Isotretinoin exposure during pregnancy: A population-based study in the Netherlands

Objective: To estimate isotretinoin exposure in Dutch pregnant women despite the implemented pregnancy prevention programme (PPP) and second, to analyse the occurrence of adverse fetal or neonatal outcomes in these isotretinoin exposed pregnancies.Design: Population-based study.Setting: The Netherlands.Participants: A cohort of 203 962

Evidence and Extrapolation: Mechanisms for Regulating Off-Label Uses of Drugs and Devices

A recurring, foundational issue for evidence-based regulation is deciding whether to extend governmental approval from an existing use with sufficient current evidence of safety and efficacy to a novel use for which such evidence is currently lacking. This extrapolation issue arises in the medicines context when an approved drug or device that is already being marketed is being considered (1) for new conditions (such as off-label diagnostic categories), (2) for new patients (such as new subpopulations), (3) for new dosages or durations, or (4) as the basis for approving a related drug or device (such as a generic or biosimilar drug). Although the logic of preapproval testing and the precautionary principle—first, do no harm—would counsel in favor of prohibiting extrapolation approvals until after traditional safety and efficacy evidence exists, such delays would unreasonably sacrifice beneficial uses. The harm of accessing unsafe products must be balanced against the harm of restricting access to effective products. In fact, the Food and Drug Administration\u27s (FDA\u27s) current regulations in many ways reject the precautionary principle because they largely permit individual physicians to prescribe medications for off-label uses before any testing tailored to those uses has been done. The FDA\u27s approach empowers physicians, but overshoots the mark by allowing enduring use of drugs and devices with insubstantial support of safety and efficacy. This Article instead proposes a more dynamic and evolving evidence-based regime that charts a course between the Scylla and Charybdis of the overly conservative precautionary principle on one hand, and the overly liberal FDA regime on the other. Our approach calls for improvements in reporting, testing, and enforcement regulations to provide a more layered and nuanced system of regulatory incentives. First, we propose a more thoroughgoing reporting of off-label use (via the disclosure of diagnostic codes and detailing data) in manufacturers\u27 annual reports to the FDA, in the adverse event reports to the FDA, in Medicare/Medicaid reimbursement requests, and, for a subset of FDA-designated drugs, in prescriptions themselves. Second, we would substantially expand the agency\u27s utilization of postmarket testing, and we provide a novel framework for evaluating the need for postmarket testing. Finally, our approach calls for a tiered labeling system that would allow regulators and courts to draw finer reimbursement and liability distinctions among various drug uses, and would provide the agency both the regulatory teeth and the flexibility it presently lacks. Together, these reforms would improve the role of the FDA in the informational marketplace underlying physicians\u27 prescribing decisions. This evolutionary extrapolation framework could also be applied to other contexts

The Value Driven Pharmacist: Basics of Access, Cost, and Quality 2nd Edition

https://digitalcommons.butler.edu/butlerbooks/1017/thumbnail.jp

Functional Text Analysis of Oath for Engineers: Its Meta-functions and Linguistic Characteristics

This paper aims at investigating the language structure of the oath for engineers in the light of Systemic Functional Linguistics and examining how the oath is textualized to accomplish its roles and objectives as the guiding principle which sets the ideals and obligation of professional engineers. Hence, the main objective of this study is to identify the pattern of the text\u27s structure by analyzing its metafunctions comprising the textual, interpersonal, and ideational functions. The main data used in this study is the text of oath for engineers as subscribed by the members of professional engineers in USA and Canada. The results of data analysis showed that the text has special features characterizing the genre of oath and its purpose as indicated by 1) the predominance of declarative clauses, 2) the equal USAge of marked and unmarked themes representing the setting and reaction phases in the text, 3) the typical form of zig-zag pattern of the thematic organization, and  4) the dominant use of material processes indicating that the text construes the world more in terms of action with engineers at its center, 5) the validity of proposition of the oath for the present time when the engineers subscribe to the oath and to the actual situation for the future time as indicated by the tense of the clauses in the text. Thus, unfolding the discourse of oath in English for engineering class is beneficial to increase learning interactions in which reading is treated as the focus of the teaching as well as enhancing students\u27 individual development as a part of character education

A 65-year experience treating acne, including 26 years with oral isotretinoin

Este artigo especial foi extraído de uma palestra proferida pelo Prof. Sebastião Sampaio e elaborado em conjunto com a Profa Edileia Bagatin. Reflete a experiência dos autores no tratamento das principais formas de acne nos períodos pré e pós a introdução da isotretinoína oral que revolucionou a abordagem da doença. Esta droga representa a única opção capaz de levar à remissão prolongada ou cura da acne por atuar em todos os mecanismos etiopatogênicos conhecidos até o momento. Evidentemente, deve ser prescrita de acordo com as recomendações vigentes e reservada para casos de difícil controle, com tendência a cicatrizes e com sérias repercussões psico-sociais. Outras modalidades terapêuticas, tópicas e/ou sistêmicas, devem ser consideradas no início do tratamento e nos casos de intensidade leve a moderada.This special article is based on the contents of a lecture given by Sampaio and was written together with Bagatin. It is a summary of the authors’ experience treating various forms of acne before and after the introduction of oral isotretinoin, which revolutionized the management of the disease. Nowadays, this drug is considered the unique option to obtain a prolonged remission or cure of acne due to its action in all etiopathogenic factors involved in the disease. Therefore it should be prescribed in accordance to current recommendations, as well as for difficult cases, including those showing tendency to scars or serious psychological and social repercussions. Other topical and/or systemic therapeutic modalities should be considered in the initial approach and for mild and moderate cases

Особливості вживання художніх засобів у сучасних пісенних англомовних текстах (на матеріалі текстів гурту «Manowar»)

(uk) Дослідження у галузі лінгвістики тексту є завжди актуальними, оскільки п о в’язані зі сферою, щопостійно оновлюється, поширюється за рахунок появи нових текстів художньої літератури та масової культури. Одним із цікавих та досить плідних поприщ для дослідження є сучасна музика, а саме тексти пісень. У статті проаналізовано особливості вживання художніх засобів у сучасних пісенних англомовних текстах (на матеріалі текстів рок-гурту «Manowar»).(ru) Исследования в области лингвистики текста никогда не утратят актуальности, поскольку они связаны с постоянно обновляющейся сферой, которая пополняется все новыми и новыми образцами художественной литературы и массовой культуры. Одним из достаточно плодотворных поприщ для исследования является современная музыка, а именно тексты песен. В статье проанализированы особенности использования стилистических выразительных средств в текстах современных англоязычных песен (на материале текстов рок-группы «Manowar»)