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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. A Comprehensive Review of Computational Methods for Automatic Prediction of Schizophrenia With Insight Into Indigenous Populations

Author

Randall Ratana, Hamid Sharifzadeh, Jamuna Krishnan, and Shaoning Pang

Subjects
psychosis, schizophrenia, computational methods, language dysfunction, culture, Psychiatry, RC435-571
Abstract

Psychiatrists rely on language and speech behavior as one of the main clues in psychiatric diagnosis. Descriptive psychopathology and phenomenology form the basis of a common language used by psychiatrists to describe abnormal mental states. This conventional technique of clinical observation informed early studies on disturbances of thought form, speech, and language observed in psychosis and schizophrenia. These findings resulted in language models that were used as tools in psychosis research that concerned itself with the links between formal thought disorder and language disturbances observed in schizophrenia. The end result was the development of clinical rating scales measuring severity of disturbances in speech, language, and thought form. However, these linguistic measures do not fully capture the richness of human discourse and are time-consuming and subjective when measured against psychometric rating scales. These linguistic measures have not considered the influence of culture on psychopathology. With recent advances in computational sciences, we have seen a re-emergence of novel research using computing methods to analyze free speech for improving prediction and diagnosis of psychosis. Current studies on automated speech analysis examining for semantic incoherence are carried out based on natural language processing and acoustic analysis, which, in some studies, have been combined with machine learning approaches for classification and prediction purposes.

Published
2019
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5. 3055 Reconstruction of Patient-specific Distal Airway Regeneration Patterns in COPD

Author

Seyed Babak Mahjour, Kazunori Gomi, Samir Rustam, Phurbu Dolma, Jamuna Krishnan, Olivier Elemento, Frank D’Ovidio, Timothy S. Blackwell, Scott Randell, and Renat Shaykhiev

Subjects
Medicine
Abstract

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to reconstruct patient-specific distal airway patterns at the tissue- and single-cell resolution and develop personalized distal airway models based on utilization of patient-derived DABCs and autologous region-specific stromal cells. METHODS/STUDY POPULATION: Patient-specific distal airway units, containing parental small bronchiole (12th generation) and daughter airway branches, including pre-terminal/terminal bronchioles, leading to alveoli (3-7 units/lung), were dissected. Epithelial and stromal cells were isolated from these units and processed for ddSeq single-cell RNA-sequencing (n=6 samples). Autologous DABCs and stromal cells were isolated, propagated, biobanked, and used for establishment of patient-specific distal airway models (3D-organoids and air-liquid interface-based airway wall model; n=10 samples). Region-specific tissue patterns were evaluated using immunofluorescence and laser-capture microdissection (LCM; n=6 samples). RESULTS/ANTICIPATED RESULTS: Single-cell-based human distal airway transcriptome map (constructed based on the analysis of >6,500 distal airway cells obtained from 6 subjects) identified physiological and COPD-relevant distal airway differentiation patterns, including distal airway-specific secretory phenotype (DASP) characterized with high expression of secretoglobins 3A2 and 3A1, surfactant proteins SFTPB and SFTPA2, and mucin 1, unique signatures of DABCs, and stromal (fibroblasts, smooth muscle, endothelial cell subpopulations) and immune (macrophage, T cells, B cell, mast cells). Immunofluorescence analysis and LCM confirmed distribution of cell type-specific markers with differential expression patterns of DABC and DASP signatures. Patient-derived DABC-stromal co-culture models reproduced 3 regenerative patterns: 1) physiological (high DABC-clonogenic potency, establishment of polarized differentiated organoids and DASP-expressing epithelia); 2) hypo-regenerative (failure of DABCs to form clones, spheres and mechanically stable differentiated epithelial barrier); and 3) hyperplastic (generation of DABC hyperplasia accompanied in some COPD samples by mucous-cell hyperplasia mimicking in vivo remodeling patterns). DISCUSSION/SIGNIFICANCE OF IMPACT: Patient-specific maps and models of distal airway regeneration patterns have been established in this study, which can be used to identify candidate pathways that mediate disease-relevant airway remodeling and potentially utilized as pre-clinical platforms for developing personalized therapeutic approaches to suppress the progression of distal airway remodeling in chronic lung diseases, including COPD.

Published
2019
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6. FEASIBILITY OF REAL-TIME COMBINED PATIENT AND PROVIDER TEACHING TO IMPROVE GUIDELINE-DIRECTED THERAPY IN COPD EXACERBATION

Author

Jamuna Krishnan, Xian Wu, Meredith Turetz, Mark A. Sonnick, Maya Viavant, Lorenzo Bean, Jessica Snead, and Maria Spinelli

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Copd exacerbation, business.industry, medicine, Guideline, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine, Intensive care medicine, business
Published
2020
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7. IMPACT Trial: Triple Versus Dual Therapy for COPD Results in Decreased Rate of Exacerbations

Author

Dana Zappetti and Jamuna Krishnan

Subjects
Pulmonary and Respiratory Medicine, COPD, medicine.medical_specialty, business.industry, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, 030212 general & internal medicine, Dual therapy, business
Published
2018
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9. Fluticasone Furoate-Vilanterol Decreases COPD Exacerbations in a Pragmatic Trial

Author

Dana Zappetti and Jamuna Krishnan

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, business.industry, Critical Care and Intensive Care Medicine, medicine.disease, Pragmatic trial, Fluticasone furoate/vilanterol, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, medicine, 030212 general & internal medicine, business
Published
2017
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