Analysis of Drug Test Results Before and After the US Declaration of a National Emergency Concerning the COVID-19 Outbreak.

This substance use epidemiology study uses a commercial urine drug testing (UDT) service’s data to compare UDT results for cocaine, fentanyl, heroin, and methamphetamine before vs after US declaration of coronavirus disease 2019 (COVID-19) as a national emergency among patients diagnosed with or at risk of substance use disorders.

The Time Is Now to End the HIV Epidemic.

In his State of the Union Address on February 5, 2019, President Donald J. Trump announced his administration's goal to end the domestic HIV epidemic. Following the announcement of the Ending the HIV Epidemic: A Plan for America initiative, the president proposed $291 million in new funding for the fiscal year 2020 Department of Health and Human Services (HHS) budget to implement a new initiative to reduce the number of new HIV infections by 75% in the next five years (2025) and by 90% in the next 10 years (2030).

Racial/Ethnic and Age Group Differences in Opioid and Synthetic Opioid-Involved Overdose Deaths Among Adults Aged ≥18 Years in Metropolitan Areas - United States, 2015-2017.

Among the 47,600 opioid-involved overdose deaths in the United States in 2017, 59.8% (28,466) involved synthetic opioids (1). Since 2013, synthetic opioids, particularly illicitly manufactured fentanyl (IMF), including fentanyl analogs, have been fueling the U.

ENHANCE: results of a global open-label trial of drotrecogin alfa (activated) in children with severe sepsis.

Objective: To gather additional 28-day all-cause mortality data and safety information for pediatric patients with severe sepsis who received drotrecogin alfa (activated) (DrotAA).

Design And Setting: Single-arm, open-label, multicentered study conducted in 59 study sites in 15 countries.

Patients: One-hundred eighty-eight children (term newborn to <18 yrs old) with severe sepsis were consecutively enrolled in the study.

The Pediatric Multiple Organ Dysfunction Score (P-MODS): development and validation of an objective scale to measure the severity of multiple organ dysfunction in critically ill children.

Objective: To develop and then prospectively validate an objective scale to grade multiple organ system dysfunction in a large population of critically ill children.

Design: Prospective, observational cohort study.

Setting: A pediatric intensive care unit at a tertiary care pediatric teaching hospital.

Tumor necrosis factor-alpha-induced caspase activation mediates endotoxin-related cardiac dysfunction.

Objective: Sepsis-induced cardiac dysfunction is a serious clinical syndrome characterized by hypotension, decreased systemic vascular resistance, and elevated cardiac index. Although cytokines such as tumor necrosis factor (TNF)-alpha have been shown to play a significant role early in this response, the downstream effects of TNF-alpha signaling on cardiac function, specifically its relationship to apoptosis, have not been fully elucidated.

Design: Previous studies from our laboratory have identified endotoxin-induced apoptosis in cardiac cells in vitro.

Fresh whole blood versus reconstituted blood for pump priming in heart surgery in infants.

Background: In an attempt to reduce the coagulopathic and inflammatory responses seen after cardiopulmonary bypass, the use of fresh whole blood during heart operations has become the standard of care for neonates and infants at many institutions. We compared the use of fresh whole blood with the use of a combination of packed red cells and fresh-frozen plasma (reconstituted blood) for priming of the cardiopulmonary bypass circuit.

Methods: We conducted a single-center, randomized, double-blind, controlled trial involving children less than one year of age who underwent open-heart surgery.

Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury.

We have recently demonstrated that macrophage migration inhibitory factor (MIF) is a myocardial depressant protein and that MIF mediates late, prolonged cardiac dysfunction after endotoxin challenge in mice. Because many factors, including endotoxin, have been implicated in the pathogenesis of cardiac dysfunction after burn injury, we tested the hypothesis that MIF might also be the mediator of prolonged cardiac dysfunction in this model. At 4 h after 40% total body surface area burn in anesthetized mice, serum MIF levels increased significantly compared with baseline (2.

Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis.

Objective: In a phase 3 trial, recombinant human activated protein C (drotrecogin alfa [activated]) significantly reduced mortality in adult patients with severe sepsis. We have now performed a preliminary analysis of the safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in pediatric patients with severe sepsis.

Design And Setting: Open-label, nonrandomized, sequential, 2-part study conducted in 11 medical centers in the United States and United Kingdom.

Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor.

Macrophage migration inhibitory factor (MIF) is a pluripotent proinflammatory cytokine that is ubiquitously expressed in organs, including the heart. However, no specific role for MIF in modulating cardiac performance has yet been described. Therefore, we examined cardiac MIF expression in mice after LPS challenge (4 mg/kg) and tested the hypothesis that MIF is a mediator of LPS-induced cardiac dysfunction.

IRAK1 deletion disrupts cardiac Toll/IL-1 signaling and protects against contractile dysfunction.

Myocardial contractile dysfunction accompanies both systemic and cardiac insults. Septic shock and burn trauma can lead to reversible contractile deficits, whereas ischemia and direct inflammation of the heart can precipitate transient or permanent impairments in contractility. Many of the insults that trigger contractile dysfunction also activate the innate immune system.

Pediatric critical care medicine: planning for our research future.

Objective: To introduce to the pediatric critical care medicine community a new program in pediatric critical care medicine at the National Institutes of Health.

Data Source: Summary of literature review and conference proceedings.

Data Synthesis: At the National Institute of Child Health and Human Development (NICHD), a new program in pediatric critical care and rehabilitation research has been established in the National Center for Medical Rehabilitation Research.

Recombinant human activated protein C for the treatment of severe sepsis: is there a role in pediatrics?

Sepsis with organ failure (severe sepsis) remains an important cause of morbidity and mortality among children. The clinical pathophysiology of severe sepsis reflects a coordinated activation of the innate immune response, including elaboration of proinflammatory cytokines and the induction of the extrinsic pathway of coagulation (sepsis-induced coagulopathy). These proinflammatory and procoagulant pathways are linked, and are similarly coregulated by a number of proteins and factors, including protein C.

Improving the outcome of septic shock in children.

Sepsis is an important cause of pediatric morbidity and mortality. Improving the outcome of pediatric sepsis requires diverse efforts, including prevention, early recognition, improvements in early management and transport, and physiology-directed care. Awareness that septic shock represents a pathophysiologic host response to infection has prompted investigation of immune mediators and coagulation factors as potential targets for anti-sepsis therapies.