Mifepristone (RU-486®) as a Schedule IV Controlled Drug-Implications for a Misleading Drug Policy on Women's Health Care.

BACKGROUND: Mifepristone (RU-486) has been approved for abortion in Taiwan since 2000. Mifepristone was the first non-addictive medicine to be classified as a schedule IV controlled drug. As a case of the "misuse" of "misuse of drugs laws," the policy and consequences of mifepristone-assisted abortion for pregnant women could be compared with those of illicit drug use for drug addicts. METHODS: The rule-making process of mifepristone regulation was analyzed from various aspects of legitimacy, social stigma, women's human rights, and access to health care. RESULTS AND DISCUSSION: The restriction policy on mifepristone regulation in Taiwan has raised concerns over the legitimacy of listing a non-addictive substance as a controlled drug, which may produce stigma and negatively affect women's reproductive and privacy rights. Such a restriction policy and social stigma may lead to the unwillingness of pregnant women to utilize safe abortion services. Under the threat of the COVID-19 pandemic, the US FDA's action on mifepristone prescription and dispensing reminds us it is time to consider a change of policy. CONCLUSIONS: Listing mifepristone as a controlled drug could impede the acceptability and accessibility of safe mifepristone use and violates women's right to health care.

Flap Reconstruction of the Oropharyngeal Defect After Tumor Resection via Combined Transcervical and Transoral Approach in Patients With HPV-Positive and -Negative Oropharyngeal Squamous Cell Carcinoma.

Objective: To investigate a novel surgical approach of combined transcervical parapharyngeal space (PPS) with the transoral approach to dissect oropharyngeal cancer. Methods: 31 patients who were pathologically diagnosed with oropharyngeal cancer and had undergone surgical treatment in Beijing Tongren Hospital during June 2018 and December 2020 were enrolled. All patients were squamous cell carcinoma patients. There were 25 males and 6 females, and the age ranged between 44 and 70 years old. The number of patients with T1, T2, T3, and T4 stage disease was 8, 15, 8, and 0, respectively, according to the American Joint Committee on Cancer staging method, 8th edition. After the dissection of the submandibular and cervical lymph nodes, the parapharyngeal space was exposed, and the parapharyngeal space lymph node and the outer borderline of the tumor were dissected, and then the inner borderline of the tumor was dissected via a transoral approach; the tumor was dissected en bloc, and the defects were reconstructed with the flap from the neck through the parapharyngeal space. Results: Among the patients enrolled, 21 were HPV positive and 10 were HPV negative. 8 patients were free of lymph node metastasis. The tumor resection margins were negative in all 31 patients. Safe and sufficient excision of tumors was feasible by this new surgical approach, avoiding complications associated with mandibulotomy or lip-splitting. All patients had no obvious dysfunctions of swallowing and voice. By the time of this follow-up, none died caused by OPSCC, and only two patients suffered from local recurrence. The 3-year survival rate is 100%, and the 3-year recurrence-free survival rate is 84.58%. Conclusion: The surgical approach of combined transcervical parapharyngeal space with the transoral approach was effective and safe. On this basis, this approach has the advantage of fewer postoperative complications and better functional results.

Effect of dialectical behavior group therapy on the anxiety and depression of medical students under the normalization of epidemic prevention and control for the COVID-19 epidemic: a randomized study.

BACKGROUND: During the epidemic, the mental health of college students was generally poor, especially anxiety and depression, which should be treated using counseling and intervention. This study aimed to observe the influence of dialectical behavior therapy on the anxiety and depression of medical students during the normalization of the prevention and control of the COVID-19 epidemic. METHODS: A total of 26 medical students (experimental group) were treated with dialectical behavior therapy intervention for 4 weeks. Changes in depression, anxiety, and stress levels were assessed by the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder (GAD-7) scale, the Somatic Self-rating Scale (SSS), and the Perceived Stress Scale (PSS-10). This group was compared with 26 medical students (control group) without intervention. RESULTS: The value-added scores of the PHQ-9 (t=2.543, P=0.014) and GAD-7 scales (t=3.790, P=0.000) in the experimental group were significantly higher than those in the control group, while in the SSS scale, the value-added score of the depressive symptoms subscale (t=2.234, P=0.030) in the experimental group was significantly higher than that of the control group. For the total score of the PSS-10 scale (t=2.435, P=0.018), the value-added score of the experimental group was significantly higher than that of the control group. CONCLUSIONS: The intervention of dialectical behavior therapy can effectively alleviate the depression and anxiety of medical students during the normalization of epidemic prevention and control. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048784.

People living with HIV easily lose their immune response to SARS-CoV-2: result from a cohort of COVID-19 cases in Wuhan, China.

BACKGROUND: To date, whether the immune response for SARS-CoV-2 infection among people living with HIV(PLWH) is different from HIV-naïve individuals is still not clear. METHODS: In this cohort study, COVID-19 patients admitted to hospitals in Wuhan between January 15 and April 1, 2020, were enrolled. Patients were categorized into PLWH and HIV-naïve group. All patients were followed up regularly (every 15 days) until November 30, 2020, and the immune response towards SARS-CoV-2 was observed. RESULTS: Totally, 18 PLWH and 185 HIV-naïve individuals with COVID-19 were enrolled. The positive conversion rates of IgG were 56% in PLWH and 88% in HIV-naïve patients respectively, and the peak was on the 45th day after COVID-19 onset. However, the positive rate of IgG dropped to 12% in PLWH and 33% among HIV-naïve individuals by the end of the study. The positive conversion rate of IgG among asymptomatic carriers is significantly lower than that among patients with moderate disease (AOR = 0.24, 95% CI 0.07-0.85). PLWH had a lower IgG seroconversion rate (AOR = 0.11, 95% CI 0.03-0.39) and shorter IgG duration (AHR = 3.99, 95% CI 1.43-11.13) compared to HIV-naïve individuals. Patients with higher lymphocyte counts at onset had a lower positive conversion rate (AOR = 0.30, 95% CI 0.10-0.87) and shorter duration for IgG (AHR = 4.01, 95% CI 1.78-9.02). CONCLUSIONS: The positive conversion rate of IgG for SARS-CoV-2 was relatively lower and quickly lost in PLWH.

Improvement to the subjective well-being of pet ownership may have positive psychological influence during COVID-19 epidemic.

The COVID-19 epidemic and government intervention measures may have adverse effects on people's mental health. To explore the influence of pets on the intervention of people's psychological problems during the COVID-19 epidemic, an online survey was carried out between April 9 and April 29, 2020. A total of 756 participants replied to this questionnaire. Mental health variables were assessed, and the comparison of behavior changes among pet owners and pets on positive mental well-being during COVID-19 epidemic. Comparative analysis was performed; compared with individuals without pets (n = 575), pet owners (n = 181) had a higher prevalence of insomnia (p = 0.006). Living in Wuhan city was a risk factor for people with psychological stress (p < 0.05). Dog owners exhibited lower than average scores of insomnia and uncertainty of infection than cat owners (p = 0.004). People with more than one pet exhibited lower than average scores of depression than having one pet (p = 0.040). For analysis of psychological effects of pets on people, the role of pets in subjective feeling and positive psychological changes of pet owner was significantly different. Pet owners relieve that psychological pressure through behavioral changes towards their pets in early stage. Pets provided positive subjective well-being and psychological effects for their owners.

Promising Enzymes for Inhibitors Development Against COVID-19.

After the emergence of COVID-19 in 2019, it has now become a pandemic. COVID-19 has brought painful disasters to people all over the world. It not only threatens lives and health but also induces economic crises. At present, promising methods to eradicate COVID-19 mainly include drugs and vaccines. Enzyme inhibitors have always been a reliable strategy for the treatment of related diseases. Scientists worldwide have worked together to study COVID-19, obtained the structure of key SARS-CoV-2 associated enzymes, and reported the research of inhibitors of these enzymes. This article summarizes COVID-19-related enzyme inhibitors' recent development, mainly including 3CLpro, PLpro, TMPRSS2, and RdRp inhibitors, hoping to provide valuable weapons in the ensuing battle against COVID-19.

The trans-omics landscape of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.

People Living with HIV Easily lose their Immune Response to SARS-CoV-2: Result From A Cohort of COVID-19 Cases in Wuhan, China.

Background To date, whether the immune response for SARS-CoV-2 infection among people living with HIV(PLWH) is different from HIV-naïve individuals is still not clear. Methods In this cohort study, COVID-19 patients admitted to hospital in Wuhan between January 15 and April 1, 2020, were enrolled. Patients were categorized into PLWH and HIV-naïve group. All patients were followed up regularly (every fifteen days) until November 30, 2020, and the immune response towards SARS-CoV-2 was observed. Results Totally, 18 PLWH and 185 HIV-naïve individuals with COVID-19 were enrolled. The positive conversion rates of IgG were 56% in PLWH and 88% in HIV-naïve patients respectively, and the peak was on the 45th day after COVID-19 onset. However, the positive rate of IgG dropped to 12% in PLWH and 33% among HIV-naïve individuals by the end of the study. The positive conversion rate of IgG among asymptomatic carriers is significantly lower than that among moderate patients (AOR = 0.18, 95% CI: 0.05-0.65) and PLWH had a lower IgG seroconversion rate compared to the HIV-naive group (AOR = 0.22, 95% CI: 0.05-0.90). Patients with lower lymphocyte counts at onset had a higher positive conversion rate (AOR = 0.29, 95% CI: 0.09-0.90) and longer duration for IgG (AHR = 4.01, 95% CI: 1.78-9.02). Conclusions The positive conversion rate of IgG for SARS-CoV-2 was relatively lower and quickly lost in PLWH, which meant PLWH was in a disadvantaged situation when affected with COVID-19.

Nurses' core emergency competencies for COVID-19 in China: A cross-sectional study.

AIM: To investigate nurses' core emergency competencies for handling the coronavirus disease-19 (COVID-19) and analyse the factors associated with those competencies. BACKGROUND: COVID-19 has become a major global public health event. Nursing staff have played an important role in COVID-19 prevention and control. Understanding their emergency competencies for handling COVID-19, and the potential disadvantages will help governments to develop targeted training policies and improve nurses' capacities in relation to pandemics and emergency preparedness. INTRODUCTION: COVID-19 is a disastrous infectious disease, but the competencies of nurses in China to handle COVID-19 have not been well documented. METHODS: We conducted a cross-sectional survey on nurses from 22 provinces of China in February 2020. The scores of self-report questionnaires were used to analyse their competencies for core emergency care, and linear regression analysis was used to explore influential factors. RESULTS: A total of 2570 nurses participated. The study revealed that nurses had a good grasp of COVID-19 knowledge, but the majority of nurses lacked experience in isolation ward work and emergency training. We found that age, professional title, work department, major work content, total work time, disaster rescue history, emergency training and infectious disease training were associated with core emergency competencies. CONCLUSIONS: Chinese nurses were qualified for handling COVID-19 but still need to strengthen the accumulation of practical experience. IMPLICATIONS FOR NURSING: Nurses should actively participate in emergencies to strengthen their operational capacity, whether in training or actual practice. IMPLICATIONS FOR NURSING/HEALTH POLICY: Managers should improve relevant policies to ensure that nurses have more opportunities to participate in the practical training of health emergencies and explore effective training methods to improve the ability of nurses to respond to these.

Transmission roles of symptomatic and asymptomatic COVID-19 cases: a modeling study (preprint)

ObjectiveAge-dependent asymptomatic and symptomatic transmission dynamics of COVID-19 have not been well quantified due to limited data. MethodsThrough a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. ResultsThe difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.72% lower transmissibility rate than symptomatic cases, and 74.10% (95%CI: 65.85% - 80.72%) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.22% (95%CI: 22.97% - 34.56%). Simulation showed that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate the spreading. ConclusionAsymptomatic COVID-19 cases play a significant role in transmission. Vaccine Strategies prioritizing the population between 30-60 years old are likely to have the most population-level benefits.

Longitudinal multi-omics transition associated with fatality in critically ill COVID-19 patients.

PURPOSE: Critically ill COVID-19 patients have significantly increased risk of death. Although several circulating biomarkers are thought to be related to COVID-19 severity, few studies have focused on the characteristics of critically ill patients with different outcomes. The objective of this study was to perform a longitudinal investigation of the potential mechanisms affecting the prognosis of critically ill COVID-19 patients. METHODS: In addition to clinical data, 113 whole blood samples and 85 serum samples were collected from 33 severe and critical COVID-19 patients without selected comorbidities. Multi-omics analysis was then performed using longitudinal samples. RESULTS: Obvious transcriptional transitions were more frequent in critical survivors than in critical non-survivors, indicating that phase transition may be related to survival. Based on analysis of differentially expressed genes during transition, the erythrocyte differentiation pathway was significantly enriched. Furthermore, clinical data indicated that red blood cell counts showed greater fluctuation in survivors than in non-survivors. Moreover, declining red blood cell counts and hemoglobin levels were validated as prognostic markers of poor outcome in an independent cohort of 114 critical COVID-19 patients. Protein-metabolite-lipid network analysis indicated that tryptophan metabolism and melatonin may contribute to molecular transitions in critical COVID-19 patients with different outcomes. CONCLUSIONS: This study systematically and comprehensively depicted the longitudinal hallmarks of critical COVID-19 patients and indicated that multi-omics transition may impact the prognosis. TAKE HOME MESSAGE: Frequent transcriptional phase transitions may contribute to outcome in critically ill COVID-19 patients. Furthermore, fluctuation in red blood cell and hemoglobin levels may relate to poor prognosis. The biological function of melatonin was suppressed in COVID-19 non-survivors, which may provide a potential theoretical basis for clinical administration.

Government Intervention Measures Effectively Control COVID-19 Epidemic in Wuhan, China.

The Coronavirus disease 2019 (COVID-19) outbreak has been brought under control through a nationwide effort, and now it has become a global pandemic and the situation seems grim. We summarized the measures taken in Wuhan and analyzed the effects to comprehensively describe the factors involved in controlling the COVID-19 in China. In China, several measures such as the lockdown of Wuhan, restriction of traffic and communities, increasing hospital beds, nationwide support from medical staff, epidemic prevention equipment and supplies, and establishment of makeshift shelter hospitals have been taken. The lockdown of Wuhan reduced the propagation of cases to other cities in Hubei province and throughout China, traffic and community restrictions reduced the flow of population and the spread of disease, increasing wards and beds and medical personnel reduced the incidence of severe cases and mortality, the establishment of the Fangcang shelter hospitals provided a good isolation and monitoring environment, and further reduced the spread and fatality of the disease. The fact that China was able to control the spread of COVID-19 within three months without a specific drug or vaccine suggests that these measures are more adequate and effective.

Clinical manifestations and maternal and perinatal outcomes with COVID-19.

Coronavirus disease 2019 (COVID-19) is a novel type of highly contagious pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the COVID-19 outbreak unfolds, more and more pregnant women are infected with SARS-CoV-2, concerns have been raised about its clinical manifestations in pregnancy and the potential risk of vertical transmission from mother to fetus in pregnant women. Hence, in this review, we summarize the latest research progress related to COVID-19 epidemiology and the reported data of pregnant women with COVID-19 and discuss the clinical manifestations, treatments, maternal and perinatal outcomes, and intrauterine vertical transmission potential of such virus. Reported data suggest that symptoms in pregnant women are similar to those in other populations and that there is no evidence of vertical transmission from mother to child. In the meantime, considering the good prognosis of most of the infected mothers and infants and absence of serious obstetric complications in pregnant women with COVID-19, it is not recommended to give birth as soon as possible, and it is necessary to extend the gestational period reasonably.

Clinical Characteristics and Outcomes of Childbearing-Age Women With COVID-19 in Wuhan: Retrospective, Single-Center Study.

BACKGROUND: Since December 2019, an outbreak of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly in Wuhan and worldwide. However, previous studies on pregnant patients were limited. OBJECTIVE: The aim of this study is to evaluate the clinical characteristics and outcomes of pregnant and nonpregnant women with COVID-19. METHODS: This study retrospectively collected epidemiological, clinical, laboratory, imaging, management, and outcome data of 43 childbearing-age women patients (including 17 pregnant and 26 nonpregnant patients) who presented with laboratory-confirmed COVID-19 in Tongji Hospital, Wuhan, China from January 19 to March 2, 2020. Clinical outcomes were followed up to March 28, 2020. RESULTS: Of the 43 childbearing-age women in this study, none developed a severe adverse illness or died. The median ages of pregnant and nonpregnant women were 33.0 and 33.5 years, respectively. Pregnant women had a markedly higher proportion of history exposure to hospitals within 2 weeks before onset compared to nonpregnant women (9/17, 53% vs 5/26, 19%, P=.02) and a lower proportion of other family members affected (4/17, 24% vs 19/26, 73%, P=.004). Fever (8/17, 47% vs 18/26, 69%) and cough (9/17, 53% vs 12/26, 46%) were common onsets of symptoms for the two groups. Abdominal pain (n=4, 24%), vaginal bleeding (n=1, 6%), reduced fetal movement (n=1, 6%), and increased fetal movement (n=2, 13%) were observed at onset in the 17 pregnant patients. Higher neutrophil and lower lymphocyte percent were observed in the pregnant group compared to the nonpregnant group (79% vs 56%, P<.001; 15% vs 33%, P<.001, respectively). In both groups, we observed an elevated concentration of high-sensitivity C-reactive protein, erythrocyte sedimentation rate, aminotransferase, and lactate dehydrogenase. Concentrations of alkaline phosphatase and D-dimer in the pregnant group were significantly higher than those of the nonpregnant group (119.0 vs 48.0 U/L, P<.001; 2.1 vs 0.3µg/mL, P<.001, respectively). Both pregnant (4/10, 40%) and nonpregnant (8/15, 53%) women tested positive for influenza A virus. A majority of pregnant and nonpregnant groups received antiviral (13/17, 76% vs 25/26, 96%) and antibiotic (13/17, 76% vs 23/26, 88%) therapy. Additionally, both pregnant (2/11, 18%) and nonpregnant (2/19, 11%) recovered women redetected positive for SARS-CoV-2 after discharge. CONCLUSIONS: The epidemiology and clinical and laboratory features of pregnant women with COVID-19 were diverse and atypical, which increased the difficulty of diagnosis. Most pregnant women with COVID-19 were mild and moderate, and rarely developed severe pneumonia or severe adverse outcomes.

A Case Report of Neonatal 2019 Coronavirus Disease in China.

In December 2019, the coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and now has spread in many countries. Pregnant women are a population susceptible to COVID-19 and are more likely to have complications and even progress to severe illness. We report a case of neonatal COVID-19 in China with pharyngeal swabs testing positive by real-time reverse-transcription polymerase chain reaction assay 36 hours after birth. However, whether the case is a vertical transmission from mother to child remains to be confirmed.

Coronavirus disease 2019 in pregnant women: a report based on 116 cases.

BACKGROUND: The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series. OBJECTIVE: To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. RESULTS: The median gestational age on admission was 38+0 (interquartile range, 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks' gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.

Transmissibility of SARS-CoV-2 during incubation period: Epidemiologic evidence from 178 confirmed clusters in China (preprint)

An outbreak of novel coronavirus (SARS-CoV-2) was identified in China in December 2019, and has spread rapidly to more than 200 countries and areas in four months. A few studies have reported that transmissibility exists during the late incubation period based on one single infection cluster caused by SARS-CoV-2. Here based on 178 SARS-CoV-2 clusters confirmed in Zhejiang Province, we analyzed the epidemic link between all 212 secondary cases with their previous cases, and found 49 secondary cases (from 26 clusters), which were 23.11% (49/212) of the total secondary cases infected from previous cases during the latter’s incubation period. The median days from the last exposure of secondary cases to the onset of previous cases was 2.0 days (IQR: 1.00~5.00 days, 90th percentile: 9.00 days) .This study has shown transmission of the SARS-CoV-2 during the incubation period and indicated that some cases might be infectious soon after they were exposed to a prior transmitter. The results highlight the importance of extending the contact group for medical observation and isolation to those in contact with the index case nine (90th percentile) or more days before the latter’s illness onset, when medical resources were sufficient.