ABSTRACT
Intro: Ritonavir-boosted nirmatrelvir has shown efficacy in reducing the rate of hospitalisation and 28-day mortality among unvaccinated populations with COVID-19. The role of Ritonavir-boosted nirmatrelvir among high risk hospitalised COVID-19 patients remained uncertain. Our study aimed to assess the efficacy of Ritonavir-boosted nirmatrelvir in reducing disease progression among high-risk hospitalised COVID-19 patients. Method(s): This is a retrospective case-control study (ratio 1:1) among hospitalised COVID-19 patients with mild-moderate severity, within 5 days of illness, and had at least one risk factor for severe disease. Treatment group (case) received Nirmatrelvir and Ritonavir twice daily for 5 days. Historical controls before the introduction of Ritonavir-boosted nirmatrelvir were obtained in the same hospital. Both groups received standard of care. The primary outcome was rate of clinical progression from non-hypoxia to hypoxia. Finding(s): 200 patients from January to July 2022 were included in the analysis, where 108 (54%) were male, mean age of 63.7 (SD 17.1), 95% completed primary COVID-19 vaccination and 91 (45.5%) had evidence of pneumonia (moderate severity). Most common comorbids were hypertension(65%), diabetes mellitus(40%) and overweight(36%). Clinical progression to hypoxia was significantly lower in the treatment group (4%) compared to the control group (18%) (OR=0.190, 95% CI: 0.0618 - 0.583). Comparing case to control, the rates of ICU admission were 1% vs 3%, mechanical ventilation 0% vs 2% and inpatient mortality 2% vs 2%. 97% patients completed Ritonavir-boosted nirmatrelvir in the treatment group. Conclusion(s): Among high-risk hospitalised COVID-19 patients who received ritonavir-boosted nirmatrevir, they were 81% less likely to experience desaturation. Ritonavir-boosted Nirmatrelvir remains beneficial among highly vaccinated populations during the Omicron wave in COVID-19 pandemic.Copyright © 2023
ABSTRACT
Background: Oral mucositis (OM) is a debilitating side effect of concomitant chemoradiotherapy (CRT) for head and neck cancer (HNC). EC-18 may effectively mitigate OM by minimizing the CRT-induced innate immune response. This Phase II, 2-stage trial evaluated safety, tolerability, and efficacy of EC- 18 in reducing the duration, incidence, and trajectory of severe OM (SOM) in HNC patients. Methods: Patients (n = 105) with pathologically confirmed oral cavity, oropharynx, hypopharynx, or nasopharynx squamous cell cancers who received intensity-modulated radiation therapy (IMRT;with ≥ 55 Gy on ≥ 2 oral sites) and weekly or tri-weekly cisplatin were studied. In Stage 1, 24 patients were randomized (n = 6 per arm) to receive 500, 1000, or 2000 mg of EC-18, or placebo. Following independent Data Safety Monitoring Board review, 81 patients in Stage 2 received EC-18 2000 mg (n = 41) or placebo (n = 40) throughout CRT. WHO OM grade was assessed twice weekly during IMRT and then once weekly for up to 6 weeks post-IMRT. The primary efficacy endpoint was duration of SOM during the active and short-term follow-up (STFU) periods in the compliant per-protocol population (PP). Much of Stage 2 was conducted during peak periods of the COVID-19 pandemic which measurably impacted patient compliance relative to test medication dosing and planned radiation. Consequently, to assess efficacy most accurately, the PP population was analyzed (with at least 4 weeks of study drug dosing, minimum cumulative radiation of 55 Gy, 80% study drug compliance in the first 28 days of dosing, and without using not-allowed-therapy). Results: Patient demographics and baseline characteristics were balanced between groups. Adverse events (AEs) were comparable amongst cohorts without drug-related severe AEs. In the PP, the median duration of SOM from baseline through STFU was 0 day in the EC-18 group (n = 22) v 13.5 days in the placebo group (n = 20). SOM incidence through STFU (45.5% v 70%) and opioid use (time to onset: 32.3 v 26.0 days;and duration: 32.8 v 37.5 days) favored EC-18 v placebo. Results of the covariates analyses suggested that EC-18 favorably impacted SOM incidence in patients who experienced SOM treated with weekly low-dose cisplatin (n = 26;37.5% v placebo 70.0%) and HPV+ tumors (n = 29;35.3% v placebo 66.7%;Table). One-year long-term follow-up for tumor outcomes is ongoing. Conclusions: EC-18 safely mitigated the development and the time course of SOM in CRT-treated HNC patients. In addition, EC-18 may provide substantial benefits to subpopulations of HPV+ HNC patients treated with low dose cisplatin.
ABSTRACT
The COVID-19 (Coronavirus Disease 2019) broke out in the late of 2019. On January 23 in Wuhan, and later in all other cities of the country, there were taken measures to control the spread of the virus through quarantine measures. This article focused on East China and attempted to assess comprehensively the environmental impact of the COVID-19 outbreak. This study analyzed satellite observational data of sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and aerosol optical depth (AOD) in the period before the outbreak of the epidemic and during the implementation of preventive measures and control of COVID-19, as well as compared it with the data obtained in the same period of 2019. The results of the analysis showed that the COVID-19 lockdown improved air quality in the short term, but as soon as coal consumption at power plants and refineries returned to normal levels due to the resumption of their work, pollution levels returned to their previous level. The levels of CO and NO2 showed the most significant decrease (20 and 30%), since they were mainly associated with a decrease in economic growth and transport restrictions that led to a change in energy consumption and a reduction in emissions. This study can complement the scientific community and environmental protection policy makers, not only to assess the impact of outbreak on air quality, but also for its effectiveness as a simple alternative program of action to improve air quality. © The Author(s).