Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study.

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

A Probiotic Formula for Modulation of Colorectal Cancer Risk via Reducing CRC-Associated Bacteria.

Gut microbiota dysbiosis with increased pathogenic bacteria and decreased beneficial bacteria is associated with colorectal cancer (CRC) development. This study examined the effect of a newly developed probiotic formula in modulating CRC-related bacteria. We developed a probiotic formula containing three bifidobacteria (B. adolescentis, B. longum, and B. bifidum) based on the identification of bacterial species that showed significant correlations with CRC-related bacteria including Fusobacterium nucleatum (Fn), Lachnoclostridium sp. m3, Clostridium hathewayi (Ch), and Bacteroides clarus (Bc). We co-cultured Fn with each bifidobacterium or the combined formula and examined the growth of Fn by qPCR. The three individual bifidobacteria significantly inhibited the growth of Fn compared to the control treatment (24~65% inhibition; all p < 0.001). The combination of the three bifidobacteria showed a greater inhibitory effect on Fn growth (70% inhibition) than the individual bifidobacteria (all p < 0.05). We further examined the effect of the probiotic formula in a pilot study of 72 subjects (40 on probiotics; 32 with no intervention) for 4 weeks and followed them up for 12 weeks. The relative fecal abundances of the bifidobacteria in the formula and the CRC-related markers (Fn, m3, Ch, and Bc) were quantitated by qPCR before and after the intervention, and the combined CRC risk score (4Bac; Fn, m3, Ch, and Bc) was evaluated. Subjects with probiotics intervention showed significantly increased abundances of the bifidobacteria from week 2 to week 5 compared to baseline (p < 0.05), and the abundances dropped to baseline levels after the cessation of the intervention. There were significant decreases in the levels of CRC-related markers (Fn and m3) and the CRC risk score (4Bac) from week 2 to week 12 compared to baseline levels (p < 0.05) in the intervention group but not in the control group. A novel probiotic formula containing B. adolescentis, B. longum, and B. bifidum was effective in inhibiting the growth of F. nucleatum in vitro and improving the gut microbial environment against CRC development.

Introduction to Special Issue: Topics Related to Real Estate Market Efficiency.

The efficiency of the real estate market is a major concern for homeowners, investors, lenders, policymakers, and researchers. Modern academic literature has mostly moved beyond an early emphasis on formal tests of informational efficiency. The Grossman and Stiglitz (The American Economic Review 70:393-408, 1980) paradox holds that perfect informational efficiency is impossible and the joint hypothesis problem implies that market efficiency is not even testable. Instead, researchers now commonly examine the speed, accuracy, and persistence of price movements in response to new information, as the allocative efficiency of a market ultimately depends on its degree of informational (and operational) efficiency. This special issue is devoted to exploring these issues.

Information Frictions in Real Estate Markets: Recent Evidence and Issues.

This article reviews research on the economics of information in real estate. It covers equity investment in private and public markets and intermediation by brokers. The review shows how, by examining the nature and extent of information frictions in these important markets, research has improved our understanding of potential market failures and corrections which can improve market functioning.

The association between daily total physical activity and risk of cardiovascular disease among hypertensive patients: a 10-year prospective cohort study in China.

BACKGROUND: The effect of high levels of physical activity and relationship between daily total physical activity and the risk of cardiovascular disease (CVD) among hypertensive people were not clear. This study aimed to explore the optimum level of physical activity for CVD prevention. METHODS: Data used in the present study was derived from the sub-study of China Kadoorie Biobank study (CKB) in Jiangsu province of China. The CKB was a prospective cohort study established during 2004-2008. At baseline, 53,259 participants aged 35-74 years were recruited for the CKB Jiangsu sub-study conducted in Wuzhong district of Suzhou City. Among those 53,259 participants, the 20,179 hypertensive individuals were our study population. The outcome events were cardiovascular diseases (CVDs), while the independent variable was total daily physical activity. The Cox proportional hazard models were introduced to investigate the association between total physical activity and CVDs, reporting as hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: During a 10.1-year follow-up, 2419 CVD cases were identified. After adjustment for potential confounding factors, compared with participants at the lowest level of daily total physical activity, the hazard ratios for CVDs were 0.87 (95%CI: 0.79-0.97), 0.73 (95%CI: 0.65-0.83) and 0.75 (95%CI: 0.65-0.85) for participants within 2, 3 and 4 quartiles of physical activity. Such a negative association between total physical activity and CVDs were also observed among participants by gender and age-group, but within patients with stage 1 hypertension only. Moreover, the association of physical activity with CVDs was U-shape and the lowest HR (0.63, 95%CI: 0.54-0.74) was observed at 35.4 MET-h/d of total physical activity. CONCLUSIONS: Total daily physical activity was negatively associated with CVDs among hypertensive adults in China, and this association was U-shape. It has some public health implications that community-based total physical activity intervention campaigns can be of help for CVDs prevention among hypertensive people in China.