Search

Your search keyword '"McGlothlin, A"' showing total 4,606 results
Start Over Author "McGlothlin, A"
4,606 results on '"McGlothlin, A"'

102. The relationship of self-efficacy, self-advocacy and multicultural counselling competency of school counsellors: A structural equation model

Author

Aydogan, Mustafa, McGlothlin, Jason, and Jencius, Marty

Abstract

School counsellors are the main drivers of change in creating a multicultural environment for all students. This study used structural equation modelling to investigate directional relationships among self-efficacy, self-advocacy and multicultural counselling competence in a sample of school counsellors (N= 306). The data were collected from 306 practising school counsellors in the US. The results suggested that self-advocacy was statistically related to self-efficacy, in turn self-efficacy was associated with multicultural counselling competence. Structural model indicated that self-advocacy had a strong indirect effect on multicultural counselling competence mediated by self-efficacy. Accordingly, the findings implicate that school counsellors could start with smaller and realistic projects in working with diverse school populations as their positive experiences in this area could increase their ability to advocate for multicultural school environments.

Published
2024
Full Text
View/download PDF

103. The Clinical Pharmacology of Intranasal l-Methamphetamine

Author

Mendelson, John E, McGlothlin, Dana, Harris, Debra S, Foster, Elyse, Everhart, Tom, Jacob, Peyton, and Jones, Reese T

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Trials and Supportive Activities, Substance Misuse, Drug Abuse (NIDA only), Methamphetamine, Clinical Research, Cardiovascular, Administration, Intranasal, Adult, Biological Availability, Blood Pressure, Body Temperature, Echocardiography, Heart Rate, Humans, Middle Aged, Pain Measurement, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

BackgroundWe studied the pharmacology of l-methamphetamine, the less abused isomer, when used as a nasal decongestant.Methods12 subjects self-administered l-methamphetamine from a nonprescription inhaler at the recommended dose (16 inhalations over 6 hours) then at 2 and 4 (32 and 64 inhalations) times this dose. In a separate session intravenous phenylephrine (200 microg) and l-methamphetamine (5 mg) were given to define alpha agonist pharmacology and bioavailability. Physiological, cardiovascular, pharmacokinetic, and subjective effects were measured.ResultsPlasma l-methamphetamine levels were often below the level of quantification so bioavailability was estimated by comparing urinary excretion of the intravenous and inhaled doses, yielding delivered dose estimates of 74.0 +/- 56.1, 124.7 +/- 106.6, and 268.1 +/- 220.5 microg for ascending exposures (mean 4.2 +/- 3.3 microg/inhalation). Physiological changes were minimal and not dose-dependent. Small decreases in stroke volume and cardiac output suggesting mild cardiodepression were seen.ConclusionInhaled l-methamphetamine delivered from a non-prescription product produced minimal effects but may be a cardiodepressant.

Published
2008

105. In response: Letter on update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol

Author

Lindsell, Christopher J., McGlothlin, Anna, Nwosu, Samuel, Rice, Todd W., Hall, Alex, Bernard, Gordon R., Busse, Laurence W., Ely, E. Wesley, Fowler, Alpha A., Gaieski, David F., Hinson, Jeremiah S., Hooper, Michael H., Jackson, James C., Kelen, Gabor D., Levine, Mark, Martin, Greg S., Rothman, Richard E., Sevransky, Jonathan E., Viele, Kert, Wright, David W., and Hager, David N.

Published
2020
Full Text
View/download PDF

107. Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial

Author

Lindsell, Christopher J., McGlothlin, Anna, Nwosu, Samuel, Rice, Todd W., Hall, Alex, Bernard, Gordon R., Busse, Laurence W., Ely, E. Wesley, Fowler, Alpha A., Gaieski, David F., Hinson, Jeremiah S., Hooper, Michael H., Jackson, James C., Kelen, Gabor D., Levine, Mark, Martin, Greg S., Rothman, Richard E., Sevransky, Jonathan E., Viele, Kert, Wright, David W., and Hager, David N.

Published
2019
Full Text
View/download PDF

108. Conservation and Convergence of Genetic Architecture in the Adaptive Radiation of Anolis Lizards

Author

Megan E. Kobiela, Jonathan B. Losos, Jason J. Kolbe, Joel W. McGlothlin, Edmund D. Brodie, and Helen V. Wright

Subjects
Constraint (information theory), biology, Phylogenetic tree, Evolutionary biology, Phylogenetics, Adaptive radiation, Convergence (relationship), biology.organism_classification, Anolis, Genetic architecture, Selection (genetic algorithm), Ecology, Evolution, Behavior and Systematics
Abstract

The G matrix, which quantifies the genetic architecture of traits, is often viewed as an evolutionary constraint. However, G can evolve in response to selection and may also be viewed as a product of adaptive evolution. Convergent evolution of G in similar environments would suggest that G evolves adaptively, but it is difficult to disentangle such effects from phylogeny. Here, we use the adaptive radiation of Anolis lizards to ask whether convergence of G accompanies the repeated evolution of habitat specialists, or ecomorphs, across the Greater Antilles. We measured G in seven species representing three ecomorphs (trunk-crown, trunk- ground, and grass-bush). We found that the overall structure of G does not converge. Instead, the structure of G is well conserved and displays a phylogenetic signal consistent with Brownian motion. However, several elements of G showed signatures of convergence, indicating that some aspects of genetic architecture have been shaped by selection. Most notably, genetic correlations between limb traits and body traits were weaker in long-legged trunk-ground species, suggesting effects of recurrent selection on limb length. Our results demonstrate that common selection pressures may have subtle but consistent effects on the evolution of G, even as its overall structure remains conserved.

Published
2022
Full Text
View/download PDF

109. ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery

Author

Dana P. McGlothlin, John Granton, Walter Klepetko, Maurice Beghetti, Erika B. Rosenzweig, Paul A. Corris, Evelyn Horn, Manreet K. Kanwar, Karen McRae, Antonio Roman, Ryan Tedford, Roberto Badagliacca, Sonja Bartolome, Raymond Benza, Marco Caccamo, Rebecca Cogswell, Celine Dewachter, Laura Donahoe, Elie Fadel, Harrison W. Farber, Jeffrey Feinstein, Veronica Franco, Robert Frantz, Michael Gatzoulis, Choon Hwa (Anne) Goh, Marco Guazzi, Georg Hansmann, Stuart Hastings, Paul M. Heerdt, Anna Hemnes, Antoine Herpain, Chih-Hsin Hsu, Kim Kerr, Nicholas A. Kolaitis, Jasleen Kukreja, Michael Madani, Stuart McCluskey, Michael McCulloch, Bernhard Moser, Manchula Navaratnam, Göran Rådegran, Cara Reimer, Laurent Savale, Oksana A. Shlobin, Jana Svetlichnaya, Keith Swetz, Jessica Tashjian, Thenappan Thenappan, Carmine Dario Vizza, Shawn West, Warren Zuckerman, Andreas Zuckermann, and Teresa De Marco

Subjects
Pulmonary and Respiratory Medicine, Transplantation, hypertension, pulmonary, Hypertension, Pulmonary, risk assessment, heart failure, anesthesia, congenital heart disease, pediatric pulmonary hypertension, consensus, pulmonary arterial hypertension, pulmonary hypertension, risk factors, Surgery, surgery, humans, hypertension, pulmonary, Cardiology and Cardiovascular Medicine
Abstract

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.

Published
2022
Full Text
View/download PDF

111. Augustine's Resurrection Framework: Clarifying and Connecting Senses of "Resurrection".

Author

McGlothlin, Thomas D.

Subjects
*RESURRECTION, *THEOLOGY, *SPIRITUALISM
Abstract

Augustine combined two distinctions to develop an elegant interpretive framework for embracing multiple senses of "resurrection," resolving tensions that had bedeviled predecessors such as Irenaeus and Tertullian. The first distinction was between the general resurrection of the body and an accompanying bodily transformation restricted to the saved. The second distinction, which he shared with many fourth-century authors but may have drawn most directly from Tyconius, was between a "first," spiritual resurrection experienced now by the baptized and a "second," bodily resurrection experienced eschatologically by all. Scholars have noted both distinctions separately but not explored how Augustine came to adopt them and use them in combination. Augustine deployed these distinctions together to resolve theological problems caused by apparent Pauline connections between the "first" resurrection of believers and the "second" resurrection of all. [ABSTRACT FROM AUTHOR]

Published
2024

114. Coteaching in Counselor Education: Preparing Doctoral Students for Future Teaching

Author

Baltrinic, Eric R., Jencius, Marty, and McGlothlin, Jason

Abstract

This phenomenological study explored 10 counselor education doctoral students' coteaching experiences with faculty members. Three coteaching structures identified from the data were relational, operational, and developmental. A definition of coteaching supported by the findings is presented. Implications for counselor education programs, limitations, and directions for future research are discussed.

Published
2016
Full Text
View/download PDF

116. HEAVY HAULIN': Air Lift's LoadLifter 7500 XL makes the '17 Super Duty even more capable

Author

McGlothlin, Mike

Subjects
Pickup trucks, Editors, Company business planning, Sports and fitness, Travel, recreation and leisure
Abstract

AIR LIFT COMPANY'S LOADLIFTER 7500 XL brings 7,500 pounds' worth of load-leveling capacity to the freshest heavy-duty offerings from Ford, Ram, and GM. With our '17 Ford F-350 being prepped [...]

Published
2019

117. THE PARTY BARGE: A Duramax-powered 1972 Suburban with seating for 12

Author

McGlothlin, Mike

Subjects
eBay Inc., Online information services, Online information service, Sports and fitness, Travel, recreation and leisure
Abstract

WHEN YOU OWN 300 ACRES OF WOODED central Missouri backcountry, it pays to have a vehicle that can traverse the mud, rock, and hills you're bound to encounter. For homebuilder [...]

Published
2019

119. A Retrospective Review of Reimbursement in Revision Total Hip Arthroplasty: A Disparity Between Case Complexity and RVU Compensation

Author

Arpan Patel, Victoria Oladipo, Benjamin Kerzner, Jonathan D. McGlothlin, and Brett R. Levine

Subjects
Reoperation, Arthroplasty, Replacement, Hip, Operative Time, Humans, Orthopedics and Sports Medicine, Hip Prosthesis, Medicare, United States, Aged, Retrospective Studies
Abstract

Revision total hip arthroplasties (THA) are time-consuming, expensive, and technically challenging. Today's Current Procedural Terminology (CPT) codes and relative value units (RVU) may in fact disincentivize surgeons to perform revision THAs. Our study reviewed labor and time investments for each component-specific revision THA and analyzed the gap between procedural value billed and final reimbursement.A retrospective review of 165 primary and revision THAs were validated using operative notes and billing records. We stratified revision THAs by standard CPT coding (with modifiers) as single acetabular component, single femoral component, femoral head plus polyethylene liner (head/liner) exchange, all-components, and spacer placement for infection. Operative time, RVUs, total charges, deductions, and final reimbursement data was collected. Mann-Whitney U tests studied final reimbursement per minute vs per RVU in revision and primary THAs.Our cohort consisted of 27 primary THAs, 26 acetabular component revisions, 32 head/liner exchanges, 26 femoral component revisions, 27 all-component revisions, and 27 spacer placements. Compared to primary THAs, every revision subgroup except for head/liner exchanges were found to reimburse less per minute and all revision subgroups reimbursed less per RVU (P.05).Physicians face less reimbursement per minute and per RVU for revision THAs. With cuts in reimbursement set forth by Centers for Medicare and Medicaid Services (CMS) and insurers, revisions may be financially unfavorable. This ultimately will lead to an impending access to care problem in the future. Our study supports the need to re-examine the RVU allocation amongst revision THAs and evaluate changes to the Current Procedural Terminology (CPT) coding system.

Published
2022
Full Text
View/download PDF

120. PET-CR as a potential surrogate endpoint in untreated DLBCL: meta-analysis and implications for clinical trial design

Author

Kristine Broglio, Lale Kostakoglu, Carol Ward, Federico Mattiello, Denis Sahin, Tina Nielsen, Anna McGlothlin, Corrine F. Elliott, Thomas Witzig, Laurie H. Sehn, Marek Trnĕný, Umberto Vitolo, Maurizio Martelli, Margaret Foster, Barbara Wendelberger, Grzegorz Nowakowski, and Donald A. Berry

Subjects
Clinical Trials as Topic, Cancer Research, Oncology, Humans, Bayes Theorem, Lymphoma, Large B-Cell, Diffuse, Hematology, Disease-Free Survival, Biomarkers
Abstract

This study's focus is the association of end-of-therapy (EOT) PET results with progression-free (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma receiving first-line chemoimmunotherapy. We develop a Bayesian hierarchical model for predicting PFS and OS from EOT PET-complete response (PET-CR) using a literature-based meta-analysis of 20 treatment arms and a substudy of 4 treatment arms in 3 clinical trials for which we have patient-level data. The PET-CR rate in our substudy was 72%. The modeled estimates for hazard ratio (PET-CR/non-PET-CR) were 0.13 for PFS (95% CI 0.10, 0.16) and 0.10 for OS (CI 0.07, 0.12). Hazard ratios varied little by patient subtype and were confirmed by the overall meta-analysis. We link these findings to designing future clinical trials and show how our model can be used in adapting the sample size of a trial to accumulating results regarding treatment benefits on PET-CR and a survival endpoint.

Published
2022
Full Text
View/download PDF

121. The road not taken: Evolution of tetrodotoxin resistance in the Sierra garter snake ( Thamnophis couchii ) by a path less travelled

Author

Jessica S. Reimche, Robert E. del Carlo, Edmund D. Brodie, Joel W. McGlothlin, Karen Schlauch, Michael E. Pfrender, Normand Leblanc, and Chris R. Feldman

Subjects
Predatory Behavior, Colubridae, Genetics, Animals, Tetrodotoxin, Salamandridae, Adaptation, Physiological, Ecology, Evolution, Behavior and Systematics
Abstract

The repeated evolution of tetrodotoxin (TTX) resistance provides a model for testing hypotheses about the mechanisms of convergent evolution. This poison is broadly employed as a potent antipredator defence, blocking voltage-gated sodium channels (Na

Published
2022
Full Text
View/download PDF

122. The Staphylococcus aureus Network Adaptive Platform Trial Protocol: New Tools for an Old Foe

Author

Steven Y C, Tong, Jocelyn, Mora, Asha C, Bowen, Matthew P, Cheng, Nick, Daneman, Anna L, Goodman, George S, Heriot, Todd C, Lee, Roger J, Lewis, David C, Lye, Robert K, Mahar, Julie, Marsh, Anna, McGlothlin, Zoe, McQuilten, Susan C, Morpeth, David L, Paterson, David J, Price, Jason A, Roberts, J Owen, Robinson, Sebastiaan J, van Hal, Genevieve, Walls, Steve A, Webb, Lyn, Whiteway, Dafna, Yahav, and Joshua S, Davis

Subjects
Microbiology (medical), Staphylococcus aureus, Infectious Diseases, Humans, Bacteremia, Staphylococcal Infections, Anti-Bacterial Agents
Abstract

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%–30%. Despite this

Published
2022
Full Text
View/download PDF

123. A Retrospective Review of Relative Value Units in Revision Total Knee Arthroplasty: A Dichotomy Between Surgical Complexity and Reimbursement

Author

Arpan Patel, Victoria A. Oladipo, Benjamin Kerzner, Jonathan D. McGlothlin, and Brett R. Levine

Subjects
Reoperation, Current Procedural Terminology, Operative Time, Humans, Orthopedics and Sports Medicine, Arthroplasty, Replacement, Knee, Retrospective Studies
Abstract

Revision total knee arthroplasties (TKA) are costly, time-intensive, and technically demanding procedures. There are concerns regarding the valuation of Current Procedural Terminology (CPT) codes and the assigned relative value units (RVU) as a potential disincentive to perform revision TKAs. This study evaluated the labor and time investment for each component-specific revision and assessed the disparities between procedural value billed and reimbursement.A retrospective review of 154 primary and revision TKA cases were thoroughly vetted using operative notes and internal billing data. Revision TKAs were stratified by single femoral component, single tibial component, polyethylene liner only, all-component, and spacer placement for prosthetic infection. Operative time, RVUs billed, total charges, deductions, and reimbursements were recorded. Mann-Whitney U tests compared final reimbursement per minute and per RVU between revision and primary TKAs.There were 28 primary TKAs, 11 femoral component revisions, 25 tibial component revisions, 25 liner exchanges, 37 all-component revisions, and 28 spacer placements. Revisions involving the tibial component, all-components, and placement of spacers were reimbursed less dollars per minute than primary TKAs (P.05). Controlling for RVUs, liner exchanges and all-component revisions had fewer dollars per RVU than primary TKAs (P.05).As revision complexity increases, physicians face less reimbursement per minute and per RVU. With reductions set by CMS and private insurers, revisions may be financially unfavorable and lead to restrictions and access to care problems. Our data supports the need for reevaluating RVU allocation amongst revision procedures with potential updates to the CPT coding system.

Published
2022
Full Text
View/download PDF

124. A first-in-human study in healthy subjects of the safety and pharmacokinetics of CNM-Au8, a suspension of catalytically active gold nanocrystals with remyelinating and neuroprotective properties

Author

Kanhai, Kawita MS, primary, Zuiker, RGJA, additional, Houghton, W, additional, Kramer, WG, additional, McBride, Kyle, additional, Moerland, M, additional, Dorfman, Adam, additional, McGlothlin, Misty, additional, Hotchkin, Michael, additional, Mortenson, Mark, additional, Etherington, Rob, additional, and Groeneveld, Geert Jan, additional

Published
2023
Full Text
View/download PDF

125. Results from the first four regimens of the HEALEY ALS Platform Trial (PL5.004)

Author

Paganoni, Sabrina, primary, Berry, James, additional, Quintana, Melanie, additional, Macklin, Eric, additional, Saville, Benjamin, additional, Andrews, Jinsy, additional, Shefner, Jeremy, additional, Fournier, Christina, additional, Babu, Suma, additional, Maragakis, Nicholas, additional, Oskarsson, Bjorn, additional, Detry, Michelle, additional, Chase, Marianne, additional, Sherman, Alex, additional, Yu, Hong, additional, Pothier, Lindsay, additional, Drake, Kristin, additional, Chibnik, Lori, additional, Bind, Marie-Abele, additional, Vestrucci, Matteo, additional, McGlothlin, Anna, additional, Marion, Joseph, additional, Duda, Petra, additional, Harvey, Brittany, additional, Qureshi, Irfan, additional, Donohue, Mary, additional, Granit, Volkan, additional, Grossman, Katheryn, additional, Glanzman, Robert, additional, Hotchkin, Michael, additional, Goldberg, Y Paul, additional, Leitner, Melanie, additional, Hayden, Michael, additional, and Cudkowicz, Merit, additional

Published
2023
Full Text
View/download PDF

126. Emphysema Detection in the Course of Lung Cancer Screening: Optimizing a Rare Opportunity to Impact Population Health

Author

Mulshine, James L., primary, Aldigé, Carolyn R., additional, Ambrose, Laurie Fenton, additional, Armato, Samuel G., additional, Avila, Ricardo S., additional, Cham, Matt, additional, Estepar, Raul San Jose, additional, Fain, Sean B., additional, Gazourian, Lee, additional, Gierada, David S., additional, Hatt, Charles, additional, Henschke, Claudia I., additional, Hoyos, Jody, additional, Lynch, David A., additional, McGlothlin, Anita K., additional, Oudkerk, Matthijs, additional, Pasquinelli, Mary, additional, Pinsky, Paul, additional, Pyenson, Bruce, additional, Rizzo, Albert A., additional, Ross, Sheila M., additional, Schmitz, Kathryn H., additional, Silva, Mario, additional, Okwuosa, Tochukwu, additional, Washko, George, additional, Wisnivesky, Juan, additional, Yankelevitz, David F., additional, and Zulueta, Javier J., additional

Published
2023
Full Text
View/download PDF

127. In response: Letter on update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol

Author

Christopher J. Lindsell, Anna McGlothlin, Samuel Nwosu, Todd W. Rice, Alex Hall, Gordon R. Bernard, Laurence W. Busse, E. Wesley Ely, Alpha A. Fowler, David F. Gaieski, Jeremiah S. Hinson, Michael H. Hooper, James C. Jackson, Gabor D. Kelen, Mark Levine, Greg S. Martin, Richard E. Rothman, Jonathan E. Sevransky, Kert Viele, David W. Wright, and David N. Hager

Subjects
Medicine (General), R5-920
Abstract

Trial registration ClinicalTrials.gov : NCT03509350 . Registered on 26 April 2018.

Published
2020
Full Text
View/download PDF

128. A blueprint for a multi-disease, multi-domain Bayesian adaptive platform trial incorporating adult and paediatric subgroups: the Staphylococcus aureus Network Adaptive Platform trial

Author

Mahar, RK, McGlothlin, A, Dymock, M, Lee, TC, Lewis, RJ, Lumley, T, Mora, J, Price, DJ, Saville, BR, Snelling, T, Turner, R, Webb, SA, Davis, JS, Tong, SYC, Marsh, JA, Mahar, RK, McGlothlin, A, Dymock, M, Lee, TC, Lewis, RJ, Lumley, T, Mora, J, Price, DJ, Saville, BR, Snelling, T, Turner, R, Webb, SA, Davis, JS, Tong, SYC, and Marsh, JA

Abstract

The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a multifactorial Bayesian adaptive platform trial that aims to improve the way that S. aureus bloodstream infection, a globally common and severe infectious disease, is treated. In a world first, the SNAP trial will simultaneously investigate the effects of multiple intervention modalities within multiple groups of participants with different forms of S. aureus bloodstream infection. Here, we formalise the trial structure, modelling approach, and decision rules that will be used for the SNAP trial. By summarising the statistical principles governing the design, our hope is that the SNAP trial will serve as an adaptable template that can be used to improve comparative effectiveness research efficiency in other disease areas.Trial registration NCT05137119 . Registered on 30 November 2021.

Published
2023

129. Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

Author

Higgins, A.M., Berry, L.R., Lorenzi, E., Murthy, S., McQuilten, Z., Mouncey, P.R., Al-Beidh, F., Annane, D., Arabi, Y.M., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Charles, W.N., Cove, M., Detry, M.A., Estcourt, L.J., Fagbodun, E.O., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Horvat, C.M., Huang, D.T., Ichihara, N., Lamontagne, F., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Parry-Billings, K., Peters, S.E.C., Reyes, L.F., Rowan, K.M., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Stronach, L.M., 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., Derde, L.P.G., Gordon, A.C., Webb, S.A., Lawler, P.R., Higgins, A.M., Berry, L.R., Lorenzi, E., Murthy, S., McQuilten, Z., Mouncey, P.R., Al-Beidh, F., Annane, D., Arabi, Y.M., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Charles, W.N., Cove, M., Detry, M.A., Estcourt, L.J., Fagbodun, E.O., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Horvat, C.M., Huang, D.T., Ichihara, N., Lamontagne, F., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Parry-Billings, K., Peters, S.E.C., Reyes, L.F., Rowan, K.M., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Stronach, L.M., 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., Derde, L.P.G., Gordon, A.C., Webb, S.A., and Lawler, P.R.

Abstract

Item does not contain fulltext, IMPORTANCE: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. OBJECTIVE: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. INTERVENTIONS: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). MAIN OUTCOMES AND MEASURES: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. RESULTS: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06

Published
2023

130. 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

Lawler, P.R., Derde, L.P.G., Veerdonk, F.L. van de, McVerry, B.J., Huang, D.T., Berry, L.R., Lorenzi, E., Kimmenade, R.R.J. van, Gommans, F., Vaduganathan, M., Leaf, D.E., Baron, R.M., Kim, E.Y., Frankfurter, C., Epelman, S., Kwan, Y., Grieve, R., O'Neill, S., Sadique, Z., Puskarich, M., Marshall, J.C., Higgins, A.M., Mouncey, P.R., Rowan, K.M., Al-Beidh, F., Annane, D., Arabi, Y.M., Au, C., Beane, A., Bentum-Puijk, W. van, Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Cecconi, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Ezekowitz, J., Fitzgerald, M., Gattas, D., Godoy, L.C., Goossens, H., Haniffa, R., Harrison, D.A., Hills, T., Horvat, C.M., Ichihara, N., Lamontagne, F., Linstrum, K.M., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McQuilten, Z., Murthy, S., Nichol, A.D., Owen, D.R.J., Parke, R.L., Parker, J.C., Pollock, K.M., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Singh, V., Turgeon, A.F., Turner, A.M., Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., Berry, S., Gordon, A.C., McArthur, C.J., Webb, S.A., Lawler, P.R., Derde, L.P.G., Veerdonk, F.L. van de, McVerry, B.J., Huang, D.T., Berry, L.R., Lorenzi, E., Kimmenade, R.R.J. van, Gommans, F., Vaduganathan, M., Leaf, D.E., Baron, R.M., Kim, E.Y., Frankfurter, C., Epelman, S., Kwan, Y., Grieve, R., O'Neill, S., Sadique, Z., Puskarich, M., Marshall, J.C., Higgins, A.M., Mouncey, P.R., Rowan, K.M., Al-Beidh, F., Annane, D., Arabi, Y.M., Au, C., Beane, A., Bentum-Puijk, W. van, Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Cecconi, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Ezekowitz, J., Fitzgerald, M., Gattas, D., Godoy, L.C., Goossens, H., Haniffa, R., Harrison, D.A., Hills, T., Horvat, C.M., Ichihara, N., Lamontagne, F., Linstrum, K.M., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McQuilten, Z., Murthy, S., Nichol, A.D., Owen, D.R.J., Parke, R.L., Parker, J.C., Pollock, K.M., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Singh, V., Turgeon, A.F., Turner, A.M., Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., Berry, S., Gordon, A.C., McArthur, C.J., and Webb, S.A.

Abstract

Item does not contain fulltext, 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 surv

Published
2023

134. A first-in-human study in healthy subjects of the safety and pharmacokinetics of CNM-Au8, a suspension of catalytically active gold nanocrystals with remyelinating and neuroprotective properties

Author

KMS Kanhai, RGJA Zuiker, W Houghton, WG Kramer, K McBride, M Moerland, Adam Dorfman, Misty McGlothlin, M Hotchkin, M Mortenson, R Etherington, and GJ Groeneveld

Abstract

CNM-Au8 is a suspension of catalytically-active gold nanocrystals, developed to treat neurodegenerative disease. A first-in-human single- and multiple-ascending dose study was performed to assess safety and pharmacokinetics of CNM-Au8. The single-dose phase enrolled 40 subjects; the multiple-dose phase 48 subjects. Doses ranged from 15 to 90 mg CNM-Au8 and were administered by qualified clinical staffper os. Safety was assessed by adverse events, vitals, ECGs and laboratory measurements.The most frequently reported related adverse event was mild abdominal pain (20%) of transient nature. Plasma half-life was 11.5 to 26.2 days, a first dose tmaxranged from 3.3 - 3.5 hours. CNM-Au8 displayed a safety profile and pharmacokinetic properties supportive of its advancement to Phase 2 and Phase 3 clinical trials.

Published
2023
Full Text
View/download PDF

135. Results from the first four regimens of the HEALEY ALS Platform Trial (PL5.004)

Author

Sabrina Paganoni, James Berry, Melanie Quintana, Eric Macklin, Benjamin Saville, Jinsy Andrews, Jeremy Shefner, Christina Fournier, Suma Babu, Nicholas Maragakis, Bjorn Oskarsson, Michelle Detry, Marianne Chase, Alex Sherman, Hong Yu, Lindsay Pothier, Kristin Drake, Lori Chibnik, Marie-Abele Bind, Matteo Vestrucci, Anna McGlothlin, Joseph Marion, Petra Duda, Brittany Harvey, Irfan Qureshi, Mary Donohue, Volkan Granit, Katheryn Grossman, Robert Glanzman, Michael Hotchkin, Y Paul Goldberg, Melanie Leitner, Michael Hayden, and Merit Cudkowicz

Published
2023
Full Text
View/download PDF

136. 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

138. Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support–free days in patients hospitalized with COVID-19

Author

Writing Committee for the REMAP-CAP Investigators, Lawler, PR, Derde, LPG, Van de Veerdonk, FL, McVerry, BJ, Huang, DT, Berry, LR, Lorenzi, E, Van Kimmenade, R, Gommans, F, Vaduganathan, M, Leaf, DE, Baron, RM, Kim, EY, Frankfurter, C, Epelman, S, Kwan, Y, Grieve, R, O'Neill, S, Sadique, Z, Puskarich, M, Marshall, JC, Higgins, AM, Mouncey, PR, Rowan, KM, Al-Beidh, F, Annane, D, Arabi, YM, Au, C, Beane, A, Van Bentum-Puijk, W, Bonten, MJM, Bradbury, CA, Brunkhorst, FM, Burrell, A, Buzgau, A, Buxton, M, Cecconi, M, Cheng, AC, Cove, M, Detry, MA, Estcourt, LJ, Ezekowitz, J, Fitzgerald, M, Gattas, D, Godoy, LC, Goossens, H, Haniffa, R, Harrison, DA, Hills, T, Horvat, CM, Ichihara, N, Lamontagne, F, Linstrum, KM, McAuley, DF, McGlothlin, A, McGuinness, SP, McQuilten, Z, Murthy, S, Nichol, AD, Owen, DRJ, Parke, RL, Parker, JC, Pollock, KM, Reyes, LF, Saito, H, Santos, MS, Saunders, CT, Seymour, CW, Shankar-Hari, M, Singh, V, Turgeon, AF, Turner, AM, Zarychanski, R, Green, C, Lewis, RJ, Angus, DC, Berry, S, Gordon, AC, McArthur, CJ, and Webb, SA

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

140. Brace yourself: a flood of water lawsuits is coming: Russell McGlothlin and Matt Kline from international law firm O'Melveny & Myers explain why US courtrooms could soon be flooded with lawsuits in an effort to secure scarce water supplies

Author

McGlothlin, Russell and Kline, Matt

Subjects
O'Melveny & Myers L.L.P. -- International economic relations -- Cases, Climate change -- Cases, Law firms -- International economic relations -- Cases, Litigation -- Cases, International law -- Cases, Water supply -- Cases -- United States -- California, Company legal issue, Lawsuit/litigation, Business, Business, international, Petroleum, energy and mining industries
Abstract

RESEARCHERS ARE WARNING THE US to brace for a 'megadrought,' with large reservoirs in the Colorado River basin already showing signs of another year of alarming declines. As water levels [...]

Published
2020

142. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19

Author

Bradbury, Charlotte A., Lawler, Patrick R., Stanworth, Simon J., McVerry, Bryan J., McQuilten, Zoe, Higgins, Alisa M., Mouncey, Paul R., Al-Beidh, Farah, Rowan, Kathryn M., Berry, Lindsay R., Lorenzi, Elizabeth, Zarychanski, Ryan, Arabi, Yaseen M., Annane, Djillali, Beane, Abi, Van Bentum-Puijk, Wilma, Bhimani, Zahra, Bihari, Shailesh, Bonten, Marc J. M., Brunkhorst, Frank M., Buzgau, Adrian, Buxton, Meredith, Carrier, Marc, Cheng, Allen C., Cove, Matthew, Detry, Michelle A., Estcourt, Lise J., Fitzgerald, Mark, Girard, Timothy D., Goligher, Ewan C., Goossens, Herman, Haniffa, Rashan, Hills, Thomas, Huang, David T., Horvat, Christopher M., Hunt, Beverley J., Ichihara, Nao, Lamontagne, Francois, Leavis, Helen L., Linstrum, Kelsey M., Litton, Edward, Marshall, John C., McAuley, Daniel F., McGlothlin, Anna, McGuinness, Shay P., Middeldorp, Saskia, Montgomery, Stephanie K., Morpeth, Susan C., Murthy, Srinivas, Neal, Matthew D., Nichol, Alistair D., Parke, Rachael L., Parker, Jane C., Reyes, Luis, Saito, Hiroki, Santos, Marlene S., Saunders, Christina T., Serpa-Neto, Ary, Seymour, Christopher W., Shankar-Hari, Manu, Singh, Vanessa, Tolppa, Timo, Turgeon, Alexis F., Turner, Anne M., van de Veerdonk, Frank L., Green, Cameron, Lewis, Roger J., Angus, Derek C., McArthur, Colin J., Berry, Scott, Derde, Lennie P. G., Webb, Steve A., Gordon, Anthony C., Depuydt, Pieter, De Waele, Jan, De Bus, Liesbet, Fierens, Jan, Vermassen, Joris, REMAP-CAP Investigators, University of Bristol [Bristol], University Health Network, University of Toronto, University of Oxford, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Monash University [Melbourne], Imperial College London, University of Manitoba [Winnipeg], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University Medical Center [Utrecht], St. Michael's Hospital, 215522, CS-2016-16-011, RP-2015-06-18, National Institutes of Health, NIH, U.S. Department of Defense, DOD, National Institute of General Medical Sciences, NIGMS, National Institute of Neurological Disorders and Stroke, NINDS, Gordon and Betty Moore Foundation, GBMF, Medtronic, Baxter International, Medical Center, University of Pittsburgh, CancerCare Manitoba Foundation, CCMF, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD, Wellcome Trust, WT, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, LAM Therapeutics, Canadian Institutes of Health Research, IRSC: 158584, Medical Research Council, MRC, National Institute for Health and Care Research, NIHR, European Commission, EC, National Heart and Lung Institute, NHLI, Queen's University Belfast, QUB: US8962032, National Health and Medical Research Council, NHMRC: APP1101719, National Medical Research Council, NMRC, Health Research Council of New Zealand, HRC: 16/631, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Innovate UK, Horizon 2020, Pharmaceuticals Bayer, Swedish Orphan Biovitrum, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support: This study was funded by the following: the Platform for European Preparedness Against (Re-)Emerging Epidemics (PREPARE) consortium of the European Union, FP7-HEALTH-2013-INNOVATION-1 (grant 602525), the Rapid European COVID-19 Emergency Research Response (RECOVER) consortium of the European Union’s Horizon 2020 Research and Innovation Programme (grant 101003589), the Australian National Health and Medical Research Council (grant APP1101719), the Health Research Council of New Zealand (grant 16/631), the Canadian Institute of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program (grant 158584), the NIHR and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (grant CTN 2014-012), the University of Pittsburgh Medical Center (UPMC) Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (grant PHRC-20-0147), the Minderoo Foundation, and the Wellcome Trust Innovations Project (grant 215522). Dr Shankar-Hari is funded by an NIHR clinician scientist fellowship (grant CS-2016-16-011) and Dr Gordon is funded by an NIHR research professorship (grant RP-2015-06-18)., The REMAP-CAP platform is supported by the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Canadian Critical Care Clinical Trials Group, the Irish Critical Care Clinical Trials Network, the UK Critical Care Research Group and the International Forum of Acute Care Trialists., REMAP-CAP was supported in the Netherlands by the Research Collaboration Critical Care the Netherlands, reported receipt of personal fees from Lilly, BMS-Pfizer, Bayer, Amgen, Novartis, Janssen, Portola, Ablynx, and Grifols. Dr Lawler reported receipt of personal fees from Novartis, CorEvitas, and Brigham and Women’s Hospital and royalties from McGraw-Hill Publishing. Dr McVerry reported receipt of grants from the National Heart, Lung, and Blood Institute and Bayer Pharmaceuticals and personal fees from Boehringer Ingelheim. Dr L. Berry reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Lorenzi reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Zarychanski reported receipt of grants from the Canadian Institutes of Health Research, LifeArc, Research Manitoba, the CancerCare Manitoba Foundation, Peter Munk Cardiac Centre, and the Thistledown Foundation and research operating support as the Lyonel G. Israels Research Chair in Hematology. Dr Bonten reported membership in international study steering committees, advisory boards, and independent data safety and monitoring committees funded by Janssen Vaccines, Merck Sharp & Dohme, AstraZeneca, Pfizer, and Sanofi Pasteur (all reimbursements to UMC Utrecht). Dr Brunkhorst reported receipt of grants from Jena University Hospital. Dr Buxton reported receipt of a gift from the Breast Cancer Research Foundation and contracts with Amgen and Eisai. Dr Carrier reported receipt of grants from BMS-Pfizer and personal fees from Bayer, Sanofi, Servier, Leo Phama, and BMS-Pfizer to his institution. Dr Cove reported receipt of grants from the National Medical Research Council and personal fees from Baxter and Medtronic. Dr Estcourt reported receipt of grants from the UK National Institute for Health Research (NIHR) and the European Union Horizon 2020 Research and Innovation Programme. Dr Haniffa reported receipt of grants from the UK Research and Innovation/Medical Research Council African Critical Care Registry Network. Dr Horvat reported receipt of grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Dr Ichihara reported being affiliated with the Department of Healthcare Quality Assessment, University of Tokyo, which is a social collaboration supported by the National Clinical Database, Johnson & Johnson, and Nipro Corporation. Dr Marshall reported receipt of personal fees from AM Pharma and Critical Care Medicine. Dr McAuley reported receipt of personal fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Lilly, Vir Biotechnology, Faron Pharmaceutical, and SOBI and grants from the NIHR, the Wellcome Trust, Innovate UK, the UK Medical Research Council, and the Northern Ireland Health and Social Care Research and Development Division, in addition, Dr McAuley had a Queen’s University Belfast patent for novel treatment for inflammatory disease (US8962032), was co-director of research at the Intensive Care Society until June 2021, and was director of the Efficacy and Mechanisms Evaluation Program for the UK Medical Research Council/NIHR. Dr Middeldorp reported receipt of personal fees from Daiichi Sankyo, Bayer, Pfizer, Boehringer Ingelheim, Portola/Alexion, AbbVie, BMS-Pfizer, Sanofi, and Viatris, all paid to his institution, and grants from Daiichi Sankyo, Bayer, Pfizer, and Boehringer Ingelheim. Dr Neal reported equity in Haima Therapeutics, receipt of personal fees from Janssen Pharma and Haemonetics, and receipt of grants from Instrumentation Laboratory, the National Institutes of Health, and the Department of Defense. Dr Nichol reported receipt of personal fees from AM Pharma, paid to his university, and grants from Baxter. Dr Parke reported receipt of grants from Fisher and Paykel Healthcare NZ. Dr Serpa-Neto reported receipt of personal fees from Drager and Endpoint Health. Dr Seymour reported receipt of grants from the Gordon and Betty Moore Foundation and the National Institutes of Health/National Institute of General Medical Sciences. Dr Lewis reported being senior medical scientist at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr S. Berry reported being an employee with an ownership role at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Derde reported being a coordinating committee member for the European Clinical Research Alliance on Infectious Diseases, a member of the Dutch Intensivists Task Force on Acute Infectious Threats, a member of the International Scientific Advisory Board for Sepsis Canada, and a member of the Dutch Academy of Sciences’ Pandemic Preparedness Plan committee. Dr Gordon reported receipt of personal fees from 30 Respiratory, paid to his institution. No other disclosures were reported., European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), Investigators, REMAP-CAP Writing Committee for the REMAP-CAP, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, and Intensive Care Medicine

Subjects
Adult, Male, Platelet Aggregation Inhibitors/adverse effects, Critical Illness, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Hemorrhage, Aspirin/adverse effects, Hemorrhage/chemically induced, INFECTION, Humans, COAGULOPATHY, Aspirin, Anticoagulants, COVID-19, Bayes Theorem, Venous Thromboembolism, General Medicine, Middle Aged, Respiration, Artificial, COVID-19 Drug Treatment, Critical Illness/mortality, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Purinergic P2Y Receptor Antagonists/adverse effects, Purinergic P2Y Receptor Antagonists, COVID-19/complications, Female, Human medicine, Anticoagulants/adverse effects, Platelet Aggregation Inhibitors, Venous Thromboembolism/drug therapy
Abstract

Contains fulltext : 248713.pdf (Publisher’s version ) (Closed access) 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

144. UNLEASHING DIESEL POWER.

Author

MCGLOTHLIN, MIKE

Subjects
LIGHTNING, SOLENOIDS, DIESEL motors, TURBOCHARGERS
Abstract

It takes a different approach, featuring a lower vane resistance rating than the Type-S. This adjustment compensates for the heightened load generated by performance-modified trucks, particularly those with injector upgrades and either stock or upgraded turbos. It's worth noting that, until the hold-down bracket bolt is precisely torqued to specification, the solenoid may exert outward pressure, a common trait even in stock VGT solenoids. The Type-S solenoid caters to a wide range of trucks, including stock ones, tuned models, and those with upgraded VGTs. [Extracted from the article]

Published
2023

145. The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol: a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial

Author

Hager, David N., Hooper, Michael H., Bernard, Gordon R., Busse, Laurence W., Ely, E. Wesley, Fowler, Alpha A., Gaieski, David F., Hall, Alex, Hinson, Jeremiah S., Jackson, James C., Kelen, Gabor D., Levine, Mark, Lindsell, Christopher J., Malone, Richard E., McGlothlin, Anna, Rothman, Richard E., Viele, Kert, Wright, David W., Sevransky, Jonathan E., and Martin, Greg S.

Published
2019
Full Text
View/download PDF

146. Conan the Existentialist Hero.

Author

McGlothlin, James C.

Subjects
PHILOSOPHY, EXISTENTIALISM, ESSAYS
Abstract

The article delves into a reconsideration of Charles Hoffman's 1974 essay, "Conan the Existentialist," exploring its argument connecting Robert E. Howard's Conan stories to existentialist philosophy. It states that Hoffman's analysis aligns the character Conan with existentialist philosophy, highlighting Conan's self-governance and absence of predetermined intent as emblematic of existentialist ideals.

Published
2023

150. Heterogeneous treatment effects of therapeutic-dose heparin in patients hospitalized for COVID-19

Author

Goligher, EC, Lawler, PR, Jensen, TP, Talisa, V, Berry, LR, Lorenzi, E, McVerry, BJ, Chang, C-CH, Leifer, E, Bradbury, C, Berger, J, Hunt, BJ, Castellucci, LA, Kornblith, LZ, Gordon, AC, McArthur, C, Webb, S, Hochman, J, Neal, MD, Zarychanski, R, Berry, S, Angus, DC, Aday, A, Ahuja, T, Al-Beidh, F, Annane, D, Arabi, YM, Aryal, D, Baumann Kreuziger, L, Beane, A, Berger, JS, Berry, SM, Bhimani, Z, Bihari, S, Billett, HH, Bond, L, Bonten, M, Bradbury, CA, Brooks, MM, Brunkhorst, F, Buxton, M, Buzgau, A, Carrier, M, Castelucci, LA, Chekuri, S, Chen, J-T, Cheng, AC, Chkhikvadze, T, Coiffard, B, Contreras, A, Costantini, TW, Cushman, M, De Brouwer, S, Derde, LPG, Detry, MA, Duggal, A, Džavík, V, Effron, MB, Eng, HF, Escobedo, J, Estcourt, LJ, Everett, BM, Farkough, ME, Fergusson, DA, Fitzgerald, M, Fowler, RA, Froess, JD, Fu, Z, Galanaud, J-P, Galen, BT, Gandotra, S, Girard, TD, Godoy, LD, Gong, MN, Goodman, AL, Goossens, H, Green, C, Greenstein, YY, Gross, PL, Guerrero, RM, Hamburg, N, Haniffa, R, Hanna, G, Hanna, N, Hedge, SM, Hendrickson, CM, Higgins, AM, Hindenburg, AA, Hite, RD, Hochman, JS, Hope, AA, Horowitz, JM, Horvat, CM, Houston, BL, Huang, DT, Hudock, K, Husain, M, Hyzy, RC, Iyer, V, Jacobson, JR, Jayakumar, D, Kahn, SR, Keller, NM, Khan, A, Kim, Y, Kim, KS, Kindzelski, A, King, AJ, Kirwan, B-A, Knudson, MM, Kornblith, AE, Krishnan, V, Kumar, A, Kutcher, ME, Laffan, MA, Lamontagne, F, Le Gal, G, Leeper, CM, Leifer, ES, Lewis, RJ, Lim, G, Lima, FG, Linstrum, K, Litton, E, Lopez-Sendon, J, Lopez-Sendon Moreno, JL, Lother, SA, Madrona, SG, Malhotra, S, Marcos Martin, M, Marshall, JC, Marten, N, Martinez, AS, Martinez, M, Mateos Garcia, E, Matthay, MA, Mavromichalis, S, McArthur, CJ, McAuley, DF, McDonald, EG, McGlothlin, A, McGuinness, SP, McQuilten, ZK, Middeldorp, S, Montgomery, SK, Moore, SC, Mouncey, PR, Murthy, S, Nair, GB, Nair, R, Nichol, AD, Nicolau, JC, Nunez-Garcia, B, Pandey, A, Park, JJ, Park, PK, Parke, RL, Parker, JC, Parnia, S, Paul, JD, Pompilio, M, Prekker, M, Quigley, JG, Reynolds, HR, Rosenson, RS, Rost, NS, Rowan, K, Santos, MO, Santos, FO, Santos, M, Satterwhite, L, Saunders, CT, Schreiber, J, Schutgens, REG, Seymour, CW, Shankar Hari, M, Sheehan, JP, Siegal, DM, Silva Jr., DG, Singhal, AB, Slutsky, AS, Solvason, D, Stanworth, SJ, Tritschler, T, Turgeon, AF, Turner, AM, Van Bentum-Puijk, W, Van de Veerdonk, FL, Van Diepen, S, Vazquez Grande, G, Wahid, L, Wareham, V, Webb, SA, Wells, B, Widmer, RJ, Wilson, JG, Yuriditsky, E, Zampieri, F, and Zhong, Y

Abstract

Importance Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making. Objective To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE. Design, Setting, and Participants Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial. Exposures Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis. Main Outcomes and Measures Organ support–free days, assigning a value of −1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival. Results Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support–free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support–free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI 90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR

Published
2023

Catalog

Books, media, physical & digital resources
See catalog results