Comparison of Methods of Assessment and Results of Traditional Osce with Electronic-Osce

Introduction: The onset and rise of COVID-19 and its sudden progression to a worldwide pandemic lead medical and dental institutes to change their way of teaching and conducting assessments to distance learning as compared to the previously applied conventional approaches. Teaching and assessment during this era have changed vastly, earlier it was solely traditional/live Objective Structured Clinical Examination (OSCE) but due to the current circumstances electronic/online OSCE (E-OSCE) method was introduced. In Pakistan also, Pakistan Medical Council (PMC) and the College of Physicians and Surgeons of Pakistan (CPSP) conducted online exams so that the scheduled exams do not get delayed. Aim(s): The main objective of this paper is to measure the reliability of an E-OSCE and to compare it with the traditional OSCE. Methodology: This was a cross-sectional study which got conducted at the Rawal Institute of Health Sciences, Islamabad. Traditional OSCEs and E-OSCEs were conducted with 71 participants including final year students and house officers. Each OSCEs had 10 stations, including one interactive station in traditional OSCE. Students' scores in both the OSCEs were collected and paired t-test was used to compare the mean scores at p<0.05. Result(s): Total number of house officers were 27 and final year students were 44. The scores of 71 participants were collected. The difference between mean scores of house officers' traditional OSCE and E-OSCE was statistically significant (p=0.000). The difference between final year students traditional OSCE and E-OSCE was also statistically significant (p=0.020). Finally, the overall difference between traditional OSCE and E-OSCE was also statistically significant (p=0.000) Practical implication: The main objective of this study was to assess the reliability of an E-OSCE and to compare whether the electronic method of conducting OSCE is more reliable than the traditional method of conducting OSCE. Conclusion(s): Despite limitations and the biases, the results of E-OSCE proved to be better than traditional OSCE. Further research needs to be conducted on E-OSCE to control the factors causing biases and limitations.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

The Infant Transcriptome in Meningococcal Septic Shock: A Force in Precision Cellular Dysfunction Suggesting a Cytokine Storm?

BACKGROUND AND AIM: The ideal biomarker(s) to track evolution and the underlying basis of sepsis remain elusive. We hypothesized that assessing differential mRNA gene expression may aid in tracking sepsis pathogenesis in infants with meningococcal septic shock (MSS). METHOD(S): Temporal paediatric gene expression datasets from Meningococcal Group B sepsis studies in the United Kingdom (MSS1, 29 samples) and Holland (MSS2, 41 samples) underwent Principal Component Analysis (PCA) and Gene Set Enrichment Analysis (GSEA). RESULT(S): Gene-expression clustering algorithm for both datasets demonstrated a baseline state on admission, an intermediate state, and a final state. Additionally, PCA plots suggested a gene-expression trajectory. The MSS1 study showed that 410 genes differentiated survivors from a nonsurvivor, including the ICAM-3 gene. Moreover GSEA t-Test identified apoptosis to be significantly differently (p = 0.02 and q = 0.15) associated with the fatal case compared to the four survivors in MSS1. Also in MSS1, we identified a genesignature for cytokine production which included 5 genes (CLC, HFE, HLA-F, NLRP3, TNFRSF1B) from the cytokine GSEA gene panel. The genes NLRP3 and TNFRSF1B have been noted in the cytokine storm of Coronavirus infection. Also Transcript Time Course Analysis (TTCA) confirmed differential gene function associated with Coronavirus. CONCLUSION(S): Transcriptomic analysis in two independent datasets in infants with MSS identified a trajectorial pattern. Further, the transcriptome expression differed between survivors and non-survivors, suggesting differences in cytokine signalling. Including the existence of genes associated with the cytokine storm of SARS-CoV2. The exploitability of transcriptome analysis to guide therapy and prognosis requires further investigation. (Figure Presented).

In-Vitro and in-Vivovascular Endothelial Growth Factor Subtypes a & B in Severe Acute Respiratory Syndrome Pathogenesis

BACKGROUND AND AIM: Increased Vascular Endothelial Growth Factor (VEGFA) Gene Expression (GE) has been documented in SARS-CoV2 infection. We wished to understand the relationship of VEGFA and VEGF B GE in both Murine SARS-CoV and Human SARS-CoV-2 in-vitro models of infection. METHOD(S): Secondary analysis of datasets from mice given nasal installation of SARS-CoV (MA15), MS1 (GSE33266MCV-1) and MS2 (GSE68820) from pulmonary tissues was undertaken. This allowed viral dose and temporal response analysis, respectively. Also studied were In-vitro Human hACE2 cells infected with SARS-CoV2 (dataset INV, GSE169158). Gene expression (GE) VEGF sub-types were analysed using Qlucore Omics Explorer (QOE) and gene enrichment functional profiling through the g:Profiler online platform. RESULT(S): For Murine studies, MA15 instillation compared to controls in MS1, lead to down-regulation of both VEGFB (MA15 10

The impact of COVID-19 on Intensive Care recruitment

Introduction: Recruitment in intensive care has long been discussed, with the pandemic bringing this into sharp focus. Most anaesthetists in training were fully redeployed into ICU rotas or provided technical expertise. As surge rotas settle and a 'new normal' is regained, the challenge of ICU consultant recruitment needs to be addressed. Historically, ICUs have been predominantly staffed by consultants trained in both anaesthetics and intensive care medicine (ICM), but the challenges of this career path have been augmented by COVID-19. Forecasts suggest a concerning supply shortage of both anaesthetic and ICM consultants.1 The latest recruitment round for ICM has been the most competitive year for applications (ratio 2.9:1 in 2021 compared to 1.49:1 in 2020).2 However, the anaesthetic/ICM dual-training contribution to this workforce has worryingly decreased from approximately twothirds to less than a half. But what factors are causing this and has COVID-19 redeployment worsened this? Objectives: As we emerge from the second wave of the pandemic, we assessed the attitudes of anaesthetists about future careers in intensive care. Methods: We performed a brief electronic survey of 100 dual-or single-specialty anaesthetists in training from four LETBs across England who were redeployed to ICU. Results: Our survey showed that 29% had a negative experience that dissuaded them from pursuing ICM careers or, in some circumstances, relinquish their ICM training number altogether. Promisingly, 64% had a positive experience, and of these 39% reaffirmed their desire to pursue a career in ICU and 13% developed a new interest in pursuing a career in ICU since their redeployment. Positive factors included, 'teamwork', 'complexity of patients' and 'adding variety to my anaesthetic practice'. Prominent negative factors were 'additional exams', 'two separate portfolios' and 'high risk of burnout'. Respondents suggested changes to attract more anaesthetists to dual-accredit with ICM. This included the removal of hurdles such as additional exams, separate portfolios, and duplicated assessments. The additional training time was also highlighted, particularly given that trainees already contribute significantly to ICM rotas. There was a need for more flexibility in training with dual trainees wanting to undertake advanced training modules like their anaesthetic counterparts. They also reported wanting more anaesthetic sessions in their future job plans possibly reflecting the desire for varied practice as a consultant. Conclusion: Although COVID-19 has had a positive effect by increasing ICM applications, this may be at the expense of dual-trained anaesthetic/ICM trainees. FFICM should consider the factors which dissuade these applicants and its future impact on skills available in ICU. Both the RCoA and the FFICM have recently announced changes to curricula and e-portfolio which may close some of these gaps. The pandemic has grabbed the attention of a few anaesthetists and presented an opportunity to work in a team that solves difficult physiological puzzles, rapidly escalates capacity, and increasingly focuses on staff wellbeing. We should capitalise on this and hope that COVID-19 will result in the conversion of some of our anaesthetic colleagues into dual-specialty ICM consultants.

Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide (ENZ) + AAP for metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy (ADT): Overall survival (OS) results of 2 randomised phase III trials from the STAMPEDE protocol

Background: AAP or ENZ added to ADT improves outcomes for mHSPC. Any benefit of combining ENZ & AAP in this disease setting is uncertain. Methods: STAMPEDE is a multi-arm, multi-stage (MAMS), platform protocol conducted at 117 sites in the UK & Switzerland. 2 trials with no overlapping controls randomised mHSPC patients (pts) 1:1 to ADT +/- AAP (1000mg od AA + 5mg od P) or AAP + ENZ (160mg od). Treatment was continued to progression. From Jan 2016 docetaxel 75mg/m2 3-weekly with P 10mg od was permitted + ADT. Using meta-analysis methods, we tested for evidence of a difference in OS and secondary outcomes (as described previously: failure-free, metastatic progression-free, progression-free & prostate cancer specific survival) across the 2 trials using data frozen 3 Jul 2022. All confidence intervals (CI) 95%. Restricted mean survival times (RMST) restricted to 84 months (m). Results: Between Nov 2011 & Jan 2014, 1003 pts were randomised ADT +/- AAP & between Jul 2014 & Mar 2016, 916 pts were randomised ADT +/- AAP + ENZ. Randomised groups were well balanced across both trials. Pt cohort: age, median 68 years (yr), IQR 63, 72;PSA prior to ADT, median 95.7 ng/ml, IQR 26.5, 346;de novo 94%, relapsed after radical treatment, 6%. In AAP + ENZ trial, 9% had docetaxel + ADT. OS benefit in AAP + ENZ trial, HR 0.65 (CI 0.55‒0.77) p = 1.4×10-6;in AAP trial, HR 0.62 (0.53, 0.73) p = 1.6×10-9. No evidence of a difference in treatment effect (interaction HR 1.05 CI 0.83‒1.32, p = 0.71) or between-trial heterogeneity (I2 p = 0.70). Same for secondary end-points. % (CI) of pts reporting grade 3-5 toxicity in 1st 5 yr: AAP trial, ADT: 38.5 (34.2-42.8), + AAP: 54.4 (50.0-58.8);AAP + ENZ trial, ADT: 45.2 (40.6 – 49.8), + AAP + ENZ: 67.9 (63.5 – 72.2);most frequently increased with AAP or AAP + ENZ = liver derangement, hypertension. At 7 yr in AAP trial (median follow-up: 95.8m), % (CI) pts alive with ADT: 30 (26, 34) versus with ADT + AAP: 48 (43, 52);RMST: ADT: 50.4m, ADT + AAP: 60.6m, p = 6.6 x 10-9. Conclusions: ENZ + AAP need not be combined for mHSPC. Clinically important improvements in OS when adding AAP to ADT are maintained at 7 yr. Clinical trial identification: NCT00268476. Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London. Funding: Cancer Research UK, Medical Research Council, Janssen, Astellas. Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca;Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion;Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research;Financial Interests, Institutional, Research Grant: Janssen, Astellas;Non-Financial Interests, Principal Investigator: Janssen, Astellas;Non-Financial Interests, Advisory Role: Janssen, AstraZeneca. W.R. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics, Janssen, Astellas;Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer;Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi, Roche;Financial Interests, Personal, Advisory Board, 2018, 2019: Orion;Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag;Financial Interests, Personal, Advisory Board, 2020: Amgen;Financial Interests, Personal, Invited Speaker, 2020: ESMO;Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX;Financial Interests, Institutional, Advisory Board, 2018, 2019, 2022: Bayer;Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag, Roche, MSD Merck Sharp & Dohme, Pfizer;Financial Interests, Institutional, Advisory Board, 2018: AAA International, Menarini Silicon Biosystems;Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma;Financial Interests, Institutional, Advisory B ard, 2019: Tolero Pharmaceuticals;Financial Interests, Personal, Invited Speaker, 2021, 2022: SAKK, DESO;Financial Interests, Institutional, Advisory Board, 2021: Telixpharma, BMS, AAA International, Novartis, Modra Pharmaceuticas Holding B.V.;Financial Interests, Institutional, Other, Steering Committee 2021: Amgen;Financial Interests, Institutional, Advisory Board, 2021, 2022: Orion, Bayer;Financial Interests, Personal, Invited Speaker, 2021: SAKK, SAKK, SAMO - IBCSG (Swiss Academy of Multidisciplinary oncology);Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome;Financial Interests, Personal, 2021: RSI (Televisione Svizzera Italiana);Financial Interests, Institutional, Invited Speaker, 2021: Silvio Grasso Consulting;Financial Interests, Institutional, Other, Faculty activity 2022: WebMD-Medscape;Financial Interests, Institutional, Advisory Board, 2022: Myriad genetics, AstraZeneca;Financial Interests, Institutional, Invited Speaker, 2022: TOLREMO;Financial Interests, Personal, Other, Travel support 2022: AstraZeneca;Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas;Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems, Aranda;Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. C. Pezaro: Financial Interests, Personal, Advisory Board, Ad board Dec 2020: Advanced Accelerator Applications;Financial Interests, Personal, Advisory Board, Aug 2021: Astellas;Financial Interests, Personal, Advisory Board, Oct 2021: Bayer;Financial Interests, Personal, Invited Speaker, Sept-Oct 2020: AstraZeneca;Financial Interests, Personal, Invited Speaker, Oct 2020: Janssen;Financial Interests, Personal, Advisory Board, July-Sept 2022: Pfizer. Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer: sanofi;Financial Interests, Institutional, Invited Speaker, research grant for CHROME study: sanofi;Other, Other, support to attend meetings or advisory boards in the past: Astellas,Jaansen,Bayer;Other, Other, Sponsorship to attend ASCO meeting 2022: Bayer. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen;Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas, Janssen, Novartis, Pfizer, Sanofi;Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology. L.C. brown: Financial Interests, Institutional, Research Grant, £170k educational grant for the FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca;Financial Interests, Institutional, Funding, Various grants awarded to my institution for work undertaken as part of the STAMPEDE Trial: janssen pharmaceuticals;Non-Financial Interests, Other, I am a member of the CRUK CERP funding advisory panel and my Institution also receive grant funding from CRUK for the STAMPEDE and FOCUS4 trials: Cancer Research UK. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL;Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis;Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London;Non-Financial Interests, Advisory Role, rEECur: University of Birmingham;Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis;Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen;Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi;Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi;Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck;Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer;Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen, Astellas;Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca. All other authors have declared no conflicts of interest.

HRCT Features Of COVID-19 In Relation To Duration Of Disease

BACKGROUND: Despite the fact that much has been written on various aspects of COVID-19, literature lacks a detailed and accurate description of HRCT findings in relation to the duration of the disease. The aim of this study was to investigate the difference in HRCT scan findings depending on the time after onset of the disease. The objective of the study is to identify and compare findings of HRCT scan at different time points after onset of the disease. METHODS: A total of 224 patients, scanned over a period of 2 months, were placed in one of the four groups at the time of their scan depending on the days lapsed after their symptoms appeared. All scans were carried out on the same machine. Findings in each group were recorded and compared. A finding showing significant difference between groups indicates its importance in describing the course of the disease. Analysis was done on SPSS 23. RESULTS: Ground glass opacities in posterior segments of one or more lobes was the most common feature and had a significant association with first 5 days of the disease (p=.027). Interlobular thickening and subpleural reticulation, are found between 3-5 days or later in the course of the disease (p=.000). CONCLUSION: Ground glass opacities located in posterior segments are the predominant feature in patients who are scanned up to 5 days after their symptoms appear. This feature is the most common in scans done in asymptomatic cases too. Interlobular septal thickening and subpleural reticulation start appearing at 3 days of disease process.

LBA4 Abiraterone acetate plus prednisolone (AAP) with or without enzalutamide (ENZ) added to androgen deprivation therapy (ADT) compared to ADT alone for men with high-risk non-metastatic (M0) prostate cancer (PCa): Combined analysis from two comparisons in the STAMPEDE platform protocol

Background: Patients (pts) with high-risk M0 PCa are treated with ADT and when indicated, local radiotherapy (RT). Intensifying hormone treatment with AAP, ENZ or apalutamide continuous to progression improves outcomes of metastatic PCa but its efficacy in M0 PCa starting ADT is unknown. Methods: STAMPEDE is a multi-arm, multi-stage trial that, as part of 2 separate comparisons randomised PCa pts with M0 node positive or high-risk node negative (>1 T3/4, PSA ≥40ng/ml, Gleason 8-10 or relapsing) 1:1 to ADT (control) vs ADT with AAP (1000mg AA + 5mg P od) or ADT vs ADT with AAP + ENZ (160mg od) for 2 years (y), unless RT was omitted when treatment could be to progression. The primary end-point was metastasis-free survival (MFS, time to death or distant metastases). The sub-group of pts who received ADT +/- AAP was partially reported with metastatic pts in 2017 so one-sided type 1 error rate was set to 1.25%. All analyses were pre-specified, pooled using meta-analyses methods and stratified as described previously. Data frozen 3rd August 2021. Results: 1974 M0 pts at 113 sites in UK & Switzerland were randomised, 914 (Nov 2011 to Jan 2014) to ADT +/- AAP & 1060 (Mar 2016 to Jul 2014) to ADT +/- AAP + ENZ. Groups were well balanced: median age 68 y, range 43-86;median PSA 34 ng/ml, range 0.4-2773;Gleason 8-10, 79%;node positive 39%;planned for RT 85%. Median months to stopping AAP, 23.7 (IQR: 17.6-24.1);AAP when given with ENZ, 20.7 (IQR: 4.4-24);ENZ, 23.2 (IQR: 6.3-24). 180 MFS events occurred in the research group and 306 in the control group. AAP-based therapy improved MFS (HR 0.53, 95% CI 0.44-0.64, P=2.9×10- 11) & survival (HR 0.60, 95% CI 0.48-0.73, P=9.3×10-7): 6-y MFS from 69% to 82%, 6-y survival from 77% to 86%. Treatment effect was consistent in major subgroups and between AAP & AAP + ENZ randomisation periods (MFS HR=0.54, 95% CI 0.43-0.68;HR=0.53, 95% CI 0.39-0.71 respectively;interaction HR = 1.02, 95% CI: 0.70-1.50, p=0.908). Conclusions: 2 y of AAP-based therapy significantly improves MFS & survival of high-risk M0 PCa starting ADT and should be considered a new standard of care. Clinical trial identification: NCT00268476. Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London. Funding: Cancer Research UK, Medical Research Council, Astellas, Janssen. Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Invited Speaker: Astellas;Financial Interests, Personal, Advisory Board: Astellas;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: Sapience;Financial Interests, Personal, Advisory Board: Orion;Financial Interests, Personal, Royalties: Janssen;Financial Interests, Institutional, Research Grant: Janssen;Financial Interests, Institutional, Research Grant: Astellas;Non-Financial Interests, Principal Investigator: Janssen;Non-Financial Interests, Advisory Role: Janssen;Non-Financial Interests, Advisory Role: AstraZeneca;Non-Financial Interests, Principal Investigator: Astellas. L.C. Brown: Financial Interests, Institutional, Research Grant, FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca. N. Clarke: Financial Interests, Personal, Invited Speaker: Astellas;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Ferring;Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Personal, Advisory Board: Astellas;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Ferring;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Inst tutional, Research Grant: AstraZeneca. W. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics;Financial Interests, Personal, Invited Speaker, Speaker fee: Janssen;Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer;Financial Interests, Personal, Invited Speaker, Speaker fee: Astellas;Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics. R. Jones: Financial Interests, Personal, Advisory Board, advisory board attendance: AstraZeneca;Financial Interests, Personal, Advisory Board, advisory board attendance: Astellas;Financial Interests, Personal, Invited Speaker, Honoraria for speaking: Astellas;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Clovis;Financial Interests, Personal, Advisory Board: Exelixis;Financial Interests, Personal, Advisory Board: Ipsen;Financial Interests, Personal, Invited Speaker: Ipsen;Financial Interests, Personal, Advisory Board: Bristol Myers Squipp;Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Invited Speaker: Merck Serono;Financial Interests, Personal, Advisory Board: Merck Sharpe Dome;Financial Interests, Personal, Invited Speaker: Merck Sharpe Dome;Financial Interests, Personal, Invited Speaker: Pfizer;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Institutional, Other, IDMC membership: Roche;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Institutional, Other, IDMC member: Stab;Financial Interests, Personal, Advisory Board: Novartis / AAA;Financial Interests, Institutional, Invited Speaker: Janssen;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker: Tail;Financial Interests, Institutional, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Invited Speaker: BioXcel;Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb;Financial Interests, Institutional, Invited Speaker: Novartis / AAA;Financial Interests, Institutional, Invited Speaker: Roche;Financial Interests, Institutional, Invited Speaker: MSK. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi;Financial Interests, Personal, Advisory Board, 2018, 2019: Orion;Financial Interests, Personal, Advisory Board, 2018: Roche;Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag;Financial Interests, Personal, Advisory Board, 2020: Amgen;Financial Interests, Personal, Invited Speaker, 2020: ESMO;Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX;Financial Interests, Institutional, Advisory Board, 2018, 2019: Bayer;Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag;Financial Interests, Institutional, Advisory Board, 2020: Roche;Financial Interests, Institutional, Advisory Board, 2018: AAA International;Financial Interests, Institutional, Advisory Board, 2018: Menarini Silicon Biosystems;Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma;Financial Interests, Institutional, Advisory Board, 2019: Tolero Pharmaceuticals;Financial Interests, Institutional, Advisory Board, 2020: MSD Merck Sharp & Dohme;Financial Interests, Institutional, Advisory Board, 2020: Pfizer;Financial Interests, Personal, Invited Speaker, 2021: SAKK;Financial Interests, Institutional, Advisory Board, 2021: Telixpharma;Financial Interests, Institutional, Other, Steering Committee 2021: Amgen;Financial Interests, Institutional, Invited Speaker, 2021: DESO;Financial Interests, Institutional, Advisory Board, 2021: BMS;Financial Interests, Institutional, Advisory Board, 2021: AAA International;Financial Interests, Institutional, Advisory Board, 2021: Orion;F nancial Interests, Personal, Invited Speaker, 2021: SAKK;Financial Interests, Personal, Invited Speaker, 2021: SAKK;Financial Interests, Institutional, Advisory Board, 2021: Bayer;Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome;Financial Interests, Personal, Other, 2021: RSI (Televisione Svizzera Italiana);Financial Interests, Personal, Invited Speaker, 2021: SAMO - IBCSG;Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas;Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems;Non-Financial Interests, Advisory Role, 2019: Aranda;Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. S. Chowdhury: Financial Interests, Personal, Advisory Board: Astellas;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Personal, Advisory Board: Huma;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Novartis/AAA;Financial Interests, Personal, Advisory Board: Beigene;Financial Interests, Personal, Advisory Board: Remedy Bio;Financial Interests, Personal, Advisory Board: Athenex;Financial Interests, Personal, Advisory Board: Telix;Financial Interests, Personal, Advisory Board: Clovis Oncology;Financial Interests, Personal, Stocks/Shares: Curve Life;Financial Interests, Institutional, Research Grant: Clovis Oncology;Non-Financial Interests, Advisory Role, Non-compensated advice: NHS England;Non-Financial Interests, Advisory Role: NICE NHS England. Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer:Sanofi;Other, support to attend meetings or advisory boards in the past: Astellas, Jaansen, Bayer. C. Parker: Financial Interests, Personal, Advisory Board, Education Steering Committee: Bayer;Financial Interests, Personal, Invited Speaker, Speaker at prostate cancer educational events: Janssen;Financial Interests, Personal, Advisory Board, Advisory board on apalutamide: Janssen;Financial Interests, Personal, Advisory Board, Advisory board: Clarity Pharmaceuticals;Financial Interests, Personal, Advisory Board, Advisory board on relugolix: Myovant;Financial Interests, Personal, Advisory Board, Advisory board: ITM Oncologics. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen;Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas;Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Janssen;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Novartis;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Pfizer;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Sanofi. M.K. Parmar: Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen;Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen;Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi;Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facili ate licence extensions internationally for docetaxel: Sanofi;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Clovis;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Novartis;Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Astellas;Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca. All other authors have declared no conflicts of interest.

Clinical characteristics of children with COVID-19: a multicenter study in the United Arab Emirates

Background: To date, coronavirus disease-2019 (COVID-19) has infected over 82 million people globally. The first confirmed case in the United Arab Emirates (UAE)was reported on 29th January 2020. Current data suggests that children with COVID-19 have a mild disease course. There is a lack of extensive published data about COVID-19 infection among children in the Arabian Gulf region.

Study of Naturally-derived Biomolecules as Therapeutics against SARS-CoV-2 Viral Spike Protein

The SARS-CoV2 virus, the causative agent for COVID-19 disease has to lead to more than 3.1 million deaths and crossed 146 million infections worldwide so far. Although vaccines development and emergency authorization has been approved by several governments, there has been great concern about its side effects for the long term and its effectiveness against new mutated strains. A resurgence of COVID-19 or related disease can be catastrophic. There is an urgent need to look for effective antiviral agents for many coronavirus strains with minimum side-effects, and maximum efficacy globally. Several, naturally-derived biomolecules have proved their excellent effect on several infectious diseases in a multi-mode fashion by targeting several pathways as well as increasing efficacy with high safety profile. Integrate computational prediction design was used in the study to examine the pharmacology of bioactive compounds of natural origin against SARS-CoV2 spike protein. Keeping these facts we have computationally examined 16 naturally occurring compounds using to evaluate their effectiveness against the SARS-CoV2 virus using the molecular docking technique. Hesperidin derivatives are known to ameliorate diabetes, co-morbidity for coronavirus, as well as help in preventing post coronavirus complications. We found the binding free energy of Hesperidin with spike protein to be -7.57 kcal/mol, the aglycone derivative to be 6.93 kcal/mol, hesperidin monoacetyl derivative to be -7.82 kcal/mol, and hesperidin pentaacetyl derivative to be -8.39 kcal/mol. Our findings revealed that acetylated derivatives of hesperidin showed significant improved remarked binding affinity while aglycone derivative hesperetin showed a decrease in binding affinity. Our studies give a new direction where natural bioactive compounds and their derivatives can be modulated and used after clinical trials to effectively inhibit coronavirus infection as well as diabetes simultaneously with a high safety profile.

Caputo SIR model for COVID-19 under optimized fractional order.

Everyone is talking about coronavirus from the last couple of months due to its exponential spread throughout the globe. Lives have become paralyzed, and as many as 180 countries have been so far affected with 928,287 (14 September 2020) deaths within a couple of months. Ironically, 29,185,779 are still active cases. Having seen such a drastic situation, a relatively simple epidemiological SIR model with Caputo derivative is suggested unlike more sophisticated models being proposed nowadays in the current literature. The major aim of the present research study is to look for possibilities and extents to which the SIR model fits the real data for the cases chosen from 1 April to 15 March 2020, Pakistan. To further analyze qualitative behavior of the Caputo SIR model, uniqueness conditions under the Banach contraction principle are discussed and stability analysis with basic reproduction number is investigated using Ulam-Hyers and its generalized version. The best parameters have been obtained via the nonlinear least-squares curve fitting technique. The infectious compartment of the Caputo SIR model fits the real data better than the classical version of the SIR model (Brauer et al. in Mathematical Models in Epidemiology 2019). Average absolute relative error under the Caputo operator is about 48% smaller than the one obtained in the classical case ( ν = 1 ). Time series and 3D contour plots offer social distancing to be the most effective measure to control the epidemic.

Comparison between Prophylactic versus Therapeutic Doses of Low-Molecular-Weight Heparin in Severely Ill Coronavirus Disease 2019 Patients in Relation to Disease Progression and Outcome

Introduction: The predominant coagulation abnormalities in patients with coronavirus disease 2019 (COVID-19) suggest a hypercoagulable state and are consistent with uncontrolled clinical observations of an increased risk of venous thromboembolism. Aim and Objectives: To compare the effect of prophylactic versus therapeutic doses of enoxaparin in the treatment of severe cases of COVID-19 infection. Materials and Methods: This was a retrospective observational study conducted at Latifa hospital, Dubai. Fifty-nine patients enrolled from March to June 2020 and divided into 2 groups: patients who received the prophylactic dose of enoxaparin (group 1) and patients who received the therapeutic dose of enoxaparin (group 2). Results: The mean age of all cases was 47.2 ± 10.4 years, while the mean weight was 76.4 ± 13.4 kg. Males represented 79.7% of cases. Blood group "O"was the most frequent blood group (40.9%). None of the cases were smokers or using alcohol. Bronchial asthma, lung diseases, diabetes mellitus, hypertension, CKD, cardiac disease, thyroid disease, and immunodeficiency were present in 1.7, 1.7, 39, 27.1, 5.1, 1.7, 5.1, and 1.7% respectively. There was no significant difference between both study groups regarding personal and medical characteristics, except for hypertension where 35.9% of group 2 (therapeutic) cases were hypertensive compared to 10% of group 1 cases (prophylactic). There was a significant difference between both study groups regarding inflammatory markers improvement duration, duration of MV and O2 support duration, with longer duration among (therapeutic) group 2 cases compared to group 1 cases (prophylactic). There was a highly significant difference between both study groups regarding ICU admission, as 64% of group 1 cases were admitted compared to 25% of group 1 cases. Similarly, 38.5% of group 2 cases needed MV compared to only 10% of group 1 cases, which was statistically significant. There was no significant difference between both groups regarding bleeding tendency and mortality (p value 0.54). Conclusion: Our results showed that use of prophylactic dose of enoxaparin might have some benefits compared to the therapeutic dose in terms of less duration of ICU and hospital stay, duration of oxygen support, need and duration of MV, and normalization of inflammatory markers. However, there was no significant difference between the 2 regimens regarding the mortality.

Caputo SIR Model for COVID-19 under Optimized Fractional Order (preprint)

Everyone is talking about coronavirus from last couple of months due to its exponential spread throughout the globe. Lives have become paralyzed and as many as 180 countries are so far affected with 928,287 (14 September, 2020) deaths within couple of months. Ironically, 29,185,779 are still active cases. Having seen such drastic situation, a relatively simple epidemiological SIR model with Caputo derivative is suggested unlike more sophisticated models being proposed nowadays in the current literature. Major aim of the present research study is to look for possibilities and extents to which the SIR model fits the real data for the cases chosen from 01 April to 15 March, 2020, Pakistan. To further analyze qualitative behavior of the Caputo SIR model, uniqueness conditions under the Banach contraction principle are discussed and stability analysis with basic reproduction number is investigated using Ulam-Hyers and its generalized version. Best parameters have been obtained via nonlinear least-squares curve fitting technique. The infectious compartment of the Caputo SIR model fits the real data better than classical version of the SIR model [4]. Average absolute relative error under the Caputo operator is about 48% smaller than the one obtained in the classical case (ν = 1). Time series and 3D contour plots offer social distancing to be the most effective measure to control the epidemic.