Disparities in Telemedicine Utilization During COVID-19 Pandemic: Analysis of Demographic Data from a Large Academic Orthopaedic Practice.

Background: The coronavirus-19 (COVID-19) pandemic has prompted a shift in health-care provision toward implementation of telemedicine. This study investigated demographic information on orthopaedic telemedicine utilization at a single academic orthopaedic institution in an effort to identify factors associated with telemedicine usage. Methods: Demographic and appointment data were collected from the electronic medical record during equivalent time periods prior to the onset of the COVID pandemic (pre-COVID) and during the COVID pandemic (peri-COVID). Multivariate analyses were performed to identify demographic and socioeconomic correlates of telemedicine utilization. Results: There was a significant increase in telemedicine visits between the eras of study, with significant differences in telemedicine usage in association with age, sex, marital status, English as the primary language, and insurance type (p < 0.001). Multivariate analyses found American Indian/Alaska Native (adjusted odds ratio [aOR] = 0.487, p = 0.004), Black/African American (aOR = 0.622, p < 0.001), Native Hawaiian/other Pacific Islander (aOR = 0.676, p = 0.003), and Asian (aOR = 0.731, p < 0.001) race to be significantly associated with decreased telemedicine usage. Additionally, male sex (aOR = 0.878, p < 0.001) and a non-commercial insurance plan (p < 0.001) were significantly associated with decreased telemedicine usage. Conclusions: Non-White race, non-commercial insurance plans, and male sex were associated with decreased telemedicine utilization. Further investigation is needed to characterize and better identify underlying factors contributing to disparities in telemedicine access and utilization.

Selective covalent targeting of GPX4 using masked nitrile-oxide electrophiles.

We recently described glutathione peroxidase 4 (GPX4) as a promising target for killing therapy-resistant cancer cells via ferroptosis. The onset of therapy resistance by multiple types of treatment results in a stable cell state marked by high levels of polyunsaturated lipids and an acquired dependency on GPX4. Unfortunately, all existing inhibitors of GPX4 act covalently via a reactive alkyl chloride moiety that confers poor selectivity and pharmacokinetic properties. Here, we report our discovery that masked nitrile-oxide electrophiles, which have not been explored previously as covalent cellular probes, undergo remarkable chemical transformations in cells and provide an effective strategy for selective targeting of GPX4. The new GPX4-inhibiting compounds we describe exhibit unexpected proteome-wide selectivity and, in some instances, vastly improved physiochemical and pharmacokinetic properties compared to existing chloroacetamide-based GPX4 inhibitors. These features make them superior tool compounds for biological interrogation of ferroptosis and constitute starting points for development of improved inhibitors of GPX4.

Diacylfuroxans Are Masked Nitrile Oxides That Inhibit GPX4 Covalently.

GPX4 represents a promising yet difficult-to-drug therapeutic target for the treatment of, among others, drug-resistant cancers. Although most GPX4 inhibitors rely on a chloroacetamide moiety to modify covalently the protein's catalytic selenocysteine residue, the discovery and mechanistic elucidation of structurally diverse GPX4-inhibiting molecules have uncovered novel electrophilic warheads that bind and inhibit GPX4. Here, we report our discovery that diacylfuroxans can act as masked nitrile oxide prodrugs that inhibit GPX4 covalently with unique cellular and biochemical reactivity compared to existing classes of GPX4 inhibitors. These observations illuminate a novel molecular mechanism of action for biologically active furoxans and also expand the collection of reactive groups capable of targeting GPX4.