Differences in testing for drugs of abuse amongst racial and ethnic groups at children's hospitals.

OBJECTIVES: Racial and ethnic differences in drug testing have been described among adults and newborns. Less is known regarding testing patterns among children and adolescents. We sought to describe the association between race and ethnicity and drug testing at US children's hospitals. We hypothesized that non-Hispanic White children undergo drug testing less often than children from other groups. METHODS: We conducted a retrospective cohort study of emergency department (ED)-only encounters and hospitalizations for children diagnosed with a condition for which drug testing may be indicated (abuse or neglect, burns, malnutrition, head injury, vomiting, altered mental status or syncope, psychiatric, self-harm, and seizure) at 41 children's hospitals participating in the Pediatric Health Information System during 2018 and 2021. We compared drug testing rates among (non-Hispanic) Asian, (non-Hispanic) Black, Hispanic, and (non-Hispanic) White children overall, by condition and patient cohort (ED-only vs. hospitalized) and across hospitals. RESULTS: Among 920,755 encounters, 13.6% underwent drug testing. Black children were tested at significantly higher rates overall (adjusted odds ratio [aOR]: 1.18; 1.05-1.33) than White children. Black-White testing differences were observed in the hospitalized cohort (aOR: 1.42; 1.18-1.69) but not among ED-only encounters (aOR: 1.07; 0.92-1.26). Asian, Hispanic, and White children underwent testing at similar rates. Testing varied by diagnosis and across hospitals. CONCLUSIONS: Hospitalized Black children were more likely than White children to undergo drug testing at US children's hospitals, though this varied by diagnosis and hospital. Our results support efforts to better understand and address healthcare disparities, including the contributions of implicit bias and structural racism.

Flavonoid-Phenolic Acid Hybrids Are Potent Inhibitors of Ferroptosis via Attenuation of Mitochondrial Impairment.

Cinnamic acid, ferulic acid, and the flavonoids quercetin and taxifolin (dihydroquercetin) are naturally occurring compounds found in plants. They are often referred to as polyphenols and are known, among others, for their pharmacological effects supporting health through the inhibition of aging processes and oxidative stress. To improve their bioavailability, pharmacological activities, and safety, the creation of novel flavonoid-phenolic acid hybrids is an area of active research. Previous work showed that such hybridization products of phenolic acids and flavonoids enhanced the resilience of neuronal cells against oxidative stress in vitro, and attenuated cognitive impairment in a mouse model of Alzheimer's disease (AD) in vivo. Notably, the therapeutic effects of the hybrid compounds we obtained were more pronounced than the protective activities of the respective individual components. The underlying mechanisms mediated by the flavonoid-phenolic acid hybrids, however, remained unclear and may differ from the signaling pathways activated by the originating structures of the respective individual phenolic acids or flavonoids. In this study, we characterized the effects of four previously described potent flavonoid-phenolic acid hybrids in models of oxidative cell death through ferroptosis. Ferroptosis is a type of iron-dependent regulated cell death characterized by lipid peroxidation and mitochondrial ROS generation and has been linked to neurodegenerative conditions. In models of ferroptosis induced by erastin or RSL3, we analyzed mitochondrial (lipid) peroxidation, mitochondrial membrane integrity, and Ca2+ regulation. Our results demonstrate the strong protective effects of the hybrid compounds against ROS formation in the cytosol and mitochondria. Importantly, these protective effects against ferroptosis were not mediated by radical scavenging activities of the phenolic hybrid compounds but through inhibition of mitochondrial complex I activity and reduced mitochondrial respiration. Our data highlight the effects of flavonoid-phenolic acid hybrids on mitochondrial metabolism and further important mitochondrial parameters that collectively determine the health and functionality of mitochondria with a high impact on the integrity and survival of the neuronal cells.