Showing papers by "Federal University of São Paulo published in 2021"
University of Oxford1, Federal University of São Paulo2, University of the Witwatersrand3, Stellenbosch University4, Liverpool School of Tropical Medicine5, University of Sheffield6, University of London7, Newcastle upon Tyne Hospitals NHS Foundation Trust8, University Hospital Southampton NHS Foundation Trust9, University Hospitals Bristol NHS Foundation Trust10, Guy's and St Thomas' NHS Foundation Trust11, University Hospitals Birmingham NHS Foundation Trust12, St George's, University of London13, AstraZeneca14, North Bristol NHS Trust15, University College Hospital16, University of Hull17, Escola Bahiana de Medicina e Saúde Pública18, Federal University of Rio Grande do Norte19, Northwest University (China)20, Universidade Federal de Santa Maria21, Glasgow Dental Hospital and School22, Boston Children's Hospital23, Universidade Federal do Rio Grande do Sul24, Western General Hospital25, University of Glasgow26, Cambridge University Hospitals NHS Foundation Trust27, University of Cambridge28, Nottingham University Hospitals NHS Trust29, Aneurin Bevan University Health Board30
TL;DR: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.
3,741 citations
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
University of Washington1, St George’s University Hospitals NHS Foundation Trust2, McMaster University3, Agostino Gemelli University Polyclinic4, Emory University5, Federal University of São Paulo6, Ottawa Hospital7, St Thomas' Hospital8, University of Michigan9, Cooper University Hospital10, University of Kansas11, University of Amsterdam12, United Arab Emirates University13, University of Pittsburgh14, King Saud bin Abdulaziz University for Health Sciences15, University of São Paulo16, University of Minnesota17, Population Health Research Institute18, University of Toronto19, Humanitas University20, University of Kentucky21, Ghent University Hospital22, University of Tokyo23, Peking Union Medical College Hospital24, Hebron University25, Monash University26, Copenhagen University Hospital27, Liverpool School of Tropical Medicine28, Vanderbilt University29, Harvard University30, Brigham and Women's Hospital31, University of Ulsan32, University of Manitoba33, Makerere University34, Faculdade de Medicina de São José do Rio Preto35, Mount Sinai Hospital, Toronto36, Medanta37, University of the Witwatersrand38, New York University39, Washington University in St. Louis40, University of Alberta41, Hennepin County Medical Center42, University of Pennsylvania43, Hebrew University of Jerusalem44, Hadassah Medical Center45, Hochschule Hannover46, Brown University47
TL;DR: The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications as discussed by the authors, which are either strong or weak, or in the form of best practice statements.
Abstract: Background
Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.
Methods
We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.
Results
The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.
Conclusion
The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.
893 citations
TL;DR: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks as discussed by the authors.
862 citations
University of Washington1, St George’s University Hospitals NHS Foundation Trust2, McMaster University3, Agostino Gemelli University Polyclinic4, Emory University5, Federal University of São Paulo6, Ottawa Hospital7, St Thomas' Hospital8, University of Michigan9, Cooper University Hospital10, University of Kansas11, University of Amsterdam12, United Arab Emirates University13, University of Pittsburgh14, King Saud bin Abdulaziz University for Health Sciences15, University of São Paulo16, University of Minnesota17, Population Health Research Institute18, University of Toronto19, Humanitas University20, University of Kentucky21, Ghent University Hospital22, University of Tokyo23, Peking Union Medical College Hospital24, Hebron University25, Monash University26, Copenhagen University Hospital27, Liverpool School of Tropical Medicine28, Vanderbilt University29, Brigham and Women's Hospital30, University of Ulsan31, University of Manitoba32, Makerere University33, Faculdade de Medicina de São José do Rio Preto34, National Institutes of Health35, Mount Sinai Hospital, Toronto36, Medanta37, University of the Witwatersrand38, New York University39, Washington University in St. Louis40, University of Alberta41, Hennepin County Medical Center42, Royal Brisbane and Women's Hospital43, University of Pennsylvania44, Hebrew University of Jerusalem45, Hochschule Hannover46, Brown University47
TL;DR: The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications as mentioned in this paper, which are either strong or weak, or in the form of best practice statements.
Abstract: Background
Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.
Methods
We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.
Results
The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.
Conclusion
The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.
664 citations
TL;DR: This work shows that inflammasomes are activated in response to SARS-CoV-2 infection in vitro and in COVID-19 patients, contributing to the exacerbated inflammatory response, impacting disease progression and clinical outcome.
Abstract: Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19.
556 citations
University of Cologne1, University of Genoa2, Post Graduate Institute of Medical Education and Research3, Westmead Hospital4, University of Sydney5, Federal University of São Paulo6, Medical University of Graz7, University of California, San Diego8, Innsbruck Medical University9, University of Lagos10, McGill University Health Centre11, Fudan University12, Radboud University Nijmegen13, University of Rennes14, Duke University15, University of Texas Health Science Center at San Antonio16, University of Texas at Austin17, Federal University of Paraná18, University of Texas Health Science Center at Houston19, Cardiff University20, Center for Infectious Disease Research and Policy21
TL;DR: It is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty, and recommended first-line therapy is either voriconazole or isavuconazole, while azole resistance is a concern.
Abstract: Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
519 citations
University of London1, National Institute for Health Research2, University of Auckland3, Anglia Ruskin University4, University of Cambridge5, Sun Yat-sen University6, Queen's University Belfast7, The Fred Hollows Foundation8, Mbarara University of Science and Technology9, Ministry of Health and Family Welfare10, University of Geneva11, St Thomas' Hospital12, Leeds Teaching Hospitals NHS Trust13, Southwest University of Visual Arts14, Orbis International15, International Agency for the Prevention of Blindness16, University of Cape Town17, University Hospitals Birmingham NHS Foundation Trust18, University of Michigan19, Emory University20, Johns Hopkins University21, Massachusetts Eye and Ear Infirmary22, University of São Paulo23, University of Nairobi24, Seva Foundation25, Tilganga Institute of Ophthalmology26, Heidelberg University27, The George Institute for Global Health28, University of New South Wales29, L V Prasad Eye Institute30, College of Health Sciences, Bahrain31, Muhimbili University of Health and Allied Sciences32, International Institute of Minnesota33, University of the West Indies34, University of Melbourne35, Kenya Medical Training College36, Federal University of São Paulo37, Capital Medical University38, National University of Singapore39, Singapore National Eye Center40, Pan American Health Organization41, Brien Holden Vision Institute42, University of Calabar43
TL;DR: In this paper, the authors defined eye health as maximised vision, ocular health, and functional ability, thereby contributing to overall health and wellbeing, social inclusion, and quality of life.
435 citations
University of Oxford1, University of Siena2, Federal University of São Paulo3, Newcastle upon Tyne Hospitals NHS Foundation Trust4, University Hospitals Birmingham NHS Foundation Trust5, Liverpool School of Tropical Medicine6, AstraZeneca7, Northwest University (China)8, University of the Witwatersrand9, University Hospitals Bristol NHS Foundation Trust10, University of Bristol11, University of Glasgow12, University College London13, Wellcome Trust Centre for Human Genetics14, South African Medical Research Council15
TL;DR: A further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses are presented.
Abstract: Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, MHRA, with a regimen of two standard doses given with an interval of between 4 and 12 weeks The planned rollout in the UK will involve vaccinating people in high risk categories with their first dose immediately, and delivering the second dose 12 weeks laterHere we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered
Methods: We present data from phase III efficacy trials of ChAdOx1 nCoV-19 in the United Kingdom and Brazil, and phase I/II clinical trials in the UK and South Africa, against symptomatic disease caused by SARS-CoV-2 The data cut-off date for these analyses was 7th December 2020 The accumulated cases of COVID-19 disease at this cut-off date exceeds the number required for a pre-specified final analysis, which is also presented As previously described, individuals over 18 years of age were randomised 1:1 to receive two standard doses (SD) of ChAdOx1 nCoV-19 (5x1010 viral particles) or a control vaccine/saline placebo In the UK trial efficacy cohort a subset of participants received a lower dose (LD, 22x1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose All cases with a nucleic acid amplification test (NAAT) were adjudicated for inclusion in the analysis, by a blinded independent endpoint review committee Studies are registered at ISRCTN89951424 and ClinicalTrialsgov; NCT04324606, NCT04400838, and NCT04444674
Findings: 17,177 baseline seronegative trial participants were eligible for inclusion in the efficacy analysis, 8948 in the UK, 6753 in Brazil and 1476 in South Africa, with 619 documented NAAT +ve infections of which 332 met the primary endpoint of symptomatic infection >14 days post dose 2The primary analysis of overall vaccine efficacy >14 days after the second dose including LD/SD and SD/SD groups, based on the prespecified criteria was 667% (574%, 740%) There were no hospitalisations in the ChAdOx1 nCoV-19 group after the initial 21 day exclusion period, and 15 in the control groupVaccine efficacy after a single standard dose of vaccine from day 22 to day 90 post vaccination was 76% (59%, 86%), and modelled analysis indicated that protection did not wane during this initial 3 month period Similarly, antibody levels were maintained during this period with minimal waning by day 90 day (GMR 066, 95% CI 059, 074)In the SD/SD group, after the second dose, efficacy was higher with a longer prime-boost interval: VE 824% 95%CI 627%, 917% at 12+ weeks, compared with VE 549%, 95%CI 327%, 697% at <6 weeks These observations are supported by immunogenicity data which showed binding antibody responses more than 2-fold higher after an interval of 12 or more weeks compared with and interval of less than 6 weeks GMR 219 (212, 226) in those who were 18-55 years of age
Interpretation: ChAdOx1 nCoV-19 vaccination programmes aimed at vaccinating a large proportion of the population with a single dose, with a second dose given after a 3 month period is an effective strategy for reducing disease, and may be the optimal for rollout of a pandemic vaccine when supplies are limited in the short term
Trial Registration: Studies are registered at ISRCTN89951424 and ClinicalTrialsgov; NCT04324606, NCT04400838, and NCT04444674
Funding: UKRI, NIHR, CEPI, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D’OR, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and Astra Zeneca
Conflict of Interest: Oxford University has entered into a partnership with Astra Zeneca for further development of ChAdOx1 nCoV-19 SCG is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine TL is named as aninventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project PMF is a consultant to Vaccitech AJP is Chair of UK DeptHealth and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI), but does not participate in discussions on COVID-19 vaccines, and is a member of the WHO’sSAGE AJP and SNF are NIHR Senior Investigator The views expressed in this article do not necessarily represent the views of DHSC, JCVI, NIHR or WHO AVSH reports personal feesfrom Vaccitech, outside the submitted work and has a patent on ChAdOx1 licensed to Vaccitech, and may benefit from royalty income to the University of Oxford from sales of this vaccine by AstraZeneca and sublicensees MS reports grants from NIHR, non-financial support fromAstraZeneca, during the conduct of the study; grants from Janssen, grants fromGlaxoSmithKline, grants from Medimmune, grants from Novavax, grants and non-financialsupport from Pfizer, grants from MCM, outside the submitted work CG reports personal fees from the Duke Human Vaccine Institute, outside of the submitted work SNF reports grants from Janssen and Valneva, outside the submitted work ADD reports grants and personal fees from AstraZeneca, outside of the submitted work In addition, ADD has a patent manufacturingprocess for ChAdOx vectors with royalties paid to AstraZeneca, and a patent ChAdOx2 vector with royalties paid to AstraZeneca The other authors declare no competing interests
428 citations
TL;DR: In this paper, the authors compared the efficacy and safety of therapeutic versus prophylactic anticoagulation in patients hospitalised with COVID-19 in 31 sites in Brazil, and found that in the case of stable patients, in-hospital oral rivaroxaban (20 mg or 15 mg daily) or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed
326 citations
TL;DR: In this paper, the authors reviewed the existing literature and knowledge of ACE2 in COVID-19 setting and focused on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential.
Abstract: COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which SARS-CoV-2 enters the host cells and is highly expressed in the heart, kidneys, and lungs and shed into the plasma. ACE2 is a key regulator of the renin-angiotensin-aldosterone system (RAAS). SARS-CoV-2 causes ACE/ACE2 balance disruption and RAAS activation, which leads ultimately to COVID-19 progression, especially in patients with comorbidities, such as hypertension, diabetes mellitus, and cardiovascular disease. Therefore, ACE2 expression may have paradoxical effects, aiding SARS-CoV-2 pathogenicity, yet conversely limiting viral infection. This article reviews the existing literature and knowledge of ACE2 in COVID-19 setting and focuses on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential.
Universidade Federal de Goiás1, Pontifícia Universidade Católica de São Paulo2, Rio de Janeiro State University3, Federal University of Pernambuco4, Pontifícia Universidade Católica do Rio Grande do Sul5, Federal University of São Paulo6, University of São Paulo7, Federal University of Bahia8, Universidade Federal do Rio Grande do Sul9, Federal University of Paraná10, State University of Campinas11, Federal University of Rio de Janeiro12, State University of Santa Cruz13, Federal University of Pará14, University of Brasília15, Estácio S.A.16, Escola Bahiana de Medicina e Saúde Pública17, University of Caxias do Sul18, Universidade Federal de Santa Catarina19, Universidade Federal do Espírito Santo20, Sao Paulo State University21, Universidade Federal de Mato Grosso22, Pontifícia Universidade Católica do Paraná23, Pontifícia Universidade Católica de Goiás24, Universidade Federal de Juiz de Fora25, Universidade Estadual de Maringá26, Federal University of Uberlandia27
TL;DR: The Brazilian Guidelines of Hypertension -2020 as mentioned in this paper have been published for the first time in the year 2020, and are based on the definition, epidemiology, and primary prevention.
Abstract: Content 1. Definition, Epidemiology, and Primary Prevention 528 1.1 Definition of Hypertension 528 […] Brazilian Guidelines of Hypertension – 2020
TL;DR: Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality.
Abstract: Objective To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19). Design Randomised, open label trial. Setting Nine hospitals in Brazil, 8 May to 17 July 2020. Participants Adults with confirmed covid-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the tocilizumab group. Interventions Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care (n=65) versus standard care alone (n=64). Main outcome measure The primary outcome, clinical status measured at 15 days using a seven level ordinal scale, was analysed as a composite of death or mechanical ventilation because the assumption of odds proportionality was not met. Results A total of 129 patients were enrolled (mean age 57 (SD 14) years; 68% men) and all completed follow-up. All patients in the tocilizumab group and two in the standard care group received tocilizumab. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (odds ratio 1.54, 95% confidence interval 0.66 to 3.66; P=0.32). Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group (odds ratio 6.42, 95% confidence interval 1.59 to 43.2). Adverse events were reported in 29 of 67 (43%) patients who received tocilizumab and 21 of 62 (34%) who did not receive tocilizumab. Conclusions In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality. Trial registration ClinicalTrials.gov NCT04403685.
McMaster University1, University of Washington2, United Arab Emirates University3, Copenhagen University Hospital4, St Thomas' Hospital5, University of Michigan6, King Saud bin Abdulaziz University for Health Sciences7, Albert Einstein College of Medicine8, University of Toronto9, Rhode Island Hospital10, Brown University11, Utrecht University12, NewYork–Presbyterian Hospital13, Peking Union Medical College Hospital14, Federal University of São Paulo15, Humanitas University16, University of Ulsan17, National Institutes of Health18, Jagiellonian University Medical College19, Population Health Research Institute20, University of Manitoba21, University at Buffalo22, Homi Bhabha National Institute23, Baylor College of Medicine24, Vanderbilt University25, University of Milano-Bicocca26, King Saud Medical City27, The George Institute for Global Health28, Royal North Shore Hospital29, University of Virginia30, University of Dammam31, Emory University32, University of Pennsylvania33, Agostino Gemelli University Polyclinic34, St George’s University Hospitals NHS Foundation Trust35
TL;DR: The Surviving Sepsis Campaign Coronavirus Diease 2019 (SCCD) 2019 panel as mentioned in this paper provided guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU.
Abstract: Background The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. Methods The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Results The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. Conclusion The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.
22 Feb 2021
TL;DR: In this paper, there has been noteworthy concern about the impact of COVID-19 pandemic on health services including the management of cancer including cancer management, in addition to being considered at higher risk for worse outcom...
Abstract: PURPOSEThere has been noteworthy concern about the impact of COVID-19 pandemic on health services including the management of cancer. In addition to being considered at higher risk for worse outcom...
Free University of Berlin1, Hospital Kuala Lumpur2, Cleveland Clinic3, Mater Dei Hospital4, University of Zurich5, Kantonsspital St. Gallen6, Medical University of Vienna7, Montreal Children's Hospital8, University of Cincinnati9, University of Southern Denmark10, Technische Universität München11, Opole University12, Federal University of Paraná13, University of Southampton14, Federal University of São Paulo15, New York University16, University of Debrecen17, Istanbul University18, Pompeu Fabra University19, University of Coimbra20, Vrije Universiteit Brussel21, Bethel University22, Laval University23, Hiroshima University24, Medical University of South Carolina25, Hannover Medical School26, Rappaport Faculty of Medicine27, Koç University28, Mahidol University29, University of Helsinki30, Royal Free Hospital31, Fraunhofer Society32, National and Kapodistrian University of Athens33, University of Groningen34, Nippon Medical School35, University of Milan36, Universidad Nacional de Asunción37, Johns Hopkins University38, Hacettepe University39, University of Paris40, University of Mainz41, University of Perugia42, University of Toronto43, University of Copenhagen44, Aarhus University Hospital45, Peking University46
TL;DR: This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS) on 3 December 2020 as mentioned in this paper, with the participation of 64 delegates of 50 national and international societies and from 31 countries.
Abstract: This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
TL;DR: Differences in conceptual definition of sarcopenia in the elderly and in CKD are discussed, as well as etiology of sarc Openia, prevalence, outcome, and interventions that attempted to reverse the loss of muscle mass, strength and mobility in CKd and ESKD patients are described.
Abstract: The term sarcopenia was first introduced in 1988 by Irwin Rosenberg to define a condition of muscle loss that occurs in the elderly. Since then, a broader definition comprising not only loss of muscle mass, but also loss of muscle strength and low physical performance due to ageing or other conditions, was developed and published in consensus papers from geriatric societies. Sarcopenia was proposed to be diagnosed based on operational criteria using two components of muscle abnormalities, low muscle mass and low muscle function. This brought awareness of an important nutritional derangement with adverse outcomes for the overall health. In parallel, many studies in patients with chronic kidney disease (CKD) have shown that sarcopenia is a prevalent condition, mainly among patients with end stage kidney disease (ESKD) on hemodialysis (HD). In CKD, sarcopenia is not necessarily age-related as it occurs as a result of the accelerated protein catabolism from the disease and from the dialysis procedure per se combined with low energy and protein intakes. Observational studies showed that sarcopenia and especially low muscle strength is associated with worse clinical outcomes, including worse quality of life (QoL) and higher hospitalization and mortality rates. This review aims to discuss the differences in conceptual definition of sarcopenia in the elderly and in CKD, as well as to describe etiology of sarcopenia, prevalence, outcome, and interventions that attempted to reverse the loss of muscle mass, strength and mobility in CKD and ESKD patients.
TL;DR: Arketamine might produce fast-onset and sustained antidepressant effects in humans with favorable safety profile, like previously reported with animals; further controlled-trials are needed.
Abstract: We aimed to analyze the efficacy and safety of arketamine, the R(−)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery–Asberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion to 10.4 after one day, a mean difference of 20.3 points [CI 95% 13.6–27.0; p < 0.001]; dissociation was nearly absent. Arketamine might produce fast-onset and sustained antidepressant effects in humans with favorable safety profile, like previously reported with animals; further controlled-trials are needed.
TL;DR: The COVID-19 pandemic has a negative impact on physical activity and physical activity programs should be encouraged, while respecting the necessary social distancing to prevent the spread of Severe Acute Respiratory Syndrome Coronavirus 2.
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a strong negative impact on economic and social life worldwide. It has also negatively influenced people’s general health and quality of life. The aim of the present study was to study the impact of social distancing on physical activity level, and the association between mood state (depression and anxiety level) or sex with actual physical activity levels, the change in physical activity caused by social distancing period, the adhesion level to social distancing, the adoption time of social distancing, family income and age. A self-administered questionnaire with personal, quarantine, physical activity, and mood state disorders information’s was answered by 2140 Brazilians of both sex who were recruited through online advertising. The physical activity level adopted during the period of social distancing (2.9 ± 1.1) was lower than that adopted prior to the pandemic period (3.5 ± 0.8, p < 0.001). Thirty percent of the participants presented symptoms of moderate/severe depression and 23.3% displayed moderate/severe anxiety symptoms. A greater presence of symptoms related to anxiety and depression were associated with low physical activity levels, low family monthly income, and younger age. A higher percentage of men who had no mood disorders was observed among those who were very active than among those less active. The COVID-19 pandemic has a negative impact on physical activity. Those who reduced their level of physical activity had the highest levels of mood disorders. Therefore, physical activity programs should be encouraged, while respecting the necessary social distancing to prevent the spread of Severe Acute Respiratory Syndrome Coronavirus 2.
University of Washington1, St George’s University Hospitals NHS Foundation Trust2, McMaster University3, Agostino Gemelli University Polyclinic4, Emory University5, Federal University of São Paulo6, Ottawa Hospital7, St Thomas' Hospital8, University of Michigan9, Cooper University Hospital10, University of Kansas11, University of Amsterdam12, United Arab Emirates University13, University of Pittsburgh14, King Saud bin Abdulaziz University for Health Sciences15, University of São Paulo16, University of Minnesota17, Population Health Research Institute18, University of Toronto19, University of Kentucky20, Ghent University Hospital21, University of Tokyo22, Peking Union Medical College Hospital23, Hebron University24, Monash University25, Copenhagen University Hospital26, Liverpool School of Tropical Medicine27, Vanderbilt University28, Brigham and Women's Hospital29, University of Ulsan30, University of Manitoba31, Makerere University32, Faculdade de Medicina de São José do Rio Preto33, National Institutes of Health34, Mount Sinai Hospital, Toronto35, Medanta36, University of the Witwatersrand37, New York University38, Washington University in St. Louis39, University of Alberta40, Hennepin County Medical Center41, Royal Brisbane and Women's Hospital42, University of Pennsylvania43, Hebrew University of Jerusalem44, Hochschule Hannover45, Brown University46
TL;DR: This paper used topic identification and sentiment analysis to explore a large number of tweets in both countries with a high number of spreading and deaths by COVID-19, Brazil, and the USA.
TL;DR: In this paper, a systematic review conducted with a comprehensive search including formal databases, COVID-19 or SARS-CoV-2 data sources, grey literature, and manual search is presented.
Abstract: AIMS: To identify, systematically evaluate and summarise the best available evidence on the frequency of long COVID-19 (post-acute COVID-19 syndrome), its clinical manifestations, and the criteria used for diagnosis. METHODS: Systematic review conducted with a comprehensive search including formal databases, COVID-19 or SARS-CoV-2 data sources, grey literature, and manual search. We considered for inclusion clinical trials, observational longitudinal comparative and non-comparative studies, cross-sectional, before-and-after, and case series. We assessed the methodological quality by specific tools based on the study designs. We presented the results as a narrative synthesis regarding the frequency and duration of long COVID-19, signs and symptoms, criteria used for diagnosis, and potential risk factors. RESULTS: We included 25 observational studies with moderate to high methodological quality, considering 5440 participants. The frequency of long COVID-19 ranged from 4.7% to 80%, and the most prevalent signs/symptoms were chest pain (up to 89%), fatigue (up to 65%), dyspnea (up to 61%), and cough and sputum production (up to 59%). Temporal criteria used to define long COVID-19 varied from 3 to 24 weeks after acute phase or hospital discharge. Potentially associated risk factors were old age, female sex, severe clinical status, a high number of comorbidities, hospital admission, and oxygen supplementation at the acute phase. However, limitations related to study designs added uncertainty to this finding. None of the studies assessed the duration of signs/symptoms. CONCLUSION: The frequency of long COVID-19 reached up to 80% over the studies included and occurred between 3 and 24 weeks after acute phase or hospital discharge. Chest pain, fatigue, dyspnea, and cough were the most reported clinical manifestations attributed to the condition. Based on these systematic review findings, there is an urgent need to understand this emerging, complex and challenging medical condition. Proposals for diagnostic criteria and standard terminology are welcome.
University of Paris1, Istituto Superiore di Sanità2, University of Padua3, Charité4, University of Helsinki5, Oslo University Hospital6, Clínica Alemana7, Innsbruck Medical University8, Imperial College London9, University of Zagreb10, Federal University of São Paulo11, Canadian Blood Services12, NHS Blood and Transplant13, University of Pennsylvania14, Eurotransplant15
TL;DR: In this paper, the effect of the COVID-19 pandemic on transplantation and investigate if the pandemic was associated with heterogeneous adaptation in terms of organ transplantation, with ensuing consequences for waitlisted patients.
Abstract: Summary Background Preliminary data suggest that COVID-19 has reduced access to solid organ transplantation. However, the global consequences of the COVID-19 pandemic on transplantation rates and the effect on waitlisted patients have not been reported. We aimed to assess the effect of the COVID-19 pandemic on transplantation and investigate if the pandemic was associated with heterogeneous adaptation in terms of organ transplantation, with ensuing consequences for waitlisted patients. Methods In this population-based, observational, before-and-after study, we collected and validated nationwide cohorts of consecutive kidney, liver, lung, and heart transplants from 22 countries. Data were collected from Jan 1 to Dec 31, 2020, along with data from the same period in 2019. The analysis was done from the onset of the 100th cumulative COVID-19 case through to Dec 31, 2020. We assessed the effect of the pandemic on the worldwide organ transplantation rate and the disparity in transplant numbers within each country. We estimated the number of waitlisted patient life-years lost due to the negative effects of the pandemic. The study is registered with ClinicalTrials.gov , NCT04416256 . Findings Transplant activity in all countries studied showed an overall decrease during the pandemic. Kidney transplantation was the most affected, followed by lung, liver, and heart. We identified three organ transplant rate patterns, as follows: countries with a sharp decrease in transplantation rate with a low COVID-19-related death rate; countries with a moderate decrease in transplantation rate with a moderate COVID-19-related death rate; and countries with a slight decrease in transplantation rate despite a high COVID-19-related death rate. Temporal trends revealed a marked worldwide reduction in transplant activity during the first 3 months of the pandemic, with losses stabilising after June, 2020, but decreasing again from October to December, 2020. The overall reduction in transplants during the observation time period translated to 48 239 waitlisted patient life-years lost. Interpretation We quantified the impact of the COVID-19 pandemic on worldwide organ transplantation activity and revealed heterogeneous adaptation in terms of organ transplantation, both at national levels and within countries, with detrimental consequences for waitlisted patients. Understanding how different countries and health-care systems responded to COVID-19-related challenges could facilitate improved pandemic preparedness, notably, how to safely maintain transplant programmes, both with immediate and non-immediate life-saving potential, to prevent loss of patient life-years. Funding French national research agency (INSERM) ATIP Avenir and Fondation Bettencourt Schueller.
University of Cologne1, Cornell University2, NewYork–Presbyterian Hospital3, Federal University of Rio de Janeiro4, Collaborative Drug Discovery5, University of California, San Diego6, Innsbruck Medical University7, University of Nizwa8, University of Genoa9, Federal University of São Paulo10, Masaryk University11, Goethe University Frankfurt12, Amrita Institute of Medical Sciences and Research Centre13, Medical University of Graz14, University of Manchester15, Wayne State University16, University of Melbourne17, Peter MacCallum Cancer Centre18, Heidelberg University19, Hamad Medical Corporation20, University of Exeter21, University of Hong Kong22, University of Minnesota23, University of Hamburg24, University of Belgrade25, University of Angers26, University of Colombo27, University of Delhi28, Radboud University Nijmegen29, National and Kapodistrian University of Athens30, Palacký University, Olomouc31, Federal University of Paraná32, University of Texas Health Science Center at San Antonio33, Sheba Medical Center34, Trinity College, Dublin35, University of Toronto36, Universitas Kristen Indonesia37, University of Indonesia38
TL;DR: The One World One Guideline initiative as mentioned in this paper has been used to incorporate regional differences in the epidemiology and management of rare mold infections, including Fusarium, Lomentospora, Scedosporium, dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces and Purpureocillium species.
Abstract: With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.
Raul G Nogueira1, Mohamad Abdalkader2, Muhammed M. Qureshi2, Michael Frankel1 +269 more•Institutions (98)
TL;DR: In this paper, the authors measured the global impact of the COVID-19 pandemic on the volumes of the volumes for medical care in the United Kingdom and the United States.
Abstract: BackgroundThe COVID-19 pandemic led to profound changes in the organization of health care systems worldwide.AimsWe sought to measure the global impact of the COVID-19 pandemic on the volumes for m...
University of Coimbra1, Autonomous University of Barcelona2, Kuwait University3, Montreal Children's Hospital4, University of Cincinnati Academic Health Center5, Federal University of São Paulo6, Russian National Research Medical University7, I.M. Sechenov First Moscow State Medical University8, Guy's Hospital9, Hiroshima University10, Campbelltown Hospital11, Mashhad University of Medical Sciences12, Koç University13, Mahidol University14, University of Cape Town15, University of Mainz16, Sun Yat-sen University17, Charité18
TL;DR: In this article, the impact of chronic spontaneous urticaria (CSU) on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society is reviewed.
Abstract: Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle-aged women. It usually lasts for several years (> 1 year in 25-75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1 -antihistamines, even at higher doses, and third- and fourth-line therapies (omalizumab and ciclosporin) control the disease only in two-thirds of H1 -antihistamine-resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health-related quality of life (HRQoL), particularly when CSU is associated with angio-oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio-oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.
University of Paris1, Wake Forest University2, Gandhi Medical College3, Max Super Speciality Hospital4, University of Adelaide5, McMaster University6, King Saud bin Abdulaziz University for Health Sciences7, Columbia University8, Pontifical Catholic University of Chile9, Erasmus University Rotterdam10, University of Toronto11, University of Melbourne12, Peking Union Medical College Hospital13, Shaare Zedek Medical Center14, Mayo Clinic15, University of Maryland, College Park16, University of Montpellier17, University of Ulsan18, Federal University of São Paulo19, Vrije Universiteit Brussel20, University of Maryland, Baltimore21, University of Manchester22, Paris 12 Val de Marne University23, University of the Witwatersrand24, Cedars-Sinai Medical Center25, University of Michigan26, University of Genoa27, Christian Medical College & Hospital28, Alexandra Hospital29, Monash University30, University of Lausanne31, Medical University of Vienna32, University of Oxford33, Mahidol University34, University of Amsterdam35, King's College London36, Guy's and St Thomas' NHS Foundation Trust37, Imperial College London38, Tata Memorial Hospital39
TL;DR: Using a Delphi process, an international panel of experts developed clinical practice statements on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) in areas where evidence is absent or limited as discussed by the authors.
Abstract: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable). Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. Trial registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.
King Saud bin Abdulaziz University for Health Sciences1, Saint Louis University Hospital2, University Health System3, University of the Algarve4, University of Pittsburgh5, Humanitas University6, Peking Union Medical College Hospital7, University of Toronto8, Sunnybrook Health Sciences Centre9, The Chinese University of Hong Kong10, University of Oxford11, University of Amsterdam12, Utrecht University13, Vanderbilt University14, Federal University of São Paulo15, Emory University16, Katholieke Universiteit Leuven17, St George’s University Hospitals NHS Foundation Trust18, University of Paris19, Université libre de Bruxelles20, University of Milano-Bicocca21
TL;DR: The COVID-19 pandemic has highlighted key elements of emergency preparedness, such as having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols as discussed by the authors.
Abstract: Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients.
TL;DR: Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE’s sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.
Abstract: The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE’s sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.