factor IIV

High interindividual variability (IIV) of the clinical response to epidermal growth factor receptor (EGFR) inhibitors such as osimertinib in non-small-cell lung cancer (NSCLC) might be related to the IIV in plasma exposure. The aim of this study was to evaluate the exposure-response relationship for toxicity and efficacy of osimertinib in unselected patients with advanced EGFR-mutant NSCLC. This retrospective analysis included 87 patients treated with osimertinib. Exposure-toxicity analysis was performed in the entire cohort and survival analysis only in second-line patients ( n = 45)...

BACKGROUND: Sacrectomy carries significant risk of bleeding; however, specific risk factors, apart from medical comorbidities and tumor type, for this life-threatening complication remain unclear. This study describes two cases of massive bleeding, including one death during sacrectomy attributable to adherence of the internal iliac vein (IIV) and its neuroforaminal tributaries from sacral insufficiency fractures. OBSERVATIONS: The authors presented two cases involving patients who received sacrectomy for a chordoma and experienced massive bleeding from the IIV due to adherence of the IIV and its neuroforaminal tributaries around sacral insufficiency fractures...

Aims and background: A number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to characterize the influencing factors of their pharmacokinetics. This review described PPK models of anti-PD-1 mAbs that investigate the magnitude and types of covariate effects in PK parameters, provide a reference for building PPK models of other anti-PD-1 mAbs, and identify areas requiring additional research to facilitate the application of PPK models...

PURPOSE: This study aimed to analyze characteristics, treatment, long-term outcomes, and prognostic factors for children, adolescents and young adults with rhabdomysosarcoma (RMS). METHODS: This retrospective historical study included 75 patients with RMS treated between 2002 and 2019. Clinical data and follow-up results were collected including all diagnosis, treatment and prognosis information. RESULTS: Patients median-age-at-diagnosis was 6 years...

AIMS: Locally advanced rectal cancer (LARC) is an area of unmet medical need with one third of patients dying from their disease. With response to neoadjuvant chemo-radiotherapy being a major prognostic factor, trial SAKK 41/16 assessed potential benefits of adding regorafenib to capecitabine-amplified neoadjuvant radiotherapy in LARC patients. METHODS: Patients received regorafenib at three dose levels (40/80/120 mg once daily) combined with capecitabine 825 mg/m2 bidaily and local radiotherapy...

dsRNA sensing triggers antiviral responses against RNA and DNA viruses in diverse eukaryotes. In Drosophila, Invertebrate iridescent virus 6 (IIV-6), a large DNA virus, triggers production of small interfering RNAs (siRNAs) by the dsRNA sensor Dicer-2. Here, we show that host RNA polymerase II (RNAPII) bidirectionally transcribes specific AT-rich regions of the IIV-6 DNA genome to generate dsRNA. Both replicative and naked IIV-6 genomes trigger production of dsRNA in Drosophila cells, implying direct sensing of invading DNA...

INTRODUCTION: Seasonal inactivated influenza vaccine (IIV) is routinely recommended during pregnancy to protect both mothers and infants from complications following influenza infection. While previous studies have evaluated the risk of major structural birth defects in infants associated with prenatal administration of monovalent pandemic IIV, fewer studies have evaluated the risk associated with prenatal seasonal IIV. METHODS: We conducted a population-based cohort study of 125,866 singleton births between 2012 and 2016 in Western Australia...

CONTEXT: Poor sleep is common in collegiate student athletes and is associated with heterogenous self-reported complaints at baseline. However, exploration of the long-term implications of poor sleep at baseline has been less well studied. OBJECTIVE: To examine the implications of insufficient sleep at baseline, and factors such as symptom reporting and neurocognitive performance at baseline associated with insufficient sleep, for risk of sport-related concussion (SRC)...

Contextual stressors, such as engagement in burdensome emotion regulation known as expressive suppression (ES), can result in transient but clinically meaningful decrement in performance on measures of executive functioning (EF). The goal of the present investigation was to examine whether intra-individual variability (IIV-I), which has been identified as an indicator of cognitive weakness, could serve as a marker of vulnerability to EF decrements due to both naturally-occurring and experimentally-manipulated ES...

OBJECTIVE: Patients with rheumatic disease (RD) have an increased risk of influenza and its complications. Despite inactivated influenza vaccine (IIV) recommendations, IIV uptake in patients with RD is suboptimal, a problem of increasing importance in the COVID-19 era. We estimated the frequency of IIV hesitancy and associated factors among Canadian patients with RD. METHODS: A cross-sectional vaccine hesitancy survey was completed by rheumatology clinic patients (November 2019 to January 2020)...

OBJECTIVE: To explore associations between intraindividual variability (IIV) in sleep patterns and sleep problems, lifestyle factors, and mental and physical health in individuals with chronic insomnia. METHODS: Cross-sectional study of 1720 adults with chronic insomnia (67.8% female, mean age = 44.5) who completed online self-report questionnaires and kept a sleep diary (for at least 10 out of 14 days). Linear regression analyses examined IIV in sleep patterns as independent variables, and sleep problems, lifestyle factors, and mental and physical health outcomes as dependent variables...

Although sleep problems are common in children with ADHD, their extent, preceding risk factors, and the association between neurocognitive performance and neurobiological processes in sleep and ADHD, are still largely unknown. We examined sleep variables in school-aged children with ADHD, addressing their intra-individual variability (IIV) and considering potential precursor symptoms as well as the chronotype. Additionally, in a subgroup of our sample, we investigated associations with neurobehavioral functioning ( n = 44)...

BACKGROUND: Relative vaccine effectiveness (rVE) are metrics commonly reported to compare absolute VE (aVE) of 2 vaccine products. METHODS: Estimates of rVE for enhanced influenza vaccines (eIV) vs standard inactivated influenza vaccine (IIV) have been assessed across different seasons, influenza-specific endpoints, and nonspecific endpoints (eg, all-cause cardiovascular hospitalizations). To illustrate the challenges of comparability across studies, we conducted a scenario analysis to evaluate the effects of varying absolute VE (aVE) of IIV (ie, as compared with placebo) on the interpretation of rVE of eIV vs IIV...

Annual influenza vaccination is often recommended for pregnant women and young children to reduce the risk of severe influenza. However, most studies investigating the safety, immunogenicity, and efficacy or effectiveness of influenza vaccines are conducted in healthy adults. In this evidence-based clinical review, we provide an update on the safety profile, immunogenicity, and efficacy/effectiveness of inactivated influenza vaccines (IIVs) in healthy pregnant women and children <5 years old. Six electronic databases were searched until May 27, 2021...

BACKGROUND AND OBJECTIVES: REC-2282 is a novel histone deacetylase inhibitor that has shown antitumor activity in in vitro and in vivo models of malignancy.  The aims of this study were to characterize the population pharmacokinetics of REC-2282 (AR-42) from the first-in-human (NCT01129193) and phase I acute myeloid leukemia trials (NCT01798901) and to evaluate potential sources of variability. Additionally, we sought to understand alternate body size descriptors as sources of inter-individual variability (IIV), which was significant for dose-normalized maximum observed concentration and area under the concentration-time curve (AUC)...

Smoking is a cause of serious diseases in smokers including chronic respiratory diseases. This study aimed to evaluate the tobacco harm reduction (THR) potential of an electronic vapor product (EVP, my blu™) compared to a Kentucky Reference Cigarette (3R4F), and assessed endpoints related to chronic respiratory diseases. Endpoints included: cytotoxicity, barrier integrity (TEER), cilia function, immunohistochemistry, and pro-inflammatory markers. In order to more closely represent the user exposure scenario, we have employed the in vitro 3D organotypic model of human airway epithelium (MucilAir™, Epithelix) for respiratory assessment...

AIMS: Meltdose tacrolimus (Envarsus) is marketed as a formulation with a more consistent exposure. Due to the narrow therapeutic window, therapeutic drug monitoring is essential to maintain adequate exposure. The primary objective of this study was to develop a population pharmacokinetic (PK) model of Envarsus among liver transplant patients and select a limited sampling strategy (LSS) for AUC estimation. The secondary objective was to investigate potential covariates including CYP3A/IL genotype suitable for initial dose optimization when converting to Envarsus...

Objective: To provide the risk stratification method of hepatoblastoma (HB) suitable for implementation in China and explore the new treatment method for high-risk HB patients. Methods: A total of 100 cases of children and adolescents under 18 years old with newly diagnosed HB in Sun Yat-sen University Cancer Center and Sun Yat-sen University First Affiliated Hospital from September 2014 to September 2018 were included. According to the clinical stage, AFP level, pathological subtype and other factors, patients were stratified into four groups: extremely low-, low-, intermediate- and high-risk...

Eperisone is an oral muscle relaxant used to treat musculoskeletal diseases, which exhibits high pharmacokinetic (PK) variability in bioequivalence studies. The aim of this study was to characterize the PKs of eperisone following its oral administration to Korean volunteers through the conduct of a noncompartmental and population analysis. A total of 360 concentration-time measurements collected on two separate occasions from 15 healthy volunteers during a bioequivalent study of eperisone 50 mg (Murex® ) were used in the PK analysis...

Flu virus infection is a common cause of acute respiratory illness, with the major incidence in pediatric age, high morbidity, and mortality. The flu vaccine is recommended for all people aged ≥6 months, unless specific contraindications are present. Younger and older age, pregnancy, chronic diseases like asthma, and immunodeficiency are risk factors for severe complications following flu infection. Thus, these categories represent the target for flu vaccine strategies in most countries. Inactivated influenza vaccine (IIV), recombinant influenza vaccine (RIV) or live-attenuated influenza virus (LAIV) are currently available, with specific precautions and contraindications...