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3. Guidelines and standards for the study of death and recalled experiences of death––a multidisciplinary consensus statement and proposed future directions

Author

Parnia, Sam, Post, Stephen G, Lee, Matthew T, Lyubomirsky, Sonja, Aufderheide, Tom P, Deakin, Charles D, Greyson, Bruce, Long, Jeffrey, Gonzales, Anelly M, Huppert, Elise L, Dickinson, Analise, Mayer, Stephan, Locicero, Briana, Levin, Jeff, Bossis, Anthony, Worthington, Everett, Fenwick, Peter, and Shirazi, Tara Keshavarz

Subjects
Biomedical and Clinical Sciences, Philosophy and Religious Studies, Applied Ethics, Cardiovascular, Heart Disease, Brain Disorders, Neurosciences, Brain, Cardiopulmonary Resuscitation, Consciousness, Heart Arrest, Humans, Mental Recall, death, cardiac arrest, resuscitation, death by brain death criteria, near-death experiences, out-of-body experiences, external visual awareness, recalled experience of death (RED) coma, cardiopulmonary resuscitation-induced consciousness, post-intensive care syndrome, General Science & Technology
Abstract

An inadvertent consequence of advances in stem cell research, neuroscience, and resuscitation science has been to enable scientific insights regarding what happens to the human brain in relation to death. The scientific exploration of death is in large part possible due to the recognition that brain cells are more resilient to the effects of anoxia than assumed. Hence, brain cells become irreversibly damaged and "die" over hours to days postmortem. Resuscitation science has enabled life to be restored to millions of people after their hearts had stopped. These survivors have described a unique set of recollections in relation to death that appear universal. We review the literature, with a focus on death, the recalled experiences in relation to cardiac arrest, post-intensive care syndrome, and related phenomena that provide insights into potential mechanisms, ethical implications, and methodologic considerations for systematic investigation. We also identify issues and controversies related to the study of consciousness and the recalled experience of cardiac arrest and death in subjects who have been in a coma, with a view to standardize and facilitate future research.

Published
2022

4. AWAreness during REsuscitation - II: A multi-center study of consciousness and awareness in cardiac arrest

Author

Parnia, Sam, Keshavarz Shirazi, Tara, Patel, Jignesh, Tran, Linh, Sinha, Niraj, O'Neill, Caitlin, Roellke, Emma, Mengotto, Amanda, Findlay, Shannon, McBrine, Michael, Spiegel, Rebecca, Tarpey, Thaddeus, Huppert, Elise, Jaffe, Ian, Gonzales, Anelly M., Xu, Jing, Koopman, Emmeline, Perkins, Gavin D, Vuylsteke, Alain, Bloom, Benjamin M., Jarman, Heather, Nam Tong, Hiu, Chan, Louisa, Lyaker, Michael, Thomas, Matthew, Velchev, Veselin, Cairns, Charles B., Sharm, Rahul, Kulstad, Erik, Scherer, Elizabeth, O'Keeffe, Terence, Foroozesh, Mahtab, Abe, Olumayowa, Ogedegbe, Chinwe, Girgis, Amira, Pradhan, Deepak, and Deakin, Charles D.

Published
2023
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10. The effect of particulate matter pollution on bronchial epithelial cell responses

Author

Parnia, Sam

Subjects
616.238071
Abstract

Asthma is increasing in prevalence around the world. It is clinically characterised by shortness of breath, wheeze and cough and pathologically by increased Th2 inflammation, mucus hypersecretion and airway remodelling Epidemiological studies have linked inhalation of particulate matter (PM) with asthma, and although exposure has been shown to lead to acute airway inflammation, there is uncertainty regarding the mechanisms underlying the inflammatory response and the contribution of particulate matter to airway remodelling and asthma chronicity. In this study the effects of diesel exhaust particles (DEP) and residual oil fly ash (ROFA) on bronchial epithelial cell activation are investigated. It is postulated that DEP leads to inflammatory effects on bronchial epithelial cells as measured by the release of IL-8 via release of EGFR ligands and activation of the epidermal growth factor receptor (EGFR). In addition, it is further hypothesised that exposure of bronchial epithelial cells to DEP and ROFA leads to increased mucin gene expression. Recognising the contribution of IL-13 as a key allergic mediator in asthma it is postulated that DEP and IL-13 are synergistic in their effects on bronchial epithelial cells. Bronchial epithelial cells were cultured and exposed to DEP or ROFA. Methylene Blue assay was used to measure cell number, LDH assay to measure cell toxicity, TAQMAN RT-PCR to measure gene expression and ELISA to measure growth factor and cytokine release. In response to DEP > 50Jlgiml there was a modest increase in cytotoxicity in H292 cells and primary bronchial epithelial cells (PBEC) but not in 16HBEo - cells. DEP did not cause increased IL-8 release from H292 or 16HBEocells. Using PBEC there was significantly increased IL-8 gene and protein expression in response to DEP. IL-8 was released via activation of the EGFR. This was demonstrated by neutralisation of the EGFR and involved the shedding of the EGFR ligands Transforming Growth Factor a (TGFa) and Amphiregulin (AR). DEP and ROFA led to enhanced expression of gel forming and membrane bound mucin genes. DEP enhanced the gel forming mucin, MUC2 as well as the membrane bound mucins MUC1 and MUC4. ROFA led to enhanced induction of the gel forming mucins MUC5AC, MUC5B and MUC2 as well as the membrane bound mucin gene; MUC4. The inflammatory effects of DEP were enhanced in an additive fashion in the presence of the Th2 cytokines IL-4 and IL-13, suggesting that these effects of DEP may be more marked in asthmatic airways where Th2 cytokines are over-expressed. DEP activates bronchial epithelial cells through activation of the EGFR. This may contribute to inflammation and remodelling responses that are found in asthma. The increase in mucin gene expression may be a normal protective mechanism but may contribute to the symptoms and pathology of asthma. These changes may, in part, account for the recent epidemiological trends in asthma prevalence.

Published
2007

14. A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19

Author

Bowdish, Michael E., primary, Barkauskas, Christina E., additional, Overbey, Jessica R., additional, Gottlieb, Robert L., additional, Osman, Keren, additional, Duggal, Abhijit, additional, Marks, Mary E., additional, Hupf, Jonathan, additional, Fernandes, Eustace, additional, Leshnower, Bradley G., additional, Golob, Jonathan L., additional, Iribarne, Alexander, additional, Rassias, Athos J., additional, Moquete, Ellen G., additional, O’Sullivan, Karen, additional, Chang, Helena L., additional, Williams, Judson B., additional, Parnia, Sam, additional, Patel, Nirav C., additional, Desai, Nimesh D., additional, Vekstein, Andrew M., additional, Hollister, Beth A., additional, Possemato, Tammie, additional, Romero, Christian, additional, Hou, Peter C., additional, Burke, Elizabeth, additional, Hayes, Jack, additional, Grossman, Fred, additional, Itescu, Silviu, additional, Gillinov, Marc, additional, Pagani, Francis D., additional, O’Gara, Patrick T., additional, Mack, Michael J., additional, Smith, Peter K., additional, Bagiella, Emilia, additional, Moskowitz, Alan J., additional, and Gelijns, Annetine C., additional

Published
2023
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16. Awareness During Resuscitation - II: A Multi-Center Study of Consciousness and Awareness in Cardiac Arrest

Author

parnia, sam, primary, Keshavarz Shirazi, Tara, additional, Patel, Jignesh K., additional, Tran, Linh, additional, Sinha, Niraj, additional, Caitlin, O'Neill, additional, Roellke, Emma, additional, Mengotto, Amanda, additional, Findlay, Shannon, additional, McBrine, Michael, additional, Spiegel, Rebecca, additional, Tarpey, Thaddeus, additional, Huppert, Elise, additional, Jaffe, Ian S., additional, Gonzales, Anelly M., additional, Xu, Jing, additional, Koopman, Emmeline, additional, Perkins, Gavin D., additional, Vuylsteke, Alain, additional, Bloom, Ben, additional, Jarman, Heather, additional, Nam Tong, Hiu, additional, Chan, Louisa, additional, Michael, Lyaker, additional, Thomas, Matthew, additional, Velchev, Veselin, additional, Cairns, Charles, additional, Sharma, Rahul, additional, Kulstad, Erik, additional, Schrerer, Elizabeth, additional, O'Keeffe, Terence, additional, Foroozesh, Mahtab, additional, Abe, Olumayowa, additional, Ogedegbe, Chinwe, additional, Girgis, Amira, additional, Pradhan, Deepak, additional, and Deakin, Charles, additional

Published
2023
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18. AWARE—AWAreness during REsuscitation—A prospective study

Author

Parnia, Sam, Spearpoint, Ken, de Vos, Gabriele, Fenwick, Peter, Goldberg, Diana, Yang, Jie, Zhu, Jiawen, Baker, Katie, Killingback, Hayley, McLean, Paula, Wood, Melanie, Zafari, A. Maziar, Dickert, Neal, Beisteiner, Roland, Sterz, Fritz, Berger, Michael, Warlow, Celia, Bullock, Siobhan, Lovett, Salli, McPara, Russell Metcalfe Smith, Marti-Navarette, Sandra, Cushing, Pam, Wills, Paul, Harris, Kayla, Sutton, Jenny, Walmsley, Anthony, Deakin, Charles D., Little, Paul, Farber, Mark, Greyson, Bruce, and Schoenfeld, Elinor R.

Published
2014
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26. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Author

Goligher, Ewan C, Bradbury, Charlotte A, McVerry, Bryan J, Lawler, Patrick R, Berger, Jeffrey S, Gong, Michelle N, Carrier, Marc, Reynolds, Harmony R, Kumar, Anand, Turgeon, Alexis F, Kornblith, Lucy Z, Kahn, Susan R, Marshall, John C, Kim, Keri S, Houston, Brett L, Derde, Lennie PG, Cushman, Mary, Tritschler, Tobias, Angus, Derek C, Godoy, Lucas C, McQuilten, Zoe, Kirwan, Bridget-Anne, Farkouh, Michael E, Brooks, Maria M, Lewis, Roger J, Berry, Lindsay R, Lorenzi, Elizabeth, Gordon, Anthony C, Berry, Scott M, McArthur, Colin J, Neal, Matthew D, Hochman, Judith S, Webb, Steven A, Zarychanski, Ryan, Ahuja, Tania, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Kreuziger, Lisa Baumann, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Contreras, Aira, Costantini, Todd W, de Brouwer, Sophie, Detry, Michelle A, Duggal, Abhijit, Dzavik, Vladimir, Effron, Mark B, Eng, Heather F, Escobedo, Jorge, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Froess, Joshua D, Fu, Zhuxuan, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, Girard, Timothy D, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Haniffa, Rashan, Hegde, Sheila M, Hendrickson, Carolyn M, Higgins, Alisa M, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Huang, David T, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei, King, Andrew J, Kornblith, Aaron E, Kutcher, Matthew E, Laffan, Michael A, Lamontagne, Francois, Le Gal, Gregoire, Leeper, Christine M, Leifer, Eric S, Lim, George, Lima, Felipe Gallego, Linstrum, Kelsey, Litton, Edward, Lopez-Sendon, Jose, Lother, Sylvain A, Marten, Nicole, Marinez, Andrea Saud, Martinez, Mary, Garcia, Eduardo Mateos, Mavromichalis, Stavroula, McAuley, Daniel F, McDonald, Emily G, McGlothlin, Anna, McGuinness, Shay P, Middeldorp, Saskia, Montgomery, Stephanie K, Mouncey, Paul R, Murthy, Srinivas, Nair, Girish B, Nair, Rahul, Nichol, Alistair D, Nicolau, Jose C, Nunez-Garcia, Brenda, Park, John J, Park, Pauline K, Parke, Rachael L, Parker, Jane C, Parnia, Sam, Paul, Jonathan D, Pompilio, Mauricio, Quigley, John G, Rosenson, Robert S, Rost, Natalia S, Rowan, Kathryn, Santos, Fernanda O, Santos, Marlene, Santos, Mayler O, Satterwhite, Lewis, Saunders, Christina T, Schreiber, Jake, Schutgens, Roger EG, Seymour, Christopher W, Siegal, Deborah M, Silva, Delcio G, Singhal, Aneesh B, Slutsky, Arthur S, Solvason, Dayna, Turner, Anne M, Van Bentum-Puijk, Wilma, van de Veerdonk, Frank L, van Diepen, Sean, Vazquez-Grande, Gloria, Wahid, Lana, Wareham, Vanessa, Widmer, R Jay, Wilson, Jennifer G, Yuriditsky, Eugene, Zhong, Yongqi, Investigators, REMAP-CAP, Investigators, ACTIV-4a, Investigators, ATTACC, NIHR, National Institute for Health Research, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institutes of Health, NIH: 1OT2HL156812-01, AR7-162822, OTA-20-011, RP-2015-06-18, National Heart, Lung, and Blood Institute, NHLBI, Amgen, CancerCare Manitoba Foundation, CCMF, University of Manitoba, UM, Health Research Board, HRB: CTN 2014-012, Canadian Institutes of Health Research, CIHR: 158584, 447335, COVID-19, National Institute for Health Research, NIHR, European Commission, EC: 602525, FP7-HEALTH-2013-INNOVATION, National Health and Medical Research Council, NHMRC: APP1101719, APP1116530, Health Research Council of New Zealand, HRC: 16/631, Eisai, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Université Pierre et Marie Curie, UPMC, Horizon 2020: 101003589, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, REMAP-CAP was supported by the European Union through FP7-HEALTH-2013-INNOVATION: the Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) consortium (grant 602525) and the Horizon 2020 research and innovation program: the Rapid European Covid-19 Emergency Research response (RECOVER) consortium (grant 101003589) and by grants from the Australian National Health and Medical Research Council (APP1101719 and APP1116530), the Health Research Council of New Zealand (16/631), the Canadian Institutes of Health Research (Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant 158584 and COVID-19 Rapid Research Operating Grant 447335), the U.K. National Institute for Health Research (NIHR) and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (CTN 2014-012), the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (PHRC-20-0147), the Minderoo Foundation, Amgen, Eisai, the Global Coalition for Adaptive Research, and the Wellcome Trust Innovations Project (215522). The ATTACC platform was supported by grants from the Canadian Institutes of Health Research, LifeArc, Thistledown Foundation, Research Manitoba, CancerCare Manitoba Foundation, Victoria General Hospital Foundation, Ontario Ministry of Health, and the Peter Munk Cardiac Centre. The ACTIV-4a platform was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and administered through OTA-20-011 and was supported in part by NIH agreement 1OT2HL156812-01. Dr. Goligher is the recipient of an Early Career Investigator award from the Canadian Institutes of Health Research (grant AR7-162822). Dr. Gordon is funded by an NIHR Research Professorship (RP-2015-06-18). Dr. Turgeon is funded by a Canada Research Chair-Tier 2. Dr. Zarychanski is the recipient of the Lyonel G. Israels Research Chair in Hematology (University of Manitoba)., Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, Investigators, REMAP-CAP, Investigators, ACTIV-4a, Investigators, ATTACC, REMAP-CAP Investigators, ACTIV-4a Investigators, and ATTACC Investigators

Subjects
Male, covid-19, anticoagulation, adaptive platform trial, [SDV]Life Sciences [q-bio], Critical Illness, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Hemorrhage, 030204 cardiovascular system & hematology, heparin, COVID-19/drug therapy, 03 medical and health sciences, 0302 clinical medicine, Medicine, General & Internal, Hemorrhage/chemically induced, General & Internal Medicine, Odds Ratio, thrombosis, covid-19, Humans, 030212 general & internal medicine, Hospital Mortality, Treatment Failure, Heparin/administration & dosage, anticoagulation, 11 Medical and Health Sciences, Aged, Anticoagulants/administration & dosage, Science & Technology, Thrombosis/prevention & control, Heparin, low molecular weight heparin, Anticoagulants, COVID-19, Thrombosis, General Medicine, Middle Aged, Respiration, Artificial, 3. Good health, COVID-19 Drug Treatment, critical care, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Logistic Models, ACTIV-4a Investigators, Female, Human medicine, ATTACC Investigators, REMAP-CAP Investigators, Covid-19, Life Sciences & Biomedicine
Abstract

BACKGROUNDThrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.METHODSIn an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.RESULTSThe trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support–free days was 1 (interquartile range, −1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, −1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio CONCLUSIONSIn critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707. opens in new tab, NCT04505774. opens in new tab, NCT04359277. opens in new tab, and NCT04372589. opens in new tab.)

Published
2021

27. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Author

REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Goligher, Ewan C, Bradbury, Charlotte A, McVerry, Bryan J, Lawler, Patrick R, Berger, Jeffrey S, Gong, Michelle N, Carrier, Marc, Reynolds, Harmony R, Kumar, Anand, Turgeon, Alexis F, Kornblith, Lucy Z, Kahn, Susan R, Marshall, John C, Kim, Keri S, Houston, Brett L, Derde, Lennie PG, Cushman, Mary, Tritschler, Tobias, Angus, Derek C, Godoy, Lucas C, McQuilten, Zoe, Kirwan, Bridget-Anne, Farkouh, Michael E, Brooks, Maria M, Lewis, Roger J, Berry, Lindsay R, Lorenzi, Elizabeth, Gordon, Anthony C, Ahuja, Tania, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Contreras, Aira, Costantini, Todd W, de Brouwer, Sophie, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Eng, Heather F, Escobedo, Jorge, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Froess, Joshua D, Fu, Zhuxuan, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, Girard, Timothy D, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Haniffa, Rashan, Hegde, Sheila M, Hendrickson, Carolyn M, Higgins, Alisa M, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Huang, David T, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei, King, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, Kutcher, Matthew E, Laffan, Michael A, Lamontagne, Francois, Le Gal, Grégoire, Leeper, Christine M, Leifer, Eric S, Lim, George, Gallego Lima, Felipe, Linstrum, Kelsey, Litton, Edward, Lopez-Sendon, Jose, Lother, Sylvain A, Marten, Nicole, Saud Marinez, Andréa, Martinez, Mary, Mateos Garcia, Eduardo, Mavromichalis, Stavroula, McAuley, Daniel F, McDonald, Emily G, McGlothlin, Anna, McGuinness, Shay P, Middeldorp, Saskia, Montgomery, Stephanie K, Mouncey, Paul R, Murthy, Srinivas, Nair, Girish B, Nair, Rahul, Nichol, Alistair D, Nicolau, Jose C, Nunez-Garcia, Brenda, Park, John J, Park, Pauline K, Parke, Rachael L, Parker, Jane C, Parnia, Sam, Paul, Jonathan D, Pompilio, Mauricio, Quigley, John G, Rosenson, Robert S, Rost, Natalia S, Rowan, Kathryn, Santos, Fernanda O, Santos, Marlene, Santos, Mayler O, Satterwhite, Lewis, Saunders, Christina T, Schreiber, Jake, Schutgens, Roger EG, Seymour, Christopher W, Siegal, Deborah M, Silva, Delcio G, Singhal, Aneesh B, Slutsky, Arthur S, Solvason, Dayna, Stanworth, Simon J, Turner, Anne M, van Bentum-Puijk, Wilma, van de Veerdonk, Frank L, van Diepen, Sean, Vazquez-Grande, Gloria, Wahid, Lana, Wareham, Vanessa, Widmer, R Jay, Wilson, Jennifer G, Yuriditsky, Eugene, Zhong, Yongqi, Berry, Scott M, McArthur, Colin J, Neal, Matthew D, Hochman, Judith S, Webb, Steven A, Zarychanski, Ryan, Bradbury, Charlotte A [0000-0001-5248-8165], McVerry, Bryan J [0000-0002-1175-4874], Lawler, Patrick R [0000-0001-5155-5071], Carrier, Marc [0000-0001-8296-2972], Kim, Keri S [0000-0002-8480-4801], Houston, Brett L [0000-0002-8776-4083], Cushman, Mary [0000-0002-7871-6143], Tritschler, Tobias [0000-0002-8775-0511], Godoy, Lucas C [0000-0001-6171-1269], Gordon, Anthony C [0000-0002-0419-547X], Ahuja, Tania [0000-0003-1833-4124], Aryal, Diptesh [0000-0002-1431-8293], Baumann Kreuziger, Lisa [0000-0002-1171-0548], Beane, Abi [0000-0001-7046-1580], Coiffard, Benjamin [0000-0002-8896-5346], Detry, Michelle A [0000-0002-2794-1439], Escobedo, Jorge [0000-0003-1942-7402], Estcourt, Lise J [0000-0003-4309-9162], Everett, Brendan M [0000-0002-6331-5224], Fu, Zhuxuan [0000-0002-9190-195X], Galen, Benjamin T [0000-0001-8172-258X], Girard, Timothy D [0000-0002-9833-4871], Greenstein, Yonatan Y [0000-0002-5718-4408], Haniffa, Rashan [0000-0002-8288-449X], Hegde, Sheila M [0000-0001-8157-8899], Hendrickson, Carolyn M [0000-0003-4662-2385], Higgins, Alisa M [0000-0001-8295-7559], Hindenburg, Alexander A [0000-0002-1232-2168], Horvat, Christopher M [0000-0002-1593-2252], Huang, David T [0000-0001-7649-1633], Jacobson, Jeffrey R [0000-0001-8929-994X], Kim, Yuri [0000-0001-5978-5779], King, Andrew J [0000-0002-9809-0563], Kutcher, Matthew E [0000-0003-4566-5359], Leifer, Eric S [0000-0001-6888-8307], Litton, Edward [0000-0002-5125-6829], Mateos Garcia, Eduardo [0000-0002-0904-4056], Mouncey, Paul R [0000-0002-8510-8517], Nunez-Garcia, Brenda [0000-0002-0355-4557], Parnia, Sam [0000-0002-6158-4404], Quigley, John G [0000-0003-3116-4545], Saunders, Christina T [0000-0003-4325-9568], Yuriditsky, Eugene [0000-0003-2263-9297], Zhong, Yongqi [0000-0002-4042-7450], Neal, Matthew D [0000-0001-8931-6236], and Apollo - University of Cambridge Repository

Subjects
Male, Heparin, Critical Illness, Anticoagulants, COVID-19, Hemorrhage, Thrombosis, Middle Aged, Respiration, Artificial, COVID-19 Drug Treatment, Logistic Models, Odds Ratio, Humans, Female, Hospital Mortality, Treatment Failure, Aged
Abstract

BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio

Published
2021

28. CPR-related cognitive activity, consciousness, awareness and recall, and its management: A scoping review

Author

West, Rebecca L., Otto, Quentin, Drennan, Ian R., Rudd, Sarah, Bottiger, Bernd W., Parnia, Sam, Soar, Jasmeet, West, Rebecca L., Otto, Quentin, Drennan, Ian R., Rudd, Sarah, Bottiger, Bernd W., Parnia, Sam, and Soar, Jasmeet

Abstract

Background: There are increasing numbers of reports of cognitive activity, consciousness, awareness and recall related to cardiopulmonary resuscitation (CPR) and interventions such as the use of sedative and analgesic drugs during CPR. Objectives: This scoping review aims to describe the available evidence concerning CPR-related cognitive activity, consciousness, awareness and recall and interventions such as the use of sedative and analgesic drugs during CPR. Methods: A literature search was conducted of Medline, Embase and CINAHL from inception to 21 October 2021. We included case studies, observational studies, review studies and grey literature. Results: We identified 8 observational studies including 40,317 patients and 464 rescuers, and 26 case reports including 33 patients. The reported prevalence of CPR-induced consciousness was between 0.23% to 0.9% of resuscitation attempts, with 48-59% of experienced professional rescuers surveyed estimated to have observed CPR-induced consciousness. CPR-induced consciousness is associated with professional rescuer CPR, witnessed arrest, a shockable rhythm, increased return of spontaneous circulation (ROSC), and survival to hospital discharge when compared to patients without CPR-induced consciousness. Few studies of sedation for CPR-induced consciousness were identified. Although local protocols for treating CPR-induced consciousness exist, there is no widely accepted guidance. Conclusions: CPR-related cognitive activity, consciousness, awareness and recall is uncommon but increasingly reported by professional rescuers. The data available was heterogeneous in nature and not suitable for progression to a systematic review process. Although local treatment protocols exist for management of CPR-induced consciousness, there are no widely accepted treatment guidelines. More studies are required to investigate the management of CPR-induced consciousness.

Published
2022

32. 2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group

Author

Wyckoff, Myra H., primary, Singletary, Eunice M., additional, Soar, Jasmeet, additional, Olasveengen, Theresa M., additional, Greif, Robert, additional, Liley, Helen G., additional, Zideman, David, additional, Bhanji, Farhan, additional, Andersen, Lars W., additional, Avis, Suzanne R., additional, Aziz, Khalid, additional, Bendall, Jason C., additional, Berry, David C., additional, Borra, Vere, additional, Böttiger, Bernd W., additional, Bradley, Richard, additional, Bray, Janet E., additional, Breckwoldt, Jan, additional, Carlson, Jestin N., additional, Cassan, Pascal, additional, Castrén, Maaret, additional, Chang, Wei-Tien, additional, Charlton, Nathan P., additional, Cheng, Adam, additional, Chung, Sung Phil, additional, Considine, Julie, additional, Costa-Nobre, Daniela T., additional, Couper, Keith, additional, Dainty, Katie N., additional, Davis, Peter G., additional, de Almeida, Maria Fernanda, additional, de Caen, Allan R., additional, de Paiva, Edison F., additional, Deakin, Charles D., additional, Djärv, Therese, additional, Douma, Matthew J., additional, Drennan, Ian R., additional, Duff, Jonathan P., additional, Eastwood, Kathryn J., additional, El-Naggar, Walid, additional, Epstein, Jonathan L., additional, Escalante, Raffo, additional, Fabres, Jorge G., additional, Fawke, Joe, additional, Finn, Judith C., additional, Foglia, Elizabeth E., additional, Folke, Fredrik, additional, Freeman, Karoline, additional, Gilfoyle, Elaine, additional, Goolsby, Craig A., additional, Grove, Amy, additional, Guinsburg, Ruth, additional, Hatanaka, Tetsuo, additional, Hazinski, Mary Fran, additional, Heriot, George S., additional, Hirsch, Karen G., additional, Holmberg, Mathias J., additional, Hosono, Shigeharu, additional, Hsieh, Ming-Ju, additional, Hung, Kevin K.C., additional, Hsu, Cindy H., additional, Ikeyama, Takanari, additional, Isayama, Tetsuya, additional, Kapadia, Vishal S., additional, Kawakami, Mandira Daripa, additional, Kim, Han-Suk, additional, Kloeck, David A., additional, Kudenchuk, Peter J., additional, Lagina, Anthony T., additional, Lauridsen, Kasper G., additional, Lavonas, Eric J., additional, Lockey, Andrew S., additional, Malta Hansen, Carolina, additional, Markenson, David, additional, Matsuyama, Tasuku, additional, McKinlay, Christopher J.D., additional, Mehrabian, Amin, additional, Merchant, Raina M., additional, Meyran, Daniel, additional, Morley, Peter T., additional, Morrison, Laurie J., additional, Nation, Kevin J., additional, Nemeth, Michael, additional, Neumar, Robert W., additional, Nicholson, Tonia, additional, Niermeyer, Susan, additional, Nikolaou, Nikolaos, additional, Nishiyama, Chika, additional, O’Neil, Brian J., additional, Orkin, Aaron M., additional, Osemeke, Osokogu, additional, Parr, Michael J., additional, Patocka, Catherine, additional, Pellegrino, Jeffrey L., additional, Perkins, Gavin D., additional, Perlman, Jeffrey M., additional, Rabi, Yacov, additional, Reynolds, Joshua C., additional, Ristagno, Giuseppe, additional, Roehr, Charles C., additional, Sakamoto, Tetsuya, additional, Sandroni, Claudio, additional, Sawyer, Taylor, additional, Schmölzer, Georg M., additional, Schnaubelt, Sebastian, additional, Semeraro, Federico, additional, Skrifvars, Markus B., additional, Smith, Christopher M., additional, Smyth, Michael A., additional, Soll, Roger F., additional, Sugiura, Takahiro, additional, Taylor-Phillips, Sian, additional, Trevisanuto, Daniele, additional, Vaillancourt, Christian, additional, Wang, Tzong-Luen, additional, Weiner, Gary M., additional, Welsford, Michelle, additional, Wigginton, Jane, additional, Wyllie, Jonathan P., additional, Yeung, Joyce, additional, Nolan, Jerry P., additional, Berg, Katherine M., additional, Abelairas-Gómez, Cristian, additional, Barcala-Furelos, Roberto, additional, Beerman, Stephen B., additional, Bierens, Joost, additional, Cacciola, Sofia, additional, Cellini, Jacqueline, additional, Claesson, Andreas, additional, Court, Rachael, additional, D’Arrigo, Sonia, additional, De Brier, Niels, additional, Dunne, Cody L., additional, Elsenga, Hylmar E., additional, Johnson, Samantha, additional, Kleven, Gunn, additional, Maconochie, Ian, additional, Mecrow, Tom, additional, Morgan, Patrick, additional, Otto, Quentin, additional, Palmieri, Tina L., additional, Parnia, Sam, additional, Pawar, Rahul, additional, Pereira, João, additional, Rudd, Sarah, additional, Scapigliati, Andrea, additional, Schmidt, Andrew, additional, Seesink, Jeroen, additional, Sempsrott, Justin R., additional, Szpilman, David, additional, Warner, David S., additional, Webber, Jonathon B., additional, and West, Rebecca L, additional

Published
2022
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33. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Author

Lawler, Patrick R, Golighe, Ewan C, Berge, Jeffrey S, Neal, Matthew D, McVerry, Bryan J, Nicolau, Jose C, Gong, Michelle N, Carrier, Marc, Rosenson, Robert S, Reynolds, Harmony R, Turgeon, Alexis F, Escobedo, Jorge, Huang, David T, Bradbury, Charlotte A, Houston, Brett L, Kornblith, Lucy Z, Kumar, Anand, Kah, Susan RN, Cushman, Mary, McQuilten, Zoe, Slutsky, Arthur S, Kim, Keri S, Gordon, Anthony C, Kirwan, Bridget-Anne, Brooks, Maria M, Higgins, Alisa M, Lewis, Roger J, Lorenzi, Elizabeth, Berry, Scott M, Berry, Lindsay R, Angus, Derek C, McArthur, Colin J, Webb, Steven A, Farkouh, Michael E, Hochman, Judith S, Zarychanski, Ryan, Aday, Aaron W, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Kreuziger, Lisa Baumann, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadzw, Tamta, Coiffard, Benjamin, Costantini, Todd W, de Brouwer, Sophie, Derde, Lennie PG, Detry, Michelle A, Duggal, Abhijit, Dzavik, Vladimir, Effron, Mark B, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, Garcia-Madrona, Sebastian, Girard, Timothy D, Godoy, Lucas C, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Hamburg, Naomi M, Haniffa, Rashan, Hanna, George, Hanna, Nicholas, Hegde, Sheila M, Hendrickson, Carolyn M, Hite, R Duncan, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Iyer, Vivek N, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei L, Kin, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, Krishnan, Vidya, Kutcher, Matthew E, Laffan, Michael A, Lamontagne, Francois, Le Gal, Gregoire, Leeper, Christine M, Leifer, Eric S, Lim, George, Lima, Felipe Gallego, Linstrum, Kelsey, Litton, Edward, Lopez-Sendon, Jose, Moreno, Jose L Lopez-Sendon, Lother, Sylvain A, Malhotra, Saurabh, Marcos, Miguel, Marinez, Andrea Saud, Marshall, John C, Marten, Nicole, Matthay, Michael A, McAuley, Daniel F, McDonald, Emily G, McGlothlin, Anna, McGuinness, Shay P, Middeldorp, Saskia, Montgomery, Stephanie K, Moore, Steven C, Guerreor, Raquel Morillo, Mouncey, Paul R, Murthy, Srinivas, Nair, Girish B, Nair, Rahul, Nichol, Alistair D, Nunez-Garcia, Brenda, Pandey, Ambarish, Park, Pauline K, Parke, Rachael L, Parker, Jane C, Parnia, Sam, Paul, Jonathan D, Gonzalez, Yessica S Perez, Pompilio, Mauricio, Prekker, Matthew E, Quigley, John G, Rost, Natalia S, Rowan, Kathryn, Santos, Fernanda O, Santos, Marlene, Santos, Mayler Olombrada, Satterwhite, Lewis, Saunders, Christina T, Schutgens, Roger EG, Seymour, Christopher W, Siegal, Deborah M, Jr, Silva Delcio G, Shankar-Hari, Manu, Sheehan, John P, Singhal, Aneesh B, Solvaso, Dayna, Stanworth, Simon J, Tritschler, Tobias, Turner, Anne M, Van Bentum-Puijk, Wilma, van de Veerdonk, Frank L, van Diepen, Sean, Vazquez-Grande, Gloria, Wahid, Lana, Wareham, Vanessa, Wells, Bryan J, Widmer, R Jay, Wilson, Jennifer G, Yuriditsky, Eugene, Zampieri, Fernando G, Investigators, ATTACC, Investigators, ACTIV-4a, Investigators, REMAP-CAP, Investigators, ATTACC, Investigators, ACTIV-4a, Investigators, REMAP-CAP, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 215522, AR7-162822, CS-2016-16-011, RP-2015-06-18, National Institutes of Health, NIH: 1OT2HL156812-01, OTA-20-011, UL1TR001445, National Heart, Lung, and Blood Institute, NHLBI, Breast Cancer Research Foundation, BCRF, National Center for Advancing Translational Sciences, NCATS, New York University, NYU, Medical Center, University of Pittsburgh, CancerCare Manitoba Foundation, CCMF, University of Manitoba, UM, Health Research Board, HRB: CTN 2014-012, Canadian Institutes of Health Research, CIHR, National Institute for Health Research, NIHR, European Commission, EC: 602525, FP7-HEALTH-2013-INNOVATION, National Health and Medical Research Council, NHMRC: APP1101719, APP1116530, Health Research Council of New Zealand, HRC: 158584, 16/631, 447335, Canada Research Chairs, Eisai, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Horizon 2020: 101003589, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, The ATTACC platform was supported by grants from the Canadian Institutes of Health Research, LifeArc Foundation, Thistledown Foundation, Research Manitoba, Ontario Ministry of Health, Peter Munk Cardiac Centre, CancerCare Manitoba Foundation, and Victoria General Hospital Foundation. The ACTIV-4a platform was sponsored by the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH) (grant numbers, OTA-20-011 and 1OT2HL156812-01). The pilot program (PROTECT) was funded in part by a grant (UL1TR001445) from the New York University Clinical and Translational Science Award program, supported by the National Center for Advancing Translational Sciences of the NIH. The REMAP-CAP platform was supported by the European Union through FP7-HEALTH-2013-INNOVATION: the Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) consortium (602525) and the Horizon 2020 research and innovation program: the Rapid European Covid-19 Emergency Research response (RECOVER) consortium (101003589), by the Australian National Health and Medical Research Council (APP1101719 and APP1116530), the Health Research Council of New Zealand (16/631), the Canadian Institutes of Health Research (Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant [158584] and Covid-19 Rapid Research Operating Grant [447335]), the U.K. National Institute for Health Research (NIHR) and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (CTN 2014-012), the Learning While Doing Program at the University of Pittsburgh Medical Center, the Breast Cancer Research Foundation, the French Ministry of Health (PHRC-20-0147), the Minderoo Foundation, Am-gen, Eisai, the Global Coalition for Adaptive Research, and the Wellcome Trust Innovations Project (215522). Dr. Goligher is the recipient of an Early Career Investigator award from the Canadian Institutes of Health Research (grant AR7-162822). Dr. Gordon is supported by an NIHR Research Professorship (RP-2015-06-18), Dr. Shankar-Hari by an NIHR Clinician Scientist Fellowship (CS-2016-16-011), and Dr. Turgeon by a Canada Research Chair (Tier 2). Dr. Zarychanski is the recipient of the Lyonel G. Israels Research Chair in Hematology (University of Manitoba)., Listed are data that were included in the analysis involving patients with moderate severity of coronavirus disease 2019 (Covid-19). The denominators of patients in the anticoagulation group and the thrombophylaxis group are un-equal owing to response-adaptive randomization. The baseline characteristics of the patients according to d-dimer level are provided in Table S2 in the Supplementary Appendix. To convert the values for creatinine to micromoles per liter, multiply by 88.4. ULN denotes upper limit of the normal range. † Race or ethnic group was reported by the patients. ‡ The body-mass index is the weight in kilograms divided by the square of the height in meters. § Severe cardiovascular disease was defined as a baseline history of heart failure, myocardial infarction, coronary artery disease, peripheral arterial disease, or cerebrovascular disease (stroke or transient ischemic attack) in the ATTACC (Antithrombotic Therapy to Ameliorate Complications of Covid-19) and ACTIV-4a (A Multicenter, Adaptive, Ran-domized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19) platforms and as a baseline history of New York Heart Association class IV symptoms in the REMAP-CAP platform (Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia). ¶ Chronic respiratory disease was defined as a baseline history of asthma, chronic obstructive pulmonary disease, bron-chiectasis, interstitial lung disease, primary lung cancer, pulmonary hypertension, active tuberculosis, or the receipt of home oxygen therapy. ‖ Not listed are 74 patients who were coenrolled in the REMAP-CAP Antiplatelet Domain (39 in the anticoagulation group and 35 in the thromboprophylaxis group). ** In REMAP-CAP, levels of oxygen support (including no support) below the level of high-flow nasal cannula were not reported. †† The relative proportion of patients who were randomly assigned in each platform was imbalanced owing to imple-mentation of response-adaptive randomization in ATTACC on December 15, 2020. ‡‡ A total of 215 patients who were enrolled in the ATTACC platform were funded by the ACTIV4a platform by the National Heart, Lung, and Blood Institute. §§ Other participating countries were Mexico, Nepal, Australia, the Netherlands, and Spain., ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, Lawler, Patrick R [0000-0001-5155-5071], Neal, Matthew D [0000-0001-8931-6236], McVerry, Bryan J [0000-0002-1175-4874], Carrier, Marc [0000-0001-8296-2972], Escobedo, Jorge [0000-0003-1942-7402], Huang, David T [0000-0001-7649-1633], Bradbury, Charlotte A [0000-0001-5248-8165], Houston, Brett L [0000-0002-8776-4083], Kornblith, Lucy Z [0000-0002-1861-9691], Kim, Keri S [0000-0002-8480-4801], Gordon, Anthony C [0000-0002-0419-547X], Higgins, Alisa M [0000-0001-8295-7559], Aday, Aaron W [0000-0001-6243-3432], Aryal, Diptesh [0000-0002-1431-8293], Baumann Kreuziger, Lisa [0000-0002-1171-0548], Beane, Abi [0000-0001-7046-1580], Coiffard, Benjamin [0000-0002-8896-5346], Derde, Lennie PG [0000-0002-3577-5629], Detry, Michelle A [0000-0002-2794-1439], Estcourt, Lise J [0000-0003-4309-9162], Everett, Brendan M [0000-0002-6331-5224], Galen, Benjamin T [0000-0001-8172-258X], Girard, Timothy D [0000-0002-9833-4871], Godoy, Lucas C [0000-0001-6171-1269], Greenstein, Yonatan Y [0000-0002-5718-4408], Haniffa, Rashan [0000-0002-8288-449X], Hanna, George [0000-0001-8737-3843], Hegde, Sheila M [0000-0001-8157-8899], Hendrickson, Carolyn M [0000-0003-4662-2385], Hite, R Duncan [0000-0002-2625-8750], Hindenburg, Alexander A [0000-0002-1232-2168], Horvat, Christopher M [0000-0002-1593-2252], Jacobson, Jeffrey R [0000-0001-8929-994X], Kim, Yuri [0000-0001-5978-5779], King, Andrew J [0000-0002-9809-0563], Kutcher, Matthew E [0000-0003-4566-5359], Lima, Felipe Gallego [0000-0003-1204-5743], Lopez-Sendon Moreno, Jose L [0000-0001-9414-3990], Marcos, Miguel [0000-0003-1269-4487], McGlothlin, Anna [0000-0002-9079-6166], Mouncey, Paul R [0000-0002-8510-8517], Nunez-Garcia, Brenda [0000-0002-0355-4557], Parnia, Sam [0000-0002-6158-4404], Quigley, John G [0000-0003-3116-4545], Saunders, Christina T [0000-0003-4325-9568], Shankar-Hari, Manu [0000-0002-5338-2538], Sheehan, John P [0000-0002-4328-2613], Tritschler, Tobias [0000-0002-8775-0511], Yuriditsky, Eugene [0000-0003-2263-9297], Zampieri, Fernando G [0000-0001-9315-6386], Angus, Derek C [0000-0002-7026-5181], Apollo - University of Cambridge Repository, NIHR, and National Institute for Health Research

Subjects
Male, covid-19, anticoagulation, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 030204 cardiovascular system & hematology, heparin, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Hemorrhage/chemically induced, 030212 general & internal medicine, Hospital Mortality, Heparin/administration & dosage, anticoagulation, 11 Medical and Health Sciences, Anticoagulants/administration & dosage, Thrombosis/prevention & control, low molecular weight heparin, General Medicine, Heparin, Middle Aged, Thrombosis, Patient Discharge, 3. Good health, Coagulation, Original Article, Female, ATTACC Investigators, medicine.symptom, Covid-19, Life Sciences & Biomedicine, medicine.drug, Adult, medicine.medical_specialty, medicine.drug_class, adaptive platform trial, Low molecular weight heparin, Inflammation, Hemorrhage, COVID-19/drug therapy, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, medicine, Humans, Intensive care medicine, Survival analysis, Aged, Science & Technology, business.industry, SARS-CoV-2, Anticoagulants, COVID-19, Odds ratio, Heparin, Low-Molecular-Weight, medicine.disease, Survival Analysis, COVID-19 Drug Treatment, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Heparin, Low-Molecular-Weight/therapeutic use, ACTIV-4a Investigators, Human medicine, REMAP-CAP Investigators, business
Abstract

BACKGROUNDThrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.METHODSIn this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.RESULTSThe trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.CONCLUSIONSIn noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589. opens in new tab, NCT04505774. opens in new tab, NCT02735707. opens in new tab, and NCT04359277. opens in new tab.)

Published
2021

34. 2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

Author

Wyckoff, Myra H., primary, Singletary, Eunice M., additional, Soar, Jasmeet, additional, Olasveengen, Theresa M., additional, Greif, Robert, additional, Liley, Helen G., additional, Zideman, David, additional, Bhanji, Farhan, additional, Andersen, Lars W., additional, Avis, Suzanne R., additional, Aziz, Khalid, additional, Bendall, Jason C., additional, Berry, David C., additional, Borra, Vere, additional, Böttiger, Bernd W., additional, Bradley, Richard, additional, Bray, Janet E., additional, Breckwoldt, Jan, additional, Carlson, Jestin N., additional, Cassan, Pascal, additional, Castrén, Maaret, additional, Chang, Wei-Tien, additional, Charlton, Nathan P., additional, Cheng, Adam, additional, Chung, Sung Phil, additional, Considine, Julie, additional, Costa-Nobre, Daniela T., additional, Couper, Keith, additional, Dainty, Katie N., additional, Davis, Peter G., additional, de Almeida, Maria Fernanda, additional, de Caen, Allan R., additional, de Paiva, Edison F., additional, Deakin, Charles D., additional, Djärv, Therese, additional, Douma, Matthew J., additional, Drennan, Ian R., additional, Duff, Jonathan P., additional, Eastwood, Kathryn J., additional, El-Naggar, Walid, additional, Epstein, Jonathan L., additional, Escalante, Raffo, additional, Fabres, Jorge G., additional, Fawke, Joe, additional, Finn, Judith C., additional, Foglia, Elizabeth E., additional, Folke, Fredrik, additional, Freeman, Karoline, additional, Gilfoyle, Elaine, additional, Goolsby, Craig A., additional, Grove, Amy, additional, Guinsburg, Ruth, additional, Hatanaka, Tetsuo, additional, Hazinski, Mary Fran, additional, Heriot, George S., additional, Hirsch, Karen G., additional, Holmberg, Mathias J., additional, Hosono, Shigeharu, additional, Hsieh, Ming-Ju, additional, Hung, Kevin K.C., additional, Hsu, Cindy H., additional, Ikeyama, Takanari, additional, Isayama, Tetsuya, additional, Kapadia, Vishal S., additional, Kawakami, Mandira Daripa, additional, Kim, Han-Suk, additional, Kloeck, David A., additional, Kudenchuk, Peter J., additional, Lagina, Anthony T., additional, Lauridsen, Kasper G., additional, Lavonas, Eric J., additional, Lockey, Andrew S., additional, Malta Hansen, Carolina, additional, Markenson, David, additional, Matsuyama, Tasuku, additional, McKinlay, Christopher J.D., additional, Mehrabian, Amin, additional, Merchant, Raina M., additional, Meyran, Daniel, additional, Morley, Peter T., additional, Morrison, Laurie J., additional, Nation, Kevin J., additional, Nemeth, Michael, additional, Neumar, Robert W., additional, Nicholson, Tonia, additional, Niermeyer, Susan, additional, Nikolaou, Nikolaos, additional, Nishiyama, Chika, additional, O’Neil, Brian J., additional, Orkin, Aaron M., additional, Osemeke, Osokogu, additional, Parr, Michael J., additional, Patocka, Catherine, additional, Pellegrino, Jeffrey L., additional, Perkins, Gavin D., additional, Perlman, Jeffrey M., additional, Rabi, Yacov, additional, Reynolds, Joshua C., additional, Ristagno, Giuseppe, additional, Roehr, Charles C., additional, Sakamoto, Tetsuya, additional, Sandroni, Claudio, additional, Sawyer, Taylor, additional, Schmölzer, Georg M., additional, Schnaubelt, Sebastian, additional, Semeraro, Federico, additional, Skrifvars, Markus B., additional, Smith, Christopher M., additional, Smyth, Michael A., additional, Soll, Roger F., additional, Sugiura, Takahiro, additional, Taylor-Phillips, Sian, additional, Trevisanuto, Daniele, additional, Vaillancourt, Christian, additional, Wang, Tzong-Luen, additional, Weiner, Gary M., additional, Welsford, Michelle, additional, Wigginton, Jane, additional, Wyllie, Jonathan P., additional, Yeung, Joyce, additional, Nolan, Jerry P., additional, Berg, Katherine M., additional, Abelairas-Gómez, Cristian, additional, Barcala-Furelos, Roberto, additional, Beerman, Stephen B., additional, Bierens, Joost, additional, Cacciola, Sofia, additional, Cellini, Jacqueline, additional, Claesson, Andreas, additional, Court, Rachael, additional, D'Arrigo, Sonia, additional, De Brier, Niels, additional, Dunne, Cody L., additional, Elsenga, Hylmar E., additional, Johnson, Samantha, additional, Kleven, Gunn, additional, Maconochie, Ian, additional, Mecrow, Tom, additional, Morgan, Patrick, additional, Otto, Quentin, additional, Palmieri, Tina L., additional, Parnia, Sam, additional, Pawar, Rahul, additional, Pereira, João, additional, Rudd, Sarah, additional, Scapigliati, Andrea, additional, Schmidt, Andrew, additional, Seesink, Jeroen, additional, Sempsrott, Justin R., additional, Szpilman, David, additional, Warner, David S., additional, Webber, Jonathon B., additional, and West, Rebecca L., additional

Published
2021
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36. A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe ARDS From COVID-19.

Author

Bowdish, Michael E., Barkauskas, Christina E., Overbey, Jessica R., Gottlieb, Robert L., Osman, Keren, Duggal, Abhijit, Marks, Mary E., Hupf, Jonathan, Fernandes, Eustace, Leshnower, Bradley G., Golob, Jonathan L., Iribarne, Alexander, Rassias, Athos J., Moquete, Ellen G., O’Sullivan, Karen, Chang, Helena L., Williams, Judson B., Parnia, Sam, Patel, Nirav C., and Desai, Nimesh D.

Subjects
STROMAL cells, ARTIFICIAL respiration, ADULT respiratory distress syndrome
Abstract

Rationale: There are limited therapeutic options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents.Objectives: Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-induced respiratory failure.Methods: Patients were randomized to two infusions of 2 million cells/kg or sham infusions, in addition to standard of care. We hypothesized that cell therapy would be superior to sham-control for the primary endpoint of 30-day mortality. The key secondary endpoint was ventilator-free survival within 60 days, accounting for deaths and withdrawals in a ranked analysis.Measurements and Main Results: At the third interim analysis, the Data and Safety Monitoring Board recommended that the trial halt enrollment as the pre-specified mortality reduction from 40% to 23% was unlikely to be achieved (n=222 out of planned 300). Thirty-day mortality was 37.5% (42/112) in cell recipients versus 42.7% (47/110) in control patients (RR 0.88;95% CI 0.64,1.21;p=0.43). There were no significant differences in days alive off ventilation within 60 days (median rank 117.3 [IQR:60.0,169.5] in cell patients and 102.0 [IQR:54.0,162.5] in controls; higher is better). Resolution or improvement of ARDS at 30-days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) of control patients (OR 1.36;95% CI 0.57, 3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar.Conclusions: Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate/severe COVID-related acute respiratory distress syndrome. Clinical trial registration available at www.Clinicaltrials: gov, ID:NCT04371393. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). [ABSTRACT FROM AUTHOR]

Published
2023
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37. Toward harmonization of strategies for investigating lucidity in AD/ADRD: A preliminary research framework.

Author

Gilmore‐Bykovskyi, Andrea, Griffin, Joan M., Mueller, Kimberly D., Parnia, Sam, and Kolanowski, Ann

Abstract

Episodes of lucidity (ELs) in Alzheimer's disease and Alzheimer's disease‐related dementias (AD/ADRD), have garnered increasing attention as an important area of research. Efforts to study lucidity suffer from a lack of clear definitional criteria, inconsistent conceptualization, and diverse approaches to operationalizing features of these events. To advance systematic investigation of ELs in AD/ADRD, there is a need for clarity and precision in labeling event attributes, markers, and specific measurement strategies that enable operational harmonization across distinct approaches to investigating the relatively broad and nascent phenomenon. To that end, we propose a preliminary research framework to guide harmonization of approaches to investigating ELs in AD/ADRD. Our goal is to provide an initial schematic that encourages uniform labeling of operational decisions about ELs. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk

Author

Brosnahan, Shari B., primary, Chen, Xian Jie Cindy, additional, Chung, Juri, additional, Altshuler, Diana, additional, Islam, Shahidul, additional, Thomas, Sarun V., additional, Winner, Megan D., additional, Greco, Allison A., additional, Divers, Jasmin, additional, Spiegler, Peter, additional, Sterman, Daniel H., additional, and Parnia, Sam, additional

Published
2021
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48. 2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

Author

Wyckoff, Myra H., Singletary, Eunice M., Soar, Jasmeet, Olasveengen, Theresa M., Greif, Robert, Liley, Helen G., Zideman, David, Bhanji, Farhan, Andersen, Lars W., Avis, Suzanne R., Aziz, Khalid, Bendall, Jason C., Berry, David C., Borra, Vere, B��ttiger, Bernd W., Bradley, Richard, Bray, Janet E., Breckwoldt, Jan, Carlson, Jestin N., Cassan, Pascal, Castr��n, Maaret, Chang, Wei-Tien, Charlton, Nathan P., Cheng, Adam, Chung, Sung Phil, Considine, Julie, Costa-Nobre, Daniela T., Couper, Keith, Dainty, Katie N., Davis, Peter G., de Almeida, Maria Fernanda, de Caen, Allan R., de Paiva, Edison F., Deakin, Charles D., Dj��rv, Therese, Douma, Matthew J., Drennan, Ian R., Duff, Jonathan P., Eastwood, Kathryn J., Epstein, Jonathan L., Escalante, Raffo, Fabres, Jorge G., Fawke, Joe, Finn, Judith C., Foglia, Elizabeth E., Folke, Fredrik, Freeman, Karoline, Gilfoyle, Elaine, Goolsby, Craig A., Grove, Amy, Guinsburg, Ruth, Hatanaka, Tetsuo, Hazinski, Mary Fran, Heriot, George S., Hirsch, Karen G., Holmberg, Mathias J., Hosono, Shigeharu, Hsieh, Ming-Ju, Hung, Kevin K.C., Hsu, Cindy H., Ikeyama, Takanari, Isayama, Tetsuya, Kapadia, Vishal S., Kawakami, Mandira, Kim, Han-Suk, Kloeck, David A., Kudenchuk, Peter J., Lagina, Anthony T., Lauridsen, Kasper G., Lavonas, Eric J., Lockey, Andrew S., Malta Hansen, Carolina, Markenson, David, Matsuyama, Tasuku, McKinlay, Christopher J.D., Mehrabian, Amin, Merchant, Raina M., Meyran, Daniel, Morley, Peter T., Morrison, Laurie J., Nation, Kevin J., Nemeth, Michael, Neumar, Robert W., Nicholson, Tonia, Niermeyer, Susan, Nikolaou, Nikolaos, Nishiyama, Chika, O���Neil, Brian J., Orkin, Aaron M., Osemeke, Osokogu, Parr, Michael J., Patocka, Catherine, Pellegrino, Jeffrey L., Perkins, Gavin D., Perlman, Jeffrey M., Rabi, Yacov, Reynolds, Joshua C., Ristagno, Giuseppe, Roehr, Charles C., Sakamoto, Tetsuya, Sandroni, Claudio, Sawyer, Taylor, Schm��lzer, Georg M., Schnaubelt, Sebastian, Semeraro, Federico, Skrifvars, Markus B., Smith, Christopher M., Smyth, Michael A., Soll, Roger F., Sugiura, Takahiro, Taylor-Phillips, Sian, Trevisanuto, Daniele, Vaillancourt, Christian, Wang, Tzong-Luen, Weiner, Gary M., Welsford, Michelle, Wigginton, Jane, Wyllie, Jonathan P., Yeung, Joyce, Nolan, Jerry P., Berg, Katherine M., Abelairas-G��mez, Cristian, Barcala-Furelos, Roberto, Beerman, Stephen B., Bierens, Joost, Cacciola, So���a, Cellini, Jacqueline, Claesson, Andreas, Court, Rachael, D'Arrigo, Sonia, De Brier, Niels, Dunne, Cody L., Elsenga, Hylmar E., Johnson, Samantha, Kleven, Gunn, Maconochie, Ian, Mecrow, Tom, Morgan, Patrick, Otto, Quentin, Palmieri, Tina L., Parnia, Sam, Pawar, Rahul, Pereira, Jo��o, Rudd, Sarah, Scapigliati, Andrea, Schmidt, Andrew, Seesink, Jeroen, Sempsrott, Justin R., Szpilman, David, Warner, David S., Webber, Jonathon B., and West, Rebecca L.

Subjects
610 Medicine & health
Published
2021
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49. 2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group

Author

Wyckoff, Myra H., Singletary, Eunice M., Soar, Jasmeet, Olasveengen, Theresa M., Greif, Robert, Liley, Helen G., Zideman, David, Bhanji, Farhan, Andersen, Lars W., Avis, Suzanne R., Aziz, Khalid, Bendall, Jason C., Berry, David C., Borra, Vere, B��ttiger, Bernd W., Bradley, Richard, Bray, Janet E., Breckwoldt, Jan, Carlson, Jestin N., Cassan, Pascal, Castr��n, Maaret, Chang, Wei-Tien, Charlton, Nathan P., Cheng, Adam, Chung, Sung Phil, Considine, Julie, Costa-Nobre, Daniela T., Couper, Keith, Dainty, Katie N., Davis, Peter G., de Almeida, Maria Fernanda, de Caen, Allan R., de Paiva, Edison F., Deakin, Charles D., Dj��rv, Therese, Douma, Matthew J., Drennan, Ian R., Duff, Jonathan P., Eastwood, Kathryn J., Epstein, Jonathan L., Escalante, Raffo, Fabres, Jorge G., Fawke, Joe, Finn, Judith C., Foglia, Elizabeth E., Folke, Fredrik, Freeman, Karoline, Gilfoyle, Elaine, Goolsby, Craig A., Grove, Amy, Guinsburg, Ruth, Hatanaka, Tetsuo, Hazinski, Mary Fran, Heriot, George S., Hirsch, Karen G., Holmberg, Mathias J., Hosono, Shigeharu, Hsieh, Ming-Ju, Hung, Kevin K.C., Hsu, Cindy H., Ikeyama, Takanari, Isayama, Tetsuya, Kapadia, Vishal S., Kawakami, Mandira, Kim, Han-Suk, Kloeck, David A., Kudenchuk, Peter J., Lagina, Anthony T., Lauridsen, Kasper G., Lavonas, Eric J., Lockey, Andrew S., Malta Hansen, Carolina, Markenson, David, Matsuyama, Tasuku, McKinlay, Christopher J.D., Mehrabian, Amin, Merchant, Raina M., Meyran, Daniel, Morley, Peter T., Morrison, Laurie J., Nation, Kevin J., Nemeth, Michael, Neumar, Robert W., Nicholson, Tonia, Niermeyer, Susan, Nikolaou, Nikolaos, Nishiyama, Chika, O���Neil, Brian J., Orkin, Aaron M., Osemeke, Osokogu, Parr, Michael J., Patocka, Catherine, Pellegrino, Jeffrey L., Perkins, Gavin D., Perlman, Jeffrey M., Rabi, Yacov, Reynolds, Joshua C., Ristagno, Giuseppe, Roehr, Charles C., Sakamoto, Tetsuya, Sandroni, Claudio, Sawyer, Taylor, Schm��lzer, Georg M., Schnaubelt, Sebastian, Semeraro, Federico, Skrifvars, Markus B., Smith, Christopher M., Smyth, Michael A., Soll, Roger F., Sugiura, Takahiro, Taylor-Phillips, Sian, Trevisanuto, Daniele, Vaillancourt, Christian, Wang, Tzong-Luen, Weiner, Gary M., Welsford, Michelle, Wigginton, Jane, Wyllie, Jonathan P., Yeung, Joyce, Nolan, Jerry P., Berg, Katherine M., Abelairas-G��mez, Cristian, Barcala-Furelos, Roberto, Beerman, Stephen B., Bierens, Joost, Cacciola, Sofia, Cellini, Jacqueline, Claesson, Andreas, Court, Rachael, D���Arrigo, Sonia, De Brier, Niels, Dunne, Cody L., Elsenga, Hylmar E., Johnson, Samantha, Kleven, Gunn, Maconochie, Ian, Mecrow, Tom, Morgan, Patrick, Otto, Quentin, Palmieri, Tina L., Parnia, Sam, Pawar, Rahul, Pereira, Jo��o, Rudd, Sarah, Scapigliati, Andrea, Schmidt, Andrew, Seesink, Jeroen, Sempsrott, Justin R., Szpilman, David, Warner, David S., Webber, Jonathon B., and West, Rebecca L

Subjects
610 Medicine & health
Published
2021
Full Text
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50. sj-pdf-1-aop-10.1177_10600280211028882 – Supplemental material for Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk

Author

Brosnahan, Shari B., Chen, Xian Jie Cindy, Chung, Juri, Altshuler, Diana, Islam, Shahidul, Thomas, Sarun V., Winner, Megan D., Greco, Allison A., Divers, Jasmin, Spiegler, Peter, Sterman, Daniel H., and Parnia, Sam

Subjects
FOS: Clinical medicine, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental material, sj-pdf-1-aop-10.1177_10600280211028882 for Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk by Shari B. Brosnahan, Xian Jie Cindy Chen, Juri Chung, Diana Altshuler, Shahidul Islam, Sarun V. Thomas, Megan D. Winner, Allison A. Greco, Jasmin Divers, Peter Spiegler, Daniel H. Sterman and Sam Parnia in Annals of Pharmacotherapy

Published
2021
Full Text
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