Assessment of neuropsychiatric adverse events in influenza patients treated with oseltamivir: a comprehensive review.

After reports from Japan of neuropsychiatric adverse events (NPAEs) in children taking oseltamivir phosphate (hereafter referred to as oseltamivir [Tamiflu; F. Hoffmann-La Roche Ltd, Basel, Switzerland]) during and after the 2004--5 influenza season, Roche explored possible reasons for the increase in reporting rate and presented regular updates to the US FDA and other regulatory authorities. This review summarizes the results of a comprehensive assessment of the company's own preclinical and clinical studies, post-marketing spontaneous adverse event reporting, epidemiological investigations utilizing health claims and medical records databases and an extensive review of the literature, with the aim of answering the following questions: (i) what the types and rates of neuropsychiatric abnormalities reported in patients with influenza are, and whether these differ in patients who have received oseltamivir compared with those who have not; (ii) what levels of oseltamivir and its active metabolite, oseltamivir carboxylate are achieved in the CNS; (iii) whether oseltamivir and oseltamivir carboxylate have pharmacological activity in the CNS; and (iv) whether there are genetic differences between Japanese and Caucasian patients that result in different levels of oseltamivir and/or oseltamivir carboxylate in the CNS, differences in their metabolism or differences in their pharmacological activity in the CNS.

Perspectives on the use of data mining in pharmaco-vigilance.

In the last 5 years, regulatory agencies and drug monitoring centres have been developing computerised data-mining methods to better identify reporting relationships in spontaneous reporting databases that could signal possible adverse drug reactions. At present, there are no guidelines or standards for the use of these methods in routine pharmaco-vigilance. In 2003, a group of statisticians, pharmaco-epidemiologists and pharmaco-vigilance professionals from the pharmaceutical industry and the US FDA formed the Pharmaceutical Research and Manufacturers of America-FDA Collaborative Working Group on Safety Evaluation Tools to review best practices for the use of these methods.

Assessing the risk of birth defects associated with antiretroviral exposure during pregnancy.

Objective: The purpose of this study was to examine teratogenic risk of antiretroviral (ARV) drugs.

Study Design: The Antiretroviral Pregnancy Registry (APR) monitors prenatal exposures to ARV drugs and pregnancy outcome through a prospective exposure-registration cohort. Statistical inference uses exact methods for binomial proportions.

The reporting odds ratio and its advantages over the proportional reporting ratio.

Purpose: The proportional reporting ratio (PRR) is the proportion of spontaneous reports for a given drug that are linked to a specific adverse outcome, divided by the corresponding proportion for all or several other drugs. The PRR is similar to the proportional mortality ratio (PMR), an old epidemiologic measure calculated from death registries and constructed in similar fashion to the PRR. The PMR has important deficiencies, however, which the PRR shares.

Health outcomes among patients receiving oseltamivir.

Purpose: Oseltamivir was approved by the FDA for the treatment of influenza in 1999. The primary objective was to compare health outcomes among influenza patients who were treated with oseltamivir and those who were not.

Methods: The patient population included UnitedHealthcare members who received an influenza diagnosis during the 1999-2000 influenza season, divided into those who were dispensed oseltamivir on the same day (N = 3211) and those who were not dispensed oseltamivir (N = 19,985).

Rational emotive behavior therapy: disputing irrational philosophies.

This article provides an overview of the concepts and techniques of rational emotive behavior therapy to distinguish it from cognitive-behavioral therapy. Rational emotive behavior therapy proposes that psychological disturbance is largely created and maintained through irrational philosophies consisting of internal absolutistic demands. This therapy strives to produce sustained and profound cognitive, emotive, and behavioral change through active, vigorous disputation of underlying irrational philosophies.

Skin reactions in patients with influenza treated with oseltamivir: a retrospective cohort study.

Oseltamivir phosphate is an FDA-approved treatment for influenza that has been available for prescription use in the USA since 1999. The present report describes findings from a post-marketing safety study of skin reactions associated with oseltamivir use. All patients in the claims-derived Ingenix Research Database with a physician diagnosis of influenza and/or a dispensing of oseltamivir between 1 December 1999 and 31 March 2002 were identified.