1,098 results on '"Thompson, B. Taylor"'
Search Results
2. 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
3. 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
4. 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
5. 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
- Full Text
- View/download PDF
6. 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
7. 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
8. 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
9. 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
10. 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
11. 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
12. PROLONGED MECHANICAL VENTILATION IN ACUTE RESPIRATORY DISTRESS SYNDROME
- Author
-
Andrianopoulos, Ioannis, Giannakoulis, Vassilis G., Papoutsi, Eleni, Papathanakos, Georgios, Koulouras, Vasilios, Thompson, B. Taylor, and Siempos, Ilias I.
- Published
- 2024
- Full Text
- View/download PDF
13. 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
14. 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
15. Sleep apnea and respiratory anomaly detection from a wearable band and oxygen saturation
- Author
-
Ganglberger, Wolfgang, Bucklin, Abigail A., Tesh, Ryan A., Da Silva Cardoso, Madalena, 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
- Published
- 2022
- Full Text
- View/download PDF
16. Lopinavir/ritonavir for treatment of non-hospitalized patients with COVID-19: a randomized clinical trial
- Author
-
Kaizer, Alexander M., Shapiro, Nathan I., Wild, Jessica, Brown, Samuel M., Cwik, B. Jessica, Hart, Kimberly W., Jones, Alan E., Pulia, Michael S., Self, Wesley H., Smith, Clay, Smith, Stephanie A., Ng, Patrick C., Thompson, B. Taylor, Rice, Todd W., Lindsell, Christopher J., and Ginde, Adit A.
- Published
- 2023
- Full Text
- View/download PDF
17. Prolonged Prone Position Ventilation Is Associated With Reduced Mortality in Intubated COVID-19 Patients
- Author
-
Okin, Daniel, Huang, Ching-Ying, Alba, George A., Jesudasen, Sirus J., Dandawate, Nupur A., Gavralidis, Alexander, Chang, Leslie L., Moin, Emily E., Ahmad, Imama, Witkin, Alison S., Hardin, C. Corey, Hibbert, Kathryn A., Kadar, Aran, Gordan, Patrick L., Lee, Hang, Thompson, B. Taylor, Bebell, Lisa M., and Lai, Peggy S.
- Published
- 2023
- Full Text
- View/download PDF
18. 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
- Full Text
- View/download PDF
19. 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
- Full Text
- View/download PDF
20. From ICU Syndromes to ICU Subphenotypes: Consensus Report and Recommendations For Developing Precision Medicine in ICU
- Author
-
Gordon, Anthony C., primary, Alipanah-Lechner, Narges, additional, Bos, Lieuwe D., additional, Dianti, Jose, additional, Diaz, Janet Victoria, additional, Finfer, Simon, additional, Fujii, Tomoko, additional, Giamarellos-Bourboulis, Evangelos J., additional, Goligher, Ewan C., additional, Gong, Michelle Ng, additional, Karakike, Eleni, additional, Liu, Vincent, additional, Lumlertgul, Nuttha, additional, Marshall, John C., additional, Menon, David K., additional, Meyer, Nuala J, additional, Munroe, Elizabeth S., additional, Myatra, Sheila N., additional, Ostermann, Marlies, additional, Prescott, Hallie C, additional, Randolph, Adrienne G., additional, Schenck, Edward J., additional, Seymour, Christopher W, additional, Shankar-Hari, Manu, additional, Singer, Mervyn, additional, Smit, Marry R., additional, Tanaka, Aiko, additional, Taccone, Fabio Silvio, additional, Thompson, B. Taylor, additional, Torres, Lisa K, additional, Van der Poll, Tom, additional, Vincent, Jean-Louis, additional, and Calfee, Carolyn S, additional
- Published
- 2024
- Full Text
- View/download PDF
21. Trial of Early Antiviral Therapies during Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19: a summary of the protocol and analysis plan for a decentralized randomized controlled trial
- Author
-
Kaizer, Alexander M., Wild, Jessica, Lindsell, Christopher J., Rice, Todd W., Self, Wesley H., Brown, Samuel, Thompson, B. Taylor, Hart, Kimberly W., Smith, Clay, Pulia, Michael S., Shapiro, Nathan I., and Ginde, Adit A.
- Published
- 2022
- Full Text
- View/download PDF
22. 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
- Full Text
- View/download PDF
23. 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
- Full Text
- View/download PDF
24. 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
25. 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
26. 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
27. 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
28. 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
- Full Text
- View/download PDF
29. Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis: The ASTER Randomized Clinical Trial.
- Author
-
Ware, Lorraine B., Files, D. Clark, Fowler, Alpha, Aboodi, Michael S., Aggarwal, Neil R., Brower, Roy G., Chang, Steven Y., Douglas, Ivor S., Fields, Scott, Foulkes, Andrea S., Ginde, Adit A., Harris, Estelle S., Hendey, Gregory W., Hite, R. Duncan, Huang, Weixing, Lai, Poying, Liu, Kathleen D., Thompson, B. Taylor, and Matthay, Michael A.
- Subjects
CRITICALLY ill ,ARTIFICIAL respiration ,ADULT respiratory distress syndrome ,ACETAMINOPHEN ,RENAL replacement therapy ,SEPSIS - Abstract
Key Points: Question: Does acetaminophen (paracetamol) improve respiratory, circulatory, or kidney dysfunction in critically ill patients with sepsis, and is acetaminophen more effective in patients with higher plasma cell-free hemoglobin? Findings: In this randomized clinical trial that included 447 adults, acetaminophen was safe but the number of days alive and free of organ support was not meaningfully different in the acetaminophen arm (20.2 days) vs the placebo arm (19.6 days). There was no significant interaction between cell-free hemoglobin levels and acetaminophen. Meaning: Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill patients with sepsis. Importance: Acetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates. Objective: To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo. Design, Setting, and Participants: Phase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up. Adults with sepsis and respiratory or circulatory organ dysfunction were enrolled in the emergency department or intensive care unit of 40 US academic hospitals within 36 hours of presentation. Intervention: Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days. Main Outcome and Measures: The primary end point was days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28. Treatment effect modification was evaluated for acetaminophen by prerandomization plasma cell-free hemoglobin level higher than 10 mg/dL. Results: Of 447 patients enrolled (mean age, 64 [SD, 15] years, 51% female, mean Sequential Organ Failure Assessment [SOFA] score, 5.4 [SD, 2.5]), 227 were randomized to acetaminophen and 220 to placebo. Acetaminophen was safe with no difference in liver enzymes, hypotension, or fluid balance between treatment arms. Days alive and free of organ support to day 28 were not meaningfully different for acetaminophen (20.2 days; 95% CI, 18.8 to 21.6) vs placebo (19.6 days; 95% CI, 18.2 to 21.0; P =.56; difference, 0.6; 95% CI, −1.4 to 2.6). Among 15 secondary outcomes, total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen arm as was the rate of development of acute respiratory distress syndrome within 7 days (2.2% vs 8.5% acetaminophen vs placebo; P =.01; difference, −6.3; 95% CI, −10.8 to −1.8). There was no significant interaction between cell-free hemoglobin levels and acetaminophen. Conclusions and Relevance: Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04291508 This randomized trial assesses whether acetaminophen would increase the number of days alive and free of organ support to day 28 among critically ill patients with sepsis and respiratory or circulatory organ dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
30. Early Mortality in Clinical Trials of Acute Respiratory Distress Syndrome.
- Author
-
Giannakoulis, Vassilis G., Schenck, Edward J., Papoutsi, Eleni, Price, David R., Villar, Jesús, Sarwath, Hina, Schmidt, Frank, Thompson, B. Taylor, Choi, Augustine M. K., and Siempos, Ilias I.
- Subjects
ADULT respiratory distress syndrome ,CLINICAL trials ,LACTOSE intolerance - Abstract
The article focuses on early mortality among patients with acute respiratory distress syndrome (ARDS) within the context of randomized controlled trials. It hypothesizes that early deaths, occurring within 3 days of randomization, exhibit distinct baseline characteristics, clinical trajectories, and proteomic profiles compared to late deaths. It highlight potential biomarkers associated with early mortality in ARDS, providing insights for prognosis and therapeutic strategies.
- Published
- 2024
- Full Text
- View/download PDF
31. Stability of ARDS subphenotypes over time in two randomised controlled trials
- Author
-
Delucchi, Kevin, Famous, Katie R, Ware, Lorraine B, Parsons, Polly E, Thompson, B Taylor, and Calfee, Carolyn S
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Lung ,Rare Diseases ,Clinical Research ,Clinical Trials and Supportive Activities ,Acute Respiratory Distress Syndrome ,Biomarkers ,Female ,Hospital Mortality ,Humans ,Male ,Models ,Statistical ,Phenotype ,Positive-Pressure Respiration ,Randomized Controlled Trials as Topic ,Respiratory Distress Syndrome ,Time Factors ,Treatment Outcome ,ARDS Network ,acute lung injury ,acute respiratory distress syndrome ,endotypes ,precision medicine ,subphenotypes ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
RationaleTwo distinct acute respiratory distress syndrome (ARDS) subphenotypes have been identified using data obtained at time of enrolment in clinical trials; it remains unknown if these subphenotypes are durable over time.ObjectiveTo determine the stability of ARDS subphenotypes over time.MethodsSecondary analysis of data from two randomised controlled trials in ARDS, the ARMA trial of lung protective ventilation (n=473; patients randomised to low tidal volumes only) and the ALVEOLI trial of low versus high positive end-expiratory pressure (n=549). Latent class analysis (LCA) and latent transition analysis (LTA) were applied to data from day 0 and day 3, independent of clinical outcomes.Measurements and main resultsIn ALVEOLI, LCA indicated strong evidence of two ARDS latent classes at days 0 and 3; in ARMA, evidence of two classes was stronger at day 0 than at day 3. The clinical and biological features of these two classes were similar to those in our prior work and were largely stable over time, though class 2 demonstrated evidence of progressive organ failures by day 3, compared with class 1. In both LCA and LTA models, the majority of patients (>94%) stayed in the same class from day 0 to day 3. Clinical outcomes were statistically significantly worse in class 2 than class 1 and were more strongly associated with day 3 class assignment.ConclusionsARDS subphenotypes are largely stable over the first 3 days of enrolment in two ARDS Network trials, suggesting that subphenotype identification may be feasible in the context of clinical trials.
- Published
- 2018
32. Identifying clinical and biochemical phenotypes in acute respiratory distress syndrome secondary to coronavirus disease-2019
- Author
-
Ranjeva, Sylvia, Pinciroli, Riccardo, Hodell, Evan, Mueller, Ariel, Hardin, C. Corey, Thompson, B. Taylor, and Berra, Lorenzo
- Published
- 2021
- Full Text
- View/download PDF
33. Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy
- Author
-
Famous, Katie R, Delucchi, Kevin, Ware, Lorraine B, Kangelaris, Kirsten N, Liu, Kathleen D, Thompson, B Taylor, and Calfee, Carolyn S
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Acute Respiratory Distress Syndrome ,Lung ,Clinical Trials and Supportive Activities ,Rare Diseases ,Clinical Research ,Good Health and Well Being ,Biomarkers ,Female ,Fluid Therapy ,Humans ,Logistic Models ,Male ,Outcome and Process Assessment ,Health Care ,Phenotype ,Positive-Pressure Respiration ,Randomized Controlled Trials as Topic ,Respiratory Distress Syndrome ,subphenotype ,acute lung injury ,fluid therapy ,ARDS Network ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
RationaleWe previously identified two acute respiratory distress syndrome (ARDS) subphenotypes in two separate randomized controlled trials with differential response to positive end-expiratory pressure.ObjectivesTo identify these subphenotypes in a third ARDS cohort, to test whether subphenotypes respond differently to fluid management strategy, and to develop a practical model for subphenotype identification.MethodsWe used latent class analysis of baseline clinical and plasma biomarker data to identify subphenotypes in FACTT (Fluid and Catheter Treatment Trial; n = 1,000). Logistic regression was used to test for an interaction between subphenotype and treatment for mortality. We used stepwise modeling to generate a model for subphenotype identification in FACTT and validated its accuracy in the two cohorts in which we previously identified ARDS subphenotypes.Measurements and main resultsWe confirmed that a two-class (two-subphenotype) model best described the study population. Subphenotype 2 was again characterized by higher inflammatory biomarkers and hypotension. Fluid management strategy had significantly different effects on 90-day mortality in the two subphenotypes (P = 0.0039 for interaction); mortality in subphenotype 1 was 26% with fluid-liberal strategy versus 18% with fluid-conservative, whereas mortality in subphenotype 2 was 40% with fluid-liberal strategy versus 50% in fluid-conservative. A three-variable model of IL-8, bicarbonate, and tumor necrosis factor receptor-1 accurately classified the subphenotypes.ConclusionsThis analysis confirms the presence of two ARDS subphenotypes that can be accurately identified with a limited number of variables and that responded differently to randomly assigned fluid management. These findings support the presence of ARDS subtypes that may require different treatment approaches.
- Published
- 2017
34. Design and Rationale of the Reevaluation of Systemic Early Neuromuscular Blockade Trial for Acute Respiratory Distress Syndrome.
- Author
-
Huang, David T, Angus, Derek C, Moss, Marc, Thompson, B Taylor, Ferguson, Niall D, Ginde, Adit, Gong, Michelle Ng, Gundel, Stephanie, Hayden, Douglas L, Hite, R Duncan, Hou, Peter C, Hough, Catherine L, Iwashyna, Theodore J, Liu, Kathleen D, Talmor, Daniel S, Yealy, Donald M, and Reevaluation of Systemic Early Neuromuscular Blockade Protocol Committee and the National Institutes of Health National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network Investigators
- Subjects
Reevaluation of Systemic Early Neuromuscular Blockade Protocol Committee and the National Institutes of Health National Heart ,Lung ,and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network Investigators ,Humans ,Respiratory Distress Syndrome ,Adult ,Atracurium ,Neuromuscular Blocking Agents ,Respiration ,Artificial ,Positive-Pressure Respiration ,Neuromuscular Blockade ,Mortality ,Cause of Death ,Feasibility Studies ,Mental Recall ,Muscle Strength ,adult ,clinical trial ,interdisciplinary communication ,methods ,respiratory distress syndrome ,Respiratory Distress Syndrome ,Rare Diseases ,Clinical Research ,Patient Safety ,Prevention ,Clinical Trials and Supportive Activities ,Lung ,Acute Respiratory Distress Syndrome ,Respiratory - Abstract
The Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial is a multicenter, randomized trial designed to assess the efficacy and safety of early neuromuscular blockade in patients with moderate to severe acute respiratory distress syndrome. This document provides background for interpretation of the trial results, and highlights unique design approaches that may inform future trials of acute illness. We describe the process by which ROSE was chosen as the inaugural trial of the multidisciplinary Prevention and Early Treatment of Acute Lung Injury Network, provide the trial methodology using the Consolidated Standards of Reporting Trials framework, and discuss key design challenges and their resolution. Four key design issues proved challenging-feasibility, choice of sedation depth in the control group, impact of emphasizing early treatment on enrollment criteria and protocol execution, and choice of positive end-expiratory pressure strategy. We used literature, an iterative consensus model, and internal surveys of current practice to inform design choice. ROSE will provide definitive, Consolidated Standards of Reporting Trials adherent data on early neuromuscular blockade for future patients with acute respiratory distress syndrome. Our multidisciplinary approach to trial design may be of use to other trials of acute illness. Clinical trial registered with www.clinicaltrials.gov (NCT02509078).
- Published
- 2017
35. Ventilator-induced Lung Injury
- Author
-
Beitler, Jeremy R, Malhotra, Atul, and Thompson, B Taylor
- Subjects
Acute Respiratory Distress Syndrome ,Patient Safety ,Rare Diseases ,Lung ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Respiratory ,Humans ,Lung Injury ,Respiratory Distress Syndrome ,Respiratory Mechanics ,Ventilator-Induced Lung Injury ,Ventilator-induced lung injury ,Acute lung injury ,Acute respiratory distress syndrome ,Mechanical ventilation ,Respiratory mechanics ,Clinical Sciences ,Respiratory System - Abstract
Prevention of ventilator-induced lung injury (VILI) can attenuate multiorgan failure and improve survival in at-risk patients. Clinically significant VILI occurs from volutrauma, barotrauma, atelectrauma, biotrauma, and shear strain. Differences in regional mechanics are important in VILI pathogenesis. Several interventions are available to protect against VILI. However, most patients at risk of lung injury do not develop VILI. VILI occurs most readily in patients with concomitant physiologic insults. VILI prevention strategies must balance risk of lung injury with untoward side effects from the preventive effort, and may be most effective when targeted to subsets of patients at increased risk.
- Published
- 2016
36. Plasma Concentrations of Soluble Suppression of Tumorigenicity-2 and Interleukin-6 Are Predictive of Successful Liberation From Mechanical Ventilation in Patients With the Acute Respiratory Distress Syndrome*
- Author
-
Alladina, Jehan W, Levy, Sean D, Hibbert, Kathryn A, Januzzi, James L, Harris, R Scott, Matthay, Michael A, Thompson, B Taylor, and Bajwa, Ednan K
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Lung ,Assistive Technology ,Bioengineering ,Clinical Research ,Respiratory ,Adult ,Airway Extubation ,Biomarkers ,Female ,Fluid Therapy ,Humans ,Interleukin-1 Receptor-Like 1 Protein ,Interleukin-6 ,Male ,Middle Aged ,Predictive Value of Tests ,Respiratory Distress Syndrome ,Ventilator Weaning ,acute respiratory distress syndrome ,biomarkers ,critical care ,interleukin-6 protein ,human ,mechanical ventilation ,mechanical ventilator weaning ,suppression of tumorigenicity-2 protein ,human ,National Heart ,Lung ,and Blood Institute Acute Respiratory Distress Syndrome Network ,Nursing ,Public Health and Health Services ,Emergency & Critical Care Medicine ,Clinical sciences - Abstract
ObjectivesSoluble suppression of tumorigenicity-2 and interleukin-6 concentrations have been associated with the inflammatory cascade of acute respiratory distress syndrome. We determined whether soluble suppression of tumorigenicity-2 and interleukin-6 levels can be used as prognostic biomarkers to guide weaning from mechanical ventilation and predict the need for reintubation.Design, setting, and patientsWe assayed plasma soluble suppression of tumorigenicity-2 (n = 826) concentrations and interleukin-6 (n = 755) concentrations in the Fluid and Catheter Treatment Trial, a multicenter randomized controlled trial of conservative fluid management in acute respiratory distress syndrome. We tested whether soluble suppression of tumorigenicity-2 and interleukin-6 levels were associated with duration of mechanical ventilation, the probability of passing a weaning assessment, and the need for reintubation.Measurements and main resultsIn models adjusted for Acute Physiology and Chronic Health Evaluation score and other relevant variables, patients with higher day 0 and day 3 median soluble suppression of tumorigenicity-2 and interleukin-6 concentrations had decreased probability of extubation over time (day 0 soluble suppression of tumorigenicity-2: hazard ratio, 0.85; 95% CI, 0.72-1.00; p = 0.05; day 0 interleukin-6: hazard ratio, 0.64; 95% CI, 0.54-0.75; p < 0.0001; day 3 soluble suppression of tumorigenicity-2: hazard ratio, 0.64; 95% CI, 0.54-0.75; p < 0.0001; and day 3 interleukin-6: hazard ratio, 0.73; 95% CI, 0.62-0.85; p = 0.0001). Higher biomarker concentrations were also predictive of decreased odds of passing day 3 weaning assessments (soluble suppression of tumorigenicity-2: odds ratio, 0.62: 95% CI, 0.44-0.87; p = 0.006 and interleukin-6: odds ratio, 0.61; 95% CI, 0.43-0.85; p = 0.004) and decreased odds of passing a spontaneous breathing trial (soluble suppression of tumorigenicity-2: odds ratio, 0.45; 95% CI, 0.28-0.71; p = 0.0007 and interleukin-6 univariate analysis only: odds ratio, 0.55; 95% CI, 0.36-0.83; p = 0.005). Finally, higher biomarker levels were significant predictors of the need for reintubation for soluble suppression of tumorigenicity-2 (odds ratio, 3.23; 95% CI, 1.04-10.07; p = 0.04) and for interleukin-6 (odds ratio, 2.58; 95% CI, 1.14-5.84; p = 0.02).ConclusionsHigher soluble suppression of tumorigenicity-2 and interleukin-6 concentrations are each associated with worse outcomes during weaning of mechanical ventilation and increased need for reintubation in patients with acute respiratory distress syndrome. Biomarker-directed ventilator management may lead to improved outcomes in weaning of mechanical ventilation in patients with acute respiratory distress syndrome.
- Published
- 2016
37. Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria
- Author
-
Beitler, Jeremy R, Sands, Scott A, Loring, Stephen H, Owens, Robert L, Malhotra, Atul, Spragg, Roger G, Matthay, Michael A, Thompson, B Taylor, and Talmor, Daniel
- Subjects
Paediatrics ,Biomedical and Clinical Sciences ,Lung ,Clinical Research ,Rare Diseases ,Acute Respiratory Distress Syndrome ,Respiratory ,Adult ,Aged ,Female ,Humans ,Inhalation ,Male ,Middle Aged ,Reference Values ,Respiration ,Artificial ,Respiratory Distress Syndrome ,Respiratory Function Tests ,Respiratory Rate ,Tidal Volume ,Ventilator-Induced Lung Injury ,Ventilators ,Mechanical ,Acute respiratory distress syndrome ,Acute lung injury ,Ventilator-induced lung injury ,Respiratory mechanics ,Mechanical ventilation ,Patient-ventilator dyssynchrony ,Patient–ventilator dyssynchrony ,Clinical Sciences ,Public Health and Health Services ,Emergency & Critical Care Medicine ,Clinical sciences - Abstract
PurposeBreath stacking dyssynchrony generates higher tidal volumes than intended, potentially increasing lung injury risk in acute respiratory distress syndrome (ARDS). Lack of validated criteria to quantify breath stacking dyssynchrony contributes to its under-recognition. This study evaluates performance of novel, objective criteria for quantifying breath stacking dyssynchrony (BREATHE criteria) compared to existing definitions and tests if neuromuscular blockade eliminates high-volume breath stacking dyssynchrony in ARDS.MethodsAirway flow and pressure were recorded continuously for up to 72 h in 33 patients with ARDS receiving volume-preset assist-control ventilation. The flow-time waveform was integrated to calculate tidal volume breath-by-breath. The BREATHE criteria considered five domains in evaluating for breath stacking dyssynchrony: ventilator cycling, interval expiratory volume, cumulative inspiratory volume, expiratory time, and inspiratory time.ResultsThe observed tidal volume of BREATHE stacked breaths was 11.3 (9.7-13.3) mL/kg predicted body weight, significantly higher than the preset volume [6.3 (6.0-6.8) mL/kg; p
- Published
- 2016
38. Individualized PEEP to optimise respiratory mechanics during abdominal surgery: a pilot randomised controlled trial
- Author
-
Fernandez-Bustamante, Ana, Sprung, Juraj, Parker, Robert A., Bartels, Karsten, Weingarten, Toby N., Kosour, Carolina, Thompson, B. Taylor, and Vidal Melo, Marcos F.
- Published
- 2020
- Full Text
- View/download PDF
39. Molecular Phenotypes of Acute Respiratory Distress Syndrome in the ROSE Trial Have Differential Outcomes and Gene Expression Patterns That Differ at Baseline and Longitudinally over Time.
- Author
-
Sinha, Pratik, Neyton, Lucile, Sarma, Aartik, Wu, Nelson, Jones, Chayse, Zhuo, Hanjing, Liu, Kathleen D., Sanchez Guerrero, Estella, Ghale, Rajani, Love, Christina, Mick, Eran, Delucchi, Kevin L., Langelier, Charles R., Thompson, B. Taylor, Matthay, Michael A., and Calfee, Carolyn S.
- Subjects
ADULT respiratory distress syndrome ,GENE expression ,PHENOTYPES ,BLOOD proteins ,TISSUE remodeling - Abstract
Rationale: Two molecular phenotypes have been identified in acute respiratory distress syndrome (ARDS). In the ROSE (Reevaluation of Systemic Early Neuromuscular Blockade) trial of cisatracurium in moderate to severe ARDS, we addressed three unanswered questions: 1) Do the same phenotypes emerge in a more severe ARDS cohort with earlier recruitment; 2) Do phenotypes respond differently to neuromuscular blockade? and 3) What biological pathways most differentiate inflammatory phenotypes? Methods: We performed latent class analysis in ROSE using preenrollment clinical and protein biomarkers. In a subset of patients (n = 134), we sequenced whole-blood RNA using enrollment and Day 2 samples and performed differential gene expression and pathway analyses. Informed by the differential gene expression analysis, we measured additional plasma proteins and evaluated their abundance relative to gene expression amounts. Measurements and Main Results: In ROSE, we identified the hypoinflammatory (60.4%) and hyperinflammatory (39.6%) phenotypes with similar biological and clinical characteristics as prior studies, including higher mortality at Day 90 for the hyperinflammatory phenotype (30.3% vs. 61.6%; P < 0.0001). We observed no treatment interaction between the phenotypes and randomized groups for mortality. The hyperinflammatory phenotype was enriched for genes associated with innate immune response, tissue remodeling, and zinc metabolism at Day 0 and collagen synthesis and neutrophil degranulation at Day 2. Longitudinal changes in gene expression patterns differed dependent on survivorship. For most highly expressed genes, we observed correlations with their corresponding plasma proteins' abundance. However, for the class-defining plasma proteins in the latent class analysis, no correlation was observed with their corresponding genes' expression. Conclusions: The hyperinflammatory and hypoinflammatory phenotypes have different clinical, protein, and dynamic transcriptional characteristics. These findings support the clinical and biological potential of molecular phenotypes to advance precision care in ARDS. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
40. Volume Delivered During Recruitment Maneuver Predicts Lung Stress in Acute Respiratory Distress Syndrome.
- Author
-
Beitler, Jeremy R, Majumdar, Rohit, Hubmayr, Rolf D, Malhotra, Atul, Thompson, B Taylor, Owens, Robert L, Loring, Stephen H, and Talmor, Daniel
- Subjects
Lung ,Humans ,Respiratory Distress Syndrome ,Adult ,Tidal Volume ,Positive-Pressure Respiration ,Predictive Value of Tests ,Middle Aged ,Female ,Male ,Stress ,Physiological ,Respiratory Distress Syndrome ,acute lung injury ,acute respiratory distress syndrome ,positive-pressure respiration ,respiratory mechanics ,ventilator-induced lung injury ,Adult ,Stress ,Physiological ,Emergency & Critical Care Medicine ,Clinical Sciences ,Nursing ,Public Health and Health Services - Abstract
ObjectiveGlobal lung stress varies considerably with low tidal volume ventilation for acute respiratory distress syndrome. High stress despite low tidal volumes may worsen lung injury and increase risk of death. No widely available parameter exists to assess global lung stress. We aimed to determine whether the volume delivered during a recruitment maneuver (V(RM)) is inversely associated with lung stress and mortality in acute respiratory distress syndrome.DesignSubstudy of an acute respiratory distress syndrome clinical trial on esophageal pressure-guided positive end-expiratory pressure titration.SettingU.S. academic medical center.PatientsForty-two patients with acute respiratory distress syndrome in whom airflow, airway pressure, and esophageal pressure were recorded during the recruitment maneuver.InterventionsA single recruitment maneuver was performed before initiating protocol-directed ventilator management. Recruitment maneuvers consisted of a 30-second breath hold at 40 cm H2O airway pressure under heavy sedation or paralysis. V(RM) was calculated by integrating the flow-time waveform during the maneuver. End-inspiratory stress was defined as the transpulmonary (airway minus esophageal) pressure during end-inspiratory pause of a tidal breath and tidal stress as the transpulmonary pressure difference between end-inspiratory and end-expiratory pauses.Measurements and main resultsV(RM) ranged between 7.4 and 34.7 mL/kg predicted body weight. Lower V(RM) predicted high end-inspiratory and tidal lung stress (end-inspiratory: β = -0.449; 95% CI, -0.664 to -0.234; p < 0.001; tidal: β = -0.267; 95% CI, -0.423 to -0.111; p = 0.001). After adjusting for PaO2/FIO2 and either driving pressure, tidal volume, or plateau pressure and positive end-expiratory pressure, V(RM) remained independently associated with both end-inspiratory and tidal stress. In unadjusted analysis, low V(RM) predicted increased risk of death (odds ratio, 0.85; 95% CI, 0.72-1.00; p = 0.026). V(RM) remained significantly associated with mortality after adjusting for study arm (odds ratio, 0.84; 95% CI, 0.71-1.00; p = 0.022).ConclusionsLow V(RM) independently predicts high lung stress and may predict risk of death in patients with acute respiratory distress syndrome.
- Published
- 2016
41. PROLONGED MECHANICAL VENTILATION IN ACUTE RESPIRATORY DISTRESS SYNDROME
- Author
-
Andrianopoulos, Ioannis, primary, Giannakoulis, Vassilis G., additional, Papoutsi, Eleni, additional, Papathanakos, Georgios, additional, Koulouras, Vasilios, additional, Thompson, B. Taylor, additional, and Siempos, Ilias I., additional
- Published
- 2023
- Full Text
- View/download PDF
42. Estimating Dead-Space Fraction for Secondary Analyses of Acute Respiratory Distress Syndrome Clinical Trials
- Author
-
Beitler, Jeremy R, Thompson, B Taylor, Matthay, Michael A, Talmor, Daniel, Liu, Kathleen D, Zhuo, Hanjing, Hayden, Douglas, Spragg, Roger G, and Malhotra, Atul
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Lung ,Clinical Research ,Respiratory ,Good Health and Well Being ,APACHE ,Adult ,Aged ,Female ,Humans ,Male ,Middle Aged ,Randomized Controlled Trials as Topic ,Reproducibility of Results ,Research Design ,Respiratory Dead Space ,Respiratory Distress Syndrome ,Respiratory Function Tests ,United States ,acute lung injury ,acute respiratory distress syndrome ,capnography ,clinical trials as topic ,respiratory dead space ,Nursing ,Public Health and Health Services ,Emergency & Critical Care Medicine ,Clinical sciences - Abstract
ObjectivesPulmonary dead-space fraction is one of few lung-specific independent predictors of mortality from acute respiratory distress syndrome. However, it is not measured routinely in clinical trials and thus altogether ignored in secondary analyses that shape future research directions and clinical practice. This study sought to validate an estimate of dead-space fraction for use in secondary analyses of clinical trials.DesignAnalysis of patient-level data pooled from acute respiratory distress syndrome clinical trials. Four approaches to estimate dead-space fraction were evaluated: three required estimating metabolic rate; one estimated dead-space fraction directly.SettingU.S. academic teaching hospitals.PatientsData from 210 patients across three clinical trials were used to compare performance of estimating equations with measured dead-space fraction. A second cohort of 3,135 patients from six clinical trials without measured dead-space fraction was used to confirm whether estimates independently predicted mortality.InterventionsNone.Measurements and main resultsDead-space fraction estimated using the unadjusted Harris-Benedict equation for energy expenditure was unbiased (mean ± SD Harris-Benedict, 0.59 ± 0.13; measured, 0.60 ± 0.12). This estimate predicted measured dead-space fraction to within ±0.10 in 70% of patients and ±0.20 in 95% of patients. Measured dead-space fraction independently predicted mortality (odds ratio, 1.36 per 0.05 increase in dead-space fraction; 95% CI, 1.10-1.68; p < 0.01). The Harris-Benedict estimate closely approximated this association with mortality in the same cohort (odds ratio, 1.55; 95% CI, 1.21-1.98; p < 0.01) and remained independently predictive of death in the larger Acute Respiratory Distress Syndrome Network cohort. Other estimates predicted measured dead-space fraction or its association with mortality less well.ConclusionsDead-space fraction should be measured in future acute respiratory distress syndrome clinical trials to facilitate incorporation into secondary analyses. For analyses where dead-space fraction was not measured, the Harris-Benedict estimate can be used to estimate dead-space fraction and adjust for its association with mortality.
- Published
- 2015
43. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial.
- Author
-
Wilson, Jennifer G, Liu, Kathleen D, Zhuo, Hanjing, Caballero, Lizette, McMillan, Melanie, Fang, Xiaohui, Cosgrove, Katherine, Vojnik, Rosemary, Calfee, Carolyn S, Lee, Jae-Woo, Rogers, Angela J, Levitt, Joseph, Wiener-Kronish, Jeanine, Bajwa, Ednan K, Leavitt, Andrew, McKenna, David, Thompson, B Taylor, and Matthay, Michael A
- Subjects
Humans ,Treatment Outcome ,Mesenchymal Stem Cell Transplantation ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Respiratory Distress Syndrome ,Clinical Research ,Regenerative Medicine ,Clinical Trials and Supportive Activities ,Rare Diseases ,Acute Respiratory Distress Syndrome ,Stem Cell Research ,Stem Cell Research - Nonembryonic - Human ,Lung ,Patient Safety ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Respiratory ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences - Abstract
BackgroundNo effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS.MethodsThe STem cells for ARDS Treatment (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial. Patients were enrolled in the intensive care units at University of California, San Francisco, CA, USA, Stanford University, Stanford, CA, USA, and Massachusetts General Hospital, Boston, MA, USA, between July 8, 2013, and Jan 13, 2014. Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube, a PaO2:FiO2 less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure (PEEP), and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph. The first three patients were treated with low dose MSCs (1 million cells/kg predicted bodyweight [PBW]), the next three patients received intermediate dose MSCs (5 million cells/kg PBW), and the final three patients received high dose MSCs (10 million cells/kg PBW). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with ClinicalTrials.gov, number NCT01775774.FindingsNo prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients. Serious adverse events were subsequently noted in three patients during the weeks after the infusion: one patient died on study day 9, one patient died on study day 31, and one patient was discovered to have multiple embolic infarcts of the spleen, kidneys, and brain that were age-indeterminate, but thought to have occurred before the MSC infusion based on MRI results. None of these severe adverse events were thought to be MSC-related.InterpretationA single intravenous infusion of allogeneic, bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS. Based on this phase 1 experience, we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory, systemic, and biological endpoints.FundingThe National Heart, Lung, and Blood Institute.
- Published
- 2015
44. Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome
- Author
-
Liu, Kathleen D, Wilson, Jennifer G, Zhuo, Hanjing, Caballero, Lizette, McMillan, Melanie L, Fang, Xiaohui, Cosgrove, Katherine, Calfee, Carolyn S, Lee, Jae-Woo, Kangelaris, Kirsten N, Gotts, Jeffrey E, Rogers, Angela J, Levitt, Joseph E, Wiener-Kronish, Jeanine P, Delucchi, Kevin L, Leavitt, Andrew D, McKenna, David H, Thompson, B Taylor, and Matthay, Michael A
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Rare Diseases ,Clinical Research ,Stem Cell Research - Nonembryonic - Human ,Clinical Trials and Supportive Activities ,Acute Respiratory Distress Syndrome ,Lung ,Biotechnology ,Transplantation ,Stem Cell Research ,Regenerative Medicine ,5.2 Cellular and gene therapies ,Development of treatments and therapeutic interventions ,Respiratory ,Acute lung injury ,Clinical trial ,Mesenchymal stem/stromal cell ,Pulmonary edema ,Public Health and Health Services ,Clinical sciences - Abstract
BackgroundDespite advances in supportive care, moderate-severe acute respiratory distress syndrome (ARDS) is associated with high mortality rates, and novel therapies to treat this condition are needed. Compelling pre-clinical data from mouse, rat, sheep and ex vivo perfused human lung models support the use of human mesenchymal stem (stromal) cells (MSCs) as a novel intravenous therapy for the early treatment of ARDS.MethodsThis article describes the study design and challenges encountered during the implementation and phase 1 component of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of bone marrow-derived human MSCs for moderate-severe ARDS. A trial enrolling 69 subjects is planned (9 subjects in phase 1, 60 subjects in phase 2 treated with MSCs or placebo in a 2:1 ratio).ResultsThis report describes study design features that are unique to a phase 1 trial in critically ill subjects and the specific challenges of implementation of a cell-based therapy trial in the ICU.ConclusionsExperience gained during the design and implementation of the START study will be useful to investigators planning future phase 1 clinical trials based in the ICU, as well as trials of cell-based therapy for other acute illnesses.Trial registrationClinical trials registrationNCT01775774 and NCT02097641.
- Published
- 2014
45. Prevalence and Impact of Active and Passive Cigarette Smoking in Acute Respiratory Distress Syndrome
- Author
-
Hsieh, S Jean, Zhuo, Hanjing, Benowitz, Neal L, Thompson, B Taylor, Liu, Kathleen D, Matthay, Michael A, and Calfee, Carolyn S
- Subjects
Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Clinical Research ,Tobacco Smoke and Health ,Rare Diseases ,Substance Misuse ,Tobacco ,Lung ,Acute Respiratory Distress Syndrome ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Cancer ,Cardiovascular ,Stroke ,Respiratory ,Good Health and Well Being ,APACHE ,Acute Lung Injury ,Adult ,Age Factors ,Aged ,Alcohol Drinking ,Comorbidity ,Female ,Health Status ,Humans ,Male ,Middle Aged ,Nitrosamines ,Prevalence ,Pyridines ,Respiratory Distress Syndrome ,Smoking ,Socioeconomic Factors ,Tobacco Smoke Pollution ,4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol ,acute respiratory distress syndrome ,cigarette smoking ,lung injury ,mortality ,National Heart ,Lung ,and Blood Institute Acute Respiratory Distress Syndrome Network ,National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Network ,Clinical Sciences ,Nursing ,Public Health and Health Services ,Emergency & Critical Care Medicine ,Clinical sciences - Abstract
ObjectivesCigarette smoke exposure has recently been found to be associated with increased susceptibility to trauma- and transfusion-associated acute respiratory distress syndrome. We sought to determine 1) the incidence of cigarette smoke exposure in a diverse multicenter sample of acute respiratory distress syndrome patients and 2) whether cigarette smoke exposure is associated with severity of lung injury and mortality in acute respiratory distress syndrome.DesignAnalysis of the Albuterol for the Treatment of Acute Lung Injury and Omega Acute Respiratory Distress Syndrome Network studies.SettingAcute Respiratory Distress Syndrome Network hospitals.PatientsThree hundred eighty-one patients with acute respiratory distress syndrome.InterventionsNone.Measurements and main results4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol, a validated tobacco-specific marker, was measured in urine samples from subjects enrolled in two National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network randomized controlled trials. Urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels were consistent with active smoking in 36% of acute respiratory distress syndrome patients and with passive smoking in 41% of nonsmokers (vs 20% and 40% in general population, respectively). Patients with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels in the active smoking range were younger and had a higher incidence of alcohol misuse, fewer comorbidities, lower severity of illness, and less septic shock at enrollment compared with patients with undetectable 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels. Despite this lower severity of illness, the severity of lung injury did not significantly differ based on biomarker-determined smoking status. Cigarette smoke exposure was not significantly associated with death after adjusting for differences in age, alcohol use, comorbidities, and severity of illness.ConclusionsIn this first multicenter study of biomarker-determined cigarette smoke exposure in acute respiratory distress syndrome patients, we found that active cigarette smoke exposure was significantly more prevalent among acute respiratory distress syndrome patients compared to population averages. Despite their younger age, better overall health, and lower severity of illness, smokers by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol had similar severity of lung injury as patients with undetectable 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. These findings suggest that active cigarette smoking may increase susceptibility to acute respiratory distress syndrome in younger, healthier patients.
- Published
- 2014
46. Sound and light levels in intensive care units in a large urban hospital in the United States
- Author
-
Leone, Michael J., Dashti, Hassan S., Coughlin, Brian, Tesh, Ryan A., Quadri, Syed A., Bucklin, Abigail A., Adra, Noor, Krishnamurthy, Parimala Velpula, Ye, Elissa M., Hemmige, Aashritha, Rajan, Subapriya, Panneerselvam, Ezhil, Higgins, Jasmine, Ayub, Muhammad Abubakar, Ganglberger, Wolfgang, Paixao, Luis, Houle, Timothy T., Thompson, B. Taylor, Johnson-Akeju, Oluwaseun, Saxena, Richa, Kimchi, Eyal, Cash, Sydney S., Thomas, Robert J., and Westover, M. Brandon
- Subjects
Physiology ,Physiology (medical) - Abstract
Intensive care units (ICUs) may disrupt sleep. Quantitative ICU studies of concurrent and continuous sound and light levels and timings remain sparse in part due to the lack of ICU equipment that monitors sound and light. Here, we describe sound and light levels across three adult ICUs in a large urban United States tertiary care hospital using a novel sensor. The novel sound and light sensor is composed of a Gravity Sound Level Meter for sound level measurements and an Adafruit TSL2561 digital luminosity sensor for light levels. Sound and light levels were continuously monitored in the room of 136 patients (mean age = 67.0 (8.7) years, 44.9% female) enrolled in the Investigation of Sleep in the Intensive Care Unit study (ICU-SLEEP; Clinicaltrials.gov: #NCT03355053), at the Massachusetts General Hospital. The hours of available sound and light data ranged from 24.0 to 72.2 hours. Average sound and light levels oscillated throughout the day and night. On average, the loudest hour was 17:00 and the quietest hour was 02:00. Average light levels were brightest at 09:00 and dimmest at 04:00. For all participants, average nightly sound levels exceeded the WHO guideline of < 35 decibels. Similarly, mean nightly light levels varied across participants (minimum: 1.00 lux, maximum: 577.05 lux). Sound and light events were more frequent between 08:00 and 20:00 than between 20:00 and 08:00 and were largely similar on weekdays and weekend days. Peaks in distinct alarm frequencies (Alarm 1) occurred at 01:00, 06:00, and at 20:00. Alarms at other frequencies (Alarm 2) were relatively consistent throughout the day and night, with a small peak at 20:00. In conclusion, we present a sound and light data collection method and results from a cohort of critically ill patients, demonstrating excess sound and light levels across multiple ICUs in a large tertiary care hospital in the United States. ClinicalTrials.gov, #NCT03355053. Registered 28 November 2017, https://clinicaltrials.gov/ct2/show/NCT03355053.
- Published
- 2023
47. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials
- Author
-
Calfee, Carolyn S, Delucchi, Kevin, Parsons, Polly E, Thompson, B Taylor, Ware, Lorraine B, Matthay, Michael A, and Network, the NHLBI ARDS
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Rare Diseases ,Lung ,Clinical Trials and Supportive Activities ,Acute Respiratory Distress Syndrome ,2.1 Biological and endogenous factors ,Aetiology ,Respiratory ,Good Health and Well Being ,APACHE ,Adult ,Aged ,Bicarbonates ,Biomarkers ,Female ,Humans ,Inflammation ,Inflammation Mediators ,Male ,Middle Aged ,Models ,Statistical ,Phenotype ,Respiration ,Artificial ,Respiratory Distress Syndrome ,Sepsis ,Time Factors ,Vasoconstrictor Agents ,NHLBI ARDS Network ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundSubphenotypes have been identified within heterogeneous diseases such as asthma and breast cancer, with important therapeutic implications. We assessed whether subphenotypes exist within acute respiratory distress syndrome (ARDS), another heterogeneous disorder.MethodsWe used data from two ARDS randomised controlled trials (ARMA trial and ALVEOLI trial), sponsored by the National Heart, Lung, and Blood Institute. We applied latent class modelling to identify subphenotypes using clinical and biological data. We modelled data from both studies independently. We then tested the association of subphenotypes with clinical outcomes in both cohorts and with the response to positive end-expiratory pressure (PEEP) in the ALVEOLI cohort.FindingsWe analysed data for 1022 patients: 473 in the ARMA cohort and 549 in the ALVEOLI cohort. Independent latent class models indicated that a two-class (ie, two subphenotype) model was the best fit for both cohorts. In both cohorts, we identified a hyperinflammatory subphenotype (phenotype 2) that was characterised by higher plasma concentrations of inflammatory biomarkers, a higher prevalence of vasopressor use, lower serum bicarbonate concentrations, and a higher prevalence of sepsis than phenotype 1. Participants in phenotype 2 had higher mortality and fewer ventilator-free days and organ failure-free days in both cohorts than did those in phenotype 1 (p
- Published
- 2014
48. Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome
- Author
-
Truwit, Jonathon D, Bernard, Gordon R, Steingrub, Jay, Matthay, Michael A, Liu, Kathleen D, Albertson, Timothy E, Brower, Roy G, Shanholtz, Carl, Rock, Peter, Douglas, Ivor S, deBoisblanc, Bennett P, Hough, Catherine L, Hite, R Duncan, and Thompson, B Taylor
- Subjects
Sepsis ,Lung ,Acute Respiratory Distress Syndrome ,Clinical Trials and Supportive Activities ,Patient Safety ,Infectious Diseases ,Rare Diseases ,Hematology ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Inflammatory and immune system ,Respiratory ,Infection ,Good Health and Well Being ,Adult ,Aged ,Creatine Kinase ,Double-Blind Method ,Female ,Fluorobenzenes ,Hospital Mortality ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Liver Failure ,Male ,Middle Aged ,Pyrimidines ,Renal Insufficiency ,Respiratory Distress Syndrome ,Rosuvastatin Calcium ,Sulfonamides ,Survival Analysis ,Treatment Failure ,National Heart ,Lung ,and Blood Institute ARDS Clinical Trials Network ,Medical and Health Sciences ,General & Internal Medicine - Abstract
BackgroundIn the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS.MethodsWe conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14.ResultsThe study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range.ConclusionsRosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.).
- Published
- 2014
49. Rosuvastatin for sepsis-associated acute respiratory distress syndrome.
- Author
-
National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, Truwit, Jonathon D, Bernard, Gordon R, Steingrub, Jay, Matthay, Michael A, Liu, Kathleen D, Albertson, Timothy E, Brower, Roy G, Shanholtz, Carl, Rock, Peter, Douglas, Ivor S, deBoisblanc, Bennett P, Hough, Catherine L, Hite, R Duncan, and Thompson, B Taylor
- Subjects
National Heart ,Lung ,and Blood Institute ARDS Clinical Trials Network ,Humans ,Sepsis ,Liver Failure ,Respiratory Distress Syndrome ,Adult ,Sulfonamides ,Fluorobenzenes ,Pyrimidines ,Creatine Kinase ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Treatment Failure ,Hospital Mortality ,Survival Analysis ,Double-Blind Method ,Adult ,Aged ,Middle Aged ,Female ,Male ,Renal Insufficiency ,Rosuvastatin Calcium ,Respiratory Distress Syndrome ,National Heart ,Lung ,and Blood Institute ARDS Clinical Trials Network ,General & Internal Medicine ,Medical and Health Sciences - Abstract
BackgroundIn the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS.MethodsWe conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14.ResultsThe study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range.ConclusionsRosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.).
- Published
- 2014
50. A New Global Definition of Acute Respiratory Distress Syndrome
- Author
-
Matthay, Michael A., primary, Arabi, Yaseen, additional, Arroliga, Alejandro C, additional, Bernard, Gordon, additional, Bersten, Andrew D, additional, Brochard, Laurent J., additional, Calfee, Carolyn S, additional, Combes, Alain, additional, Daniel, Brian M, additional, Ferguson, Niall D, additional, Gong, Michelle N, additional, Gotts, Jeffrey E, additional, Herridge, Margaret S., additional, Laffey, John G., additional, Liu, Kathleen D, additional, Machado, Flavia R, additional, Martin, Thomas R., additional, McAuley, Danny F., additional, Mercat, Alain, additional, Moss, Marc, additional, Mularski, Richard A, additional, Pesenti, Antonio, additional, Qiu, Haibo, additional, Ramakrishnan, Nagarajan, additional, Ranieri, V. Marco, additional, Riviello, Elisabeth D., additional, Rubin, Eileen, additional, Slutsky, Arthur S., additional, Thompson, B. Taylor, additional, Twagirumugabe, Theogene, additional, Ware, Lorraine B, additional, and Wick, Katherine D., additional
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.