Browsing by Subject "COVID-19 drug treatment"

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    Prolonged Exposure to Remdesivir Inhibits the Human Ether-A-Go-Go-Related Gene Potassium Current
    (Wolters Kluwer, 2023-09-01) Amarh, Enoch; Tisdale, James E.; Overholser, Brian R.; Pharmacology and Toxicology, School of Medicine
    Remdesivir, approved for the treatment of COVID-19, has been associated with heart-rate corrected QT interval (QTc) prolongation and torsade de pointes in case reports. However, data are conflicting regarding the ability of remdesivir to inhibit the human ether-a-go-go-related gene (hERG) -related current. The objective of this study was to investigate the effects remdesivir and its primary metabolite, GS-441524, on hERG-related currents. Human embryonic kidney 293 cells stably expressing hERG were treated with various concentrations of remdesivir and GS-441524. The effects of acute and prolonged exposure on hERG-related current were assessed using whole-cell configuration of voltage-clamp protocols. Acute exposure to remdesivir and GS-441524 had no effect on hERG currents and the half-activation voltage (V 1/2 ). Prolonged treatment with 100 nM and 1 µM remdesivir significantly reduced peak tail currents and hERG current density. The propensity for remdesivir to prolong QTc intervals and induce torsade de pointes in predisposed patients warrants further investigation.
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    Racial and Ethnic Disparities in Buprenorphine and Extended-Release Naltrexone Filled Prescriptions During the COVID-19 Pandemic
    (American Medical Association, 2022) Nguyen, Thuy; Ziedan, Engy; Simon, Kosali; Miles, Jennifer; Crystal, Stephen; Samples, Hillary; Gupta, Sumedha; Economics, School of Liberal Arts
    Importance: COVID-19 disrupted delivery of buprenorphine and naltrexone treatment for opioid use disorder (OUD), and during the pandemic, members of racial and ethnic minority groups experienced increased COVID-19 and opioid overdose risks compared with White individuals. However, whether filled buprenorphine and naltrexone prescriptions varied across racial and ethnic groups during the COVID-19 pandemic remains unknown. Objective: To investigate whether disruptions in filled buprenorphine and naltrexone prescriptions differed by race and ethnicity and insurance status or payer type. Design, setting, and participants: This cross-sectional study used retail pharmacy claims from May 2019 to June 2021 from the Symphony Health database, which includes 92% of US retail pharmacy claims, with race and ethnicity data spanning all insurance status and payer categories. Interrupted time series were used to estimate levels and trends of dispensed buprenorphine and naltrexone prescriptions before and after pandemic onset. Included individuals were those who filled buprenorphine and extended-release naltrexone prescriptions. Data were analyzed from July 2021 through March 2022. Main outcomes and measures: Weekly rates of dispensed buprenorphine and extended-release naltrexone prescription fills per 1000 patients and proportion of longer (ie, ≥14 days' supply) buprenorphine prescription fills were calculated. Analyses were stratified by patient race and ethnicity and further by insurance status and payer type for White and Black patients. Results: A total of 1 556 860 individuals who filled buprenorphine prescriptions (4359 Asian [0.3%], 94 657 Black [6.1%], 55 369 Hispanic [3.6%], and 664 779 White [42.7%]) and 127 506 individuals who filled extended-release naltrexone prescriptions (344 Asian [0.3%], 8186 Black [6.4%], 5343 Hispanic [4.2%], and 53 068 White [41.6%]) from May 6, 2019, to June 5, 2021, were analyzed. Prepandemic increases in buprenorphine fill rate flattened for all groups after COVID-19 onset (30.5 percentage point difference in trend; P < .001) compared with prepandemic trends. Significant level decreases in buprenorphine fills (ranging from 2.5% for Black patients; P = .009 to 4.0% for Hispanic patients; P = .009) at pandemic onset were observed for members of racial and ethnic minority groups but not White patients. At pandemic onset, rate of buprenorphine fills decreased in level for Medicare and cash-paying patients but with greater decreases for Black patients (Medicare: 10.0%; P < .001; cash: 20.0%; P < .001) than White patients (Medicare: 3.5%; P = .004; cash: 15.0%; P < .001). No decreases were found among Medicaid patients. Unlike buprenorphine, extended-release naltrexone had uniform level (from 10.0% for White patients with private insurance; P < .001 to 23.3% for Black patients with Medicare; P < .001) and trend (from 15.5 percentage points for White patients with Medicaid; P = .001 to 52.0 percentage points for Black patients with private insurance; P < .001) decreases across groups. Conclusions and relevance: This study found that the COVID-19 pandemic was associated with immediate decreases in filled buprenorphine prescriptions by members of racial and ethnic minority groups but not White individuals. These findings suggest that members of racial and ethnic minority groups had larger losses in buprenorphine access during the pandemic across payer types.
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    A Telehealth-Based Randomized Controlled Trial: A Model for Outpatients Trials of Off-Label Medications During the COVID-19 Pandemic
    (Sage, 2021-08) Keyhani, Salomeh; Kelly, J. Daniel; Bent, Stephen; Boscardin, W. John; Shlipak, Michael G.; Leonard, Sam; Abraham, Ann; Lum, Emily; Lau, Nicholas; Austin, Charles; Oldenburg, Catherine E.; Zillich, Allan; Lopez, Lenny; Zhang, Ying; Lietman, Tom; Bravata, Dawn M.; Medicine, School of Medicine
    The study was registered at clinicaltrials.gov: NCT04363203