International Changes in COVID-19 Clinical Trajectories Across 315 Hospitals and 6 Countries: Retrospective Cohort Study.

COVID-19 SARS-CoV-2 electronic health records federated study laboratory trajectory meta-analysis retrospective cohort study severe COVID-19

Journal

Journal of medical Internet research
ISSN: 1438-8871
Titre abrégé: J Med Internet Res
Pays: Canada
ID NLM: 100959882

Informations de publication

Date de publication:
11 10 2021
Historique:
received: 23 06 2021
accepted: 02 09 2021
revised: 02 09 2021
pubmed: 18 9 2021
medline: 15 10 2021
entrez: 17 9 2021
Statut: epublish

Résumé

Many countries have experienced 2 predominant waves of COVID-19-related hospitalizations. Comparing the clinical trajectories of patients hospitalized in separate waves of the pandemic enables further understanding of the evolving epidemiology, pathophysiology, and health care dynamics of the COVID-19 pandemic. In this retrospective cohort study, we analyzed electronic health record (EHR) data from patients with SARS-CoV-2 infections hospitalized in participating health care systems representing 315 hospitals across 6 countries. We compared hospitalization rates, severe COVID-19 risk, and mean laboratory values between patients hospitalized during the first and second waves of the pandemic. Using a federated approach, each participating health care system extracted patient-level clinical data on their first and second wave cohorts and submitted aggregated data to the central site. Data quality control steps were adopted at the central site to correct for implausible values and harmonize units. Statistical analyses were performed by computing individual health care system effect sizes and synthesizing these using random effect meta-analyses to account for heterogeneity. We focused the laboratory analysis on C-reactive protein (CRP), ferritin, fibrinogen, procalcitonin, D-dimer, and creatinine based on their reported associations with severe COVID-19. Data were available for 79,613 patients, of which 32,467 were hospitalized in the first wave and 47,146 in the second wave. The prevalence of male patients and patients aged 50 to 69 years decreased significantly between the first and second waves. Patients hospitalized in the second wave had a 9.9% reduction in the risk of severe COVID-19 compared to patients hospitalized in the first wave (95% CI 8.5%-11.3%). Demographic subgroup analyses indicated that patients aged 26 to 49 years and 50 to 69 years; male and female patients; and black patients had significantly lower risk for severe disease in the second wave than in the first wave. At admission, the mean values of CRP were significantly lower in the second wave than in the first wave. On the seventh hospital day, the mean values of CRP, ferritin, fibrinogen, and procalcitonin were significantly lower in the second wave than in the first wave. In general, countries exhibited variable changes in laboratory testing rates from the first to the second wave. At admission, there was a significantly higher testing rate for D-dimer in France, Germany, and Spain. Patients hospitalized in the second wave were at significantly lower risk for severe COVID-19. This corresponded to mean laboratory values in the second wave that were more likely to be in typical physiological ranges on the seventh hospital day compared to the first wave. Our federated approach demonstrated the feasibility and power of harmonizing heterogeneous EHR data from multiple international health care systems to rapidly conduct large-scale studies to characterize how COVID-19 clinical trajectories evolve.

Sections du résumé

BACKGROUND
Many countries have experienced 2 predominant waves of COVID-19-related hospitalizations. Comparing the clinical trajectories of patients hospitalized in separate waves of the pandemic enables further understanding of the evolving epidemiology, pathophysiology, and health care dynamics of the COVID-19 pandemic.
OBJECTIVE
In this retrospective cohort study, we analyzed electronic health record (EHR) data from patients with SARS-CoV-2 infections hospitalized in participating health care systems representing 315 hospitals across 6 countries. We compared hospitalization rates, severe COVID-19 risk, and mean laboratory values between patients hospitalized during the first and second waves of the pandemic.
METHODS
Using a federated approach, each participating health care system extracted patient-level clinical data on their first and second wave cohorts and submitted aggregated data to the central site. Data quality control steps were adopted at the central site to correct for implausible values and harmonize units. Statistical analyses were performed by computing individual health care system effect sizes and synthesizing these using random effect meta-analyses to account for heterogeneity. We focused the laboratory analysis on C-reactive protein (CRP), ferritin, fibrinogen, procalcitonin, D-dimer, and creatinine based on their reported associations with severe COVID-19.
RESULTS
Data were available for 79,613 patients, of which 32,467 were hospitalized in the first wave and 47,146 in the second wave. The prevalence of male patients and patients aged 50 to 69 years decreased significantly between the first and second waves. Patients hospitalized in the second wave had a 9.9% reduction in the risk of severe COVID-19 compared to patients hospitalized in the first wave (95% CI 8.5%-11.3%). Demographic subgroup analyses indicated that patients aged 26 to 49 years and 50 to 69 years; male and female patients; and black patients had significantly lower risk for severe disease in the second wave than in the first wave. At admission, the mean values of CRP were significantly lower in the second wave than in the first wave. On the seventh hospital day, the mean values of CRP, ferritin, fibrinogen, and procalcitonin were significantly lower in the second wave than in the first wave. In general, countries exhibited variable changes in laboratory testing rates from the first to the second wave. At admission, there was a significantly higher testing rate for D-dimer in France, Germany, and Spain.
CONCLUSIONS
Patients hospitalized in the second wave were at significantly lower risk for severe COVID-19. This corresponded to mean laboratory values in the second wave that were more likely to be in typical physiological ranges on the seventh hospital day compared to the first wave. Our federated approach demonstrated the feasibility and power of harmonizing heterogeneous EHR data from multiple international health care systems to rapidly conduct large-scale studies to characterize how COVID-19 clinical trajectories evolve.

Identifiants

pubmed: 34533459
pii: v23i10e31400
doi: 10.2196/31400
pmc: PMC8510151
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e31400

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR000005
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS098023
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NICHD NIH HHS
ID : T32 HD040128
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001420
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES017885
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL148394
Pays : United States
Organisme : NLM NIH HHS
ID : R01 LM012095
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008685
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001998
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Organisme : NLM NIH HHS
ID : T32 LM012203
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001857
Pays : United States
Organisme : NLM NIH HHS
ID : T15 LM007092
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001878
Pays : United States
Organisme : British Heart Foundation
ID : FS/19/52/34563
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : R01 HG009174
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210967
Pays : United States
Organisme : NLM NIH HHS
ID : R01 LM013345
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002541
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002240
Pays : United States
Organisme : NHLBI NIH HHS
ID : L40 HL148910
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002366
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001450
Pays : United States

Investigateurs

James R Aaron (JR)
Giuseppe Agapito (G)
Adem Albayrak (A)
Mario Alessiani (M)
Anna Alloni (A)
Danilo F Amendola (DF)
Li LLJ Anthony (LLLJ)
Bruce J Aronow (BJ)
Fatima Ashraf (F)
Andrew Atz (A)
Paul Avillach (P)
Paula S Azevedo (PS)
James Balshi (J)
Brett K Beaulieu-Jones (BK)
Douglas S Bell (DS)
Antonio Bellasi (A)
Riccardo Bellazzi (R)
Vincent Benoit (V)
Michele Beraghi (M)
José Luis Bernal Sobrino (JLB)
Mélodie Bernaux (M)
Romain Bey (R)
Alvar Blanco Martínez (AB)
Martin Boeker (M)
Clara-Lea Bonzel (CL)
John Booth (J)
Silvano Bosari (S)
Florence T Bourgeois (FT)
Robert L Bradford (RL)
Gabriel A Brat (GA)
Stéphane Bréant (S)
Carlos Tadeu Breda Neto (CTB)
Nicholas W Brown (NW)
William A Bryant (WA)
Mauro Bucalo (M)
Anita Burgun (A)
Tianxi Cai (T)
Mario Cannataro (M)
Aldo Carmona (A)
Charlotte Caucheteux (C)
Julien Champ (J)
Jin Chen (J)
Krista Chen (K)
Luca Chiovato (L)
Lorenzo Chiudinelli (L)
Kelly Cho (K)
James J Cimino (JJ)
Tiago K Colicchio (TK)
Sylvie Cormont (S)
Sébastien Cossin (S)
Jean B Craig (JB)
Juan Luis Cruz Bermúdez (JLC)
Jaime Cruz Rojo (JC)
Arianna Dagliati (A)
Mohamad Daniar (M)
Christel Daniel (C)
Priyam Das (P)
Anahita Davoudi (A)
Batsal Devkota (B)
Julien Dubiel (J)
Loic Esteve (L)
Hossein Estiri (H)
Shirley Fan (S)
Robert W Follett (RW)
Thomas Ganslandt (T)
Noelia García Barrio (NG)
Lana X Garmire
Nils Gehlenborg (N)
Alon Geva (A)
Tobias Gradinger (T)
Alexandre Gramfort (A)
Romain Griffier (R)
Nicolas Griffon (N)
Olivier Grisel (O)
Alba Gutiérrez-Sacristán (A)
David A Hanauer (DA)
Christian Haverkamp (C)
Bing He (B)
Darren W Henderson (DW)
Martin Hilka (M)
Yuk-Lam Ho (YL)
John H Holmes (JH)
Chuan Hong (C)
Petar Horki (P)
Kenneth M Huling (KM)
Meghan R Hutch (MR)
Richard W Issitt (RW)
Anne Sophie Jannot (AS)
Vianney Jouhet (V)
Mark S Keller (MS)
Chris J Kennedy (CJ)
Katie Kirchoff (K)
Jeffrey G Klann (JG)
Isaac S Kohane (IS)
Ian D Krantz (ID)
Detlef Kraska (D)
Ashok K Krishnamurthy (AK)
Sehi L'Yi (S)
Trang T Le (TT)
Judith Leblanc (J)
Andressa RR Leite (ARR)
Guillaume Lemaitre (G)
Leslie Lenert (L)
Damien Leprovost (D)
Molei Liu (M)
Ne Hooi Will Loh (NHW)
Qi Long (Q)
Sara Lozano-Zahonero (S)
Yuan Luo (Y)
Kristine E Lynch (KE)
Sadiqa Mahmood (S)
Sarah Maidlow (S)
Adeline Makoudjou (A)
Alberto Malovini (A)
Kenneth D Mandl (KD)
Chengsheng Mao (C)
Anupama Maram (A)
Patricia Martel (P)
Marcelo R Martins (MR)
Aaron J Masino (AJ)
Maria Mazzitelli (M)
Arthur Mensch (A)
Marianna Milano (M)
Marcos F Minicucci (MF)
Bertrand Moal (B)
Jason H Moore (JH)
Cinta Moraleda (C)
Jeffrey S Morris (JS)
Michele Morris (M)
Karyn L Moshal (KL)
Sajad Mousavi (S)
Danielle L Mowery (DL)
Douglas A Murad (DA)
Shawn N Murphy (SN)
Thomas P Naughton (TP)
Antoine Neuraz (A)
Kee Yuan Ngiam (KY)
Wanjiku FM Njoroge (WFM)
James B Norman (JB)
Jihad Obeid (J)
Marina P Okoshi (MP)
Karen L Olson (KL)
Gilbert S Omenn (GS)
Nina Orlova (N)
Brian D Ostasiewski (BD)
Nathan P Palmer (NP)
Nicolas Paris (N)
Lav P Patel (LP)
Miguel Pedrera Jimenez (MP)
Emily R Pfaff (ER)
Danielle Pillion (D)
Hans U Prokosch (HU)
Robson A Prudente (RA)
Víctor Quirós González (VQ)
Rachel B Ramoni (RB)
Maryna Raskin (M)
Siegbert Rieg (S)
Gustavo Roig Domínguez (GR)
Pablo Rojo (P)
Carlos Sáez (C)
Elisa Salamanca (E)
Malarkodi J Samayamuthu (MJ)
L Nelson Sanchez-Pinto (LN)
Arnaud Sandrin (A)
Nandhini Santhanam (N)
Janaina CC Santos (JC)
Javier W Sanz (JW)
Maria Savino (M)
Emily R Schriver (ER)
Petra Schubert (P)
Juergen Schuettler (J)
Luigia Scudeller (L)
Neil J Sebire (NJ)
Pablo Serrano Balazote (PS)
Patricia Serre (P)
Arnaud Serret-Larmande (A)
Zahra Shakeri (Z)
Domenick Silvio (D)
Piotr Sliz (P)
Jiyeon Son (J)
Charles Sonday (C)
Andrew M South (AM)
Anastasia Spiridou (A)
Amelia LM Tan (ALM)
Bryce WQ Tan (BWQ)
Byorn WL Tan (BWL)
Suzana E Tanni (SE)
Deanne M Taylor (DM)
Ana I Terriza Torres (AIT)
Valentina Tibollo (V)
Patric Tippmann (P)
Carlo Torti (C)
Enrico M Trecarichi (EM)
Yi-Ju Tseng (YJ)
Andrew K Vallejos (AK)
Gael Varoquaux (G)
Margaret E Vella (ME)
Guillaume Verdy (G)
Jill-Jênn Vie (JJ)
Shyam Visweswaran (S)
Michele Vitacca (M)
Kavishwar B Wagholikar (KB)
Lemuel R Waitman (LR)
Xuan Wang (X)
Demian Wassermann (D)
Griffin M Weber (GM)
Zongqi Xia (Z)
Xin Xiong (X)
Nadir Yehya (N)
William Yuan (W)
Alberto Zambelli (A)
Harrison G Zhang (HG)
Daniel Zoeller (D)
Chiara Zucco (C)

Commentaires et corrections

Type : ErratumIn

Informations de copyright

©Griffin M Weber, Harrison G Zhang, Sehi L'Yi, Clara-Lea Bonzel, Chuan Hong, Paul Avillach, Alba Gutiérrez-Sacristán, Nathan P Palmer, Amelia Li Min Tan, Xuan Wang, William Yuan, Nils Gehlenborg, Anna Alloni, Danilo F Amendola, Antonio Bellasi, Riccardo Bellazzi, Michele Beraghi, Mauro Bucalo, Luca Chiovato, Kelly Cho, Arianna Dagliati, Hossein Estiri, Robert W Follett, Noelia García Barrio, David A Hanauer, Darren W Henderson, Yuk-Lam Ho, John H Holmes, Meghan R Hutch, Ramakanth Kavuluru, Katie Kirchoff, Jeffrey G Klann, Ashok K Krishnamurthy, Trang T Le, Molei Liu, Ne Hooi Will Loh, Sara Lozano-Zahonero, Yuan Luo, Sarah Maidlow, Adeline Makoudjou, Alberto Malovini, Marcelo Roberto Martins, Bertrand Moal, Michele Morris, Danielle L Mowery, Shawn N Murphy, Antoine Neuraz, Kee Yuan Ngiam, Marina P Okoshi, Gilbert S Omenn, Lav P Patel, Miguel Pedrera Jiménez, Robson A Prudente, Malarkodi Jebathilagam Samayamuthu, Fernando J Sanz Vidorreta, Emily R Schriver, Petra Schubert, Pablo Serrano Balazote, Byorn WL Tan, Suzana E Tanni, Valentina Tibollo, Shyam Visweswaran, Kavishwar B Wagholikar, Zongqi Xia, Daniela Zöller, The Consortium For Clinical Characterization Of COVID-19 By EHR (4CE), Isaac S Kohane, Tianxi Cai, Andrew M South, Gabriel A Brat. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 11.10.2021.

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Auteurs

Griffin M Weber (GM)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Harrison G Zhang (HG)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Sehi L'Yi (S)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Clara-Lea Bonzel (CL)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Chuan Hong (C)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Paul Avillach (P)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Alba Gutiérrez-Sacristán (A)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Nathan P Palmer (NP)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Amelia Li Min Tan (ALM)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Xuan Wang (X)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

William Yuan (W)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Nils Gehlenborg (N)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Anna Alloni (A)

BIOMERIS (BIOMedical Research Informatics Solutions), Pavia, Italy.

Danilo F Amendola (DF)

Clinical Research Unit, Botucatu Medical School, São Paulo State University, Botucatu, Brazil.

Antonio Bellasi (A)

Division of Nephrology, Department of Medicine, Ente Ospedaliero Cantonale, Lugano, Switzerland.

Riccardo Bellazzi (R)

Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.

Michele Beraghi (M)

Information Technology Department, Azienda Socio-Sanitaria Territoriale di Pavia, Pavia, Italy.

Mauro Bucalo (M)

BIOMERIS (BIOMedical Research Informatics Solutions), Pavia, Italy.

Luca Chiovato (L)

Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy.

Kelly Cho (K)

Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston, MA, United States.

Arianna Dagliati (A)

Department of Electrical Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.

Hossein Estiri (H)

Department of Medicine, Massachusetts General Hospital, Boston, MA, United States.

Robert W Follett (RW)

Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Noelia García Barrio (N)

Health Informatics, Hospital Universitario 12 de Octubre, Madrid, Spain.

David A Hanauer (DA)

Department of Learning Health Sciences, University of Michigan Medical School, Ann Arbor, MI, United States.

Darren W Henderson (DW)

Department of Biomedical Informatics, University of Kentucky, Lexington, KY, United States.

Yuk-Lam Ho (YL)

Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston, MA, United States.

John H Holmes (JH)

Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.
Institute for Biomedical Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.

Meghan R Hutch (MR)

Department of Preventive Medicine, Northwestern University, Chicago, IL, United States.

Ramakanth Kavuluru (R)

Institute for Biomedical Informatics, University of Kentucky, Lexington, KY, United States.

Katie Kirchoff (K)

Medical University of South Carolina, Charleston, SC, United States.

Jeffrey G Klann (JG)

Department of Medicine, Massachusetts General Hospital, Boston, MA, United States.

Ashok K Krishnamurthy (AK)

Department of Computer Science, Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

Trang T Le (TT)

Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.

Molei Liu (M)

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States.

Ne Hooi Will Loh (NHW)

Department of Anaesthesia, National University Health System, Singapore, Singapore.

Sara Lozano-Zahonero (S)

Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.

Yuan Luo (Y)

Department of Preventive Medicine, Northwestern University, Chicago, IL, United States.

Sarah Maidlow (S)

Michigan Institute for Clinical & Health Research Informatics, University of Michigan, Ann Arbor, MI, United States.

Adeline Makoudjou (A)

Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.

Alberto Malovini (A)

Laboratory of Informatics and Systems Engineering for Clinical Research, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy.

Marcelo Roberto Martins (MR)

Clinical Hospital of Botucatu Medical School, São Paulo State University, Botucatu, Brazil.

Bertrand Moal (B)

Informatique et archivistique médicales unit, Bordeaux University Hospital, Bordeaux, France.

Michele Morris (M)

Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, United States.

Danielle L Mowery (DL)

Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.

Shawn N Murphy (SN)

Department of Neurology, Massachusetts General Hospital, Boston, MA, United States.

Antoine Neuraz (A)

Department of Biomedical Informatics, Hôpital Necker-Enfants Malade, Assistance Publique Hôpitaux de Paris, University of Paris, Paris, France.

Kee Yuan Ngiam (KY)

Department of Biomedical Informatics, Institute for Digital Medicine, National University Health System, Singapore, Singapore.

Marina P Okoshi (MP)

Internal Medicine Department, Botucatu Medical School, São Paulo State University, Botucatu, Brazil.

Gilbert S Omenn (GS)

Department of Computational Medicine & Bioinformatics, Internal Medicine, Human Genetics, and Public Health, University of Michigan, Ann Arbor, MI, United States.

Lav P Patel (LP)

Division of Medical Informatics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, United States.

Miguel Pedrera Jiménez (M)

Health Informatics, Hospital Universitario 12 de Octubre, Madrid, Spain.

Robson A Prudente (RA)

Internal Medicine Department, Botucatu Medical School, São Paulo State University, Botucatu, Brazil.

Malarkodi Jebathilagam Samayamuthu (MJ)

Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, United States.

Fernando J Sanz Vidorreta (FJ)

Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Emily R Schriver (ER)

Data Analytics Center, University of Pennsylvania Health System, Philadelphia, PA, United States.

Petra Schubert (P)

Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston, MA, United States.

Pablo Serrano Balazote (P)

Health Informatics, Hospital Universitario 12 de Octubre, Madrid, Spain.

Byorn Wl Tan (BW)

Department of Medicine, National University Health System, Singapore, Singapore.

Suzana E Tanni (SE)

Internal Medicine Department, Botucatu Medical School, São Paulo State University, Botucatu, Brazil.

Valentina Tibollo (V)

Laboratory of Informatics and Systems Engineering for Clinical Research, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy.

Shyam Visweswaran (S)

Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, United States.

Kavishwar B Wagholikar (KB)

Department of Medicine, Massachusetts General Hospital, Boston, MA, United States.

Zongqi Xia (Z)

Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States.

Daniela Zöller (D)

Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
see Authors' Contributions, .

Isaac S Kohane (IS)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Tianxi Cai (T)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

Andrew M South (AM)

Section of Nephrology, Department of Pediatrics, Brenner Children's Hospital, Wake Forest School of Medicine, Winston Salem, NC, United States.

Gabriel A Brat (GA)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States.

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