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1. A New Global Definition of Acute Respiratory Distress Syndrome.

Author

Arabi, Yaseen, Arroliga, Alejandro, Bernard, Gordon, Bersten, Andrew, Brochard, Laurent, Calfee, Carolyn, Combes, Alain, Daniel, Brian, Ferguson, Niall, Gong, Michelle, Gotts, Jeffrey, Herridge, Margaret, Laffey, John, Liu, Kathleen, Machado, Flavia, Martin, Thomas, McAuley, Danny, Mercat, Alain, Moss, Marc, Mularski, Richard, Pesenti, Antonio, Qiu, Haibo, Ramakrishnan, Nagarajan, Ranieri, V, Riviello, Elisabeth, Rubin, Eileen, Slutsky, Arthur, Thompson, B, Twagirumugabe, Theogene, Ware, Lorraine, Wick, Katherine, and Matthay, Michael

Subjects
ARDS, acute lung injury, pulmonary edema, Humans, Prospective Studies, Reproducibility of Results, Respiratory Distress Syndrome, Oximetry, Oxygen
Abstract

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Published
2024

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

Author

Hills, Thomas, Lorenzi, Elizabeth, Berry, Lindsay, Shyamsundar, Murali, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Aryal, Diptesh, Au, Carly, Beane, Abigail, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Burrell, Aidan, Buxton, Meredith, Calfee, Carolyn, Cecconi, Maurizio, Cheng, Allen, Cove, Matthew, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goligher, Ewan, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Harrison, David, Hashmi, Madiha, Higgins, Alisa, Huang, David, Ichihara, Nao, Jayakumar, Deva, Kruger, Peter, Lamontagne, François, Lampro, Lamprini, Lawler, Patrick, Marshall, John, Mason, Alexina, McGlothlin, Anna, McGuinness, Shay, McQuilten, Zoe, McVerry, Bryan, Mouncey, Paul, Murthy, Srinivas, Neal, Matthew, Nichol, Alistair, OKane, Cecilia, Parke, Rachael, Parker, Jane, Rabindrarajan, Ebenezer, Reyes, Luis, Rowan, Kathryn, Saito, Hiroki, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Shankar-Hari, Manu, Sinha, Pratik, Thompson, B, Turgeon, Alexis, Turner, Anne, van de Veerdonk, Frank, Weis, Sebastian, Young, Ian, Zarychanski, Ryan, McArthur, Colin, Angus, Derek, Berry, Scott, Derde, Lennie, Webb, Steve, Gordon, Anthony, McAuley, Daniel, and Lewis, Roger

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

Published
2023

3. Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock.

Author

Busse, Laurence, Boldt, David, Deane, Adam, Gong, Michelle, Ham, Kealy, Khanna, Ashish, Ostermann, Marlies, McCurdy, Michael, Thompson, B, Tumlin, James, Adams, Christopher, Hodges, Tony, Bellomo, Rinaldo, Leisman, Daniel, Handisides, Damian, Chawla, Lakhmir, and Albertson, Timothy

Subjects
ARDS, Angiotensin II, Norepinephrine, Renin–angiotensin system, Septic, Shock
Abstract

BACKGROUND: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. METHODS: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. RESULTS: Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2-161.5], p = 0.0028). Similarly, oxygenation index decreased by - 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus - 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI - 8.6 to - 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5-47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. CONCLUSIONS: In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

Published
2023

4. Solar Energetic Particle-Associated Coronal Mass Ejections Observed by the Mauna Loa Solar Observatory Mk3 and Mk4 Coronameters

Author

Richardson, I. G., Cyr, O. C. St, Burkepile, J. T., Xie, H., and Thompson, B. J.

Subjects
Astrophysics - Solar and Stellar Astrophysics
Abstract

We report on the first comprehensive study of the coronal mass ejections (CMEs) associated with $\sim$25 MeV solar energetic proton (SEP) events in 1980-2013 observed in the low/inner corona by the Mauna Loa Solar Observatory (MLSO) Mk3 and Mk4 coronameters. Where possible, these observations are combined with spacebased observations from the Solar Maximum Mission C/P, P78-1 SOLWIND or SOHO/LASCO coronagraphs. The aim of the study is to understand directly-measured (rather than inferred from proxies) CME motions in the low to middle corona and their association with SEP acceleration, and hence attempt to identify early signatures that are characteristic of SEP acceleration in ground-based CME observations that may be used to warn of impending SEP events. Although we find that SEP events are associated with CMEs that are on average faster and wider than typical CMEs observed by MLSO, a major challenge turns out to be determining reliable estimates of the CME dynamics in the low corona from the 3-minute cadence Mk3/4 observations since different analysis techniques can produce inconsistent results. This complicates the assessment of what early information on a possible SEP event is available from these low coronal observations, Comment: To be published in Solar Physics

Published
2023
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5. Psychophysical discrimination of radially varying polarization entoptic phenomena

Author

Pushin, D. A., Kapahi, C., Silva, A. E., Cory, D. G., Kulmaganbetov, M., Mungalsingh, M., Singh, T., Thompson, B., and Sarenac, D.

Subjects
Physics - Medical Physics, Physics - Optics
Abstract

The incorporation of structured light techniques into vision science has enabled more selective probes of polarization related entoptic phenomena. Diverse sets of stimuli have become accessible in which the spatially dependant optical properties can be rapidly controlled and manipulated. For example, past studies with human perception of polarization have dealt with stimuli that appear to vary azimuthally. This is mainly due to the constraint that the typically available degree of freedom to manipulate the phase shift of light rotates the perceived pattern around a person's point of fixation. Here we create a structured light stimulus that is perceived to vary purely along the radial direction and test discrimination sensitivity to inwards and outwards radial motion. This is accomplished by preparing a radial state coupled to an orbital angular momentum state that matches the orientation of the dichroic elements in the macula. The presented methods offering a new dimension of exploration serve as a direct compliment to previous studies and may provide new insights into characterizing macular pigment density profiles and assessing the health of the macula.

Published
2023

6. Heliophysics Discovery Tools for the 21st Century: Data Science and Machine Learning Structures and Recommendations for 2020-2050

Author

McGranaghan, R. M., Thompson, B., Camporeale, E., Bortnik, J., Bobra, M., Lapenta, G., Wing, S., Poduval, B., Lotz, S., Murray, S., Kirk, M., Chen, T. Y., Bain, H. M., Riley, P., Tremblay, B., Cheung, M., and Delouille, V.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Astrophysics - Solar and Stellar Astrophysics, Computer Science - Artificial Intelligence, Computer Science - Machine Learning
Abstract

Three main points: 1. Data Science (DS) will be increasingly important to heliophysics; 2. Methods of heliophysics science discovery will continually evolve, requiring the use of learning technologies [e.g., machine learning (ML)] that are applied rigorously and that are capable of supporting discovery; and 3. To grow with the pace of data, technology, and workforce changes, heliophysics requires a new approach to the representation of knowledge., Comment: 4 pages; Heliophysics 2050 White Paper

Published
2022

7. Gas accretion and Ram Pressure Stripping of Haloes in Void Walls

Author

Thompson, B. B., Smith, R., and Kraljic, K.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We conduct hydrodynamical cosmological zoom simulations of fourteen voids to study the ability of haloes to accrete gas at different locations throughout the voids at z = 0. Measuring the relative velocity of haloes with respect to their ambient gas, we find that a tenth of the haloes are expected to be unable to accrete external gas due to its fast flow passed them (so called 'fast flow haloes'). These are typically located near void walls. We determine that these haloes have recently crossed the void wall and are still moving away from it. their motion counter to that of ambient gas falling towards the void wall results in fast flows that make external gas accretion very challenging, and often cause partial gas loss via the resultant ram pressures. Using an analytical approach, we model the impact of such ram pressures on the gas inside haloes of different masses. A halo's external gas accretion is typically cut off, with partial stripping of halo gas. For masses below a few times 10$^{9}$ M$_{\odot}$, their halo gas is heavily truncated but not completely stripped. We identify numerous examples of haloes with a clear jelly-fish like gas morphology, indicating their surrounding gas is being swept away, cutting them off from further external accretion. These results highlight how, even in the relatively low densities of void walls, a fraction of galaxies can interact with large-scale flows in a manner that has consequences for their gas content and ability to accrete gas., Comment: 13 pages, 8 figures

Published
2022
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8. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension.

Author

Miller, Chadwick, Oldmixon, Katherine, Park, Pauline, Rice, Todd, Ringwood, Nancy, Semler, Matthew, Steingrub, Jay, Talmor, Daniel, Thompson, B, Yealy, Donald, Self, Wesley, Shapiro, Nathan, Douglas, Ivor, Brower, Roy, Brown, Samuel, Exline, Matthew, Ginde, Adit, Gong, Michelle, Grissom, Colin, Hayden, Douglas, Hough, Catherine, Huang, Weixing, Iwashyna, Theodore, Jones, Alan, Khan, Akram, Lai, Poying, and Liu, Kathleen

Subjects
Humans, Fluid Therapy, Sepsis, Hypotension, Time Factors, Treatment Outcome, Vasoconstrictor Agents
Abstract

BACKGROUND: Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited. METHODS: In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed. RESULTS: A total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, -2134 ml; 95% confidence interval [CI], -2318 to -1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, -0.9 percentage points; 95% CI, -4.4 to 2.6; P = 0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups. CONCLUSIONS: Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028.).

Published
2023

10. Remote Sensing of Coronal Forces During a Solar Prominence Eruption

Author

Uritsky, V. M., Thompson, B. J., and DeVore, C. R.

Subjects
Astrophysics - Solar and Stellar Astrophysics, Physics - Plasma Physics, Physics - Space Physics
Abstract

We present a new methodology -- the Keplerian Optical Dynamics Analysis (KODA) -- for analyzing the dynamics of dense, cool material in the solar corona. The technique involves adaptive spatiotemporal tracking of propagating intensity gradients and their characterization in terms of time-evolving Keplerian areas swept out by the position vectors of moving plasma blobs. Whereas gravity induces purely ballistic motions consistent with Kepler's second law, non-central forces such as the Lorentz force introduce non-zero torques resulting in more complex motions. KODA algorithms enable direct evaluation of the line-of-sight component of the net torque density from the image-plane projection of the areal acceleration. The method is applied to the prominence eruption of 2011 June 7, observed by the Solar Dynamics Observatory's Atmospheric Imaging Assembly. Results obtained include quantitative estimates of the magnetic forces, field intensities, and blob masses and energies across a vast region impacted by the post-reconnection redistribution of the prominence material. The magnetic pressure and energy are strongly dominant during the early, rising phase of the eruption, while the dynamic pressure and kinetic energy become significant contributors during the subsequent falling phases. Measured intensive properties of the prominence blobs are consistent with those of typical active-region prominences; measured extensive properties are compared with those of the whole pre-eruption prominence and the post-eruption coronal mass ejection of 2011 June 7, all derived by other investigators and techniques. We argue that KODA provides valuable information on characteristics of erupting prominences that are not readily available via alternative means, thereby shedding new light on their environment and evolution., Comment: 22 pages, 12 figures, 3 tables

Published
2022
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11. The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19

Author

Rogers, Angela J, Wentworth, Deborah, Phillips, Andrew, Shaw-Saliba, Katy, Dewar, Robin L, Aggarwal, Neil R, Babiker, Abdel G, Chang, Weizhong, Dharan, Nila J, Davey, Victoria J, Higgs, Elizabeth S, Gerry, Norman, Ginde, Adit A, Hayanga, JW Awori, Highbarger, Helene, Highbarger, Jeroen L, Jain, Mamta K, Kan, Virginia, Kim, Kami, Lallemand, Perrine, Leshnower, Bradley G, Lutaakome, Joseph K, Matthews, Gail, Mourad, Ahmad, Mylonakis, Eleftherios, Natarajan, Ven, Padilla, Maria L, Pandit, Lavannya M, Paredes, Roger, Pett, Sarah, Ramachandruni, Srikanth, Rehman, M Tauseef, Sherman, Brad T, Files, D Clark, Brown, Samuel M, Matthay, Michael A, Thompson, B Taylor, Neaton, James D, Lane, H Clifford, Lundgren, Jens D, Sahner, David, Tierney, John, Vogel, Susan E, Herpin, Betsey R, Smolskis, Mary C, McKay, Laura A, Cahill, Kelly, Crew, Page, Sardana, Ratna, Raim, Sharon Segal, Hensely, Lisa, Lorenzo, Johsua, Mock, Rebecca, Zuckerman, Judith, Atri, Negin, Miller, Mark, Vallee, David, Chung, Lucy, Kang, Nayon, and Barrett, Kevin

Subjects
Prevention, Vaccine Related, Emerging Infectious Diseases, Infectious Diseases, Clinical Research, Lung, Biodefense, Inflammatory and immune system, Infection, Good Health and Well Being, Adult, COVID-19, Cross-Sectional Studies, Humans, Male, Nucleocapsid, SARS-CoV-2, ACTIV-3/TICO Study Group, Clinical Sciences, Public Health and Health Services
Abstract

BackgroundLevels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19.ObjectiveTo evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2.DesignCross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge.Setting114 centers in 10 countries.ParticipantsAdults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms.MeasurementsBaseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively.ResultsPlasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity.LimitationsPlasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available.ConclusionElevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients.Primary funding sourceU.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Published
2022

12. Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery.

Author

Douin, David J, Siegel, Lianne, Grandits, Greg, Phillips, Andrew, Aggarwal, Neil R, Baker, Jason, Brown, Samuel M, Chang, Christina C, Goodman, Anna L, Grund, Birgit, Higgs, Elizabeth S, Hough, Catherine L, Murray, Daniel D, Paredes, Roger, Parmar, Mahesh, Pett, Sarah, Polizzotto, Mark N, Sandkovsky, Uriel, Self, Wesley H, Young, Barnaby E, Babiker, Abdel G, Davey, Victoria J, Kan, Virginia, Gelijns, Annetine C, Matthews, Gail, Thompson, B Taylor, Lane, H Clifford, Neaton, James D, Lundgren, Jens D, and Ginde, Adit A

Subjects
Humans, Antibodies, Monoclonal, Treatment Outcome, Aftercare, Patient Discharge, Aged, COVID-19, SARS-CoV-2, monoclonal antibodies, outcomes assessment, Clinical Trials and Supportive Activities, Clinical Research, Good Health and Well Being, Medical and Health Sciences, Respiratory System
Abstract

Rationale: Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Objectives: Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery. Methods: We used pooled data from three clinical trials of neutralizing monoclonal antibodies to compare: 1) the hospital discharge approach; 2) the TICO (Therapeutics for Inpatients with COVID-19) trials sustained recovery approach; and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-ICU setting without organ failure or major extrapulmonary manifestations of COVID-19. We defined discordance as a difference between time to recovery. Measurements and Main Results: Discordance between the hospital discharge and comprehensive approaches occurred in 170 (20%) of 850 enrolled participants, including 126 hospital readmissions and 24 deaths after initial hospital discharge. Discordant participants were older (median age, 68 vs. 59 years; P

Published
2022

13. Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19

Author

Barkauskas, Christina, Mylonakis, Eleftherios, Poulakou, Garyfallia, Young, Barnaby E, Vock, David M, Siegel, Lianne, Engen, Nicole, Grandits, Greg, Mosaly, Nilima R, Vekstein, Andrew M, Rogers, Ralph, Shehadeh, Fadi, Kaczynski, Matthew, Mylona, Evangelia K, Syrigos, Konstantinos N, Rapti, Vasiliki, Lye, David C, Hui, Diong Shiau, Leither, Lindsay, Knowlton, Kirk U, Jain, Mamta K, Marines-Price, Rubria, Osuji, Alice, Overcash, J Scott, Kalomenidis, Ioannis, Barmparessou, Zafeiria, Waters, Michael, Zepeda, Karla, Chen, Peter, Torbati, Sam, Kiweewa, Francis, Sebudde, Nicholus, Almasri, Eyad, Hughes, Alyssa, Bhagani, Sanjay R, Rodger, Alison, Sandkovsky, Uriel, Gottlieb, Robert L, Nnakelu, Eriobu, Trautner, Barbara, Menon, Vidya, Lutaakome, Joseph, Matthay, Michael, Robinson, Philip, Protopapas, Konstantinos, Koulouris, Nikolaos, Kimuli, Ivan, Baduashvili, Amiran, Braun, Dominique L, Günthard, Huldrych F, Ramachandruni, Srikanth, Kidega, Robert, Kim, Kami, Hatlen, Timothy J, Phillips, Andrew N, Murray, Daniel D, Jensen, Tomas O, Padilla, Maria L, Accardi, Evan X, Shaw-Saliba, Katy, Dewar, Robin L, Teitelbaum, Marc, Natarajan, Ven, Laverdure, Sylvain, Highbarger, Helene C, Rehman, M Tauseef, Vogel, Susan, Vallée, David, Crew, Page, Atri, Negin, Schechner, Adam J, Pett, Sarah, Hudson, Fleur, Badrock, Jonathan, Touloumi, Giota, Brown, Samuel M, Self, Wesley H, North, Crystal M, Ginde, Adit A, Chang, Christina C, Kelleher, Anthony, Nagy-Agren, Stephanie, Vasudeva, Shikha, Looney, David, Nguyen, Hien H, Sánchez, Adriana, Weintrob, Amy C, Grund, Birgit, Sharma, Shweta, Reilly, Cavan S, Paredes, Roger, Bednarska, Agnieszka, Gerry, Norman P, Babiker, Abdel G, Davey, Victoria J, Gelijns, Annetine C, Higgs, Elizabeth S, Kan, Virginia, Matthews, Gail, and Thompson, B Taylor

Subjects
Clinical Research, Clinical Trials and Supportive Activities, Lung, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Adult, Designed Ankyrin Repeat Proteins, Double-Blind Method, Humans, Recombinant Fusion Proteins, SARS-CoV-2, Treatment Outcome, COVID-19 Drug Treatment, ACTIV-3/TICO Study Group, Clinical Sciences, Public Health and Health Services
Abstract

BackgroundEnsovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.ObjectiveTo investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.DesignDouble-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978).SettingMultinational, multicenter trial.ParticipantsAdults hospitalized with COVID-19.InterventionIntravenous ensovibep, 600 mg, or placebo.MeasurementsEnsovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90.ResultsAn independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR

Published
2022

16. Lessons from an international trial evaluating vaccination strategies for recovered inpatients with COVID-19 (VATICO).

Author

Mylonakis, Eleftherios, Lutaakome, Joseph, Jain, Mamta, Rogers, Angela, Moltó, José, Benet, Susana, Mourad, Ahmad, Files, D, Mugerwa, Henry, Kityo, Cissy, Kiweewa, Francis, Nalubega, Mary, Kitonsa, Jonathan, Nabenkema, Evelyn, Murray, Daniel, Braun, Dominique, Kamel, Dena, Higgs, Elizabeth, Hatlen, Timothy, Kan, Virginia, Sanchez, Adriana, Tierney, John, Denner, Eileen, Wentworth, Deborah, Babiker, Abdel, Davey, Victoria, Gelijns, Annetine, Matthews, Gail, Thompson, B, Lane, H, Neaton, James, and Lundgren, Jens

Subjects
COVID-19, COVID-19 Vaccines, Humans, Inpatients, Randomized Controlled Trials as Topic, Vaccination
Abstract

The protection provided by natural versus hybrid immunity from COVID-19 is unclear. We reflect on the challenges from trying to conduct a randomized post-SARS-CoV-2 infection vaccination trial study with rapidly evolving scientific data, vaccination guidelines, varying international policies, difficulties with vaccine availability, vaccine hesitancy, and a constantly evolving virus.

Published
2022

18. Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock

Author

Leisman, Daniel E., Handisides, Damian R., Chawla, Lakhmir S., Albertson, Timothy E., Busse, Laurence W., Boldt, David W., Deane, Adam M., Gong, Michelle N., Ham, Kealy R., Khanna, Ashish K., Ostermann, Marlies, McCurdy, Michael T., Thompson, B. Taylor, Tumlin, James S., Adams, Christopher D., Hodges, Tony N., and Bellomo, Rinaldo

Published
2023
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19. RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19

Author

Wick, Katherine D, Siegel, Lianne, Neaton, James D, Oldmixon, Cathryn, Lundgren, Jens, Dewar, Robin L, Lane, H Clifford, Thompson, B Taylor, and Matthay, Michael A

Subjects
Clinical Research, Clinical Trials and Supportive Activities, Good Health and Well Being, Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing, Biomarkers, COVID-19, Humans, Interleukin-6, Prognosis, Receptor for Advanced Glycation End Products, ACTIV-3/TICO study group, Antigen, Clinical practice, Cytokines, Pulmonology
Abstract

BackgroundThe value of the soluble receptor for advanced glycation end-products (sRAGE) as a biomarker in COVID-19 is not well understood. We tested the association between plasma sRAGE and illness severity, viral burden, and clinical outcomes in hospitalized patients with COVID-19 who were not mechanically ventilated.MethodsBaseline sRAGE was measured among participants enrolled in the ACTIV-3/TICO trial of bamlanivimab for hospitalized patients with COVID-19. Spearman's rank correlation was used to assess the relationship between sRAGE and other plasma biomarkers, including viral nucleocapsid antigen. Fine-Gray models adjusted for baseline supplemental oxygen requirement, antigen level, positive endogenous anti-nucleocapsid antibody response, sex, age, BMI, diabetes mellitus, renal impairment, corticosteroid treatment, and log2-transformed IL-6 level were used to assess the association between baseline sRAGE and time to sustained recovery. Cox regression adjusted for the same factors was used to assess the association between sRAGE and mortality.ResultsAmong 277 participants, baseline sRAGE was strongly correlated with viral plasma antigen concentration (ρ = 0.57). There was a weaker correlation between sRAGE and biomarkers of systemic inflammation, such as IL-6 (ρ = 0.36) and CRP (ρ = 0.20). Participants with plasma sRAGE in the highest quartile had a significantly lower rate of sustained recovery (adjusted recovery rate ratio, 0.64 [95% CI, 0.43-0.90]) and a higher unadjusted risk of death (HR, 4.70 [95% CI, 2.01-10.99]) compared with participants in the lower quartiles.ConclusionElevated plasma sRAGE in hospitalized, nonventilated patients with COVID-19 was an indicator of both clinical illness severity and plasma viral load. Plasma sRAGE in the highest quartile was associated with a lower likelihood of sustained recovery and higher unadjusted risk of death. These findings, which we believe to be novel, indicate that plasma sRAGE may be a promising biomarker for COVID-19 prognostication and clinical trial enrichment.Trial RegistrationClinicalTrials.gov NCT04501978.FundingNIH (5T32GM008440-24, 18X107CF6, HHSN261201500003I, R35HL140026, and OT2HL156812).

Published
2022

20. Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

Author

Group, ACTIV-3 Therapeutics for Inpatients with COVID-19 Study, Self, Wesley H, Sandkovsky, Uriel, Reilly, Cavan S, Vock, David M, Gottlieb, Robert L, Mack, Michael, Golden, Kevin, Dishner, Emma, Vekstein, Andrew, Ko, Emily R, Der, Tatyana, Franzone, John, Almasri, Eyad, Fayed, Mohamed, Filbin, Michael R, Hibbert, Kathryn A, Rice, Todd W, Casey, Jonathan D, Hayanga, J Awori, Badhwar, Vinay, Leshnower, Bradley G, Sharifpour, Milad, Knowlton, Kirk U, Peltan, Ithan D, Bakowska, Elizieta, Kowalska, Justyna, Bowdish, Michael E, Sturek, Jeffrey M, Rogers, Angela J, Files, D Clark, Mosier, Jarrod M, Gong, Michelle N, Douin, David J, Hite, R Duncan, Trautner, Barbara W, Jain, Mamta K, Gardner, Edward M, Khan, Akram, Jensen, Jens-Ulrik, Matthay, Michael A, Ginde, Adit A, Brown, Samuel M, Higgs, Elizabeth S, Pett, Sarah, Weintrob, Amy C, Chang, Christina C, Murrary, Daniel D, Günthard, Huldrych F, Moquete, Ellen, Grandits, Greg, Engen, Nicole, Grund, Birgit, Sharma, Shweta, Cao, Huyen, Gupta, Rajesh, Osei, Suzette, Margolis, David, Zhu, Qing, Polizzotto, Mark N, Babiker, Abdel G, Davey, Victoria J, Kan, Virginia, Thompson, B Taylor, Gelijns, Annetine C, Neaton, James D, Lane, H Clifford, Jundgren, Jens D, Tierney, John, Barrett, Kevin, Herpin, Betsey R, Smolskis, Mary C, Voge, Susan E, McNay, Laura A, Cahill, Kelly, Crew, Page, Kirchoff, Matthew, Sardana, Ratna, Raim, Sharon Segal, Chiu, Joseph, Hensley, Lisa, Lorenzo, Josua, Mock, Rebecca, Shaw-Saliba, Katy, Zuckerman, Judith, Adam, Stacey J, Currier, Judy, Read, Sarah, Hughes, Eric, Amos, Laura, Carlsen, Amy, Carter, Anita, Davis, Bionca, Denning, Eileen, DuChene, Alain, Harrison, Merrie, Kaiser, Payton, Koopmeiners, Joseph, Meger, Sue, and Murray, Thomas

Subjects
Clinical Trials and Supportive Activities, Lung, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Adolescent, Adult, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing, Double-Blind Method, Female, Humans, Male, Middle Aged, SARS-CoV-2, Treatment Outcome, COVID-19 Drug Treatment, ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study Group, Clinical Sciences, Medical Microbiology, Public Health and Health Services, Microbiology
Abstract

BackgroundWe aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.MethodsIn this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.FindingsBetween Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.InterpretationNeither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.FundingUS National Institutes of Health and Operation Warp Speed.

Published
2022

21. Rapid Automated Analysis of Skull Base Tumor Specimens Using Intraoperative Optical Imaging and Artificial Intelligence

Author

Jiang, Cheng, Bhattacharya, Abhishek, Linzey, Joseph, Joshi, Rushikesh S., Cha, Sung Jik, Srinivasan, Sudharsan, Alber, Daniel, Kondepudi, Akhil, Urias, Esteban, Pandian, Balaji, Al-Holou, Wajd, Sullivan, Steve, Thompson, B. Gregory, Heth, Jason, Freudiger, Chris, Khalsa, Siri, Pacione, Donato, Golfinos, John G., Camelo-Piragua, Sandra, Orringer, Daniel A., Lee, Honglak, and Hollon, Todd

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Artificial Intelligence, Computer Science - Machine Learning
Abstract

Background: Accurate diagnosis of skull base tumors is essential for providing personalized surgical treatment strategies. Intraoperative diagnosis can be challenging due to tumor diversity and lack of intraoperative pathology resources. Objective: To develop an independent and parallel intraoperative pathology workflow that can provide rapid and accurate skull base tumor diagnoses using label-free optical imaging and artificial intelligence. Method: We used a fiber laser-based, label-free, non-consumptive, high-resolution microscopy method ($<$ 60 sec per 1 $\times$ 1 mm$^\text{2}$), called stimulated Raman histology (SRH), to image a consecutive, multicenter cohort of skull base tumor patients. SRH images were then used to train a convolutional neural network (CNN) model using three representation learning strategies: cross-entropy, self-supervised contrastive learning, and supervised contrastive learning. Our trained CNN models were tested on a held-out, multicenter SRH dataset. Results: SRH was able to image the diagnostic features of both benign and malignant skull base tumors. Of the three representation learning strategies, supervised contrastive learning most effectively learned the distinctive and diagnostic SRH image features for each of the skull base tumor types. In our multicenter testing set, cross-entropy achieved an overall diagnostic accuracy of 91.5%, self-supervised contrastive learning 83.9%, and supervised contrastive learning 96.6%. Our trained model was able to identify tumor-normal margins and detect regions of microscopic tumor infiltration in whole-slide SRH images. Conclusion: SRH with trained artificial intelligence models can provide rapid and accurate intraoperative analysis of skull base tumor specimens to inform surgical decision-making., Comment: Published as journal article

Published
2021
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22. The prognostic value of early measures of the ventilatory ratio in the ARDS ROSE trial

Author

Monteiro, Ana Carolina Costa, Vangala, Sitaram, Wick, Katherine D, Delucchi, Kevin L, Siegel, Emily R, Thompson, B Taylor, Liu, Kathleen D, Sapru, Anil, Sinha, Pratik, and Matthay, Michael A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Patient Safety, Clinical Trials and Supportive Activities, Rare Diseases, Clinical Research, Good Health and Well Being, APACHE, Humans, Kaplan-Meier Estimate, Neuromuscular Blockade, Prognosis, Respiratory Distress Syndrome, Ventilatory ratio, VR, ARDS, Neuromuscular blockade, APACHE-III, ROSE trial, NHLBI PETAL Network, Medical and Health Sciences, Emergency & Critical Care Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundThe ventilatory ratio (VR, [minute ventilation × PaCO2]/[predicted body weight × 100 × 37.5]) is associated with mortality in ARDS. The aims of this study were to test whether baseline disease severity or neuromuscular blockade (NMB) modified the relationship between VR and mortality.MethodsThis was a post hoc analysis of the PETAL-ROSE trial, which randomized moderate-to-severe ARDS patients to NMB or control. Survival among patients with different VR trajectories or VR cutoff above and below the median was assessed by Kaplan-Meier analysis. The relationships between single-day or 48-h VR trajectories with 28- or 90-day mortality were tested by logistic regression. Randomization allocation to NMB and markers of disease severity were tested as confounders by multivariable regression and interaction term analyses.ResultsPatients with worsening VR trajectories had significantly lower survival compared to those with improving VR (n = 602, p  2 (median) at day 1 had a significantly lower 90-day survival compared to patients with VR ≤ 2 (HR 1.36, 95% CI 1.10-1.69). VR at day 1 was significantly associated with 28-day mortality (OR = 1.40, 95% CI 1.15-1.72). There was no interaction between NMB and VR for 28-day mortality. APACHE-III had a significant interaction with VR at baseline for the outcome of 28-day mortality, such that the relationship between VR and mortality was stronger among patients with lower APACHE-III. There was a significant association between rising VR trajectory and mortality that was independent of NMB, baseline PaO2/FiO2 ratio and generalized markers of disease severity (Adjusted OR 1.81, 95% CI 1.28-2.84 for 28-day and OR 2.07 95% CI 1.41-3.10 for 90-day mortality). APACHE-III and NMB were not effect modifiers in the relationship between VR trajectory and mortality.ConclusionsElevated baseline and day 1 VR were associated with higher 28-day mortality. The relationship between baseline VR and mortality was stronger among patients with lower APACHE-III. APACHE-III was not an effect modifier for the relationship between VR trajectory and mortality, so that the VR trajectory may be optimally suited for prognostication and predictive enrichment. VR was not different between patients randomized to NMB or control, indicating that VR can be utilized without correcting for NMB.

Published
2022

23. Advancing precision medicine for acute respiratory distress syndrome

Author

Beitler, Jeremy R, Thompson, B Taylor, Baron, Rebecca M, Bastarache, Julie A, Denlinger, Loren C, Esserman, Laura, Gong, Michelle N, LaVange, Lisa M, Lewis, Roger J, Marshall, John C, Martin, Thomas R, McAuley, Daniel F, Meyer, Nuala J, Moss, Marc, Reineck, Lora A, Rubin, Eileen, Schmidt, Eric P, Standiford, Theodore J, Ware, Lorraine B, Wong, Hector R, Aggarwal, Neil R, and Calfee, Carolyn S

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Orphan Drug, Lung, Acute Respiratory Distress Syndrome, Respiratory, Good Health and Well Being, COVID-19, Humans, Precision Medicine, Respiratory Distress Syndrome, Public Health and Health Services, Other Medical and Health Sciences, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome. Understanding of the complex pathways involved in lung injury pathogenesis, resolution, and repair has grown considerably in recent decades. Nevertheless, to date, only therapies targeting ventilation-induced lung injury have consistently proven beneficial, and despite these gains, ARDS morbidity and mortality remain high. Many candidate therapies with promise in preclinical studies have been ineffective in human trials, probably at least in part due to clinical and biological heterogeneity that modifies treatment responsiveness in human ARDS. A precision medicine approach to ARDS seeks to better account for this heterogeneity by matching therapies to subgroups of patients that are anticipated to be most likely to benefit, which initially might be identified in part by assessing for heterogeneity of treatment effect in clinical trials. In October 2019, the US National Heart, Lung, and Blood Institute convened a workshop of multidisciplinary experts to explore research opportunities and challenges for accelerating precision medicine in ARDS. Topics of discussion included the rationale and challenges for a precision medicine approach in ARDS, the roles of preclinical ARDS models in precision medicine, essential features of cohort studies to advance precision medicine, and novel approaches to clinical trials to support development and validation of a precision medicine strategy. In this Position Paper, we summarise workshop discussions, recommendations, and unresolved questions for advancing precision medicine in ARDS. Although the workshop took place before the COVID-19 pandemic began, the pandemic has highlighted the urgent need for precision therapies for ARDS as the global scientific community grapples with many of the key concepts, innovations, and challenges discussed at this workshop.

Published
2022

24. Sleep Apnea and Respiratory Anomaly Detection from a Wearable Band and Oxygen Saturation

Author

Ganglberger, Wolfgang, Bucklin, Abigail A., Tesh, Ryan A., Cardoso, Madalena Da Silva, Sun, Haoqi, Leone, Michael J., Paixao, Luis, Panneerselvam, Ezhil, Ye, Elissa M., Thompson, B. Taylor, Akeju, Oluwaseun, Kuller, David, Thomas, Robert J., and Westover, M. Brandon

Subjects
Electrical Engineering and Systems Science - Signal Processing, Computer Science - Machine Learning
Abstract

Objective: Sleep related respiratory abnormalities are typically detected using polysomnography. There is a need in general medicine and critical care for a more convenient method to automatically detect sleep apnea from a simple, easy-to-wear device. The objective is to automatically detect abnormal respiration and estimate the Apnea-Hypopnea-Index (AHI) with a wearable respiratory device, compared to an SpO2 signal or polysomnography using a large (n = 412) dataset serving as ground truth. Methods: Simultaneously recorded polysomnographic (PSG) and wearable respiratory effort data were used to train and evaluate models in a cross-validation fashion. Time domain and complexity features were extracted, important features were identified, and a random forest model employed to detect events and predict AHI. Four models were trained: one each using the respiratory features only, a feature from the SpO2 (%)-signal only, and two additional models that use the respiratory features and the SpO2 (%)-feature, one allowing a time lag of 30 seconds between the two signals. Results: Event-based classification resulted in areas under the receiver operating characteristic curves of 0.94, 0.86, 0.82, and areas under the precision-recall curves of 0.48, 0.32, 0.51 for the models using respiration and SpO2, respiration-only, and SpO2-only respectively. Correlation between expert-labelled and predicted AHI was 0.96, 0.78, and 0.93, respectively. Conclusions: A wearable respiratory effort signal with or without SpO2 predicted AHI accurately. Given the large dataset and rigorous testing design, we expect our models are generalizable to evaluating respiration in a variety of environments, such as at home and in critical care., Comment: Co-First Authors: Wolfgang Ganglberger, Abigail A. Bucklin Co-Senior Authors: Robert J. Thomas, M. Brandon Westover

Published
2021

25. Toward Optimal Acute Respiratory Distress Syndrome Outcomes Recognizing the Syndrome and Identifying Its Causes

Author

Kotas, Maya E and Thompson, B Taylor

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Lung, Clinical Research, Pediatric, Management of diseases and conditions, 7.3 Management and decision making, Respiratory, Humans, Respiration, Artificial, Respiratory Distress Syndrome, Acute respiratory distress syndrome, ARDS, ARDS risk factors, Lung protective ventilation, Nursing, Emergency & Critical Care Medicine, Clinical sciences
Abstract

Acute respiratory distress syndrome is a common condition among critically ill patients, but remains under-recognized and undertreated. Under-recognition may result from confusion over the clinical inclusion criteria, as well as a misunderstanding of the complex relationship between the clinical syndrome, the variable histopathologic patterns, and the myriad clinical disorders that cause acute respiratory distress syndrome. The identification of the clinical syndrome and determination of the causal diagnosis are both required to optimize patient outcomes. Here we review the definition, discuss pitfalls in recognizing acute respiratory distress syndrome and consider an approach to ascertain specific etiologies of acute respiratory distress syndrome.

Published
2021

27. The Berlin definition of acute respiratory distress syndrome: should patients receiving high-flow nasal oxygen be included?

Author

Matthay, Michael A, Thompson, B Taylor, and Ware, Lorraine B

Subjects
Acute Respiratory Distress Syndrome, Lung, Rare Diseases, Clinical Research, Respiratory, COVID-19, Early Diagnosis, Humans, Oxygen Inhalation Therapy, Patient Selection, Respiratory Insufficiency, SARS-CoV-2, Severity of Illness Index, Time-to-Treatment, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract

The 2012 Berlin definition of acute respiratory distress syndrome (ARDS) provided validated support for three levels of initial arterial hypoxaemia that correlated with mortality in patients receiving ventilatory support. Since 2015, high-flow nasal oxygen (HFNO) has become widely used as an effective therapeutic support for acute respiratory failure, most recently in patients with severe COVID-19. We propose that the Berlin definition of ARDS be broadened to include patients treated with HFNO of at least 30 L/min who fulfil the other criteria for the Berlin definition of ARDS. An expanded definition would make the diagnosis of ARDS more widely applicable, allowing patients at an earlier stage of the syndrome to be recognised, independent of the need for endotracheal intubation or positive-pressure ventilation, with benefits for the testing of early interventions and the study of factors associated with the course of ARDS. We identify key questions that could be addressed in refining an expanded definition of ARDS, the implementation of which could lead to improvements in clinical practice and clinical outcomes for patients.

Published
2021

29. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial

Author

Tierney, John, Vogel, Susan E., McNay, Laura A., Cahill, Kelly, Crew, Page, Sardana, Ratna, Segal Raim, Sharo, Shaw-Saliba, Katy, Atri, Negin, Miller, Mark, Vallee, David, Chung, Lucy, Delph, Yvette, Adam, Stacey J., Read, Sarah, Draghia-Akli, Ruxandra, Harrigan, Rachel, Carlsen, Amy, Carter, Anita, DuChene, Alain, Eckroth, Kate, Frase, Alex, Harrison, Merrie, Meger, Sue, Quan, Kien, Quan, Siu Fun, Reilly, Cavan, Thompson, Greg, Walski, Jamie, Moskowitz, Alan J., Bagiella, Emilia, Moquete, Ellen, O'Sullivan, Karen, Marks, Mary E., Accardi, Evan, Kinzel, Emily, Bedoya, Gabriela, Gupta, Lopa, Overbey, Jessica R., Padillia, Maria L., Santos, Milerva, Gillinov, Marc A., Miller, Marissa A., Taddei-Peters, Wendy C., Fenton, Kathleen, Smith, Peter K., Vekstein, Andrew M., Ko, Emily R., Al-Hegelan, Mashael S., McGowan, Lauren M., Motta, Mary, Howell, Shauna, Bent, Francine, Kalager, Rachel, Chan, Emmanuel, Aloor, Heather L., Griffin, S. Michelle, Covington, Anna, McLendon-Arvik, Beth, Bussadori, Barbara, Miller-Bell, Mary, Sampey, Cathy, Gaver, Vincent, Hollister, Beth A., Giangiacomo, Dana M., Pauley, Alena, Patel, Aashay, Classon, Chris, Frazier, Madison, Osborne, Robyn, Conlon, Debbi H., Joshi, Marybeth, Gottlieb, Robert L., Mack, Michael, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Bettacchi, Christopher, Golden, Kevin, Duhaime, Erin, Ryan, Madison, Tallmadge, Catherine, Estrada, Lorie, Jones, Felecia, Villa, Samantha, Wang, Samantha, Robert, Raven, Coleman, Tanquinisha, Clariday, Laura, Baker, Rebecca, Hurutado-Rodriguez, Mariana, Iram, Nazia, Fresnedo, Michelle, Davis, Allyson, Leonard, Kiara, Ramierez, Noelia, Thammavong, Jon, Duque, Krizia, Turner, Emma, Fisher, Tammy, Robinson, Dianna, Ransom, Desirae, Maldonado, Nicholas, Lusk, Erica, Killian, Aaron, Palacios, Adriana, Solis, Edilia, Jerrow, Janet, Watts, Matthew, Whitacre, Heather, Cothran, Elizabeth, Bender, William, Miller, Jeffrey, Nugent, Katherine, Farrington, Woodrow, Baio, Kim T., McBride, Mary K., Fielding, Michele, Mathewson, Sonya, Porte, Kristina, Haley, Elizabeth, Rogers, Susan, Tyler, Derrick, Perin, Emerson, Costello, Briana, Postalian, Alexander, Sohail, Rizwan, Hinsu, Punit, Watson, Carolyn, Kappenman, Casey, Chen, James, Walker, Kim, Fink, Melyssa, Phillip, Gabrielle, Mahon, Kim, Sturgis, Lydia, Maher, Patrick, Rogers, Linda, Ng, Nicole, Marshall, Jason, Bassily-Marcus, Adel, Cohen, Ivy, Ramoo, Shamini, Malhotra, Aryan, Kessler, Jonathan, Goetz, Rebekah, Badhwar, Vinay, Hayanga, Jeremiah, Giblin Sutton, Lisa, Williams, Roger, Berry Bartolo, Elizabeth, Walker, Dmitry, Bunner, Robin, Glaze, Chad, Aucremanne, Tanja, Bishop, James, Kelley, Macey, Peterson, Autumn, Sauerborn, Erica, Reckart, Robin, Miller, Brittany, Mittel, Aaron, Darmanian, Anita, Rosen, Amanda, Madahar, Purnema, Schicchi, John, Gosek, Katarzyna, Dzierba, Amy, Wahab, Romina, Eng, Connie, Al-Saadi, Mukhtar, Zahiruddin, Faisal, Syed, Mohi, George, Michael, Patel, Varsha, Onwunyi, Chisom, Barroso da Costa, Rosa, North, Crystal, Ringwood, Nancy, Fitzgerald, Laura, Muzikansky, Ariela, Morse, Richard, Brower, Roy G., Reineck, Lora A., Bienstock, Karen, Hou, Peter, Steingrub, Jay S., Tidswell, Mark A., Kozikowski, Lori-Ann, Kardos, Cynthia, De Souza, Leslie, Talmor, Daniel, Shapiro, Nathan, Hibbert, Kathryn, Brait, Kelsey, Kone, Mamary, Hendey, Gregory, Kangelaris, Kirsten N., Ashktorab, Kimia, Gropper, Rachel, Agrawal, Anika, Timothy, Kelly, Zhou, Hanjing, Hughes, Alyssa, Garcia, Rebekah, Torres, Adrian, Hernandez-Almaraz, Maria Elena, Vojnik, Rosemary, Perez, Cynthia, McDowell, Jordan, Chang, Steven Y., Vargas, Julia, Moss, Marc, McKeehan, Jeffrey, Higgins, Carrie, Johnson, Emily, Slaughter, Suzanne, Wyles, David, Hiller, Terra, Oakes, Judy, Garcia, Ana, Gravitz, Stephanie, Lyle, Carolynn, Swanson, Diandra, Gong, Michelle Ng., Richardson, Lynnne D., Chen, Jen-Ting, Moskowitz, Ari, Mohamed, Amira, Lopez, Brenda, Amosu, Omowunmi, Tzehaie, Hiwet, Boujid, Sabah, Bixby, Billie, Lopez, Anitza A., Durley, JaVon, Gilson, Boris, Hite, R. Duncan, Wang, Henry, Wiedemann, Hebert P., Mehkri, Omar, Ashok, Kiran, King, Alexander, Brennan, Connery, Exline, Matthew C., Englert, Joshua A., Karow, Sarah, Schwartz, Elizabeth, So, Preston, So, Madison, Krol, Olivia F., Briceno Parra, Genesis I., Mills, Emmanuel Nii Lantei, Oh, Minn, Pena, Jose, Martínez, Jesús Alejandro, Jackman, Susan E., Bayoumi, Emad, Pascual, Ethan, Caudill, Antonina, Chen, Po-En, Richardson, Tabia, Clapham, Gregg J., Herrera, Lisa, Ojukwu, Cristabelle, Fine, Devin, Gomez, Millie J., Choi-Kuaea, Yunhee, Weissberg, Gwendolyn, Isip, Katherine, Mattison, Brittany, Tran, Dana, Emilov Dukov, Jennifer, Chung, Paul, Kang, Bo Ran, Escobar, Lauren, Tran, Trung, Baig, Saba, Wallick, Julie A., Duven, Alexandria M., Fletcher, Dakota D., Gundel, Stephanie, Fuentes, Megan, Newton, Maranda, Peterson, Emily, Jiang, Kelsey, Files, D. Clark, Miller, Chadwick, Lematty, Caitlin, Rasberry, April, Warden, Ashley, Bledsoe, Joseph, Knowlton, Kirk, Knox, Daniel B., Klippel, Carolyn, Armbruster, Brent P., Applegate, Darrin, Imel, Karah, Fergus, Melissa, Rahmati, Kasra, Jensen, Hannah, Aston, Valerie T., Jeppson, Joshua, Marshall, J. Hunter, Lumpkin, Jenna, Smith, Cassie, Burke, Tyler, Gray, Andrew, Paine, Robert, Callahan, Sean, Yamane, Misty, Waddoups, Lindsey, Rice, Todd W., Johnson, Jakea, Gray, Christopher, Hays, Margaret, Roth, Megan, Musick, Sarah, Miller, Karen, Semler, Matthew W., Popielski, Laura, Kambo, Amy, Viens, Kimberly, Turner, Melissa, Vjecha, Michael J., Denyer, Rachel, Khosla, Rahul, Rajendran, Bindu, Gonzales, Melissa, Moriarty, Theresa, Biswas, Kousick, Harrington, Cristin, Garcia, Amanda, Bremer, Tammy, Burke, Tara, Koker, Brittany, Pittman, David, Vasudeva, Shikha S., Anholm, James D., Specht, Lennard, Rodriguez, Aimee, Ngo, Han, Duong, Lien, Previte, Matthew, Raben, Dorthe, Nielsen, Charlotte B., Friis Larsen, Jakob, Peters, Lars, Matthews, Gail, Kelleher, Anthony, Polizzotto, Mark, Carey, Catherine, Chang, Christina, Dharan, Nila, Hough, Sally, Virachit, Sophie, Davidson, Sarah, Bice, Daniel J., Ognenovska, Katherine, Cabrera, Gesalit, Flynn, Ruth, Abdelghany, Mazin, Baseler, Beth, Teitelbaum, Marc, Holley, H. Preston, Jankelevich, Shirley, Adams, Amy, Becker, Nancy, Doleny, Suzanne, Hissey, Debbie, Simpson, Shelly, Kim, Mi Ha, Beeler, Joy, Harmon, Liam, Vanderpuye, Sharon, Yeon, Lindsey, Frye, Leanna, Rudzinski, Erin, Buehn, Molly, Eccard-Koons, Vanessa, Frary, Sadie, MacDonalad, Leah, Cash, Jennifer, Hoopengardner, Lisa, Linton, Jessica, Nelson, Michaela, Spinelli-Nadzam, Mary, Proffitt, Calvin, Lee, Christopher, Engel, Theresa, Fontaine, Laura, Osborne, CK, Hohn, Matt, Galcik, Michael, Thompson, DeeDee, Sandrus, Jen, Manchard, Jon, Giri, Jiwan, Kopka, Stacy, Chang, Weizhong, Sherman, Brad T., Rupert, Adam W., Highbarger, Helene, Baseler, Michael, Lallemand, Perrine, Rehman, Tauseef, Imamichi, Tom, Laverdure, Sylvain, Paudel, Sharada, Cook, Kyndal, Haupt, Kendra, Hazen, Allison, Badralmaa, Yunden, Highbarger, Jeroen, McCormack, Ashley, Gerry, Norman P., Smith, Kenneth, Patel, Bhakti, Domeraski, Nadia, Hoover, Marie L., DuChateau, Nadine, Flosi, Adam, Nelson, Rich, Stojanovic, Jelena, Wenner, Christine, Brown, Samuel M, Barkauskas, Christina E, Grund, Birgit, Sharma, Shweta, Phillips, Andrew N, Leither, Lindsay, Peltan, Ithan D, Lanspa, Michael, Gilstrap, Daniel L, Mourad, Ahmad, Lane, Kathleen, Beitler, Jeremy R, Serra, Alexis L, Garcia, Ivan, Almasri, Eyad, Fayed, Mohamed, Hubel, Kinsley, Harris, Estelle S, Middleton, Elizabeth A, Barrios, Macy A G, Mathews, Kusum S, Goel, Neha N, Acquah, Samuel, Mosier, Jarrod, Hypes, Cameron, Salvagio Campbell, Elizabeth, Khan, Akram, Hough, Catherine L, Wilson, Jennifer G, Levitt, Joseph E, Duggal, Abhijit, Dugar, Siddharth, Goodwin, Andrew J, Terry, Charles, Chen, Peter, Torbati, Sam, Iyer, Nithya, Sandkovsky, Uriel S, Johnson, Nicholas J, Robinson, Bryce R H, Matthay, Michael A, Aggarwal, Neil R, Douglas, Ivor S, Casey, Jonathan D, Hache-Marliere, Manuel, Georges Youssef, J, Nkemdirim, William, Leshnower, Brad, Awan, Omar, Pannu, Sonal, O'Mahony, Darragh Shane, Manian, Prasad, Awori Hayanga, J W, Wortmann, Glenn W, Tomazini, Bruno M, Miller, Robert F, Jensen, Jens-Ulrik, Murray, Daniel D, Bickell, Nina A, Zatakia, Jigna, Burris, Sarah, Higgs, Elizabeth S, Natarajan, Ven, Dewar, Robin L, Schechner, Adam, Kang, Nayon, Arenas-Pinto, Alejandro, Hudson, Fleur, Ginde, Adit A, Self, Wesley H, Rogers, Angela J, Oldmixon, Cathryn F, Morin, Haley, Sanchez, Adriana, Weintrob, Amy C, Cavalcanti, Alexandre Biasi, Davis-Karim, Anne, Engen, Nicole, Denning, Eileen, Taylor Thompson, B, Gelijns, Annetine C, Kan, Virginia, Davey, Victoria J, Lundgren, Jens D, Babiker, Abdel G, Neaton, James D, and Lane, H Clifford

Published
2023
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30. Dexamethasone in hospitalised patients with COVID-19: addressing uncertainties

Author

Matthay, Michael A and Thompson, B Taylor

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Dexamethasone, Glucocorticoids, Humans, Pandemics, Pragmatic Clinical Trials as Topic, SARS-CoV-2, COVID-19 Drug Treatment, Public Health and Health Services, Other Medical and Health Sciences, Cardiovascular medicine and haematology, Clinical sciences
Published
2020

31. Direct discrimination of structured light by humans

Author

Sarenac, D., Kapahi, C., Silva, A. E., Cory, D. G., Thompson, B., and Pushin, D. A.

Subjects
Physics - Optics, Physics - Medical Physics
Abstract

We predict and experimentally verify an entoptic phenomenon through which humans are able to perceive and discriminate structured light with space-varying polarization. Direct perception and discrimination is possible through the observation of distinct profiles induced by the interaction between the polarization gradients in a uniform-intensity beam and the radially symmetric dichroic elements that are centered on the foveola in the macula of the human eye. A psychophysical study was conducted where optical states with coupled polarization and orbital angular momentum (OAM) were directed onto the retina of participants. The participants were able to correctly discriminate between two states, differentiated by OAM =\pm7, with an average success probability of 77.6 % (average sensitivity d^\prime=1.7, t(9) = 5.9, p = 2\times 10^{-4}). These results enable new methods of robustly characterizing the structure of the macula, probing retina signalling pathways, and conducting experiments with non-separable optical states and human detectors.

Published
2019
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32. Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks.

Author

Hollon, Todd C, Pandian, Balaji, Adapa, Arjun R, Urias, Esteban, Save, Akshay V, Khalsa, Siri Sahib S, Eichberg, Daniel G, D'Amico, Randy S, Farooq, Zia U, Lewis, Spencer, Petridis, Petros D, Marie, Tamara, Shah, Ashish H, Garton, Hugh JL, Maher, Cormac O, Heth, Jason A, McKean, Erin L, Sullivan, Stephen E, Hervey-Jumper, Shawn L, Patil, Parag G, Thompson, B Gregory, Sagher, Oren, McKhann, Guy M, Komotar, Ricardo J, Ivan, Michael E, Snuderl, Matija, Otten, Marc L, Johnson, Timothy D, Sisti, Michael B, Bruce, Jeffrey N, Muraszko, Karin M, Trautman, Jay, Freudiger, Christian W, Canoll, Peter, Lee, Honglak, Camelo-Piragua, Sandra, and Orringer, Daniel A

Subjects
Humans, Brain Neoplasms, Monitoring, Intraoperative, Spectrum Analysis, Raman, Probability, Algorithms, Computer Systems, Image Processing, Computer-Assisted, Clinical Trials as Topic, Deep Learning, Neural Networks, Computer, Monitoring, Intraoperative, Spectrum Analysis, Raman, Image Processing, Computer-Assisted, Neural Networks, Computer, Medical and Health Sciences, Immunology
Abstract

Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery1. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive2,3. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce4. In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH)5-7, a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20-30 min)2. In a multicenter, prospective clinical trial (n = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory.

Published
2020

37. High prevalence of sleep-disordered breathing in the intensive care unit — a cross-sectional study

Author

Bucklin, Abigail A., Ganglberger, Wolfgang, Quadri, Syed A., Tesh, Ryan A., Adra, Noor, Da Silva Cardoso, Madalena, Leone, Michael J., Krishnamurthy, Parimala Velpula, Hemmige, Aashritha, Rajan, Subapriya, Panneerselvam, Ezhil, Paixao, Luis, Higgins, Jasmine, Ayub, Muhammad Abubakar, Shao, Yu-Ping, Ye, Elissa M., Coughlin, Brian, Sun, Haoqi, Cash, Sydney S., Thompson, B. Taylor, Akeju, Oluwaseun, Kuller, David, Thomas, Robert J., and Westover, M. Brandon

Published
2022
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38. Redefining critical illness

Author

Maslove, David M., Tang, Benjamin, Shankar-Hari, Manu, Lawler, Patrick R., Angus, Derek C., Baillie, J. Kenneth, Baron, Rebecca M., Bauer, Michael, Buchman, Timothy G., Calfee, Carolyn S., dos Santos, Claudia C., Giamarellos-Bourboulis, Evangelos J., Gordon, Anthony C., Kellum, John A., Knight, Julian C., Leligdowicz, Aleksandra, McAuley, Daniel F., McLean, Anthony S., Menon, David K., Meyer, Nuala J., Moldawer, Lyle L., Reddy, Kiran, Reilly, John P., Russell, James A., Sevransky, Jonathan E., Seymour, Christopher W., Shapiro, Nathan I., Singer, Mervyn, Summers, Charlotte, Sweeney, Timothy E., Thompson, B. Taylor, van der Poll, Tom, Venkatesh, Balasubramanian, Walley, Keith R., Walsh, Timothy S., Ware, Lorraine B., Wong, Hector R., Zador, Zsolt E., and Marshall, John C.

Published
2022
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40. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome

Author

Moss, Marc, Huang, David T, Brower, Roy G, Ferguson, Niall D, Ginde, Adit A, Gong, MN, Grissom, Colin K, Gundel, Stephanie, Hayden, Douglas, Hite, R Duncan, Hou, Peter C, Hough, Catherine L, Iwashyna, Theodore J, Khan, Akram, Liu, Kathleen D, Talmor, Daniel, Thompson, B Taylor, Ulysse, Christine A, Yealy, Donald M, and Angus, Derek C

Subjects
Clinical Research, Lung, Bioengineering, Cardiovascular, Acute Respiratory Distress Syndrome, Rare Diseases, Clinical Trials and Supportive Activities, Respiratory, Good Health and Well Being, Adult, Aged, Atracurium, Combined Modality Therapy, Conscious Sedation, Female, Hospital Mortality, Humans, Male, Middle Aged, Neuromuscular Blockade, Neuromuscular Blocking Agents, Positive-Pressure Respiration, Respiratory Distress Syndrome, Treatment Failure, National Heart, Lung, and Blood Institute PETAL Clinical Trials Network, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThe benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear.MethodsWe randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of

Published
2019

41. Prospective Assessment of the Feasibility of a Trial of Low-Tidal Volume Ventilation for Patients with Acute Respiratory Failure.

Author

Lanspa, Michael J, Gong, Michelle Ng, Schoenfeld, David A, Lee, Kathleen Tiffany, Grissom, Colin K, Hou, Peter C, Serpa-Neto, Ary, Brown, Samuel M, Iwashyna, Theodore J, Yealy, Donald M, Hough, Catherine L, Brower, Roy G, Calfee, Carolyn S, Hyzy, Robert C, Matthay, Michael A, Miller, Russell R, Steingrub, Jay S, Thompson, B Taylor, Miller, Chadwick D, Clemmer, Terry P, Hendey, Gregory W, Huang, David T, Mathews, Kusum S, Qadir, Nida, Tidswell, Mark, and The National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network

Subjects
The National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network, Humans, Respiratory Insufficiency, Acute Disease, Tidal Volume, Treatment Outcome, Respiration, Artificial, Incidence, Hospital Mortality, Survival Rate, Follow-Up Studies, Prospective Studies, Feasibility Studies, Middle Aged, Intensive Care Units, United States, Female, Male, Clinical Trials as Topic, acute respiratory distress syndrome, low-stretch ventilation, low–tidal volume ventilation, lung-protective ventilation, mechanical ventilation, Clinical Trials and Supportive Activities, Acute Respiratory Distress Syndrome, Clinical Research, Rare Diseases, Patient Safety, Lung, Respiratory, Good Health and Well Being, low-tidal volume ventilation
Abstract

RationaleLow-tidal volume ventilation (LTVV; 6 ml/kg) benefits patients with acute respiratory distress syndrome and may aid those with other causes of respiratory failure. Current early ventilation practices are poorly defined.ObjectivesWe observed patients with acute respiratory failure to assess the feasibility of a pragmatic trial of LTVV and to guide experimental design.MethodsWe prospectively enrolled consecutive patients with acute respiratory failure admitted to intensive care units expected to participate in the proposed trial. We collected clinical data as well as information on initial and daily ventilator settings and inpatient mortality. We estimated the benefit of LTVV using predictive linear and nonlinear models. We simulated models to estimate power and feasibility of a cluster-randomized trial of LTVV versus usual care in acute respiratory failure.ResultsWe included 2,484 newly mechanically ventilated patients (31% with acute respiratory distress syndrome) from 49 hospitals. Hospital mortality was 28%. Mean initial tidal volume was 7.1 ml/kg predicted body weight (95% confidence interval, 7.1-7.2), with 78% of patients receiving tidal volumes less than or equal to 8 ml/kg. Our models estimated a mortality benefit of 0-2% from LTVV compared with usual care. Simulation of a stepped-wedged cluster-randomized trial suggested that enrollment of 106,361 patients would be necessary to achieve greater than 90% power.ConclusionsUse of initial tidal volumes less than 8 ml/kg predicted body weight was common at hospitals participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. After considering the size and budgetary requirement for a cluster-randomized trial of LTVV versus usual care in acute respiratory failure, the PETAL Network deemed the proposed trial infeasible. A rapid observational study and simulations to model anticipated power may help better design trials.

Published
2019

42. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial.

Author

Matthay, Michael A, Calfee, Carolyn S, Zhuo, Hanjing, Thompson, B Taylor, Wilson, Jennifer G, Levitt, Joseph E, Rogers, Angela J, Gotts, Jeffrey E, Wiener-Kronish, Jeanine P, Bajwa, Ednan K, Donahoe, Michael P, McVerry, Bryan J, Ortiz, Luis A, Exline, Matthew, Christman, John W, Abbott, Jason, Delucchi, Kevin L, Caballero, Lizette, McMillan, Melanie, McKenna, David H, and Liu, Kathleen D

Subjects
Humans, Disease-Free Survival, Treatment Outcome, Mesenchymal Stem Cell Transplantation, Severity of Illness Index, Hospital Mortality, Multivariate Analysis, Proportional Hazards Models, Risk Assessment, Statistics, Nonparametric, Survival Analysis, Prospective Studies, Double-Blind Method, Adult, Aged, Middle Aged, Academic Medical Centers, United States, Female, Male, Patient Safety, Respiratory Distress Syndrome, Rare Diseases, Stem Cell Research, Acute Respiratory Distress Syndrome, Stem Cell Research - Nonembryonic - Human, Clinical Trials and Supportive Activities, Clinical Research, Lung, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Respiratory, Good Health and Well Being, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract

BackgroundTreatment with bone-marrow-derived mesenchymal stromal cells (MSCs) has shown benefits in preclinical models of acute respiratory distress syndrome (ARDS). Safety has not been established for administration of MSCs in critically ill patients with ARDS. We did a phase 2a trial to assess safety after administration of MSCs to patients with moderate to severe ARDS.MethodsWe did a prospective, double-blind, multicentre, randomised trial to assess treatment with one intravenous dose of MSCs compared with placebo. We recruited ventilated patients with moderate to severe ARDS (ratio of partial pressure of oxygen to fractional inspired oxygen

Published
2019

43. Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial

Author

Ginde, Adit A., Paredes, Roger, Murray, Thomas A., Engen, Nicole, Grandits, Greg, Vekstein, Andrew, Ivey, Noel, Mourad, Ahmad, Sandkovsky, Uriel, Gottlieb, Robert L., Berhe, Mezgebe, Jain, Mamta K., Marines-Price, Rubria, Agbor Agbor, Barbine Tchamba, Mateu, Lourdes, España-Cueto, Sergio, Lladós, Gemma, Mylonakis, Eleftherios, Rogers, Ralph, Shehadeh, Fadi, Filbin, Michael R., Hibbert, Kathryn A., Kim, Kami, Tran, Thanh, Morris, Peter E., Cassity, Evan P., Trautner, Barbara, Pandit, Lavannya M., Knowlton, Kirk U., Leither, Lindsay, Matthay, Michael A., Rogers, Angela J., Drake, Wonder, Jones, Beatrice, Poulakou, Garyfallia, Syrigos, Konstantinos N., Fernández-Cruz, Eduardo, Natale, Marisa Di, Almasri, Eyad, Balerdi-Sarasola, Leire, Bhagani, Sanjay R., Boyle, Katherine L., Casey, Jonathan D., Chen, Peter, Douin, David J., Files, D. Clark, Günthard, Huldrych F., Hite, R. Duncan, Hyzy, Robert C., Khan, Akram, Kibirige, Moses, Kidega, Robert, Kiweewa, Francis, Jensen, Jens-Ulrik, Leshnower, Bradley G., Lutaakome, Joseph K., Manian, Prasad, Menon, Vidya, Morales-Rull, Jose Luis, O'Mahony, D. Shane, Overcash, J. Scott, Ramachandruni, Srikant, Steingrub, Jay S., Taha, Hassan S., Waters, Michael, Young, Barnaby E., Phillips, Andrew N., Murray, Daniel D., Jensen, Tomas O., Padilla, Maria L., Sahner, David, Shaw-Saliba, Katy, Dewar, Robin L., Teitelbaum, Marc, Natarajan, Ven, Rehman, M. Tauseef, Pett, Sarah, Hudson, Fleur, Touloumi, Giota, Brown, Samuel M., Self, Wesley H., Chang, Christina C., Sánchez, Adriana, Weintrob, Amy C., Hatlen, Timothy, Grund, Birgit, Sharma, Shweta, Reilly, Cavan S., Garbes, Pedro, Esser, Mark T., Templeton, Alison, Babiker, Abdel G., Davey, Victoria J., Gelijns, Annetine C., Higgs, Elizabeth S., Kan, Virginia, Matthews, Gail, Thompson, B. Taylor, Neaton, James D., Lane, H. Clifford, and Lundgren, Jens D.

Published
2022
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44. Oxygen-Free Days as an Outcome Measure in Clinical Trials of Therapies for COVID-19 and Other Causes of New-Onset Hypoxemia

Author

Moskowitz, Ari, Shotwell, Matthew S., Gibbs, Kevin W., Harkins, Michelle, Rosenberg, Yves, Troendle, James, Merck, Lisa H., Files, D. Clark, de Wit, Marjolein, Hudock, Kristin, Thompson, B. Taylor, Gong, Michelle N., Ginde, Adit A., Douin, David J., Brown, Samuel M., Rubin, Eileen, Joly, Meghan Morrison, Wang, Li, Lindsell, Christopher J., Bernard, Gordon R., Semler, Matthew W., Collins, Sean P., and Self, Wesley H.

Published
2022
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45. Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Author

Kouli, O, Murray, V, Bhatia, S, Cambridge, WA, Kawka, M, Shafi, S, Knight, SR, Kamarajah, SK, McLean, KA, Glasbey, JC, Khaw, RA, Ahmed, W, Akhbari, M, Baker, D, Borakati, A, Mills, E, Thavayogan, R, Yasin, I, Raubenheimer, K, Ridley, W, Sarrami, M, Zhang, G, Egoroff, N, Pockney, P, Richards, T, Bhangu, A, Creagh-Brown, B, Edwards, M, Harrison, EM, Lee, M, Nepogodiev, D, Pinkney, T, Pearse, R, Smart, N, Vohra, R, Sohrabi, C, Jamieson, A, Nguyen, M, Rahman, A, English, C, Tincknell, L, Kakodkar, P, Kwek, I, Punjabi, N, Burns, J, Varghese, S, Erotocritou, M, McGuckin, S, Vayalapra, S, Dominguez, E, Moneim, J, Salehi, M, Tan, HL, Yoong, A, Zhu, L, Seale, B, Nowinka, Z, Patel, N, Chrisp, B, Harris, J, Maleyko, I, Muneeb, F, Gough, M, James, CE, Skan, O, Chowdhury, A, Rebuffa, N, Khan, H, Down, B, Fatimah Hussain, Q, Adams, M, Bailey, A, Cullen, G, Fu, YXJ, McClement, B, Taylor, A, Aitken, S, Bachelet, B, Brousse de Gersigny, J, Chang, C, Khehra, B, Lahoud, N, Lee Solano, M, Louca, M, Rozenbroek, P, Rozitis, E, Agbinya, N, Anderson, E, Arwi, G, Barry, I, Batchelor, C, Chong, T, Choo, LY, Clark, L, Daniels, M, Goh, J, Handa, A, Hanna, J, Huynh, L, Jeon, A, Kanbour, A, Lee, A, Lee, J, Lee, T, Leigh, J, Ly, D, McGregor, F, Moss, J, Nejatian, M, O'Loughlin, E, Ramos, I, Sanchez, B, Shrivathsa, A, Sincari, A, Sobhi, S, Swart, R, Trimboli, J, Wignall, P, Bourke, E, Chong, A, Clayton, S, Dawson, A, Hardy, E, Iqbal, R, Le, L, Mao, S, Marinelli, I, Metcalfe, H, Panicker, D, R, HH, Ridgway, S, Tan, HH, Thong, S, Van, M, Woon, S, Woon-Shoo-Tong, XS, Yu, S, Ali, K, Chee, J, Chiu, C, Chow, YW, Duller, A, Nagappan, P, Ng, S, Selvanathan, M, Sheridan, C, Temple, M, Do, JE, Dudi-Venkata, NN, Humphries, E, Li, L, Mansour, LT, Massy-Westropp, C, Fang, B, Farbood, K, Hong, H, Huang, Y, Joan, M, Koh, C, Liu, YHA, Mahajan, T, Muller, E, Park, R, Tanudisastro, M, Wu, JJG, Chopra, P, Giang, S, Radcliffe, S, Thach, P, Wallace, D, Wilkes, A, Chinta, SH, Li, J, Phan, J, Rahman, F, Segaran, A, Shannon, J, Zhang, M, Adams, N, Bonte, A, Choudhry, A, Colterjohn, N, Croyle, JA, Donohue, J, Feighery, A, Keane, A, McNamara, D, Munir, K, Roche, D, Sabnani, R, Seligman, D, Sharma, S, Stickney, Z, Suchy, H, Tan, R, Yordi, S, Ahmed, I, Aranha, M, El Sabawy, D, Garwood, P, Harnett, M, Holohan, R, Howard, R, Kayyal, Y, Krakoski, N, Lupo, M, McGilberry, W, Nepon, H, Scoleri, Y, Urbina, C, Ahmad Fuad, MF, Ahmed, O, Jaswantlal, D, Kelly, E, Khan, MHT, Naidu, D, Neo, WX, O'Neill, R, Sugrue, M, Abbas, JD, Abdul-Fattah, S, Azlan, A, Barry, K, Idris, NS, Kaka, N, Mc Dermott, D, Mohammad Nasir, MN, Mozo, M, Rehal, A, Shaikh Yousef, M, Wong, RH, Curran, E, Gardner, M, Hogan, A, Julka, R, Lasser, G, Ní Chorráin, N, Ting, J, Browne, R, George, S, Janjua, Z, Leung Shing, V, Megally, M, Murphy, S, Ravenscroft, L, Vedadi, A, Vyas, V, Bryan, A, Sheikh, A, Ubhi, J, Vannelli, K, Vawda, A, Adeusi, L, Doherty, C, Fitzgerald, C, Gallagher, H, Gill, P, Hamza, H, Hogan, M, Kelly, S, Larry, J, Lynch, P, Mazeni, NA, O'Connell, R, O'Loghlin, R, Singh, K, Abbas Syed, R, Ali, A, Alkandari, B, Arnold, A, Arora, E, Azam, R, Breathnach, C, Cheema, J, Compton, M, Curran, S, Elliott, JA, Jayasamraj, O, Mohammed, N, Noone, A, Pal, A, Pandey, S, Quinn, P, Sheridan, R, Siew, L, Tan, EP, Tio, SW, Toh, VTR, Walsh, M, Yap, C, Yassa, J, Young, T, Agarwal, N, Almoosawy, SA, Bowen, K, Bruce, D, Connachan, R, Cook, A, Daniell, A, Elliott, M, Fung, HKF, Irving, A, Laurie, S, Lee, YJ, Lim, ZX, Maddineni, S, McClenaghan, RE, Muthuganesan, V, Ravichandran, P, Roberts, N, Shaji, S, Solt, S, Toshney, E, Arnold, C, Baker, O, Belais, F, Bojanic, C, Byrne, M, Chau, CYC, De Soysa, S, Eldridge, M, Fairey, M, Fearnhead, N, Guéroult, A, Ho, JSY, Joshi, K, Kadiyala, N, Khalid, S, Khan, F, Kumar, K, Lewis, E, Magee, J, Manetta-Jones, D, Mann, S, McKeown, L, Mitrofan, C, Mohamed, T, Monnickendam, A, Ng, AYKC, Ortu, A, Patel, M, Pope, T, Pressling, S, Purohit, K, Saji, S, Shah Foridi, J, Shah, R, Siddiqui, SS, Surman, K, Utukuri, M, Varghese, A, Williams, CYK, Yang, JJ, Billson, E, Cheah, E, Holmes, P, Hussain, S, Murdock, D, Nicholls, A, Patel, P, Ramana, G, Saleki, M, Spence, H, Thomas, D, Yu, C, Abousamra, M, Brown, C, Conti, I, Donnelly, A, Durand, M, French, N, Goan, R, O'Kane, E, Rubinchik, P, Gardiner, H, Kempf, B, Lai, YL, Matthews, H, Minford, E, Rafferty, C, Reid, C, Sheridan, N, Al Bahri, T, Bhoombla, N, Rao, BM, Titu, L, Chatha, S, Field, C, Gandhi, T, Gulati, R, Jha, R, Jones Sam, MT, Karim, S, Patel, R, Saunders, M, Sharma, K, Abid, S, Heath, E, Kurup, D, Patel, A, Ali, M, Cresswell, B, Felstead, D, Jennings, K, Kaluarachchi, T, Lazzereschi, L, Mayson, H, Miah, JE, Reinders, B, Rosser, A, Thomas, C, Williams, H, Al-Hamid, Z, Alsadoun, L, Chlubek, M, Fernando, P, Gaunt, E, Gercek, Y, Maniar, R, Ma, R, Matson, M, Moore, S, Morris, A, Nagappan, PG, Ratnayake, M, Rockall, L, Shallcross, O, Sinha, A, Tan, KE, Virdee, S, Wenlock, R, Donnelly, HA, Ghazal, R, Hughes, I, Liu, X, McFadden, M, Misbert, E, Mogey, P, O'Hara, A, Peace, C, Rainey, C, Raja, P, Salem, M, Salmon, J, Tan, CH, Alves, D, Bahl, S, Baker, C, Coulthurst, J, Koysombat, K, Linn, T, Rai, P, Sharma, A, Shergill, A, Ahmed, M, Ahmed, S, Belk, LH, Choudhry, H, Cummings, D, Dixon, Y, Dobinson, C, Edwards, J, Flint, J, Franco Da Silva, C, Gallie, R, Gardener, M, Glover, T, Greasley, M, Hatab, A, Howells, R, Hussey, T, Khan, A, Mann, A, Morrison, H, Ng, A, Osmond, R, Padmakumar, N, Pervaiz, F, Prince, R, Qureshi, A, Sawhney, R, Sigurdson, B, Stephenson, L, Vora, K, Zacken, A, Cope, P, Di Traglia, R, Ferarrio, I, Hackett, N, Healicon, R, Horseman, L, Lam, LI, Meerdink, M, Menham, D, Murphy, R, Nimmo, I, Ramaesh, A, Rees, J, Soame, R, Dilaver, N, Adebambo, D, Brown, E, Burt, J, Foster, K, Kaliyappan, L, Knight, P, Politis, A, Richardson, E, Townsend, J, Abdi, M, Ball, M, Easby, S, Gill, N, Ho, E, Iqbal, H, Matthews, M, Nubi, S, Nwokocha, JO, Okafor, I, Perry, G, Sinartio, B, Vanukuru, N, Walkley, D, Welch, T, Yates, J, Yeshitila, N, Bryans, K, Campbell, B, Gray, C, Keys, R, Macartney, M, Chamberlain, G, Khatri, A, Kucheria, A, Lee, STP, Reese, G, Roy choudhury, J, Tan, WYR, Teh, JJ, Ting, A, Kazi, S, Kontovounisios, C, Vutipongsatorn, K, Amarnath, T, Balasubramanian, N, Bassett, E, Gurung, P, Lim, J, Panjikkaran, A, Sanalla, A, Alkoot, M, Bacigalupo, V, Eardley, N, Horton, M, Hurry, A, Isti, C, Maskell, P, Nursiah, K, Punn, G, Salih, H, Epanomeritakis, E, Foulkes, A, Henderson, R, Johnston, E, McCullough, H, McLarnon, M, Morrison, E, Cheung, A, Cho, SH, Eriksson, F, Hedges, J, Low, Z, May, C, Musto, L, Nagi, S, Nur, S, Salau, E, Shabbir, S, Thomas, MC, Uthayanan, L, Vig, S, Zaheer, M, Zeng, G, Ashcroft-Quinn, S, Brown, R, Hayes, J, McConville, R, French, R, Gilliam, A, Sheetal, S, Shehzad, MU, Bani, W, Christie, I, Franklyn, J, Khan, M, Russell, J, Smolarek, S, Varadarassou, R, Ahmed, SK, Narayanaswamy, S, Sealy, J, Shah, M, Dodhia, V, Manukyan, A, O'Hare, R, Orbell, J, Chung, I, Forenc, K, Gupta, A, Agarwal, A, Al Dabbagh, A, Bennewith, R, Bottomley, J, Chu, TSM, Chu, YYA, Doherty, W, Evans, B, Hainsworth, P, Hosfield, T, Li, CH, McCullagh, I, Mehta, A, Thaker, A, Thompson, B, Virdi, A, Walker, H, Wilkins, E, Dixon, C, Hassan, MR, Lotca, N, Tong, KS, Batchelor-Parry, H, Chaudhari, S, Harris, T, Hooper, J, Johnson, C, Mulvihill, C, Nayler, J, Olutobi, O, Piramanayagam, B, Stones, K, Sussman, M, Weaver, C, Alam, F, Al Rawi, M, Andrew, F, Arrayeh, A, Azizan, N, Hassan, A, Iqbal, Z, John, I, Jones, M, Kalake, O, Keast, M, Nicholas, J, Patil, A, Powell, K, Roberts, P, Sabri, A, Segue, AK, Shah, A, Shaik Mohamed, SA, Shehadeh, A, Shenoy, S, Tong, A, Upcott, M, Vijayasingam, D, Anarfi, S, Dauncey, J, Devindaran, A, Havalda, P, Komninos, G, Mwendwa, E, Norman, C, Richards, J, Urquhart, A, Allan, J, Cahya, E, Hunt, H, McWhirter, C, Norton, R, Roxburgh, C, Tan, JY, Ali Butt, S, Hansdot, S, Haq, I, Mootien, A, Sanchez, I, Vainas, T, Deliyannis, E, Tan, M, Vipond, M, Chittoor Satish, NN, Dattani, A, De Carvalho, L, Gaston-Grubb, M, Karunanithy, L, Lowe, B, Pace, C, Raju, K, Roope, J, Taylor, C, Youssef, H, Munro, T, Thorn, C, Wong, KHF, Yunus, A, Chawla, S, Datta, A, Dinesh, AA, Field, D, Georgi, T, Gwozdz, A, Hamstead, E, Howard, N, Isleyen, N, Jackson, N, Kingdon, J, Sagoo, KS, Schizas, A, Yin, L, Aung, E, Aung, YY, Franklin, S, Han, SM, Kim, WC, Martin Segura, A, Rossi, M, Ross, T, Tirimanna, R, Wang, B, Zakieh, O, Ben-Arzi, H, Flach, A, Jackson, E, Magers, S, Olu abara, C, Rogers, E, Sugden, K, Tan, H, Veliah, S, Walton, U, Asif, A, Bharwada, Y, Bowley, D, Broekhuizen, A, Cooper, L, Evans, N, Girdlestone, H, Ling, C, Mann, H, Mehmood, N, Mulvenna, CL, Rainer, N, Trout, I, Gujjuri, R, Jeyaraman, D, Leong, E, Singh, D, Smith, E, Anderton, J, Barabas, M, Goyal, S, Howard, D, Joshi, A, Mitchell, D, Weatherby, T, Badminton, R, Bird, R, Burtle, D, Choi, NY, Devalia, K, Farr, E, Fischer, F, Fish, J, Gunn, F, Jacobs, D, Johnston, P, Kalakoutas, A, Lau, E, Loo, YNAF, Louden, H, Makariou, N, Mohammadi, K, Nayab, Y, Ruhomaun, S, Ryliskyte, R, Saeed, M, Shinde, P, Sudul, M, Theodoropoulou, K, Valadao-Spoorenberg, J, Vlachou, F, Arshad, SR, Janmohamed, AM, Noor, M, Oyerinde, O, Saha, A, Syed, Y, Watkinson, W, Ahmadi, H, Akintunde, A, Alsaady, A, Bradley, J, Brothwood, D, Burton, M, Higgs, M, Hoyle, C, Katsura, C, Lathan, R, Louani, A, Mandalia, R, Prihartadi, AS, Qaddoura, B, Sandland-Taylor, L, Thadani, S, Thompson, A, Walshaw, J, Teo, S, Ali, S, Bawa, JH, Fox, S, Gargan, K, Haider, SA, Hanna, N, Hatoum, A, Khan, Z, Krzak, AM, Li, T, Pitt, J, Tan, GJS, Ullah, Z, Wilson, E, Cleaver, J, Colman, J, Copeland, L, Coulson, A, Davis, P, Faisal, H, Hassan, F, Hughes, JT, Jabr, Y, Mahmoud Ali, F, Nahaboo Solim, ZN, Sangheli, A, Shaya, S, Thompson, R, Cornwall, H, De Andres Crespo, M, Fay, E, Findlay, J, Groves, E, Jones, O, Killen, A, Millo, J, Thomas, S, Ward, J, Wilkins, M, Zaki, F, Zilber, E, Bhavra, K, Bilolikar, A, Charalambous, M, Elawad, A, Eleni, A, Fawdon, R, Gibbins, A, Livingstone, D, Mala, D, Oke, SE, Padmakumar, D, Patsalides, MA, Payne, D, Ralphs, C, Roney, A, Sardar, N, Stefanova, K, Surti, F, Timms, R, Tosney, G, Bannister, J, Clement, NS, Cullimore, V, Kamal, F, Lendor, J, McKay, J, Mcswiggan, J, Minhas, N, Seneviratne, K, Simeen, S, Valverde, J, Watson, N, Bloom, I, Dinh, TH, Hirniak, J, Joseph, R, Kansagra, M, Lai, CKN, Melamed, N, Patel, J, Randev, J, Sedighi, T, Shurovi, B, Sodhi, J, Vadgama, N, Abdulla, S, Adabavazeh, B, Champion, A, Chennupati, R, Chu, K, Devi, S, Haji, A, Schulz, J, Testa, F, Davies, P, Gurung, B, Howell, S, Modi, P, Pervaiz, A, Zahid, M, Abdolrazaghi, S, Abi Aoun, R, Anjum, Z, Bawa, G, Bhardwaj, R, Brown, S, Enver, M, Gill, D, Gopikrishna, D, Gurung, D, Kanwal, A, Kaushal, P, Khanna, A, Lovell, E, McEvoy, C, Mirza, M, Nabeel, S, Naseem, S, Pandya, K, Perkins, R, Pulakal, R, Ray, M, Reay, C, Reilly, S, Round, A, Seehra, J, Shakeel, NM, Singh, B, Vijay Sukhnani, M, Brown, L, Desai, B, Elzanati, H, Godhaniya, J, Kavanagh, E, Kent, J, Kishor, A, Liu, A, Norwood, M, Shaari, N, Wood, C, Wood, M, Brown, A, Chellapuri, A, Ferriman, A, Ghosh, I, Kulkarni, N, Noton, T, Pinto, A, Rajesh, S, Varghese, B, Wenban, C, Aly, R, Barciela, C, Brookes, T, Corrin, E, Goldsworthy, M, Mohamed Azhar, MS, Moore, J, Nakhuda, S, Ng, D, Pillay, S, Port, S, Abdullah, M, Akinyemi, J, Islam, S, Kale, A, Lewis, A, Manjunath, T, McCabe, H, Misra, S, Stubley, T, Tam, JP, Waraich, N, Chaora, T, Ford, C, Osinkolu, I, Pong, G, Rai, J, Risquet, R, Ainsworth, J, Ayandokun, P, Barham, E, Barrett, G, Barry, J, Bisson, E, Bridges, I, Burke, D, Cann, J, Cloney, M, Coates, S, Cripps, P, Davies, C, Francis, N, Green, S, Handley, G, Hathaway, D, Hurt, L, Jenkins, S, Johnston, C, Khadka, A, McGee, U, Morris, D, Murray, R, Norbury, C, Pierrepont, Z, Richards, C, Ross, O, Ruddy, A, Salmon, C, Shield, M, Soanes, K, Spencer, N, Taverner, S, Williams, C, Wills-Wood, W, Woodward, S, Chow, J, Fan, J, Guest, O, Hunter, I, Moon, WY, Arthur-Quarm, S, Edwards, P, Hamlyn, V, McEneaney, L, N D, G, Pranoy, S, Ting, M, Abada, S, Alawattegama, LH, Ashok, A, Carey, C, Gogna, A, Haglund, C, Hurley, P, Leelo, N, Liu, B, Mannan, F, Paramjothy, K, Ramlogan, K, Raymond-Hayling, O, Shanmugarajah, A, Solichan, D, Wilkinson, B, Ahmad, NA, Allan, D, Amin, A, Bakina, C, Burns, F, Cameron, F, Campbell, A, Cavanagh, S, Chan, SMZ, Chapman, S, Chong, V, Edelsten, E, Ekpete, O, El Sheikh, M, Ghose, R, Hassane, A, Henderson, C, Hilton-Christie, S, Husain, M, Hussain, H, Javid, Z, Johnson-Ogbuneke, J, Johnston, A, Khalil, M, Leung, TCC, Makin, I, Muralidharan, V, Naeem, M, Patil, P, Ravichandran, S, Saraeva, D, Shankey-Smith, W, Sharma, N, Swan, R, Waudby-West, R, Wilkinson, A, Wright, K, Balasubramanian, A, Bhatti, S, Chalkley, M, Chou, WK, Dixon, M, Evans, L, Fisher, K, Gandhi, P, Ho, S, Lau, YB, Lowe, S, Meechan, C, Murali, N, Musonda, C, Njoku, P, Ochieng, L, Pervez, MU, Seebah, K, Shaikh, I, Sikder, MA, Vanker, R, Alom, J, Bajaj, V, Coleman, O, Finch, G, Goss, J, Jenkins, C, Kontothanassis, A, Liew, MS, Ng, K, Outram, M, Shakeel, MM, Tawn, J, Zuhairy, S, Chapple, K, Cinnamond, A, Coleman, S, George, HA, Goulder, L, Hare, N, Hawksley, J, Kret, A, Luesley, A, Mecia, L, Porter, H, Puddy, E, Richardson, G, Sohail, B, Srikaran, V, Tadross, D, Tobin, J, Tokidis, E, Young, L, Ashdown, T, Bratsos, S, Koomson, A, Kufuor, A, Lim, MQ, Shah, S, Thorne, EPC, Warusavitarne, J, Xu, S, Abigail, S, Ahmed, A, Ahmed, J, Akmal, A, Al-Khafaji, M, Amini, B, Arshad, M, Bogie, E, Brazkiewicz, M, Carroll, M, Chandegra, A, Cirelli, C, Deng, A, Fairclough, S, Fung, YJ, Gornell, C, Green, RL, Green, SV, Gulamhussein, AHM, Isaac, AG, Jan, R, Jegatheeswaran, L, Knee, M, Kotecha, J, Kotecha, S, Maxwell-Armstrong, C, McIntyre, C, Mendis, N, Naing, TKP, Oberman, J, Ong, ZX, Ramalingam, A, Saeed Adam, A, Tan, LL, Towell, S, Yadav, J, Anandampillai, R, Chung, S, Hounat, A, Ibrahim, B, Jeyakumar, G, Khalil, A, Khan, UA, Nair, G, Owusu-Ayim, M, Wilson, M, Kanani, A, Kilkelly, B, Ogunmwonyi, I, Ong, L, Samra, B, Schomerus, L, Shea, J, Turner, O, Yang, Y, Amin, M, Blott, N, Clark, A, Feather, A, Forrest, M, Hague, S, Hamilton, K, Higginbotham, G, Hope, E, Karimian, S, Loveday, K, Malik, H, McKenna, O, Noor, A, Onsiong, C, Patel, B, Radcliffe, N, Shah, P, Tye, L, Verma, K, Walford, R, Yusufi, U, Zachariah, M, Casey, A, Doré, C, Fludder, V, Fortescue, L, Kalapu, SS, Karel, E, Khera, G, Smith, C, Appleton, B, Ashaye, A, Boggon, E, Evans, A, Faris Mahmood, H, Hinchcliffe, Z, Marei, O, Silva, I, Spooner, C, Thomas, G, Timlin, M, Wellington, J, Yao, SL, Abdelrazek, M, Abdelrazik, Y, Bee, F, Joseph, A, Mounce, A, Parry, G, Vignarajah, N, Biddles, D, Creissen, A, Kolhe, S, K, T, Lea, A, Ledda, V, O'Loughlin, P, Scanlon, J, Shetty, N, Weller, C, Abdalla, M, Adeoye, A, Bhatti, M, Chadda, KR, Chu, J, Elhakim, H, Foster-Davies, H, Rabie, M, Tailor, B, Webb, S, Abdelrahim, ASA, Choo, SY, Jiwa, A, Mangam, S, Murray, S, Shandramohan, A, Aghanenu, O, Budd, W, Hayre, J, Khanom, S, Liew, ZY, McKinney, R, Moody, N, Muhammad-Kamal, H, Odogwu, J, Patel, D, Roy, C, Sattar, Z, Shahrokhi, N, Sinha, I, Thomson, E, Wonga, L, Bain, J, Khan, J, Ricardo, D, Bevis, R, Cherry, C, Darkwa, S, Drew, W, Griffiths, E, Konda, N, Madani, D, Mak, JKC, Meda, B, Odunukwe, U, Preest, G, Raheel, F, Rajaseharan, A, Ramgopal, A, Risbrooke, C, Selvaratnam, K, Sethunath, G, Tabassum, R, Taylor, J, Thakker, A, Wijesingha, N, Wybrew, R, Yasin, T, Ahmed Osman, A, Alfadhel, S, Carberry, E, Chen, JY, Drake, I, Glen, P, Jayasuriya, N, Kawar, L, Myatt, R, Sinan, LOH, Siu, SSY, Tjen, V, Adeboyejo, O, Bacon, H, Barnes, R, Birnie, C, D'Cunha Kamath, A, Hughes, E, Middleton, S, Owen, R, Schofield, E, Short, C, Smith, R, Wang, H, Willett, M, Zimmerman, M, Balfour, J, Chadwick, T, Coombe-Jones, M, Do Le, HP, Faulkner, G, Hobson, K, Shehata, Z, Beattie, M, Chmielewski, G, Chong, C, Donnelly, B, Drusch, B, Ellis, J, Farrelly, C, Feyi-Waboso, J, Hibell, I, Hoade, L, Ho, C, Jones, H, Kodiatt, B, Lidder, P, Ni Cheallaigh, L, Norman, R, Patabendi, I, Penfold, H, Playfair, M, Pomeroy, S, Ralph, C, Rottenburg, H, Sebastian, J, Sheehan, M, Stanley, V, Welchman, J, Ajdarpasic, D, Antypas, A, Azouaghe, O, Basi, S, Bettoli, G, Bhattarai, S, Bommireddy, L, Bourne, K, Budding, J, Cookey-Bresi, R, Cummins, T, Davies, G, Fabelurin, C, Gwilliam, R, Hanley, J, Hird, A, Kruczynska, A, Langhorne, B, Lund, J, Lutchman, I, McGuinness, R, Neary, M, Pampapathi, S, Pang, E, Podbicanin, S, Rai, N, Redhouse White, G, Sujith, J, Thomas, P, Walker, I, Winterton, R, Anderson, P, Barrington, M, Bhadra, K, Clark, G, Fowler, G, Gibson, C, Hudson, S, Kaminskaite, V, Lawday, S, Longshaw, A, MacKrill, E, McLachlan, F, Murdeshwar, A, Nieuwoudt, R, Parker, P, Randall, R, Rawlins, E, Reeves, SA, Rye, D, Sirkis, T, Sykes, B, Ventress, N, Wosinska, N, Akram, B, Burton, L, Coombs, A, Long, R, Magowan, D, Ong, C, Sethi, M, Williams, G, Chan, C, Chan, LH, Fernando, D, Gaba, F, Khor, Z, Les, JW, Mak, R, Moin, S, Ng Kee Kwong, KC, Paterson-Brown, S, Tew, YY, Bardon, A, Burrell, K, Coldwell, C, Costa, I, Dexter, E, Hardy, A, Khojani, M, Mazurek, J, Raymond, T, Reddy, V, Reynolds, J, Soma, A, Agiotakis, S, Alsusa, H, Desai, N, Peristerakis, I, Adcock, A, Ayub, H, Bennett, T, Bibi, F, Brenac, S, Chapman, T, Clarke, G, Clark, F, Galvin, C, Gwyn-Jones, A, Henry-Blake, C, Kerner, S, Kiandee, M, Lovett, A, Pilecka, A, Ravindran, R, Siddique, H, Sikand, T, Treadwell, K, Akmal, K, Apata, A, Barton, O, Broad, G, Darling, H, Dhuga, Y, Emms, L, Habib, S, Jain, R, Jeater, J, Kan, CYP, Kathiravelupillai, A, Khatkar, H, Kirmani, S, Kulasabanathan, K, Lacey, H, Lal, K, Manafa, C, Mansoor, M, McDonald, S, Mittal, A, Mustoe, S, Nottrodt, L, Oliver, P, Papapetrou, I, Pattinson, F, Raja, M, Reyhani, H, Shahmiri, A, Small, O, Soni, U, Aguirrezabala Armbruster, B, Bunni, J, Hakim, MA, Hawkins-Hooker, L, Howell, KA, Hullait, R, Jaskowska, A, Ottewell, L, Thomas-Jones, I, Vasudev, A, Clements, B, Fenton, J, Gill, M, Haider, S, Lim, AJM, Maguire, H, McMullan, J, Nicoletti, J, Samuel, S, Unais, MA, White, N, Yao, PC, Yow, L, Boyle, C, Brady, R, Cheekoty, P, Cheong, J, Chew, SJHL, Chow, R, Ganewatta Kankanamge, D, Mamer, L, Mohammed, B, Ng Chieng Hin, J, Renji Chungath, R, Royston, A, Sharrad, E, Sinclair, R, Tingle, S, Treherne, K, Wyatt, F, Maniarasu, VS, Moug, S, Appanna, T, Bucknall, T, Hussain, F, Owen, A, Parry, M, Parry, R, Sagua, N, Spofforth, K, Yuen, ECT, Bosley, N, Hardie, W, Moore, T, Regas, C, Abdel-Khaleq, S, Ali, N, Bashiti, H, Buxton-Hopley, R, Constantinides, M, D'Afflitto, M, Deshpande, A, Duque Golding, J, Frisira, E, Germani Batacchi, M, Gomaa, A, Hay, D, Hutchison, R, Iakovou, A, Iakovou, D, Ismail, E, Jefferson, S, Jones, L, Khouli, Y, Knowles, C, Mason, J, McCaughan, R, Moffatt, J, Morawala, A, Nadir, H, Neyroud, F, Nikookam, Y, Parmar, A, Pinto, L, Ramamoorthy, R, Richards, E, Thomson, S, Trainer, C, Valetopoulou, A, Vassiliou, A, Wantman, A, Wilde, S, Dickinson, M, Rockall, T, Senn, D, Wcislo, K, Zalmay, P, Adelekan, K, Allen, K, Bajaj, M, Gatumbu, P, Hang, S, Hashmi, Y, Kaur, T, Kawesha, A, Kisiel, A, Woodmass, M, Adelowo, T, Ahari, D, Alhwaishel, K, Atherton, R, Clayton, B, Cockroft, A, Curtis Lopez, C, Hilton, M, Ismail, N, Kouadria, M, Lee, L, MacConnachie, A, Monks, F, Mungroo, S, Nikoletopoulou, C, Pearce, L, Sara, X, Shahid, A, Suresh, G, Wilcha, R, Atiyah, A, Davies, E, Dermanis, A, Gibbons, H, Hyde, A, Lawson, A, Lee, C, Leung-Tack, M, Li Saw Hee, J, Mostafa, O, Nair, D, Pattani, N, Plumbley-Jones, J, Pufal, K, Ramesh, P, Sanghera, J, Saram, S, Scadding, S, See, S, Stringer, H, Torrance, A, Vardon, H, Wyn-Griffiths, F, Brew, A, Kaur, G, Soni, D, Tickle, A, Akbar, Z, Appleyard, T, Figg, K, Jayawardena, P, Johnson, A, Kamran Siddiqui, Z, Lacy-Colson, J, Oatham, R, Rowlands, B, Sludden, E, Turnbull, C, Allin, D, Ansar, Z, Azeez, Z, Dale, VH, Garg, J, Horner, A, Jones, S, Knight, S, McGregor, C, McKenna, J, McLelland, T, Packham-Smith, A, Rowsell, K, Spector-Hill, I, Adeniken, E, Baker, J, Bartlett, M, Chikomba, L, Connell, B, Deekonda, P, Dhar, M, Elmansouri, A, Gamage, K, Goodhew, R, Hanna, P, Knight, J, Luca, A, Maasoumi, N, Mahamoud, F, Manji, S, Marwaha, PK, Mason, F, Oluboyede, A, Pigott, L, Razaq, AM, Richardson, M, Saddaoui, I, Wijeyendram, P, Yau, S, Atkins, W, Liang, K, Miles, N, Praveen, B, Ashai, S, Braganza, J, Common, J, Cundy, A, Davies, R, Guthrie, J, Handa, I, Iqbal, M, Ismail, R, Jones, C, Jones, I, Lee, KS, Levene, A, Okocha, M, Olivier, J, Smith, A, Subramaniam, E, Tandle, S, Wang, A, Watson, A, Wilson, C, Chan, XHF, Khoo, E, Montgomery, C, Norris, M, Pugalenthi, PP, Common, T, Cook, E, Mistry, H, Shinmar, HS, Agarwal, G, Bandyopadhyay, S, Brazier, B, Carroll, L, Goede, A, Harbourne, A, Lakhani, A, Lami, M, Larwood, J, Martin, J, Merchant, J, Pattenden, S, Pradhan, A, Raafat, N, Rothwell, E, Shammoon, Y, Sudarshan, R, Vickers, E, Wingfield, L, Ashworth, I, Azizi, S, Bhate, R, Chowdhury, T, Christou, A, Davies, L, Dwaraknath, M, Farah, Y, Garner, J, Gureviciute, E, Hart, E, Jain, A, Javid, S, Kankam, HK, Kaur Toor, P, Kaz, R, Kermali, M, Khan, I, Mattson, A, McManus, A, Murphy, M, Nair, K, Ngemoh, D, Norton, E, Olabiran, A, Parry, L, Payne, T, Pillai, K, Price, S, Punjabi, K, Raghunathan, A, Ramwell, A, Raza, M, Ritehnia, J, Simpson, G, Smith, W, Sodeinde, S, Studd, L, Subramaniam, M, Thomas, J, Towey, S, Tsang, E, Tuteja, D, Vasani, J, Vio, M, Badran, A, Adams, J, Anthony Wilkinson, J, Asvandi, S, Austin, T, Bald, A, Bix, E, Carrick, M, Chander, B, Chowdhury, S, Cooper Drake, B, Crosbie, S, D Portela, S, Francis, D, Gallagher, C, Gillespie, R, Gravett, H, Gupta, P, Ilyas, C, James, G, Johny, J, Jones, A, Kinder, F, MacLeod, C, Macrow, C, Maqsood-Shah, A, Mather, J, McCann, L, McMahon, R, Mitham, E, Mohamed, M, Munton, E, Nightingale, K, O'Neill, K, Onyemuchara, I, Senior, R, Shanahan, A, Sherlock, J, Spyridoulias, A, Stavrou, C, Stokes, D, Tamang, R, Taylor, E, Trafford, C, Uden, C, Waddington, C, Yassin, D, Zaman, M, Bangi, S, Cheng, T, Chew, D, Hussain, N, Imani-Masouleh, S, Mahasivam, G, McKnight, G, Ng, HL, Ota, HC, Pasha, T, Ravindran, W, Shah, K, Vishnu K, S, Zaman, S, Carr, W, Cope, S, Eagles, EJ, Howarth-Maddison, M, Li, CY, Reed, J, Ridge, A, Stubbs, T, Teasdaled, D, Umar, R, Worthington, J, Dhebri, A, Kalenderov, R, Alattas, A, Arain, Z, Bhudia, R, Chia, D, Daniel, S, Dar, T, Garland, H, Girish, M, Hampson, A, Kyriacou, H, Lehovsky, K, Mullins, W, Omorphos, N, Vasdev, N, Venkatesh, A, Waldock, W, Bhandari, A, Brown, G, Choa, G, Eichenauer, CE, Ezennia, K, Kidwai, Z, Lloyd-Thomas, A, Macaskill Stewart, A, Massardi, C, Sinclair, E, Skajaa, N, Smith, M, Tan, I, Afsheen, N, Anuar, A, Azam, Z, Bhatia, P, Davies-kelly, N, Dickinson, S, Elkawafi, M, Ganapathy, M, Gupta, S, Khoury, EG, Licudi, D, Mehta, V, Neequaye, S, Nita, G, Tay, VL, Zhao, S, Botsa, E, Cuthbert, H, Elliott, J, Furlepa, M, Lehmann, J, Mangtani, A, Narayan, A, Nazarian, S, Parmar, C, Shah, D, Shaw, C, Zhao, Z, Beck, C, Caldwell, S, Clements, JM, French, B, Kenny, R, Kirk, S, Lindsay, J, McClung, A, McLaughlin, N, Watson, S, Whiteside, E, Alyacoubi, S, Arumugam, V, Beg, R, Dawas, K, Garg, S, Lloyd, ER, Mahfouz, Y, Manobharath, N, Moonesinghe, R, Morka, N, Patel, K, Prashar, J, Yip, S, Adeeko, ES, Ajekigbe, F, Bhat, A, Evans, C, Farrugia, A, Gurung, C, Long, T, Malik, B, Manirajan, S, Newport, D, Rayer, J, Ridha, A, Ross, E, Saran, T, Sinker, A, Waruingi, D, Allen, R, Al Sadek, Y, Alves do Canto Brum, H, Asharaf, H, Ashman, M, Balakumar, V, Barrington, J, Baskaran, R, Berry, A, Bhachoo, H, Bilal, A, Boaden, L, Chia, WL, Covell, G, Crook, D, Dadnam, F, Davis, L, De Berker, H, Doyle, C, Fox, C, Gruffydd-Davies, M, Hafouda, Y, Hill, A, Hubbard, E, Hunter, A, Inpadhas, V, Jamshaid, M, Jandu, G, Jeyanthi, M, Jones, T, Kantor, C, Kwak, SY, Malik, N, Matt, R, McNulty, P, Miles, C, Mohomed, A, Myat, P, Niharika, J, Nixon, A, O'Reilly, D, Parmar, K, Pengelly, S, Price, L, Ramsden, M, Turnor, R, Wales, E, Waring, H, Wu, M, Yang, T, Ye, TTS, Zander, A, Zeicu, C, Bellam, S, Francombe, J, Kawamoto, N, Rahman, MR, Sathyanarayana, A, Tang, HT, Cheung, J, Hollingshead, J, Page, V, Sugarman, J, Wong, E, Chiong, J, Fung, E, Kan, SY, Kiang, J, Kok, J, Krahelski, O, Liew, MY, Lyell, B, Sharif, Z, Speake, D, Alim, L, Amakye, NY, Chandrasekaran, J, Chandratreya, N, Drake, J, Owoso, T, Thu, YM, Abou El Ela Bourquin, B, Alberts, J, Chapman, D, Rehnnuma, N, Ainsworth, K, Carpenter, H, Emmanuel, T, Fisher, T, Gabrel, M, Guan, Z, Hollows, S, Hotouras, A, Ip Fung Chun, N, Jaffer, S, Kallikas, G, Kennedy, N, Lewinsohn, B, Liu, FY, Mohammed, S, Rutherfurd, A, Situ, T, Stammer, A, Taylor, F, Thin, N, Urgesi, E, Zhang, N, Ahmad, MA, Bishop, A, Bowes, A, Dixit, A, Glasson, R, Hatta, S, Hatt, K, Larcombe, S, Preece, J, Riordan, E, Fegredo, D, Haq, MZ, Li, C, McCann, G, Stewart, D, Baraza, W, Bhullar, D, Burt, G, Coyle, J, Deans, J, Devine, A, Hird, R, Ikotun, O, Manchip, G, Ross, C, Storey, L, Tan, WWL, Tse, C, Warner, C, Whitehead, M, Wu, F, Court, EL, Crisp, E, Huttman, M, Mayes, F, Robertson, H, Rosen, H, Sandberg, C, Smith, H, Al Bakry, M, Ashwell, W, Bajaj, S, Bandyopadhyay, D, Browlee, O, Burway, S, Chand, CP, Elsayeh, K, Elsharkawi, A, Evans, E, Ferrin, S, Fort-Schaale, A, Iacob, M, I, K, Impelliziere Licastro, G, Mankoo, AS, Olaniyan, T, Otun, J, Pereira, R, Reddy, R, Saeed, D, Simmonds, O, Singhal, G, Tron, K, Wickstone, C, Williams, R, Bradshaw, E, De Kock Jewell, V, Houlden, C, Knight, C, Metezai, H, Mirza-Davies, A, Seymour, Z, Spink, D, and Wischhusen, S

Published
2022
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48. Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

Author

Self, Wesley H., Sandkovsky, Uriel, Reilly, Cavan S., Vock, David M., Gottlieb, Robert L., Mack, Michael, Golden, Kevin, Dishner, Emma, Vekstein, Andrew, Ko, Emily R., Der, Tatyana, Franzone, John, Almasri, Eyad, Fayed, Mohamed, Filbin, Michael R., Hibbert, Kathryn A., Rice, Todd W., Casey, Jonathan D., Hayanga, J. Awori, Badhwar, Vinay, Leshnower, Bradley G., Sharifpour, Milad, Knowlton, Kirk U., Peltan, Ithan D., Bakowska, Elizieta, Kowalska, Justyna, Bowdish, Michael E., Sturek, Jeffrey M., Rogers, Angela J., Files, D. Clark, Mosier, Jarrod M., Gong, Michelle N., Douin, David J., Hite, R. Duncan, Trautner, Barbara W., Jain, Mamta K., Gardner, Edward M., Khan, Akram, Jensen, Jens-Ulrik, Matthay, Michael A., Ginde, Adit A., Brown, Samuel M., Higgs, Elizabeth S., Pett, Sarah, Weintrob, Amy C., Chang, Christina C., Murrary, Daniel D., Günthard, Huldrych F., Moquete, Ellen, Grandits, Greg, Engen, Nicole, Grund, Birgit, Sharma, Shweta, Cao, Huyen, Gupta, Rajesh, Osei, Suzette, Margolis, David, Zhu, Qing, Polizzotto, Mark N., Babiker, Abdel G., Davey, Victoria J., Kan, Virginia, Thompson, B. Taylor, Gelijns, Annetine C., Neaton, James D., Lane, H. Clifford, Jundgren, Jens D., Tierney, John, Barrett, Kevin, Herpin, Betsey R., Smolskis, Mary C., Voge, Susan E., McNay, Laura A., Cahill, Kelly, Crew, Page, Kirchoff, Matthew, Sardana, Ratna, Raim, Sharon Segal, Chiu, Joseph, Hensley, Lisa, Lorenzo, Josua, Mock, Rebecca, Shaw-Saliba, Katy, Zuckerman, Judith, Adam, Stacey J., Currier, Judy, Read, Sarah, Hughes, Eric, Amos, Laura, Carlsen, Amy, Carter, Anita, Davis, Bionca, Denning, Eileen, DuChene, Alain, Harrison, Merrie, Kaiser, Payton, Koopmeiners, Joseph, Meger, Sue, Murray, Thomas, Quan, Kien, Quan, Siu Fun, Thompson, Greg, Walski, Jamie, Wentworth, Deborah, Moskowitz, Alan J., Bagiella, Emilia, O'Sullivan, Karen, Marks, Mary E., Accardi, Evan, Kinzel, Emily, Bedoya, Gabriela, Gupta, Lopa, Overbey, Jessica R., Padillia, Maria L., Santos, Milerva, Gillinov, Marc A., Miller, Marissa A., Taddei-Peters, Wendy C., Fenton, Kathleen, Berhe, Mezgebe, Haley, Clinton, Bettacchi, Christopher, Duhaime, Erin, Ryan, Madison, Burris, Sarah, Jones, Felecia, Villa, Samantha, Want, Samantha, Robert, Raven, Coleman, Tanquinisha, Clariday, Laura, Baker, Rebecca, Hurutado-Rodriguez, Marian, Iram, Nazia, Fresnedo, Michelle, Davis, Allyson, Leonard, Kiara, Ramierez, Noelia, Thammavong, Jon, Duque, Krizia, Turner, Emma, Fisher, Tammy, Robinson, Dianna, Ransom, Desirae, Lusk, Erica, Killian, Aaron, Palacious, Adriana, Solis, Edilia, Jerrow, Janet, Watts, Matthew, Whitacre, Heather, Cothran, Elizabeth, Smith, Peter K., Barkauskas, Christina E., Dreyer, Grace R., Witte, Marie, Mosaly, Nilima, Mourad, Ahmad, Holland, Thomas L., Lane, Kathleen, Bouffler, Andrew, McGowan, Lauren M., Motta, Marry, Tipton, Gregory, Stallings, Ben, Stout, Gennifer, McLendon-Arvik, Beth, Hollister, Beth A., Giangiacomo, Dana M., Sharma, Sunil, Pappers, Brian, McCarthy, Paul, Krupica, Troy, Sarwari, Arif, Reece, Rebecca, Fornaresio, Lisa, Glaze, Chad, Evans, Raquel, Preamble, Katarina, Sutton, Lisa Giblin, Buterbaugh, Sabrina, Bartolo, Elizabeth Berry, Williams, Roger, Bunner, Robin, Bender, William, Miller, Jeffrey, Baio, Kim T., McBride, Mary K., Fielding, Michele, Mathewson, Sonya, Porte, Kristina, Maton, Missy, Ponder, Chari, Haley, Elizabeth, Spainhour, Christine, Rogers, Susan, Tyler, Derrick, Wald-Dickler, Noah, Hutcheon, Douglass, Towfighi, Amytis, Lee, May M., Lewis, Meghan R., Spellberg, Brad, Sher, Linda, Sharma, Aniket, Olds, Anna P., Justino, Chris, Lozano, Edward, Romero, Chris, Leong, Janet, Rodina, Valentina, Possemato, Tammie, Escobar, Jose, Chiu, Charlene, Weissman, Kevin, Barros, Andrew, Enfield, Kyle B., Kadl, Alexandra, Green, China J., Simon, Rachel M., Fox, Ashley, Thornton, Kara, Parrino, Patrick E., Spindel, Stephen, Bansal, Aditya, Baumgarten, Katherine, Hand, Jonathan, Vonderhaar, Derek, Nossaman, Bobby, Laudun, Sylvia, Ames, DeAnna, Broussard, Shane, Hernandez, Nilmo, Isaac, Geralyn, Dinh, Huan, Zheng, Yiling, Tran, Sonny, McDaniel, Hunter, Crovetto, Nicolle, Miller, Leslie, Schelle, Beth, McLean, Sherry, Rothbaum, Howard R., Alvarez, Michael S., Kalan, Shivam P., Germann, Heather H., Hendershot, Jennifer, Maroney, Karen, Herring, Karen, Cook, Sharri, Paul, Pam, Madathil, Ronson J., Rabin, Joseph, Levine, Andrea, Saharia, Kapil, Tabatabai, Ali, Lau, Christine, Gammie, James S., Peguero, Maya-Loren, McKernan, Kimberley, Audette, Matthew, Fleischmann, Emily, Akbari, Freshta, Lee, Maia, Lee, Myounghee, Chi, Andrew, Salehi, Hanna, Pariser, Alan, Nguyen, Phuong Tran, Moore, Jessica, Gee, Adrienne, Vincent, Shelika, Zuckerman, Richard A., Iribarne, Alexander, Metzler, Sara, Shipman, Samantha, Caccia, Taylor, Johnson, Haley, Newton, Crystallee, Parr, Doug, Rodriguez, Vicente, Bokhart, Gordon, Eichman, Sharon M., North, Crystal, Oldmixon, Cathryn, Ringwood, Nancy, Fitzgerald, Laura, Morin, Haley D., Muzikansky, Ariela, Morse, Richard, Brower, Roy G., Reineck, Lora A., Aggarwal, Neil R., Bienstock, Karen, Hou, Peter, Steingrub, Jay, Tidswell, Mark A., Kozikowski, Lori-Ann, Kardos, Cynthia, DeSouza, Leslie, Thornton-Thompson, Sherell, Talmor, Daniel, Shapiro, Nathan, Banner-Goodspeed, Valerie, Boyle, Katherine L., Hayes, Sharon, Jones, Alan E., Galbraith, James, Nandi, Utsav, Peacock, Rebekah K., Parry, Blair Alden, Margolin, Justin D., Brait, Kelsey, Beakes, Caroline, Kangelaris, Kirsten N., Yee, Kimberly J., Ashktorab, Kimia, Jauregui, Alejandra E., Zhuo, Hanjing, Hendey, Gregory, Hubel, Kinsley A., Hughes, Alyssa R., Garcia, Rebekah L., Wilson, Jennifer G., Vojnik, Rosemary, Roque, Jonasel, Perez, Cynthia, Lim, George W., Chang, Steven Y., Beutler, Rebecca, Agarwal, Trisha, Vargas, Julia, Moss, Marc, Baduashvili, Amiran, Chauhan, Lakshmi, Finck, Lani L., Howell, Michelle, Hyzy, Robert C., Park, Pauline K., Nelson, Kristine, McSparron, Jake I., Co, Ivan N., Wang, Bonnie R., Jia, Shijing, Sullins, Barbara, Hanna, Sinan, Olbrich, Norman, Richardson, Lynne D., Nair, Rahul, Offor, Obiageli, Lopez, Brenda, Amosu, Omowunmi, Tzehaie, Hiwet, Terndrup, Thomas E., Wiedemann, Herbert P., Duggal, Abhijit, Thiruchelvam, Nirosshan, Ashok, Kiran, King, Alexander H., Mehkri, Omar, Hudock, Kristin, Kiran, Simra, More, Harshada, Roads, Tammy, Martinkovic, Jamie, Kennedy, Sarah, Robinson, Bryce H., Hough, Catherine L., Krol, Olivia F., Kinjal, Mistry, Mills, Emmanuel, McDougal, Madeline, Deshmukh, Rupali, Chen, Peter, Torbati, Sam S., Matusov, Yuri, Choe, June, Hindoyan, Niree A., Jackman, Susan E., Bayoumi, Emad, Wynter, Timothy, Caudill, Antonina, Pascual, Ethan, Clapham, Gregg J., Herrera, Lisa, Ojukwu, Cristabelle, Mehdikhani, Shaunt, O'Mahony, D. Shane, Nyatsatsang, Sonam T., Wilson, David M., Wallick, Julie A., Miller, Chadwick, Gibbs, Keven W., Flores, Lori S., LaRose, Mary E., Landreth, Leigha D., Morris, Peter E., Sturgill, Jamie L., Cassity, Evan P., Dhar, Sanjay, Montgomery-Yates, Ashley A., Pasha, Sara N., Mayer, Kirby P., Bissel, Brittany, Bledsoe, Joseph, Brown, Samuel, Lanspa, Michael, Leither, Lindsey, Armbruster, Brent P., Montgomery, Quinn, Applegate, Darrin, Kumar, Naresh, Fergus, Melissa, Serezlic, Erna, Imel, Karah, Palmer, Ghazal, Webb, Brandon, Aston, Valerie T., Johnson, Jakea, Gray, Christopher, Hays, Margaret, Roth, Megan, Sánchez, Adriana, Popielski, Laura, Rivasplata, Heather, Turner, Melissa, Vjecha, Michael, Petersen, Tianna, Kamel, Dena, Hansen, Laura, Lucas, Claudia Sanchez, DellaValle, Natalie, Gonzales, Sonia, Scott, James, Wyles, David, Douglas, Ivor, Haukoos, Jason, Kamis, Kevin, Robinson, Caitlin, Baker, Jason V., Frosch, Anne, Goldsmith, Rachael, Jibrell, Hodan, Lo, Melanie, Klaphake, Jonathan, Mackedanz, Shari, Ngo, Linh, Garcia-Myers, Kelly, Markowitz, Norman, Pastor, Erika, Ramesh, Mayur, Brar, Indira, Rivers, Emanuel, Kumar, Princy, Menna, Maximiliano, Biswas, Kousick, Harrington, Cristin, Delp, Alex, Pandit, Lavannya, Hines-Munson, Casey, Van, John, Dillon, Laura, Want, Yiqun, Lichtenberger, Paola, Baracco, Gio, Ramos, Carol, Bjork, Lauren, Sueiro, Melyssa, Tien, Phyllis, Freasier, Heather, Buck, Theresa, Nekach, Hafida, Nagy-Agren, Stephanie, Vasudeva, Shikha, Ochalek, Tracy, Roller, Brentin, Nguyen, Chinh, Mikail, Amani, Raben, Dorthe, Jensen, Tomas O., Aagaard, Bitten, Nielsen, Charlotte B., Krapp, Katharina, Nykjær, Bente Rosdahl, Kanne, Katja Lisa, Grevsen, Anne Louise, Joensen, Zillah Maria, Bruun, Tina, Bojesen, Ane, Woldbye, Frederik, Normand, Nick E., Esmann, Frederik V.L., Clausen, Clara Lundetoft, Hovmand, Nichlas, Pedersen, Karen Brorup, Thorlacius-Ussing, Louise, Tinggaard, Michaela, Høgsberg, Dorthe S., Rastoder, Ema, Kamstrup, Thobias, Bergsøe, Christina Marisa, Østergaard, Lars, Stærke, Nina Breinholt, Johansen, Isik S., Knudtzen, Fredrikke C., Larsen, Lykke, Hertz, Mathias A., Fabricius, Thilde, Helleberg, Marie, Gerstoft, Jan, Jensen, Tomas Østergaard, Lindegaard, Birgitte, Pedersen, Thomas Ingemann, Røge, Birgit Thorup, Løfberg, Sandra Valborg, Hansen, Thomas Michael, Nielsen, Ariella Denize, von Huth, Sebastian Leicht, Nielsen, Henrik, Thisted, Rikke Krog, Podlekareva, Daria, Johnsen, Stine, Andreassen, Helle Frost, Pedersen, Lars, Lindnér, Cecilia Ebba Clara Ellinor, Wiese, Lothar, Knudsen, Lene Surland, Nytofte, Nikolaj Julian Skrøder, Havmøller, Signe Ravn, Paredes, Roger, Exposito, Maria, Fernández-Cruz, Eduardo, Muñoz, José, Arribas, Jose R., Estrada, Vicente, Horcajada, Juan P., Burgos, Joaquin, Morales-Rull, Jose Luis, Braun, Dominique L., West, Emily, M'Rabeth-Bensalah, Khadija, Eichinger, Mareile L., Grüttner-Durmaz, Manuela, Grube, Christina, Zink, Veronika, Horban, Andrzej, Bednarska, Agnieszka, Jurek, Natalia, Fätkenheuer, Gerd, Malinm, Jakob J., Matthews, Gail, Kelleher, Anthony, Cabrera, Gesalit, Carey, Catherine, Hough, Sally, Virachit, Sophie, Zhong, Amy, Young, Barnaby E., Chia, Po Ying, Lee, Tau Hong, Lin, Ray J., Lye, David, Ong, Sean, Puah, Ser Hon, Yeo, Tsin Wen, Diong, Shiau Hui, Ongko, Juwinda, Hudson, Fleur, Parmar, Mahesh KB, Goodman, Anna, Badrock, Jonathan, Gregory, Adam, Harris, Nicola, Touloumi, Giota, Pantaz, Nikos, Gioukari, Vicky, Lutaakome, Joseph, Kityo, Cissy M., Mugerwa, Henry, Kiweewa, Francis, Osinusi, Anu, Tipple, Craig, Willis, Angela, Peppercorn, Amanda, Watson, Helen, Alexander, Elizabeth, Mogalian, Erik, Lin, Leo, Ding, Xiao, Yan, Li, Girardet, Jean-Luc, Ma, Ji, Hong, Zhi, Adams, Amy, Albert, Sara, Balde, Abby, Baracz, Michelle, Baseler, Beth, Becker, Nancy, Bielica, Mona, Billouin-Frazier, Shere, Cash, Jennifer, Choudhary, Jay, Dolney, Suzanne, Dixon, Mary, Eyler, Carolyn, Frye, Leanna, Galcik, Michael, Gertz, Jensen, Giebeig, Lisa, Gulati, Neelam, Hankinson, Liz, Hissey, Debbie, Hogarty, Debi, Hohn, Matt, Holley, H Preston, Hoopengardner, Lisa, Huber, Lynda, Jankelevich, Shirley, Krauss, Gary, Lake, Eileen, Linton, Jessica, MacDonald, Leah, Manandhar, Meryan, Spinelli-Nadzam, Mary, Oluremi, Charles, Proffitt, Calvin, Rudzinski, Erin, Sandrus, Jen, Schaffhauser, Marylu, Schechner, Adam, Suders, Connie, Gerry, Norman P., Smith, Kenneth, Solomon, Courtney, Kubernac, Amanda, Rashid, Marium, Patel, Bhakti, Kubernac, Robert, Murphy, Joseph, Hoover, Marie L., Brown, Craig, DuChateau, Nadine, Flosi, Adam, Johnson, Les, Treagus, Amy, and Wenner, Christine

Published
2022
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49. The Gaia-ESO Survey: Matching Chemo-Dynamical Simulations to Observations of the Milky Way

Author

Thompson, B. B., Few, C. G., Bergemann, M., Gibson, B. K., MacFarlane, B. A., Serenelli, A., Gilmore, G., Randich, S., Vallenari, A., Alfaro, E. J., Bensby, T., Francois, P., Korn, A. J., Bayo, A., Carraro, G., Casey, A. R., Costado, M. T., Donati, P, Franciosini, E., Frasca, A., Hourihane, A., Jofre, P., Hill, V., Heiter, U., Koposov, S. E., Lanzafame, A., Lardo, C., de Laverny, P., Lewis, J., Magrini, L., Marconi, G., Masseron, T., Monaco, L., Morbidelli, L., Pancino, E., Prisinzano, L., Recio-Blanco, A., Sacco, G., Sousa, S. G., Tautvaisiene, G., Worley, C. C., and Zaggia, S.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

The typical methodology for comparing simulated galaxies with observational surveys is usually to apply a spatial selection to the simulation to mimic the region of interest covered by a comparable observational survey sample. In this work we compare this approach with a more sophisticated post-processing in which the observational uncertainties and selection effects (photometric, surface gravity and effective temperature) are taken into account. We compare a `solar neighbourhood analogue' region in a model Milky Way-like galaxy simulated with RAMSES-CH with fourth release Gaia-ESO survey data. We find that a simple spatial cut alone is insufficient and that observational uncertainties must be accounted for in the comparison. This is particularly true when the scale of uncertainty is large compared to the dynamic range of the data, e.g. in our comparison, the [Mg/Fe] distribution is affected much more than the more accurately determined [Fe/H] distribution. Despite clear differences in the underlying distributions of elemental abundances between simulation and observation, incorporating scatter to our simulation results to mimic observational uncertainty produces reasonable agreement. The quite complete nature of the Gaia-ESO survey means that the selection function has minimal impact on the distribution of observed age and metal abundances but this would become increasingly more important for surveys with narrower selection functions., Comment: Accepted for publication in MNRAS; 13 pages, 7 figures, 1 table

Published
2017
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50. Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study

Author

Sinha, Pratik, Delucchi, Kevin L, Thompson, B Taylor, McAuley, Daniel F, Matthay, Michael A, and Calfee, Carolyn S

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Clinical Trials and Supportive Activities, Clinical Research, Infectious Diseases, Good Health and Well Being, Acute Lung Injury, Adult, Aged, Cohort Studies, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Latent Class Analysis, Male, Middle Aged, Respiratory Distress Syndrome, Rosuvastatin Calcium, Sepsis, Survival Rate, ARDS, Subphenotypes, Latent class analysis, Statins, NHLBI ARDS Network, Public Health and Health Services, Emergency & Critical Care Medicine, Clinical sciences
Abstract

PurposeUsing latent class analysis (LCA), we have consistently identified two distinct subphenotypes in four randomized controlled trial cohorts of ARDS. One subphenotype has hyper-inflammatory characteristics and is associated with worse clinical outcomes. Further, within three negative clinical trials, we observed differential treatment response by subphenotype to randomly assigned interventions. The main purpose of this study was to identify ARDS subphenotypes in a contemporary NHLBI Network trial of infection-associated ARDS (SAILS) using LCA and to test for differential treatment response to rosuvastatin therapy in the subphenotypes.MethodsLCA models were constructed using a combination of biomarker and clinical data at baseline in the SAILS study (n = 745). LCA modeling was then repeated using an expanded set of clinical class-defining variables. Subphenotypes were tested for differential treatment response to rosuvastatin.ResultsThe two-class LCA model best fit the population. Forty percent of the patients were classified as the "hyper-inflammatory" subphenotype. Including additional clinical variables in the LCA models did not identify new classes. Mortality at day 60 and day 90 was higher in the hyper-inflammatory subphenotype. No differences in outcome were observed between hyper-inflammatory patients randomized to rosuvastatin therapy versus placebo.ConclusionsLCA using a two-subphenotype model best described the SAILS population. The subphenotypes have features consistent with those previously reported in four other cohorts. Addition of new class-defining variables in the LCA model did not yield additional subphenotypes. No treatment effect was observed with rosuvastatin. These findings further validate the presence of two subphenotypes and demonstrate their utility for patient stratification in ARDS.

Published
2018

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