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1. Crowd-sourced machine learning prediction of long COVID using data from the National COVID Cohort Collaborative.

Author

Bergquist, Timothy, Loomba, Johanna, Pfaff, Emily, Xia, Fangfang, Zhao, Zixuan, Zhu, Yitan, Mitchell, Elliot, Bhattacharya, Biplab, Shetty, Gaurav, Munia, Tamanna, Delong, Grant, Tariq, Adbul, Butzin-Dozier, Zachary, Ji, Yunwen, Li, Haodong, Coyle, Jeremy, Shi, Seraphina, Philips, Rachael, Mertens, Andrew, Pirracchio, Romain, van der Laan, Mark, Colford, John, Hubbard, Alan, Gao, Jifan, Chen, Guanhua, Velingker, Neelay, Li, Ziyang, Wu, Yinjun, Stein, Adam, Huang, Jiani, Dai, Zongyu, Long, Qi, Naik, Mayur, Holmes, John, Mowery, Danielle, Wong, Eric, Parekh, Ravi, Getzen, Emily, Hightower, Jake, and Blase, Jennifer

Subjects
COVID-19, Community challenge, Evaluation, Long COVID, Machine learning, PASC, Humans, COVID-19, Machine Learning, SARS-CoV-2, United States, Algorithms, Post-Acute COVID-19 Syndrome, Cohort Studies, Crowdsourcing
Abstract

BACKGROUND: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. METHODS: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). FINDINGS: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. INTERPRETATION: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. FUNDING: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

Published
2024

2. NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study

Author

Reese, Justin T, Coleman, Ben, Chan, Lauren, Blau, Hannah, Callahan, Tiffany J, Cappelletti, Luca, Fontana, Tommaso, Bradwell, Katie R, Harris, Nomi L, Casiraghi, Elena, Valentini, Giorgio, Karlebach, Guy, Deer, Rachel, McMurry, Julie A, Haendel, Melissa A, Chute, Christopher G, Pfaff, Emily, Moffitt, Richard, Spratt, Heidi, Singh, Jasvinder A, Mungall, Christopher J, Williams, Andrew E, and Robinson, Peter N

Subjects
Microbiology, Biological Sciences, Emerging Infectious Diseases, Coronaviruses, Lung, Infectious Diseases, Kidney Disease, Good Health and Well Being, Acute Kidney Injury, Anti-Inflammatory Agents, Non-Steroidal, COVID-19, COVID-19 Testing, Cohort Studies, Humans, Pandemics, Retrospective Studies, NSAIDs, Cyclooxygenase inhibitors, Observational study, Medical Microbiology, Virology
Abstract

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community-acquired pneumonia. Observations shortly after the start of the COVID-19 pandemic in 2020 suggested that ibuprofen was associated with an increased risk of adverse events in COVID-19 patients, but subsequent observational studies failed to demonstrate increased risk and in one case showed reduced risk associated with NSAID use.MethodsA 38-center retrospective cohort study was performed that leveraged the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative. A propensity-matched cohort of 19,746 COVID-19 inpatients was constructed by matching cases (treated with NSAIDs at the time of admission) and 19,746 controls (not treated) from 857,061 patients with COVID-19 available for analysis. The primary outcome of interest was COVID-19 severity in hospitalized patients, which was classified as: moderate, severe, or mortality/hospice. Secondary outcomes were acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality at any time following COVID-19 diagnosis.ResultsLogistic regression showed that NSAID use was not associated with increased COVID-19 severity (OR: 0.57 95% CI: 0.53-0.61). Analysis of secondary outcomes using logistic regression showed that NSAID use was not associated with increased risk of all-cause mortality (OR 0.51 95% CI: 0.47-0.56), invasive ventilation (OR: 0.59 95% CI: 0.55-0.64), AKI (OR: 0.67 95% CI: 0.63-0.72), or ECMO (OR: 0.51 95% CI: 0.36-0.7). In contrast, the odds ratios indicate reduced risk of these outcomes, but our quantitative bias analysis showed E-values of between 1.9 and 3.3 for these associations, indicating that comparatively weak or moderate confounder associations could explain away the observed associations.ConclusionsStudy interpretation is limited by the observational design. Recording of NSAID use may have been incomplete. Our study demonstrates that NSAID use is not associated with increased COVID-19 severity, all-cause mortality, invasive ventilation, AKI, or ECMO in COVID-19 inpatients. A conservative interpretation in light of the quantitative bias analysis is that there is no evidence that NSAID use is associated with risk of increased severity or the other measured outcomes. Our results confirm and extend analogous findings in previous observational studies using a large cohort of patients drawn from 38 centers in a nationally representative multicenter database.

Published
2022

3. The National COVID Cohort Collaborative (N3C): Rationale, Design, Infrastructure, and Deployment

Author

Haendel, Melissa A, Chute, Christopher G, Bennett, Tellen D, Eichmann, David A, Guinney, Justin, Kibbe, Warren A, Payne, Philip RO, Pfaff, Emily R, Robinson, Peter N, Saltz, Joel H, Spratt, Heidi, Suver, Christine, Wilbanks, John, Wilcox, Adam B, Williams, Andrew E, Wu, Chunlei, Blacketer, Clair, Bradford, Robert L, Cimino, James J, Clark, Marshall, Colmenares, Evan W, Francis, Patricia A, Gabriel, Davera, Graves, Alexis, Hemadri, Raju, Hong, Stephanie S, Hripscak, George, Jiao, Dazhi, Klann, Jeffrey G, Kostka, Kristin, Lee, Adam M, Lehmann, Harold P, Lingrey, Lora, Miller, Robert T, Morris, Michele, Murphy, Shawn N, Natarajan, Karthik, Palchuk, Matvey B, Sheikh, Usman, Solbrig, Harold, Visweswaran, Shyam, Walden, Anita, Walters, Kellie M, Weber, Griffin M, Zhang, Xiaohan Tanner, Zhu, Richard L, Amor, Benjamin, Girvin, Andrew T, Manna, Amin, Qureshi, Nabeel, Kurilla, Michael G, Michael, Sam G, Portilla, Lili M, Rutter, Joni L, Austin, Christopher P, and Gersing, Ken R

Subjects
COVID-19, Computer Security, Data Analysis, Data Science, Ethics Committees, Research, Government Regulation, Humans, Information Dissemination, Intersectoral Collaboration, National Institutes of Health (U.S.), United States, N3C Consortium, EHR data, SARS-CoV-2, clinical data model harmonization, collaborative analytics, open science, Information and Computing Sciences, Engineering, Medical and Health Sciences, Medical Informatics
Abstract

ObjectiveCoronavirus disease 2019 (COVID-19) poses societal challenges that require expeditious data and knowledge sharing. Though organizational clinical data are abundant, these are largely inaccessible to outside researchers. Statistical, machine learning, and causal analyses are most successful with large-scale data beyond what is available in any given organization. Here, we introduce the National COVID Cohort Collaborative (N3C), an open science community focused on analyzing patient-level data from many centers.Materials and methodsThe Clinical and Translational Science Award Program and scientific community created N3C to overcome technical, regulatory, policy, and governance barriers to sharing and harmonizing individual-level clinical data. We developed solutions to extract, aggregate, and harmonize data across organizations and data models, and created a secure data enclave to enable efficient, transparent, and reproducible collaborative analytics.ResultsOrganized in inclusive workstreams, we created legal agreements and governance for organizations and researchers; data extraction scripts to identify and ingest positive, negative, and possible COVID-19 cases; a data quality assurance and harmonization pipeline to create a single harmonized dataset; population of the secure data enclave with data, machine learning, and statistical analytics tools; dissemination mechanisms; and a synthetic data pilot to democratize data access.ConclusionsThe N3C has demonstrated that a multisite collaborative learning health network can overcome barriers to rapidly build a scalable infrastructure incorporating multiorganizational clinical data for COVID-19 analytics. We expect this effort to save lives by enabling rapid collaboration among clinicians, researchers, and data scientists to identify treatments and specialized care and thereby reduce the immediate and long-term impacts of COVID-19.

Published
2021

4. Electronic Medical Record Search Engine (EMERSE): An Information Retrieval Tool for Supporting Cancer Research

Author

Hanauer, David A, Barnholtz-Sloan, Jill S, Beno, Mark F, Del Fiol, Guilherme, Durbin, Eric B, Gologorskaya, Oksana, Harris, Daniel, Harnett, Brett, Kawamoto, Kensaku, May, Benjamin, Meeks, Eric, Pfaff, Emily, Weiss, Janie, and Zheng, Kai

Subjects
Information and Computing Sciences, Health Services and Systems, Information Systems, Health Sciences, Clinical Research, Cancer, Electronic Health Records, Humans, Information Storage and Retrieval, Natural Language Processing, Neoplasms, Search Engine, Software
Abstract

PurposeThe Electronic Medical Record Search Engine (EMERSE) is a software tool built to aid research spanning cohort discovery, population health, and data abstraction for clinical trials. EMERSE is now live at three academic medical centers, with additional sites currently working on implementation. In this report, we describe how EMERSE has been used to support cancer research based on a variety of metrics.MethodsWe identified peer-reviewed publications that used EMERSE through online searches as well as through direct e-mails to users based on audit logs. These logs were also used to summarize use at each of the three sites. Search terms for two of the sites were characterized using the natural language processing tool MetaMap to determine to which semantic types the terms could be mapped.ResultsWe identified a total of 326 peer-reviewed publications that used EMERSE through August 2019, although this is likely an underestimation of the true total based on the use log analysis. Oncology-related research comprised nearly one third (n = 105; 32.2%) of all research output. The use logs showed that EMERSE had been used by multiple people at each site (nearly 3,500 across all three) who had collectively logged into the system > 100,000 times. Many user-entered search queries could not be mapped to a semantic type, but the most common semantic type for terms that did match was "disease or syndrome," followed by "pharmacologic substance."ConclusionEMERSE has been shown to be a valuable tool for supporting cancer research. It has been successfully deployed at other sites, despite some implementation challenges unique to each deployment environment.

Published
2020

5. Evolving phenotypes of non-hospitalized patients that indicate long COVID

Author

ESTIRI, Hossein, Strasser, Zachary, Brat, Gabriel, Semenov, Yevgeniy, Patel, Chirag, Murphy, Shawn, Aaron, James, Agapito, Giuseppe, Albayrak, Adem, Alessiani, Mario, Amendola, Danilo, Anthony, Li, Aronow, Bruce, Ashraf, Fatima, Atz, Andrew, Avillach, Paul, Balshi, James, Beaulieu-Jones, Brett, Bell, Douglas, Bellasi, Antonio, Bellazzi, Riccardo, Benoit, Vincent, Beraghi, Michele, Sobrino, José Luis Bernal, Bernaux, Mélodie, Bey, Romain, Martínez, Alvar Blanco, Boeker, Martin, Bonzel, Clara-Lea, Booth, John, Bosari, Silvano, Bourgeois, Florence, Bradford, Robert, Bréant, Stéphane, Brown, Nicholas, Bryant, William, Bucalo, Mauro, Burgun, Anita, Cai, Tianxi, Cannataro, Mario, Carmona, Aldo, Caucheteux, Charlotte, Champ, Julien, Chen, Jin, Chen, Krista, Chiovato, Luca, Chiudinelli, Lorenzo, Cho, Kelly, Cimino, James, Colicchio, Tiago, Cormont, Sylvie, COSSIN, Sébastien, Craig, Jean, Bermúdez, Juan Luis Cruz, Rojo, Jaime Cruz, Dagliati, Arianna, Daniar, Mohamad, Daniel, Christel, Davoudi, Anahita, Devkota, Batsal, Dubiel, Julien, Esteve, Loic, Fan, Shirley, Follett, Robert, Gaiolla, Paula, Ganslandt, Thomas, Barrio, Noelia García, Garmire, Lana, Gehlenborg, Nils, GEVA, Alon, Gradinger, Tobias, Gramfort, Alexandre, Griffier, Romain, Griffon, Nicolas, Grisel, Olivier, Gutiérrez-Sacristán, Alba, Hanauer, David, Haverkamp, Christian, He, Bing, Henderson, Darren, Hilka, Martin, Holmes, John, Hong, Chuan, Horki, Petar, Huling, Kenneth, HUTCH, Meghan, Issitt, Richard, Jannot, Anne Sophie, Jouhet, Vianney, Keller, Mark, Kirchoff, Katie, Klann, Jeffrey, Kohane, Isaac, Krantz, Ian, Kraska, Detlef, Krishnamurthy, Ashok, L’Yi, Sehi, Le, Trang, Leblanc, Judith, Leite, Andressa, Lemaitre, Guillaume, Lenert, Leslie, Leprovost, Damien, Liu, Molei, LOH, Ne Hooi Will, Lozano-Zahonero, Sara, Luo, Yuan, Lynch, Kristine, Mahmood, Sadiqa, Maidlow, Sarah, Malovini, Alberto, Mandl, Kenneth, Mao, Chengsheng, Maram, Anupama, Martel, Patricia, Masino, Aaron, Mazzitelli, Maria, Mensch, Arthur, Milano, Marianna, Minicucci, Marcos, Moal, Bertrand, Moore, Jason, Moraleda, Cinta, Morris, Jeffrey, MORRIS, Michele, Moshal, Karyn, Mousavi, Sajad, Mowery, Danielle, Murad, Douglas, Naughton, Thomas, Neuraz, Antoine, Ngiam, Kee Yuan, Norman, James, Obeid, Jihad, Okoshi, Marina, Olson, Karen, Omenn, Gilbert, Orlova, Nina, Ostasiewski, Brian, Palmer, Nathan, Paris, Nicolas, Patel, Lav, Jimenez, Miguel Pedrera, Pfaff, Emily, Pillion, Danielle, Prokosch, Hans, Prudente, Robson, González, Víctor Quirós, Ramoni, Rachel, Raskin, Maryna, RIEG, Siegbert, Domínguez, Gustavo Roig, Rojo, Pablo, Sáez, Carlos, Salamanca, Elisa, Samayamuthu, Malarkodi, Sandrin, Arnaud, Santos, Janaina, Savino, Maria, SCHRIVER, Emily, Schubert, Petra, Schuettler, Juergen, Scudeller, Luigia, Sebire, Neil, Balazote, Pablo Serrano, Serre, Patricia, Serret-Larmande, Arnaud, Shakeri, Zahra, Silvio, Domenick, Sliz, Piotr, SON, Jiyeon, Sonday, Charles, South, Andrew, Spiridou, Anastasia, Tan, Amelia, Tan, Bryce, Tan, Byorn, Tanni, Suzana, Taylor, Deanne, Terriza Torres, Ana, Tibollo, Valentina, Tippmann, Patric, Torti, Carlo, Trecarichi, Enrico, Tseng, Yi-Ju, Vallejos, Andrew, Varoquaux, Gael, Vella, Margaret, Verdy, Guillaume, Vie, Jill-Jênn, Visweswaran, Shyam, Vitacca, Michele, Wagholikar, Kavishwar, Waitman, Lemuel, Wang, Xuan, Wassermann, Demian, Weber, Griffin, XIA, Zongqi, Yehya, Nadir, Yuan, William, Zambelli, Alberto, Zhang, Harrison, Zoeller, Daniel, Zucco, Chiara, Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Service d'informatique médicale et biostatistiques [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), This work was supported by the National Human Genome Research Institute grant 3U01HG008685-05S2 and the National Library of Medicine grant T15LM007092., École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), and Université Paris Cité (UPCité)

Subjects
medicine.medical_specialty, Neurological disorder, Chest pain, MESH: Phenotype, Article, 03 medical and health sciences, 0302 clinical medicine, Post-Acute COVID-19 Syndrome, Diabetes mellitus, Internal medicine, Machine learning, medicine, Chronic fatigue syndrome, Humans, Electronic health records, Post-acute sequelae of SARS-CoV-2, MESH: COVID-19, 030304 developmental biology, Retrospective Studies, 0303 health sciences, MESH: Humans, business.industry, Medical record, Type 2 Diabetes Mellitus, COVID-19, Retrospective cohort study, MESH: Retrospective Studies, General Medicine, medicine.disease, 3. Good health, Dysgeusia, Phenotypes, Phenotype, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, 030217 neurology & neurosurgery, Research Article, Cohort study
Abstract

Background For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of PASC phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection. Methods In this retrospective electronic health record (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3–6 and 6–9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston Metropolitan Area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized. Results We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients’ medical records 2 months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.60, 95% CI [1.94–3.46]), alopecia (OR 3.09, 95% CI [2.53–3.76]), chest pain (OR 1.27, 95% CI [1.09–1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22–2.10]), shortness of breath (OR 1.41, 95% CI [1.22–1.64]), pneumonia (OR 1.66, 95% CI [1.28–2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22–1.64]) is one of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65. Conclusions The findings of this study confirm many of the post-COVID-19 symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63% of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.

Published
2021
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6. Multinational characterization of neurological phenotypes in patients hospitalized with COVID-19

Author

Le, Trang, Gutiérrez-Sacristán, Alba, Son, Jiyeon, Hong, Chuan, South, Andrew, Beaulieu-Jones, Brett, Loh, Ne Hooi Will, Luo, Yuan, Morris, Michele, Ngiam, Kee Yuan, Patel, Lav, Samayamuthu, Malarkodi, Schriver, Emily, Tan, Amelia, Moore, Jason, Cai, Tianxi, Omenn, Gilbert, Avillach, Paul, Kohane, Isaac, Visweswaran, Shyam, Mowery, Danielle, Xia, Zongqi, Aaron, James, Agapito, Giuseppe, Albayrak, Adem, Alessiani, Mario, Amendola, Danilo, Angoulvant, François, Anthony, Li, Aronow, Bruce, Atz, Andrew, Balshi, James, Bell, Douglas, Bellasi, Antonio, Bellazzi, Riccardo, Benoit, Vincent, Beraghi, Michele, Bernal Sobrino, José Luis, Bernaux, Mélodie, Bey, Romain, Blanco Martínez, Alvar, Boeker, Martin, Bonzel, Clara-Lea, Booth, John, Bosari, Silvano, Bourgeois, Florence, Bradford, Robert, Brat, Gabriel, Bréant, Stéphane, Brown, Nicholas, Bryant, William, Bucalo, Mauro, Burgun, Anita, Cannataro, Mario, Carmona, Aldo, Caucheteux, Charlotte, Champ, Julien, Chen, Krista, Chen, Jin, Chiovato, Luca, Chiudinelli, Lorenzo, Cimino, James, Colicchio, Tiago, Cormont, Sylvie, Cossin, Sébastien, Craig, Jean, Cruz Bermúdez, Juan Luis, Cruz Rojo, Jaime, Dagliati, Arianna, Daniar, Mohamad, Daniel, Christel, Davoudi, Anahita, Devkota, Batsal, Dubiel, Julien, Esteve, Loic, Fan, Shirley, Follett, Robert, Gaiolla, Paula, Ganslandt, Thomas, García Barrio, Noelia, Garmire, Lana, Gehlenborg, Nils, Geva, Alon, Gradinger, Tobias, Gramfort, Alexandre, Griffier, Romain, Griffon, Nicolas, Grisel, Olivier, Hanauer, David, Haverkamp, Christian, He, Bing, Henderson, Darren, Hilka, Martin, Holmes, John, Horki, Petar, Huling, Kenneth, Hutch, Meghan, Issitt, Richard, Jannot, Anne Sophie, Jouhet, Vianney, Kavuluru, Ramakanth, Keller, Mark, Kirchoff, Katie, Klann, Jeffrey, Krantz, Ian, Kraska, Detlef, Krishnamurthy, Ashok, L’yi, Sehi, Leblanc, Judith, Leite, Andressa, Lemaitre, Guillaume, Lenert, Leslie, Leprovost, Damien, Liu, Molei, Lozano-Zahonero, Sarah, Lynch, Kristine, Mahmood, Sadiqa, Maidlow, Sarah, Makoudjou Tchendjou, Adeline, Malovini, Alberto, Mandl, Kenneth, Mao, Chengsheng, Maram, Anupama, Martel, Patricia, Masino, Aaron, Matheny, Michael, Maulhardt, Thomas, Mazzitelli, Maria, Mcduffie, Michael, Mensch, Arthur, Ashraf, Fatima, Milano, Marianna, Minicucci, Marcos, Moal, Bertrand, Moraleda, Cinta, Morris, Jeffrey, Moshal, Karyn, Mousavi, Sajad, Murad, Douglas, Murphy, Shawn, Naughton, Thomas, Neuraz, Antoine, Norman, James, Obeid, Jihad, Okoshi, Marina, Olson, Karen, Orlova, Nina, Ostasiewski, Brian, Palmer, Nathan, Paris, Nicolas, Pedrera Jimenez, Miguel, Pfaff, Emily, Pillion, Danielle, Prokosch, Hans, Prudente, Robson, Quirós González, Víctor, Ramoni, Rachel, Raskin, Maryna, Rieg, Siegbert, Roig Domínguez, Gustavo, Rojo, Pablo, Sáez, Carlos, Salamanca, Elisa, Sandrin, Arnaud, Santos, Janaina, Savino, Maria, Schuettler, Juergen, Scudeller, Luigia, Sebire, Neil, Balazote, Pablo Serrano, Serre, Patricia, Serret-Larmande, Arnaud, Shakeri, Zahra, Silvio, Domenick, Sliz, Piotr, Sonday, Charles, Spiridou, Anastasia, Tan, Bryce, Tan, Byorn, Tanni, Suzana, Taylor, Deanne, Terriza-Torres, Ana, Tibollo, Valentina, Tippmann, Patric, Torti, Carlo, Trecarichi, Enrico, Tseng, Yi-Ju, Vallejos, Andrew, Varoquaux, Gael, Vella, Margaret, Vie, Jill-Jênn, Vitacca, Michele, Wagholikar, Kavishwar, Waitman, Lemuel, Wassermann, Demian, Weber, Griffin, William, Yuan, Yehya, Nadir, Zambelli, Alberto, Zhang, Harrison, Zoeller, Daniela, Zucco, Chiara, Unité d'informatique médicale, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), AS is funded by National Institutes of Health (NIH) National Heart Lung, and Blood Institute (NHLBI) K23HL148394 and L40HL148910, and NIH-National Center for Advancing Translational Sciences (NCATS) UL1TR001420. JM is funded by NIH-National Institute of Allergy and Infectious Disease (NIAD) AI11679. LP is funded by NCATS Clinical and Translational Science Award (CTSA) Number UL1TR002366. GO is funded by NIH National Institute of Environmental Health Sciences (NIEHS) P30ES017885 and National Cancer Institute (NCI) U24CA210967. SV is funded by NIH-National Library of Medicine (NLM) R01LM012095 and NCATS UL1TR001857. DM is funded by NCATS CTSA Number UL1-TR001878. ZX is funded by NIH National Institute of Neurological Disorders and Stroke (NINDS) R01NS098023., Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Cancer Institute, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), University of Pennsylvania Perelman School of Medicine, Harvard Medical School, University of Pittsburgh, Wake Forest School of Medicine, National University Health Systems, Northwestern University, University of Kansas Medical Center, University of Pennsylvania Health System, University of Michigan, University of Kentucky, University Magna Graecia of Catanzaro, INC., Lombardia Region Health System, Universidade Estadual Paulista (UNESP), Assistance Publique-Hôpitaux de Paris, Tan Tock Seng Hospital, University of Cincinnati, Medical University of South Carolina, St. Luke’s University Health Network, David Geffen School of Medicine at UCLA, ASST Papa Giovanni XXIII, University of Pavia, APHP Greater Paris University Hospital, ASST Pavia, Hospital Universitario, University of Freiburg, Informatics and Virtual Environments (DRIVE), IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, University of North Carolina, BIOMERIS (BIOMedical Research Informatics Solutions), CEA, LIRMM, Boston Children’s Hospital, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, University of Alabama at Birmingham, Bordeaux University Hospital/ERIAS-Inserm U1219 BPH, Children’s Hospital of Philadelphia, Inria Centre de Paris, Heidelberg University, and Pain Medicine Boston Children’s Hospital, University of Michigan Medical School, MSHI Medical University of South Carolina, Massachusetts General Hospital, The Children’s Hospital of Philadelphia, University Hospital, Clevy.io, Harvard T.H. Chan School of Public Health, VA Salt Lake City Health Care System, Veterans Affairs Medical Center, PSL Université Paris, School of Biomedical Informatics, Great Ormond Street Hospital for Children, University of Erlangen-Nürnberg, Office of Research and Development, Universitat Politècnica de València, Nurse Department of FMB-Medicine School of Botucatu, FAU Erlangen-Nürnberg, National University Hospital, Chang Gung University, Medical College of Wisconsin, McGill University, Inria Lille, ICS S Maugeri IRCCS, University of Missouri, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), and Université Paris Cité (UPC)

Subjects
Male, Epidemiology, Cross-sectional study, Disease, Severity of Illness Index, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Child, Prevalence, MESH: COVID-19, 030212 general & internal medicine, Young adult, Child, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Multidisciplinary, MESH: Infant, Newborn, Middle Aged, MESH: Infant, 3. Good health, Neurology, MESH: Young Adult, Child, Preschool, Medicine, Female, Encephalitis, Adult, MESH: Pandemics, medicine.medical_specialty, Adolescent, Science, Myelitis, MESH: Nervous System Diseases, Article, Young Adult, 03 medical and health sciences, Medical research, MESH: Cross-Sectional Studies, MESH: Severity of Illness Index, Internal medicine, Severity of illness, medicine, Humans, Pandemics, MESH: Prevalence, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, Newborn, COVID-19, Infant, MESH: Adult, medicine.disease, MESH: Male, Confidence interval, Cross-Sectional Studies, Relative risk, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Nervous System Diseases, business, MESH: Female, Neurological disorders, 030217 neurology & neurosurgery
Abstract

Made available in DSpace on 2022-04-29T08:35:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Division of Intramural Research, National Institute of Allergy and Infectious Diseases Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases National Institute of Allergy and Infectious Diseases National Center for Advancing Translational Sciences National Heart, Lung, and Blood Institute National Institute of Environmental Health Sciences U.S. National Library of Medicine National Institute of Neurological Disorders and Stroke Division of Cancer Prevention, National Cancer Institute Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January–September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7–7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7–10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19–25%), cerebrovascular diseases (24%, 13–35%), nontraumatic intracranial hemorrhage (34%, 20–50%), encephalitis and/or myelitis (37%, 17–60%) and myopathy (72%, 67–77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease. Department of Biostatistics Epidemiology and Informatics University of Pennsylvania Perelman School of Medicine Department of Biomedical Informatics Harvard Medical School Department of Neurology University of Pittsburgh, Biomedical Science Tower 3, Suite 7014, 3501 5th Avenue Department of Pediatrics Wake Forest School of Medicine Department of Critical Care National University Health Systems Department of Preventive Medicine Northwestern University Department of Biomedical Informatics University of Pittsburgh Department of Surgery National University Health Systems Department of Internal Medicine University of Kansas Medical Center Data Analytics Center University of Pennsylvania Health System Department of Computational Medicine and Bioinformatics University of Michigan Department of Biomedical Informatics University of Kentucky Department of Legal Economic and Social Sciences University Magna Graecia of Catanzaro Health Catalyst INC. Department of Surgery ASST Pavia Lombardia Region Health System Clinical Research Unit of Botucatu Medical School São Paulo State University Pediatric Emergency Department Hôpital Necker-Enfants Malades Assistance Publique-Hôpitaux de Paris National Center for Infectious Diseases Tan Tock Seng Hospital Departments of Biomedical Informatics Pediatrics Cincinnati Children’s Hospital Medical Center University of Cincinnati Department of Pediatrics Medical University of South Carolina Department of Surgery St. Luke’s University Health Network Department of Medicine David Geffen School of Medicine at UCLA UOC Ricerca Innovazione e Brand Reputation ASST Papa Giovanni XXIII Department of Electrical Computer and Biomedical Engineering University of Pavia IT Department Innovation & Data APHP Greater Paris University Hospital I.T. Department ASST Pavia Health Informatics Hospital Universitario, 12 de Octubre Strategy and Transformation Department APHP Greater Paris University Hospital Faculty of Medicine and Medical Center University of Freiburg Digital Research Informatics and Virtual Environments (DRIVE), Great Ormond Street Hospital for Children Scientific Direction IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano North Carolina Translational and Clinical Sciences (NC TraCS) Institute University of North Carolina BIOMERIS (BIOMedical Research Informatics Solutions) Department of Biomedical Informatics HEGP APHP Greater Paris University Hospital Department of Medical and Surgical Sciences Data Analytics Research Center University Magna Graecia of Catanzaro Department of Anesthesia St. Luke’s University Health Network Université Paris-Saclay Inria CEA INRIA Sophia-Antipolis–ZENITH Team LIRMM Computational Health Informatics Program Boston Children’s Hospital Department of Internal Medicine University of Kentucky Unit of Internal Medicine and Endocrinology Istituti Clinici Scientifici Maugeri SpA SB IRCCS Department of Internal Medicine and Therapeutics University of Pavia Informatics Institute University of Alabama at Birmingham IAM Unit Bordeaux University Hospital/ERIAS-Inserm U1219 BPH Biomedical Informatics Center Medical University of South Carolina Clinical Research Informatics Boston Children’s Hospital Department of Biomedical and Health Informatics Children’s Hospital of Philadelphia SED/SIERRA Inria Centre de Paris Health Information Technology & Services University of Michigan Internal Medicine Department Botucatu Medical School São Paulo State University Heinrich-Lanz-Center for Digital Health University Medicine Mannheim Heidelberg University Department of Anesthesiology Critical Care and Pain Medicine Boston Children’s Hospital Department of Learning Health Sciences University of Michigan Medical School MSHI Medical University of South Carolina Department of Medicine Massachusetts General Hospital Division of Human Genetics Department of Pediatrics The Children’s Hospital of Philadelphia Center for Medical Information and Communication Technology University Hospital Renaissance Computing Institute/Department of Computer Science University of North Carolina Clinical Research Unit Saint Antoine Hospital APHP Greater Paris University Hospital Clevy.io Department of Biostatistics Harvard T.H. Chan School of Public Health VA Informatics and Computing Infrastructure VA Salt Lake City Health Care System MICHR Informatics University of Michigan Laboratory of Informatics and Systems Engineering for Clinical Research Istituti Clinici Scientifici Maugeri SpA SB IRCCS Harvard Catalyst Harvard Medical School Clinical Research Unit Paris Saclay APHP Greater Paris University Hospital Department of Anesthesiology and Critical Care Children’s Hospital of Philadelphia VA Informatics and Computing Infrastructure Tennessee Valley Healthcare System Veterans Affairs Medical Center École Normale Supérieure PSL Université Paris BIG-ARC The University of Texas Health Science Center at Houston School of Biomedical Informatics Pediatric Infectious Disease Department Hospital Universitario, 12 de Octubre Department of Infectious Diseases Great Ormond Street Hospital for Children Department of Neurology Massachusetts General Hospital Internal Medicine Department of Botucatu Medical School São Paulo State University Department of Pediatrics Boston Children’s Hospital Center for Biomedical Informatics Wake Forest School of Medicine Department of Medical Informatics University of Erlangen-Nürnberg Department of Veterans Affairs Office of Research and Development Biomedical Data Science Lab ITACA Institute Universitat Politècnica de València Nurse Department of FMB-Medicine School of Botucatu Management Engineering ASST Pavia Lombardia Region Health System Department of Anesthesiology University Hospital Erlangen FAU Erlangen-Nürnberg Critical Care Medicine Department of Medicine St. Luke’s University Health Network Department of Medicine National University Hospital Department of Information Management Chang Gung University Clinical & Translational Science Institute Medical College of Wisconsin Montréal Neurological Institute McGill University SequeL Inria Lille Respiratory Department ICS S Maugeri IRCCS Department of Health Management and Informatics University of Missouri Department of Oncology ASST Papa Giovanni XXIII Clinical Research Unit of Botucatu Medical School São Paulo State University Internal Medicine Department Botucatu Medical School São Paulo State University Internal Medicine Department of Botucatu Medical School São Paulo State University Division of Intramural Research, National Institute of Allergy and Infectious Diseases: AI11679 Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases: AI11679 National Institute of Allergy and Infectious Diseases: AI11679 National Center for Advancing Translational Sciences: CTSA Award #UL1TR001878 National Center for Advancing Translational Sciences: CTSA Award #UL1TR002366 National Heart, Lung, and Blood Institute: K23HL148394 National Institute of Environmental Health Sciences: P30ES017885 U.S. National Library of Medicine: R01LM012095 National Institute of Neurological Disorders and Stroke: R01NS098023 Division of Cancer Prevention, National Cancer Institute: U24CA210967 National Center for Advancing Translational Sciences: UL1TR001420 National Center for Advancing Translational Sciences: UL1TR001857

Published
2021
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7. Administrative coding is specific, but not sensitive, for identifying eosinophilic esophagitis

Author

Rybnicek, David A., Hathorn, Kelly E., Pfaff, Emily R., Bulsiewicz, William J., Shaheen, Nicholas J., and Dellon, Evan S.

Subjects
Adult, Male, Academic Medical Centers, Adolescent, Databases, Factual, Incidence, Infant, Eosinophilic Esophagitis, Middle Aged, Sensitivity and Specificity, Article, Young Adult, International Classification of Diseases, Child, Preschool, North Carolina, Humans, Female, Registries, Child, Aged, Retrospective Studies
Abstract

The use of administrative databases to conduct population-based studies of eosinophilic esophagitis (EoE) in the United States is limited because it is unknown whether the International Classification of Diseases, Ninth Revision (ICD-9) code for EoE, 530.13, accurately identifies those who truly have the disease. The aim of this retrospective study was to validate the ICD-9 code for identifying cases of EoE in administrative data. Confirmed cases of EoE as per consensus guidelines (symptoms of esophageal dysfunction and ≥15 eosinophils per high-power field on biopsy after 8 weeks of twice daily proton pump inhibitor therapy) were identified in the University of North Carolina (UNC) EoE Clinicopathologic Database from 2008 to 2010; 2008 was the first year in which the 530.13 code was approved. Using the Carolina Data Warehouse, the administrative database for patients seen in the UNC system, all diagnostic and procedure codes were obtained for these cases. Then, with the EoE cases as the reference standard, we re-queried the Carolina Data Warehouse over the same time frame for all patients seen in the system (n=308,372) and calculated the sensitivity and specificity of the ICD-9 code 530.13 as a case definition of EoE. To attempt to refine the case definition, we added procedural codes in an iterative fashion to optimize sensitivity and specificity, and restricted our analysis to privately insured patients. We also conducted a sensitivity analysis with 2011 data to identify trends in the operating parameters of the code. We identified 226 cases of EoE at UNC to serve as the reference standard. The ICD-9 code 530.13 yielded a sensitivity of 37% (83/226; 95% confidence interval: 31-43%) and specificity of 99% (308,111/308,146; 95% confidence interval: 98-100%). These operating parameters were not substantially altered if the case definition required a procedure code for endoscopy or if cases were limited to those with commercial insurance. However, in 2011, the sensitivity of the code had increased to 61%, while the specificity remained at 99%. The ICD-9 code for EoE, 530.13, had excellent specificity for identifying cases of EoE in administrative data, although this high specificity was achieved at an academic center. Additionally, the sensitivity of the code appears to be increasing over time, and the threshold at which it will stabilize is not known. While use of this administrative code will still miss a number of cases, those identified in this manner are highly likely to have the disease.

Published
2013

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