Search

Your search keyword '"McVerry, Bryan J"' showing total 18 results
Start Over Author "McVerry, Bryan J" Topic critical illness
18 results on '"McVerry, Bryan J"'

1. Simvastatin in Critically Ill Patients with Covid-19.

Author

Hills TE, Lorenzi E, Berry LR, Shyamsundar M, Al-Beidh F, Annane D, Arabi Y, Aryal D, Au C, Beane A, Bhimani Z, Bonten M, Bradbury CA, Brunkhorst FM, Burrell A, Buxton M, Calfee CS, Cecconi M, Cheng AC, Cove ME, Detry MA, Estcourt LJ, Fitzgerald M, Goligher EC, Goossens H, Green C, Haniffa R, Harrison DA, Hashmi M, Higgins AM, Horvat C, Huang DT, Ichihara N, Jayakumar D, Kruger PS, Lamontagne F, Lampro L, Lawler PR, Marshall JC, Mason AJ, McGlothlin A, McGuinness S, McQuilten ZK, McVerry BJ, Mouncey PR, Murthy S, Neal MD, Nichol AD, O'Kane CM, Parke RL, Parker JC, Rabindrarajan E, Reyes LF, Rowan KM, Saito H, Santos M, Saunders CT, Seymour CW, Shankar-Hari M, Sinha P, Thompson BT, Turgeon AF, Turner AM, van de Veerdonk F, Weis S, Young IS, Zarychanski R, Lewis RJ, McArthur CJ, Angus DC, Berry SM, Derde LPG, Webb SA, Gordon AC, and McAuley DF

Subjects
Humans, Bayes Theorem, COVID-19 Drug Treatment, Hospital Mortality, Treatment Outcome, COVID-19 mortality, COVID-19 therapy, Critical Illness mortality, Critical Illness therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Simvastatin therapeutic use
Abstract

Background: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear., Methods: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2)., Results: Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control., Conclusions: Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.)., (Copyright © 2023 Massachusetts Medical Society.)

Published
2023
Full Text
View/download PDF

2. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

Author

Bradbury CA, Lawler PR, Stanworth SJ, McVerry BJ, McQuilten Z, Higgins AM, Mouncey PR, Al-Beidh F, Rowan KM, Berry LR, Lorenzi E, Zarychanski R, Arabi YM, Annane D, Beane A, van Bentum-Puijk W, Bhimani Z, Bihari S, Bonten MJM, Brunkhorst FM, Buzgau A, Buxton M, Carrier M, Cheng AC, Cove M, Detry MA, Estcourt LJ, Fitzgerald M, Girard TD, Goligher EC, Goossens H, Haniffa R, Hills T, Huang DT, Horvat CM, Hunt BJ, Ichihara N, Lamontagne F, Leavis HL, Linstrum KM, Litton E, Marshall JC, McAuley DF, McGlothlin A, McGuinness SP, Middeldorp S, Montgomery SK, Morpeth SC, Murthy S, Neal MD, Nichol AD, Parke RL, Parker JC, Reyes LF, Saito H, Santos MS, Saunders CT, Serpa-Neto A, Seymour CW, Shankar-Hari M, Singh V, Tolppa T, Turgeon AF, Turner AM, van de Veerdonk FL, Green C, Lewis RJ, Angus DC, McArthur CJ, Berry S, Derde LPG, Webb SA, and Gordon AC

Subjects
Adult, Anticoagulants adverse effects, Anticoagulants therapeutic use, Aspirin adverse effects, Aspirin therapeutic use, Bayes Theorem, Female, Hemorrhage chemically induced, Humans, Male, Middle Aged, Purinergic P2Y Receptor Antagonists adverse effects, Purinergic P2Y Receptor Antagonists therapeutic use, Respiration, Artificial, COVID-19 complications, COVID-19 mortality, COVID-19 therapy, Critical Illness mortality, Critical Illness therapy, Platelet Aggregation Inhibitors adverse effects, Platelet Aggregation Inhibitors therapeutic use, Venous Thromboembolism drug therapy, Venous Thromboembolism etiology, COVID-19 Drug Treatment
Abstract

Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain., Objective: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19., Design, Setting, and Participants: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021)., Interventions: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis., Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions., Results: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm)., Conclusions and Relevance: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days., Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

Published
2022
Full Text
View/download PDF

3. Monitoring Research Blood Sampling in Critically Ill Patients: Avoiding Iatrogenic Anemia.

Author

Baron RM, Christman JW, Liu KD, Matthay MA, Self WH, McVerry BJ, Hite RD, Paine R 3rd, Wurfel MM, Shapiro NI, Adams PW, Schmidt EP, and Ringwood N

Subjects
Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Anemia prevention & control, Biological Monitoring standards, Blood Specimen Collection standards, Critical Illness, Iatrogenic Disease prevention & control, Practice Guidelines as Topic
Published
2020
Full Text
View/download PDF

4. Increased Alternative Complement Pathway Function and Improved Survival during Critical Illness.

Author

Bain W, Li H, van der Geest R, Moore SR, Olonisakin TF, Ahn B, Papke E, Moghbeli K, DeSensi R, Rapport S, Saul M, Hulver M, Xiong Z, Mallampalli RK, Ray P, Morris A, Ma L, Doi Y, Zhang Y, Kitsios GD, Kulkarni HS, McVerry BJ, Ferreira VP, Nouraie M, and Lee JS

Subjects
Aged, Animals, Female, Humans, Male, Mice, Middle Aged, Pennsylvania epidemiology, Pneumonia epidemiology, Retrospective Studies, Complement Pathway, Alternative immunology, Critical Illness therapy, Pneumonia immunology, Pneumonia therapy, Survival Analysis
Abstract

Rationale: Complement is crucial for host defense but may also drive dysregulated inflammation. There is limited understanding of alternative complement function, which can amplify all complement activity, during critical illness. Objectives: We examined the function and key components of the alternative complement pathway in a series of critically ill patients and in a mouse pneumonia model. Methods: Total classical (CH50) and alternative complement (AH50) function were quantified in serum from 321 prospectively enrolled critically ill patients and compared with clinical outcomes. Alternative pathway (AP) regulatory factors were quantified by ELISA ( n  = 181) and examined via transcriptomics data from external cohorts. Wild-type, Cfb -/- , and C3 -/- mice were infected intratracheally with Klebsiella pneumoniae (KP) and assessed for extrapulmonary dissemination. Measurements and Main Results: AH50 greater than or equal to median, but not CH50 greater than or equal to median, was associated with decreased 30-day mortality (adjusted odds ratio [OR], 0.53 [95% confidence interval (CI), 0.31-0.91]), independent of chronic liver disease. One-year survival was improved in patients with AH50 greater than or equal to median (adjusted hazard ratio = 0.59 [95% CI, 0.41-0.87]). Patients with elevated AH50 had increased levels of AP factors B, H, and properdin, and fewer showed a "hyperinflammatory" subphenotype (OR, 0.30 [95% CI, 0.18-0.49]). Increased expression of proximal AP genes was associated with improved survival in two external cohorts. AH50 greater than or equal to median was associated with fewer bloodstream infections (OR, 0.67 [95% CI, 0.45-0.98). Conversely, depletion of AP factors, or AH50 less than median, impaired in vitro Elevated AP function is associated with improved survival during critical illness, possibly because of enhanced immune capacity.Cfb -/- mice demonstrated increased extrapulmonary dissemination and serum inflammatory markers after intratracheal KP infection compared with wild type. Conclusions: Elevated AP function is associated with improved survival during critical illness, possibly because of enhanced immune capacity.

Published
2020
Full Text
View/download PDF

5. Ketamine Infusion for Adjunct Sedation in Mechanically Ventilated Adults.

Author

Groetzinger LM, Rivosecchi RM, Bain W, Bahr M, Chin K, McVerry BJ, and Barbash I

Subjects
Adult, Cohort Studies, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Respiration, Artificial adverse effects, Retrospective Studies, Analgesics administration & dosage, Critical Illness therapy, Hypnotics and Sedatives administration & dosage, Ketamine administration & dosage, Respiration, Artificial trends
Abstract

Background: Many critically ill patients receive ketamine for adjunct sedation despite a paucity of evidence on its use, dosing, and monitoring in this setting., Objective: To describe the dosing and safety considerations of ketamine for adjunct sedation in a population of mechanically ventilated critically ill patients targeting light sedation., Methods: We conducted a retrospective review of mechanically ventilated patients receiving continuous ketamine infusion between January 2012 and April 2016. Data included dosing, effect of ketamine on other sedatives, total sedative use, Riker Sedation-Agitation Scale (SAS) scores, adverse drug reactions (ADRs), and hemodynamic variables., Results: Ninety-one patients were included in the analysis. Ketamine was infused at a median dosage of 0.41 mg/kg/hour (range 0.04-2.5 mg/kg/hr) for up to 14.7 days (median 2.8 days). Concomitant sedatives were reduced or discontinued, without the initiation of an additional sedative, in 57 patients (63%) within 24 hours of initiating ketamine. Propofol was most commonly discontinued (16 patients, 36%), followed by benzodiazepines (12 patients, 27%). There was an increase in the number of SAS scores documented in goal in the 24-hour period after ketamine initiation compared with the immediate 24 hours before (61% vs 55%, p=0.001). Patients were less frequently agitated, defined as SAS >4, after the initiation of ketamine (27% vs 33%, p=0.005). Seven patients (7.7%) required discontinuation of ketamine infusion for an ADR. There were no significant changes in hemodynamic variables after the initiation of ketamine., Conclusions: Continuous ketamine infusion for adjunct light sedation was well tolerated in a cohort of critically ill adults, with an acceptable safety profile. Prospective studies of ketamine infusion are warranted to further establish its efficacy as a sedative in this population., (© 2017 Pharmacotherapy Publications, Inc.)

Published
2018
Full Text
View/download PDF

6. Dysbiosis in the intensive care unit: Microbiome science coming to the bedside.

Author

Kitsios GD, Morowitz MJ, Dickson RP, Huffnagle GB, McVerry BJ, and Morris A

Subjects
Animals, Critical Care, Evidence-Based Medicine, Humans, Intensive Care Units, Models, Animal, Critical Illness, Dysbiosis microbiology, Microbiota
Abstract

Complex microbial communities within the human body, constituting the microbiome, have a broad impact on human health and disease. A growing body of research now examines the role of the microbiome in patients with critical illness, such as sepsis and acute respiratory failure. In this article, we provide an introduction to microbiome concepts and terminology and we systematically review the current evidence base of the critical-illness microbiome, including 51 studies in animal models and pediatric and adult critically ill patients. We further examine how this emerging scientific discipline may transform the way we manage infectious and inflammatory diseases in intensive care units. The evolving molecular, culture-independent techniques offer the ability to study microbial communities in unprecedented depth and detail, and in the short-term, may enable us to diagnose and treat infections in critical care more precisely and effectively. Longer term, these tools may also give us insights in the underlying pathophysiology of critical illness and reveal previously unsuspected targets for innovative, microbiome-targeted therapeutics. We finally propose a roadmap for future studies in the field for transforming critical care from its current isolated focus on the host to a more personalized paradigm addressing both human and microbial contributions to critical illness., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Published
2017
Full Text
View/download PDF

7. 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, 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, and Le Gal, Grégoire

Subjects
Clinical Trials and Supportive Activities, Clinical Research, Comparative Effectiveness Research, Cardiovascular, Good Health and Well Being, Aged, Anticoagulants, COVID-19, Critical Illness, Female, Hemorrhage, Heparin, Hospital Mortality, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Respiration, Artificial, Thrombosis, Treatment Failure, COVID-19 Drug Treatment, REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Medical and Health Sciences, General & Internal Medicine
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

Published
2021

8. 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, and Kutcher, Matthew E

Subjects
REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Humans, Thrombosis, Critical Illness, Hemorrhage, Heparin, Anticoagulants, Treatment Failure, Respiration, Artificial, Hospital Mortality, Logistic Models, Odds Ratio, Aged, Middle Aged, Female, Male, COVID-19, Clinical Research, Cardiovascular, Clinical Trials and Supportive Activities, Comparative Effectiveness Research, General & Internal Medicine, Medical and Health Sciences
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

Published
2021

9. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

Author

Arabi, Yaseen M, Gordon, Anthony C, Derde, Lennie PG, Nichol, Alistair D, Murthy, Srinivas, Beidh, Farah Al, Annane, Djillali, Swaidan, Lolowa Al, Beane, Abi, Beasley, Richard, Berry, Lindsay R, Bhimani, Zahra, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen, De Jong, Menno, Detry, Michelle A, Duffy, Eamon J, Estcourt, Lise J, Fitzgerald, Mark, Fowler, Rob, Girard, Timothy D, Goligher, Ewan C, Goossens, Herman, Haniffa, Rashan, Higgins, Alisa M, Hills, Thomas E, Horvat, Christopher M, Huang, David T, King, Andrew J, Lamontagne, Francois, Lawler, Patrick R, Lewis, Roger, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Malakouti, Salim, McAuley, Daniel F, McGlothlin, Anna, Mcguinness, Shay, McVerry, Bryan J, Montgomery, Stephanie K, Morpeth, Susan C, Mouncey, Paul R, Orr, Katrina, Parke, Rachael, Parker, Jane C, Patanwala, Asad E, Rowan, Kathryn M, Santos, Marlene S, Saunders, Christina T, Seymour, Christopher W, Shankar-Hari, Manu, Tong, Steven YC, Turgeon, Alexis F, Turner, Anne M, Van de Veerdonk, Frank Leo, Zarychanski, Ryan, Green, Cameron, Berry, Scott, Marshall, John C, McArthur, Colin, Angus, Derek C, and Webb, Steven A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Comparative Effectiveness Research, Clinical Research, Clinical Trials and Supportive Activities, Good Health and Well Being, Adult, Antiviral Agents, Bayes Theorem, Critical Illness, Drug Combinations, Humans, Hydroxychloroquine, Lopinavir, Ritonavir, SARS-CoV-2, COVID-19 Drug Treatment, Adaptive platform trial, Intensive care, Pneumonia, Pandemic, COVID-19, Lopinavir-ritonavir, REMAP-CAP Investigators, Public Health and Health Services, Emergency & Critical Care Medicine, Clinical sciences
Abstract

PurposeTo study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsCritically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable.ResultsWe randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively).ConclusionAmong critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.

Published
2021

10. Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial

Author

Writing Committee for the REMAP-CAP Investigators, Lawler, Patrick R, Derde, Lennie PG, van de Veerdonk, Frank L, McVerry, Bryan J, Huang, David T, Berry, Lindsay R, Lorenzi, Elizabeth, van Kimmenade, Roland, Gommans, Frank, Vaduganathan, Muthiah, Leaf, David E, Baron, Rebecca M, Kim, Edy Y, Frankfurter, Claudia, Epelman, Slava, Kwan, Yvonne, Grieve, Richard, O'Neill, Stephen, Sadique, Zia, Puskarich, Michael, Marshall, John C, Higgins, Alisa M, Mouncey, Paul R, Rowan, Kathryn M, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Au, Carly, Beane, Abi, van Bentum-Puijk, Wilma, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Burrell, Aidan, Buzgau, Adrian, Buxton, Meredith, Cecconi, Maurizio, Cheng, Allen C, Cove, Matthew, Detry, Michelle A, Estcourt, Lise J, Ezekowitz, Justin, Fitzgerald, Mark, Gattas, David, Godoy, Lucas C, Goossens, Herman, Haniffa, Rashan, Harrison, David A, Hills, Thomas, Horvat, Christopher M, Ichihara, Nao, Lamontagne, Francois, Linstrum, Kelsey M, McAuley, Daniel F, McGlothlin, Anna, McGuinness, Shay P, McQuilten, Zoe, Murthy, Srinivas, Nichol, Alistair D, Owen, David RJ, Parke, Rachael L, Parker, Jane C, Pollock, Katrina M, Reyes, Luis Felipe, Saito, Hiroki, Santos, Marlene S, Saunders, Christina T, Seymour, Christopher W, Shankar-Hari, Manu, Singh, Vanessa, Turgeon, Alexis F, Turner, Anne M, Zarychanski, Ryan, Green, Cameron, Lewis, Roger J, Angus, Derek C, Berry, Scott, Gordon, Anthony C, McArthur, Colin J, Webb, Steve A, and Apollo - University of Cambridge Repository

Subjects
Male, Renin-Angiotensin System, Hospitalization, Angiotensin Receptor Antagonists, Critical Illness, Humans, COVID-19, Female, Angiotensin-Converting Enzyme Inhibitors, Bayes Theorem, Receptors, Chemokine, Middle Aged, COVID-19 Drug Treatment
Abstract

IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE: In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.

Published
2023

12. Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Author

Writing Committee for the REMAP-CAP Investigators, Estcourt, Lise J, Turgeon, Alexis F, McQuilten, Zoe K, McVerry, Bryan J, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Arnold, Donald M, Beane, Abigail, Bégin, Philippe, van Bentum-Puijk, Wilma, Berry, Lindsay R, Bhimani, Zahra, Birchall, Janet E, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Buxton, Meredith, Callum, Jeannie L, Chassé, Michaël, Cheng, Allen C, Cove, Matthew E, Daly, James, Derde, Lennie, Detry, Michelle A, De Jong, Menno, Evans, Amy, Fergusson, Dean A, Fish, Matthew, Fitzgerald, Mark, Foley, Claire, Goossens, Herman, Gordon, Anthony C, Gosbell, Iain B, Green, Cameron, Haniffa, Rashan, Harvala, Heli, Higgins, Alisa M, Hills, Thomas E, Hoad, Veronica C, Horvat, Christopher, Huang, David T, Hudson, Cara L, Ichihara, Nao, Laing, Emma, Lamikanra, Abigail A, Lamontagne, François, Lawler, Patrick R, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, MacLennan, Sheila, Marshall, John, McAuley, Daniel F, McDyer, John F, McGlothlin, Anna, McGuinness, Shay, Miflin, Gail, Montgomery, Stephanie, Mouncey, Paul R, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane C, Priddee, Nicole, Purcell, Damian FJ, Reyes, Luis F, Richardson, Peter, Robitaille, Nancy, Rowan, Kathryn M, Rynne, Jennifer, Saito, Hiroki, Santos, Marlene, Saunders, Christina T, Serpa Neto, Ary, Seymour, Christopher W, Silversides, Jon A, Tinmouth, Alan A, Triulzi, Darrell J, Turner, Anne M, van de Veerdonk, Frank, Walsh, Timothy S, Wood, Erica M, Berry, Scott, Lewis, Roger J, Menon, David K, McArthur, Colin, Zarychanski, Ryan, Angus, Derek C, Webb, Steve A, Roberts, David J, Shankar-Hari, Manu, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Investigators, Writing Committee for the REMAP-CAP, Writing Comm REMAP-CAP Investigators, Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institutes of Health, NIH, National Institute of Child Health and Human Development, NICHD, Pittsburgh Foundation, Breast Cancer Research Foundation, BCRF, Bristol-Myers Squibb, BMS, GlaxoSmithKline, GSK, Medtronic, Baxter International, Manitoba Medical Service Foundation, MMSF, CancerCare Manitoba Foundation, CCMF, Wellcome Trust, WT, University of Manitoba, UM, Health Research Board, HRB: PHRC-20-0147, National Blood Authority, NBA, Llywodraeth Cymru, Translational Breast Cancer Research Consortium, TBCRC, Canadian Institutes of Health Research, IRSC: 158584, CTN 2014-012, Medical Research Council, MRC, National Institute for Health Research, NIHR, Department of Health and Social Care, DH, European Commission, EC: APP194811, National Heart and Lung Institute, NHLI, National Health and Medical Research Council, NHMRC: 2015-06-18, 2016-16-011, APP1101719, APP2002132, Health Research Council of New Zealand, HRC: 16/631, 447335, Monash University, MU, Ministère des Affaires Sociales et de la Santé: 215522, Seventh Framework Programme, FP7, Université Pierre et Marie Curie, UPMC, Innovate UK, Horizon 2020, Pharmaceuticals Bayer, Minderoo Foundation, Dr Fitzgerald reported receiving grants from the PREPARE Network and the European Commission. Dr Gordon reported receiving grants from the National Institute for Health Research and receiving personal fees from 30 Respiratory, GlaxoSmithKline, and Bristol Myers Squibb. Dr Gosbell reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Haniffa reported receiving grants from the Wellcome Trust Innovations Project, the Minderoo Foundation, and the UK Research and Innovation African Critical Care Registry Network. Dr Higgins reported receiving grants from the National Health and Medical Research Council, the Minderoo Foundation, and the National Blood Authority. Dr Hills reported receiving grants from the Health Research Council of New Zealand. Dr Hoad reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Horvat reported receiving grants from the National Institute of Child Health and Human Development. Dr Huang reported receiving grants from the Breast Cancer Research Foundation. Dr Lamontagne reported receiving grants from the Canadian Institutes of Health Research. Dr Lawler reported receiving consulting fees from Novartis, Coronna LLC, and Brigham and Women’s Hospital, receiving royalties from McGraw-Hill Publishing, and receiving grants from the Canadian Institutes of Health Research, the LifeArc Foundation, the National Institutes of Health, the Peter Munk Cardiac Centre, the Ted Rogers Centre for Heart Research, the Thistledown Foundation, and the province of Ontario. Dr Lorenzi reported receiving personal fees from Berry Consultants. Dr Marshall reported receiving personal fees from AM-Pharma (data and safety monitoring board chair) and Critical Care Medicine (associate editor). Dr McAuley reported receiving personal fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Eli Lilly, Vir Biotechnology, Faron Pharmaceuticals, and Sobi, receiving grants from the National Institute for Health Research, Wellcome Trust, Innovate UK, the Medical Research Council, and the Northern Ireland Health and Social Care Research and Development Division, and holding a patent for an anti-inflammatory treatment that was issued to Queen’s University Belfast. Dr McGlothlin reported receiving grants from the PREPARE Network, the European Commission, and the Global Coalition for Adapative Research. Mr Mouncey reported receiving grants from the European Union, the PREPARE Network, the National Institute for Health Research, and European Union Horizon 2020. Dr Nichol reported receiving grants from the Health Research Board of Ireland and Baxter and receiving personal fees from AM-Pharma. Dr Parke reported receiving grants from Fisher and Paykel Healthcare Ltd. Ms Parker reported receiving grants from Monash University. Mr Richardson reported receiving funding from the Welsh government. Dr Rowan reported receiving grants from the European Commission and the National Institute for Health Research. Dr Saunders reported receiving grants from the PREPARE Network, the European Commission, and the Global Coalition for Adapative Research. Dr Serpa Neto reported receiving personal fees from Drager and Endpoint Health. Dr Tinmouth reported receiving grants and personal fees from the Canadian Blood Services. Ms Turner reported receiving grants from the Health Research Council of New Zealand. Dr van de Veerdonk reported receiving personal fees from Gilead, Sobi, and GlaxoSmithKline. Dr Wood reported receiving grants from the Australian Medical Research Future Fund. Dr S. Berry reported being an employee of Berry Consultants with an ownership role. Dr Lewis reported being an employee of Berry Consultants. Dr Menon reported receiving grants from the National Institute for Health Research. Dr McArthur reported receiving grants from the Health Research Council of New Zealand. Dr Zarychanski reported receiving grants from the Canadian Institutes of Health Research, the University of Manitoba, LifeArc, the Thistledown Foundation, Research Manitoba, the CancerCare Manitoba Foundation, the Victoria General Hospital Foundation, the Peter Munk Cardiac Centre, and the Manitoba Medical Services Foundation. Dr Webb reported receiving grants from the National Health and Medical Research Council and the Minderoo Foundation. Dr Shankar-Hari reported receiving grants from the National Institute for Clinical Research. No other disclosures were reported., nonprofit sponsors: Monash University, Melbourne, Australia (Australasian sponsor), Utrecht Medical Center, Utrecht, the Netherlands (European sponsor), St Michael’s Hospital, Toronto, Ontario, Canada (Canadian sponsor), and the Global Coalition for Adaptive Research, San Francisco, California (US sponsor). This study was additionally funded by grant 602525 FP7-health-2013-innovation-1 from the European Union Platform for European Preparedness Against Reemerging Epidemics, grants APP1101719 and APP1116530 from the Australian National Health and Medical Research Council, grant APP2002132 from the Australian Medical Research Future Fund, grant 16/631 from the New Zealand Health Research Council, grant 447335 from the Canadian Institutes of Health Research COVID-19 Rapid Research, grant 158584 from the Canadian Institutes of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program, grant CTN 2014-012 from the Health Research Board of Ireland, grant PHRC-20-0147 from the French Ministry of Health, and grant 215522 from the Wellcome Trust Innovations Project and funding from the National Institute for Health Research, the Department of Health and Social Care, the EU Programme Emergency Support Instrument, the NHS Blood and Transplant Research and Development Programme, the National Institute for Health Research, the National Institute for Health Research Imperial Biomedical Research Centre, the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the Pittsburgh Foundation, and the Minderoo Foundation. The Australian government funds the Australian Red Cross Lifeblood for the provision of blood products and services. The collection of plasma in the United Kingdom was funded by European Union SoHo grants from the Department of Health and Social Care. Dr Turgeon is the Canada Research Chair in Critical Care Neurology and Trauma. Dr McQuilten is supported by emerging leader fellowship APP194811 from the National Health and Medical Research Council. Dr Gordon is funded by research professorship 2015-06-18 from the National Institute for Health Research. Dr Shankar-Hari is funded by clinician scientist fellowship 2016-16-011 from the National Institute for Health Research., In Canada, the trial has been funded by the Canadian Institute of Health Research, Strategy for Patient-Oriented Research (CIHR-SPOR) Innovative Clinical Trials Program Grant (no. 158584) for CAD $1,497,200, for the recruitment of 300 patients., The Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) consortium is funded by the European Union (FP7-HEALTH-2013-INNOVATION-1, grant number 602525). Within the PREPARE consortium, the trial has funding for the recruitment of approximately 4000 patients., REMAP-CAP was supported in the Netherlands by the Research Collaboration Critical Care the Netherlands (RCC-Net)., Funding sources for the REMAP-CAP trial are specified in the core protocol documents. This domain has received domain-specific funding from the Australian Medical Research Future Fund (MRFF)., reported receiving grants from the National Institute for Health Research and European Union Horizon 2020. Dr Turgeon reported receiving grants from the Canadian Institutes of Health Research. Dr McQuilten reported receiving grants from the Australian Medical Research Future Fund. Dr McVerry reported receiving grants from the Pittsburgh Foundation, the Translational Breast Cancer Research Consortium, UPMC Learning While Doing Program, National Heart, Lung, and Blood Institute, and Bayer Pharmaceuticals and receiving personal fees from Boehringer Ingelheim. Dr Annane reported receiving grants from the French Ministry of Health and Solidarity. Dr Arnold reported receiving grants from the Canadian Institutes of Health Research. Ms Beane reported receiving grants and salary support from Wellcome Trust. Ms Bentum-Puijk reported receiving grants from the European Commission and the European Union. Dr L. Berry reported receiving grants from Berry Consultants. Dr Bradbury reported receiving personal fees from Lilly, Bristol Myers Squibb, Pfizer, Bayer, Amgen, Novartis, Janssen, Portola Advisors, and Ablynx. Dr Buxton reported receiving personal fees from the Breast Cancer Research Foundation, Amgen, and Eisai. Dr Callum reported receiving grants from the Canadian Blood Services and Octapharma. Dr Cove reported receiving grants from National University Health System, receiving consulting fees from Medtronic and Baxter, and holding a US patent for removal of carbon dioxide via dialysis. Dr Daly reported receiving grants from the Australian Red Cross Lifeblood, which is funded by the Australian government. Dr Derde reported receiving grants from University Medical Center Utrecht, being a member of the COVID-19 guideline committee of the Surviving Sepsis Campaign/ European Society of Intensive Care Medicine and European Society of Intensive Care Medicine COVID-19 taskforce, and serving as chair of the Dutch intensivists taskforce acute infectious threats. Dr Detry reported receiving grants from the European Union Platform for European Preparedness Against Reemerging Epidemics (PREPARE) consortium, the Australian National Health and Medical Research Council, the Health Research Council of New Zealand, and the UPMC Learning While Doing Program. Dr De Jong reported receiving personal fees from Roche Scientific, Shionogi Scientific, and Janssen., The current regions are: x Europe, with funding from a European Union FP7 grant (FP7-HEALTH-2013-INNOVATION-1, grant number 602525), to support the enrollment of 4000 participants. This funding terminates in 2021. x Australia and New Zealand. In Australia the project has received funding from a NHMRC Project Grant (APP1101719), to support the enrollment of 2000 participants. This funding terminates in December 2021, although some extension may be feasible. In New Zealand the project has received funding from a HRC Programme Grant (16/631), to support the enrollment of 800 participants. This funding terminates in November 2021. x Canada. In Canada the project has received funding for a CIHR grant (158584), to support the enrollment of 300 participants. This funding terminates in 2022. x United States. In the US, funding has been received from UPMC health system for recruitment internally at all UPMC hospitals (>40) and to support a US regional coordinating center. Philanthropic support is being provided through GCAR. Additional funds are being pursued., The REMAP-CAP platform is supported by the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Canadian Critical Care Trials Group, the Irish Critical Care, European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), NIHR, National Institute for Health Research, Medical Microbiology and Infection Prevention, AII - Infectious diseases, and Intensive Care Medicine

Subjects
Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 030204 cardiovascular system & hematology, Logistic regression, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Critical Illness/therapy, Vasoconstrictor Agents, 030212 general & internal medicine, Hospital Mortality, Treatment Failure, 11 Medical and Health Sciences, Original Investigation, Mortality rate, General Medicine, Middle Aged, Intensive care unit, Writing Committee for the REMAP-CAP Investigators, 3. Good health, Female, Life Sciences & Biomedicine, COVID-19/therapy, Adult, medicine.medical_specialty, Randomization, Respiration, Artificial/statistics & numerical data, Critical Illness, ABO Blood-Group System, 03 medical and health sciences, Medicine, General & Internal, Internal medicine, General & Internal Medicine, medicine, Humans, Adverse effect, COVID-19 Serotherapy, Aged, Mechanical ventilation, Science & Technology, business.industry, Immunization, Passive, Vasoconstrictor Agents/therapeutic use, COVID-19, Odds ratio, Length of Stay, Respiration, Artificial, Logistic Models, Human medicine, business
Abstract

Importance The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.Objective To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19.Design, Setting, and Participants The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021.Interventions The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916).Main Outcomes and Measures The primary ordinal end point was organ support–free days (days alive and free of intensive care unit–based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned –1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support–free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support–free days; cardiovascular support–free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events.Results Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support–free days was 0 (IQR, –1 to 16) in the convalescent plasma group and 3 (IQR, –1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR Conclusions and Relevance Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support–free days.Trial Registration ClinicalTrials.gov Identifier: NCT02735707

Published
2021
Full Text
View/download PDF

13. Perceived utility of electrodiagnostic testing in critical illness myopathy and polyneuropathy: A survey of intensive care unit providers.

Author

Isfort, Michael, McVerry, Bryan J., Shutter, Lori, Kim, Minji, and Lacomis, David

Abstract

Introduction/Aims: Critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) are common disorders associated with substantial morbidity. Electrodiagnostic studies (EDx) are effective in diagnosing CIM/CIP and identifying mimicking conditions. We surveyed intensive care unit (ICU) providers to better understand their approach to ICU‐acquired weakness (ICU‐AW) and the perceived utility of EDx. Methods: This was a single health system, Web‐based survey of ICU providers. Results: Survey responses were received from 52 providers with a response rate of 22.1%. Most providers were somewhat familiar with CIM/CIP and median perceived prevalence was 30–49%. The majority (92.3%) of providers had no standard evaluation approach for ICU‐AW. Electrodiagnostic testing was commonly considered, but many providers obtained it infrequently in presumed CIM/CIP cases. Electrodiagnostic studies were used to rule out other causes of weakness or to confirm the diagnosis of CIM/CIP. Many providers ordered EDx within 1 wk of identifying weakness. Finally, EDx were overshadowed by personal experience as the most helpful management tool for ICU‐AW. Discussion: Overall, ICU providers perceive that CIM/CIP are commonly encountered, but they may not have a standard approach to evaluation. Clinical experience increased familiarity of ICU‐AW and is central to management. EDx results are usually thought to be helpful, albeit not often ordered, and more study is needed to determine when implementation is of most assistance. Increasing education and developing institutional standards may lead to increased awareness and improved evaluation of CIM/CIP, but more study is needed to determine if algorithmic approaches would change patient outcomes. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

14. Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice.

Author

Singamsetty, Srikanth, Shah, Faraaz Ali, Guo, Lanping, Watanabe, Yoshio, McDonald, Sherie, Sharma, Rohit, Zhang, Yingze, Alonso, Laura C., O'Donnell, Christopher P., and McVerry, Bryan J.

Subjects
ANALYSIS of variance, ANIMAL experimentation, CATASTROPHIC illness, DIABETES, ENZYME-linked immunosorbent assay, GLUCOSE, HYPERGLYCEMIA, IMMUNOHISTOCHEMISTRY, MEDICAL protocols, MICE, NUTRITION, RESEARCH funding, SEPSIS, STATISTICS, T-test (Statistics), PHENOTYPES, DATA analysis
Abstract

Copyright of Applied Physiology, Nutrition & Metabolism is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2016
Full Text
View/download PDF

15. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

Author

REMAP-CAP Investigators, Gordon, Anthony C, Mouncey, Paul R, Al-Beidh, Farah, Rowan, Kathryn M, Nichol, Alistair D, Arabi, Yaseen M, Annane, Djillali, Beane, Abi, Van Bentum-Puijk, Wilma, Berry, Lindsay R, Bhimani, Zahra, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Buzgau, Adrian, Cheng, Allen C, Detry, Michelle A, Duffy, Eamon J, Estcourt, Lise J, Fitzgerald, Mark, Goossens, Herman, Haniffa, Rashan, Higgins, Alisa M, Hills, Thomas E, Horvat, Christopher M, Lamontagne, Francois, Lawler, Patrick R, Leavis, Helen L, Linstrum, Kelsey M, Litton, Edward, Lorenzi, Elizabeth, Marshall, John C, Mayr, Florian B, McAuley, Daniel F, McGlothlin, Anna, McGuinness, Shay P, McVerry, Bryan J, Montgomery, Stephanie K, Morpeth, Susan C, Murthy, Srinivas, Orr, Katrina, Parke, Rachael L, Parker, Jane C, Patanwala, Asad E, Pettilä, Ville, Rademaker, Emma, Santos, Marlene S, Saunders, Christina T, Seymour, Christopher W, Shankar-Hari, Manu, Sligl, Wendy I, Turgeon, Alexis F, Turner, Anne M, Van De Veerdonk, Frank L, Zarychanski, Ryan, Green, Cameron, Lewis, Roger J, Angus, Derek C, McArthur, Colin J, Berry, Scott, Webb, Steve A, and Derde, Lennie PG

Subjects
Adult, Male, Critical Illness, COVID-19, Middle Aged, Antibodies, Monoclonal, Humanized, Receptors, Interleukin-6, Respiration, Artificial, 3. Good health, COVID-19 Drug Treatment, Intensive Care Units, Odds Ratio, Humans, Female, Hospital Mortality, Aged
Abstract

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).

16. 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, and Zarychanski, Ryan

Subjects
Male, Heparin, Critical Illness, Anticoagulants, COVID-19, Hemorrhage, Thrombosis, Middle Aged, Respiration, Artificial, 3. Good health, 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

17. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

Author

Gordon, A.C., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Nichol, A.D., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buzgau, A., Cheng, A.C., Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Lamontagne, F., Lawler, P.R., Leavis, H.L., Linstrum, K.M., Litton, E., Lorenzi, E., Marshall, J.C., Mayr, F.B., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Murthy, S., Orr, K., Parke, R.L., Parker, J.C., Patanwala, A.E., Pettilä, V., Rademaker, E., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Sligl, W.I., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Schouten, J.A., Pickkers, P., Webb, S.A., Derde, L.P.G., Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), REMAP-CAP Investigators, Pour la France: Bruno Megarbane, Inserm U1144, European Project: 602386,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,CREDITS4HEALTH(2013), European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), NIHR, National Institute for Health Research, Gordon, Anthony C [0000-0002-0419-547X], Mouncey, Paul R [0000-0002-8510-8517], Beane, Abi [0000-0001-7046-1580], Bradbury, Charlotte A [0000-0001-5248-8165], Detry, Michelle A [0000-0002-2794-1439], Duffy, Eamon J [0000-0002-4515-5116], Estcourt, Lise J [0000-0003-4309-9162], Haniffa, Rashan [0000-0002-8288-449X], Higgins, Alisa M [0000-0001-8295-7559], Hills, Thomas E [0000-0003-0322-5822], Horvat, Christopher M [0000-0002-1593-2252], Lawler, Patrick R [0000-0001-5155-5071], Litton, Edward [0000-0002-5125-6829], Mayr, Florian B [0000-0002-2298-9011], McVerry, Bryan J [0000-0002-1175-4874], Patanwala, Asad E [0000-0003-3999-4703], Saunders, Christina T [0000-0003-4325-9568], Shankar-Hari, Manu [0000-0002-5338-2538], Angus, Derek C [0000-0002-7026-5181], Derde, Lennie PG [0000-0002-3577-5629], Apollo - University of Cambridge Repository, Investigators, REMAP-CAP, HAL UVSQ, Équipe, Credits-based, people-centric approach for the adoption of healthy life-styles and balanced Mediterranean diet in the frame of social participation and innovation for health promotion. - CREDITS4HEALTH - - EC:FP7:HEALTH2013-09-01 - 2016-08-31 - 602386 - VALID, and Platform foR European Preparedness Against (Re-)emerging Epidemics - PREPARE - - EC:FP7:HEALTH2014-02-01 - 2019-01-31 - 602525 - VALID

Subjects
Male, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 030204 cardiovascular system & hematology, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Interquartile range, middle aged, Credible interval, Odds Ratio, odds ratio, 030212 general & internal medicine, Hospital Mortality, humans, 11 Medical and Health Sciences, adult, Hazard ratio, Covid19, General Medicine, Middle Aged, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], aged, Intensive Care Units, Antibodies, Monoclonal, Humanized/adverse effects, COVID-19/complications, Original Article, Female, Adult, medicine.medical_specialty, Critical Care, Critical Illness, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Tocilizumab, male, Internal medicine, General & Internal Medicine, medicine, Humans, Aged, hospital mortality, business.industry, SARS-CoV-2, COVID-19, Odds ratio, Receptors, Interleukin-6, Respiration, Artificial, COVID-19 Drug Treatment, Coronavirus, Sarilumab, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], chemistry, Receptors, Interleukin-6/antagonists & inhibitors, REMAP-CAP Investigators, interleukin-6 receptor antagonists, coronavirus disease, business
Abstract

BACKGROUNDThe efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.METHODSWe evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support–free days, on an ordinal scale combining in-hospital death (assigned a value of −1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support–free days, or both.RESULTSBoth tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support–free days was 10 (interquartile range, −1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, −1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists.CONCLUSIONSIn critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707. opens in new tab.)

Published
2021
Full Text
View/download PDF

18. Hyperinsulinemia predicts survival in a hyperglycemic mouse model of critical illness.

Author

Woodske, Matthew E., Yokoe, Takuya, Zou, Baobo, Romano, Lia C., Rosa, Taylor C., Garcia-Ocana, Adolfo, Alonso, Laura C., O'Donnell, Christopher P., and McVerry, Bryan J.

Subjects
*HYPERGLYCEMIA, *LABORATORY mice, *PHYSIOLOGICAL effects of insulin, *BLOOD pressure measurement, *ANIMAL mortality, *CATASTROPHIC illness
Abstract

The article discusses a study which analyzes the hypothesis that relative endogenous insulin deficiency is related with adverse results in hyperglycemia-related critical illnesses. The study involved 8-12 week-old male C57BL/6J mice that passed through surgical insertion of indwelling femoral arterial and venous catheters. Accordingly, their blood pressures were observed, recorded, and kept for off-line analysis. Results revealed the association of hyperglycemia with mortality.

Published
2009
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results