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Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase-1 (COX-1) inhibition. We performed a multicenter double-blind trial to investigate the efficacy of 3 aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2–dependent vascular thromboresistance. Patients on chronic once-daily low-dose aspirin (n = 245) were randomized (1:1:1) to receive 100 mg of aspirin 1, 2, or 3 times daily for 2 weeks. Serum thromboxane B2 (sTXB2), a validated biomarker of platelet COX-1 activity, and urinary prostacyclin metabolite (PGIM) excretion were measured at randomization and after 2 weeks, as primary surrogate end points of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the twice-daily and thrice-daily regimens showed substantially reduced interindividual variability and lower median (interquartile range) values for sTXB2 (ng/mL) compared with the once-daily arm: 4 (2.1-6.7; n = 79), 2.5 (1.4-5.65, n = 79), and 19.3 (9.7-40; n = 85), respectively. Urinary PGIM was comparable in the 3 arms. Urinary TXM was reduced by 35% in both experimental arms. Patients in the thrice-daily arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75 to 100 once daily for cardiovascular prophylaxis appears to be largely inadequate in reducing platelet activation in the vast majority of patients with ET. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement with further reductions (EudraCT 2016-002885-30).

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by enhanced platelet production and thrombotic complications. The inhibition of platelet cyclooxygenase (COX) activity by the standard once-daily aspirin is mostly incomplete due to accelerated thrombopoiesis. The phase II Aspirin Regimens in EsSential thrombocythemia (ARES) trial has recently compared the efficacy of once- vs. twice- or three-times daily low-dose aspirin in inhibiting platelet thromboxane (TX) A2 production, as reflected by serum (s) TXB2 measurements. The present substudy characterized the determinants of the highly variable response to the standard aspirin 100 mg once-daily regimen in fully compliant patients with ET and the effects of the experimental dosing regimens on response variability. By multivariable analysis, the platelet count (directly) and cytoreductive treatment (inversely) were significantly associated with sTXB2 values in 218 patients with ET. However, the platelet count positively correlated with sTXB2 in patients not being treated with cytoreductive drugs (ρ = 0.51, P

Once-daily (od), low-dose aspirin (75–100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. ARES is a parallel-arm, placebo-controlled, randomized, dose-finding, phase II trial enrolling 300 ET patients to address two main questions. First, whether twice or three times 100 mg aspirin daily dosing is superior to the standard od regimen in inhibiting platelet thromboxane (TX)A2 production, without inhibiting vascular prostacyclin biosynthesis. Second, whether long-term persistence of superior biochemical efficacy can be safely maintained with multiple vs. single dosing aspirin regimen. Considering that the primary study end point is serum TXB2, a surrogate biomarker of clinical efficacy, a preliminary exercise of reproducibility and validation of this biomarker across all the 11 participating centers was implemented. The results of this preliminary phase demonstrate the importance of controlling reproducibility of biomarkers in multicenter trials and the feasibility of using serum TXB2 as a reliable end point for dose-finding studies of novel aspirin regimens.

Once-daily (od), low-dose aspirin (75–100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. ARES is a parallel-arm, placebo-controlled, randomized, dose-finding, phase II trial enrolling 300 ET patients to address two main questions. First, whether twice or three times 100 mg aspirin daily dosing is superior to the standard od regimen in inhibiting platelet thromboxane (TX)A2 production, without inhibiting vascular prostacyclin biosynthesis. Second, whether long-term persistence of superior biochemical efficacy can be safely maintained with multiple vs. single dosing aspirin regimen. Considering that the primary study end point is serum TXB2, a surrogate biomarker of clinical efficacy, a preliminary exercise of reproducibility and validation of this biomarker across all the 11 participating centers was implemented. The results of this preliminary phase demonstrate the importance of controlling reproducibility of biomarkers in multicenter trials and the feasibility of using serum TXB2 as a reliable end point for dose-finding studies of novel aspirin regimens.

The RUVIVAL Publication Series is part of the open source learning project RUVIVAL. All topics of RUVIVAL Volume 1 are related on several levels and are part of restoration engineering. Each contribution in this publication is connected to further interactive multimedia material, which can be reached under http://www.hoou.de. The literature review papers are a collaboration of Master students, PhD students and researchers at the Institute of Wastewater Management and Water Protection (AWW) at Hamburg University of Technology. This volume consists of 3 literature review papers. The first reviews agroforestry, the practice of including trees or other woody perennial plants into agricultural systems, including crop and livestock production. It explains the challenges and benefits of this practice and provides an example of its implementation within the Slope Farming Project in Arba Minch, Ethiopia. The second paper introduces the concept of living terraces, which constitute a combination of erosion control measures on slopes. They are similar to contour hedgerows, but are constructed with the aim of accumulating soil on the uphill side of the tree row, so that in the long run, bench terraces are formed on their own. Their role as part of rainwater harvesting practices is explained in more depth in the paper. Finally, the third literature review provides insight into check dams, structures built across channels to reduce erosion by lowering water speed and accumulating sediments during floods. Check dams are often introduced in degraded areas and they represent one of the most used stabilisation measures worldwide, because of their relative simplicity and easy implementation. This paper also introduces a well-known case study in the Loess Plateau, China. Die RUVIVAL-Publikationsreihe ist Teil des Open-Source-Lernprojekts RUVIVAL. Alle Themen von RUVIVAL Volume 1 stehen auf mehreren Ebenen miteinander in Beziehung und sind Teil des Restaurierungsingenieurwesens. Jeder Beitrag in dieser Publikation ist mit weiteren interaktiven Lerninhalten verbunden, die unter http://www.hoou.de eingesehen werden können. Die Literaturübersichten sind eine Zusammenarbeit von Masterstudent*innen, Doktorand*innen und Forschenden des Instituts für Abwasserwirtschaft und Gewässerschutz (AWW) der Technischen Universität Hamburg. Diese Ausgabe besteht aus 3 Literaturübersichten. Die erste befasst sich mit der Agroforstwirtschaft, der Praxis der Einbeziehung von Baumarten oder anderen mehrjährigen Holzpflanzen in landwirtschaftliche Systeme, einschließlich der Nutzpflanzen- und Tierproduktion. Erläutert werden die Herausforderungen und Vorteile dieser Praxis, ergänzt durch ein Beispiel für ihre Umsetzung im Rahmen des Slope Farming Project in Arba Minch, Äthiopien. Der zweite Beitrag stellt das Konzept der lebenden Terrassen vor, die eine Kombination von Erosionsschutzmaßnahmen an Hängen darstellen. Sie ähneln den Kontur-Hecken, werden aber mit dem Ziel konstruiert, an der Hangseite der Gehölzreihen Boden anzustauen, so dass sich auf lange Sicht selbständig Terassenbänke bilden. Ihre Rolle als Teil der Regenwassernutzung wird in der Publikation näher erläutert. Schließlich gibt die dritte Literaturübersicht Einblicke in die Thematik der Geröllsprerren, die über Wasserläufe gebaut werden, um die Erosion durch Senkung der Wassergeschwindigkeit und Anhäufung von Sedimenten bei Überschwemmungen zu verringern. Geröllsprerren werden häufig in von Erosion beeinträchtigten Gegenden angewandt und stellen aufgrund ihrer relativen Einfachheit und leichten Umsetzbarkeit eine der weltweit am häufigsten verwendeten Stabilisierungsmaßnahmen dar. Des weiteren stellt diese Publikation auch eine Fallstudie im Löss-Plateau in China vor.