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.

GOVERNMENT DEBT AS THE INTEGRAL PORTFOLIO OF ASSETS AND LIABILITIES GENERATED BY DEBT

The paper analyses the possibilities of optimal government (national) debt management, trying to maximize the made-up net value for the debtor with the help of funds borrowed by the government. The integral portfolio of debtor assets and debt service liabilities, based on the borrowed funds, is chosen as a solution for the above-described problem. In the paper, an asset is understood as a position of government expenditures, where funds borrowed by the government are used and create a quantifiable profit (value) or the measurable damage or loss is avoided if funds are borrowed. Actually, liabilities are the main debt service positions. Naturally, the value generated by assets, as well as funds spent to settle the liabilities, could be analytically adequately evaluated only in stochastic dimension. Consequently, multidimensional multicriteria stochastic optimization technique is used as a technical solution to the formulated problem. In analytical decisions, the budget funds borrowed by the government are treated as marginal funds. Taking into account a completely new decision technique that has been invoked for government debt management, the methods of decisions are described quite particularly. First published online: 02 Oct 201

Part I: State of the Art on Building Integrated Solar Thermal Systems

Energy use in buildings represents 40% of the total primary energy used in EU and therefore developing effective energy alternatives is imperative. Solar Energy Systems (STS) will have a main role to play as they they contribute directly to heating and cooling of buildings and the provision of domestic hot water. STS are typically mounted on building roofs with no attempt to incorporate them into the building envelope, creating aesthetic challenges and space availability problems. The actions will foster and accellerate long-term development in STS through critical review, experimentation, simulation and demonstration of viable systems for full incorporation and integration into the traditional building envelope. Viable solutions will also consider economic constraints, resulting in cost effective Building Integrated STS. Additionally factors like structural integrity, weather impact protection, fire and noise protection will be considered. The most important benefit of this Action is the increased adoption of RES in buildings. Three generic European regions are considered; Southern Mediterranean; Central Continental and Northern Maritime Europe, to fully explore the Pan-European nature of STS integration. The Action consortium presents a critical mass of European knowledge, expertise, resources, skills and R&D in the area of STS, supporting innovation and conceptual thinking

Mechanical properties of self-compacting concrete reinforced with polypropylene fibres

The properties of hardened concrete can be significantly improved by fibres. However, the addition of fibres to fresh concrete results in a loss of workability. Self-compacting concrete (SCC) is an innovative concrete that is able to flow under its own weight, completely filling formwork and achieving full compaction without vibration. In the present study, the workability and mechanical properties of SCC with fly ash reinforced with monofilament polypropylene fibres were investigated. Two cement contents at 350 and 450 kg m-3 were studied as well with four fibre contents at 3, 6, 9 and 12 kg m-3. The water/cement ratio, fly ash and superplasticiser contents were kept constant at 0 40, 120 kg m-3 and 1% of cement content respectively. Slump flow, J ring, V funnel and air content tests were conducted for evaluating the fluidity, filling ability and segregation risk of the fresh concretes. Unit weight, compressive strength, splitting tensile strength, flexural strength, pulse velocity and elasticity modulus of concrete were determined. The materials used in this study exhibit no problems with mixing or workability when the fibre distribution is uniform. The polypropylene fibres enhance the strength of SCC significantly, without causing well known problems associated with steel fibres. © W. S. Maney & Son Ltd. 2011

The effect of fixed investments on Lithuanian economy

Eurasian Studies in Business and Economics book series (EBES, volume 14/1) Series Print ISSN 2364-5067, Series Online ISSN 2364-5075; https://doi.org/10.1007/978-3-030-53536-0Aim of the research is to provide the theoretical backgrounds for significance of fixed investments, to estimate the changes of fixed investment growth and structure and to explore the efficiency of fixed investments and it impact on Lithuania economy. The research show that the level of investments in Lithuania was 21–29% from GDP in 2001–2008. Over the last 7 years (2011–2017), investments amounted to 19% of GDP on average. The growth of investments after the financial crisis is especially high in equipment sector. It is noticeable that many Lithuanian businesses still hesitate when it comes to making important investment decisions. Firstly, uncertainty in the market causes troubles in evaluating future changes of products and services demand. Secondly, companies seek to accumulate own funds to implement investment projects in order to avoid credit liabilitiesBioekonomikos plėtros fakultetasVytauto Didžiojo universiteta

Comparison of fatal or irreversible events with extended-duration betrixaban versus standard dose enoxaparin in acutely Ill medical patients: An APEX trial substudy

Background-Extended-duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. Methods and Results-This was a post hoc analysis of the APEX trial-a multicenter, double-blind, randomized controlled trial comparing extended-duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time-to-first event analysis. In patients with positive D-dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [P=0.002]). Conclusions-Among hospitalized medically ill patients, extended-duration betrixaban demonstrated an 48 30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin

Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely III Medical Patients: An APEX Trial Substudy

BACKGROUND: Extended-duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. METHODS AND RESULTS: This was a post hoc analysis of the APEX trial-a multicenter, double-blind, randomized controlled trial comparing extended-duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time-to-first event analysis. In patients with positive D-dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [P=0.002]). CONCLUSIONS: Among hospitalized medically ill patients, extended-duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01583218.status: publishe