Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial.

BACKGROUND: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV. METHODS AND FINDINGS: Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 µg/mL (25.2, 33.4), 58.5 µg/mL (49.4, 69.3), and 257.2 µg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 µg/mL (8.8, 13.3) and 22.8 µg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 µg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 µg/mL (2.5, 4.6), 6.5 µg/mL (5.6, 7.5), and 27.2 µg/mL (23.9, 31.0) with IV dosing; 0.97 µg/mL (0.65, 1.4) and 3.1 µg/mL (2.2, 4.3) with SC dosing, and 2.6 µg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titer ADA at a lone time point. VRC07-523LS has an estimated mean half-life of 42 days across all doses and routes (95% CI: 40.5, 43.5), over twice as long as VRC01 (15 days). CONCLUSIONS: VRC07-523LS was safe and well tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens. TRIAL REGISTRATION: ClinicalTrials.gov/ NCT03387150 (posted on 21 December 2017).

Pandemic Fatigue and Preferences for COVID-19 Public Health and Social Measures in China: Nationwide Discrete Choice Experiment.

BACKGROUND: Information on the public's preferences for current public health and social measures (PHSMs) and people's mental health under PHSMs is insufficient. OBJECTIVE: This study aimed to quantify the public's preferences for varied PHSMs and measure the level of pandemic fatigue in the COVID-19 normalization stage in China. METHODS: A nationwide cross-sectional study with a discrete choice experiment and psychometric scales was conducted to assess public preferences for and attitudes toward PHSMs, using the quota sampling method. The COVID-19 Pandemic Fatigue Scale (CPFS) was used to screen fatigue levels among respondents. The multinomial logit model, latent class model, and Mann-Whitney test were used for statistical analysis. We also conducted subgroup analysis based on sex, age, monthly income, mental health status, and pandemic fatigue status. RESULTS: A total of 689 respondents across China completed the survey. The discrete choice experiment revealed that respondents attached the greatest importance to the risk of COVID-19 infection within 3 months (45.53%), followed by loss of income within 3 months (30.69%). Vulnerable populations (low-income populations and elderly people) were more sensitive to the risk of infection, while younger respondents were more sensitive to income loss and preferred nonsuspension of social places and transportation. Migrants and those with pandemic fatigue had less acceptance of the mandatory booster vaccination and suspension of transportation. Additionally, a higher pandemic fatigue level was observed in female respondents, younger respondents, migrants, and relatively lower-income respondents (CPFS correlation with age: r=-0.274, P<.001; correlation with monthly income: r=-0.25, P<.001). Mandatory booster COVID-19 vaccination was also not preferred by respondents with a higher level of pandemic fatigue, while universal COVID-19 booster vaccination was preferred by respondents with a lower level of pandemic fatigue. CONCLUSIONS: Pandemic fatigue is widely prevalent in respondents across China, and respondents desired the resumption of normal social life while being confronted with the fear of COVID-19 infection in the normalization stage of COVID-19 in China. During future pandemics, the mental burden and adherence of residents should be considered for the proper implementation of PHSMs.

Inverted Classroom Teaching of Physiology in Basic Medical Education: Bibliometric Visual Analysis.

Background: Over the last decade, there has been growing interest in inverted classroom teaching (ICT) and its various forms within the education sector. Physiology is a core course that bridges basic and clinical medicine, and ICT in physiology has been sporadically practiced to different extents globally. However, students' and teachers' responses and feedback to ICT in physiology are diverse, and the effectiveness of a modified ICT model integrated into regular teaching practice in physiology courses is difficult to assess objectively and quantitatively. Objective: This study aimed to explore the current status and development direction of ICT in physiology in basic medical education using bibliometric visual analysis of the related literature. Methods: A bibliometric analysis of the ICT-related literature in physiology published between 2000 and 2023 was performed using CiteSpace, a bibliometric visualization tool, based on the Web of Science database. Moreover, an in-depth review was performed to summarize the application of ICT in physiology courses worldwide, along with identification of research hot spots and development trends. Results: A total of 42 studies were included for this bibliometric analysis, with the year 2013 marking the commencement of the field. University staff and doctors working at affiliated hospitals represent the core authors of this field, with several research teams forming cooperative relationships and developing research networks. The development of ICT in physiology could be divided into several stages: the introduction stage (2013-2014), extensive practice stage (2015-2019), and modification and growth stage (2020-2023). Gopalan C is the author with the highest citation count of 5 cited publications and has published 14 relevant papers since 2016, with a significant surge from 2019 to 2022. Author collaboration is generally limited in this field, and most academic work has been conducted in independent teams, with minimal cross-team communication. Authors from the United States published the highest number of papers related to ICT in physiology (18 in total, accounting for over 43% of the total papers), and their intermediary centrality was 0.24, indicating strong connections both within the country and internationally. Chinese authors ranked second, publishing 8 papers in the field, although their intermediary centrality was only 0.02, suggesting limited international influence and lower overall research quality. The topics of ICT in physiology research have been multifaceted, covering active learning, autonomous learning, student performance, teaching effect, blended teaching, and others. Conclusions: This bibliometric analysis and literature review provides a comprehensive overview of the history, development process, and future direction of the field of ICT in physiology. These findings can help to strengthen academic exchange and cooperation internationally, while promoting the diversification and effectiveness of ICT in physiology through building academic communities to jointly train emerging medical talents.

The influence of placenta microbiota of normal term pregnant women on immune regulation during pregnancy.

BACKGROUND: The concerted regulation of placenta microbiota and the immune responses secures the occurrence and development of pregnancy, while few studies reported this correlation. This study aimed to explore the relationship between the placenta microbiota and immune regulation during pregnancy. METHODS: Twenty-six healthy pregnant women scheduled for elective cesarean section in the First Affiliated Hospital of Jinan University who met the inclusion criteria were recruited. Placenta and peripheral venous blood samples were collected. Microbiota in placental tissue was detected using high-throughput sequencing. Flow cytometry was used to detect immune cells in placental tissue and peripheral venous blood. ELISA and Luminex liquid chip technology were used to detect the content of cytokines in placental tissue and peripheral venous blood, respectively. RESULTS: The placental microbiota has stimulating effects on the local immunity of the placenta and mainly stimulates the placental balance ratio CD56 + CD16 + /CD56 + CD16 and the placental macrophages, that is, it plays the role of immune protection and supporting nutrition. The stimulating effect of placental microbiota on maternal systemic immunity mainly induces peripheral Treg cells and B lymphocytes. CONCLUSION: The placental microbiota may be an important factor mediating local immune regulation in the placenta, and placental microbiota participates in the regulatory function of the maternal immune system.

A Randomised Clinical Trial of the Safety and Pharmacokinetics of VRC07-523LS Administered via Different Routes and Doses (HVTN 127/HPTN 087).

Background: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the only bnAb HIV prevention efficacy studies to date, the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. Greater efficacy is required before passively administered bnAbs become a viable option for HIV prevention; furthermore subcutaneous (SC) or intramuscular (IM) administration may be preferred. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. Methods: Participants were recruited between 02 February 2018 and 09 October 2018. 124 healthy participants without HIV were randomized to receive five VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), SC (T4: 2.5 mg/kg, T5: 5 mg/kg) or IM (T6: 2.5 mg/kg or P6: placebo) routes at four-month intervals. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA after the first dose through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum pharmacokinetics. Neutralization activity was measured in a TZM-bl assay and anti-drug antibodies (ADA) were assayed using a tiered bridging assay testing strategy. Results: Injections were well-tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusions were generally well-tolerated, with infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals) following the first administration were 29.0 µg/mL (25.2, 33.4), 58.5 µg/mL (49.4, 69.3), and 257.2 µg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 µg/mL (8.8, 13.3) and 22.8 µg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 µg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM concentrations immediately prior to the second administration were 3.4 µg/mL (2.5, 4.6), 6.5 µg/mL (5.6, 7.5), and 27.2 µg/mL (23.9, 31.0) with IV dosing; 0.97 µg/mL (0.65, 1.4) and 3.1 µg/mL (2.2, 4.3) with SC dosing, and 2.6 µg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titres, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titre ADA at a lone timepoint. VRC07-523LS has an estimated mean half-life of 42 days (95% CI: 40.5, 43.5), approximately twice as long as VRC01. Conclusions: VRC07-523LS was safe and well-tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens.

Protein dose-sparing effect of AS01B adjuvant in a randomized preventive HIV vaccine trial of ALVAC-HIV (vCP2438) and adjuvanted bivalent subtype C gp120.

BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled HIV vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at two dose levels in healthy HIV-uninfected adults. Trial registration URL https://clinicaltrials.gov/ct2/show/NCT03122223 and registration number NCT03122223. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200µg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40µg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% females, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40µg gp120/AS01B group were higher than in either of the 200µg gp120 groups. CONCLUSIONS: The 40µg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses.

A real-world data validation of the value of early-stage SIR modelling to public health.

Performance of Susceptible-Infected-Recovered (SIR) model in the early stage of a novel epidemic may be hindered by data availability. Additionally, the traditional SIR model may oversimplify the disease progress, and knowledge about the virus and transmission is limited early in the epidemic, resulting in a greater uncertainty of such modelling. We aimed to investigate the impact of model inputs on the early-stage SIR projection using COVID-19 as an illustration to evaluate the application of early infection models. We constructed a modified SIR model using discrete-time Markov chain to simulate daily epidemic dynamics and estimate the number of beds needed in Wuhan in the early stage of COVID-19 epidemic. We compared eight scenarios of SIR projection to the real-world data (RWD) and used root mean square error (RMSE) to assess model performance. According to the National Health Commission, the number of beds occupied in isolation wards and ICUs due to COVID-19 in Wuhan peaked at 37,746. In our model, as the epidemic developed, we observed an increasing daily new case rate, and decreasing daily removal rate and ICU rate. This change in rates contributed to the growth in the needs of bed in both isolation wards and ICUs. Assuming a 50% diagnosis rate and 70% public health efficacy, the model based on parameters estimated using data from the day reaching 3200 to the day reaching 6400 cases returned a lowest RMSE. This model predicted 22,613 beds needed in isolation ward and ICU as on the day of RWD peak. Very early SIR model predictions based on early cumulative case data initially underestimated the number of beds needed, but the RMSEs tended to decline as more updated data were used. Very-early-stage SIR model, although simple but convenient and relatively accurate, is a useful tool to provide decisive information for the public health system and predict the trend of an epidemic of novel infectious disease in the very early stage, thus, avoiding the issue of delay-decision and extra deaths.

Understanding influencing attributes of COVID-19 vaccine preference and willingness-to-pay among Chinese and American middle-aged and elderly adults: A discrete choice experiment and propensity score matching study.

Background and objective: COVID-19 has imposed burdens on public health systems globally. Owing to the urgency of vaccination, this study aimed at comparing the differences in preference and willingness to pay of COVID-19 vaccine among Chinese and American middle-aged and elderly adults. Methods: A cross-sectional survey containing demographic questions, rating their acceptance of COVID-19 vaccination with and without recommendations from friends, family members or employers (the social cues referred to in our study), and a discrete choice experiment understanding COVID-19 vaccine preference and willingness to pay was conducted to collect data. Propensity score matching was utilized to adjust confounding factors of baseline characteristics and the relative importance of respondents' preference for each attribute and its level was estimated using a conditional logit model. Then, willingness to pay was calculated. Results: In total, 3,494 (2,311 and 1,183 from China and the United States, respectively) completed the questionnaire, among which 3,444 questionnaires were effective. After propensity score matching, 1,604 respondents with 802 from the US and 802 from China were included. Under the influence of the social cues, Chinese respondents' vaccine acceptance decreased from 71.70 to 70.70%, while American respondents' vaccine acceptance increased from 74.69 to 75.81%. The discrete choice experiment showed that American respondents regarded the efficacy of COVID-19 vaccine as the most important attribute, whereas Chinese respondents attached the highest importance to the cost of vaccination. But overall, the COVID-19 vaccine with the higher efficacy, the milder adverse effect, the lower cost, and the longer duration will promote the preference of the public in both countries. Additionally, the public were willing to spend the most money for a reduction in COVID-19 vaccine adverse effect from moderate to very mild (37.476USD for the United States, 140.503USD for China), followed by paying for the 1% improvement in its efficacy and paying for the one-month extension of its duration. Conclusion: Given the impact of social cues on vaccine acceptance, Chinese government should promote reasonable vaccine-related information to improve national vaccination acceptance. Meanwhile, considering the influence of COVID-19 attributes on public preference and willingness to pay, regulating the vaccine pricing, improving the efficacy of the vaccine, reducing its adverse effect, and prolonging the duration of the vaccine works will contribute to vaccine uptake.

All HER2-negative breast cancer patients need gBRCA testing: cost-effectiveness and clinical benefits.

BACKGROUND: The OlympiA trial demonstrated the benefits of adjuvant usage of olaparib for high-risk patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) and germline BRCA (gBRCA) mutation. This provoked thoughts on the clinical criteria of gBRCA testing. This study aims to estimate the costs and benefits of gBRCA testing and adjuvant olaparib therapy for patients with triple-negative breast cancer (TNBC) and hormone-receptor (HR)-positive and HER2-negative BC in China and the United States of America (USA). METHODS: We used a Markov chain decision tree analytic model to compare three gBRCA screening policies in China and the USA: (1) no gBRCA testing; (2) selected gBRCA testing and (3) universal gBRCA testing for nonmetastatic TNBC and HR-positive HER2-negative BC patients. We modelled the benefit of systemic therapy and risk-reducing surgeries among patients identified with pathogenic or likely pathogenic variants (PVs) in BRCA1 and BRCA2. RESULTS: Changing from the selected gBRCA testing to the universal gBRCA testing in TNBC patients is cost-effective, with the incremental cost-effectiveness ratios (ICERs) being 10991.1 and 56518.2 USD/QALY in China and the USA, respectively. Expanding universal gBRCA testing to HR-positive HER2-negative BC and TNBC patients has ICERs of 2023.3 and 16611.1 USD/QALY in China and the USA, respectively. DISCUSSION: By performing gBRCA testing on all HER2-negative BC patients, adjuvant olaparib can be offered to high-risk patients with a PV in BRCA1 or BRCA2. These patients are also candidates for risk-reducing surgeries, an important aspect of their survivorship care, and these interventions can improve survival outcomes. With the willingness-to-pay thresholds being 31,500.0 and 100,000.0 USD per QALY gained in China and the USA, respectively, universal gBRCA testing is likely cost-effective for all HER2-negative BC patients. This simplified criterion of gBRCA testing for BC is recommended for adoption by current guidelines in China and the USA.

Serum Anion Gap Level Predicts All-Cause Mortality in Septic Patients: A Retrospective Study Based on the MIMIC III Database.

PURPOSE: Sepsis is a significant threat in the intensive care unit (ICU) worldwide because it has high morbidity and mortality rates. Early recognition and diagnosis of sepsis are essential for the prevention of adverse outcomes. The present study aimed to quantitatively assess the association between serum anion gap (AG) levels and 30- and 90-day all-cause mortality among sepsis patients. METHODS: Clinical data of patients diagnosed with sepsis were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association between serum AG levels and all-cause mortality. A receiver operating characteristic (ROC) curve was drawn to quantify the efficacy of using the serum AG level to predict all-cause mortality. RESULTS: A total of 3811 patients were included in the study. The Kaplan-Meier curves showed that patients with higher serum AG levels had a shorter survival time than those with lower levels. Serum AG levels were found to be highly effective in predicting all-cause mortality secondary to sepsis (30-day: AUROC = 0.703; 90-day: AUROC = 0.696). The Cox regression model further indicated that the serum AG level was an independent risk factor for 30- and 90-day mortality in sepsis (HR 3.44, 95% CI 2.97-3.99 for 30-day; HR 3.17, 95% CI 2.76-3.65 for 90-day, P < 0.001 for both). CONCLUSIONS: High serum AG may be considered as an alternative parameter for predicting the death risk in sepsis when other variables are not immediately available. Prospective large-scale studies are needed to support its predictive value in the clinic.

The Construct Structures of Psychological and Behavioral Responses to COVID-19 Pandemic in Pregnant Women.

Aim: The present study aimed to investigate the construct structure behind the psychosocial response, behavioral response, prenatal depression, and post-traumatic stress disorder (PTSD) in pregnant women during the COVID-19 pandemic in China. Method: The validated Chinese version of the Edinburgh Postnatal Depression Scale (EPDS), PTSD CheckList (PCL)-6, and two newly established scales for COVID-19-related psychological and behavioral responses were used. Structural equation modeling (SEM) analysis was applied to evaluate the structural relationships of psychological and behavioral responses during the COVID-19 pandemic. Results: Of the 1,908 mothers who completed the questionnaires, 1,099 met the criteria for perinatal depression, and 287 were positively screened for PTSD, where 264 women exceed the cut-off points for both. Pregnant women with full-time or part-time jobs tended to have the lowest scores of EPDS (10.07 ± 5.11, P < 0.001) and stress levels (23.85 ± 7.96, P = 0.004), yet they were more likely to change their behavior in accordance with the COVID-19 outbreak (13.35 ± 3.42, P = 0.025). The structural model fit the data (χ2 = 43.260, p < 0.001) and resulted in satisfactory fit indices (CFI = 0.984, TLI = 0.959, RMSEA = 0.072, and χ2/df = 10.815), all path loadings were significant (p < 0.05). The SEM indicates that the level of QoL was attributable to the occurrence of PND, leading to PTSD, and COVID-19 related behavioral and psychological responses. Conclusion: The inter-relationships between the COVID-19-related psychosocial and behavioral responses have been assessed, indicating that the pandemic increased the burden of perinatal depression. Psychoeducation, as well as other psychological interventions, may be needed to alleviate the COVID-19-based anxiety and increase their engagement in protective behaviors.

Acceptance of and Preference for COVID-19 Vaccination in India, the United Kingdom, Germany, Italy, and Spain: An International Cross-Sectional Study.

Objective: India and Europe have large populations, a large number of Coronavirus disease 2019 (COVID-19) cases, and different healthcare systems. This study aims to investigate the differences between the hesitancy toward and preference for COVID-19 vaccines in India and four European countries, namely, the United Kingdom (UK), Germany, Italy, and Spain. Methodology: We conducted a cross-national survey for distribution in India, the UK, Germany, Italy, and Spain. More specifically, a discrete choice experiment (DCE) was conducted to evaluate vaccine preferences, and Likert scales were used to probe the underlying factors that contribute to vaccination acceptance. Propensity score matching (PSM) was performed to directly compare India and European countries. Results: A total of 2565 respondents (835 from India and 1730 from the specified countries in Europe) participated in the survey. After PSM, more than 82.5% of respondents from India positively accepted the COVID-19 vaccination, whereas 79.9% of respondents from Europe had a positive attitude; however, the proportion in Europe changed to 81.6% in cases in which the vaccine was recommended by friends, family, or employers. The DCE found that the COVID-19 vaccine efficacy was the most important factor for respondents in India and the four European nations (41.8% in India and 47.77% in Europe), followed by the vaccine cost (28.06% in India and 25.88% in Europe). Conclusion: Although most respondents in both regions showed high acceptance of COVID-19 vaccines, either due to general acceptance or acceptance as a result of social cues, the vaccination coverage rate shows apparent distinctions. Due to the differences in COVID-19 situations, public health systems, cultural backgrounds, and vaccine availability, the strategies for COVID-19 vaccine promotion should be nation-dependent.

Preferences for Attributes of Initial COVID-19 Diagnosis in the United States and China During the Pandemic: Discrete Choice Experiment With Propensity Score Matching.

BACKGROUND: China and the United States play critical leading roles in the global effort to contain the COVID-19 virus. Therefore, their population's preferences for initial diagnosis were compared to provide policy and clinical insights. OBJECTIVE: We aim to quantify and compare the public's preferences for medical management of fever and the attributes of initial diagnosis in the case of presenting symptoms during the COVID-19 pandemic in China and the United States. METHODS: We conducted a cross-sectional study from January to March 2021 in China and the United States using an online discrete choice experiment (DCE) questionnaire distributed through Amazon Mechanical Turk (MTurk; in the United States) and recruited volunteers (in China). Propensity score matching (PSM) was used to match the 2 groups of respondents from China and the United States to minimize confounding effects. In addition, the respondents' preferences for different diagnosis options were evaluated using a mixed logit model (MXL) and latent class models (LCMs). Moreover, demographic data were collected and compared using the chi-square test, Fisher test, and Mann-Whitney U test. RESULTS: A total of 9112 respondents (5411, 59.4%, from China and 3701, 40.6%, from the United States) who completed our survey were included in our analysis. After PSM, 1240 (22.9%) respondents from China and 1240 (33.5%) from the United States were matched for sex, age, educational level, occupation, and annual salary levels. The segmented sizes of 3 classes of respondents from China were 870 (70.2%), 270 (21.8%), and 100 (8.0%), respectively. Meanwhile, the US respondents' segmented sizes were 269 (21.7%), 139 (11.2%), and 832 (67.1%), respectively. Respondents from China attached the greatest importance to the type of medical institution (weighted importance=40.0%), while those from the United States valued the waiting time (weighted importance=31.5%) the most. Respondents from China preferred the emergency department (coefficient=0.973, reference level: online consultation) and fever clinic (a special clinic for the treatment of fever patients for the prevention and control of acute infectious diseases in China; coefficient=0.974, reference level: online consultation), while those from the United States preferred private clinics (general practices; coefficient=0.543, reference level: online consultation). Additionally, shorter waiting times, COVID-19 nucleic acid testing arrangements, higher reimbursement rates, and lower costs were always preferred. CONCLUSIONS: Improvements in the availability of COVID-19 testing and medical professional skills and increased designated health care facilities may help boost potential health care seeking during COVID-19 and prevent unrecognized community spreading of SARS-CoV-2 in China and the United States. Moreover, to better prevent future waves of pandemics, identify undiagnosed patients, and encourage those undiagnosed to seek health care services to curb the pandemic, the hierarchical diagnosis and treatment system needs improvement in China, and the United States should focus on reducing diagnosis costs and raising the reimbursement rate of medical insurance.

A Comparison of Vaccine Hesitancy of COVID-19 Vaccination in China and the United States.

OBJECTIVES: To investigate the differences in vaccine hesitancy and preference of the currently available COVID-19 vaccines between two countries, namely, China and the United States (U.S.). METHOD: A cross-national survey was conducted in both China and the United States, and discrete choice experiments, as well as Likert scales, were utilized to assess vaccine preference and the underlying factors contributing to vaccination acceptance. Propensity score matching (PSM) was performed to enable a direct comparison between the two countries. RESULTS: A total of 9077 (5375 and 3702 from China and the United States, respectively) respondents completed the survey. After propensity score matching, over 82.0% of respondents from China positively accepted the COVID-19 vaccination, while 72.2% of respondents from the United States positively accepted it. Specifically, only 31.9% of Chinese respondents were recommended by a doctor to have COVID-19 vaccination, while more than half of the U.S. respondents were recommended by a doctor (50.2%), local health board (59.4%), or friends and families (64.8%). The discrete choice experiments revealed that respondents from the United States attached the greatest importance to the efficacy of COVID-19 vaccines (44.41%), followed by the cost of vaccination (29.57%), whereas those from China held a different viewpoint, that the cost of vaccination covered the largest proportion in their trade-off (30.66%), and efficacy ranked as the second most important attribute (26.34%). Additionally, respondents from China tended to be much more concerned about the adverse effect of vaccination (19.68% vs. 6.12%) and have a lower perceived severity of being infected with COVID-19. CONCLUSION: Although the overall acceptance and hesitancy of COVID-19 vaccination in both countries are high, underpinned distinctions between these countries were observed. Owing to the differences in COVID-19 incidence rates, cultural backgrounds, and the availability of specific COVID-19 vaccines in the two countries, vaccine rollout strategies should be nation-dependent.

Psychobehavioral Responses, Post-Traumatic Stress and Depression in Pregnancy During the Early Phase of COVID-19 Outbreak.

Objective: The novel coronavirus disease (COVID-19) outbreak has aroused a range of negative effects. Such considerable influence can be greater in vulnerable populations including pregnant women. This study aimed to assess the presence of prenatal depression (PND, as an important risk factor of postpartum depression) and post-traumatic stress disorder (PTSD) and to characterize infection-induced preventive behaviors and psychological responses in the early phase of COVID-19 outbreak. Methods: Based on a population-based sample of pregnant women from all regions in China, presence of probable PND and suspected PTSD were assessed using the Edinburgh Postnatal Depression Scale (≥13) and the PTSD Checklist (≥14), respectively. A web-based questionnaire was used to assess psychological and behavioral responses to COVID-19. Results: Among a total of 1908 questionnaires returned, 1901 women provided valid data (mean [SD] age, 28.9 [4.7] years). High prevalence of probable PND (34%) and suspected PTSD (40%) among pregnant women was observed. Those with suspected PTSD presented six times higher risk of probable PND than the non-suspected (OR=7.83, 95% CI: 6.29-9.75; p<0.001). Most women (91%-96%) reported anxiousness about infection of themselves and the members within their social network. Lack of security and loss of freedom were reported in approximately two-thirds of pregnant women. More frequent preventive behaviors, including handwashing, use of facemasks, and staying at home, were undertaken in more than 80% of the sample. Anxiousness of miscarriage and preterm birth were prevalent (>75%). Conclusions: High prevalence of PND and PTSD and high levels of anxiety suggest profound impacts of the present outbreak on mental health. This calls for special attention and support for vulnerable populations. Mental health care should become part of public health measures during the present outbreak and should continue to be intensified to empower the health system for post-outbreak periods.

Sildenafil for pulmonary hypertension in neonates: An updated systematic review and meta-analysis.

OBJECTIVES: To provide an updated review and meta-analysis on the efficacy and safety of sildenafil for treating persistent pulmonary hypertension in neonates (PPHN). METHODS: PubMed/Medline, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science were searched from the inception of publication to January 2021. The principal outcomes include oxygenation parameters, hemodynamic metrics and echocardiographic measurements, as well as adverse outcomes. RESULTS: A total of eight studies were included with 216 term and premature neonates with PPHN. Compelling evidence showed the use of sildenafil could improve the prognosis of PPHN neonates, compared with baseline or placebo in neonates with PPHN, and a time-dependent pattern of the improvements can be observed. After 24 h of treatment, the Oxygenation index suggested a steady decrease (SD: -1.80, 95% confidence interval [CI]: -2.92, -0.67) and sildenafil exerted peak effects after 72 h of treatment (SD: -4.02, 95% CI: -5.45, -2.59). No clinically significant side effects were identified. Egger's test and funnel plots of the major outcomes were performed, and the publication bias was not significant. CONCLUSION: Improvements were shown in oxygenation index, pulmonary arterial pressure, and adverse outcomes after using sildenafil for PPHN in neonates. However, future research with robust longitudinal or randomized controlled design is still needed.

Where does fear originate in the brain? A coordinate-based meta-analysis of explicit and implicit fear processing.

Processing of fear is of crucial importance for human survival and it can generally occur at explicit and implicit conditions. It is worth noting that explicit and implicit fear processing produces different behavioral and neurophysiological outcomes. The present study capitalizes on the Activation Likelihood Estimation (ALE) method of meta-analysis to identify: (a) the "core" network of fear processing in healthy individuals; (b) common and specific neural activations associated with explicit and implicit processing of fear. Following PRISMA guidelines, a total of 92 fMRI and PET studies were included in the meta-analysis. The overall analysis show that the core fear network comprises the amygdala, pulvinar, and fronto-occipital regions. Both implicit and explicit fear processing activated amygdala, declive, fusiform gyrus, and middle frontal gyrus, suggesting that these two types of fear processing share a common neural substrate. Explicit fear processing elicited more activations at the pulvinar and parahippocampal gyrus, suggesting visual attention/orientation and contextual association play important roles during explicit fear processing. In contrast, implicit fear processing elicited more activations at the cerebellum-amygdala-cortical pathway, indicating an 'alarm' system underlying implicit fear processing. These findings have shed light on the neural mechanism underlying fear processing at different levels of awareness.

The Influence of Average Temperature and Relative Humidity on New Cases of COVID-19: Time-Series Analysis.

BACKGROUND: The influence of meteorological factors on the transmission and spread of COVID-19 is of interest and has not been investigated. OBJECTIVE: This study aimed to investigate the associations between meteorological factors and the daily number of new cases of COVID-19 in 9 Asian cities. METHODS: Pearson correlation and generalized additive modeling (GAM) were performed to assess the relationships between daily new COVID-19 cases and meteorological factors (daily average temperature and relative humidity) with the most updated data currently available. RESULTS: The Pearson correlation showed that daily new confirmed cases of COVID-19 were more correlated with the average temperature than with relative humidity. Daily new confirmed cases were negatively correlated with the average temperature in Beijing (r=-0.565, P<.001), Shanghai (r=-0.47, P<.001), and Guangzhou (r=-0.53, P<.001). In Japan, however, a positive correlation was observed (r=0.416, P<.001). In most of the cities (Shanghai, Guangzhou, Hong Kong, Seoul, Tokyo, and Kuala Lumpur), GAM analysis showed the number of daily new confirmed cases to be positively associated with both average temperature and relative humidity, especially using lagged 3D modeling where the positive influence of temperature on daily new confirmed cases was discerned in 5 cities (exceptions: Beijing, Wuhan, Korea, and Malaysia). Moreover, the sensitivity analysis showed, by incorporating the city grade and public health measures into the model, that higher temperatures can increase daily new case numbers (beta=0.073, Z=11.594, P<.001) in the lagged 3-day model. CONCLUSIONS: The findings suggest that increased temperature yield increases in daily new cases of COVID-19. Hence, large-scale public health measures and expanded regional research are still required until a vaccine becomes widely available and herd immunity is established.