Voretigene Neparvovec Exploratory Analysis (VNEAN): R-shiny app for the comprehensive and dynamic visualization of voretigene neparvovec clinical trial data

Purpose : R-shiny apps can be useful in maintaining and analyzing data collected in clinical trials of rare diseases, where a suite of measures is used to characterize retinal and visual function, functional vision, and safety courses over time following the treatment. In a phase 3 trial, participants with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD), an ultra-rare genetic disorder, received bilateral, subretinal injections of gene augmentation therapy, voretigene neparvovec and followed-up annually. We explored the development of a novel data visualization tool, VNEAN (R-shiny application), to help in maintenance and analyses of complex trial data into a visual storytelling form that is easier to understand for healthcare audience. Methods : We developed an interactive and dynamic application using Shiny package for R programming language. This app improves the ability to explore the longitudinal trajectory of main efficacy outcomes (mobility testing and full-field light sensitivity) in concert with other data, including visual function and safety that can be visualized overall and in subsets. Results : This app has 11 modules of data analyses (Figure 1), including longitudinal visualization, analyses of correlation between changes, and timeline of adverse events. It presents the durability in improvement of functional vision, retinal and visual function, and the safety data at the group, subset and participant levels. The dynamic interface allows the user to define a subset based on the measures at baseline and/or their changes and select measures and/or timepoints. Conclusions : COVID-19 demonstrated digital engagement at its peak. The R shiny app has the potential to provide alternative data visualization and interpretations of analyses that offer a comprehensive representation of the data generated in rare diseases, not easily achievable via traditional didactic lectures and static data methods. This patient-centric and enduring visualization approach enables health care professionals to learn and retain information for the management and engagement of IRD patients in their clinical practice. Additionally, this application can progress the knowledge and understanding of treatment effects of rare diseases and help inform the design of future small- or largescale trials.

From Inferior Vena Cava to Right Atrium: A Rare Case of a Unique Large Burden Thrombus in a Patient with Antiphospholipid Syndrome

Introduction: Antiphospholipid Syndrome is a condition where self-antibodies are directed against phospholipid binding proteins resulting in thrombosis and/or pregnancy loss. Diagnosis is made via history, physical, positive anticardiolipin and anti-beta-2-glycoprotein antibodies. We describe a case of a large thrombus in a previously diagnosed patient with antiphospholipid syndrome and discuss the need for prophylaxis in these patients. Case Report: 34-year-old G7P1161 Hispanic female with past medical history of uncontrolled diabetes mellitus type 2 presents with an acute onset of sharp abdominal pain radiating to the back associated with nausea, non-bloody non-bilious emesis and dysuria. Vital signs on admission are significant for tachycardia and hypertension. Labs are noteworthy for elevated Creatinine at 1.7 mg/dl, thrombocytopenia, transaminitis, elevated Ddimer at 14272 ng/ml. Urine analysis is positive for nitrites, trace leukocytes and bacteria. Her serum pregnancy test and COVID PCR are negative. CT Abdomen/Pelvis with contrast revealed an extensive thrombus in the Inferior Vena Cava (IVC) to the Right Atrium (RA), also extending into the hepatic veins and upper lumbar veins. Moderate perinephric fat stranding is also noted around bilateral kidneys. Ultrasound of the abdomen reveals cholelithiasis without evidence of acute cholecystitis. Venous Doppler of lower extremities reveals patent deep veins. Patient was started on heparin drip immediately and intravenous Cefepime. Interventional Radiology performed mechanical thrombectomy. Hematology was consulted and converted patient to Warfarin with an INR goal of 2.5-3. Patient was discharged and instructed to follow up with hematology. Discussion: There are few case reports of extensive thrombi ranging from IVC to RA with most cases occurring in elderly population. We present a unique case of an extensive thrombus ranging not only from the IVC to RA but also extending into the hepatic veins and the upper lumbar veins. The patient described has a history of multiple spontaneous abortions with her only successful preterm birth required daily therapeutic Lovenox during pregnancy. Her recurrent pregnancy loss and current large burden thrombus can be attributed to her antiphospholipid syndrome. This begs the question whether these patients should be started on prophylaxis anticoagulation. There have been limited studies with aspirin and warfarin which at times demonstrated positive results. Our patient had her thrombus identified incidentally due to an admission for pyelonephritis. If her thrombus was not recognized in time, outcomes could have been devastating. In conclusion, there should be further studies to determine the efficacy of anticoagulation prophylaxis in patients with positive antiphospholipid antibodies. (Figure Presented).

REPORT- Varying pattern of blood gases, ferritin, procalcitonin, C-Reactive protein, interleukin 6 and lactate dehydrogenase in Covid-19 patients suffering from diverse Co-Morbid, suspected cytokine storm and periodic effects of antiviral and steroidal treatments

This study depicted varying pattern of inflammatory markers and blood gases of selected SARS Covid-19 patients with triggered cytokine storm, during their stay in ICUs, HDUs, on ventilators for 21 days. All were treated with Antiviral (remdesivir), steroid (dexamethason) and antipyretic (paracetamol) medications. Procalcitonin, PCT, C-reactive protein CRP, Interleukin 6 (IL6) and Lactate dehydrogenase (LDH) blood gases pressure (pO2, pCO2), coagulation (D-Dimer DD) and Iron storage proteins (Ferritin Ft) were analyzed by fully automated analyzers. All biomarkers of each patient category was statistically compared with days 1st, 4th, 7th versus 10th, 14th and 17th days and reported as significant where p<0.05, to assess progression, worsening or recovery status. IL6 (P<0.0224, P< 0.0228) and CRP (P<0.0277) exhibited none or mild statistical significance difference, with the exception of Ferritin (P<0.0185;P<0.0088) and D Dimer (P<0.0086), demonstrating slow recovery, revealing stronger cytokine storming assault. LDH, pCO2 and pO2 exhibited variable significance difference when data of earlier days were compared with recovery phase, thus advocating blended treatment or progressing of disease. Analysis confirms overwhelming pathogenesis of SARS Covid-19 distinctive cytokine storm, which needed to be cautiously monitored as infection progressed using pro-inflammatory biomarkers as indicators of recovery or worsening of the disease.

Machine Learning Approach for Predicting COVID-19 Suspect Using Non-contact Vital Signs Monitoring System by RGB Camera

The emergence of several SARS-CoV-2 variants, especially, the new variant strains B.1.1.7 lineage and 20C/501Y.V2 have highly accelerated the COVID-19 pandemic. A large number of COVID-19 patients are not getting the chance of admitting to the hospitals. Therefore, this pandemic situation accelerates the method of non-contact evaluation of patients along with prediction system of COVID-19 suspects. To feed this interest, a non-contact vital signs monitoring and COVID-19 suspect prediction system is developed. The study can measure heart rate, respiratory rate, and blood oxygen saturation simultaneously using low-cost RGB camera. A predictive model is developed using supervised learning algorithms for predicting the COVID suspect. Among the implemented algorithms, Support Vector Machine ensures a high accuracy of 97.92%. The accuracy of the non-contact vital signs monitoring system is also compared with commercial sensors. Among seven participants, the absolute error (AE) of heart rate was 2.11 for two participants and AE ≤ 4.06 for the other five participants. AE for oxygen saturation was 0.0 for four participants and AE ≤ 1.0 for three participants. Commercially, mean bias for heart rate varies from 2.08 to 8.06 and mean bias for SpO2 is ± 2. The mean bias of the heart rate for this research varies from 2.11 to 4.06 and for SpO2 varies from 0 to 1. Both of them are in a commercially acceptable range. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

An Ensemble Approach for the Diagnosis of COVID-19 from Speech and Cough Sounds

Mass COVID-19 infections detection has shown to be a very hard problem. In this work, we describe our systems developed to diagnose COVID-19 cases based on coughing sounds and speech. We propose a hybrid configuration that employs Convolution Neural Network (CNN), Time Delay Neural Network (TDNN) and Long Short-Term Memory (LSTM) for the extraction of coughing sound and speech embeddings. Moreover, the proposed framework utilizes SpecAugment-based on-the-fly data augmentation and multi-level statistics pooling for mapping frame level information into utterance level embedding. We employ classical support vector machines, random forests, AdaBoost, decision trees, and logistic regression classifiers for the final decision making, to determine whether the given feature is from a COVID-19 negative or positive patient. We also adopt an end-to-end approach employing ResNet model with a one-class softmax loss function for making positive versus negative decision over the high resolution hand-crafted features. Experiments are carried out on the two subsets, denoted as COVID-19 Speech Sounds (CSS) and COVID-19 Cough Sounds (CCS), from the Cambridge COVID-19 Sound database and experimental results are reported on the development and test sets of these subsets. Our approach outperforms the baselines provided by the challenge organizers on the development set, and shows that using speech to help remotely detect early COVID-19 infections and eventually other respiratory diseases is likely possible, which opens a new opportunity for a promising cheap and scalable pre-diagnosis way to better handle pandemics. © 2021, Springer Nature Switzerland AG.

Profiling of inflammatory biomarkers in mild to critically ill severe acute respiratory syndrome corona virus-19 (SARS Covid-19) patients from Karachi, Pakistan. (Special Issue.)

SARS-Covid-19 infection got spread in many countries and WHO declared it as a serious global Pandemic. Pro-inflammatory cytokines storm generated by Covid-19 infection hyper-activates inflammatory response in host body, resulting in elevated release of inflammatory biomarkers. Present article describes the characteristic profile of these inflammatory and related biomarkers in a total of 48 critically ill Covid-19 patients, (Male = 38, F = 10), with mildly ill to severe, critically ill status and thus grouped accordingly. Inflammatory Biomarkers, Ferritin, ProCalcitonin, CReactive Protein, coagulation marker-D-Dimer, chemical analytes, Protein, Albumin, BUN, Bilirubin, Creatinine, and enzymes, Lactate Dehydrogenase, P-Glutamyl transpeptidases, Alkaline phosphatase were routine analyzed by standard methods described earlier. D-dimer, Ferritin, CRP and Procalcitonin exhibited variable alterations (P<0.05 to P<0.001), more markedly in critically ill patients than in the mild and severe. Biochemical analytes and enzymatic parameters showed elevated levels (P<0.05 to P<0.01) mostly in critically ill category of patients when compared with mild or severe, except total protein and albumin, which remained non-significant. It is concluded that cytokine, chemokines and pro-inflammatory markers, which released in abnormally high concentrations in Covid-19 patients of variable syndrome intensity, are significant indicators of disease severity, progression and success of treatments. As the pharmacological options may vary with the different stages of the disease therefore identifying the correct stage of the disease may be very useful in selecting the best option.

Corporate social responsibility in the time of COVID-19

The purpose of this study is to integrate all the facts and concepts related to corporate social responsibilities especially in unprecedented situation called COVID 19. The authors explain what all activities contribute to corporate social responsibility and how various organisations are capitalising this situation to build up their brand and establish rapport with their customers and stakeholders. Drawing on amendment in Companies act 2013 and its repercussions in the company’s policy and CSR practices, this study examines role played by Companies act in providing solutions to major issues like malnutrition, Poverty, Unemployment through CSR. Study results indicates changes in funding scenario in NGO during pandemic and problem and challenges faced by NGO in raising funds from the organisations as companies have reduced their CSR budget due to pandemic. The CSR experts need to generate a combination of multiple strategies and customised solutions to handle the economic issues and problems

Human rights dimensions of COVID-19 responses in Bangladesh: challenges and recommendations

Purpose: The purpose of this paper is to scrutinize the human rights dimensions of COVID-19 responses in Bangladesh through a viewpoint methodology in four critical areas: freedom of opinion and expression;access to information;protection of health-care workers;and marginalized populations’ access to health care. However, these responses remain non-aligned with the international human rights law obligations of Bangladesh, which undermines the human rights and dignity of its population. Based on the responses shaping and aggravating the situation, this paper concludes with some recommendations, which can be helpful for Bangladesh for better human rights responses in these areas, should a parallel situation emerge in the future. Design/methodology/approach: This paper scrutinizes the human rights dimensions of COVID-19 responses in Bangladesh through a viewpoint methodology. Findings: The responses of Bangladesh remain non-aligned with international human rights law obligations of Bangladesh, which undermines the human rights and dignity of its population. Originality/value: This paper concludes with some recommendations, which can be helpful for Bangladesh for better human rights responses in these areas, should a parallel situation emerge in the future. © 2021, Emerald Publishing Limited.

Education beyond COVID-19 –the world academic coalition

The recent outbreak of the contagious Coronavirus infection that is considered to be the greatest health threat after the Spanish flu pandemic in 1918 impacted the lives of people belonging to all sectors of society. Besides affecting the economy of all the countries it created a major disruption to the mental health of the general public irrespective of the part of the earth they belong to. The rate of spread of the infection was high and in many scenarios remained asymptomatic. This peculiar nature of this disease mandated the governments across the globe to ban the free functioning of public places. Schools, Colleges, Universities, Restaurants, etc. were ordered to remain closed. This was adopted by the governments as a measure to control the spread of the disease. The education sector also underwent a massive hit as a result of this pandemic. The world economic forum reported that more than 1.2 billion children belonging to 186 countries around the globe are not attending regular schools as the schools remain closed to control the spread rate of the disease. As per the statement of the World Health Organization (WHO), it is believed that this pandemic caused devastation to the lives of nearly 28,584,158 people across the world. The students, teachers, and parents suffered psychologically as they have not experienced a situation of this sort earlier. The decline in job opportunities as a consequence of the economic slowdown created panic in the minds of young graduates. The drastic shift from teaching in-person to leveraging the technological advancements to conduct classes contributed in many ways to affect the mental health of students, parents, and teachers. This was a challenge for the policymakers as well. This article is devoted to exploring the different psychological disturbances experienced by students, teachers, parents, and others as a consequence of this COVID-19 pandemic on the education system. A discussion of a few of the literature already in existence in this context is carried out and suggestions to tackle this novel crisis are present. Keeping ourselves mentally strong and calm is needed to increase our productivity. This article stresses the importance of that too. Also, case studies of the impact of the COVID-19 Pandemic on the educational ecosystem of India and Ethiopia are presented. © 2021, Universitatea de Vest Vasile Goldis din Arad. All rights reserved.