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1. 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, 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, and de Beer, Aletta A

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, I

Published
2021

2. 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, 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, and van Tellingen, Martijn

Published
2021
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3. Predictors for extubation failure in COVID-19 patients using a machine learning approach

Author

Fleuren, Lucas M., Dam, Tariq A., Tonutti, Michele, de Bruin, Daan P., Lalisang, Robbert C.A., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., 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., 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., Arbous, Sesmu, Vonk, Sebastiaan J.J., Fornasa, Mattia, Machado, Tomas, Houwert, Taco, Hovenkamp, Hidde, Noorduijn Londono, Roberto, Quintarelli, Davide, Scholtemeijer, Martijn G., de Beer, Aletta A., Fleuren, Lucas M., Dam, Tariq A., Tonutti, Michele, de Bruin, Daan P., Lalisang, Robbert C.A., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., 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., 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., Arbous, Sesmu, Vonk, Sebastiaan J.J., Fornasa, Mattia, Machado, Tomas, Houwert, Taco, Hovenkamp, Hidde, Noorduijn Londono, Roberto, Quintarelli, Davide, Scholtemeijer, Martijn G., and de Beer, Aletta A.

Abstract

INTRODUCTION: Determining the optimal timing for extubation can be challenging in the intensive care. In this study, we aim to identify predictors for extubation failure in critically ill patients with COVID-19. METHODS: We used highly granular data from 3464 adult critically ill COVID patients in the multicenter Dutch Data Warehouse, including demographics, clinical observations, medications, fluid balance, laboratory values, vital signs, and data from life support devices. All intubated patients with at least one extubation attempt were eligible for analysis. Transferred patients, patients admitted for less than 24 h, and patients still admitted at the time of data extraction were excluded. Potential predictors were selected by a team of intensive care physicians. The primary and secondary outcomes were extubation without reintubation or death within the next 7 days and within 48 h, respectively. We trained and validated multiple machine learning algorithms using fivefold nested cross-validation. Predictor importance was estimated using Shapley additive explanations, while cutoff values for the relative probability of failed extubation were estimated through partial dependence plots. RESULTS: A total of 883 patients were included in the model derivation. The reintubation rate was 13.4% within 48 h and 18.9% at day 7, with a mortality rate of 0.6% and 1.0% respectively. The grandient-boost model performed best (area under the curve of 0.70) and was used to calculate predictor importance. Ventilatory characteristics and settings were the most important predictors. More specifically, a controlled mode duration longer than 4 days, a last fraction of inspired oxygen higher than 35%, a mean tidal volume per kg ideal body weight above 8 ml/kg in the day before extubation, and a shorter duration in assisted mode (< 2 days) compared to their median values. Additionally, a higher C-reactive protein and leukocyte count, a lower thrombocyte count, a lower Glasgow coma s

Published
2021

4. The Dutch Data Warehouse, a multicenter and full-admission electronic health records database for critically ill COVID-19 patients

Author

Fleuren, Lucas M., Dam, Tariq A., Tonutti, Michele, de Bruin, Daan P., Lalisang, Robbert C.A., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., 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., 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., Arbous, Sesmu, Vonk, Sebastiaan J.J., Fornasa, Mattia, Machado, Tomas, Houwert, Taco, Hovenkamp, Hidde, Noorduijn-Londono, Roberto, Quintarelli, Davide, Scholtemeijer, Martijn G., de Beer, Aletta A., Cina, Giovanni, Beudel, Martijn, Herter, Willem E., Girbes, Armand R.J., Hoogendoorn, Mark, Thoral, Patrick J., Elbers, Paul W.G., Fleuren, Lucas M., Dam, Tariq A., Tonutti, Michele, de Bruin, Daan P., Lalisang, Robbert C.A., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., 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., 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., Arbous, Sesmu, Vonk, Sebastiaan J.J., Fornasa, Mattia, Machado, Tomas, Houwert, Taco, Hovenkamp, Hidde, Noorduijn-Londono, Roberto, Quintarelli, Davide, Scholtemeijer, Martijn G., de Beer, Aletta A., Cina, Giovanni, Beudel, Martijn, Herter, Willem E., Girbes, Armand R.J., Hoogendoorn, Mark, Thoral, Patrick J., and Elbers, Paul W.G.

Abstract

Background: The Coronavirus disease 2019 (COVID-19) pandemic has underlined the urgent need for reliable, multicenter, and full-admission intensive care data to advance our understanding of the course of the disease and investigate potential treatment strategies. In this study, we present the Dutch Data Warehouse (DDW), the first multicenter electronic health record (EHR) database with full-admission data from critically ill COVID-19 patients. Methods: A nation-wide data sharing collaboration was launched at the beginning of the pandemic in March 2020. All hospitals in the Netherlands were asked to participate and share pseudonymized EHR data from adult critically ill COVID-19 patients. Data included patient demographics, clinical observations, administered medication, laboratory determinations, and data from vital sign monitors and life support devices. Data sharing agreements were signed with participating hospitals before any data transfers took place. Data were extracted from the local EHRs with prespecified queries and combined into a staging dataset through an extract–transform–load (ETL) pipeline. In the consecutive processing pipeline, data were mapped to a common concept vocabulary and enriched with derived concepts. Data validation was a continuous process throughout the project. All participating hospitals have access to the DDW. Within legal and ethical boundaries, data are available to clinicians and researchers. Results: Out of the 81 intensive care units in the Netherlands, 66 participated in the collaboration, 47 have signed the data sharing agreement, and 35 have shared their data. Data from 25 hospitals have passed through the ETL and processing pipeline. Currently, 3464 patients are included in the DDW, both from wave 1 and wave 2 in the Netherlands. More than 200 million clinical data points are available. Overall ICU mortality was 24.4%. Respiratory and hemodynamic parameters were most frequently measured throughout a patient's stay. For each

Published
2021

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