Prescribing Antibiotics in Public Primary Care Clinics in Singapore: A Retrospective Cohort Study.

BACKGROUND: Antibiotic prescription practices in primary care in Singapore have received little scholarly attention. In this study, we ascertained prescription prevalence and identified care gaps and predisposing factors. METHODS: A retrospective study was conducted on adults (>21 years old) at six public primary care clinics in Singapore. Prescriptions >14 days were excluded. Descriptive statistics were used to showcase the prevalence data. We used chi-square and logistic regression analyses to identify the factors affecting care gaps. RESULTS: A total of 141,944 (4.33%) oral and 108,357 (3.31%) topical antibiotics were prescribed for 3,278,562 visits from 2018 to 2021. There was a significant reduction in prescriptions (p < 0.01) before and after the pandemic, which was attributed to the 84% reduction in prescriptions for respiratory conditions. In 2020 to 2021, oral antibiotics were most prescribed for skin (37.7%), genitourinary (20.2%), and respiratory conditions (10.8%). Antibiotic use in the "Access" group (WHO AWaRe classification) improved from 85.6% (2018) to 92.1% (2021). Areas of improvement included a lack of documentation of reasons for antibiotic use, as well as inappropriate antibiotic prescription for skin conditions. CONCLUSION: There was a marked reduction in antibiotic prescriptions associated with the onset of the COVID-19 pandemic. Further studies could address the gaps identified here and evaluate private-sector primary care to inform antibiotic guidelines and the local development of stewardship programs.

Comprehensive Bioinformatics analysis of angiotensin-converting enzyme 2 (ACE2) (preprint)

ACE2, a member of the angiotensin converting enzyme family, plays an irreplaceable role in the renin-angiotensin system. And the variations of ACE2 are regarded as the key factor to human diseases such as the novel coronavirus pneumonia, cardiovascular disease, and tumors. Here, we summarized the mutation, expression, modification and function of the human ACE2 based on comprehensive bioinformatics analysis. Especially, the relationship between ACE2 expression and diseases, especially tumor was further discussed. ACE2 is highly conserved in different genera and families. We explored the correlation between ACE2 and disease based on the datasets of GCBI and GEO (Gene expression omnibus), and found the expression of ACE2 is related to heart failure. High prevalence of ACE2 mutations is observed in diffuse large B-cell lymphoma, uterine carcinosarcoma (UCS), and stomach adenocarcinoma (STAD). We first identified that highly expressed of ACE2 was linked to poor prognosis of overall survival for tumors of brain lower grade glioma (LGG). Specially, the expression level of ACE2 in kidney-related tumor tissues is much higher than that of normal kidney tissues. ACE2 is negatively correlated with the infiltration level of cancer-associated fibroblasts in most kinds of cancers, such as uterine corpus endometrial carcinoma (UCEC), esophageal carcinoma (ESCA), ovarian serous cystadenocarcinoma (OV) and kidney renal clear cell carcinoma (KIRC); positively correlation in testicular germ cell tumors (TGCT). The different phosphorylation sites of ACE2 were analyzed in CPTAC dataset, and the DNA methylation of ACE2 in colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), and rectum adenocarcinoma (READ) was lower than that of normal control by using SMART database. Moreover, we summarized the interaction proteins and targeted miRNAs of ACE2 through bioinformatics. Then we found the endocrine process and the regulation of systemic arterial blood pressure were involved in the functional mechanisms of ACE2 by using KEGG and GO analysis. Our study offers a relatively comprehensive understanding of ACE2.

Beneficial for mental health, exercise more or less?

Regular physical activity may improve mental health during the pandemic by reducing inflammatory responses. However, overtraining or prolonged exercise training may adversely affect mental health.

Evaluating the immediate and delayed effects of psychological need thwarting of online teaching on Chinese primary and middle school teachers' psychological well-being.

Recent studies on the effects of mandatory online teaching, resulting from the COVID-19 pandemic, have widely reported low levels of satisfaction, unwillingness to continue online teaching, and negative impacts on the psychological well-being of teachers. Emerging research has highlighted the potential role of psychological need thwarting (PNT), in terms of autonomy, competence, and relatedness thwarting, resulting from online teaching. The aim of this study was to evaluate the immediate and delayed (longitudinal) effects of PNT of online teaching on teachers' well-being (including distress and burnout), intention to continue online teaching, and job satisfaction. Moreover, data collected from both cross-sectional and longitudinal surveys allowed for a systematic validation of an important instrument in the field of teacher psychology, the Psychological Need Thwarting Scale of Online Teaching (PNTSOT), in terms of longitudinal reliability and validity. The data reveal the usefulness of the construct of PNT in terms predicting and explaining teachers' willingness to continue using online teaching as well as the degree of burnout after a period of 2 months, such that PNT is positively associated with burnout and negatively associated with willingness to continue online teaching. As such, the PNTSOT is recommended for future research evaluating the long-term psychological, affective, and intentional outcomes stemming from teachers' PNT. Moreover, based on our findings that the impact from PNT of online teaching is persistent and long-term, we suggest that school leaders provide flexible and sustained professional development, model respectful and adaptive leadership, and create opportunities for mastery for the development of community of practice that can mitigate the thwarting of teachers' autonomy, competence, and relatedness during times of uncertainty. Additionally, in terms of the psychometric properties of the PNTSOT instrument, our empirical findings demonstrate internal reliability, test-retest reliability, measurement invariance, and criterion validity (concurrent and predictive) based on cross-sectional and longitudinal data.

Setting Bias Specifications Based on Qualitative Assays With a Quantitative Cutoff Using COVID-19 as a Disease Model.

OBJECTIVES: Automated qualitative serology assays often measure quantitative signals that are compared against a manufacturer-defined cutoff for qualitative (positive/negative) interpretation. The current general practice of assessing serology assay performance by overall concordance in a qualitative manner may not detect the presence of analytical shift/drift that could affect disease classifications. METHODS: We describe an approach to defining bias specifications for qualitative serology assays that considers minimum positive predictive values (PPVs) and negative predictive values (NPVs). Desirable minimum PPVs and NPVs for a given disease prevalence are projected as equi-PPV and equi-NPV lines into the receiver operator characteristic curve space of coronavirus disease 2019 serology assays, and the boundaries define the allowable area of performance (AAP). RESULTS: More stringent predictive values produce smaller AAPs. When higher NPVs are required, there is lower tolerance for negative biases. Conversely, when higher PPVs are required, there is less tolerance for positive biases. As prevalence increases, so too does the allowable positive bias, although the allowable negative bias decreases. The bias specification may be asymmetric for positive and negative direction and should be method specific. CONCLUSIONS: The described approach allows setting bias specifications in a way that considers clinical requirements for qualitative assays that measure signal intensity (eg, serology and polymerase chain reaction).

A Tri-Channel Oxide Transistor Concept for the Rapid Detection of Biomolecules Including the SARS-CoV-2 Spike Protein.

Solid-state transistor sensors that can detect biomolecules in real time are highly attractive for emerging bioanalytical applications. However, combining upscalable manufacturing with the required performance remains challenging. Here, an alternative biosensor transistor concept is developed, which relies on a solution-processed In2 O3 /ZnO semiconducting heterojunction featuring a geometrically engineered tri-channel architecture for the rapid, real-time detection of important biomolecules. The sensor combines a high electron mobility channel, attributed to the electronic properties of the In2 O3 /ZnO heterointerface, in close proximity to a sensing surface featuring tethered analyte receptors. The unusual tri-channel design enables strong coupling between the buried electron channel and electrostatic perturbations occurring during receptor-analyte interactions allowing for robust, real-time detection of biomolecules down to attomolar (am) concentrations. The experimental findings are corroborated by extensive device simulations, highlighting the unique advantages of the heterojunction tri-channel design. By functionalizing the surface of the geometrically engineered channel with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody receptors, real-time detection of the SARS-CoV-2 spike S1 protein down to am concentrations is demonstrated in under 2 min in physiological relevant conditions.

The Effect of Primary and Middle School Teachers' Problematic Internet Use and Fear of COVID-19 on Psychological Need Thwarting of Online Teaching and Psychological Distress.

Problematic Internet use (PIU) is a risk factor for psychological distress during COVID-19, as teachers are a psychologically vulnerable population. We explored the role of PIU in terms of primary and middle school teachers' fear of COVID-19 and psychological need thwarting (PNT) of online teaching. We empirically evaluated the relationships among these research variables in explaining teachers' psychological distress during COVID-19. Online survey data were collected from 9030 teachers. A high proportion of participants demonstrated psychological distress: depression (20.4%), anxiety (26.4%), and stress (10.2%). Structural equation modeling was used to test our proposed conceptual model, wherein PIU behaviors served as predictors, mediated by fear of COVID-19 and PNT of online teaching, for teachers' psychological distress. With ideal model fit, the results of the path coefficients indicated that PIU behaviors were associated with fear of COVID-19 (p < 0.001); fear of COVID-19 and PNT of online teaching were associated with psychological distress (p < 0.001); and fear of COVID-19 was also positively associated with PNT of online teaching (p < 0.001). PSU and PSMU had an indirect positive effect on psychological distress through the mediator of fear of COVID-19 and PNT of online teaching. As such, we suggest that school administrators pay greater attention to teachers' psychological needs through efforts to enhance teachers' autonomy and relatedness from interpersonal relationships, alleviating PNT of online teaching. Our PNT of online teaching scale may also serve as a contribution for further research and practice.

Detection of Microbial Agents in Oropharyngeal and Nasopharyngeal Samples of SARS-CoV-2 Patients.

The novel coronavirus outbreak started in December 2019 and rapidly spread around the globe, leading to a global pandemic. Here we reported the association of microbial agents identified in oropharyngeal and nasopharyngeal samples from patients with SARS-CoV-2 infection, using a Pan-microarray based technology referred to as PathoChIP. To validate the efficiency of PathoChIP, reference viral genomes obtained from BEI resource and 25 SARS-CoV-2 positive clinical samples were tested. This technology successfully detected femtogram levels of SARS-CoV-2 viral RNA, which demonstrated greater sensitivity and specificity than conventional diagnostic techniques. Simultaneously, a broad range of other microorganisms, including other viruses, bacteria, fungi and parasites can be detected in those samples. We identified 7 viral, 12 bacterial and 6 fungal agents common across all clinical samples suggesting an associated microbial signature in individuals who are infected with SARS-CoV-2. This technology is robust and has a flexible detection methodology that can be employed to detect the presence of all human respiratory pathogens in different sample preparations with precision. It will be important for differentiating the causative agents of respiratory illnesses, including SARS-CoV-2.

Pre-existing Health Conditions and Epicardial Adipose Tissue Volume: Potential Risk Factors for Myocardial Injury in COVID-19 Patients.

Background: Myocardial injury is a life-threatening complication of coronavirus disease 2019 (COVID-19). Pre-existing health conditions and early morphological alterations may precipitate cardiac injury and dysfunction after contracting the virus. The current study aimed at assessing potential risk factors for COVID-19 cardiac complications in patients with pre-existing conditions and imaging predictors. Methods and Results: The multi-center, retrospective cohort study consecutively enrolled 400 patients with lab-confirmed COVID-19 in six Chinese hospitals remote to the Wuhan epicenter. Patients were diagnosed with or without the complication of myocardial injury by history and cardiac biomarker Troponin I/T (TnI/T) elevation above the 99th percentile upper reference limit. The majority of COVID-19 patients with myocardial injury exhibited pre-existing health conditions, such as hypertension, diabetes, hypercholesterolemia, and coronary disease. They had increased levels of the inflammatory cytokine interleukin-6 and more in-hospital adverse events (admission to an intensive care unit, invasive mechanical ventilation, or death). Chest CT scan on admission demonstrated that COVID-19 patients with myocardial injury had higher epicardial adipose tissue volume ([EATV] 139.1 (83.8-195.9) vs. 92.6 (76.2-134.4) cm2; P = 0.036). The optimal EATV cut-off value (137.1 cm2) served as a useful factor for assessing myocardial injury, which yielded sensitivity and specificity of 55.0% (95%CI, 32.0-76.2%) and 77.4% (95%CI, 71.6-82.3%) in adverse cardiac events, respectively. Multivariate logistic regression analysis showed that EATV over 137.1 cm2 was a strong independent predictor for myocardial injury in patients with COVID-19 [OR 3.058, (95%CI, 1.032-9.063); P = 0.044]. Conclusions: Augmented EATV on admission chest CT scan, together with the pre-existing health conditions (hypertension, diabetes, and hyperlipidemia) and inflammatory cytokine production, is associated with increased myocardial injury and mortality in COVID-19 patients. Assessment of pre-existing conditions and chest CT scan EATV on admission may provide a threshold point potentially useful for predicting cardiovascular complications of COVID-19.

The influence of pre-existing hypertension on coronavirus disease 2019 patients.

Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21% vs. 10%, P = 0.007). Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.

Pathogenesis and management of myocardial injury in coronavirus disease 2019.

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a major health crisis and a worldwide pandemic. COVID-19 is characterized by high infectivity, long incubation period, diverse clinical presentations, and strong transmission intensity. COVID-19 can cause myocardial injury as well as other cardiovascular complications, particularly in senior patients with pre-existing medical conditions. The current review summarizes the epidemiological characteristics, potential mechanisms, clinical manifestations, and recent progress in the management of COVID-19 cardiovascular complications.

Pathophysiological characteristics and therapeutic approaches for pulmonary injury and cardiovascular complications of coronavirus disease 2019.

The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major health crisis, with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) having infected over a million people around the world within a few months of its identification as a human pathogen. Initially, SARS-CoV-2 infects cells in the respiratory system and causes inflammation and cell death. Subsequently, the virus spreads out and damages other vital organs and tissues, triggering a complicated spectrum of pathophysiological changes and symptoms, including cardiovascular complications. Acting as the receptor for SARS-CoV entering mammalian cells, angiotensin converting enzyme-2 (ACE2) plays a pivotal role in the regulation of cardiovascular cell function. Diverse clinical manifestations and laboratory abnormalities occur in patients with cardiovascular injury in COVID-19, characterizing the development of this complication, as well as providing clues to diagnosis and treatment. This review provides a summary of the rapidly appearing laboratory and clinical evidence for the pathophysiology and therapeutic approaches to COVID-19 pulmonary and cardiovascular complications.