1,721,300 research outputs found
Tamoxifen and CYP2D6: A Controversy in Pharmacogenetics
Full text linkTamoxifen reduces the rate of breast cancer recurrence by about one-half. It is converted to more active metabolites by enzymes encoded by polymorphic genes, including cytochrome P450 2D6 (CYP2D6) and transported by ATP-binding cassette transporters. Genetic polymorphisms that confer reduced CYP2D6 activity or concurrent use of CYP2D6-inhibiting drugs may reduce the clinical efficacy of tamoxifen. The issue of the clinical utility of CYP2D6 genotype testing is subject to considerable and ongoing academic and clinical controversy. In this chapter, we outline tamoxifen's clinical pharmacology and give an overview of the research to date on the association between CYP2D6 inhibition and tamoxifen effectiveness. Based on the evidence to date, the impact of drug-induced and/or gene-induced inhibition of CYP2D6 activity is likely to be null or small, or at most moderate in subjects carrying two reduced function alleles. Future research should examine the effect of polymorphisms in genes encoding enzymes in tamoxifen's complete metabolic pathway, should comprehensively evaluate other biomarkers that affect tamoxifen effectiveness, such as the transport enzymes, and focus on subgroups of patients, such as premenopausal breast cancer patients, for whom tamoxifen is the only guideline approved endocrine therapy.</p
The risk of questioning the safety of drugs considered safe in pregnancy at the era of big data - the everlasting case of doxylamine [letter].
Full text linkOndansetron in pregnancy revisited: Assessment and pregnancy labelling by the European Medicines Agency (EMA) & Pharmacovigilance Risk Assessment Committee (PRAC)
No full textOndansetron is an effective antiemetic that is being widely used as a second-line treatment option for severe nausea and vomiting of pregnancy in accordance with clinical guidelines. The safety of ondansetron during pregnancy has-following publication of controversial and seemingly contradictory results-been subject to considerable academic turmoil, specifically with respect to the risk of congenital cardiac malformations and oral cleft. In July 2019, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) released an updated, comprehensive assessment report on the use of ondansetron in the first trimester. The ensuing Summary of Product Characteristics (SmPC) was updated in November 2019 with important changes to section on "Fertility, pregnancy and lactation." The SmPC now states that ondansetron should not be used in the first trimester of pregnancy. ENTIS, The European Network of Teratology Information Services, believes that the implementation of this regulatory step-which has important clinical consequences-is insufficiently substantiated and is not serving the interest of pregnant women with severe nausea and vomiting. Herein, we discuss the underlying evidence and argue the case against the EMA decision
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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