Pharmacokinetic and pharmacodynamic data from the NEOLEV1 and NEOLEV2 studies.

Objectives: To confirm that levetiracetam (LEV) demonstrates predictable pharmacokinetics(PK) at higher doses and to study the pharmacodynamics(PD) of LEV.

Design: Pharmacokinetic data from the NEOLEV1 and NEOLEV2 trials were analysed using a non-linear mixed effects modelling approach. A post hoc analysis of the effect of LEV on seizure burden was conducted.

Analysis of US Food and Drug Administration Oncology Approvals on the Characterization of Hepatic Impairment Effect and Dosing Recommendations.

Patients with cancer and advanced hepatic impairment (HI) (i.e., moderate and severe impairment) are often excluded from first-in-patient, phase II, and phase III studies.

Pharmacokinetics of darunavir and cobicistat in pregnant and postpartum women with HIV.

Objective: To evaluate darunavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery.

Design: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States.

Methods: Intensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800 mg of darunavir and 150 mg of cobicistat orally in fixed dose combination once-daily during the second trimester, third trimester, and postpartum.

Discordance Between Child-Pugh and National Cancer Institute Classifications for Hepatic Dysfunction: Implications on Dosing Recommendations for Oncology Compounds.

Guidance from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency recommends using Child-Pugh classification for pharmacokinetic evaluation in noncancer subjects with hepatic impairment (HI).

Electroencephalography Measures are Useful for Identifying Large Acute Ischemic Stroke in the Emergency Department.

Background: Early diagnosis of stroke optimizes reperfusion therapies, but behavioral measures have incomplete accuracy. Electroencephalogram (EEG) has high sensitivity for immediately detecting brain ischemia. This pilot study aimed to evaluate feasibility and utility of EEG for identifying patients with a large acute ischemic stroke during Emergency Department (ED) evaluation, as these data might be useful in the prehospital setting.

Predicting Gains With Visuospatial Training After Stroke Using an EEG Measure of Frontoparietal Circuit Function.

The heterogeneity of stroke prompts the need for predictors of individual treatment response to rehabilitation therapies. We previously studied healthy subjects with EEG and identified a frontoparietal circuit in which activity predicted training-related gains in visuomotor tracking. Here we asked whether activity in this same frontoparietal circuit also predicts training-related gains in visuomotor tracking in patients with chronic hemiparetic stroke.

Anhedonia Following Early-Life Adversity Involves Aberrant Interaction of Reward and Anxiety Circuits and Is Reversed by Partial Silencing of Amygdala Corticotropin-Releasing Hormone Gene.

Background: Anhedonia, the diminished ability to experience pleasure, is an important dimensional entity linked to depression, schizophrenia, and other emotional disorders, but its origins and mechanisms are poorly understood. We have previously identified anhedonia, manifest as decreased sucrose preference and social play, in adolescent male rats that experienced chronic early-life adversity/stress (CES). Here we probed the molecular, cellular, and circuit processes underlying CES-induced anhedonia and tested them mechanistically.