A5062147032- Trauma and Emergency Care Studies
- Abdominal Trauma and Injuries
- Statistical Methods in Clinical Trials
- Urological Disorders and Treatments
- Cardiac Arrest and Resuscitation
- Health Systems, Economic Evaluations, Quality of Life
- Emergency and Acute Care Studies
- Pharmaceutical studies and practices
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Pelvic and Acetabular Injuries
- Computational Drug Discovery Methods
- Cardiac electrophysiology and arrhythmias
- Pharmacogenetics and Drug Metabolism
- Trauma Management and Diagnosis
- Diet and metabolism studies
- Lipoproteins and Cardiovascular Health
- Treatment of Major Depression
- Venous Thromboembolism Diagnosis and Management
- Meta-analysis and systematic reviews
- Receptor Mechanisms and Signaling
- Global Health Workforce Issues
- Patient Safety and Medication Errors
- Nutrition and Health in Aging
- Digestive system and related health
- Cardiac, Anesthesia and Surgical Outcomes
Frederick National Laboratory for Cancer Research
2024
Texas Children's Hospital
2024
Leidos Biomedical Research Inc. (United States)
2024
Babcock & Wilcox (United States)
2024
Leidos (United States)
2024
University of Pennsylvania
2015-2023
University of Washington
2019-2023
University of California, San Francisco
2018-2023
University of Michigan
2023
University of Colorado Health
2023
Therapeutic agents that block the calcitonin gene–related peptide (CGRP) signaling pathway are a highly anticipated and promising new drug class for migraine therapy, especially after reports small-molecule CGRP-receptor antagonists efficacious both acute treatment prevention. Using XenoMouse technology, we successfully generated AMG 334, fully human monoclonal antibody against CGRP receptor. Here show 334 competes with [<sup>125</sup>I]-CGRP binding to receptor, <i>K</i><sub>i</sub> of 0.02...
Importance The COVID-19 pandemic led to widespread lockdowns and school closures that may have affected screen time among children. Although restrictions were strongest early in the pandemic, it is unclear how changed as progressed. Objective To evaluate change children’s from before during July 2019 through August 2021. Design, Setting, Participants This a longitudinal cohort study with repeated measures of collected 2 periods. Children aged 4 12 years their parent enrolled 3 pediatric...
The QT effects of five “QT‐positive” and one negative drug were tested to evaluate whether exposure–response analysis can detect in a small study with healthy subjects. Each was given nine subjects (six for placebo) two dose levels; positive drugs chosen cause 10 12 ms 15 20 QTcF prolongation. slope the concentration/ΔQTc effect significantly ondansetron, quinine, dolasetron, moxifloxacin, dofetilide. For lower dose, an above could not be excluded, i.e., upper bound confidence interval...
Central lines in NICUs have long dwell times. Success reducing central line-associated bloodstream infections (CLABSIs) requires a multidisciplinary team approach to line maintenance and insertion. The Perinatal Quality Collaborative of North Carolina (PQCNC) CLABSI project supported the development NICU teams including parents, implementation an action plan with unique bundle elements rigorous reporting schedule. goal was reduce rates by 75%.Thirteen participated initiative developed over 3...
Current therapies for traumatic blood loss focus on hemorrhage control and volume replacement. Severe hemorrhagic shock, however, is associated with a state of arginine vasopressin (AVP) deficiency, supplementation this hormone may decrease the need products in resuscitation.To determine whether low-dose AVP patients trauma (hereinafter referred to as patients) shock decreases their transfused during resuscitation.This randomized, double-blind placebo-controlled clinical trial included adult...
BACKGROUND The rarity of renal trauma limits its study and the strength evidence-based guidelines. Although management injuries has shifted toward a nonoperative approach, nephrectomy remains most common intervention for high-grade (HGRT). We aimed to describe contemporary HGRT in United States also evaluate clinical factors associated with after HGRT. METHODS From 2014 2017, data on (American Association Surgery Trauma grades III-V) were collected from 14 participating Level-1 centers. Data...
Monoclonal antibodies (mAbs) targeting calcitonin gene‐related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of CGRP receptor. We report data from two phase I studies assessing safety, pharmacokinetics (PK), pharmacodynamics single multiple administrations erenumab in healthy subjects patients with The results indicate that PK profile nonlinear 1 mg to 70 linear...
BACKGROUND: Admission hypocalcemia predicts both massive transfusion and mortality in severely injured patients. However, the effect of calcium derangements during resuscitation remains unexplored. We hypothesize that any or hypercalcemia (either primary from overcorrection) first 24 hours after severe injury is associated with increased mortality. METHODS: All patients at our institution protocol activation January 2013 through December 2014 were identified. Patients transferred another...
The Injury Severity Score (ISS) has been validated in numerous studies and become one of the most common trauma scoring systems since its inception. ISS equation was later modified to create New (NISS). By using three severe injuries regardless body region, NISS seems well suited describe patients penetrating trauma, where often cluster within a single region. We hypothesized that would better predict outcomes than patients.An analysis (June 2008 March 2009) all severely injured (length...
Abstract The glycine to cysteine mutation on codon 12 of KRAS (KRASG12C) is found in ~15% non-small cell lung cancers and a low percentage colorectal pancreatic adenocarcinomas. This activating pushes the balance cellular towards its active, GTP-bound (ON) state that signals downstream drives proliferation. Recently approved inhibitors KRASG12C bind sequester oncogenic protein inactive GDP-bound (OFF) state, have demonstrated clinical efficacy; however, median duration response has been...
Objective: Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder in children, adolescents, and adults. This study was conducted, part, to evaluate single-dose steady-state pharmacokinetics atomoxetine pediatric patients. Methods: an open-label, dose-titration patients with disorder. Eligible could elect participate a or discontinuation pharmacokinetic evaluation including serial plasma sample collection over 24 hours. Plasma concentrations atomoxetine,...
ABSTRACT Damage-control resuscitation in the care of critically injured trauma patients aims to limit blood loss and prevent treat coagulopathy by combining early definitive hemorrhage control, hypotensive resuscitation, balanced use products (hemostatic resuscitation) other hemostatic agents. This clinical protocol has been developed provide evidence-based recommendations for optimal damage-control with hemorrhage.
The purpose of this study was to characterize the effect potent CYP2D6 inhibition by paroxetine on atomoxetine disposition in extensive metabolizers. This a single‐blind, two‐period, sequential 22 healthy individuals. In period 1, 20 mg bid administered steady state. 2, qd for 17 days. On days 12 through 17, were coadministered. Plasma pharmacokinetics atomoxetine, 4‐hydroxyatomoxetine, and N‐desmethylatomoxetine determined at state each treatment period. after 11th 17th doses. Paroxetine...
Abstract We have compared DNA methylation in normal colon mucosa between patients with cancer and without cancer. identified significant differences the two groups at 114 to 874 genes. The majority of are pathways involved metabolism carbohydrates, lipids, amino acids. also transcript levels genes insulin signaling pathway. found that had significantly higher several hormones regulating glucose lower a glycolytic enzyme key regulator lipid homeostasis. These suggest metabolizes dietary...
Early trauma deaths have the potential for salvage with immediate surgery. We studied time from injury to death in this group qualify characteristics and quantify operating room, yielding greatest opportunity salvage.The Pennsylvania Trauma Outcomes Study (PTOS) is a comprehensive registry including all centers. PTOS was queried adult patients 1999 2010 dying within 4 hours of injury. The distribution (TD) examined subgroups according mechanism injury, hypotension (defined as systolic blood...
Multiple genome-wide association studies have identified non-coding single-nucleotide variants (SNVs) near (e.g., rs10166942[C]) or within (rs17862920[T]) the TRPM8 gene that encodes a cold thermosensor is associated with reduced migraine risk. Furthermore, and rs10166942[T]) are more prevalent in populations reside hotter colder climates, respectively. Here we assessed whether these alleles affect expression humans human physiologic responses to challenge. show decreased from chromosome...
Background and Objectives Atomoxetine is a treatment for attention‐deficit/hyperactivity disorder primarily eliminated via cytochrome P4502D6 (CYP2D6). The pharmacokinetics of atomoxetine its primary metabolites were investigated in 10 adults with hepatic impairment (6 moderate, 4 severe) age‐ sex‐matched control subjects, all being genotyped as CYP2D6 extensive metabolizers. Methods A single oral 20‐mg dose was given. Multiple blood samples collected 48 hours healthy subjects 120 patients....
Arterial shunting is a well-described method to control hemorrhage and rapidly reestablish flow, but optimal shunt dwell times remain controversial. We hypothesized that prolonged of more than 6 hours are related adverse outcomes after major arterial injury.A review (2005-2013) all patients with shunts placed traumatic injury at our urban Level I trauma center was undertaken. Patients who died prior removal (n = 7) were excluded. Shunt complications defined as dislodgement, thrombosis,...
Venous thromboembolism (VTE) after major vascular injury (MVI) is particularly challenging because the competing risk of thrombosis and embolization direct vessel must be balanced with bleeding surgical repair. We hypothesized that venous injuries, repair type, intraoperative anticoagulation would influence VTE formation MVI.A multi-institution, retrospective cohort study consecutive MVI patients was conducted at three urban, Level I centers (2005-2013). Patients neck, torso, or proximal...