1,721,108 research outputs found
State of the art of new P2Y12 antagonists
No full textThe interaction of ADP with its platelet receptor P2Y12 plays a crucial role in platelet activation and thrombogenesis. This article reviews the pharmacology and clinical trials of specific antagonists of P2Y12. Clopidogrel is a thienopyridine with proven antithrombotic efficacy, but it has some important drawbacks: (a) it is a pro-drug that needs to be metabolized to its active metabolite; (b) it has a delayed onset and offset of action and (c) there is high inter-individual variability in pharmacological response. Prasugrel is also a thienopyridine, with faster onset of action and a more uniform inhibition of platelet function compared to clopidogrel, accounting for lower incidence of ischemic events in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) and higher incidence of both non-CABG-related bleeding complications. Two direct and reversible P2Y12 antagonists, Cangrelor and ticagrelor, are characterized by rapid onset and reversal of platelet inhibition. Cangrelor is not superior to clopidogrel in preventing thrombotic events in patients undergoing PCI. Ticagrelor is superior to clopidogrel in preventing major adverse cardiac events in ACS patients, but, like prasugrel, is associated with a higher frequency of non-CABG-related bleeding complications. A shorter period of drug discontinuation before surgery is necessary in ticagrelor-treated patients compared to clopiodgrel-treated patients to limit the severity of post-surgical bleeding
PREDICTION OF OPTIMAL WARFARIN MAINTENANCE DOSE USING ADVANCED ARTIFICIAL NEURAL NETWORKS
Full text linkIntroduction. The individual response to vitamin K antagonists (VKA) is highly variable, being influenced by clinical factors and genetic variants of enzymes that are involved in the metabolism of VKA (CYP2C)) and vitamin K (VKORC1). Currently, the dose of VKA is adjusted based on measurements of the prothrombin time. In the last years, mathematical algorithms were developed for estimating the appropriate VKA dose, based on different mathematical approaches working on clinical and genetic data. Artificial Neural Networks (ANN) are computerized algorithms resembling interactive processes of the human brain, which allow to study very complex non-linear phenomena like biological systems. Aim. To evaluate the performance of new generation ANN on a large data base of patients on chronic VKA treatment. Methods. Clinical and genetic data from 377 patients (186 m; 191 f) treated with a VKA (warfarin) average weekly maintenance dose (WMD) of 23.7 mg (11.5 SD) were used to create a dose algorithm. Forty-eight variables, including demographic, clinical and genetic data (5 CYP2C9 and 3 VKORC1 genetic variants) were entered into Twist® system, which can select fundamental variables during their evolution in search for the best predictive model. The final model, based on 23 variables expressed a functional approximation of the actual dose within a validation protocol based on a tripartite division of the data set (training, testing, validation). Results. In the validation cohort, the pharmacogenetic algorithm reached high accuracy, with an average absolute error of 5.7 mg WMD. In the subset of patients requiring ≤21 mg (45 % of the cohort) and 21-49 mg (51 % of the cohort) the absolute error was 3.86 mg and 5.45 with a high percentage of subjects being correctly identified (72%, 74% respectively). Conclusion. ANN can be applied successfully for VKA maintenance dose prediction and represent a robust basis for a prospective multicentre clinical trial of the efficacy of genetically informed dose estimation for patients who require VKA
Can plasma levels of N-terminal pro-brain natriuretic peptide be useful in predicting the risk of developing chronic pulmonary hypertension in patients with pulmonary embolism?
No full textCurrent and emerging approaches for evaluating platelet disorders
No full textPlatelets play a central role in physiological hemostasis and also in pathological thrombosis. It is well established that congenital or acquired abnormalities of platelet function are associated with a heightened risk of bleeding of variable severity and excessive hemorrhage after surgery or trauma. Several kinds of different platelet function tests have been developed over the years to identify or diagnose platelet function disorders. The use of these tests for the assessment of thrombotic risk or for monitoring the effects of drugs inhibiting platelet function is not well established. Light transmission aggregometry (LTA) is the gold standard for the study of patients with defects of platelet function. Its results are affected by several pre-analytical and analytical variables. The Subcommittee on Platelet Physiology of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis published official guidelines for the standardization of the variables affecting LTA, which should be followed to harmonize the procedures across different laboratories worldwide. The lumi-aggregometer, a modification of LTA that measures platelet secretion in parallel with aggregation, is preferable to LTA for diagnosing inherited defects of platelet function, because it is more sensitive to the most common disorders, which are characterized by abnormalities of platelet secretion. LTA (or lumi-aggregometry) is useful as a first screening test of patients with the clinical suspicion of defects of platelet function, because it helps to provide an interim diagnostic hypothesis, which can then be confirmed or discounted using appropriate and specific tests
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Usefulness of PFA-100 (R) testing in the diagnostic screening of patients with suspected abnormalities of hemostasis: comparison with the bleeding time
No full textBackground: Global tests of hemostasis that are used to screen patients with clinical suspicion of bleeding disorders should help the physician to identify the phase of the hemostatic system that is abnormal and guide further diagnostic workup.Patients and methods: We compared the performance of Platelet Function Analyzer-100 (PFA-100((R))) closure time (CT) with bleeding time (BT), both of which are screening tests for primary hemostasis, in the diagnostic workup of 128 consecutive patients who were screened for bleeding disorders. The sensitivities of BT and PFA-100 CT for known defects of hemostasis were evaluated; in addition, we calculated their correlation with the levels of severity of the bleeding symptoms, which were recorded using a standardized questionnaire.Results: The sensitivity of PFA-100 testing was 71% for von Willebrand disease (VWD) [with both collagen-adenosine diphosphate (C-ADP) and collagen-epinephrine (C-EPI) cartridges]; 58% (C-EPI) and 8% (C-ADP) for platelet function disorders (PFDs); and the sensitivity of BT was 29% (VWD) and 33% (PFD). C-EPI CT was also prolonged in about 20% of patients with abnormalities of coagulation or fibrinolysis. Only the C-EPI CT was significantly associated with the levels of severity of the patients' bleeding scores.Conclusions: BT and C-EPI are insufficiently sensitive to be recommended as hemostasis screening tests. The C-ADP cartridge, which is sensitive to VWD only, might prove useful in further diagnostic workup of defects of primary hemostasis. The association of C-EPI CT with the severity of bleeding symptoms as a useful predictor of risk of bleeding in clinical practise should be tested in properly designed studies
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