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1. Modulation of the Association Between Age and Death by Risk Factor Burden in Critically Ill Patients With COVID-19

Author

Ashwin Sunderraj, BS, Chloe Cho, Xuan Cai, MS, Shruti Gupta, MD, MPH, Rupal Mehta, MD, MSCI, Tamara Isakova, MD, MMSc, David E. Leaf, MD, MMSc, Anand Srivastava, MD, MPH, STOP-COVID Investigators, Carl P. Walther, Samaya J. Anumudu, Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, Thuy-Duyen Nguyen, Shahzad Shaefi, Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, Juan D. Valencia, Sushrut S. Waikar, Zoe A. Kibbelaar, Ambarish M. Athavale, Peter Hart, Shristi Upadhyay, Ishaan Vohra, Ajiboye Oyintayo, Adam Green, Jean-Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Christopher L. Mosher, Alexandre M. Shehata, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino Williams, Samantha K. Brenner, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Miguel A. Hernán, Amy M. Zhou, Ethan C. Kim, Rebecca Lisk, Lili Chan, Kusum S. Mathews, Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Girish N. Nadkarni, Pattharawin Pattharanitima, Emily J. Gallagher, Allon N. Friedman, John Guirguis, Rajat Kapoor, Christopher Meshberger, Katherine J. Kelly, Chirag R. Parikh, Brian T. Garibaldi, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Carmen Elena Cervantes, Samir C. Gautam, Mary C. Mallappallil, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddhartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, Leon Boudourakis, H. Bryant Nguyen, Afshin Ahoubim, Leslie F. Thomas, Dheeraj Reddy Sirganagari, Pramod K. Guru, Kianoush Kashani, Shahrzad Tehranian, Yan Zhou, Paul A. Bergl, Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G. Lazarous, Seble G. Kassaye, Michal L. Melamed, Tanya S. Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Neelja Kumar, Michael Chang, Jyotsana Thakkar, Ritesh Raichoudhury, Akshay Athreya, Mohamed Farag, Edward J. Schenck, Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Ashley Macina, Sobaata Chaudhry, Benjamin Wu, Frank Modersitzki, Anand Srivastava, Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alexander J. Hodakowski, Juan Carlos Q. Velez, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, Muner MB. Mohamed, Rupali S. Avasare, David Zonies, David E. Leaf, Shruti Gupta, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Wei Wang, Heather Yang, Jeffery O. Boateng, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Ariel L. Mueller, Roberta E. Redfern, Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Chris Rowan, Farah Madhani-Lovely, Vivian S. Cruz, Kristen M. Hess, Alanna L. Jacobs, Vasil Peev, Jochen Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, Joy-Marie Hermes, Anne K. Sutherland, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Peter Cangialosi, Mark Liotta, Jared Radbel, Sonika Puri, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Jayanth S. Vatson, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui Song, Jingjing Zhang, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Katharine Senter, Moh’d A. Sharshir, Vadym V. Rusnak, Muhammad Imran Ali, Anip Bansal, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen L. Burnham, David J. Douin, Arash Rashidi, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E. Albertson, Jason Y. Adams, Steven Y. Chang, Rebecca M. Beutler, Carl E. Schulze, Etienne Macedo, Harin Rhee, Kathleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Chintan V. Shah, Vishal Jaikaransingh, Stephanie M. Toth-Manikowski, Min J. Joo, James P. Lash, Javier A. Neyra, Nourhan Chaaban, Madona Elias, Yahya Ahmad, Alfredo Iardino, Elizabeth H. Au, Jill H. Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Hayley B. Gershengorn, Bhavarth Shukla, Alessia Fornoni, Tanira Ferreira, Salim S. Hayek, Pennelope Blakely, Hanna Berlin, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’ Hayer, Chelsea Meloche, Rafey Feroze, Rayan Kaakati, Danny Perry, Abbas Bitar, Elizabeth Anderson, Kishan J. Padalia, John P. Donnelly, Andrew J. Admon, Jennifer E. Flythe, Matthew J. Tugman, Emily H. Chang, Brent R. Brown, Amanda K. Leonberg-Yoo, Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, Charles R. Vasquez, Amar D. Bansal, Natalie C. Ernecoff, Sanjana Kapoor, Siddharth Verma, Huiwen Chen, Csaba P. Kovesdy, Miklos Z. Molnar, Ambreen Azhar, S. Susan Hedayati, Mridula V. Nadamuni, Shani Shastri, Duwayne L. Willett, Samuel A.P. Short, Amanda D. Renaghan, Kyle B. Enfield, Pavan K. Bhatraju, A. Bilal Malik, Matthew W. Semler, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Nitender Goyal, Anthony J. Faugno, Caroline M. Hsu, Asma Tariq, Leah Meyer, Ravi K. Kshirsagar, Daniel E. Weiner, Aju Jose, Marta Christov, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Perry Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN:. Multicenter cohort study. SETTING:. ICUs at 68 hospitals across the United States. PATIENTS:. A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity

Published
2022
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2. Performance of crisis standards of care guidelines in a cohort of critically ill COVID-19 patients in the United States

Author

Julia L. Jezmir, Maheetha Bharadwaj, Alexander Chaitoff, Bradford Diephuis, Conor P. Crowley, Sandeep P. Kishore, Eric Goralnick, Louis T. Merriam, Aimee Milliken, Chanu Rhee, Nicholas Sadovnikoff, Sejal B. Shah, Shruti Gupta, David E. Leaf, William B. Feldman, Edy Y. Kim, Carl P. Walther, Samaya J. Anumudu, Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, Thuy-Duyen Nguyen, Shahzad Shaefi, Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, Juan D. Valencia, Sushrut S. Waikar, Zoe A. Kibbelaar, Ambarish M. Athavale, Peter Hart, Shristi Upadhyay, Ishaan Vohra, Ajiboye Oyintayo, Adam Green, Jean-Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Christopher L. Mosher, Alexandre M. Shehata, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino Williams, Samantha K. Brenner, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Miguel A. Hernán, Amy M. Zhou, Ethan C. Kim, Rebecca Lisk, Lili Chan, Kusum S. Mathews, Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Girish N. Nadkarni, Pattharawin Pattharanitima, Allon N. Friedman, John Guirguis, Rajat Kapoor, Christopher Meshberger, Katherine J. Kelly, Chirag R. Parikh, Brian T. Garibaldi, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Elena Cervantes, Samir Gautam, Mary C. Mallappallil, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, Leon Boudourakis, H. Bryant Nguyen, Afshin Ahoubim, Leslie F. Thomas, Dheeraj Reddy Sirganagari, Pramod K. Guru, Kianoush Kashani, Yan Zhou, Paul A. Bergl, Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G. Lazarous, Seble G. Kassaye, Michal L. Melamed, Tanya S. Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Neelja Kumar, Michael Chang, Ritesh Raichoudhury, Akshay Athreya, Mohamed Farag, Edward J. Schenck, Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Ashley Macina, Sobaata Chaudhry, Benjamin Wu, Frank Modersitzki, Anand Srivastava, Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alexander J. Hodakowski, Juan Carlos Q. Velez, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, Muner MB. Mohamed, Rupali S. Avasare, David Zonies, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Wei Wang, Heather Yang, Jeffery O. Boateng, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Ariel L. Mueller, Roberta Redfern, Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Chris Rowan, Farah Madhani-Lovely, Vivian S. Cruz, Kristen M. Hess, Alanna L. Jacobs, Vasil Peev, Jochen Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, Joy-Marie Hermes, Anne K. Sutherland, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Peter Cangialosi, Mark Liotta, Jared Radbel, Sonika Puri, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Jayanth S. Vatson, Shuchi Anand, Joseph E. Levitt, Suzanne M. Boyle, Rui Song, Jingjing Zhang, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Katharine Senter, Moh’d A. Sharshir, Vadym V. Rusnak, Muhammad Imran Ali, Anip Bansal, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen L. Burnham, Arash Rashidi, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E. Albertson, Jason Y. Adams, Steven Y. Chang, Rebecca M. Beutler, Etienne Macedo, Harin Rhee, Kathleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Chintan V. Shah, Vishal Jaikaransingh, Stephanie M. Toth-Manikowski, Min J. Joo, James P. Lash, Javier A. Neyra, Nourhan Chaaban, Madona Elias, Yahya Ahmad, Alfredo Iardino, Elizabeth H. Au, Jill H. Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Hayley B. Gershengorn, Bhavarth Shukla, Alessia Fornoni, Tanira Ferreira, Salim S. Hayek, Pennelope Blakely, Hanna Berlin, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’ Hayer, Chelsea Meloche, Rafey Feroze, Rayan Kaakati, Danny Perry, Abbas Bitar, Elizabeth Anderson, Kishan J. Padalia, John P. Donnelly, Andrew J. Admon, Jennifer E. Flythe, Matthew J. Tugman, Emily H. Chang, Brent R. Brown, Amanda K. Leonberg-Yoo, Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, Charles R. Vasquez, Amar D. Bansal, Natalie C. Ernecoff, Sanjana Kapoor, Siddharth Verma, Csaba P. Kovesdy, Miklos Z. Molnar, Ambreen Azhar, S. Susan Hedayati, Mridula V. Nadamuni, Shani Shastri, Duwayne L. Willett, Samuel A.P. Short, Amanda D. Renaghan, Kyle B. Enfield, Pavan K. Bhatraju, A. Bilal Malik, Matthew W. Semler, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Nitender Goyal, Anthony J. Faugno, Caroline M. Hsu, Asma Tariq, Leah Meyer, Ravi K. Kshirsagar, Daniel E. Weiner, Aju Jose, Marta Christov, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Perry Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
medical ethics, crisis standards of care, triage, critical care, intensive care, COVID-19, Medicine (General), R5-920
Abstract

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Published
2021
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3. Machine Learning Prediction of Death in Critically Ill Patients With Coronavirus Disease 2019

Author

Matthew M. Churpek, MD, MPH, PhD, Shruti Gupta, MD, MPH, Alexandra B. Spicer, MS, Salim S. Hayek, MD, Anand Srivastava, MD, MPH, Lili Chan, MD, MSCR, Michal L. Melamed, MD, MHS, Samantha K. Brenner, MD, MPH, Jared Radbel, MD, Farah Madhani-Lovely, MD, Pavan K. Bhatraju, MD, MSc, Anip Bansal, MD, Adam Green, MD, MBA, Nitender Goyal, MD, Shahzad Shaefi, MD, MPH, Chirag R. Parikh, MD, PhD, Matthew W. Semler, MD, David E. Leaf, MD, MMSc, Carl P. Walther, Samaya J. Anumudu, Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, ThuyDuyen Nguyen, Shahzad Shaefi, Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, Juan D. Valencia, Sushrut S. Waikar, Zoe A. Kibbelaar, Ambarish M. Athavale, Peter Hart, Oyintayo Ajiboye, Matthew Itteera, Adam Green, Jean-Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Christopher L. Mosher, Alexandre M. Shehata, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Metha, Aquino Williams, Samantha K. Brenner, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Miguel A. Hernán, Amy M. Zhou, Ethan C. Kim, Rebecca Lisk, Lili Chan, Kusum S. Mathews, Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily Leven, Jing G. Wang, Gohar Mosoyan, Girish N. Nadkarni, Allon N. Friedman, John Guirguis, Rajat Kapoor, Christopher Meshberger, Chirag R. Parikh, Brian T. Garibaldi, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Carmen Elena Cervantes, Samir C. Gautam, Crystal Chang, H. Bryant Nguyen, Afshin Ahoubim, Leslie F. Thomas, Pramod K. Guru, Paul A. Bergl, Yan Zhou, Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G. Lazarous, Seble G. Kassaye, Michal L. Melamed, Tanya S. Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Jyotsana Thakkar, Neelja Kumar, Michael J. Ross, Michael Chang, Ritesh Raichoudhury, Edward J. Schenck, Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Ashley Macina, Daniel W. Ross, Anand Srivastava, Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alexander J. Hodakowski, Juan Carlos Q. Velez, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, Muner MB. Mohamed, Rupali S. Avasare, David Zonies, David E. Leaf, Shruti Gupta, Rebecca M. Baron, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa Gaviria, Tanveer Shaukat, Omer Kamal, Wei Wang, Heather Yang, Jeffery O. Boateng, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Saif A. Muhsin, Ernest I. Mandel, Ariel L. Mueller, Nicholas S. Cairl, Farah Madhani-Lovely, Chris Rowan, Farah Madhai-Lovely, Vasil Peev, Jochen Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, Joy-Marie Hermes, Anne K. Sutherland, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Jared Radbel, Sonika Puri, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Jayanth Vatson, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui Song, Jingjing Zhang, Moh’d A. Sharshir, Vadym V. Rusnak, Anip Bansal, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen L. Burnham, Arash Rashidi, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E. Albertson, Jason Y. Adams, Steven Y. Chang, Rebecca M. Beutler, Carl E. Schulze, Etienne Macedo, Harin Rhee, Kathleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Chintan V. Shah, Vishal Jaikaransingh, Stephanie M. Toth-Manikowski, Min J. Joo, James P. Lash, Javier A. Neyra, Nourhan Chaaban, Alfredo Iardino, Elizabeth H. Au, Jill H. Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Hayley B. Gershengorn, Salim S. Hayek, Pennelope Blakely, Hanna Berlin, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’ Hayer, Chelsea Meloche, Rafey Feroze, Kishan J. Padalia, Jeff Leya, John P. Donnelly, Andrew J. Admon, Jennifer E. Flythe, Matthew J. Tugman, Brent R. Brown, Amanda K. Leonberg-Yoo, Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, Charles R. Vasquez, Amar D. Bansal, Natalie C. Ernecoff, Csaba P. Kovesdy, Miklos Z. Molnar, S. Susan Hedayati, Mridula V. Nadamuni, Sadaf S. Khan, Duwayne L. Willett, Samuel A.P. Short, Amanda D. Renaghan, Pavan Bhatraju, A. Bilal Malik, Matthew W. Semler, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Nitender Goyal, Anthony J. Faugno, Caroline M. Hsu, Asma Tariq, Leah Meyer, Marta Christov, Francis P. Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. Critically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019. DESIGN:. This was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration. SETTING:. Sixty-eight U.S. ICUs. PATIENTS:. Adults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao2/Fio2 ratio were the most important predictors in the eXtreme Gradient Boosting model. CONCLUSIONS:. eXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.

Published
2021
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4. Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19

Author

Kusum S. Mathews, Giampolo Greco, Gohar Mosoyan, Ilana Bass, Aparna Saha, Lili Chan, Jing Gennie Wang, Pattharawin Pattharanitima, Huei Hsun Wen, Sonali Bose, Howard Soh, Deena R. Altman, Emily J. Gallagher, Alon Yehuda Mazori, and Emily Leven

Subjects
Research design, Blood Glucose, medicine.medical_specialty, Critical Illness, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Article, Procalcitonin, End stage renal disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, law, Internal medicine, Diabetes mellitus, medicine, Humans, Hospital Mortality, 030212 general & internal medicine, Interleukin 6, Retrospective Studies, diabetes, biology, SARS-CoV-2, business.industry, Hazard ratio, C-reactive protein, COVID-19, Retrospective cohort study, General Medicine, medicine.disease, Diabetes Mellitus and Glucose Metabolism, mortality, Intensive care unit, Intensive Care Units, COVID-19 and Diabetes, Cohort, biology.protein, Population study, hyperglycemia, business, AcademicSubjects/MED00250
Abstract

Objective To explore the relationship between hyperglycemia in the presence and absence of diabetes mellitus (DM) and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19). Methods The study population comprised 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an academic, urban, quaternary-care center between March 10 and April 8, 2020. Patients were categorized based on the presence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first two days of ICU admission. The primary outcome was 14-day, all-cause, in-hospital mortality; also examined were 60-day, all-cause, in-hospital mortality and the levels of C-reactive protein (CRP), interleukin 6, procalcitonin, and lactate. Results Compared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HR) for mortality at 14 days (HR 7.51, confidence interval [CI] 1.70-33.24) and 60 days (HR 6.97, CI 1.86-26.13). Non-DM patients with EHG also featured higher levels of median CRP (306.3 mg/L, p=0.036), procalcitonin (1.26 ng/mL, p=0.028), and lactate (2.2 mmol/L, p=0.023). Conclusion In patients with critical illness from COVID-19, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. The limitations of our study include its retrospective design and relatively small cohort. However, our results suggest that the combination of elevated glucose and lactate may identify a specific cohort of individuals at high mortality risk from COVID-19, and suggest that glucose testing and control are important in individuals with COVID-19, even in those without pre-existing diabetes., Highlights • Hyperglycemic non-diabetic ICU patients with COVID-19 had increased mortality • Inflammatory markers were higher in patients with hyperglycemia without diabetes • Hyperglycemia with elevated lactate was a predictor of higher mortality • Glucocorticoid use within 48 hours of ICU stay did not impact mortality

Published
2021
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5. Kidney Recovery and Death in Critically Ill Patients With COVID-19-Associated Acute Kidney Injury Treated With Dialysis: The STOP-COVID Cohort Study

Author

Caroline M. Hsu, Shruti Gupta, Hocine Tighiouart, Nitender Goyal, Anthony J. Faugno, Asma Tariq, Ritesh Raichoudhury, Jill H. Sharma, Leah Meyer, Ravi K. Kshirsagar, Aju Jose, David E. Leaf, Daniel E. Weiner, Hsu Gupta, Goyal Faugno, Tariq Raichoudhury, Sharma Meyer, Kshirsagar Leaf, Carl P. Walther, Samaya J. Anumudu, Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, Thuy-Duyen Nguyen, Shahzad Shaefi, Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, Juan D. Valencia, Kenneth A. Bauer, Sushrut S. Waikar, Zoe A. Kibbelaar, Ambarish M. Athavale, Peter Hart, Shristi Upadhyay, Ishaan Vohra, Ajiboye Oyintayo, Adam Green, Jean-Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Christopher L. Mosher, Alexandre M. Shehata, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino WilliamsSamantha K. Brenner, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Miguel A. Hernán, Amy M. Zhou, Ethan C. Kim, Rebecca Lisk, Lili Chan, Kusum S. Mathews, Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Pattharawin Pattharanitima, Emily J. Gallagher, Allon N. Friedman, John Guirguis, Rajat Kapoor, Christopher Meshberger, Katherine J. Kelly, Chirag R. Parikh, Brian T. Garibaldi, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Carmen Elena Cervantes, Samir C. Gautam, Mary C. Mallappallil, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddhartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, Leon Boudourakis, H. Bryant Nguyen, Afshin Ahoubim, Leslie F. Thomas, Dheeraj Reddy Sirganagari, Pramod K. Guru, Kianoush Kashani, Shahrzad Tehranian, Yan Zhou, Paul A. Bergl, Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G. Lazarous, Seble G. Kassaye, Michal L. Melamed, Tanya S. Johns. Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Jyotsana Thakkar, Neelja Kumar, Michael J. Ross, Michael Chang, Akshay Athreya, Mohamed Farag, Edward J. Schenck, Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Ashley Macina, Anand Srivastava, Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alexander J. Hodakowski, Juan Carlos Q. Velez, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, Muner M.B. Mohamed, Rupali S. Avasare, David Zonies, Hanny Al-Samkari, Rebecca Karp Leaf, Rachel Rosovsky, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Wei Wang, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Ariel L. Mueller, Roberta E. Redfern, Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Chris Rowan, Farah Madhani-Lovely, Vasil Peev, Jochen Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, Joy-Marie Hermes, Anne K. Sutherland, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Peter Cangialosi, Mark Liotta, Jared Radbel, Sonika Puri, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Jayanth S. Vatson, George Karp, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui Song, Jingjing Zhang, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Moh’d A. Sharshir, Vadym V. Rusnak, Anip Bansal, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen L. Burnham, Arash Rashidi, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E. Albertson, Jason Y. Adams, Steven Y. Chang, Rebecca M. Beutler, Carl E. Schulze, Etienne Macedo, Harin RheeKa, null thleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Chintan V. Shah, Vishal Jaikaransingh, Stephanie M. Toth-Manikowski, Min J. Joo, James P. Lash, Javier A. Neyra, Nourhan Chaaban, Madona Elias, Yahya Ahmad, Rajany Dy, Alfredo Iardino, Elizabeth H. Au, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Hayley B. Gershengorn, Alessia Fornoni, Salim S. Hayek, Pennelope Blakely, Hanna Berlin, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’Hayer, Chelsea Meloche, Rafey Feroze, Kishan J. Padalia, Jeff Leya, John P. Donnelly, Andrew J. Admon, Jennifer E. Flythe, Matthew J. Tugman, Emily H. Chang, Brent R. Brown, Amanda K. Leonberg-Yoo, Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, Charles R. Vasquez, Amar D. Bansal, Natalie C. Ernecoff, Sanjana Kapoor, Siddharth Verma, Huiwen Chen, Csaba P. Kovesdy, Miklos Z. Molnar, Ambreen Azhar, S. Susan Hedayati, Mridula V. Nadamuni, Shani Shastri, Duwayne L. Willett, Samuel A.P. Short, Amanda D. Renaghan, Kyle B. Enfield, Pavan K. Bhatraju, A. Bilal Malik, Matthew W. Semler, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Marta Christov, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Savneek Chugh, Perry Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
Adult, urogenital system, SARS-CoV-2, Critical Illness, Aftercare, COVID-19, Original Investigations, Acute Kidney Injury, urologic and male genital diseases, Kidney, Patient Discharge, Cohort Studies, critical care, Intensive Care Units, Nephrology, Renal Dialysis, Risk Factors, urine output, Humans, dialysis, chronic kidney disease, Retrospective Studies
Abstract

Rationale & Objective Acute kidney injury treated with kidney replacement therapy (AKI-KRT) occurs frequently in critically ill patients with COVID-19. We examined the clinical factors that determine kidney recovery in this population. Study Design Multicenter cohort study. Setting & Participants 4221 adults with COVID-19 not receiving kidney replacement therapy who were admitted to intensive care units at 68 US hospitals with COVID-19 from March 1 to June 22, 2020 (the “ICU cohort”). Among these, 876 developed AKI-KRT after admission to the ICU (the “AKI-KRT subcohort”). Exposure(s) The ICU cohort was analyzed using AKI severity as the exposure. For the AKI-KRT subcohort, exposures included demographics, comorbidities, initial mode of KRT, and markers of illness severity at the time of dialysis initiation. Outcome(s) The outcome for the ICU cohort was estimated glomerular filtration rate (GFR) at hospital discharge. A three-level outcome including death, kidney nonrecovery, and kidney recovery at discharge, was analyzed for the AKI-KRT subcohort. Analytical approach The ICU cohort was characterized using descriptive analyses. The AKI-KRT subcohort was characterized with both descriptive analyses and multinomial logistic regression to assess factors associated with kidney nonrecovery while accounting for death. Results Among a total of 4221 patients in the ICU cohort, 2361 (56%) developed AKI, including 876 (21%) who received KRT. More severe AKI was associated with higher mortality. Among survivors, more severe AKI was associated with an increased rate of kidney nonrecovery and lower kidney function at discharge. Among the 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) had kidney nonrecovery, and 193 (22%) had kidney recovery by the time of discharge. The odds of kidney nonrecovery was greater for lower estimated GFR with odds ratios (ORs) of 2.09 (95% CI, 1.09-4.04), 4.27 (95% CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for CKD GFR categories 3, 4, and 5, respectively, compared to estimated GFR > 60 mL/min/1.73 m2. Oliguria at the time of KRT initiation was also associated with nonrecovery (OR 2.10 [95% CI, 1.14-3.88] and 4.02 [95% CI, 1.72-9.39] for patients with 50-499 and, Critically ill patients with COVID-19 often develop acute kidney injury (AKI). This study of 4221 patients demonstrated that more severe AKI was associated with greater in-hospital mortality and poorer kidney function at hospital discharge. Among the 876 patients who required dialysis for AKI, almost two-thirds died. Among those who survived to discharge, about two-thirds recovered kidney function and were discharged without the need for dialysis. Lower baseline kidney function and reduced urine output were associated with non-recovery of kidney function. Identification of such predictors is important in assessing prognosis among these critically ill patients and has implications for clinical care of individuals critically ill with COVID-19.

Published
2021

6. Hospital-Level Variation in Death for Critically Ill Patients with COVID-19

Author

Matthew M. Churpek, Shruti Gupta, Alexandra B. Spicer, William F. Parker, John Fahrenbach, Samantha K. Brenner, David E. Leaf, Carl P. Walther, Samaya J. Anumudu, Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, Thuy-Duyen Nguyen, Shahzad Shaefi, Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, Juan D. Valencia, Sushrut S. Waikar, Zoe A. Kibbelaar, Ambarish M. Athavale, Peter Hart, Shristi Upadhyay, Ishaan Vohra, Adam Green, Jean-Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Christopher L. Mosher, Alexandre M. Shehata, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino Williams, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Miguel A. Hernán, Lili Chan, Kusum S. Mathews, Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Girish N. Nadkarni, Pattharawin Pattharanitima, Emily J. Gallagher, Allon N. Friedman, John Guirguis, Rajat Kapoor, Christopher Meshberger, Katherine J. Kelly, Chirag R. Parikh, Brian T. Garibaldi, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Elena Cervantes, Samir Gautam, Mary C. Mallappallil, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, Leon Boudourakis, H. Bryant Nguyen, Afshin Ahoubim, Leslie F. Thomas, Dheeraj Reddy Sirganagari, Pramod K. Guru, Kianoush Kashani, Shahrzad Tehranian, Yan Zhou, Paul A. Bergl, Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G. Lazarous, Seble G. Kassaye, Michal L. Melamed, Tanya S. Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Neelja Kumar, Michael Chang, Jyotsana Thakkar, Ritesh Raichoudhury, Akshay Athreya, Mohamed Farag, Edward J. Schenck, Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Ashley Macina, Sobaata Chaudhry, Benjamin Wu, Frank Modersitzki, Anand Srivastava, Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alexander J. Hodakowski, Juan Carlos Q. Velez, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, Muner M. B. Mohamed, Rupali S. Avasare, David Zonies, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Wei Wang, Heather Yang, Jeffery O. Boateng, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Ariel L. Mueller, Roberta Redfern, Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Chris Rowan, Farah Madhai-Lovely, Vasil Peev, Jochen Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, Joy-Marie Hermes, Anne K. Sutherland, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Peter Cangialosi, Mark Liotta, Jared Radbel, Jag Sunderram, Sonika Puri, Jayanth S. Vatson, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui Song, Ali Arif, Jingjing Zhang, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Katharine Senter, Moh’d A. Sharshir, Vadym V. Rusnak, Muhammad Imran Ali, Terri Peters, Kathy Hughes, Anip Bansal, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen L. Burnham, Arash Rashidi, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E. Albertson, Jason Y. Adams, Steven Y. Chang, Rebecca M. Beutler, Santa Monica, Carl E. Schulze, Etienne Macedo, Harin Rhee, Kathleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Chintan V. Shah, Vishal Jaikaransingh, Stephanie M. Toth-Manikowski, Min J. Joo, James P. Lash, Javier A. Neyra, Nourhan Chaaban, Alfredo Iardino, Elizabeth H. Au, Jill H. Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Alessia Fornoni, Hayley B. Gershengorn, Salim S. Hayek, Pennelope Blakely, Hanna Berlin, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’Hayer, Chelsea Meloche, Rafey Feroze, Rayan Kaakati, Danny Perry, Abbas Bitar, Elizabeth Anderson, Kishan J. Padalia, Christopher Launius, John P. Donnelly, Andrew J. Admon, Jennifer E. Flythe, Matthew J. Tugman, Emily H. Chang, Brent R. Brown, Amanda K. Leonberg-Yoo, Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, Charles R. Vasquez, Amar D. Bansal, Natalie C. Ernecoff, Sanjana Kapoor, Siddharth Verma, Huiwen Chen, Csaba P. Kovesdy, Miklos Z. Molnar, Ambreen Azhar, S. Susan Hedayati, Mridula V. Nadamuni, Shani Shastri, Duwayne L. Willett, Samuel A. P. Short, Amanda D. Renaghan, Kyle B. Enfield, Pavan K. Bhatraju, A. Bilal Malik, Matthew W. Semler, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Nitender Goyal, Anthony J. Faugno, Caroline M. Hsu, Asma Tariq, Leah Meyer, Ravi K. Kshirsagar, Daniel E. Weiner, Marta Christov, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Perry Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, genetic structures, Coronavirus disease 2019 (COVID-19), Critical Illness, Disease, Comorbidity, Critical Care and Intensive Care Medicine, medicine.disease_cause, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Risk Factors, medicine, Humans, 030212 general & internal medicine, Hospital Mortality, Coronavirus, Aged, Retrospective Studies, Critically ill, business.industry, SARS-CoV-2, Incidence, Editorials, COVID-19, Hospital level, Middle Aged, Prognosis, Intensive care unit, Health equity, United States, Survival Rate, Intensive Care Units, Variation (linguistics), 030228 respiratory system, Emergency medicine, Female, business, Algorithms, Follow-Up Studies
Abstract

Variation in hospital mortality has been described for coronavirus disease 2019 (COVID-19), but the factors that explain these differences remain unclear.Our objective was to utilize a large, nationally representative dataset of critically ill adults with COVID-19 to determine which factors explain mortality variability.In this multicenter cohort study, we examined adults hospitalized in intensive care units with COVID-19 at 70 United States hospitals between March and June 2020. The primary outcome was 28-day mortality. We examined patient-level and hospital-level variables. Mixed-effects logistic regression was used to identify factors associated with interhospital variation. The median odds ratio (OR) was calculated to compare outcomes in higher- vs. lower-mortality hospitals. A gradient boosted machine algorithm was developed for individual-level mortality models.A total of 4,019 patients were included, 1537 (38%) of whom died by 28 days. Mortality varied considerably across hospitals (0-82%). After adjustment for patient- and hospital-level domains, interhospital variation was attenuated (OR decline from 2.06 [95% CI, 1.73-2.37] to 1.22 [95% CI, 1.00-1.38]), with the greatest changes occurring with adjustment for acute physiology, socioeconomic status, and strain. For individual patients, the relative contribution of each domain to mortality risk was: acute physiology (49%), demographics and comorbidities (20%), socioeconomic status (12%), strain (9%), hospital quality (8%), and treatments (3%).There is considerable interhospital variation in mortality for critically ill patients with COVID-19, which is mostly explained by hospital-level socioeconomic status, strain, and acute physiologic differences. Individual mortality is driven mostly by patient-level factors. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Published
2021

7. Performance of crisis standards of care guidelines in a cohort of critically ill COVID-19 patients in the United States

Author

Huei Hsun Wen, Vishal Jaikaransingh, Ernie Yap, Matthew T. Scharf, Jiahua Li, Samir Gautam, Jeffery O. Boateng, John Guirguis, Timothy E. Albertson, Shuchi Anand, Kathleen D. Liu, Amar D. Bansal, Alessia Fornoni, Caroline M. Hsu, Simon Correa, Natalie C. Ernecoff, Chris Rowan, William Feldman, Rupali S. Avasare, Maureen Brogan, Etienne Macedo, Nourhan Chaaban, Sabrina Taldone, Ryan Mocerino, Nilam P. Patel, Christopher Meshberger, Muner Mb. Mohamed, Joy-Marie Hermes, Ritesh Raichoudhury, Jamuna Krishnan, Amy M. Zhou, Abbas Bitar, Danny Perry, Barbara A. Danek, Allon N. Friedman, Salim S. Hayek, Richard G. Wunderink, Duwayne L. Willett, Moh’d A. Sharshir, Luis G. Gomez-Escobar, Wei Wang, Nicholas S. Cairl, Lisa Shea, Miguel A. Hernán, Christa A. Schorr, Rubab F. Malik, Patricia F. Kao, John Wagner, Patrick O’ Hayer, Sonika Puri, Shreyak Sharma, Mariah Thaxton, Seble G. Kassaye, Sidharth Shankar, Paul A. Bergl, Hayley B. Gershengorn, Sanjeev Gupta, Ibrahim Mohamed, Sushrut S. Waikar, Dheeraj Reddy Sirganagari, Jill H. Sharma, Gohar Mosoyan, Kyle B. Enfield, Ian A. Strohbehn, Thuy-Duyen Nguyen, Suzanne M. Boyle, Brent Brown, Rebecca V. Levy, Vasantha K. Jotwani, Alexandre M. Shehata, Maria Plataki, Julia L. Jezmir, Valerie Allusson, Jennifer Griffiths, Chirag R. Parikh, Alfredo Iardino, Emily H. Chang, Sanjana Kapoor, Tanira Ferreira, Harin Rhee, Nicholas Sadovnikoff, Aquino Williams, Vivian S. Cruz, Jay L. Koyner, Kristen M. Hess, Leon Boudourakis, Shahzad Shaefi, Vasil Peev, Omer Kamal, Ugochukwu Ugwuowo, Aromma Kapoor, Anitha Vijayan, Jared Radbel, Husam Shadid, Vadym V. Rusnak, Pattharawin Pattharanitima, Aju Jose, Yohannes Adama Melaku, Jayanth S. Vatson, Tariq U. Azam, Yahya Ahmad, William Whalen, Meghan Lee, Shani Shastri, David De La Zerda, Goni Katz-Greenberg, Hanna Berlin, Todd A. Miano, Seth Goldberg, Jatan A. Shah, Frank Modersitzki, Jag Sunderram, Anna E. Hasty, Esha M. Kapania, Samantha K. Brenner, Pennelope K. Blakely, Elizabeth H. Au, Ronaldo C. Go, Keith M. Rose, Anand Srivastava, Kathleen F. Kopecky, Ilya Berim, Alexander Chaitoff, Danyell Hall, Jingjing Zhang, Michel Chonchol, Gabriel Naimy, Sejal B. Shah, Stephanie M. Toth-Manikowski, Christina Mariyam Joy, Deepa G. Lazarous, Matthew W. Semler, Mark Liotta, Mridula V. Nadamuni, Greg L. Schumaker, Patricia Walters, Joseph E. Levitt, Steven G. Coca, Rana Hejal, Stefi Lee, Pramod Guru, Noor ul aain Bhatti, Jennifer E. Flythe, Daniel L. Edmonston, Asma Tariq, John J. Byun, Jesus Rodriguez, Mrigank S. Gupta, Andrew Vissing, Michal L. Melamed, Howard Soh, Adam E. Green, Yorg Azzi, Ladan Golestaneh, Amee Patrawalla, Amber S. Podoll, Ryan C. Spiardi, Xiaoying Deng, Ishaan Vohra, Carl P. Walther, Michael Chang, John P. Donnelly, David M. Charytan, Anthony J. Faugno, Peter Hart, Ameeka Pannu, Sandeep P. Kishore, Roberta E. Redfern, Ambreen Azhar, Meghan E. Sise, Di Pan, Sang Hoon Woo, H. Bryant Nguyen, Pavan K. Bhatraju, Bradford Diephuis, Justin Arunthamakun, Kaltrina Sedaliu, Ajiboye Oyintayo, Aimee Milliken, Andrew J Admon, Elena Cervantes, Erik T. Newman, Heather Yang, Lili Chan, Nitender Goyal, Peter Cangialosi, Arash Rashidi, David Zonies, Juan D. Valencia, Rebecca Lisk, Zoe Post, Farah Madhani-Lovely, Benjamin M. Wu, Princy N. Kumar, Ethan C. Kim, Maheetha Bharadwaj, Chintan V. Shah, A. Bilal Malik, Siddartha Bajracharya, Gabriela Bambrick-Santoyo, Conor P. Crowley, Ellen L. Burnham, Kianoush Kashani, Ashley Macina, Diana Finkel, Rebecca M. Beutler, Sowminya Arikapudi, Ayesha Ahmed, Edward J. Schenck, Kishan Padalia, Aparna Saha, Alexander J. Hodakowski, Tanya S. Johns, Rayan Kaakati, James P. Lash, Bhavarth Shukla, Mary Mallappallil, Eboni G. Price-Haywood, Steven Menez, Samaya J. Anumudu, Christopher L. Mosher, Rajat Kapoor, Harkarandeep Singh, Amanda K. Leonberg-Yoo, Rui Song, Samah Abu Omar, Laura Latta, Siddharth Verma, Steven Y. Chang, Soo Jung Cho, Emily Leven, Denzel Zhu, Jing G. Wang, Katharine Senter, Bijal Mehta, Ariel Mueller, Peter A. McCullough, Alexander S. Leidner, Milagros Yunes, Akshay Athreya, Carlos Martinez, Muhammad Imran Ali, Matthew J. Tugman, Laura Bickley, Perry Wilson, Chanu Rhee, Ambarish M. Athavale, Shruti Gupta, Samuel A.P. Short, S. Susan Hedayati, Neelja Kumar, Abeer Abu-Saif, Jeffrey M. Paer, Sobaata Chaudhry, Louis T. Merriam, Jochen Reiser, Gabriel Contreras, Eric Judd, Isha Puri, Marta Christov, Afshin Ahoubim, Leslie F. Thomas, Tanima Arora, Eric Goralnick, Elizabeth Anderson, Csaba P. Kovesdy, Alanna L. Jacobs, Marie Anne Sosa, Ashita Tolwani, Ravi K. Kshirsagar, Jason Y. Adams, Tingting Li, Javier A. Neyra, Deena R. Altman, Anip Bansal, Katherine J. Kelly, Sunita Sharma, Jean-Sebastien Rachoin, Zoe A. Kibbelaar, Celia P. Corona-Villalobos, Juan Carlos Q. Velez, Tanveer Shaukat, Leah Meyer, Kalyan Prudhvi, Edy Y. Kim, Madona Elias, Brian T. Garibaldi, Miklos Z. Molnar, Megan L. Krajewski, Sabu John, Girish N. Nadkarni, Molly Fisher, Michael Pan, Zaza Cohen, Min J. Joo, Yumeng Wen, Kapil K. Pokharel, Kusum S. Mathews, Shristi Upadhyay, Charles R. Vasquez, Amanda DeMauro Renaghan, Sergio L. Alvarez-Mulett, Rafey Feroze, Jacqueline M. Kruser, Daniel E. Weiner, Anne Sutherland, Jie Ouyang, Mohamed Farag, Gregory P. Milligan, Meaghan S. Roche, Luis A. Matute-Trochez, Chelsea Meloche, Yan Zhou, Jyotsna Bhattacharya, Sonali Bose, and David E. Leaf

Subjects
Adult, Male, Medicine (General), medicine.medical_specialty, Exacerbation, Critical Care, Organ Dysfunction Scores, Critical Illness, Population, Comorbidity, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, R5-920, Intensive care, medicine, Humans, Hospital Mortality, Intensive care medicine, education, Pandemics, intensive care, Aged, Retrospective Studies, education.field_of_study, crisis standards of care, Receiver operating characteristic, business.industry, SARS-CoV-2, Crew Resource Management, Healthcare, COVID-19, Standard of Care, Middle Aged, medicine.disease, Triage, United States, medical ethics, Cohort, Practice Guidelines as Topic, SOFA score, Female, triage, business, Algorithms
Abstract

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Published
2021

8. Prone Positioning and Survival in Mechanically Ventilated Patients With Coronavirus Disease 2019-Related Respiratory Failure

Author

Kusum S, Mathews, Howard, Soh, Shahzad, Shaefi, Wei, Wang, Sonali, Bose, Steven, Coca, Shruti, Gupta, Salim S, Hayek, Anand, Srivastava, Samantha K, Brenner, Jared, Radbel, Adam, Green, Anne, Sutherland, Amanda, Leonberg-Yoo, Alexandre, Shehata, Edward J, Schenck, Samuel A P, Short, Miguel A, Hernán, Lili, Chan, David E, Leaf, and Ugochukwu, Ugwuowo

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Critical Care and Intensive Care Medicine, medicine.disease_cause, Patient Positioning, Time-to-Treatment, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Severity of illness, Prone Position, Medicine, Humans, Hospital Mortality, Hypoxia, Survival analysis, Coronavirus, Aged, Mechanical ventilation, business.industry, Proportional hazards model, SARS-CoV-2, Hazard ratio, COVID-19, 030208 emergency & critical care medicine, Middle Aged, Respiration, Artificial, Survival Analysis, United States, Intensive Care Units, 030228 respiratory system, Respiratory failure, Emergency medicine, Female, business, Respiratory Insufficiency, Cohort study
Abstract

Objectives Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019-associated respiratory failure. Design Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of PaO2 over the corresponding FIO2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability-weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up. Setting ICUs at 68 U.S. sites. Patients Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of PaO2 over the corresponding FIO2 less than or equal to 200 mm Hg. Interventions None. Measurements and main results Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73-0.97). Conclusions In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.

Published
2021

9. Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States

Author

Jennifer E. Flythe, Magdalene M. Assimon, Matthew J. Tugman, Emily H. Chang, Shruti Gupta, Jatan Shah, Marie Anne Sosa, Amanda DeMauro Renaghan, Michal L. Melamed, F. Perry Wilson, Javier A. Neyra, Arash Rashidi, Suzanne M. Boyle, Shuchi Anand, Marta Christov, Leslie F. Thomas, Daniel Edmonston, David E. Leaf, Carl P. Walther, Samaya J. Anumudu, Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, Thuy-Duyen Nguyen, Shahzad Shaefi, Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, Juan D. Valencia, Sushrut S. Waikar, Zoe A. Kibbelaar, Ambarish M. Athavale, Peter Hart, Shristi Upadhyay, Ishaan Vohra, Adam Green, Jean-Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Christopher L. Mosher, Alexandre M. Shehata, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino Williams, Samantha K. Brenner, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Lili Chan, Kusum S. Mathews, Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Girish N. Nadkarni, Pattharawin Pattharanitima, Emily J. Gallagher, Allon N. Friedman, John Guirguis, Rajat Kapoor, Christopher Meshberger, Katherine J. Kelly, Chirag R. Parikh, Brian T. Garibaldi, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Carmen Elena Cervantes, Samir C. Gautam, Mary C. Mallappallil, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddhartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, Leon Boudourakis, H. Bryant Nguyen, Afshin Ahoubim, Kianoush Kashani, Shahrzad Tehranian, Dheeraj Reddy Sirganagari, Pramod K. Guru, Yan Zhou, Paul A. Bergl, Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G. Lazarous, Seble G. Kassaye, Tanya S. Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Neelja Kumar, Michael Chang, Jyotsana Thakkar, Ritesh Raichoudhury, Akshay Athreya, Mohamed Farag, Edward J. Schenck, Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Ashley Macina, Sobaata Chaudhry, Benjamin Wu, Frank Modersitzki, Anand Srivastava, Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alexander J. Hodakowski, Juan Carlos Q. Velez, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, Muner M.B. Mohamed, Rupali S. Avasare, David Zonies, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Wei Wang, Heather Yang, Jeffery O. Boateng, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Ariel L. Mueller, Roberta Redfern, Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Chris Rowan, Farah Madhani-Lovely, Vasil Peev, Jochen Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, Joy-Marie Hermes, Anne K. Sutherland, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Peter Cangialosi, Mark Liotta, Jared Radbel, Sonika Puri, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Jayanth S. Vatson, Joseph E. Levitt, Pablo Garcia, Rui Song, Jingjing Zhang, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Katharine Senter, Moh’d A. Sharshir, Vadym V. Rusnak, Muhammad Imran Ali, Anip Bansal, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen L. Burnham, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E. Albertson, Jason Y. Adams, Ronald Reagan, Steven Y. Chang, Rebecca M. Beutler, Santa Monica, Carl E. Schulze, Etienne Macedo, Harin Rhee, Kathleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Alissa Kunczt, Chintan V. Shah, Vishal Jaikaransingh, Stephanie M. Toth-Manikowski, Min J. Joo, James P. Lash, Nourhan Chaaban, Rajany Dy, Alfredo Iardino, Elizabeth H. Au, Jill H. Sharma, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Hayley B. Gershengorn, Salim S. Hayek, Pennelope Blakely, Hanna Berlin, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’ Hayer, Chelsea Meloche, Rafey Feroze, Rayan Kaakati, Danny Perry, Abbas Bitar, Elizabeth Anderson, Kishan J. Padalia, John P. Donnelly, Andrew J. Admon, Brent R. Brown, Amanda K. Leonberg-Yoo, Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, Charles R. Vasquez, Amar D. Bansal, Natalie C. Ernecoff, Sanjana Kapoor, Siddharth Verma, Huiwen Chen, Csaba P. Kovesdy, Miklos Z. Molnar, Ambreen Azhar, S. Susan Hedayati, Mridula V. Nadamuni, Shani Shastri, Duwayne L. Willett, Samuel A.P. Short, Amanda D. Renaghan, Kyle B. Enfield, Pavan K. Bhatraju, A. Bilal Malik, Matthew W. Semler, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Nitender Goyal, Anthony J. Faugno, Caroline M. Hsu, Asma Tariq, Leah Meyer, Ravi K. Kshirsagar, Daniel E. Weiner, Aju Jose, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Perry Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
medicine.medical_specialty, 030232 urology & nephrology, Renal function, Original Investigations, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Intensive care, medicine, critical illness, 030212 general & internal medicine, Survival analysis, Kidney, business.industry, SARS-CoV-2, Confounding, COVID-19, Retrospective cohort study, medicine.disease, medicine.anatomical_structure, Respiratory failure, Nephrology, end stage kidney disease, dialysis, business, chronic kidney disease, Kidney disease
Abstract

Rationale & Objective Underlying kidney disease is an emerging risk factor for more severe COVID-19 illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing kidney disease and investigated the association between degree of underlying kidney disease and in-hospital outcomes. Study Design Retrospective cohort study Settings & Participants 4,264 critically ill COVID-19 patients (143 dialysis patients, 521 chronic kidney disease [CKD] patients, and 3,600 patients without CKD) admitted to ICUs at 68 hospitals in the United States. Predictor(s) Presence (versus absence) of pre-existing kidney disease Outcome(s) In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/ cardiac arrest, thromboembolic event, major bleed, and acute liver injury (secondary) Analytical Approach We used standardized differences to compare patient characteristics (values >0.10 indicate a meaningful difference between groups) and multivariable adjusted Fine and Gray survival models to examine outcome associations. Results Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median [quartile 1-quartile 3] days: 4 [2-9] for dialysis patients; 7 [3-10] for CKD patients; 7 [4-10] for patients without pre-existing kidney disease). More dialysis patients (25%) reported altered mental status than those with CKD (20%, standardized difference = 0.12) and no kidney disease (12%, standardized difference = 0.36). Half of dialysis and CKD patients died within 28-days of ICU admission versus 35% of patients without pre-existing kidney disease. Compared to patients without pre-existing kidney disease, dialysis patients had a higher risk of 28-day in-hospital death (adjusted HR 1.41; 95% CI 1.09, 1.81), while patients with CKD had an intermediate risk (adjusted HR 1.25; 95% CI 1.08, 1.44). Limitations Potential residual confounding Conclusions Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies for this vulnerable population., Individuals with underlying kidney disease may be particularly vulnerable to severe COVID-19 illness, marked by multi-system organ failure, thrombosis, and a heightened inflammatory response. Among 4,264 critically ill adults with COVID-19 admitted to 68 intensive care units across the U.S., we found that both chronic kidney disease and dialysis patients had a ∼50% 28-day in-hospital mortality rate. Patients with underlying kidney disease had higher in-hospital mortality than patients without kidney disease, with patients on maintenance dialysis having the highest risk. As evidenced by differences in symptoms and clinical trajectories, patients with pre-existing kidney disease may have unique susceptibility to COVID-19-related complications which warrants additional study and special consideration in the pursuit and development of targeted therapies.

Published
2021
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10. Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19

Author

Hanny Al-Samkari, Shruti Gupta, Rebecca Karp Leaf, Wei Wang, Rachel P. Rosovsky, Samantha K. Brenner, Salim S. Hayek, Hanna Berlin, Rajat Kapoor, Shahzad Shaefi, Michal L. Melamed, Anne Sutherland, Jared Radbel, Adam Green, Brian T. Garibaldi, Anand Srivastava, Amanda Leonberg-Yoo, Alexandre M. Shehata, Jennifer E. Flythe, Arash Rashidi, Nitender Goyal, Lili Chan, Kusum S. Mathews, S. Susan Hedayati, Rajany Dy, Stephanie M. Toth-Manikowski, Jingjing Zhang, Mary Mallappallil, Roberta E. Redfern, Amar D. Bansal, Samuel A.P. Short, Mark G. Vangel, Andrew J. Admon, Matthew W. Semler, Kenneth A. Bauer, Miguel A. Hernán, David E. Leaf, Carl P. Walther, Samaya J. Anumudu, Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, Thuy-Duyen Nguyen, Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, Juan D. Valencia, Sushrut S. Waikar, Zoe A. Kibbelaar, Ambarish M. Athavale, Peter Hart, Shristi Upadhyay, Ishaan Vohra, Ajiboye Oyintayo, Jean-Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Christopher L. Mosher, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino Williams, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Amy M. Zhou, Ethan C. Kim, Rebecca Lisk, Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Pattharawin Pattharanitima, Emily J. Gallagher, Allon N. Friedman, John Guirguis, Christopher Meshberger, Katherine J. Kelly, Chirag R. Parikh, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Carmen Elena Cervantes, Samir C. Gautam, Mary C. Mallappallil, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddhartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, Leon Boudourakis, H. Bryant Nguyen, Afshin Ahoubim, Leslie F. Thomas, Dheeraj Reddy Sirganagari, Pramod K. Guru, Yan Zhou, Paul A. Bergl, Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G. Lazarous, Seble G. Kassaye, Tanya S. Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Jyotsana Thakkar, Neelja Kumar, Michael J. Ross, Michael Chang, Ritesh Raichoudhury, Akshay Athreya, Mohamed Farag, Edward J. Schenck, Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Ashley Macina, Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alexander J. Hodakowski, Juan Carlos Q. Velez, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, Muner M.B. Mohamed, Rupali S. Avasare, David Zonies, Rachel Rosovsky, Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Ariel L. Mueller, Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, Laura Bickley, Chris Rowan, Farah Madhani-Lovely, Vasil Peev, Jochen Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, Joy-Marie Hermes, Anne K. Sutherland, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Peter Cangialosi, Mark Liotta, Sonika Puri, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Jayanth S. Vatson, George Karp, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui Song, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Moh'd A. Sharshir, Vadym V. Rusnak, Muhammad Imran Ali, Anip Bansal, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen L. Burnham, Rana Hejal, Eric Judd, Laura Latta, Ashita Tolwani, Timothy E. Albertson, Jason Y. Adams, Steven Y. Chang, Rebecca M. Beutler, Carl E. Schulze, Etienne Macedo, Harin Rhee, Kathleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Chintan V. Shah, Vishal Jaikaransingh, Min J. Joo, James P. Lash, Javier A. Neyra, Nourhan Chaaban, Madona Elias, Yahya Ahmad, Alfredo Iardino, Elizabeth H. Au, Jill H. Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Hayley B. Gershengorn, Alessia Fornoni, Pennelope Blakely, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’Hayer, Chelsea Meloche, Rafey Feroze, Kishan J. Padalia, Jeff Leya, John P. Donnelly, Matthew J. Tugman, Emily H. Chang, Brent R. Brown, Amanda K. Leonberg-Yoo, Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, Charles R. Vasquez, Natalie C. Ernecoff, Sanjana Kapoor, Siddharth Verma, Huiwen Chen, Csaba P. Kovesdy, Miklos Z. Molnar, Ambreen Azhar, Mridula V. Nadamuni, Shani Shastri, Duwayne L. Willett, Amanda D. Renaghan, Kyle B. Enfield, Pavan K. Bhatraju, A. Bilal Malik, Anitha Vijayan, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Anthony J. Faugno, Caroline M. Hsu, Asma Tariq, Leah Meyer, Ravi K. Kshirsagar, Daniel E. Weiner, Marta Christov, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Savneek Chugh, Perry Wilson, Tanima Arora, and Ugochukwu Ugwuowo

Subjects
Male, medicine.medical_specialty, Critical Illness, Hemorrhage, 01 natural sciences, law.invention, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, law, Internal Medicine, medicine, Humans, 030212 general & internal medicine, 0101 mathematics, Survival rate, Original Research, Aged, Proportional hazards model, business.industry, SARS-CoV-2, Incidence (epidemiology), 010102 general mathematics, Hazard ratio, Anticoagulants, COVID-19, General Medicine, Venous Thromboembolism, Blood Coagulation Disorders, Middle Aged, Intensive care unit, United States, Survival Rate, Intensive Care Units, Emergency medicine, Observational study, Female, business, Cohort study
Abstract

Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival. Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. Setting: 67 hospitals in the United States. Participants: Adults with COVID-19 admitted to a participating ICU. Measurements: Time to death, censored at hospital discharge, or date of last follow-up. Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). Limitation: Observational design. Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. Primary Funding Source: None.

Published
2021

11. Cue weighting for speech categorization changes based on regularities in short‐term speech input

Author

Lori L. Holt, Ran Liu, and Howard Soh

Subjects
Statistical regularity, Speech perception, Acoustics and Ultrasonics, Speech recognition, Term (time), Weighting, Arts and Humanities (miscellaneous), Categorization, Duration (music), Vowel, otorhinolaryngologic diseases, Set (psychology), Psychology, psychological phenomena and processes
Abstract

The ability to flexibly adapt long‐term speech category representations to informative regularities in short‐term input is critical for on‐line speech perception. The present experiment investigates how short‐term changes in the variability of two distinct acoustic cues affect the relative weighting of the cues for speech categorization. Native English adults distinguish the vowel categories /ae/ and /E/ using both spectral and duration cues. A spectral continuum from /ae/ to /E/ was crossed with a duration continuum between the same vowels to synthesize a 2‐D grid of words ranging between “set” and “sat.” Baseline categorization data were collected from trials sampling the full grid of words; for each trial, listeners selected whether they heard set or sat. Then, they received short‐term exposure to trials drawn only from subsets of stimuli for which one cue was held constant while the other cue exhibited the full range of variability. Results reveal that listeners shift their relative cue weights, compared to baseline, to rely more on the highly variable cue for categorization. This suggests that listeners track the variability present across multiple acoustic cues and dynamically adjust speech categorization to reflect this short‐term statistical regularity. [Work supported by NIH and NSF.]

Published
2011
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