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Multiple severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) variants continue to evolve carrying flexible amino acid substitutions in the spike protein's receptor binding domain (RBD). These substitutions modify the binding of the SARS-CoV-2 to human angiotensin-converting enzyme 2 (hACE2) receptor and have been implicated in altered host fitness, transmissibility and efficacy against antibody therapeutics and vaccines. Reliably predicting the binding strength of SARS-CoV-2 variants RBD to hACE2 receptor and neutralizing antibodies (NAbs) can help assessing their fitness, and rapid deployment of effective antibody therapeutics, respectively. Here, we introduced a two-step computational framework with threefold validation that first identified dissociation constant as a reliable predictor of binding affinity in hetero-dimeric and -trimeric protein complexes. The second step implements dissociation constant as descriptor of the binding strengths of SARS-CoV-2 variants RBD to hACE2 and NAbs. Then, we examined several variants of concern (VOCs) such as Alpha, Beta, Gamma, Delta, and Omicron and demonstrated that these VOCs RBD bind to the hACE2 with enhanced affinity. Furthermore, the binding affinity of Omicron variant's RBD was reduced with majority of the RBD-directed NAbs, which is highly consistent with the experimental neutralization data. By studying the atomic contacts between RBD and NAbs, we revealed the molecular footprints of four NAbs (GH-12, P2B-1A1, Asarnow-3D11, and C118)-that may likely neutralize the recently emerged omicron variant-facilitating enhanced binding affinity. Finally, our findings suggest a computational pathway that could aid researchers identify a range of current NAbs that may be effective against emerging SARS-CoV-2 variants.
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Introduction Acute upper gastrointestinal bleeding (AUGIB) has an incidence between 84-172 per 100,000 people per year resulting in 50-70000 hospital admissions every year. Out -of-hours (OOH) endoscopy rotas for AUGIB are typically delivered by Consultant Gastroenterologists. Prior to the COVID-19 pandemic, the AUGIB OOH service was Specialty Registrar (SpR) led at Leeds Teaching Hospitals, and was felt to provide invaluable exposure and experience for SpRs in the endoscopic management of patients presenting with AUGIB. Following the start of the COVID pandemic, and subsequent redeployment of SpRs, the AUGIB OOH service has been a Consultant delivered one. The aim of this retrospective study was to compare the safety and efficacy of a SpR led OOH AUGIB service (2016 database) with a Consultant delivered service (2020-21 database) at the same trust. Methods We included adult patients (>16 years), presenting to LTHT between March and September 2016 with suspected AUGIB having an endoscopy procedure performed on a SpR led OOH rota and compared this with patients presenting with suspected AUGIB between September 2020 and March 2021 during which period the service was entirely consultant delivered. Baseline clinical, laboratory, admission Glasgow- Blatchford Score, demographic data, grade of endoscopist, place of endoscopy, findings of endoscopy and treatments applied were recorded. Primary outcome was 30-day mortality secondary to GI bleeding. Secondary outcomes included time to endoscopy and rebleed rate Results 177 patients from the 2016 database (62% male, median age 67, range 18-97) and 100 patients from the 2020-21 database (60% male, median age 63, range 18-96) were included in the study. 97.2% patients (2016) vs 93% (2020-21) had a GBS score ≥7. 30-day GI bleed related mortality was 2.89% (2016) vs 3% (2020-21) (p value 0.93). The median time to endoscopy was 16.3 hours (2016) vs 17.2 hours (2020-21). 8.9% (2016) vs 7% (2020-21) experienced a rebleed. Conclusions This study has shown that a Registrar led OOH AUGIB service has comparable outcomes to a Consultant delivered rota in important outcomes such as time to endoscopy and 30-day mortality. Where service configuration allows, a registrar led rota can aid in improving the standard of SpR training whilst also freeing up Consultants to undertake increased elective work and reduce the backlog created by the COVID-19 pandemic.
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Purpose of Study Emergency department (ED) visits for mental health (MH) concerns have increased over the past decade. While a sharp decrease was noted in overall ED volume at the start of the COVID-19 pandemic, the prevalence of visits for MH concerns was significantly higher compared to previous years. The objectives of this study were to assess the proportion and acuity of MH visits in the ED for patients aged 5-21 during the initial months of the COVID-19 pandemic compared to the previous three years. Methods Used A retrospective, cohort study was conducted in a suburban ED with 130,000 annual visits (2019) that includes a dedicated pediatric ED. Data was retrieved from the hospital's electronic medical records searching for MH chief complaints. Proportion of MH visits during the COVID- 19 pandemic year (Y4: March 1, 2020- February 28, 2021) was compared to the previous three rolling years (Y1: 2017- 18;Y2: 2018-19;Y3: 2019-20). Patients with substance abuse/ intoxication were excluded. High acuity was defined as patients presenting after intentional ingestion of a substance, direct physical harm requiring medical hospitalization, or presenting under an emergency/temporary custody order. Acuity was assessed through random sampling of each cohort. Outcomes were stratified by age: 5-13, 14-17, 18-21. Chi-square methods (including exact tests) were used to evaluate all frequency measures. All analyses were conducted using SAS software (v9.4, SAS Institute). Summary of Results During Y4, 1677 patients aged 5-21 with a MH chief complaint were identified, of whom 1505 patients met inclusion criteria. The proportion of ED visits for mental health concerns was 8.8%, compared with 4.25%, 5.07%, and 5.43% for Y1-Y3, respectively (p< 0.0001). The median age was 16 years, 74.3% were female, and 33.3% presented with high acuity. There were no statistically significant differences in overall acuity when compared to prior years. However, for the cohort aged 14-17 years, the proportion presenting with high acuity increased from Y1 to Y4 with a clinically significant increase from Y3 (14.1%) to Y4 (18.7%). Conclusions The proportion of MH encounters to the ED increased significantly during the pandemic year. Additionally, we saw a clinically significant increase in patients aged 14-17 presenting with high acuity. (Table Presented).
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Background: Stressful life events may lead to insomnia, a very common sleep disorder. Aim and Objectives: The aim of the study was to study the correlation of perceived stress levels and sleep quality among physicians during the coronavirus disease-19 Pandemic. Materials and Methods: Physicians working in Burdwan Medical College were selected as a study group and age, sex-matched controls were selected from other non-medical workers. This online survey was conducted using Google Forms. The form was shared with participants using emails and WhatsApp. In the first section of the form the importance of the study was explained and informed consent was taken from the participants. In the second part of the form, subjects were asked to fill up demographic details and relevant history;in the third part, participants were asked to fill up two scales: Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index (PSQI). Results: 128 doctors and 114 other staff participated in the present study. Doctors had significantly higher PSS and PSQI levels as compared to the other group. Doctors’ PSQI: Mean ± SD = 7.59 ± 4.37 and other staff PSQI: Mean ± SD = 5.77 ± 2.75;P: 0.00013**. Doctors’ PSS: 18.43 ± 4.04 and other staff PSS: 15.14 ± 1.7;P < 0.0001**. PSS and PSQI levels were positively correlated in both groups with r values of 0.975 for Doctors and 0.544 for other staff, respectively. Conclusions: Doctors were found to have higher PSS and PSQI levels as compared to the control group. PSS levels were found to be positively correlated with PSQI levels and more so among doctors.
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Corona Virus Disease (COVID-19) pandemic is a challenge to the healthcare system including urology which is big and formidable. The present scenario has changed the health preferences to emergency and essential services only. Reallocation of healthcare providers, wards and equipments resulted in suspension of all outpatient and elective activities to select only non-deferrable and critical procedures. Consequently, all health care workers including urologists must abide by the recommendations when dealing with the COVID-19 patients. This pandemic has also disrupted the training and education programs of urology residents also. Subsequently, in this review article, authors have discussed the influence of COVID-19 on urological practice. Authors have also reviewed the recommendations on triaging of urology procedures (emergent and non-emergent), office based urological procedures, oncologic surgeries, paediatric urology, urology-pathology interaction and economic burden on healthcare system during COVID-19 pandemic.