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1. Characterizing the Clinical Features and Atrophy Patterns of MAPT-Related Frontotemporal Dementia With Disease Progression Modeling

Author

Young, Alexandra L, Bocchetta, Martina, Seelaar, Harro, Bruffaerts, Rose, Van Damme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B, Miltenberger, Gabriel, Maruta, Carolina, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Caroppo, Paola, Moreno, Fermin, Di Fede, Giuseppe, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Branco, Miguel Castelo, Leitão, Maria João, Sanchez-Valle, Raquel, Pereira, Miguel Tábuas, Santiago, Beatriz, Gauthier, Serge, Neto, Pedro Rosa, Veldsman, Michele, Thompson, Paul, Prix, Catharina, Hoegen, Tobias, Mag Rer Nat, Elisabeth Wlasich, Loosli, Sandra, Borroni, Barbara, Schönecker, Sonja, Dr Hum Bio, Elisa Semler, Psych, Dipl, Anderl-Straub, Sarah, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Laforce, Robert, Masellis, Mario, Tartaglia, Maria Carmela, Graff, Caroline, Galimberti, Daniela, Rowe, James B, Russell, Lucy L, Finger, Elizabeth, Synofzik, Matthis, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris, Gerhard, Alex, Levin, Johannes, Convery, Rhian S, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Williams, Steven C R, Alexander, Daniel C, Rohrer, Jonathan D, Initiative, Genetic FTD, Rossor, Martin N, Fox, Nick C, Warren, Jason D, Peakman, Georgia, Woollacott, Ione, Shafei, Rachelle, Heller, Carolin, Swift, Imogen J, Moore, Katrina, Guerreiro, Rita, Bras, Jose, Thomas, David L, Nicholas, Jennifer, Mead, Simon, Todd, Emily, Meeter, Lieke, Panman, Jessica, Papma, Janne M, Poos, Jackie, van Minkelen, Rick, Pijnenburg, Yolande, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, Cash, David M, de Arriba, María, Gorostidi, Ana, Zulaica, Miren, Villanua, Jorge, Díaz, Zigor, Borrego-Ecija, Sergi, Olives, Jaume, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Greaves, Caroline V, Bargalló, Nuria, Premi, Enrico, Cosseddu, Maura, Gazzina, Stefano, Padovani, Alessandro, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, van Swieten, John, Freedman, Morris, Keren, Ron, Tang-Wai, David, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Thonberg, Hakan, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Jiskoot, Lize, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnath, Hans Otto, Bender, Benjamin, Young, Alexandra L [0000-0002-7772-781X], Todd, Emily [0000-0003-1551-5691], Cash, David M [0000-0001-7833-616X], Seelaar, Harro [0000-0003-1989-7527], Laforce, Robert [0000-0002-2031-490X], Galimberti, Daniela [0000-0002-9284-5953], Vandenberghe, Rik [0000-0001-6237-2502], Danek, Adrian [0000-0001-8857-5383], Otto, Markus [0000-0003-4273-4267], Williams, Steven CR [0000-0003-4299-1941], Apollo - University of Cambridge Repository, Genetic FTD Initiative (GENFI), Repositório da Universidade de Lisboa, and Neurology

Subjects
Male, Medizin, Hippocampus, volumetric MRI, frontotemporal dementia, Machine Learning, 0302 clinical medicine, pathology [Brain], 030212 general & internal medicine, genetics [Frontotemporal Dementia], Temporal cortex, pathology [Atrophy], Brain, Middle Aged, Magnetic Resonance Imaging, neuropsychological assessment, medicine.anatomical_structure, Frontotemporal Dementia, Disease Progression, CHAMELEON, Female, methods [Neuroimaging], Life Sciences & Biomedicine, Research Article, Frontotemporal dementia, genetics [Atrophy], Adult, Ventromedial prefrontal cortex, Clinical Neurology, Neuroimaging, MAPT protein, human, tau Proteins, methods [Image Interpretation, Computer-Assisted], Biology, Temporal lobe, 03 medical and health sciences, Atrophy, Image Interpretation, Computer-Assisted, Aged, Humans, Mutation, medicine, ddc:610, Science & Technology, MUTATIONS, medicine.disease, genetics [tau Proteins], association studies in genetics, pathology [Frontotemporal Dementia], Neurology (clinical), Neurosciences & Neurology, Neuroscience, Insula, 030217 neurology & neurosurgery, Executive dysfunction
Abstract

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., Background and objective: Mutations in the MAPT gene cause frontotemporal dementia (FTD). Most previous studies investigating the neuroanatomical signature of MAPT mutations have grouped all different mutations together and shown an association with focal atrophy of the temporal lobe. However, the variability in atrophy patterns between each particular MAPT mutation is less well characterised. We aimed to investigate whether there were distinct groups of MAPT mutation carriers based on their neuroanatomical signature. Methods: We applied Subtype and Stage Inference (SuStaIn), an unsupervised machine learning technique that identifies groups of individuals with distinct progression patterns, to characterise patterns of regional atrophy in MAPT-associated FTD within the Genetic FTD Initiative (GENFI) cohort study. Results: 82 MAPT mutation carriers were analysed, the majority of whom had P301L, IVS10+16 or R406W mutations, along with 48 healthy non-carriers. SuStaIn identified two groups of MAPT mutation carriers with distinct atrophy patterns: a 'temporal' subtype in which atrophy was most prominent in the hippocampus, amygdala, temporal cortex and insula, and a 'frontotemporal' subtype in which atrophy was more localised to the lateral temporal lobe and anterior insula, as well as the orbitofrontal and ventromedial prefrontal cortex and anterior cingulate. There was a one-to-one mapping between IVS10+16 and R406W mutations and the temporal subtype, and a near one-to-one mapping between P301L mutations and the frontotemporal subtype. There were differences in clinical symptoms and neuropsychological test scores between subtypes: the temporal subtype was associated with amnestic symptoms, whereas the frontotemporal subtype was associated with executive dysfunction. Discussion: Our results demonstrate that different MAPT mutations give rise to distinct atrophy patterns and clinical phenotype, providing insights into the underlying disease biology, and potential utility for patient stratification in therapeutic trials., The Dementia Research Centre is supported by Alzheimer's Research UK, Brain Research Trust, and The Wolfson Foundation. This work was supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and Kings College London, as well as an Alzheimer's Society grant (AS-PG-16-007). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Italian Ministry of Health (CoEN015 and Ricerca Corrente), and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant and The Bluefield Project, and the JPND GENFI-PROX grant (2019-02248). This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy ID 390857198). Nonfinancial support was also provided through the European Reference Network for Rare Neurologic Diseases (ERN-RND), 1 of 24 ERNs funded by the European Commission (ERNRND: 3HP 767231).

Published
2021
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2. Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit

Author

Guidet B., Flaatten H., Boumendil A., Morandi A., Andersen F. H., Artigas A., Bertolini G., Cecconi M., Christensen S., Faraldi L., Fjolner J., Jung C., Marsh B., Moreno R., Oeyen S., Ohman C. A., Pinto B. B., Soliman I. W., Szczeklik W., Valentin A., Watson X., Zafeiridis T., De Lange D. W., Schmutz R., Wimmer F., Eller P., Zotter K., De Buysscher P., De Neve N., Swinnen W., Abraham P., Hergafi L., Schefold J. C., Biskup E., Taliadoros I., Piza P., Lauten A., Sacher A. L., Brenner T., Franz M., Bloos F., Ebelt H., Schaller S. J., Fuest K., Rabe C., Dieck T., Steiner S., Graf T., Nia A. M., Janosi R. A., Simon P., Utzolino S., Rahmel T., Barth E., Schuster M., Dey N., Solling C., Rasmussen B. S., Rodriguez E., Rebollo S., Aguilar G., Masdeu G., Jaimes M. I., Mira A. P., Bodi M. A., Barea Mendoza J. A., Lopez-Cuenca S., Guzman M. H., Rico-Feijoo J., Ibarz M., Alvarez J. T., Forceville X., Besch G., Mentec H., Michel P., Mateu P., Vettoretti L., Bourenne J., Marin N., Guillot M., Aissaoui N., Goulenok C., Thieulot-Rolin N., Messika J., Lamhaut L., Charron C., Dempsey G., Mathew S. J., Raj A. S., Grecu I., Cupitt J., Lawton T., Clark R., Popescu M., Spittle N., Faulkner M., Cowton A., Elloway E., Williams P., Reay M., Chukkambotla S., Kumar R., Al-Subaie N., Kent L., Tamm T., Kajtor I., Burns K., Pugh R., Ostermann M., Kam E., Bowyer H., Smith N., Templeton M., Henning J., Goffin K., Kapoor R., Laha S., Chilton P., Khaliq W., Crayford A., Coetzee S., Tait M., Stoker W., Gimenez M., Pope A., Camsooksai J., Pogson D., Quigley K., Ritzema J., Hormis A., Boulanger C., Balasubramaniam M., Vamplew L., Burt K., Martin D., Craig J., Prowle J., Doyle N., Shelton J., Scott C., Donnison P., Shelton S., Frey C., Ryan C., Spray D., Barnes V., Barnes K., Ridgway S., Saha R., Clark T., Wood J., Bolger C., Bassford C., Lewandowski J., Zhao X., Humphreys S., Dowling S., Richardson N., Burtenshaw A., Stevenson C., Wilcock D., Aidoni Z., Aloizos S., Tasioudis P., Lampiri K., Zisopoulou V., Ravani I., Pagaki E., Antoniou A., Katsoulas T. A., Kounougeri A., Marinakis G., Tsimpoukas F., Spyropoulou A., Zygoulis P., Kyparissi A., Hayes I., Kelly Y., Westbrook A., Fitzpatrick G., Maheshwari D., Motherway C., Gupta M., Gurjar M., Maji I. M., Negri G., Spadaro S., Nattino G., Pedeferri M., Boscolo A., Rossi S., Calicchio G., Cubattoli L., Di Lascio G., Barbagallo M., Berruto F., Codazzi D., Bottazzi A., Fumagalli P., Negro G., Lupi G., Savelli F., Vulcano G. A., Fumagalli R., Marudi A., Lefons U., Lembo R., Babini M., Paggioro A., Parrini V., Zaccaria M., Clementi S., Gigliuto C., Facondini F., Pastorini S., Munaron S., Calamai I., Bocchi A., Adorni A., Bocci M. G., Cortegiani A., Casalicchio T., Mellea S., Graziani E., Barattini M., Brizio E., Rossi M., van Dijk I., van Lelyveld-Haas L. E. M., Ramnarain D., Jansen T., Nooteboom F., van der Voort P. H., de Lange D., Dieperink W., de Waard M. C., de Smet A. G. E., Bormans L., Dormans T., Hahn M., Kemmerer N., Strietzel H. F., Dybwik K., Legernaes T., Klepstad P., Olaussen E. B., Olsen K. I., Brresen O. M., Bjorsvik G., Maini S., Fehrle L., Czuczwar M., Krawczyk P., Zietkiewicz M., Nowak L. R., Kotfis K., Cwyl K., Gajdosz R., Biernawska J., Bohatyrewicz R., Gawda R., Grudzien P., Nasilowski P., Popek N., Cyrankiewicz W., Wawrzyniak K., Wnuk M., Maciejewski D., Studzinska D., Zukowski M., Bernas S., Piechota M., Nowak I., Fronczek J., Serwa M., Machala W., Stefaniak J., Wujtewicz M., Maciejewski P., Szymkowiak M., Adamik B., Catorze N., Branco M. C., Barros I., Barros N., Krystopchuk A., Honrado T., Sousa C., Munoz F., Rebelo M., Gomes R., Nunes J., Dias C., Fernandes A. M., Petrisor C., Constantin B., Belskiy V., Boskholov B., Kawati R., Sivik J., Nauska J., Smole D., Parenmark F., Lyren J., Rockstroh K., Ryden S., Spangfors M., Strinnholm M., Walther S., De Geer L., Nordlund P., Palsson S., Zetterquist H., Nilsson A., Thiringer K., Jungner M., Bark B., Nordling B., Skold H., Brorsson C., Persson S., Bergstrom A., Berkius J., Holmstrom J., Nalapko Y., Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Bergen (UiB), Haukeland University Hospital, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Universitat Autònoma de Barcelona (UAB), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), St George's, University of London, Aarhus University Hospital, Ghent University Hospital, Karolinska University Hospital [Stockholm], Hôpitaux Universitaires de Genève (HUG), University Medical Center [Utrecht], Utrecht University [Utrecht], Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Guidet, B, Flaatten, H, Boumendil, A, Morandi, A, Andersen, F, Artigas, A, Bertolini, G, Cecconi, M, Christensen, S, Faraldi, L, Fjolner, J, Jung, C, Marsh, B, Moreno, R, Oeyen, S, Ohman, C, Pinto, B, Soliman, I, Szczeklik, W, Valentin, A, Watson, X, Zafeiridis, T, De Lange, D, Schmutz, R, Wimmer, F, Eller, P, Zotter, K, De Buysscher, P, De Neve, N, Swinnen, W, Abraham, P, Hergafi, L, Schefold, J, Biskup, E, Taliadoros, I, Piza, P, Lauten, A, Sacher, A, Brenner, T, Franz, M, Bloos, F, Ebelt, H, Schaller, S, Fuest, K, Rabe, C, Dieck, T, Steiner, S, Graf, T, Nia, A, Janosi, R, Simon, P, Utzolino, S, Rahmel, T, Barth, E, Schuster, M, Dey, N, Solling, C, Rasmussen, B, Rodriguez, E, Rebollo, S, Aguilar, G, Masdeu, G, Jaimes, M, Mira, A, Bodi, M, Barea Mendoza, J, Lopez-Cuenca, S, Guzman, M, Rico-Feijoo, J, Ibarz, M, Alvarez, J, Forceville, X, Besch, G, Mentec, H, Michel, P, Mateu, P, Vettoretti, L, Bourenne, J, Marin, N, Guillot, M, Aissaoui, N, Goulenok, C, Thieulot-Rolin, N, Messika, J, Lamhaut, L, Charron, C, Dempsey, G, Mathew, S, Raj, A, Grecu, I, Cupitt, J, Lawton, T, Clark, R, Popescu, M, Spittle, N, Faulkner, M, Cowton, A, Elloway, E, Williams, P, Reay, M, Chukkambotla, S, Kumar, R, Al-Subaie, N, Kent, L, Tamm, T, Kajtor, I, Burns, K, Pugh, R, Ostermann, M, Kam, E, Bowyer, H, Smith, N, Templeton, M, Henning, J, Goffin, K, Kapoor, R, Laha, S, Chilton, P, Khaliq, W, Crayford, A, Coetzee, S, Tait, M, Stoker, W, Gimenez, M, Pope, A, Camsooksai, J, Pogson, D, Quigley, K, Ritzema, J, Hormis, A, Boulanger, C, Balasubramaniam, M, Vamplew, L, Burt, K, Martin, D, Craig, J, Prowle, J, Doyle, N, Shelton, J, Scott, C, Donnison, P, Shelton, S, Frey, C, Ryan, C, Spray, D, Barnes, V, Barnes, K, Ridgway, S, Saha, R, Clark, T, Wood, J, Bolger, C, Bassford, C, Lewandowski, J, Zhao, X, Humphreys, S, Dowling, S, Richardson, N, Burtenshaw, A, Stevenson, C, Wilcock, D, Aidoni, Z, Aloizos, S, Tasioudis, P, Lampiri, K, Zisopoulou, V, Ravani, I, Pagaki, E, Antoniou, A, Katsoulas, T, Kounougeri, A, Marinakis, G, Tsimpoukas, F, Spyropoulou, A, Zygoulis, P, Kyparissi, A, Hayes, I, Kelly, Y, Westbrook, A, Fitzpatrick, G, Maheshwari, D, Motherway, C, Gupta, M, Gurjar, M, Maji, I, Negri, G, Spadaro, S, Nattino, G, Pedeferri, M, Boscolo, A, Rossi, S, Calicchio, G, Cubattoli, L, Di Lascio, G, Barbagallo, M, Berruto, F, Codazzi, D, Bottazzi, A, Fumagalli, P, Negro, G, Lupi, G, Savelli, F, Vulcano, G, Fumagalli, R, Marudi, A, Lefons, U, Lembo, R, Babini, M, Paggioro, A, Parrini, V, Zaccaria, M, Clementi, S, Gigliuto, C, Facondini, F, Pastorini, S, Munaron, S, Calamai, I, Bocchi, A, Adorni, A, Bocci, M, Cortegiani, A, Casalicchio, T, Mellea, S, Graziani, E, Barattini, M, Brizio, E, Rossi, M, van Dijk, I, van Lelyveld-Haas, L, Ramnarain, D, Jansen, T, Nooteboom, F, van der Voort, P, de Lange, D, Dieperink, W, de Waard, M, de Smet, A, Bormans, L, Dormans, T, Hahn, M, Kemmerer, N, Strietzel, H, Dybwik, K, Legernaes, T, Klepstad, P, Olaussen, E, Olsen, K, Brresen, O, Bjorsvik, G, Maini, S, Fehrle, L, Czuczwar, M, Krawczyk, P, Zietkiewicz, M, Nowak, L, Kotfis, K, Cwyl, K, Gajdosz, R, Biernawska, J, Bohatyrewicz, R, Gawda, R, Grudzien, P, Nasilowski, P, Popek, N, Cyrankiewicz, W, Wawrzyniak, K, Wnuk, M, Maciejewski, D, Studzinska, D, Zukowski, M, Bernas, S, Piechota, M, Nowak, I, Fronczek, J, Serwa, M, Machala, W, Stefaniak, J, Wujtewicz, M, Maciejewski, P, Szymkowiak, M, Adamik, B, Catorze, N, Branco, M, Barros, I, Barros, N, Krystopchuk, A, Honrado, T, Sousa, C, Munoz, F, Rebelo, M, Gomes, R, Nunes, J, Dias, C, Fernandes, A, Petrisor, C, Constantin, B, Belskiy, V, Boskholov, B, Kawati, R, Sivik, J, Nauska, J, Smole, D, Parenmark, F, Lyren, J, Rockstroh, K, Ryden, S, Spangfors, M, Strinnholm, M, Walther, S, De Geer, L, Nordlund, P, Palsson, S, Zetterquist, H, Nilsson, A, Thiringer, K, Jungner, M, Bark, B, Nordling, B, Skold, H, Brorsson, C, Persson, S, Bergstrom, A, Berkius, J, Holmstrom, J, Nalapko, Y, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Guidet, Bertrand, Flaatten, Han, Boumendil, Ariane, Morandi, Alessandro, Andersen, Finn H., Artigas, Antonio, Bertolini, Guido, Cecconi, Maurizio, Christensen, Steffen, Faraldi, Loredana, Fjølner, Jesper, Jung, Christian, Marsh, Brian, Moreno, Rui, Oeyen, Sandra, Öhman, Christina Agwald, Pinto, Bernardo Bollen, Soliman, Ivo W., Szczeklik, Wojciech, Valentin, Andrea, Watson, Ximena, Zafeiridis, Tilemacho, de Lange, Dylan W., Schmutz, René, Wimmer, Franz, Eller, Philipp, Zotter, Klemen, de Buysscher, Pieter, de Neve, Nikolaa, Swinnen, Walter, Abraham, Paul, Hergafi, Leila, Schefold, Joerg C., Biskup, Ewelina, Taliadoros, Ioanni, Piza, Petr, Lauten, Alexander, Sacher, Anna Lena, Brenner, Thorsten, Franz, Marcu, Bloos, Frank, Ebelt, Henning, Schaller, Stefan J, Fuest, Kristina, Rabe, Christian, Dieck, Thorben, Steiner, Stephan, Graf, Tobia, Nia, Amir M, Janosi, Rolf Alexander, Simon, Philipp, Utzolino, Stefan, Rahmel, Tim, Barth, Eberhard, Schuster, Michael, Dey, Nilanjan, Sølling, Christoffer, Rasmussen, Bodil Steen, Rodriguez, Enver, Rebollo, Sergio, Aguilar, Gerardo, Masdeu, Gaspar, Jaimes, Marián Irazábal, Mira, Ángela Prado, Bodi, Maria A., Barea Mendoza, Jesus A., López-Cuenca, Sonia, Guzman, Marcela Homez, Rico-Feijoo, Jesú, Ibarz, Mercede, Alvarez, Josep Trenado, Forceville, Xavier, Besch, Guillaume, Mentec, Herve, Michel, Philippe, Mateu, Philippe, Vettoretti, Lucie, Bourenne, Jeremy, MARIN, Nathalie, Guillot, Max, Aissaoui, Naida, Goulenok, Cyril, Thieulot-Rolin, Nathalie, Messika, Jonathan, Lamhaut, Lionel, Charron, Cyril, Dempsey, Ged, Mathew, Shiju J, Raj, Ashok S, Grecu, Irina, Cupitt, Jason, Lawton, Tom, Clark, Richard, Popescu, Monica, Spittle, Nick, Faulkner, Maria, Cowton, Amanda, Elloway, Esme, Williams, Patricia, Reay, Michael, Chukkambotla, Srikanth, Kumar, Ravi, Al-Subaie, Nawaf, Kent, Linda, Tamm, Tiina, Kajtor, Istvan, Burns, Karen, Pugh, Richard, Ostermann, Marlie, Kam, Elisa, Bowyer, Helen, Smith, Neil, Templeton, Maie, Henning, Jeremy, Goffin, Kelly, Kapoor, Ritoo, Laha, Shondipon, Chilton, Phil, Khaliq, Waqa, Crayford, Alison, Coetzee, Samantha, Tait, Moira, Stoker, Wendy, Gimenez, Marc, Pope, Alan, Camsooksai, Julie, Pogson, David, Quigley, Kate, Ritzema, Jenny, Hormis, Anil, Boulanger, Carole, Balasubramaniam, M., Vamplew, Luke, Burt, Karen, Martin, Daniel, Craig, Jayne, Prowle, John, Doyle, Nanci, Shelton, Jonathon, Scott, Carmen, Donnison, Phil, Shelton, Sarah, Frey, Christian, Ryan, Christine, Spray, Dominic, Barnes, Veronica, Barnes, Kerry, Ridgway, Stephanie, Saha, Rajnish, Clark, Thoma, Wood, Jame, Bolger, Clare, Bassford, Christopher, Lewandowski, John, Zhao, Xiaobei, Humphreys, Sally, Dowling, Susan, Richardson, Neil, Burtenshaw, Andrew, Stevenson, Carl, Wilcock, Danielle, Aidoni, Zoi, Aloizos, Stavro, Tasioudis, Polychroni, Lampiri, Kleri, Zisopoulou, Vasiliki, Ravani, Ifigenia, Pagaki, Eumorfia, Antoniou, Angela, Katsoulas, Theodoros A., Kounougeri, Aikaterini, Marinakis, George, Tsimpoukas, Fotio, Spyropoulou, Anastasia, Zygoulis, Pari, Kyparissi, Aikaterini, Hayes, Ivan, Kelly, Yvelynne, Westbrook, Andrew, Fitzpatrick, Gerry, Maheshwari, Darshana, Motherway, Catherine, Gupta, Manish, Gurjar, Mohan, Maji, Ismail M, Negri, Giovanni, Spadaro, Savino, Nattino, Giuseppe, Pedeferri, Matteo, Boscolo, Annalisa, Rossi, Simona, Calicchio, Giuseppe, Cubattoli, Lucia, Di Lascio, Gabriella, Barbagallo, Maria, Berruto, Francesco, Codazzi, Daniela, Bottazzi, Andrea, Fumagalli, Paolo, Negro, Giancarlo, Lupi, Giuseppe, Savelli, Flavia, Vulcano, Giuseppe A., Fumagalli, Roberto, Marudi, Andrea, Lefons, Ugo, Lembo, Rita, Babini, Maria, Paggioro, Alessandra, Parrini, Vieri, Zaccaria, Maria, Clementi, Stefano, Gigliuto, Carmelo, Facondini, Francesca, Pastorini, Simonetta, Munaron, Susanna, Calamai, Italo, Bocchi, Anna, Adorni, Adele, Bocci, Maria Grazia, Cortegiani, Andrea, Casalicchio, Tiziana, Mellea, Serena, Graziani, Elia, Barattini, Massimo, Brizio, Elisabetta, Rossi, Maurizio, van Dijk, I., van Lelyveld-Haas, L.E.M., Ramnarain, D., Jansen, Tim, Nooteboom, Fleur, van der Voort, Peter HJ, de Lange, Dylan, Dieperink, Willem, de Waard, Monique C., de Smet, Annemarie G. E., Bormans, Laura, Dormans, Tom, Hahn, Michael, Kemmerer, Nicolai, Strietzel, Hans Frank, Dybwik, Knut, Legernaes, Terje, Klepstad, Pål, Olaussen, Even Braut, Olsen, Knut Inge, Brresen, Ole Mariu, Bjorsvik, Geir, Maini, Sameer, Fehrle, Lutz, Czuczwar, Miroslaw, Krawczyk, Pawel, Ziętkiewicz, Mirosław, Nowak, Łukasz R., Kotfis, Katarzyna, Cwyl, Katarzyna, Gajdosz, Ryszard, Biernawska, Jowita, Bohatyrewicz, Romuald, Gawda, Ryszard, Grudzień, Paweł, Nasiłowski, Paweł, Popek, Natalia, Cyrankiewicz, Waldemar, Wawrzyniak, Katarzyna, Wnuk, Marek, Maciejewski, Dariusz, Studzińska, Dorota, Żukowski, Maciej, Bernas, Szymon, Piechota, Mariusz, Nowak, Ilona, Fronczek, Jakub, Serwa, Marta, Machała, Waldemar, Stefaniak, Jan, Wujtewicz, Maria, Maciejewski, Paweł, Szymkowiak, Małgorzata, Adamik, Barbara, Catorze, Nuno, Branco, Miguel Castelo, Barros, Inê, Barros, Nelson, Krystopchuk, Andriy, Honrado, Teresa, Sousa, Cristina, Munoz, Francisco, Rebelo, Marta, Gomes, Rui, Nunes, Jorge, Dias, Celeste, Fernandes, Ana Margarida, Petrisor, Cristina, Constantin, Bodolea, Belskiy, Vladislav, Boskholov, Bori, Kawati, Rafael, Sivik, Joakim, Nauska, Jessica, Smole, Daniel, Parenmark, Fredric, Lyrén, Johanna, Rockstroh, Katalin, Rydén, Sara, Spångfors, Martin, Strinnholm, Morten, Walther, Sten, de Geer, Lina, Nordlund, Peter, Pålsson, Staffan, Zetterquist, Harald, Nilsson, Annika, Thiringer, Karin, Jungner, Mårten, Bark, Björn, Nordling, Berit, Sköld, Han, Brorsson, Camilla, Persson, Stefan, Bergström, Anna, Berkius, Johan, Holmström, Johanna, Nalapko, Yuiry, and Critical Care

Subjects
Male, medicine.medical_treatment, HSJ UCI, Critical Care and Intensive Care Medicine, law.invention, Life sustaining treatment, 0302 clinical medicine, Elderly, law, 80 and over, Medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Aged, 80 and over, education.field_of_study, Withholding Treatment, ddc:617, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Withholding, Intensive care unit, 3. Good health, Europe, aged, Intensive Care Units, Withdrawal, SOFA score, Human, medicine.medical_specialty, ethical aspects, Population, Intensive Care Unit, Decision Making, Ethics, Intensive care, life-sustaining therapy, NO, 03 medical and health sciences, Anesthesiology, Humans, Ethic, education, Mechanical ventilation, business.industry, 030208 emergency & critical care medicine, critical care, Life Support Care, Prospective Studie, Emergency medicine, business
Abstract

PURPOSE: To document and analyse the decision to withhold or withdraw life-sustaining treatment (LST) in a population of very old patients admitted to the ICU. METHODS: This prospective study included intensive care patients aged ≥ 80 years in 309 ICUs from 21 European countries with 30-day mortality follow-up. RESULTS: LST limitation was identified in 1356/5021 (27.2%) of patients: 15% had a withholding decision and 12.2% a withdrawal decision (including those with a previous withholding decision). Patients with LST limitation were older, more frail, more severely ill and less frequently electively admitted. Patients with withdrawal of LST were more frequently male and had a longer ICU length of stay. The ICU and 30-day mortality were, respectively, 29.1 and 53.1% in the withholding group and 82.2% and 93.1% in the withdrawal group. LST was less frequently limited in eastern and southern European countries than in northern Europe. The patient-independent factors associated with LST limitation were: acute ICU admission (OR 5.77, 95% CI 4.32-7.7), Clinical Frailty Scale (CFS) score (OR 2.08, 95% CI 1.78-2.42), increased age (each 5 years of increase in age had a OR of 1.22 (95% CI 1.12-1.34) and SOFA score [OR of 1.07 (95% CI 1.05-1.09 per point)]. The frequency of LST limitation was higher in countries with high GDP and was lower in religious countries. CONCLUSIONS: The most important patient variables associated with the instigation of LST limitation were acute admission, frailty, age, admission SOFA score and country. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NTC03134807). info:eu-repo/semantics/publishedVersion

Published
2018
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