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1. Large-scale ICU data sharing for global collaboration: the first 1633 critically ill COVID-19 patients in the Dutch Data Warehouse

Author

Fleuren, Lucas M., de Bruin, Daan P., Tonutti, Michele, Lalisang, Robbert C.A., Elbers, Paul W.G., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., Vonk, Sebastiaan J.J., Fornasa, Mattia, Machado, Tomas, Dam, Tariq, de Keizer, Nicolet F., Raeissi, Masoume, van der Meer, Nardo J.M., Rigter, Sander, Wils, Evert Jan, Frenzel, Tim, Dongelmans, Dave A., de Jong, Remko, Peters, Marco, Kamps, Marlijn J.A., Ramnarain, Dharmanand, Nowitzky, Ralph, Nooteboom, Fleur G.C.A., de Ruijter, Wouter, Urlings-Strop, Louise C., Smit, Ellen G.M., Mehagnoul-Schipper, Jannet, Dormans, Tom, Houwert, Taco, Hovenkamp, Hidde, Londono, Roberto Noorduijn, Quintarelli, Davide, Scholtemeijer, Martijn G., de Beer, Aletta A., Ercole, Ari, van der Schaar, Mihaela, Beudel, Martijn, Hoogendoorn, Mark, Girbes, Armand R.J., Herter, Willem E., Thoral, Patrick J., Roggeveen, Luca, van Diggelen, Fuda, el Hassouni, Ali, Guzman, David Romero, Bhulai, Sandjai, Ouweneel, Dagmar, Driessen, Ronald, Peppink, Jan, de Grooth, H. J., Zijlstra, G. J., van Tienhoven, A. J., van der Heiden, Evelien, Spijkstra, Jan Jaap, van der Spoel, Hans, de Man, Angelique, Klausch, Thomas, de Vries, Heder, Neree tot Babberich, Michael de, Thijssens, Olivier, Wagemakers, Lot, Berend, Julie, Silva, Virginia Ceni, Kullberg, Bob, Heunks, Leo, Juffermans, Nicole, Slooter, Arjan, Rettig, Thijs C.D., Reuland, M. C., van Manen, Laura, Montenij, Leon, van Bommel, Jasper, van den Berg, Roy, van Geest, Ellen, Hana, Anisa, Simsek, Suat, van den Bogaard, B., Pickkers, Peter, van der Heiden, Pim, van Gemeren, Claudia, Meinders, Arend Jan, de Bruin, Martha, Rademaker, Emma, van Osch, Frits, de Kruif, Martijn, Hendriks, Stefaan H.A., Schroten, Nicolas, Boelens, Age D., Arnold, Klaas Sierk, Karakus, A., Fijen, J. W., Festen-Spanjer, Barbara, Achterberg, Sefanja, Lens, Judith, van Koesveld, Jacomar, van den Tempel, Walter, Simons, Koen S., de Jager, Cornelis P.C., Oostdijk, Evelien, Labout, Joost, van der Gaauw, Bart, Reidinga, Auke C., Koetsier, Peter, Kuiper, Michael, Cornet, Alexander D., Beishuizen, Albertus, de Jong, Paul, Geutjes, Dennis, Faber, Harald J., Lutisan, Johan, Brunnekreef, Gert, Gemert, Ankie W.M.M.Koopman van, Entjes, Robert, van den Akker, Remko, Simons, Bram, Rijkeboer, A. A., Arbous, Sesmu, Aries, Marcel, van den Oever, Niels C.Gritters, van Tellingen, Martijn, Intensive Care, Medical Informatics, APH - Methodology, APH - Quality of Care, Intensive Care Medicine, Neurology, ANS - Neurodegeneration, AII - Inflammatory diseases, APH - Digital Health, Artificial intelligence, Network Institute, Computational Intelligence, Artificial Intelligence (section level), Mathematics, Intensive care medicine, VU University medical center, ACS - Microcirculation, ACS - Diabetes & metabolism, Epidemiologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and MUMC+: MA Medische Staf IC (9)

Subjects
2019-20 coronavirus outbreak, Letter, Coronavirus disease 2019 (COVID-19), Critically ill, business.industry, Information Dissemination, Critical Illness, MEDLINE, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], COVID-19, Critical Care and Intensive Care Medicine, Data warehouse, Data sharing, Intensive Care Units, SDG 3 - Good Health and Well-being, Data Warehousing, Scale (social sciences), Medicine, Humans, Operations management, business, Netherlands
Abstract

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Published
2021
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2. Assess and validate predictive performance of models for in-hospital mortality in COVID-19 patients:A retrospective cohort study in the Netherlands comparing the value of registry data with high-granular electronic health records

Author

Vagliano, Iacopo, Schut, Martijn C., Abu-Hanna, Ameen, Dongelmans, Dave A., de Lange, Dylan W., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., Rigter, Sander, Wils, Evert Jan, Frenzel, Tim, de Jong, Remko, Peters, Marco A.A., Kamps, Marlijn J.A., Ramnarain, Dharmanand, Nowitzky, Ralph, Nooteboom, Fleur G.C.A., de Ruijter, Wouter, Urlings-Strop, Louise C., Smit, Ellen G.M., Mehagnoul-Schipper, D. Jannet, Dormans, Tom, de Jager, Cornelis P.C., Hendriks, Stefaan H.A., Achterberg, Sefanja, Oostdijk, Evelien, Reidinga, Auke C., Festen-Spanjer, Barbara, Brunnekreef, Gert B., Cornet, Alexander D., van den Tempel, Walter, Boelens, Age D., Koetsier, Peter, Lens, Judith, Faber, Harald J., Karakus, A., Entjes, Robert, de Jong, Paul, Rettig, Thijs C.D., Reuland, M. C., Arbous, Sesmu, Fleuren, Lucas M., Dam, Tariq A., Thoral, Patrick J., Lalisang, Robbert C.A., Tonutti, Michele, de Bruin, Daan P., Elbers, Paul W.G., de Keizer, Nicolette F., Vagliano, Iacopo, Schut, Martijn C., Abu-Hanna, Ameen, Dongelmans, Dave A., de Lange, Dylan W., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., Rigter, Sander, Wils, Evert Jan, Frenzel, Tim, de Jong, Remko, Peters, Marco A.A., Kamps, Marlijn J.A., Ramnarain, Dharmanand, Nowitzky, Ralph, Nooteboom, Fleur G.C.A., de Ruijter, Wouter, Urlings-Strop, Louise C., Smit, Ellen G.M., Mehagnoul-Schipper, D. Jannet, Dormans, Tom, de Jager, Cornelis P.C., Hendriks, Stefaan H.A., Achterberg, Sefanja, Oostdijk, Evelien, Reidinga, Auke C., Festen-Spanjer, Barbara, Brunnekreef, Gert B., Cornet, Alexander D., van den Tempel, Walter, Boelens, Age D., Koetsier, Peter, Lens, Judith, Faber, Harald J., Karakus, A., Entjes, Robert, de Jong, Paul, Rettig, Thijs C.D., Reuland, M. C., Arbous, Sesmu, Fleuren, Lucas M., Dam, Tariq A., Thoral, Patrick J., Lalisang, Robbert C.A., Tonutti, Michele, de Bruin, Daan P., Elbers, Paul W.G., and de Keizer, Nicolette F.

Abstract

Purpose: To assess, validate and compare the predictive performance of models for in-hospital mortality of COVID-19 patients admitted to the intensive care unit (ICU) over two different waves of infections. Our models were built with high-granular Electronic Health Records (EHR) data versus less-granular registry data. Methods: Observational study of all COVID-19 patients admitted to 19 Dutch ICUs participating in both the national quality registry National Intensive Care Evaluation (NICE) and the EHR-based Dutch Data Warehouse (hereafter EHR). Multiple models were developed on data from the first 24 h of ICU admissions from February to June 2020 (first COVID-19 wave) and validated on prospective patients admitted to the same ICUs between July and December 2020 (second COVID-19 wave). We assessed model discrimination, calibration, and the degree of relatedness between development and validation population. Coefficients were used to identify relevant risk factors. Results: A total of 1533 patients from the EHR and 1563 from the registry were included. With high granular EHR data, the average AUROC was 0.69 (standard deviation of 0.05) for the internal validation, and the AUROC was 0.75 for the temporal validation. The registry model achieved an average AUROC of 0.76 (standard deviation of 0.05) in the internal validation and 0.77 in the temporal validation. In the EHR data, age, and respiratory-system related variables were the most important risk factors identified. In the NICE registry data, age and chronic respiratory insufficiency were the most important risk factors. Conclusion: In our study, prognostic models built on less-granular but readily-available registry data had similar performance to models built on high-granular EHR data and showed similar transportability to a prospective COVID-19 population. Future research is needed to verify whether this finding can be confirmed for upcoming waves.

Published
2022

3. Risk factors for adverse outcomes during mechanical ventilation of 1152 COVID-19 patients: a multicenter machine learning study with highly granular data from the Dutch Data Warehouse

Author

Fleuren, Lucas M., Tonutti, Michele, de Bruin, Daan P., Lalisang, Robbert C.A., Dam, Tariq A., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., Vonk, Sebastiaan J.J., Fornasa, Mattia, Machado, Tomas, van der Meer, Nardo J.M., Rigter, Sander, Wils, Evert Jan, Frenzel, Tim, Dongelmans, Dave A., de Jong, Remko, Peters, Marco, Kamps, Marlijn J.A., Ramnarain, Dharmanand, Nowitzky, Ralph, Nooteboom, Fleur G.C.A., de Ruijter, Wouter, Urlings-Strop, Louise C., Smit, Ellen G.M., Mehagnoul-Schipper, D. Jannet, Dormans, Tom, de Jager, Cornelis P.C., Hendriks, Stefaan H.A., Oostdijk, Evelien, Reidinga, Auke C., Festen-Spanjer, Barbara, Brunnekreef, Gert, Cornet, Alexander D., van den Tempel, Walter, Boelens, Age D., Koetsier, Peter, Lens, Judith, Achterberg, Sefanja, Faber, Harald J., Karakus, A., Beukema, Menno, Entjes, Robert, de Jong, Paul, Houwert, Taco, Hovenkamp, Hidde, Noorduijn Londono, Roberto, Quintarelli, Davide, Scholtemeijer, Martijn G., de Beer, Aletta A., Cinà, Giovanni, Beudel, Martijn, de Keizer, Nicolet F., Hoogendoorn, Mark, Girbes, Armand R.J., Herter, Willem E., Elbers, Paul W.G., Thoral, Patrick J., Rettig, Thijs C.D., Reuland, M. C., van Manen, Laura, Montenij, Leon, van Bommel, Jasper, van den Berg, Roy, van Geest, Ellen, Hana, Anisa, Boersma, W. G., van den Bogaard, B., Pickkers, Peter, van der Heiden, Pim, van Gemeren, Claudia C.W., Meinders, Arend Jan, de Bruin, Martha, Rademaker, Emma, van Osch, Frits H.M., de Kruif, Martijn, Schroten, Nicolas, Arnold, Klaas Sierk, Fijen, J. W., van Koesveld, Jacomar J.M., Simons, Koen S., Labout, Joost, van de Gaauw, Bart, Kuiper, Michael, Beishuizen, Albertus, Geutjes, Dennis, Lutisan, Johan, Grady, Bart P.X., van den Akker, Remko, Simons, Bram, Rijkeboer, A. A., Arbous, Sesmu, Aries, Marcel, van den Oever, Niels C.Gritters, van Tellingen, Martijn, Dijkstra, Annemieke, van Raalte, Rutger, Roggeveen, Luca, van Diggelen, Fuda, Hassouni, Ali el, Guzman, David Romero, Bhulai, Sandjai, Ouweneel, Dagmar, Driessen, Ronald, Peppink, Jan, de Grooth, H. J., Zijlstra, G. J., van Tienhoven, A. J., van der Heiden, Evelien, Spijkstra, Jan Jaap, van der Spoel, Hans, de Man, Angelique, Klausch, Thomas, de Vries, Heder, de Neree tot Babberich, Michael, Thijssens, Olivier, Wagemakers, Lot, van der Pol, Hilde G.A., Hendriks, Tom, Berend, Julie, Silva, Virginia Ceni, Kullberg, Bob, Heunks, Leo, Juffermans, Nicole, Slooter, Arjan, Intensive care medicine, ACS - Diabetes & metabolism, ACS - Microcirculation, Amsterdam Cardiovascular Sciences, Neurology, AII - Infectious diseases, AII - Cancer immunology, CCA - Cancer biology and immunology, AII - Inflammatory diseases, Epidemiology and Data Science, APH - Methodology, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, APH - Quality of Care, Medical Informatics, Graduate School, Nephrology, Cardiology, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, APH - Digital Health, Artificial intelligence, Network Institute, Computational Intelligence, Artificial Intelligence (section level), Mathematics, Intensive Care, Epidemiologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Medische Staf IC (9), and Internal medicine

Subjects
Icu patients, Coronavirus disease 2019 (COVID-19), Adverse outcomes, medicine.medical_treatment, Critical Care and Intensive Care Medicine, Machine learning, computer.software_genre, law.invention, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, law, SCORE, medicine, 030212 general & internal medicine, Risk factor, Research Articles, Mechanical ventilation, business.industry, RC86-88.9, Other Research Radboud Institute for Health Sciences [Radboudumc 0], COVID-19, 030208 emergency & critical care medicine, Medical emergencies. Critical care. Intensive care. First aid, Intensive care unit, Data warehouse, Data extraction, Mortality prediction, Risk factors, Artificial intelligence, business, computer
Abstract

Background The identification of risk factors for adverse outcomes and prolonged intensive care unit (ICU) stay in COVID-19 patients is essential for prognostication, determining treatment intensity, and resource allocation. Previous studies have determined risk factors on admission only, and included a limited number of predictors. Therefore, using data from the highly granular and multicenter Dutch Data Warehouse, we developed machine learning models to identify risk factors for ICU mortality, ventilator-free days and ICU-free days during the course of invasive mechanical ventilation (IMV) in COVID-19 patients. Methods The DDW is a growing electronic health record database of critically ill COVID-19 patients in the Netherlands. All adult ICU patients on IMV were eligible for inclusion. Transfers, patients admitted for less than 24 h, and patients still admitted at time of data extraction were excluded. Predictors were selected based on the literature, and included medication dosage and fluid balance. Multiple algorithms were trained and validated on up to three sets of observations per patient on day 1, 7, and 14 using fivefold nested cross-validation, keeping observations from an individual patient in the same split. Results A total of 1152 patients were included in the model. XGBoost models performed best for all outcomes and were used to calculate predictor importance. Using Shapley additive explanations (SHAP), age was the most important demographic risk factor for the outcomes upon start of IMV and throughout its course. The relative probability of death across age values is visualized in Partial Dependence Plots (PDPs), with an increase starting at 54 years. Besides age, acidaemia, low P/F-ratios and high driving pressures demonstrated a higher probability of death. The PDP for driving pressure showed a relative probability increase starting at 12 cmH2O. Conclusion Age is the most important demographic risk factor of ICU mortality, ICU-free days and ventilator-free days throughout the course of invasive mechanical ventilation in critically ill COVID-19 patients. pH, P/F ratio, and driving pressure should be monitored closely over the course of mechanical ventilation as risk factors predictive of these outcomes.

Published
2021
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4. Assess and validate predictive performance of models for in-hospital mortality in COVID-19 patients: A retrospective cohort study in the Netherlands comparing the value of registry data with high-granular electronic health records.

Author

Vagliano I, Schut MC, Abu-Hanna A, Dongelmans DA, de Lange DW, Gommers D, Cremer OL, Bosman RJ, Rigter S, Wils EJ, Frenzel T, de Jong R, Peters MAA, Kamps MJA, Ramnarain D, Nowitzky R, Nooteboom FGCA, de Ruijter W, Urlings-Strop LC, Smit EGM, Mehagnoul-Schipper DJ, Dormans T, de Jager CPC, Hendriks SHA, Achterberg S, Oostdijk E, Reidinga AC, Festen-Spanjer B, Brunnekreef GB, Cornet AD, van den Tempel W, Boelens AD, Koetsier P, Lens J, Faber HJ, Karakus A, Entjes R, de Jong P, Rettig TCD, Reuland MC, Arbous S, Fleuren LM, Dam TA, Thoral PJ, Lalisang RCA, Tonutti M, de Bruin DP, Elbers PWG, and de Keizer NF

Subjects
Electronic Health Records, Hospital Mortality, Humans, Intensive Care Units, Netherlands epidemiology, Registries, Retrospective Studies, COVID-19 epidemiology
Abstract

Purpose: To assess, validate and compare the predictive performance of models for in-hospital mortality of COVID-19 patients admitted to the intensive care unit (ICU) over two different waves of infections. Our models were built with high-granular Electronic Health Records (EHR) data versus less-granular registry data., Methods: Observational study of all COVID-19 patients admitted to 19 Dutch ICUs participating in both the national quality registry National Intensive Care Evaluation (NICE) and the EHR-based Dutch Data Warehouse (hereafter EHR). Multiple models were developed on data from the first 24 h of ICU admissions from February to June 2020 (first COVID-19 wave) and validated on prospective patients admitted to the same ICUs between July and December 2020 (second COVID-19 wave). We assessed model discrimination, calibration, and the degree of relatedness between development and validation population. Coefficients were used to identify relevant risk factors., Results: A total of 1533 patients from the EHR and 1563 from the registry were included. With high granular EHR data, the average AUROC was 0.69 (standard deviation of 0.05) for the internal validation, and the AUROC was 0.75 for the temporal validation. The registry model achieved an average AUROC of 0.76 (standard deviation of 0.05) in the internal validation and 0.77 in the temporal validation. In the EHR data, age, and respiratory-system related variables were the most important risk factors identified. In the NICE registry data, age and chronic respiratory insufficiency were the most important risk factors., Conclusion: In our study, prognostic models built on less-granular but readily-available registry data had similar performance to models built on high-granular EHR data and showed similar transportability to a prospective COVID-19 population. Future research is needed to verify whether this finding can be confirmed for upcoming waves., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2022
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