Cost-Effectiveness Analysis of Out-Of-Hospital versus In-Hospital Extracorporeal Cardiopulmonary Resuscitation for Out-Hospital Refractory Cardiac Arrest

It has been speculated that out-of-hospital cardiac arrest (OHCA) patients’ survival might be improved by implementing extracorporeal cardiopulmonary resuscitation (ECPR) before arrival to hospital. Therefore, we sought to assess the cost-effectiveness of OH-ECPR versus in-hospital (IH)-ECPR in OHCA patients in Qatar. From the hospital perspective, a conventional decision-analytic model was constructed to follow up the clinical and economic consequences of OH-ECPR versus IH-ECPR in a simulated OHCA population over one year. The primary outcome was the survival at discharge after arrest as well as the overall direct healthcare costs of managing OHCA patients. The robustness of this model was evaluated via sensitivity analyses. The OH-ECPR yielded 16% survival at discharge after arrest compared to 7% with IH-ECPR, [risk ratio (RR)=0.91; 95% CI 0.79 to 1.06; P = 0.26]. Incorporating the uncertainty associated with this survival rate, and based on the estimated willingness to pay threshold in Qatar, the OH-ECPR was cost-effective with an incremental cost-effectiveness ratio of QAR 464,589 (USD 127,634). Sensitivity and uncertainty analyses confirmed the robustness of the study outcome. This is the first cost-effectiveness evaluation of OH-ECPR versus IH-ECPR in OHCA patients. OH-ECPR is potentially an economically acceptable resuscitative strategy in Qatar.Open access funding was provided by the Qatar National Library

Molecular Mechanisms Underpinning Microparticle-Mediated Cellular Injury in Cardiovascular Complications Associated with Diabetes.

Microparticles (MPs) are small vesicles shed from the cytoplasmic membrane of healthy, activated, or apoptotic cells. MPs are very heterogeneous in size (100-1,000 nm), and they harbor proteins and surface antigens specific to cells they originate from. Virtually, all cells can shed MPs, and therefore, they can be found in all body fluids, but also entrapped in tissues. Of interest and because of their easy detection using a variety of techniques, circulating MPs were recognized as biomarkers for cell activation. MPs were also found to mediate critical actions in intercellular communication and transmitting biological messages by acting as paracrine vehicles. High plasma numbers of MPs were reported in many cardiovascular and metabolic disturbances that are closely associated with insulin resistance and low-grade inflammation and have been linked to adverse actions on cardiovascular function. This review highlights the involvement of MPs in cardiovascular complications associated with diabetes and discusses the molecular mechanisms that underpin the pathophysiological role of MPs in the onset and progression of cellular injury in diabetes.NPRP award (NPRP8-1750-3-360) from Qatar National Research Fund (a member of Qatar Foundation) and a Qatar University high collaborative grant (QUCG-CPH-2018\2019-2

A High-Realism and Cost-Effective Training Simulator for Extracorporeal Membrane Oxygenation

Medical simulators, employed in extracorporeal membrane oxygenation (ECMO), are burdened with costly equipment and low-fidelity methodologies. This dichotomy necessitated a new approach that eliminates high-costs and integrates with the critical care environment. This is especially applicable after the Coronavirus pandemic, where resources and supplies are evermore scarce. After examining the state-of-the-art and establishing a close collaboration with Hamad Medical Corporation (HMC), the main healthcare provider in Qatar, several criteria were identified to advance the cutting-edge. In this article, a high-realism, cost-effective ECMO simulator is presented. It runs on a novel blood simulation technology along with simulation modules. An instructor tablet application enables instructors to orchestrate the training experience wirelessly with real-time performance. It also includes a novel scenario designer for implementing consistent simulation curricula. A product-level simulator with high-fidelity casings is in the final integration phases. Current results include developing and testing the simulated blood circuit, simulation modules for hemorrhaging, line chattering, air bubbles noise, and a replicated console along with an integrated communications system. Nineteen specialists rated the fidelity of the system as highly realistic during a questionnaire-based study. It is expected to run a second study to evaluate the educational efficacy of the simulator as a first-of-its-kind in the region. 2013 IEEE.This work was supported by the Qatar University under Grant M-CTP-CENG-2020-1.Scopu

Addressing the challenges of ECMO simulation

This document is the Accepted Manuscript. The final, definitive version of this paper has been published in Perfusion, May 2018, published by SAGE Publishing, All rights reserved.Introduction/Aim: The patient’s condition and high-risk nature of extracorporeal membrane oxygenation (ECMO) therapy force clinical services to ensure clinicians are properly trained and always ready to deal effectively with critical situations. Simulation-based education (SBE), from the simplest approaches to the most immersive modalities, helps promote optimum individual and team performance. The risks of SBE are negative learning, inauthenticity in learning and over-reliance on the participants’ suspension of disbelief. This is especially relevant to ECMO SBE as circuit/patient interactions are difficult to fully simulate without confusing circuit alterations. Methods: Our efforts concentrate on making ECMO simulation easier and more realistic in order to reduce the current gap there is between SBE and real ECMO patient care. Issues to be overcome include controlling the circuit pressures, system failures, patient issues, blood colour and cost factors. Key to our developments are the hospital-university collaboration and research funding. Results: A prototype ECMO simulator has been developed that allows for realistic ECMO SBE. The system emulates the ECMO machine interface with remotely controllable pressure parameters, haemorrhaging, line chattering, air bubble noise and simulated blood colour change. Conclusion: The prototype simulator allows the simulation of common ECMO emergencies through innovative solutions that enhance the fidelity of ECMO SBE and reduce the requirement for suspension of disbelief from participants. Future developments will encompass the patient cannulation aspect.Peer reviewe

Preliminary Implementation of the Next Generation Cannulation Simulator

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.Extracorporeal Membrane Oxygenation (ECMO) is a highly complex/critical lifesaving procedure known to support patients with cardiac and respiratory issues. Patients on ECMO are monitored 24/7 by a team of highly trained ECMO team comprising nurses, physicians, respiratory therapists, and perfusionists promptly intervening to any potential emergency situation. Simulation-Based Training (SBT) allows clinicians to experience and practice realistic hands-on procedures and scenarios without any risk. In ECMO, cannulation is a critical procedure performed to externally reroute the blood flow so it can be re-oxygenated by the ECMO machine before being recirculated through the patient's body. In a close collaboration with Hamad Medical Corporation (HMC), this project aims to develop a cost effective, realistic, and user-friendly ECMO simulator focusing on the venous and arterial cannulation procedure, The main features of this simulator include cannulation emergencies caused by low pressure flow, excessive force, recirculation, or mispositioned wire/cannula. Therefore, the ECMO cannulation simulator will not only greatly contribute to the initial and ongoing local training of HMC ECMO clinicians but also contribute to improving patient care by lowering the risks associated with the cannulation process

Towards next generation cannulation simulators

Background: Cannulation, in extracorporeal membrane oxygenation (ECMO), is the act of inserting a cannula through the body1. For femoral veins, femoral arteries, and the jugular vein, the cannula stops at the inferior vena cava (IVC) beside the hepatic vein and at the beginning of the distal aorta, and the superior vena cava at the right atrium, respectively. Cannulation is considered a critical operation and requires intensive training. Simulation-based training (SBT) is the gold standard, allowing for training in risk-free, versatile, and realistic environments2. A research collaboration was established between Hamad Medical Corporation and Qatar University College of Engineering to support the development of the ECMO training programme. Initially an ECMO machine simulator was developed with thermochromic ink to simulate blood and modules that simulate common emergencies practitioners may face during ECMO runs3. This cannulation simulator is now being designed to close the gap in the market in relation to cost and fidelity4,5. Methods: The cannulation simulator is composed of several modules. Firstly, a 3D-printed femoral pad mold was constructed to facilitate the production of cannulation pads (Figure 1(a), (c)). Secondly, cannulation pads were designed so they are anatomically correct and ultrasound compatible. For the arteries, the superficial artery was added at the access point to simulate possible incorrect routes for the cannula. Furthermore, the orientation of the veins and arteries were set to further resemble the human anatomy, where the arteries are situated above the veins (Figure 1(a), (b)). In addition to the implementation of a closed loop linking the jugular to the femoral, cannulation access points with a pump connected to a tank between them to regulate the flow. The blood flow in the arteries was enhanced with a pump to simulate a pulsatile flow while the flow in the veins is laminar as seen in the single loop implementation (Figure 1(h)). The connection of the pump to the embedded system is shown in Figure 1(g). The junctional point in the IVC was designed in the venous loop to allow for two cannulas to pass and an alternative path simulating the renal vein was added. A force sensing resistor (FSR) was connected to detect and measure incorrect entry of the guide-wire as this, in real-time scenarios, could cause internal bleeding to the patient (Figure 1(g)). Lastly, the Y-connector showing the renal vein entry is shown in Figure 1(d) and (e). Results: Tests were done on the system namely on the FSR to recalibrate it in the presence of liquid. Tests on the pulsatile flow were conducted to optimize for realism in terms of pressure. Since both jugular and femoral cannulation access points are included, the simulator can be used for training for all ECMO modes including veno-arterial and veno-venous. After testing, the main limitations of the current prototype include the flexibility of the tubes, limits on FSR measurements, and the rigidity of the available 3D printing material. Conclusion: After implementing the stated features, the anticipated outcome is a realistic and cost-efficient ECMO cannulation simulator.qscienc

Association between periodontitis and severity of COVID-19 infection: A case–control study

Aim: COVID-19 is associated with an exacerbated inflammatory response that can result in fatal outcomes. Systemic inflammation is also a main characteristic of periodontitis. Therefore, we investigated the association of periodontitis with COVID-19 complications. Materials and Methods: A case–control study was performed using the national electronic health records of the State of Qatar between February and July 2020. Cases were defined as patients who suffered COVID-19 complications (death, ICU admissions or assisted ventilation), and controls were COVID-19 patients discharged without major complications. Periodontal conditions were assessed using dental radiographs from the same database. Associations between periodontitis and COVID 19 complications were analysed using logistic regression models adjusted for demographic, medical and behaviour factors. Results: In total, 568 patients were included. After adjusting for potential confounders, periodontitis was associated with COVID-19 complication including death (OR = 8.81, 95% CI 1.00–77.7), ICU admission (OR = 3.54, 95% CI 1.39–9.05) and need for assisted ventilation (OR = 4.57, 95% CI 1.19–17.4). Similarly, blood levels of white blood cells, D-dimer and C Reactive Protein were significantly higher in COVID-19 patients with periodontitis. Conclusion: Periodontitis was associated with higher risk of ICU admission, need for assisted ventilation and death of COVID-19 patients, and with increased blood levels of biomarkers linked to worse disease outcomes

Assessment of Broadly Reactive Responses in Patients With MERS-CoV Infection and SARS-CoV-2 Vaccination

Importance: In the ongoing COVID-19 pandemic, there remain unanswered questions regarding the nature and importance of the humoral immune response against other coronaviruses. Although coinfection of the Middle East respiratory syndrome coronavirus (MERS-CoV) with the SARS-CoV-2 has not been documented yet, several patients previously infected with MERS-CoV received the COVID-19 vaccine; data describing how preexisting MERS-CoV immunity may shape the response to SARS-CoV-2 following infection or vaccination are lacking. Objective: To characterize the cross-reactive and protective humoral responses in patients exposed to both MERS-CoV infection and SARS-CoV-2 vaccination. Design, Setting, and Participants: This cohort study involved a total of 18 sera samples collected from 14 patients with MERS-CoV infection before (n = 12) and after (n = 6) vaccination with 2 doses of COVID-19 mRNA vaccine (BNT162b2 or mRNA-1273). Of those patients, 4 had prevaccination and postvaccination samples. Antibody responses to SARS-CoV-2 and MERS-CoV were assessed as well as cross-reactive responses to other human coronaviruses. Main Outcomes and Measures: The main outcomes measured were binding antibody responses, neutralizing antibodies, and antibody-dependent cellular cytotoxicity (ADCC) activity. Binding antibodies targeting SARS-CoV-2 main antigens (spike [S], nucleocapsid, and receptor-binding domain) were detected using automated immunoassays. Cross-reactive antibodies with the S1 protein of SARS-CoV, MERS-CoV, and common human coronaviruses were analyzed using a bead-based assay. Neutralizing antibodies (NAbs) against MERS-CoV and SARS-CoV-2 as well as ADCC activity against SARS-CoV-2 were assessed. Results: A total of 18 samples were collected from 14 male patients with MERS-CoV infection (mean [SD] age, 43.8 [14.6] years). Median (IQR) duration between primary COVID-19 vaccination and sample collection was 146 (47-189) days. Prevaccination samples had high levels of anti-MERS S1 immunoglobin M (IgM) and IgG (reactivity index ranging from 0.80 to 54.7 for IgM and from 0.85 to 176.3 for IgG). Cross-reactive antibodies with SARS-CoV and SARS-CoV-2 were also detected in these samples. However, cross-reactivity against other coronaviruses was not detected by the microarray assay. Postvaccination samples showed significantly higher levels of total antibodies, IgG, and IgA targeting SARS-CoV-2 S protein compared with prevaccination samples (eg, mean total antibodies: 8955.0 AU/mL; 95% CI, -5025.0 to 22936.0 arbitrary units/mL; P =.002). In addition, significantly higher anti-SARS S1 IgG levels were detected following vaccination (mean reactivity index, 55.4; 95% CI, -9.1 to 120.0; P =.001), suggesting potential cross-reactivity with these coronaviruses. Also, anti-S NAbs were significantly boosted against SARS-CoV-2 (50.5% neutralization; 95% CI, 17.6% to 83.2% neutralization; P <.001) after vaccination. Furthermore, there was no significant increase in antibody-dependent cellular cytotoxicity against SARS-CoV-2 S protein postvaccination. Conclusions and Relevance: This cohort study found a significant boost in cross-reactive NAbs in some patients exposed to MERS-CoV and SARS-CoV-2 antigens. These findings suggest that isolation of broadly reactive antibodies from these patients may help guide the development of a pancoronavirus vaccine by targeting cross-reactive epitopes between distinct strains of human coronaviruses..This work was supported by internal funds from the Biomedical Research Center of Qatar University. Dr Nasrallah received funding from The WHO Eastern Mediterranean Regional Office (WHO-EMRO) Special Grant for COVID-19 Research

Emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis, therapeutics and vaccines

The emergence of novel and evolving variants of SARS-CoV-2 has fostered the need for change in the form of newer and more adaptive diagnostic methods for the detection of SARS-CoV-2 infections. On the other hand, developing rapid and sensitive diagnostic technologies is now more challenging due to emerging variants and varying symptoms exhibited among the infected individuals. In addition to this, vaccines remain the major mainstay of prevention and protection against infection. Novel vaccines and drugs are constantly being developed to unleash an immune response for the robust targeting of SARS-CoV-2 and its associated variants. In this review, we provide an updated perspective on the current challenges posed by the emergence of novel SARS-CoV-2 mutants/variants and the evolution of diagnostic techniques to enable their detection. In addition, we also discuss the development, formulation, working mechanisms, advantages, and drawbacks of some of the most used vaccines/therapeutic drugs and their subsequent immunological impact.Key message The emergence of novel variants of the SARS-CoV-2 in the past couple of months, highlights one of the primary challenges in the diagnostics, treatment, as well as vaccine development against the virus. Advancements in SARS-CoV-2 detection include nucleic acid based, antigen and immuno- assay-based and antibody-based detection methodologies for efficient, robust, and quick testing; while advancements in COVID-19 preventive and therapeutic strategies include novel antiviral and immunomodulatory drugs and SARS-CoV-2 targeted vaccines. The varied COVID-19 vaccine platforms and the immune responses induced by each one of them as well as their ability to battle post-vaccination infections have all been discussed in this review

Performance evaluation of five ELISA kits for detecting anti-SARS-COV-2 IgG antibodies

ObjectivesTo evaluate and compare the performances of five commercial ELISA assays (EDI, AnshLabs, Dia.Pro, NovaTec, and Lionex) for detecting anti-SARS-CoV-2 IgG. Methods70 negative control samples (collected before the COVID-19 pandemic) and samples from 101 RT-PCR-confirmed SARS-CoV-2 patients (collected at different time points from symptoms onset: ≤7, 8-14, and >14 days) were used to compare the sensitivity, specificity, agreement, positive and negative predictive values of each assay with RT-PCR. A concordance assessment between the five assays was also conducted. Cross-reactivity with other HCoV, non-HCoV respiratory viruses, non-respiratory viruses, and nuclear antigens was investigated. ResultsLionex showed the highest specificity (98.6%, 95%CI: 92.3-99.8), followed by EDI and Dia.Pro (97.1%, 95%CI: 90.2-99.2), NovaTec (85.7%, 95%CI: 75.7-92.1), then AnshLabs (75.7%, 95%CI: 64.5-84.2). All ELISA kits cross-reacted with one anti-MERS IgG positive sample except Lionex. The sensitivity was low during the early stages of the disease but improved over time. After 14 days from symptoms onset, Lionex and NovaTec showed the highest sensitivity at 87.9% (95%CI: 72.7-95.2) and 86.4% (95%CI: 78.5-91.7), respectively. The agreement with RT-PCR results based on Cohen’s kappa was as follows: Lionex (0.89)> NovaTec (0.70)> Dia.Pro (0.69)> AnshLabs (0.63)> EDI (0.55). ConclusionThe Lionex ELISA, which measures antibodies solely to the S1 protein, demonstrated the best performance.This work was made possible by grant No. RRC-2-032 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors. GKN would like to acknowledge funds from Qatar University's internal grant QUERG-CMED-2020-2