Biomarkers and clinical outcomes after tezepelumab cessation: Extended follow-up from the 2-year DESTINATION study.

Background: Long-term tezepelumab treatment in the DESTINATION study (NCT03706079) resulted in reduced asthma exacerbations, reduced biomarker levels, and improved lung function and symptom control in patients with severe, uncontrolled asthma.

Objective: To explore the time course of changes in biomarkers and clinical manifestations after treatment cessation after 2 years of tezepelumab treatment.

Methods: DESTINATION was a 2-year, phase 3, multicenter, randomized, placebo-controlled, double-blind study of tezepelumab treatment in patients (12-80 years old) with severe asthma.

Understanding Statin-Roxadustat Drug-Drug-Disease Interaction Using Physiologically-Based Pharmacokinetic Modeling.

A different drug-drug interaction (DDI) scenario may exist in patients with chronic kidney disease (CKD) compared with healthy volunteers (HVs), depending on the interplay between drug-drug and disease (drug-drug-disease interaction (DDDI)). Physiologically-based pharmacokinetic (PBPK) modeling, in lieu of a clinical trial, is a promising tool for evaluating these complex DDDIs in patients. However, the prediction confidence of PBPK modeling in the severe CKD population is still low when nonrenal pathways are involved.

A Conceptual Framework for Instructional Design of a High Acuity and Low Occurrence Event - Simulation Based Education Training of Residents, Medical Students, and Nurses in Anaphylaxis Utilizing Curated Educational Theories.

The broad goal of this educational curriculum is utilization and optimization of Simulation-Based Education (SBE) in the training of residents, medical students, and nursing staff involved in the rapid and timely recognition of Anaphylaxis and its optimized treatment. A critical gap in Anaphylaxis Diagnosis, Management, and Treatment (ADAM) has been well established across medical disciplines. It is imperative to include all members of the healthcare team, as nurses and pharmacists play key roles in anaphylaxis recognition and care.

Does the choice of applied physiologically-based pharmacokinetics platform matter? A case study on simvastatin disposition and drug-drug interaction.

Physiologically-based pharmacokinetic (PBPK) models have an important role in drug discovery/development and decision making in regulatory submissions. This is facilitated by predefined PBPK platforms with user-friendly graphical interface, such as Simcyp and PK-Sim. However, evaluations of platform differences and the potential implications for disposition-related applications are still lacking.

Hospital staff at most psychiatric clinics in Stockholm experience that patients who self-harm have too long hospital stays, with ensuing detrimental effects.

Background: Previous research on patients who self-harm has indicated potential negative effects from long hospital stays. Yet, such care has been reported to occur regularly. We conducted this questionnaire study to investigate how hospital staff, who treat self-harming patients, experience the relation between lengths of stay and self-harm behaviour, and the motives for non-beneficial hospital stays.

Model-Based Analysis Reveals a Sustained and Dose-Dependent Acceleration of Wound Healing by VEGF-A mRNA (AZD8601).

Intradermal delivery of AZD8601, an mRNA designed to produce vascular endothelial growth factor A (VEGF-A), has previously been shown to accelerate cutaneous wound healing in a murine diabetic model. Here, we develop population pharmacokinetic and pharmacodynamic models aiming to quantify the effect of AZD8601 injections on the dynamics of wound healing. A dataset of 584 open wound area measurements from 131 mice was integrated from 3 independent studies encompassing different doses, dosing timepoints, and number of doses.

Physician estimated vs. self-reported subjective memory in depressed patients treated with electroconvulsive therapy.

Subjective memory deficits are common in depression and during series of treatment with electroconvulsive therapy (ECT). There is a need for feasible assessment of memory deficit. In the Swedish National Quality Register for ECT, patients' subjective memory function is rated by a clinician.

Modified VEGF-A mRNA induces sustained multifaceted microvascular response and accelerates diabetic wound healing.

Capable of mediating efficient transfection and protein production without eliciting innate immune responses, chemically modified mRNA holds great potential to produce paracrine factors at a physiologically beneficial level, in a spatiotemporally controlled manner, and with low toxicity. Although highly promising in cardiovascular medicine and wound healing, effects of this emerging therapeutic on the microvasculature and its bioactivity in disease settings remain poorly understood. Here, we longitudinally and comprehensively characterize microvascular responses to AZD8601, a modified mRNA encoding vascular endothelial growth factor A (VEGF-A), in vivo.

Confirmatory factor analysis of the parental feeding style questionnaire with a preschool sample.

Purpose: Despite being widely used, there has not yet been a confirmatory factor analysis (CFA) on the English version of the Parental Feeding Style Questionnaire (PFSQ). Preschool is a critical time to assess parental feeding styles, and the PFSQ is one of the few measures that can be used with young children. As such, the current study conducted the first CFA on the PFSQ in an English-speaking sample in the United States to establish preliminary evidence of its factor structure.

Physiologically Based Pharmacokinetic Model of Itraconazole and Two of Its Metabolites to Improve the Predictions and the Mechanistic Understanding of CYP3A4 Drug-Drug Interactions.

Physiologically based pharmacokinetic (PBPK) modeling for itraconazole using a bottom-up approach is challenging, not only due to complex saturable pharmacokinetics (PK) and the presence of three metabolites exhibiting CYP3A4 inhibition, but also because of discrepancies in reported in vitro data. The overall objective of this study is to provide a comprehensive mechanistic PBPK model for itraconazole in order to increase the confidence in its drug-drug interaction (DDI) predictions. To achieve this, key in vitro and in vivo data for itraconazole and its major metabolites were generated.

Psychiatrists' motives for practising in-patient compulsory care of patients with borderline personality disorder (BPD).

Introduction: Patients with BPD are often subjected to compulsory care. However, as compulsory care restricts liberty and may have negative effects, it is recommended that it be used sparingly. In this study, we investigate psychiatrists' motives for practising compulsory care of BPD patients.

Human hepatocytes and cytochrome P450-selective inhibitors predict variability in human drug exposure more accurately than human recombinant P450s.

Background And Purpose: Drugs metabolically eliminated by several enzymes are less vulnerable to variable compound exposure in patients due to drug-drug interactions (DDI) or if a polymorphic enzyme is involved in their elimination. Therefore, it is vital in drug discovery to accurately and efficiently estimate and optimize the metabolic elimination profile.

Experimental Approach: CYP3A and/or CYP2D6 substrates with well described variability in vivo in humans due to CYP3A DDI and CYP2D6 polymorphism were selected for assessment of fraction metabolized by each enzyme (fm ) in two in vitro systems: (i) human recombinant P450s (hrP450s) and (ii) human hepatocytes combined with selective P450 inhibitors.

Concurrent and Longitudinal Associations Among Temperament, Parental Feeding Styles, and Selective Eating in a Preschool Sample.

Objective: To examine the associations among negative/reactive temperament, feeding styles, and selective eating in a sample of preschoolers because preschool eating behaviors likely have lasting implications for children's health.

Methods: A community sample of preschoolers aged 3-5 years (M = 4.49 years, 49.

Early executive control and risk for overweight and obesity in elementary school.

An emerging literature suggests that poor executive control (EC) may be associated with clinical weight problems, e.g., body mass index (BMI) for age percentile ≥85 in children.

Latina and Non-Latina Mothers' Perceived Health Barriers and Benefits and Their Relationship to Children's Health Behaviors.

Objectives Disparities exist in rates of overweight/obesity between Latino and non-Latino populations. Attention should be given to risk factors that may be modifiable through interventions involving both the parent and child. The current study sought to identify ethnic differences in parental health beliefs and their relation to children's health behaviors.

Stimulant Medications and Sleep for Youth With ADHD: A Meta-analysis.

Context: Mixed findings exist on whether stimulant medications alter youth sleep.

Objective: To determine the effect of stimulant medications on sleep.

Data Studies: Studies published through March 2015 were collected via CINAHL, PsycINFO, and PubMed.

Quantifying and Communicating Uncertainty in Preclinical Human Dose-Prediction.

Human dose-prediction is fundamental for ranking lead-optimization compounds in drug discovery and to inform design of early clinical trials. This tutorial describes how uncertainty in such predictions can be quantified and efficiently communicated to facilitate decision-making. Using three drug-discovery case studies, we show how several uncertain pieces of input information can be integrated into one single uncomplicated plot with key predictions, including their uncertainties, for many compounds or for many scenarios, or both.

A Meta-Analysis of the Effect of Experimental Sleep Restriction on Youth's Attention and Hyperactivity.

This meta-analysis examined the effect experimental sleep restriction has on youth's attention and hyperactivity outcomes. Thirteen published studies containing 17 independent samples were included (N = 496). Random- and fixed-effects models were used to estimate pooled effect sizes and moderator effects, respectively.

Gender differences in the relationship between impulsivity and disordered eating behaviors and attitudes.

Objective: We investigated relationships among gender, impulsivity and disordered eating in healthy college students.

Method: Participants (N=1223) were healthy, undergraduate men (28.5%) and women (71.

Sleep and food intake: A multisystem review of mechanisms in children and adults.

The foods we eat have substantial impact on our health, and excessive food intake is associated with numerous long-term health conditions. It is therefore essential to understand the factors influencing this crucial health behavior. Research has identified sleep problems as one such factor; however, little research has examined how sleep problems impact food intake.