Pharmacogenetics of Bleeding and Thromboembolic Events in Direct Oral Anticoagulant Users

Publisher Copyright: © 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and TherapeuticsThis study aimed to analyze associations between genetic variants and the occurrence of clinical outcomes in dabigatran, apixaban, and rivaroxaban users. This was a retrospective real-world study linking genotype data of three Finnish biobanks with national register data on drug dispensations and healthcare encounters. We investigated several single-nucleotide variants (SNVs) in the ABCG2, ABCB1, CES1, and CYP3A5 genes potentially associated with bleeding or thromboembolic events in direct oral anticoagulant (DOAC) users based on earlier research. We used Cox regression models to compare the incidence of clinical outcomes between carriers and noncarriers of the SNVs or haplotypes. In total, 1,806 patients on apixaban, dabigatran, or rivaroxaban were studied. The ABCB1 c.3435C>T (p.Ile1145=, rs1045642) SNV (hazard ratio (HR) 0.42, 95% confidence interval (CI), 0.18-0.98, P = 0.044) and 1236T-2677T-3435T (rs1128503-rs2032582-rs1045642) haplotype (HR 0.44, 95% CI, 0.20-0.95, P = 0.036) were associated with a reduced risk for thromboembolic outcomes, and the 1236C-2677G-3435C (HR 2.55, 95% CI, 1.03-6.36, P = 0.044) and 1236T-2677G-3435C (HR 5.88, 95% CI, 2.35-14.72, P A (rs4148738) SNV associated with a lower risk for bleeding events (HR 0.37, 95% CI, 0.16-0.89, P = 0.025) in apixaban users. ABCB1 variants are potential factors affecting thromboembolic events in rivaroxaban users and bleeding events in apixaban users. Studies with larger numbers of patients are warranted for comprehensive assessment of the pharmacogenetic associations of DOACs and their relevance for clinical practice.Peer reviewe

Beach nourishment and foredune restoration: practices and constraints along the Venetian shoreline, Italy

Artificial beach nourishment is commonly practiced along the North Adriatic coast of Italy to fight beach erosion. About 10 million m3 of sand has been placed along 45 km of coast in 10 years. The strong wind regime and the need to protect coastal habitat have drawn attention to problems associated with aeolian transport and dune reconstruction. This study analyses three nourished sites, where morphological and sedimentological data were gathered along complete beach/dune profiles. The beach/dune sediment budget over a period of 2, 6 and 10 years after the interventions and the elevation and distance of the reconstructed dunes from the shoreline were examined and compared with a natural control area. A grain size suitability evaluation was carried out, together with a verification of the effects of grain size selection in transport from the beach to the dune. The study enabled evaluation of the potential for nourishment practices to reconstruct and restore the beach/dune system. The renewed sediment availability yielded different results in term of dune supply, ranging from the total lack of dune accretion to the spontaneous formation of embryo foredunes. Dune changes do not depend on sediment used for fill, because the relatively fine grain size does not limit aeolian transport. The beach management practices (fences, raking etc.) seem to be critical, together with shoreline orientation and the consequent aeolian transport potential. In many cases, the practices are not suitable and should be redirected to achieve a satisfactory compromise between environmental protection and recreational use