Comparison of safety and efficacy between Nirmatrelvir-ritonavir and molnupiravir in the treatment of COVID-19 infection in patients with advanced kidney disease: a retrospective observational study.

Background: Nirmatrelvir-ritonavir is used in patients with coronavirus disease 2019 (COVID-19) with normal or mild renal impairment (eGFR ≥30 ml/min per 1.73 m2). There is limited data regarding its use in advanced kidney disease (eGFR <30 ml/min per 1.73 m2). We performed a retrospective territory-wide observational study evaluating the safety and efficacy of nirmatrelvir-ritonavir when compared with molnupiravir in the treatment of patients with COVID-19 with advanced kidney disease. Methods: We adopted target trial emulation using data from a territory-wide electronic health record database on eligible patients aged ≥18 years with advanced kidney disease (history of eGFR <30 ml/min per 1.73 m2) who were infected with COVID-19 and were prescribed with either molnupiravir or nirmatrelvir-ritonavir within five days of infection during the period from 16 March 2022 to 31 December 2022. A sequence trial approach and 1:4 propensity score matching was applied based on the baseline covariates including age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index (CCI), hospitalisation, eGFR, renal replacement therapy, comorbidities (cancer, respiratory disease, myocardial infarction, ischaemic stroke, diabetes, hypertension), and drug use (renin-angiotensin-system agents, beta blockers, calcium channel blockers, diuretics, nitrates, lipid lowering agents, insulins, oral antidiabetic drugs, antiplatelets, immuno-suppressants, corticosteroids, proton pump inhibitors, histamine H2 receptor antagonists, monoclonal antibody infusion) within past 90 days. Individuals were followed up from the index date until the earliest outcome occurrence, death, 90 days from index date or the end of data availability. Stratified Cox proportional hazards regression adjusted with baseline covariates was used to compare the risk of outcomes between nirmatrelvir-ritonavir recipients and molnupiravir recipients which include (i) all-cause mortality, (ii) intensive care unit (ICU) admission, (iii) ventilatory support, (iv) hospitalisation, (v) hepatic impairment, (vi) ischaemic stroke, and (vii) myocardial infarction. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (≤5; >5), and number of COVID-19 vaccine doses received (0-1; ≥2 doses). Findings: A total of 4886 patients were included (nirmatrelvir-ritonavir: 1462; molnupiravir: 3424). There were 347 events of all-cause mortality (nirmatrelvir-ritonavir: 74, 5.06%; molnupiravir: 273, 7.97%), 10 events of ICU admission (nirmatrelvir-ritonavir: 4, 0.27%; molnupiravir: 6, 0.18%), 48 events of ventilatory support (nirmatrelvir-ritonavir: 13, 0.89%; molnupiravir: 35, 1.02%), 836 events of hospitalisation (nirmatrelvir-ritonavir: 218, 23.98%; molnupiravir: 618, 28.14%), 1 event of hepatic impairment (nirmatrelvir-ritonavir: 0, 0%; molnupiravir: 1, 0.03%), 8 events of ischaemic stroke (nirmatrelvir-ritonavir: 3, 0.22%; molnupiravir: 5, 0.16%) and 9 events of myocardial infarction (nirmatrelvir-ritonavir: 2, 0.15%; molnupiravir: 7, 0.22%). Nirmatrelvir-ritonavir users had lower rates of all-cause mortality (absolute risk reduction (ARR) at 90 days 2.91%, 95% CI: 1.47-4.36%) and hospitalisation (ARR at 90 days 4.16%, 95% CI: 0.81-7.51%) as compared with molnupiravir users. Similar rates of ICU admission (ARR at 90 days -0.09%, 95% CI: -0.4 to 0.2%), ventilatory support (ARR at 90 days 0.13%, 95% CI: -0.45 to 0.72%), hepatic impairment (ARR at 90 days 0.03%, 95% CI: -0.03 to 0.09%), ischaemic stroke (ARR at 90 days -0.06%, 95% CI: -0.35 to 0.22%), and myocardial infarction (ARR at 90 days 0.07%, 95% CI: -0.19 to 0.33%) were found between nirmatrelvir-ritonavir and molnupiravir users. Consistent results were observed in relative risk adjusted with baseline characteristics. Nirmatrelvir-ritonavir was associated with significantly reduced risk of all-cause mortality (HR: 0.624, 95% CI: 0.455-0.857) and hospitalisation (HR: 0.782, 95% CI: 0.64-0.954). Interpretation: Patients with COVID-19 with advanced kidney disease receiving nirmatrelvir-ritonavir had a lower rate of all-cause mortality and hospital admission when compared with molnupiravir. Other adverse clinical outcomes were similar in both treatment groups. Funding: Health and Medical Research Fund (COVID1903010), Health Bureau, The Government of the Hong Kong Special Administrative Region, China.

Effectiveness of molnupiravir vs nirmatrelvir-ritonavir in non-hospitalised and hospitalised patients with COVID-19: a target trial emulation study.

Background: Molnupiravir and nirmatrelvir-ritonavir have emerged as promising options for COVID-19 treatment, but direct comparisons of their effectiveness have been limited. This study aimed to compare the effectiveness of these two oral antiviral drugs in non-hospitalised and hospitalised patients with COVID-19. Methods: In this target trial emulation study, we used data from a territory-wide electronic health records database on eligible patients aged ≥18 years infected with COVID-19 who were prescribed either molnupiravir or nirmatrelvir-ritonavir within five days of infection between 16 March 2022 and 31 December 2022 in the non-hospitalised and hospitalised settings in Hong Kong. A sequence trial approach and 1:1 propensity score matching was applied based on age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index, comorbidities, and drug use within past 90 days. Cox regression adjusted with patients' characteristics was used to compare the risk of effectiveness outcomes (all-cause mortality, intensive care unit (ICU) admission or ventilatory support and hospitalisation) between groups. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (<4; ≥4), and number of COVID-19 vaccine doses received (0-1; ≥2 doses). Findings: A total of 63,522 non-hospitalised (nirmatrelvir-ritonavir: 31,761; molnupiravir: 31,761) and 11,784 hospitalised (nirmatrelvir-ritonavir: 5892; molnupiravir: 5892) patients were included. In non-hospitalised setting, 336 events of all-cause mortality (nirmatrelvir-ritonavir: 71, 0.22%; molnupiravir: 265, 0.83%), 162 events of ICU admission or ventilatory support (nirmatrelvir-ritonavir: 71, 0.22%; molnupiravir: 91, 0.29%), and 4890 events of hospitalisation (nirmatrelvir-ritonavir: 1853, 5.83%; molnupiravir: 3037, 9.56%) were observed. Lower risks of all-cause mortality (absolute risk reduction (ARR) at 28 days: 0.61%, 95% CI: 0.50-0.72; HR: 0.43, 95% CI: 0.33-0.56) and hospital admission (ARR at 28 days: 3.73%, 95% CI: 3.31-4.14; HR: 0.72, 95% CI: 0.67-0.76) were observed in nirmatrelvir-ritonavir users compared to molnupiravir users. In hospitalised setting, 509 events of all-cause mortality (nirmatrelvir-ritonavir: 176, 2.99%; molnupiravir: 333, 5.65%), and 50 events of ICU admission or ventilatory support (nirmatrelvir-ritonavir: 26, 0.44%; molnupiravir: 24, 0.41%) were observed. Risk of all-cause mortality was lower for nirmatrelvir-ritonavir users than for molnupiravir users (ARR at 28 days: 2.66%, 95% CI: 1.93-3.40; HR: 0.59, 95% CI: 0.49-0.71). In both settings, there was no difference in the risk of intensive care unit admission or ventilatory support between groups. The findings were consistent across all subgroup's analyses. Interpretation: Our analyses suggest that nirmatrelvir-ritonavir was more effective than molnupiravir in reducing the risk of all-cause mortality in both non-hospitalised and hospitalised patients. When neither drug is contraindicated, nirmatrelvir-ritonavir may be considered the more effective option. Funding: HMRF Research on COVID-19, The Hong Kong Special Administrative Region (HKSAR) Government; Collaborative Research Fund, University Grants Committee, the HKSAR Government; and Research Grant from the Food and Health Bureau, the HKSAR Government; the Laboratory of Data Discovery for Health (D24H) funded by the AIR@InnoHK administered by Innovation and Technology Commission.

Financing Constraints and Firm's Productivity Under the COVID-19 Epidemic Shock: Evidence of A-Shared Chinese Companies.

Focusing on the financing barriers to firm productivity improvement under the influence of external shocks, we empirically analyze the data of A-share listed companies from 2007-2018 to determine the impact of financing constraints on total factor productivity (TFP) in the context of COVID-19 pandemic and the paths of factor use efficiency and R&D innovation efficiency on this impact using ordinary least-squares (OLS) method. We find that financing constraints are an important factor inhibiting the TFP of firms. This inhibitory effect is more serious in small-scale firms, non-state firms, and non-energy firms. Further investigation shows that the inhibitory effect of financing constraints on firms' TFP is more pronounced when firms are located in the Yangtze River Delta city cluster, the Pearl River Delta city cluster, non-port cities, and provincial capitals. The mechanism test finds that improving the efficiency of capital use and labor use can alleviate the suppressive effect of financing constraints on TFP. The alleviating impact is more significant when capital use efficiency is improved. However, increasing the efficiency of R&D innovation further strengthens the inhibitory effect of financing constraints, and this effect is more pronounced under positive external shocks.

Nous nous concentrons sur les obstacles liés au financement qui entravent l'amélioration de la productivité des entreprises lorsqu'il y a des chocs externes, et nous analysons de façon empirique l'impact des contraintes de financement sur la productivité globale des facteurs des entreprises dans le contexte de la COVID-19, ainsi que les voies permettant l'efficacité d'utilisation des facteurs et l'efficacité de l'innovation en R&D sur cet impact. Pour ce faire, nous utilisons la méthode des moindres carrés ordinaires en nous basant sur les données de sociétés cotées en bourse de 2007 à 2018. Nous constatons que les contraintes de financement représentent un facteur important qui inhibe la productivité globale des facteurs des entreprises. Cet effet inhibiteur est plus prononcé au sein des petites entreprises, des entreprises non gouvernementales et des entreprises non énergétiques. Une autre étude révèle que l'effet inhibiteur des contraintes de financement sur la productivité globale des facteurs des entreprises est plus prononcé lorsque les entreprises sont situées dans le groupe de villes du delta du fleuve Yangtze, dans le groupe de villes du delta de la rivière des Perles, dans les villes non portuaires et dans les capitales provinciales. Le test du mécanisme révèle que l'amélioration de l'efficacité de l'utilisation du capital et de la main-d'œuvre des entreprises peut atténuer l'effet suppressif des contraintes de financement sur la productivité globale des facteurs. L'impact d'atténuation est plus important lorsque l'efficacité d'utilisation du capital est améliorée. Cependant, l'augmentation de l'efficacité de l'innovation en R&D renforce encore l'effet inhibiteur des contraintes de financement, et il est plus prononcé en cas de chocs externes positifs.

Exposure to stereotype-relevant stories shapes children's implicit gender stereotypes.

Implicit math = male stereotypes have been found in early childhood and are linked to girls' disproportionate disengagement from math-related activities and later careers. Yet, little is known about how malleable children's automatic stereotypes are, especially in response to brief interventions. In a sample of 336 six- to eleven-year-olds, we experimentally tested whether exposure to a brief story vignette intervention with either stereotypical, neutral, or counter-stereotypical content (three conditions: math = boy vs. neutral vs. math = girl) could change implicit math-gender stereotypes. Results suggested that children's implicit math = male stereotypes were indeed responsive to brief stories that either reinforced or countered the widespread math = male stereotype. Children exposed to the counter-stereotypical stories showed significantly lower (and non-significant) stereotypes compared to children exposed to the stereotypical stories. Critically, exposure to stories that perpetuated math = male stereotypes significantly increased math-gender stereotypes over and above baseline, underscoring that implicit gender biases that are readily formed during this period in childhood and even brief exposure to stereotypical content can strengthen them. As a secondary question, we also examined whether changes in stereotypes might also lead to changes in implicit math self-concept. Evidence for effects on implicit self-concept were not statistically significant.

Does technology-seeking OFDI improve the productivity of Chinese firms under the COVID-19 pandemic?

This paper empirically investigates the impact of technology-seeking outward foreign direct investment (OFDI) on firms' productivity under the influence of negative external shocks, taking as a sample the investment data of Chinese firms before and during COVID-19. The results show that technology-seeking OFDI improves productivity, but not under negative external shocks. The dampening effect of such shocks is more significant when the host country is a developed country and in firms with multiple branches. Technology-seeking OFDI particularly improves the productivity of research and development and processing firms, and (among the productivity measures tested) most prominently affects total factor productivity.

High-speed railway opening and urban green productivity in the post-COVID-19: Evidence from green finance.

In an era during which the COVID-19 pandemic continues to spread, high-speed railway (HSR), as one of the key influencers of urban green development, has a significant impact on urban green finance and green productivity. This paper uses HSR as a quasi-natural experiment to study the effect of HSR openings on green productivity in Chinese cities. The empirical results show that, first, the opening of HSR is conducive to the sustained improvement of green productivity in Chinese cities. Second, the opening of HSR makes a significant contribution to the improvement of green productivity in large-scale cities as well as cities in the east and central regions. Third, the opening of HSR can positively impact urban green productivity through the mechanism of green finance development. However, this positive impact tends to first increase and then decrease over time. As the relationship between "finance" and "environment," green finance has an important impact on the green development of cities. These findings will provide positive and useful references for cities to formulate reasonable green development plans in the post-COVID-19 era.