee-running circadian rhythms. This and the specific stressors of a space mission may lead to changes in ultradian sleep regulation and in reduced sleep quantity and quality.During the mission, sleep was recorded polygrahically on tape, as was body temperature. Daytime alertness was rated subjectively by a mood questionnaire. For comparison, the same parameters were measured during a baseline period preceding the space mission. The circadian rhythms of body temperature and alertness were found to be delayed in space compared to baseline. this may mark a phase shift or the transition to a circadian state offree-run. Sleep was shorter and more disturbed. The structure of sleep was significantly altered. In space, REM latency was shorter, there was less REM sleep in the second non-REM/REM cycle, and slow- wave sleep was redistributed from the first to the second cycle. The self-assessed mood resembled sleep disturbances and adaptation tothe space environment. Reduced sleep quality and quantity are likely to result in fatigue and lower daytime performance. Countermeasures should be adopted to improve sleep of astronauts

Mild conversion of nitriles by free and immobilized nitrile-converting enzymes

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