Identification and high-throughput quantification of baicalein and its metabolites in plasma and urine

Ethnopharmacological relevance: Scutellaria baicalensis Georgi. contains varieties of function compounds, and it has been used as traditional drug for centuries. Baicalein is the highest amount of flavonoid found in Scutellaria baicalensis Georgi., which exerts various pharmacological activities and might be a promising drug to treat COVID-19. Aim of the study: The present work aims to investigate the metabolism of baicalein in humans after oral administration, and study the pharmacokinetics of BA and its seven metabolites in plasma and urine. Materials and methods: The metabolism profiling and the identification of baicalein metabolites were performed on HPLC-Q-TOF. Then a column-switching method named MPX™-2 system was applied for the high-throughput quantificationof BA and seven metabolites. Results: Seven metabolites were identified using HPLC-Q-TOF, including sulfate, glucuronide, glucoside, and methyl-conjugated metabolites. Pharmacokinetic study found that BA was extensively metabolized in vivo, and only 5.65% of the drug remained intact in the circulatory system after single dosing. Baicalein-7-O-sulfate and baicalein-6-O-glucuronide-7-O-glucuronide were the most abundant metabolites. About 7.2% of the drug was excreted through urine and mostly was metabolites. Conclusion: Seven conjugated metabolites were identified in our assay. A high-throughput HPLC-MS/MS method using column switch was established for quantifying BA and its metabolites. The method has good sensitivity and reproducibility, and successfully applied for the clinical pharmacokinetic study of baicalein and identified metabolites. We expect that our results will provide a metabolic and pharmacokinetic foundation for the potential application of baicalein in medicine. © 2022

COVID-19 Vaccination for Frail Older Adults in Singapore - Rapid Evidence Summary and Delphi Consensus Statements.

OBJECTIVE: This study aimed to synthesize available evidence on the effectiveness and safety of COVID-19 vaccines for frail older adults through a rapid review, supplemented with geriatricians' consensus statements. METHODS: References were identified through MEDLINE and Web of Science on 1st February 2021 using relevant terms related to COVID-19, vaccine, and older adults. Searches were also conducted on reference lists of review articles and Google Scholar. The content was updated on 8th April via hand searching. We included studies on Phase III randomized controlled trials, and data from real world administration of vaccines. A two-round Delphi study was conducted with 15 geriatricians to elicit their thoughts and recommendations regarding COVID-19 vaccination for frail older adults. RESULTS: Five Phase III randomized controlled efficacy trials reported vaccine efficacy ranging from 66.7% to 95% among participants aged 16 to 95. The vaccine efficacy for participants aged 65 and above is 94.7% and 86.4% for Pfizer-BioNTech and Moderna respectively. Sputnik V reported a vaccine efficacy of 91.8% for participants 60 and above. Serious adverse events were reported by 0.27% to 1% of participants who received at least one dose of the four vaccines. For the Delphi study, 16 out of 24 statements achieved consensus. The Delphi panel opined that frail or very old adults, except those with limited life expectancy, should be vaccinated due to their vulnerability. They also agree that vaccination decisions should be made by patients when possible, with the involvement of next-of-kin should the frail older adult be unable to do so. Lastly, the panel thought that frail older adults should be included in future clinical trials. CONCLUSION: In early clinical trials, there is paucity of evidence on efficacy and safety of current COVID-19 vaccines among frail older adults. Geriatricians' consensus indicate that frail older adults should be vaccinated except where life expectancy is limited. Future trials assessing efficacy and safety should include frail older adults.

The impact of the COVID-19 pandemic on the Ontario Cervical Screening Program, colposcopy and treatment services in Ontario, Canada: a population-based study.

OBJECTIVE: To describe the immediate impact of the COVID-19 pandemic on cervical screening, colposcopy and treatment volumes in Ontario, Canada. DESIGN: Population-based retrospective observational study. SETTING: Ontario, Canada. POPULATION: People with a cervix age of 21-69 years who completed at least one cervical screening cytology test, colposcopy or treatment procedure for cervical dysplasia between January 2019 and August 2020. METHODS: Administrative databases were used to compare cervical screening cytology, colposcopy and treatment procedure volumes before (historical comparator) and during the first 6 months of the COVID-19 pandemic (March-August 2020). MAIN OUTCOME MEASURES: Changes in cervical screening cytology, colposcopy and treatment volumes; individuals with high-grade cytology awaiting colposcopy. RESULTS: During the first 6 months of the COVID-19 pandemic, the monthly average number of cervical screening cytology tests, colposcopies and treatments decreased by 63.8% (range: -92.3 to -41.0%), 39.7% (range: -75.1 to -14.3%) and 31.1% (range: -43.5 to -23.6%), respectively, when compared with the corresponding months in 2019. Between March and August 2020, on average 292 (-51.0%) fewer high-grade cytological abnormalities were detected through screening each month. As of August 2020, 1159 (29.2%) individuals with high-grade screening cytology were awaiting follow-up colposcopy. CONCLUSIONS: The COVID-19 pandemic has had a substantial impact on key cervical screening and follow-up services in Ontario. As the pandemic continues, ongoing monitoring of service utilisation to inform system response and recovery is required. Future efforts to understand the impact of COVID-19-related disruptions on cervical cancer outcomes will be needed. TWEETABLE ABSTRACT: COVID-19 has had a substantial impact on cervical screening and follow-up services in Ontario, Canada.

Epidemiological and clinical characteristics of patients with COVID-19 from a designated hospital in Hangzhou City: a retrospective observational study.

INTRODUCTION: The outbreak of coronavirus disease 2019 (COVID-19) has exerted a heavy burden on public health worldwide. We aimed to investigate the epidemiological and clinical characteristics of patients with COVID-19 in a designated hospital in Hangzhou, China. METHODS: This was a retrospective study that included laboratory-confirmed cases of COVID-19 in XiXi Hospital of Hangzhou from 15 January 2020 to 30 March 2020. We reviewed and analysed the epidemiological, demographic, clinical, radiological, and laboratory features involving these cases. Age-tratification analysis was also implemented. RESULTS: We analysed 96 confirmed cases. The patients had a mean age of 43 years, with six patients younger than 18 years and 14 patients older than 60 years. No significant gender difference was discovered. Co-morbidities were commonly observed in patients aged over 40 years. Twenty eight of the patients had travelled from Wuhan City, and 51 patients were infected through close contact. Familial clusters accounted for 48 of the cases. The mean incubation time was 7 days, and the symptoms were mainly fever, cough, fatigue, and sore throat. Lymphocytopenia was observed predominantly in patients aged over 60 years. Fifty five patients presented with bilateral pulmonary lesions. The radiological changes were typically distributed in the subpleural area, and pleural effusion rarely occurred. All patients were discharged successfully. CONCLUSION: During the early stage of the COVID-19 outbreak, half of the patients from a designated hospital in Hangzhou City were discovered as familial clusters. Therefore, strict prevention and control measures during self-isolation should be implemented. Patients aged over 60 years who had underlying co-morbidities were prone to lymphocytopenia and severe infection.

Prevalence of insomnia and anxiety among healthcare workers during the COVID-19 pandemic in Jilin Province

The outbreak of the 2019 novel coronavirus disease (COVID-19) has impacted the mental health of healthcare providers at the frontline. Therefore, we conducted this study to estimate the prevalence rate of anxiety and insomnia and identify associated risk factors among healthcare workers in Jilin, China, during the period from January 25 to February 25, 2020. Zung's Self-Reported Anxiety Scale (SAS) and the Insomnia Severity Index (ISI) scale were used to diagnose anxiety and insomnia, respectively. Associated risk factors were identified through a multivariate logistic regression model. A total of 300 healthcare workers were invited and 236 completed the study. Of them, 234 (99.15%) were medical workers, 197 (83.47%) were working at frontline departments, and 159 (67.37%) were fighting against COVID-19. Fifty-seven respondents (24.15%) had anxiety (SAS index score ≥45) and 94 (39.83%) had insomnia (ISI score ≥8). Based on the multivariate analysis, contact with people from Hubei province during work (no vs not clear) [OR=0.25, 95%CI: 0.10-0.61] and personal protective equipment (PPE) (not in place vs in place) [OR=6.22, 95%CI: 2.23-17.40] were significantly correlated with anxiety. PPE (not in place vs in place) was the only significant risk factor of insomnia [OR=10.56, 95%CI: 4.00-27.87]. The prevalence of anxiety and insomnia was high in our study, reflecting the psychological impact of COVID-19 on healthcare workers. The unavailability of PPE in place was a significant risk factor of both anxiety and insomnia.