Effectiveness of Casirivimab and Imdevimab Antibody Combination in Immunocompromised Hospitalized Patients With Coronavirus Disease 2019: A Post Hoc Analysis in a Phase 1/2/3 Double-Blind Trial.

Background: Individuals who are immunocompromised (IC) are at high risk for severe coronavirus disease 2019 (COVID-19). Methods: Post hoc analyses of a double-blind trial conducted prior to Omicron (June 2020-April 2021), in hospitalized patients with COVID-19 assessed viral load, clinical outcomes, and safety of casirivimab plus imdevimab (CAS + IMD) versus placebo in IC versus overall study patients. Results: Ninety-nine of 1940 (5.1%) patients were IC. IC versus overall patients were more frequently seronegative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies (68.7% vs 41.2%) and had higher median baseline viral loads (7.21 vs 6.32 log10 copies/mL). On placebo, IC versus overall patients had slower viral load declines. CAS + IMD reduced viral load in IC and overall patients; least-squares mean difference versus placebo in time-weighted average change from baseline viral load at day 7 was -0.69 (95% confidence interval [CI], -1.25 to -.14) log10 copies/mL for IC patients and -0.31 (95% CI, -.42 to -.20) log10 copies/mL for overall patients. For IC patients, the cumulative incidence of death or mechanical ventilation at day 29 was lower with CAS + IMD (11.0%) versus placebo (17.2%), consistent with overall patients (15.7% CAS + IMD vs 18.3% placebo). IC and overall patients receiving CAS + IMD exhibited similar rates of treatment-emergent adverse events (30.4% and 26.6%, respectively), grade ≥2 hypersensitivity or infusion-related reactions (1.4% and 2.5%), and deaths (8.7% and 12.2%). Conclusions: IC patients were more likely to exhibit high viral loads and be seronegative at baseline. For susceptible SARS-CoV-2 variants, CAS + IMD reduced viral load and resulted in fewer death or mechanical ventilation events in IC and overall study patients. There were no new safety findings among IC patients. Clinical Trials Registration. NCT04426695.

The Effect of Combining the COVID-19 Vaccine with the Seasonal Influenza Vaccine on Reducing COVID-19 Vaccine Rejection Among Libyans.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine coverage remains low in Libya compared to other countries in the Eastern Mediterranean Region. This study aimed to evaluate the willingness of the general public in Libya to receive COVID-19 and seasonal influenza vaccines. Additionally, the study aimed to investigate the potential effect of combining the two vaccines to reduce COVID-19 vaccine rejection. METHODS: An anonymous nationwide online cross-sectional survey was carried out from 1st September to 16th October 2022. Libyans aged 18 years or older were recruited using convenience and snowball sampling approaches. The participants were surveyed for sociodemographic information, health status, and vaccination attitude towards COVID-19 and seasonal influenza vaccines. RESULTS: A total of 2484 participants formed the final study sample: 68.7% were females, 39.4% were aged 18-25 years, 50.4% were single, 32.5% had previous COVID-19 infection, and 47.2% experienced COVID-19 death among relatives. Three-fourths of the respondents showed COVID-19 vaccine rejection: 57.3% did not receive COVID-19 vaccination, 10.1% would not complete the primary vaccination series, and 7.8% refused booster doses. About 55.0% rejected seasonal influenza vaccination, while 1.9% reported influenza vaccine uptake and 21.2% were willing to get the influenza vaccine for the first time. Additionally, 18.8% had already received influenza vaccination in the last year and intended to get the vaccine this season, while 3.3% were unwilling to get influenza vaccination this year despite receiving it in the last influenza season. Age, sex, and occupation were significantly associated with COVID-19 and influenza vaccine rejection. Rejection of COVID-19 vaccination decreased if its combination with influenza vaccine as a single dose was suggested, with 28.2% of the COVID-19 vaccine rejector group accepting the combined vaccine as it would be safer (50.9%), needing fewer injections (24.0%), would be more effective (19.1%), and would be less expensive (3%). Approximately 73.0% of the COVID-19 vaccine rejector group refused this combination due to fear of side effects (48.7%), absence of published studies on this combination (29.8%), and considering this combination as useless (11.2%). CONCLUSION: In Libya, the prevalence of COVID-19 vaccine rejection was high, while the rejection of seasonal influenza vaccination was relatively lower. If influenza and COVID-19 vaccines are administered simultaneously as a single injection, this may reduce the rejection of the COVID-19 vaccine due to better-perceived vaccine safety and efficacy besides being more convenient in terms of the number of injections and cost.

Common coronary artery occlusions in patients with myocardial infarction.

Introduction: coronary artery disease (CAD) is a significant cardiovascular disease (CVD) that affects people worldwide. This study aimed to determine the main occluded coronary arteries in patients with myocardial infarction in Najran, Kingdom of Saudi Arabia (KSA). Methods: a retrospective cross-sectional study conducted between March 2020 and March 2021 and involving 661 myocardial infarction patients recruited from two hospitals (King Khalid Hospital and Prince Sultan Centre for Healthcare in Najran) used sampling for enrolled patients. Patients over the age of 15 years, current residents of KSA, and diagnosed with coronary artery occlusion based on at least one identifiable coronary lesion on a coronary angiography were considered eligible. We created generalized linear mixed models to investigate patients´ clinical and coronary angiographic features and identify statistically relevant components. Results: there were 661 CAD cases in this study: 548 (82.9%) males and 113 (17.1%) females, with a mean and standard deviation (SD) age of 4.03 ± 1.370 years. Ages of the 661 participants ranged from 15 to 85, who had been diagnosed with myocardial infarction were evaluated. It was found that most of the patients were in the 55-64 age range. The majority of cases (366 (55.4%) had ST-segment elevation myocardial infarction (STEMI), 187 (28.3%) had non-ST-segment elevation (NSTEMI), 101 (15.3%) had acute coronary syndrome-non-ST-segment elevation (ACS-NSTEMI), and 7 (1.1%) had acute coronary syndrome-ST-segment elevation (ACS-STEMI). Conclusion: the left anterior descending artery (LAD) is the commonest lesion found in both ST-segment elevation and non-ST-segment elevation myocardial infarction patients.

Real-world effectiveness of casirivimab and imdevimab among patients diagnosed with COVID-19 in the ambulatory setting: a retrospective cohort study using a large claims database.

OBJECTIVE: To assess the real-world effectiveness of casirivimab and imdevimab (CAS+IMD) versus no COVID-19 antibody treatment among patients diagnosed with COVID-19 in the ambulatory setting, including patients diagnosed during the Delta-dominant period prior to Omicron emergence. DESIGN: Retrospective cohort study. SETTING: Komodo Health closed claims database. PARTICIPANTS: 13 273 128 patients diagnosed with COVID-19 (December 2020 through September 2021) were treated with CAS+IMD or untreated but treatment eligible under the Emergency Use Authorization (EUA). Each treated patient was exact and propensity score matched without replacement to up to five untreated EUA-eligible patients. INTERVENTIONS: CAS+IMD. PRIMARY AND SECONDARY OUTCOME MEASURES: Composite endpoint of 30-day all-cause mortality or COVID-19-related hospitalisation. Kaplan-Meier estimators were used to calculate outcome risks overall and across subgroups: age, COVID-19 vaccination status, immunocompromised status, and timing of diagnosis (December 2020 to June 2021, and July to September 2021). Cox proportional hazards models were used to estimate adjusted HRs (aHRs) and 95% CIs. RESULTS: Among 75 159 CAS+IMD-treated and 1 670 338 EUA-eligible untreated patients, 73 759 treated patients were matched to 310 688 untreated patients; matched patients were ~50 years, ~60% were women and generally well balanced across risk factors. The 30-day risk of the composite outcome was 2.1% and 5.2% in the CAS+IMD-treated and CAS+IMD-untreated patients, respectively; equivalent to a 60% lower risk (aHR 0.40; 95% CI, 0.38 to 0.42). The effect of CAS+IMD was consistent across subgroups, including those who received a COVID-19 vaccine (aHR 0.48, 95% CI, 0.41 to 0.56), and those diagnosed during the Delta-dominant period (aHR 0.40, 95% CI, 0.38 to 0.42). CONCLUSIONS: The real-world effectiveness of CAS+IMD is consistent with the efficacy for reducing all-cause mortality or COVID-19-related hospitalisation reported in clinical trials. Effectiveness is maintained across patient subgroups, including those prone to breakthrough infections, and was effective against susceptible variants including Delta. .

Final-Year Nursing Students' Experiences During the COVID-19 Pandemic: A Scoping Review.

BACKGROUND: The transitional experience from final-year nursing students (FYNS) to newly graduated RNs (NGRN) challenges individuals' professional and personal identities. Multiple studies have documented the experiences of FYNS graduating in the pandemic, but no studies have synthesized the findings. METHOD: This scoping review examined the barriers and facilitators FYNS experience as they transitioned to become NGRN during the coronavirus disease 2019 (COVID-19) pandemic. Databases were searched for relevant articles, and articles published in peer-reviewed journals between 2019 and 2021 that focused on the support of FYNS in clinical settings in North America, Europe, and Australia were included. RESULTS: Three themes were identified: emotional turmoil and coping, clinical competence and readiness for practice, and teaching strategies. CONCLUSION: This review revealed important insight on how the pandemic affected FYNS' transition to practice and identified gaps in the literature for future research. [J Nurs Educ. 2023;62(1):6-11.].

Cost-effectiveness of casirivimab/imdevimab in patients with COVID-19 in the ambulatory setting.

BACKGROUND: Most patients infected with SARS-CoV-2, resulting in COVID-19, have only mild symptoms that can be managed in an ambulatory setting. However, a significant number of patients develop a more severe form of the disease and require hospital care, with the risk of long-term sequelae or death. Casirivimab/imdevimab is a combination of 2 recombinant human monoclonal antibodies that has been shown to significantly reduce the risk of hospitalization or death in patients with mild to moderate COVID-19 in the ambulatory setting. OBJECTIVE: To establish the cost-effectiveness of casirivimab/imdevimab in ambulatory individuals with COVID-19. METHODS: A cost-effectiveness model was constructed to simulate the natural history of COVID-19 in ambulatory patients and to identify those patients for whom casirivimab/imdevimab may be a cost-effective treatment from a US payer perspective. Patients enter the model in the ambulatory health state and can receive either active treatment with casirivimab/imdevimab or usual care. Patients can either recover from the infection or be hospitalized, from where they can recover from infection or die. Following this acute phase, patients enter a Markov model to estimate lifetime quality-adjusted life years. The model uses the risk of hospitalization in both the active treatment and usual care cohorts, and age- and sex-specific risk of mortality. Other model inputs include hospitalization costs and health-related utilities in the ambulatory acute treatment phase, the hospitalized setting, and the post-acute phase. Accounting for the heterogeneity of risk by age and comorbidities, results are presented separately for various combinations of baseline age and usual care risk in a 7 × 9 matrix. Outcomes related to "long COVID" are assessed in scenario analyses. RESULTS: In the base case, at a willingness-to-pay threshold of $100,000, treatment with casirivimab/imdevimab was found to be cost-effective in most patients, including those older than 40 years of age with a baseline hospitalization risk greater than or equal to 2% and patients aged 20 years with a baseline risk of hospitalization greater than or equal to 4%, whereas for hospitalization risk greater than or equal to 10%, casirivimab/imdevimab is dominant. Casirivimab/imdevimab was not cost-effective in patients aged 20 years with a 3% or lower risk of hospitalization or in patients aged 30 years with a 2% risk. CONCLUSIONS: This economic analysis found that casirivimab/imdevimab is a cost-effective treatment for most ambulatory patients with COVID-19. DISCLOSURES: N. Jovanoski and U. Becker are employees of F Hoffman-La Roche Ltd.; A. Kuznik and M. Hussein are employees of Regeneron Pharmaceuticals Inc. and hold stock and stock options; A. Briggs has provided consultancy to F Hoffman-La Roche Ltd. and has received consultancy fees from Merck and Co., Inc., GlaxoSmithKline plc., and Novartis. This study was funded by Regeneron Pharmaceuticals, Inc.

Reliability and Validity of an Instrument of COVID-19 Patient-Reported Symptoms in Outpatients.

Importance: Patient-reported outcome instruments are key in assessing COVID-19-related symptoms and associated burden. However, a valid and reliable instrument to assess symptom severity and progression among outpatients with COVID-19 is not yet available. Objectives: To assess the extent to which the Symptoms Evolution of COVID-19 (SE-C19) instrument is valid, reliable, and able to detect symptom changes in outpatients with COVID-19, as well as to establish a definition of symptom resolution. Design, Setting, and Participants: In this diagnostic/prognostic study, psychometric properties of SE-C19 were assessed in participants recruited into an ongoing, adaptive, phase 1/2/3, randomized, double-blind, placebo-controlled clinical trial, during 2020 to 2022. Adult outpatients with symptomatic COVID-19 were randomized 1:1:1 to receive 2.4 g or 8.0 g intravenous casirivimab and imdevimab or placebo, in outpatient centers at 114 sites, from 2 countries (US and Mexico). Main Outcomes and Measures: Reliability, validity, and sensitivity to change of the SE-C19 were assessed. SE-C19 and Patient Global Impression of Severity (PGIS) were administered daily from predose at day 1 to day 29. Results: Analysis was conducted on 657 adult outpatients (342 female patients [52.1%], 562 White patients [85.5%]), and 337 non-Hispanic patients [51.3%]. At baseline, patients reported a mean (SD) of 6.6 (3.9) symptoms (ie, rated as at least mild) with a mean (SD) of 3.8 (3.3) of these symptoms being rated as moderate or severe. Stable patients according to PGIS showed scores with intraclass correlation values indicating moderate-to-good test-retest reliability (ie, 0.50-0.90). At baseline, 20 item scores (87%) varied significantly across PGIS-defined groups, supporting the validity of the SE-C19. A symptom-resolution end point was defined after excluding the item sneezing due to its low ability to discriminate severity levels, and excluding confusion, rash, and vomiting, due to their low prevalence in this population. Symptom resolution required complete absence of all remaining items, except cough, fatigue, and headache, which could be mild or moderate in severity. A total of 19 of 23 items from the SE-C19 instrument were identified as valid and reliable to measure disease-related symptoms in outpatients with COVID-19. Conclusions and Relevance: This study identified 19 items that are valid and reliable to measure disease-related symptoms in outpatients with COVID-19, and proposed a definition of symptom resolution for potential use in future clinical trials.

Effectiveness of Subcutaneous Casirivimab and Imdevimab in Ambulatory Patients with COVID-19.

INTRODUCTION: Data on real-world effectiveness of subcutaneous (SC) casirivimab and imdevimab (CAS+IMD) for the treatment of coronavirus disease 2019 (COVID-19) are limited. The objective of this study was to assess the effectiveness of SC CAS+IMD versus no antibody treatment among patients with COVID-19. METHODS: This retrospective cohort study linked Komodo Health and CDR Maguire Health and Medical data. Patients diagnosed with COVID-19 in ambulatory settings (August 1-October 30, 2021) treated with SC CAS+IMD were exact- and propensity score-matched to fewer than five untreated treatment-eligible patients and followed for the composite endpoint of 30-day all-cause mortality or COVID-19-related hospitalization. Kaplan-Meier estimators were used to calculate outcome risk overall and across subgroups. Cox proportional-hazards models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: Of 13,522 patients treated with CAS+IMD, 12,972 were matched to 41,848 untreated patients. The 30-day composite outcome risk was 1.9% (95% CI 1.7-2.2) and 4.4% (95% CI 4.2-4.6) in the treated and untreated cohorts, respectively; treated patients had a 49% lower relative risk of the composite outcome (aHR 0.51; 95% CI 0.46-0.58) and a 67% relative risk of 30-day mortality (aHR 0.33, 95% CI 0.18-0.60). Effectiveness was consistent across vaccination status and various subgroups. DISCUSSION: Patients with COVID-19 benefitted from treatment with SC CAS+IMD versus untreated patients. The results were consistent across subgroups of patients, including older adults, immunocompromised patients, and patients vaccinated against COVID-19. Results were robust across numerous sensitivity analyses. CONCLUSION: SC CAS+IMD is effective in reducing 30-day COVID-19-related hospitalization or mortality in real-world outpatient settings during the Delta-dominant period.

Acceptance of COVID-19 Vaccine Booster Doses Using the Health Belief Model: A Cross-Sectional Study in Low-Middle- and High-Income Countries of the East Mediterranean Region.

Coronavirus disease (COVID-19) booster doses decrease infection transmission and disease severity. This study aimed to assess the acceptance of COVID-19 vaccine booster doses in low, middle, and high-income countries of the East Mediterranean Region (EMR) and its determinants using the health belief model (HBM). In addition, we aimed to identify the causes of booster dose rejection and the main source of information about vaccination. Using the snowball and convince sampling technique, a bilingual, self-administered, anonymous questionnaire was used to collect the data from 14 EMR countries through different social media platforms. Logistic regression analysis was used to estimate the key determinants that predict vaccination acceptance among respondents. Overall, 2327 participants responded to the questionnaire. In total, 1468 received compulsory doses of vaccination. Of them, 739 (50.3%) received booster doses and 387 (26.4%) were willing to get the COVID-19 vaccine booster doses. Vaccine booster dose acceptance rates in low, middle, and high-income countries were 73.4%, 67.9%, and 83.0%, respectively (p < 0.001). Participants who reported reliance on information about the COVID-19 vaccination from the Ministry of Health websites were more willing to accept booster doses (79.3% vs. 66.6%, p < 0.001). The leading causes behind booster dose rejection were the beliefs that booster doses have no benefit (48.35%) and have severe side effects (25.6%). Determinants of booster dose acceptance were age (odds ratio (OR) = 1.02, 95% confidence interval (CI): 1.01-1.03, p = 0.002), information provided by the Ministry of Health (OR = 3.40, 95% CI: 1.79-6.49, p = 0.015), perceived susceptibility to COVID-19 infection (OR = 1.88, 95% CI: 1.21-2.93, p = 0.005), perceived severity of COVID-19 (OR = 2.08, 95% CI: 137-3.16, p = 0.001), and perceived risk of side effects (OR = 0.25, 95% CI: 0.19-0.34, p < 0.001). Booster dose acceptance in EMR is relatively high. Interventions based on HBM may provide useful directions for policymakers to enhance the population's acceptance of booster vaccination.

Seeking autonomy: Grounded theory of clinical reasoning processes during simulation based experiences.

AIM: To conceptualize how undergraduate nursing students' reason and think during Simulation-Based experiences (SBE) and explore the indicators of sound clinical judgment. BACKGROUND: Nursing students' clinical reasoning processes during Simulation Based Experiences (SBE) are not well understood and underexplored. The purpose of this study is to conceptualize how undergraduate nursing students' reason and think during SBE. DESIGN: A constructivist grounded theory methodology was used to explore nursing students' clinical reasoning during SBE METHOD: A grounded theory methodology was used to explore nursing students' clinical reasoning during SBE. A purposive sample was used to recruit participants including 32 third-year nursing students. Data collection using semi-structured interviews conducted over 9 months in 2020-2021. The interviews were recorded and transcribed verbatim and the data were analyzed using the logic of constant comparison supported by memoing, theoretical sampling and conceptual mapping. RESULTS: Seeking autonomy is the core category that emerged from the participants' responses that conceptualizes the students' reasoning process during SBEs. CONCLUSION: Evidence from this grounded theory study adds validation to the practice of using SBEs to support students' clinical reasoning process and prepare them to be competent in clinical practice.

Assessing the Combined Public Health Impact of Pharmaceutical Interventions on Pandemic Transmission and Mortality: An Example in SARS CoV-2.

To assess the combined role of anti-viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission and mortality in the United States, an agent-based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID-19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April-August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non-pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID-19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment-as-prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS-CoV-2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness.

Impact of Non-viral Coinfections on Mortality of Severely Ill COVID-19 Patients in Dubai

Background: Coronavirus disease 2019 (COVID-19) infections may have been associated with secondary infection. Community-acquired or hospital-acquired such infections affect clinical outcomes. We performed a retrospective study to evaluate the impact of these infections on clinical outcomes. Methods: This was a retrospective analysis of all consecutive patients with COVID-19 admitted to the intensive care unit (ICU) of Dubai hospital. Results: Patients with secondary non-viral infections (SNIs) have higher mortality than patients without SNIs (57.3% vs. 43.7%, p=0.037). Patients with SNIs had more days on mechanical ventilation (MV) 19(11-27) vs. 5(2-10) p<0.001, more LOSICU 22 (15-33) vs. 7 (2-11) p<0.001, and more length of stay in hospital (LOSH) 28 (18-45) vs. 11.5 (6-19), p<0.001. Multiple logistic regression analyses showed that SNIs do not predict mortality. Linear logistic regression analysis showed patients with SNIs have increased length of stay in ICUs (LOSICUs), length of stay in hospitals (LOSHs), and prolonged needs for MV. Conclusion: SNIs are high in patients admitted to ICU for COVID-19 acute respiratory distress syndrome (ARDS). Although they do not impact mortality, they prolong the need for MV, LOSICU, and LOSH.

In Silico Analysis Using SARS-CoV-2 Main Protease and a Set of Phytocompounds to Accelerate the Development of Therapeutic Components against COVID-19

SARS-CoV-2, the virus that caused the widespread COVID-19 pandemic, is homologous to SARS-CoV. It would be ideal to develop antivirals effective against SARS-CoV-2. In this study, we chose one therapeutic target known as the main protease (Mpro) of SARS-CoV-2. A crystal structure (Id: 6LU7) from the protein data bank (PDB) was used to accomplish the screening and docking studies. A set of phytocompounds was used for the docking investigation. The nature of the interaction and the interacting residues indicated the molecular properties that are essential for significant affinity. Six compounds were selected, based on the docking as well as the MM-GBSA score. Pentagalloylglucose, Shephagenin, Isoacteoside, Isoquercitrin, Kappa-Carrageenan, and Dolabellin are the six compounds with the lowest binding energies (−12 to −8 kcal/mol) and show significant interactions with the target Mpro protein. The MMGBSA scores of these compounds are highly promising, and they should be investigated to determine their potential as Mpro inhibitors, beneficial for COVID-19 treatment. In this study, we highlight the crucial role of in silico technologies in the search for novel therapeutic components. Computational biology, combined with structural biology, makes drug discovery studies more rigorous and reliable, and it creates a scenario where researchers can use existing drug components to discover new roles as modulators or inhibitors for various therapeutic targets. This study demonstrated that computational analyses can yield promising findings in the search for potential drug components. This work demonstrated the significance of increasing in silico and wetlab research to generate improved structure-based medicines.

Rabies intervention in Tanzania: An innovative animal vaccination model to train One Health focused student workforces to control and eliminate rabies (preprint)

Background: : Every year at least 59,000 people are estimated to die from rabies and more than 10 million are treated with post-exposure prophylaxis (PEP). Over 99% of human rabies deaths occur in developing countries due to bites from domestic dogs. Large-scale mass dog vaccination programs can control dog rabies and, if sustained, can eliminate dog-mediated rabies. However, there has been very little investment in mass dog vaccination against rabies in sub-Saharan Africa, largely due to limited human and financial resources. To overcome this limitation, we piloted the delivery of synchronized dog vaccinations using a temporary workforce of university students. Fifty university students from Sokoine University of Agriculture and Muhimbili University of Health and Allied Sciences were selected to deliver dog vaccinations throughout the Kisarawe district in Tanzania in May 2021. We analysed the vaccination coverage achieved and the cost per dog vaccinated in delivering dog vaccinations using the university students compared to the traditional delivery. Results: : A total of 1,457 dogs and 242 cats were vaccinated across 48 villages in the Kisarawe district of Tanzania over the course of five days. The overall cost in delivering mass dog vaccinations was estimated at US$ 28,990 equating to approximately US$19.90 per vaccinated dog. Post-vaccination transects were conducted in all 48 villages where dog vaccinations were implemented, counting 387 dogs. Of these, 54% dogs (N=210) were vaccinated against rabies, 67% (N=258) were free-roaming dogs and 72% of dogs encountered were adult (N=277). The overall district-level mean vaccination coverage was estimated to be 54.3% (CI 49.3% - 59.6). Conclusions: : We demonstrated that using university students as a One Health workforce is effective in accelerating the countries’ efforts to meet the global target of eliminating dog-mediated human rabies by 2030.

Human Wharton's Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses.

Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton's jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and in ovo. The half-maximal inhibitory concentrations (IC50), cytotoxic concentration (CC50), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC50 and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC50 and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the anti-adsorption effect. In the in ovo model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.

Oncopreventive and oncotherapeutic potential of licorice triterpenoid compound glycyrrhizin and its derivatives: Molecular insights.

Licorice (Glycyrrhiza glabra) is a well-known natural herb used to treat different ailments since ancient times. Glycyrrhizin (GL), which is the primary triterpenoid compound of licorice extract, has been known to have broad-spectrum pharmacological effects. GL is cleaved into glucuronide and the aglycone, glycyrrhetinic acid (GA), which exists in two stereoisomeric forms: 18α- and 18ß-GA. It is well documented that GL and GA have great potential as anti-inflammatory, anticancer, antiviral, anti-diabetic, antioxidant, and hepatoprotective agents. Studies undertaken during the coronavirus disease 2019 pandemic suggest that GL is effective at inhibiting the viral replication of severe acute respiratory syndrome coronavirus 2. The anticancer effects of GL and GA involve modulating various signaling pathways, such as the phosphatase and tensin homolog/phosphatidylinositol 3-kinase/protein kinase B pathway, the mitogen-activated protein kinase, and the mammalian target of rapamycin/signal transducer and activator of transcription 3, which are mainly involved in regulating cancer cell death, oxidative stress, and inflammation. The potential of GL and GA in preventing cancer development and suppressing the growth and invasion of different cancer types has been reviewed in this paper. This review also provides molecular insights on the mechanism of action for the oncopreventive and oncotherapeutic effects of GL and its derivative, GA, which could help develop more specific forms of these agents for clinical use.

Efficient Framework for Detecting COVID-19 and Pneumonia from Chest X-Ray Using Deep Convolutional Network

Recently, the COVID-19 pandemic is considered the most severe infectious disease because of its rapid spreading. Radiologists still lack sufficient knowledge and experience for accurate and fast detecting COVID-19. What exacerbates things is the significant overlap between Pneumonia symptoms and COVID-19, which confuses the radiologists. It’s widely agreed that the early detection of the infected patient increases his likelihood of recovery. Chest X-ray images are considered the cheapest radiology images, and their devices are available widely. This study introduces an effective Deep Convolutional Neural Network (DCNN) called “DeepChest” for fast and accurate detection for both COVID-19 and Pneumonia in chest X-ray images. “DeepChest” runs with a small number of convolutional layers, a small number of max-pooling layers, and a small number of training iterations compared with the recent approaches and the state-of-the-art of DCNN. We conducted the experimental evaluations of the proposed approach on a data set with 7512 chest X-ray images. The proposed approach achieves an accuracy of 96.56% overall, 99.40% in detecting COVID-19, and 99.32% in detecting Pneumonia. In actual practice, the presented approach can be used as a computer-aided diagnosis tool to get accurate results in detecting Pneumonia and COVID-19 in chest X-ray images.

Emotional responses and coping strategies of medical students during the COVID-19 pandemic.

OBJECTIVES: To assess the emotional responses and coping strategies of medical students during the lockdown and social distancing measures implemented during the coronavirus disease -19 (COVID-19) pandemic. METHODS: This cross­sectional study is based on data collected from undergraduate medical students at the College of Medicine, Alfaisal University Riyadh, Saudi Arabia, during the fall semester of academic year 2020-2021. All the participants completed a self-administered online questionnaire consisting of 3 parts: demographic information, emotional response scale, and 14-item, adapted brief coping orientation to problems experienced inventory to determine the use of avoidant or approach coping strategies. Coping and emotional response scores were compared using t-test. Linear regression analysis was also performed. RESULTS: A total of 261 students from all years were included. Overall scores were higher for avoidant coping strategies. The use of avoidant coping strategies was significantly higher in females (p=0.03) and in preclinical students (p<0.001). Preclinical students had a higher mean score for anger (p=0.002). Conversely, students in the clinical phase had higher scores for anxiety (p=0.005) and sadness (p=0.027). The regression analysis of emotional responses and coping strategies suggests that avoidant coping is a predictor of anger (p=0.003) and sadness (p=0.005). CONCLUSION: Interventions to train medical students in the use of more productive and effective coping strategies may reduce negative emotional responses linked to the present COVID-19 pandemic and in the future.

Effectiveness of virtual teaching of diagnostic and interventional imaging fundamentals to Egyptian medical students: an analytical cross-sectional study

Background There is a worldwide deficit in teaching and training in the field of radiology for undergraduate medical students. This educational gap is prominent in many medical schools as most radiology curricula are a part of other specialty trainings, usually provided by non-radiologists. After COVID-19 pandemic, there was an increased trend in online education. However, questions have been raised about the efficacy and acceptance of online education. We developed a course on the principles of radiology and medical imaging basics to target Egyptian medical students. We then assessed the impact of these educational videos through several online surveys. Our "The Principles of Radiology Online Course" was delivered to students at various Egyptian medical schools;it was a prerecorded series composed of nine sessions, and each session followed the sequence of a pre-test, video, and post-test. There was a final survey to assess the overall feedback. Finally, we analyzed the results to give insight onto how teaching radiology through online lectures can help build better physicians. Results Among various medical schools around Egypt, 1396 Egyptian medical students joined this cohort. Cohort population percentage was 56% female and 44% male. Ninety-eight percent of the students agreed that this program increased their understanding of radiology. Eighty-four percent of the students found the platform friendly and easy to use. Seventy-nine percent found these webinars were more convenient compared to in-person education. Statistical significance (p-value < 0.05) was achieved in all sessions after comparing students’ pre and post-test scores, and in students’ confidence and knowledge level before and after the course. Conclusions Radiology is an underrepresented subject for a lot of medical students. Online radiology webinars have proven to be a promising method of teaching medical students key medical imaging concepts. An online course of radiology basics and principles can help improve a medical student’s knowledge and enhance overall future patient care.

Telemedicine (virtual clinic) effectively delivers the required healthcare service for pediatric ambulatory surgical patients during the current era of COVID-19 pandemic: A mixed descriptive study.

BACKGROUND: Children often suffer from congenital or acquired diseases. Ambulatory cases represent the vast majority of pediatric surgical cases. COVID-19 pandemic-associated regulatory precautions had made the process of seeking medical advice at a suitable appointment such a big problem. We utilized telemedicine (online encounter) to deliver the required healthcare service for sorting and guiding pediatric ambulatory surgical patients. In this article, we aimed to: (1) present our experience, (2) evaluate the effectiveness, and (3) document the results of this technology to solve the problem of difficult healthcare accessibility. MATERIALS AND METHODS: In this study, we compared the utilization of telemedicine (virtual clinic via video consultation) prospectively in the current era of the COVID-19 pandemic in the period from June 2020 to July 2021 to the in-person clinic encounter at the outpatient department (OPD) retrospectively in the previous year (from June 2019 until the end of May 2020) for perioperative management of pediatric ambulatory surgical patients. The study was conducted at 3 tertiary care pediatric surgery centers. The information recorded for analysis included: demographic data, surgical condition distribution, time interval from the appointment request till the actual encounter with the surgeon, conversation duration, distance traveled, and ultimate fate of the consultations. For both groups, service was evaluated after the first follow-up visit by a patient survey questionnaire (Patient Experience Assessment form) including questions relevant to each encounter. RESULTS: A total of 1124 pediatric patients with various ambulatory surgical conditions had been scheduled for virtual clinic video encounters. Of them, 1056 cases were evaluated by video consultation, supervised by their parents or caregivers, thus, achieving an attendance rate of 94%. Of the remaining cases, 2% (n = 23) were canceled and 4% (n = 45) did not attend the virtual clinic. Two-thirds of the cases live in rural /remote areas. Patients' overall satisfaction was 92%. This was in comparison to 872 pediatric ambulatory surgical patients scheduled for in-person clinic visits before the implementation of the virtual clinic. Of them, only 340 cases had attended the clinic, thus, achieving an attendance rate of 39%. Of the remaining cases, 450 cases (51.6%) were canceled and 82 cases (9.4%) did not attend the clinic (no show). About 48% of the cases live in rural areas. For this group, patients' overall satisfaction was 63%. The mean encounter duration was similar for both groups (∼ 5 min). Surgical condition distribution was also similar (p-value: 0.694). For new cases, the time interval from appointment request till the actual encounter was very short for the virtual clinic group (range: 6-15 days) as compared to the in-person clinic group (range: 30-180 days). Patients were followed up for a median period of 14 ± 3.25 months (range: 6-22 months) with no patient loss to follow-up. CONCLUSION: Telemedicine can effectively bridge the patient-physician communication gap caused by the regulatory precautions mandated by the current COVID-19 pandemic. It achieved an attendance rate of 94% and parents' / patients' overall satisfaction of 92%.