Effectiveness of regdanvimab on mortality in COVID-19 infected patients on hemodialysis

Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (COVID-19), there are lack of effective and proven treatments for end-stage renal disease (ESRD). The present study aims to evaluate the effectiveness of regdanvimab on mortality in COVID-19–infected patients on hemodialysis (HD). Methods We conducted an observational retrospective study in 230 COVID-19–infected patients on HD, of whom 77 (33.5%) were administered regdanvimab alone or in combination with dexamethasone or remdesivir during hospitalization (regdanvimab group) and 153 patients (66.5%) were not (no regdanvimab group). The primary outcome was in-hospital mortality. We compared mortality rates according to the use of regdanvimab and investigated the factors associated with mortality. Results Fifty-nine deaths occurred during hospitalization, 49 in the no regdanvimab group (32.0%) and 10 in the regdanvimab group (13.0%), and the mortality rate was significantly higher in the no regdanvimab group than that in the regdanvimab group (p = 0.001). Multivariate Cox regression analysis showed that malignancy (p = 0.001), SPO2 of <95% at admission (p = 0.003), and administration of antibiotics and regdanvimab (p = 0.007 and p = 0.002, respectively) were significantly associated factors with mortality. Conclusion Regdanvimab administration is beneficial in improving prognosis in hospitalized COVID-19 patients on HD. Considering the vulnerability to infection and high mortality of ESRD patients, regdanvimab may be considered as a therapeutic option in COVID-19 patients on HD

Safety and Effectiveness of Regdanvimab for COVID-19 Treatment: A Phase 4 Post-marketing Surveillance Study Conducted in South Korea

Introduction Regdanvimab, a neutralising monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), received approval for the treatment of coronavirus disease 2019 (COVID-19) in South Korea in 2021. The Ministry of Food and Drug Safety in South Korea mandate that new medications be re-examined for safety and effectiveness post-approval in at least 3000 individuals. This post-marketing surveillance (PMS) study was used to evaluate the safety and effectiveness of regdanvimab in real-world clinical care. Methods This prospective, multicentre, phase 4 PMS study was conducted between February 2021 and March 2022 in South Korea. Eligible patients were aged ≥ 18 years with confirmed mild COVID-19 at high risk of disease progression or moderate COVID-19. Patients were hospitalised and treated with regdanvimab (40 mg/kg, day 1) and then monitored until discharge, with a follow-up call on day 28. Adverse events (AEs) were documented, and the COVID-19 disease progression rate was used to measure effectiveness. Results Of the 3123 patients with COVID-19 infection identified, 3036 were eligible for inclusion. Approximately 80% and 5% of the eligible patients were diagnosed with COVID-19 during the delta- and omicron-dominant periods, respectively. Median (range) age was 57 (18–95) years, and 50.6% of patients were male. COVID-19 severity was assessed before treatment, and high-risk mild and moderate COVID-19 was diagnosed in 1030 (33.9%) and 2006 (66.1%) patients, respectively. AEs and adverse drug reactions (ADRs) were experienced by 684 (22.5%) and 363 (12.0%) patients, respectively. The most common ADR was increased liver function test (n = 62, 2.0%). Nine (0.3%) patients discontinued regdanvimab due to ADRs. Overall, 378 (12.5%) patients experienced disease progression after regdanvimab infusion, with extended hospitalisation/re-admission (n = 300, 9.9%) as the most common reason. Supplemental oxygen was required by 282 (9.3%) patients. Ten (0.3%) patients required intensive care monitoring and 3 (0.1%) died due to COVID-19. Conclusion This large-scale PMS study demonstrated that regdanvimab was effective against COVID-19 progression and had an acceptable safety profile when used in real-world clinical practice.This study and the journals Rapid Service fee was funded by Celltrion Inc. (Incheon, Republic of Korea)

A Stochastic Simulation Based Approach for Transportation Demand Forecast and Safety

Reliable traffic forecasts are critical for successful planning and financing of transportation projects. However, the accuracy evaluation results of the predicted traffic volumes often indicate significant discrepancies between the actual and predicted traffic volumes. These discrepancies are mainly due to both limitations and uncertainties in traffic demand forecasting models; therefore, researchers are continuously attempting to estimate the error and bias in traffic forecasts. To enhance these endeavors, a Monte Carlo simulation (MCS)- based approach is proposed in this paper as an alternative to the stochastic traffic demand forecast. This approach uses a sequential process to capture the effects of model inputs and variables on the error and bias in traffic demand forecasting. The approach proposed in this study was developed in three steps. First, the key factors causing errors and biases in traffic demand forecasts were identified based on a comprehensive review of traffic forecasting practices. Second, the effects of each variable on traffic volumes were quantified using MCS. Lastly, the statistical approach was constructed to provide an interval estimation of traffic volumes based on the findings of MCS. Through these steps, the inherent uncertainties in socioeconomic variables and heterogeneities in passenger behaviors with regard to traffic demand modeling were considered. Then, simulation experiments were conducted to investigate the applicability of the proposed approach to a real-world network. This approach is expected to reasonably capture the stochastic nature of future traffic volumes and quantify the risks associated with the error and bias in traffic demand forecasting. The findings of this study indicate that traffic forecasting practitioners can use the proposed approach with ease. The analysis results showed that the proposed approach clearly captured the changes in link traffic volumes owing to the statistical changes in the value of time (VOT). The experiments indicated that the uncertainties in VOT perceived by road users can be used to estimate the risks of toll road financing. The elasticity of traffic volume to VOT for each link, which can be used as a key input to the road project feasibility study, can be derived from the MCS-based analysis implemented in this study

COVID-19-related clinical outcomes among Korean hemodialysis patients

Background: Hemodialysis (HD) patients are more vulnerable to viral epidemics, experiencing higher mortality rates compared to individuals without chronic kidney disease (CKD). This retrospective cohort study sought to demonstrate clinical outcomes and associated factors among coronavirus disease 2019 (COVID-19) confirmed Korean HD patients.Methods: From February 2020 to November 2021, the COVID-19 Task Force Team collected clinical data for HD patients with confirmed COVID-19 via a self-report survey of nephrologists. The composite outcome included in-hospital mortality, admission to the intensive care unit (ICU), and use of mechanical ventilation. Risk factors associated with clinical outcomes were analyzed among HD patients and compared to those of individuals without CKD using the COVID-19 database from the Korea Disease Control and PreResults: A total of 380 HD patients from 206 facilities were diagnosed with COVID-19. Fever (49.5%) and cough (25.7%) were the two most common initial symptoms. The overall in-hospital fatality rate was 22.4% and even higher among ICU admission cases (64.7%). Non-survivors were older, more frequently developed shortness of breath, and were more likely to come from a nursing hospital. Compared to the age- and sex-matched non-CKD population, HD patients showed greater risk of in-hospital mortality (hazard ratio, 2.07; 95% confidence interval, 1.56-2.75; p &lt; 0.001) and composite outcome (hazard ratio, 3.50; 95% confidence interval,Conclusion: HD patients have a greater risk of in-hospital mortality and morbidity from COVID-19. Special attention should be paid to COVID-19 HD patients when they are older or present with symptoms.Y

Impact of decreased levels of total CO2 on in-hospital mortality in patients with COVID-19

Abstract Decreased total CO2 (tCO2) is significantly associated with all-cause mortality in critically ill patients. Because of a lack of data to evaluate the impact of tCO2 in patients with COVID-19, we assessed the impact of tCO2 on all-cause mortality in this study. We retrospectively reviewed the data of hospitalized patients with COVID-19 in two Korean referral hospitals between February 2020 and September 2021. The primary outcome was in-hospital mortality. We assessed the impact of tCO2 as a continuous variable on mortality using the Cox-proportional hazard model. In addition, we evaluated the relative factors associated with tCO2 ≤ 22 mmol/L using logistic regression analysis. In 4,423 patients included, the mean tCO2 was 24.8 ± 3.0 mmol/L, and 17.9% of patients with tCO2 ≤ 22 mmol/L. An increase in mmol/L of tCO2 decreased the risk of all-cause mortality by 4.8% after adjustment for age, sex, comorbidities, and laboratory values. Based on 22 mmol/L of tCO2, the risk of mortality was 1.7 times higher than that in patients with lower tCO2. This result was maintained in the analysis using a cutoff value of tCO2 24 mmol/L. Higher white blood cell count; lower hemoglobin, serum calcium, and eGFR; and higher uric acid, and aspartate aminotransferase were significantly associated with a tCO2 value ≤ 22 mmol/L. Decreased tCO2 significantly increased the risk of all-cause mortality in patients with COVID-19. Monitoring of tCO2 could be a good indicator to predict prognosis and it needs to be appropriately managed in patients with specific conditions