The impact of COVID-19 on antibiotic prescribing in primary care in England: Evaluation and risk prediction of appropriateness of type and repeat prescribing.

BACKGROUND: This study aimed to predict risks of potentially inappropriate antibiotic type and repeat prescribing and assess changes during COVID-19. METHODS: With the approval of NHS England, we used OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system and selected patients prescribed antibiotics from 2019 to 2021. Multinomial logistic regression models predicted patient's probability of receiving inappropriate antibiotic type or repeat antibiotic course for each common infection. RESULTS: The population included 9.1 million patients with 29.2 million antibiotic prescriptions. 29.1% of prescriptions were identified as repeat prescribing. Those with same day incident infection coded in the EHR had considerably lower rates of repeat prescribing (18.0%) and 8.6% had potentially inappropriate type. No major changes in the rates of repeat antibiotic prescribing during COVID-19 were found. In the 10 risk prediction models, good levels of calibration and moderate levels of discrimination were found. CONCLUSIONS: Our study found no evidence of changes in level of inappropriate or repeat antibiotic prescribing after the start of COVID-19. Repeat antibiotic prescribing was frequent and varied according to regional and patient characteristics. There is a need for treatment guidelines to be developed around antibiotic failure and clinicians provided with individualised patient information.

Impact of COVID-19 on broad-spectrum antibiotic prescribing for common infections in primary care in England: a time-series analyses using OpenSAFELY and effects of predictors including deprivation.

Background: The COVID-19 pandemic impacted the healthcare systems, adding extra pressure to reduce antimicrobial resistance. Therefore, we aimed to evaluate changes in antibiotic prescription patterns after COVID-19 started. Methods: With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system in primary care and selected patients prescribed antibiotics from 2019 to 2021. To evaluate the impact of COVID-19 on broad-spectrum antibiotic prescribing, we evaluated prescribing rates and its predictors and used interrupted time series analysis by fitting binomial logistic regression models. Findings: Over 32 million antibiotic prescriptions were extracted over the study period; 8.7% were broad-spectrum. The study showed increases in broad-spectrum antibiotic prescribing (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.36-1.38) as an immediate impact of the pandemic, followed by a gradual recovery with a 1.1-1.2% decrease in odds of broad-spectrum prescription per month. The same pattern was found within subgroups defined by age, sex, region, ethnicity, and socioeconomic deprivation quintiles. More deprived patients were more likely to receive broad-spectrum antibiotics, which differences remained stable over time. The most significant increase in broad-spectrum prescribing was observed for lower respiratory tract infection (OR 2.33; 95% CI 2.1-2.50) and otitis media (OR 1.96; 95% CI 1.80-2.13). Interpretation: An immediate reduction in antibiotic prescribing and an increase in the proportion of broad-spectrum antibiotic prescribing in primary care was observed. The trends recovered to pre-pandemic levels, but the consequence of the COVID-19 pandemic on AMR needs further investigation. Funding: This work was supported by Health Data Research UK and by National Institute for Health Research.

Toward a pan-SARS-CoV-2 vaccine targeting conserved epitopes on spike and non-spike proteins for potent, broad and durable immune responses.

BACKGROUND: The SARS-CoV-2 non-Spike (S) structural protein targets on nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, are grossly overlooked in COVID vaccine development. The current Spike-only vaccines bear an intrinsic shortfall for promotion of a fuller T cell immunity. Vaccines designed to target conserved epitopes could elicit strong cellular immune responses that would synergize with B cell responses and lead to long-term vaccine success. We pursue a universal (pan-SARS-CoV-2) vaccine against Delta, Omicrons and ever-emergent new mutants. METHODS AND FINDINGS: We explored booster immunogenicity of UB-612, a multitope-vaccine that contains S1-RBD-sFc protein and sequence-conserved promiscuous Th and CTL epitope peptides on the Sarbecovirus N, M and S2 proteins. To a subpopulation (N = 1,478) of infection-free participants (aged 18-85 years) involved in a two-dose Phase-2 trial, a UB-612 booster (third dose) was administered 6-8 months after the second dose. The immunogenicity was evaluated at 14 days post-booster with overall safety monitored until the end of study. The booster induced high viral-neutralizing antibodies against live Wuhan WT (VNT50, 1,711) and Delta (VNT50, 1,282); and against pseudovirus WT (pVNT50, 11,167) vs. Omicron BA.1/BA.2/BA.5 variants (pVNT50, 2,314/1,890/854), respectively. The lower primary neutralizing antibodies in the elderly were uplifted upon boosting to approximately the same high level in young adults. UB-612 also induced potent, durable Th1-oriented (IFN-γ+-) responses (peak/pre-boost/post-boost SFU/106 PBMCs, 374/261/444) along with robust presence of cytotoxic CD8+ T cells (peak/pre-boost/post-boost CD107a+-Granzyme B+, 3.6%/1.8%/1.8%). This UB-612 booster vaccination is safe and well tolerated without SAEs. CONCLUSIONS: By targeting conserved epitopes on viral S2, M and N proteins, UB-612 could provide potent, broad and long-lasting B-cell and T-cell memory immunity and offers the potential as a universal vaccine to fend off Omicrons and new VoCs without resorting to Omicron-specific immunogens. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04773067; ClinicalTrials.gov ID: NCT05293665; ClinicalTrials.gov ID: NCT05541861.

Calix[6]arene functionalized lanthanide metal-organic frameworks with boosted performance in identifying an anti-epidemic pharmaceutical.

A novel composite was fabricated by hybridizing terbium 1,3,5-benzenetricarboxylic MOF (TB-MOF) with Cx[6]. The obtained composite TB-Cx[6] possessed long-term stability and dispersion stability and was used for on-site analysis of the anti-COVID-19 disinfection product Prednis via a combing remote sampling technique.

Evaluating a cross-lagged panel model between problematic internet use and psychological distress and cross-level mediation of school administrator support on problematic internet use: The serial mediating role of psychological needs thwarting of online teaching and psychological distress.

Background: To reduce the transmission of COVID-19, many teachers across the globe, including teachers in China, were required to teach online. This shift to online teaching can easily result in psychological need thwarting (PNT) of teachers' psychological basic needs (autonomy, competence, and relatedness), leaving them vulnerable to negative psychological outcomes. Resulting negative emotional state may lead to problematic internet use (PIU), which can lead to further psychological distress, forming a vicious cycle. Methods: The present study was conducted using a cross-lagged panel model (with longitudinal data) and hierarchical linear modeling (HLM) (with cross-sectional data). The aims were to investigate (i) the reciprocal relationships between two specific forms of PIU [problematic social media use (PSMU) and problematic gaming (PG)] and psychological distress among schoolteachers, and (ii) the influence of administrators' support on schoolteachers' PIU through a cross-level serial mediation model (PNT of online teaching was the first mediator and psychological distress was the second mediator affected by PNT of online teaching). Primary and secondary schoolteachers (N = 980; mean age = 34.76; 82.90% females) participated in two surveys (Time 1: mid-November 2021; Time 2: early-January 2022). Results: Results indicated that (i) high psychological distress at Time 1 was associated with increased levels of PSMU and PG at Time 2. Inversely, PG at Time 1 was associated with increased psychological distress at Time 2, although PSMU at Time 1 did not have a significant influence on psychological distress at Time 2; (ii) during Time 1, increased administrative support contributed to alleviating teachers' psychological needs thwarting of online teaching, thereby lowering their psychological distress which, in turn, resulted in a decrease in PG. Conclusion: PG had a stronger negative influence on teachers' psychological distress than PSMU. To relieve teachers' PG, administrative support can alleviate teachers' psychological needs thwarting of online teaching and psychological distress. Based on this finding, school managers must consider effective ways to support teachers during mandatory online teaching.

A novel RBD-protein/peptide vaccine elicits broadly neutralizing antibodies and protects mice and macaques against SARS-CoV-2.

The development of safe and effective vaccines to respond to COVID-19 pandemic/endemic remains a priority. We developed a novel subunit protein-peptide COVID-19 vaccine candidate (UB-612) composed of: (i) receptor binding domain of SARS-CoV-2 spike protein fused to a modified single-chain human IgG1 Fc; (ii) five synthetic peptides incorporating conserved helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from SARS-CoV-2 structural proteins (three from S2 subunit, one from membrane and one from nucleocapsid), and one universal Th peptide; (iii) aluminum phosphate as adjuvant. The immunogenicity and protective immunity induced by UB-612 vaccine were evaluated in four animal models: Sprague-Dawley rats, AAV-hACE2 transduced BALB/c mice, rhesus and cynomolgus macaques. UB-612 vaccine induced high levels of neutralizing antibody and T-cell responses, in all animals. The immune sera from vaccinated animals neutralized the SARS-CoV-2 original wild-type strains and multiple variants of concern, including Delta and Omicron. The vaccination significantly reduced viral loads, lung pathology scores, and disease progression after intranasal and intratracheal challenge with SARS-CoV-2 in mice, rhesus and cynomolgus macaques. UB-612 has been tested in primary regimens in Phase 1 and Phase 2 clinical studies and is currently being evaluated in a global pivotal Phase 3 clinical study as a single dose heterologous booster.

Gender differences in the experience of burnout and its correlates among Chinese psychiatric nurses during the COVID-19 pandemic: A large-sample nationwide survey.

Psychiatric nurses often experience burnout and other mental health symptoms. However, few studies have examined these phenomena and gender-specific associated factors during the COVID-19 pandemic. We surveyed a national sample of psychiatric nurses (N = 8971) from 41 tertiary psychiatric hospitals in China as part of a large national survey conducted during the pandemic. The Maslach Burnout Inventory-Human Service Survey was used to assess burnout and the Depression, Anxiety, and Stress Scale-21 was used to assess mental health symptoms. Binary logistic regression analyses were used to explore factors associated with burnout in the entire sample and separately by gender. The overall prevalence of burnout was 27.27%, with the rate in male psychiatric nurses (32.24%) being significantly higher than that in female psychiatric nurses (25.97%). Many key demographic factors (such as the male gender and marital status), work-related variables (such as a mid-level professional title, having an administrative position, longer working hours, more monthly night shifts, and the perceived negative impact of the COVID-19 pandemic on medical work) were significantly associated with burnout in the whole sample. Moreover, burnout was associated with depression, anxiety, and stress symptoms in the whole sample. Gender-specific factors associated with burnout were also identified: burnout was associated with night shifts in male psychiatric nurses, whereas it was associated with single or married marital status, a mid-level professional title, and having an administrative position among female psychiatric nurses. The high rates of burnout and mental health symptoms in psychiatric nurses need attention from hospital administrators. While mental health symptoms, longer working hours, and the perceived impact of COVID-19 are associated with burnout in both genders, gender-specific factors also warrant special attention when developing gender-specific interventions.

Depression, Anxiety, Stress, and Their Associations With Quality of Life in a Nationwide Sample of Psychiatrists in China During the COVID-19 Pandemic.

Objectives: The COVID-19 pandemic has negatively affected wellbeing. However, the impact on the mental health status of Chinese psychiatrists and their relationship with quality of life (QOL) has not been examined. Methods: This was a national cross-sectional survey performed between January 11 and March 15, 2021. Demographic and work-related data were collected anonymously using an online questionnaire. Common mental health symptoms and QOL were assessed using the Depression Anxiety Stress Scale-Chinese version and the World Health Organization Quality of Life Schedule-Brief, respectively. Results: A total of 3,783 psychiatrists completed this questionnaire. The prevalence of depressive, anxious, and stress symptoms were 26.7% (95%CI = 25.3-28.1%), 24.1% (95%CI = 22.8-25.5%), and 11.6% (95%CI = 10-12%), respectively. Moreover, 11.1% of the participants endorsed both depressive and anxious symptoms, and 8% endorsed symptoms in all three domains. Binary logistic regression showed that aged 30-39 years (OR = 1.5, P = 0.03), male gender (OR = 1.2, P = 0.04), single (OR = 1.44, P = 0.01), and having a negative perception of the COVID-19 on healthcare (OR = 2.34, P <0.001) were factors associated with higher levels of depressive symptoms. Participants who were divorced and widowed (OR = 1.56, P = 0.03), worked more than 4 night shifts/month (OR = 1.33, P<0.001) and/or longer working years (OR = 1.71, P < 0.001), and had a negative perceived impact of the COVID-19 on healthcare (OR = 2.05, P < 0.001) were more inclined to experience anxious symptoms. In addition, psychiatrists with high QOL scores had lower odds of experiencing depressive, anxious, and stress symptoms (all P < 0.001). Multivariate analysis showed that the presence of each of the three types of mental health symptoms was independently associated with lower QOL (all P < 0.05). In addition, the depression × anxious × stress interaction was significantly correlated with lower QOL (P < 0.05). Conclusion: Approximately one-fourth of psychiatrists in China experienced depressive and anxious symptoms during the COVID-19 pandemic, and more than one-tenth reported stress. Mental health symptoms were significant contributors to lower QOL. The psychological wellbeing of psychiatrists during the pandemic requires more attention, and interventions are needed to improve the psychological wellbeing and QOL of physicians who care for individuals with mental disorders.

Turnover Intention and Its Associated Factors Among Psychiatrists in 41 Tertiary Hospitals in China During the COVID-19 Pandemic.

Background: Turnover intention, an employee's intention to voluntarily leave their jobs, affects workforce sustainability. However, scarce data are available about turnover intention and its associated factors among psychiatrists in China, especially during the COVID-19 pandemic. The current research was designed to address this gap. Methods: An anonymous, nationwide online survey was disseminated to psychiatrists in 41 psychiatric hospitals in China. We collected demographic data, job-related information (duration of employment, history of participation in the frontline work against COVID-19, job satisfaction), and participants' turnover intention in the next 12 months. Results: In total, 3,973 psychiatrists completed the survey. The sample was predominantly female (58.8%) and married (79.5%), and nearly three-fourths (73.5%) had children. More than one-third (35.6%) had a master's or doctoral degree in addition to their medical degree. The overall level of job satisfaction was moderate. The rate of turnover intention was 22.0% and was comparable in males and females (22.9% in males and 21.3% in females, respectively). Psychiatrists who had participated in the frontline work of COVID-19 were more likely to report an intention to leave their current job. Multiple regression analyses suggested that turnover intention was significantly associated with having insomnia, longer working hours, and more working days per week. Conclusion: During the pandemic period, approximately one-fifth of psychiatrists in China reported turnover intention. Factors associated with turnover intention included high job-related burdens, low job satisfaction, participation in the frontline work against COVID-19, and insomnia. To improve psychiatric workforce sustainability, policymakers and hospital administrators need to be aware of this potential challenge and address the concerns of psychiatrists in China.

A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants.

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Knowledge and attitudes of medical staff in Chinese psychiatric hospitals regarding COVID-19.

On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus COVID-19 a pandemic. There are patients in psychiatric hospitals in China who have been infected with COVID-19, however, the knowledge and attitudes of psychiatric hospital staff towards infectious diseases and their willingness to work during the COVID-19 outbreak has not yet been investigated. This study was performed to assess the knowledge and attitudes of medical staff in two Chinese mental health centers during the COVID-19 outbreak. We included 141 psychiatrists and 170 psychiatric nurses in the study. We found that during the COVID-19 epidemic, 89.51% of the medical staff of the psychiatric hospitals studied had extensive knowledge of COVID-19, and 64.63% of them received the relevant training in hospitals. Furthermore, about 77.17% of participants expressed a willingness to care for psychiatric patients suffering from COVID-19 virus infection. Independent predictors of willingness to care for patients included advanced training and experience of caring for patients with COVID-19. In conclusion, this study suggests that increased attention should be paid to the knowledge and attitudes of medical staff at psychiatric hospitals during the COVID-19 outbreak.