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1. Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational studyResearch in context

Author

Priyen Shah, Marie Voice, Leonides Calvo-Bado, Irene Rivero-Calle, Sophie Morris, Ruud Nijman, Claire Broderick, Tisham De, Irini Eleftheriou, Rachel Galassini, Aakash Khanijau, Laura Kolberg, Mojca Kolnik, Aleksandra Rudzate, Manfred G. Sagmeister, Nina A. Schweintzger, Fatou Secka, Clare Thakker, Fabian van der Velden, Clementien Vermont, Katarina Vincek, Philipp K.A. Agyeman, Aubrey J. Cunnington, Ronald De Groot, Marieke Emonts, Katy Fidler, Taco W. Kuijpers, Marine Mommert-Tripon, Karen Brengel-Pesce, Francois Mallet, Henriette Moll, Stéphane Paulus, Marko Pokorn, Andrew Pollard, Luregn J. Schlapbach, Ching-Fen Shen, Maria Tsolia, Effua Usuf, Michiel van der Flier, Ulrich von Both, Shunmay Yeung, Dace Zavadska, Werner Zenz, Victoria Wright, Enitan D. Carrol, Myrsini Kaforou, Federico Martinon-Torres, Colin Fink, Michael Levin, Jethro Herberg, Irene Rivero Calle, Manfred Sagmeister, Nina Schweintzger, Fabian Van der Velden, Taco Kuijpers, Michiel Van der Flier, Ulrich Von Both, Lucas Baumard, Evangelos Bellos, Lachlan Coin, Giselle D'Souza, Dominic Habgood-Coote, Shea Hamilton, Cllive Hoggart, Sara Hourmat, Heather Jackson, Naomi Lin, Stephanie Menikou, Samuel Nichols, Ivonne Pena Paz, Oliver Powell, Ortensia Vito, Clare Wilson, Amina Abdulla, Ladan Ali, Sarah Darnell, Rikke Jorgensen, Ian Maconochie, Sobia Mustafa, Salina Persand, Ben Walsh, Molly Stevens, Nayoung Kim, Eunjung Kim, Benjamin Pierce, Julia Dudley, Vivien Richmond, Emma Tavliavini, Ching-Chuan Liu, Shih-Min Wang, Fernando Álves González, Cristina Balo Farto, Ruth Barral-Arca, María Barreiro Castro, Xabier Bello, Mirian Ben García, Sandra Carnota, Miriam Cebey-López, María José Curras-Tuala, Carlos Durán Suárez, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Pilar Leboráns Iglesias, Nazareth Martinón-Torres, José María Martinón Sánchez, Belén Mosquera Pérez, Jacobo Pardo-Seco, Lidia Piñeiro Rodríguez, Sara Pischedda, Sara Ray Vázquez, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Miguel Sadiki Ora, Antonio Sallas, Sonia Serén Fernández, Cristina Serén Trasorras, Marisol Vilas Iglesias, Anda Balode, Arta Bãrdzdina, Dãrta Deksne, Dace Gardovska, Dagne Grãvele, Ilze Grope, Anija Meiere, Ieve Nokalna, Jana Pavãre, Zanda Pučuka, Katrīna Selecka, Dace Svile, Urzula Nora Urbãne, Kalifa Bojang, Syed M.A. Zaman, Suzanne Anderson, Anna Roca, Isatou Sarr, Momodou Saidykhan, Saffiatou Darboe, Samba Ceesay, Umberto D'alessandro, Dorine M. Borensztajn, Nienke N. Hagedoorn, Chantal Tal, Joany Zachariasse, W. Dik, Christoph Aebi, Christoph Berger, Verena Wyss, Mariama Usman, Eric Giannoni, Martin Stocker, Klara M. Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Giancarlo Natalucci, Christa Relly, Thomas Riedel, Elizabeth Cocklin, Rebecca Jennings, Joanne Johnson, Simon Leigh, Karen Newall, Sam Romaine, Maria Tambouratzi, Antonis Marmarinos, Marietta Xagorari, Kelly Syggelou, Nikos Spyridis, Jennifer Blackmore, Rebekah Harrison, Benno Kohlmaier, Daniela S. Kohlfürst, Christoph Zurl, Alexander Binder, Susanne Hösele, Manuel Leitner, Lena Pölz, Glorija Rajic, Sebastian Bauchinger, Hinrich Baumgart, Martin Benesch, Astrid Ceolotto, Ernst Eber, Siegfried Gallisti, Gunther Gores, Harald Haidl, Almuthe Hauer, Christa Hude, Markus Keldorfer, Larissa Krenn, Heidemarie Pilch, Andreas Pfleger, Klaus Pfurtscheller, Gudrun Nordberg, Tobias Niedrist, Siegfried Rödl, Andrea Skrabl-Baumgartner, Matthias Sperl, Laura Stampfer, Volker Strenger, Holger Till, Andreas Trobisch, Sabine Löffler, Juan Emmanuel Dewez, Martin Hibberd, David Bath, Alec Miners, Elizabeth Fitchett, Catherine Wedderburn, Anne Meierford, Baptiste Leurent, Marien I. De Jonge, Koen van Aerde, Wynand Alkema, Bryan van den Broek, Jolein Gloerich, Alain J. Van Gool, Stefanie Henriet, Martijn Huijnen, Ria Philipsen, Esther Willems, G.P.J.M. Gerrits, M. Van Leur, J. Heidema, L. De Haan, C.J. Miedema, C. Neeleman, C.C. Obihara, G.A. Tramper-Stranders, Rama Kandasamy, Michael J. Carter, Daniel O'Connor, Sagida Bibi, Dominic F. Kelly, Meeru Gurung, Stephen Throson, Imran Ansari, David R. Murdoch, Shrijana Shrestha, Zoe Oliver, Emma Lim, Lucille Valentine, Karen Allen, Kathryn Bell, Adora Chan, Stephen Crulley, Kirsty Devine, Daniel Fabian, Sharon King, Paul McAlinden, Sam McDonald, Anne McDonell, Alisa Pickering, Evelyn Thomson, Amanda Wood, Diane Wallia, Phil Woodsford, Frances Baxter, Ashley Bell, Mathew Rhodes, Rachel Agbeko, Christine Mackerness, Bryan Baas, Lieke Kloosterhuis, Wilma Oosthoek, Tasnim Arif, Joshua Bennet, Kalvin Collings, Ilona Van der Giessen, Alex Martin, Aqeela Rashid, Emily Rowlands, Joshua Soon, Gabriella De Vries, Mike Martin, Ravi Mistry, Manuela Zwerenz, Judith Buschbeck, Christoph Bidlingmaier, Vera Binder, Katharina Danhauser, Nikolaus Haas, Matthias Griese, Matthias Kappler, Eberhard Lurz, Georg Muench, Karl Reiter, Carola Schoen, Alexandre Pachot, Marine Mommert, Tina Plankar Srovin, Natalija Bahovec, Petra Prunk, Veronika Osterman, Tanja Avramoska, Ilse Jongerius, J.M. van den Berg, D. Schonenberg, A.M. Barendregt, D. Pajkrt, M. van der Kuip, A.M. van Furth, Evelien Sprenkeler, Judith Zandstra, G. van Mierlo, and J. Geissler

Subjects
Molecular diagnostics, Diagnostic, Febrile illness, Infectious disease, Bacterial, Viral, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016–2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92–5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07–7.59), Group A streptococcus (OR 2.73, 95% CI 1.13–6.09) and E. coli (OR 2.7, 95% CI 1.02–6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11–0.46), influenza B (OR 0.12, 95% CI 0.02–0.37) and RSV (OR 0.16, 95% CI: 0.06–0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23–0.72) and EBV (OR 0.71, 95% CI 0.56–0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.

Published
2023
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2. Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Author

Esther Willems, Jolein Gloerich, Anouk Suppers, Michiel van der Flier, Lambert P. van den Heuvel, Nicole van de Kar, Ria H.L.A. Philipsen, Maurice van Dael, Myrsini Kaforou, Victoria J. Wright, Jethro A. Herberg, Federico Martinon Torres, Michael Levin, Ronald de Groot, Alain J. van Gool, Dirk J. Lefeber, Hans J.C.T. Wessels, Marien I. de Jonge, Amina Abdulla, Christoph Aebi, Koen van Aerde, Rachel Agbeko, Philipp Agyeman, Umberto D’alessandro, Ladan Ali, Wynand Alkema, Karen Allen, Fernando Álvez González, Suzanne Anderson, Imran Ansari, Tasnim Araf, Tanja Avramoska, Bryan Baas, Natalija Bahovec, Cristina Balo Farto, Anda Balode, A.M. Barendregt, Ruth Barral-Arca, María Barreiro Castro, Arta Bārzdiņa, David Bath, Sebastian Bauchinger, Lucas Baumard, Hinrich Baumgart, Frances Baxter, Ashley Bell, Kathryn Bell, Xabier Bello, Evangelos Bellos, Martin Benesch, Mirian Ben García, Joshua Bennet, Christoph Berger, J.M. van den Berg, Sara Bernhard-Stirnemann, Sagida Bibi, Christoph Bidlingmaier, Alexander Binder, Vera Binder, Kalifa Bojang, Dorine M. Borensztajn, Ulrich von Both, Karen Brengel-Pesce, Bryan van den Broek, Judith Buschbeck, Leo Calvo-Bado, Sandra Carnota, Enitan D. Carrol, Michael J. Carter, Miriam Cebey-López, Samba Ceesay, Astrid Ceolotto, Adora Chan, Elizabeth Cocklin, Kalvin Collings, Stephen Crulley, Aubrey Cunnington, María José Curras-Tuala, Katharina Danhauser, Saffiatou Darboe, Sarah Darnell, Tisham De, Dārta Deksne, Kirsty Devine, Juan Emmanuel Dewez, Julia Dudley, Carlos Durán Suárez, Ernst Eber, Irini Eleftheriou, Marieke Emonts, Daniel Fabian, Tobias Feuchtinger, Katy Fidler, Colin Fink, A.M. van Furth, Rachel Galassini, Siegfried Gallistl, Luisa García Vicente, Dace Gardovska, J. Geissler, G.P.J.M. Gerrits, Eric Giannoni, Ilona van der Giessen, Alberto Gómez-Carballa, Jose Gómez Rial, Gunther Gores, Dagne Grāvele, Matthias Griese, Ilze Grope, Meeru Gurung, L. de Haan, Nikolaus Haas, Dominic Habgood-Coote, Nienke N. Hagedoorn, Harald Haidl, Shea Hamilton, Almuthe Hauer, J. Heidema, Ulrich Heininger, Stefanie Henriet, Jethro Herberg, Clive Hoggart, Susanne Hösele, Sara Hourmat, Christa Hude, Martijn Huijnen, Heather Jackson, Rebecca Jennings, Joanne Johnston, Ilse Jongerius, Rikke Jorgensen, Christian Kahlert, Rama Kandasamy, Matthias Kappler, Julia Keil, Markus Keldorfer, Dominic F. Kell, Eunjung Kim, Sharon King, Lieke Kloosterhuis, Daniela S. Kohlfürst, Benno Kohlmaier, Laura Kolberg, Mojca Kolnik, Larissa Krenn, Taco Kuijpers, M. van der Kuip, Pilar Leboráns Iglesias, Simon Leigh, Manuel Leitner, M. van Leur, Emma Lim, Naomi Lin, Ching-Chuan Liu, Sabine Löffler, Eberhard Lurz, Ian Maconochie, Christine Mackerness, François Mallet, Federico Martinón-Torres, Antonis Marmarinos, Alex Martin, Mike Martin, José María Martinón Sánchez, Nazareth Martinón-Torres, Paul McAlinden, Anne McDonnell, Sam McDonald, C.J. Miedema, Anija Meiere, Stephanie Menikou, G. van Mierlo, Alec Miners, Ravi Mistry, Henriëtte A. Moll, Marine Mommert, Belén Mosquera Pérez, David R. Murdoch, Sobia Mustafa, Giancarlo Natalucci, C. Neeleman, Karen Newall, Samuel Nichols, Tobias Niedrist, Anita Niederer-Loher, Ruud Nijman, Ieva Nokalna, Urzula Nora Urbāne, Gudrun Nordberg, C.C. Obihara, Daniel O'Connor, Wilma Oosthoek, Veronika Osterman, Alexandre Pachot, D. Pajkrt, Jacobo Pardo-Seco, Stéphane Paulus, Jana Pavāre, Ivonne Pena Paz, Salina Persand, Andreas Pfleger, Klaus Pfurtscheller, Ria Philipsen, Ailsa Pickering, Benjamin Pierce, Heidemarie Pilch, Lidia Piñeiro Rodríguez, Sara Pischedda, Tina Plankar Srovin, Marko Pokorn, Andrew J. Pollard, Lena Pölz, Klara M. Posfay-Barbe, Petra Prunk, Zanda Pučuka, Glorija Rajic, Aqeela Rashid, Lorenzo Redondo-Collazo, Christa Relly, Irene Rivero Calle, Sara Rey Vázquez, Mathew Rhodes, Vivien Richmond, Thomas Riedel, Anna RocaIsatou Sarr, Siegfried Rödl, Carmen Rodríguez-Tenreiro, Sam Romaine, Emily Rowlands, Miguel Sadiki Ora, Manfred G. Sagmeister, Momodou Saidykhan, Antonio Salas, Luregn J. Schlapbach, D. Schonenberg, Fatou Secka, Katrīna Selecka, Sonia Serén Fernández, Cristina Serén Trasorras, Priyen Shah, Ching-Fen Shen, Shrijana Shrestha, Aleksandra Sidorova, Andrea Skrabl-Baumgartner, Giselle D’Souza, Matthias Sperl, Evelien Sprenkeler, Nina A. Schweintzger, Laura Stampfer, Molly Stevens, Martin Stocker, Volker Strenger, Dace Svile, Kelly Syggelou, Maria Tambouratzi, Chantal Tan, Emma Tavliavini, Evelyn Thomson, Stephen Thorson, Holger Till, G.A. Tramper-Stranders, Andreas Trobisch, Maria Tsolia, Effua Usuf, Lucille Valentine, Clementien L. Vermont, Marisol Vilas Iglesias, Katarina Vincek, Marie Voice, Gabriella de Vries, Diane Wallia, Shih-Min Wang, Clare Wilson, Amanda Wood, Phil Woodsford, Victoria Wright, Marietta Xagorari, Shunmay Yeung, Joany Zachariasse, Dace Zavadska, Syed M.A. Zaman, Judith Zandstra, Werner Zenz, Christoph Zurl, and Manuela Zwerenz

Subjects
Health sciences, Glycobiology, Immunology, Glycomics, Science
Abstract

Summary: Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.

Published
2023
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3. Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis

Author

Navin P. Boeddha, MD, PhD, Gertjan J. Driessen, MD, PhD, Nienke N. Hagedoorn, MD, Daniela S. Kohlfuerst, MD, Clive J. Hoggart, PhD, Angelique L. van Rijswijk, MSc, Ebru Ekinci, MD, Debby Priem, BSc, Luregn J. Schlapbach, MD, PhD, Jethro A. Herberg, MD, PhD, Ronald de Groot, MD, PhD, Suzanne T. Anderson, MD, PhD, Colin G. Fink, PhD, Enitan D. Carrol, MD, PhD, Michiel van der Flier, MD, PhD, Federico Martinón-Torres, MD, PhD, Michael Levin, MD, PhD, Frank W. Leebeek, MD, PhD, Werner Zenz, MD, PhD, Moniek P. M. de Maat, PhD, Jan A. Hazelzet, MD, PhD, Marieke Emonts, MD, PhD, Willem A. Dik, PhD, on behalf of the EUCLIDS consortium, Michael Levin, Lachlan Coin, Stuart Gormley, Shea Hamilton, Jethro Herberg, Bernardo Hourmat, Clive Hoggart, Myrsini Kaforou, Vanessa Sancho-Shimizu, Victoria Wright, Amina Abdulla, Paul Agapow, Maeve Bartlett, Evangelos Bellos, Hariklia Eleftherohorinou, Rachel Galassini, David Inwald, Meg Mashbat, Stefanie Menikou, Sobia Mustafa, Simon Nadel, Rahmeen Rahman, Clare Thakker, S Bokhandi, Sue Power, Heather Barham, N Pathan, Jenna Ridout, Deborah White, Sarah Thurston, S Faust, S Patel, Jenni McCorkell, P Davies, Lindsey Crate, Helen Navarra, Stephanie Carter, R Ramaiah, Rekha Patel, Catherine Tuffrey, Andrew Gribbin, Sharon McCready, Mark Peters, Katie Hardy, Fran Standing, Lauren O’Neill, Eugenia Abelake, Akash Deep, Eniola Nsirim, A Pollard, Louise Willis, Zoe Young, C Royad, Sonia White, PM Fortune, Phil Hudnott, Federico Martinón-Torres, Antonio Salas, Fernando Álvez González, Ruth Barral-Arca, Miriam Cebey-López, María José CurrasTuala, Natalia García, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Andrea Grela Beiroa, Antonio Justicia Grande, Pilar Leboráns Iglesias, Alba Elena Martínez Santos, Nazareth Martinón-Torres, José María Martinón Sánchez, Beatriz Morillo Gutiérrez, Belén Mosquera Pérez, Pablo Obando Pacheco, Jacobo Pardo-Seco, Sara Pischedda, Irene Rivero Calle, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Antonio Salas Ellacuriaga, Sonia Serén Fernández, María del Sol Porto Silva, Ana Vega, Lucía Vilanova Trillo, Susana Beatriz Reyes, María Cruz León León, Álvaro Navarro Mingorance, Xavier Gabaldó Barrios, Eider Oñate Vergara, Andrés Concha Torre, Ana Vivanco, Reyes Fernández, Francisco Giménez Sánchez, Miguel Sánchez Forte, Pablo Rojo, J.Ruiz Contreras, Alba Palacios, Cristina Epalza Ibarrondo, Elizabeth Fernández Cooke, Marisa Navarro, Cristina Álvarez Álvarez, María José Lozano, Eduardo Carreras, Sonia Brió Sanagustín, Olaf Neth, Mª del Carmen Martínez Padilla, Luis Manuel Prieto Tato, Sara Guillén, Laura Fernández Silveira, David Moreno, R. de Groot, A.M. Tutu van Furth, M. van der Flier, N.P. Boeddha, G.J.A. Driessen, M. Emonts, J.A. Hazelzet, T.W. Kuijpers, D. Pajkrt, E.A.M. Sanders, D. van de Beek, A. van der Ende, H.L.A. Philipsen, A.O.A. Adeel, M.A. Breukels, D.M.C. Brinkman, C.C.M.M. de Korte, E. de Vries, W.J. de Waal, R. Dekkers, A. Dings-Lammertink, R.A. Doedens, A.E. Donker, M. Dousma, T.E. Faber, G.P.J.M. Gerrits, J.A.M. Gerver, J. Heidema, J. Homan-van der Veen, M.A.M. Jacobs, N.J.G. Jansen, P. Kawczynski, K. Klucovska, M.C.J. Kneyber, Y. Koopman-Keemink, V.J. Langenhorst, J. Leusink, B.F. Loza, I.T. Merth, C.J. Miedema, C. Neeleman, J.G. Noordzij, C.C. Obihara, A.L.T. van Overbeek – van Gils, G.H. Poortman, S.T. Potgieter, J. Potjewijd, P.P.R. Rosias, T. Sprong, G.W. ten Tussher, B.J. Thio, G.A. Tramper-Strander, M. van Deuren, H. van der Meer, A.J.M. van Kuppevelt, A.M. van Wermeskerken, W.A. Verwijs, T.F.W. Wolfs, Luregn J Schlapbach, Philipp Agyeman, Christoph Aebi, Eric Giannoni, Martin Stocker, Klara M Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Paul Hasters, Christa Relly, Walter Baer, Christoph Berger, Enitan Carrol, Stéphane Paulus, Hannah Frederick, Rebecca Jennings, Joanne Johnston, Rhian Kenwright, Colin G Fink, Elli Pinnock, Marieke Emonts, Rachel Agbeko, Suzanne Anderson, Fatou Secka, Kalifa Bojang, Isatou Sarr, Ngane Kebbeh, Gibbi Sey, Momodou Saidykhan, Fatoumatta Cole, Gilleh Thomas, Martin Antonio, Werner Zenz, Daniela S. Klobassa, Alexander Binder, Nina A. Schweintzger, Manfred Sagmeister, Hinrich Baumgart, Markus Baumgartner, Uta Behrends, Ariane Biebl, Robert Birnbacher, Jan-Gerd Blanke, Carsten Boelke, Kai Breuling, Jürgen Brunner, Maria Buller, Peter Dahlem, Beate Dietrich, Ernst Eber, Johannes Elias, Josef Emhofer, Rosa Etschmaier, Sebastian Farr, Ylenia Girtler, Irina Grigorow, Konrad Heimann, Ulrike Ihm, Zdenek Jaros, Hermann Kalhoff, Wilhelm Kaulfersch, Christoph Kemen, Nina Klocker, Bernhard Köster, Benno Kohlmaier, Eleni Komini, Lydia Kramer, Antje Neubert, Daniel Ortner, Lydia Pescollderungg, Klaus Pfurtscheller, Karl Reiter, Goran Ristic, Siegfried Rödl, Andrea Sellner, Astrid Sonnleitner, Matthias Sperl, Wolfgang Stelzl, Holger Till, Andreas Trobisch, Anne Vierzig, Ulrich Vogel, Christina Weingarten, Stefanie Welke, Andreas Wimmer, Uwe Wintergerst, Daniel Wüller, Andrew Zaunschirm, Ieva Ziuraite, and Veslava Žukovskaja

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

IMPORTANCE:. A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking. OBJECTIVES:. To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome. DESIGN:. Data from two prospective cohort studies. SETTING AND PARTICIPANTS:. Cohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission). MAIN OUTCOMES AND MEASURES:. Primary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay. RESULTS:. In cohort 1 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis. CONCLUSIONS AND RELEVANCE:. In children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, particularly in meningococcal sepsis. Future studies should confirm the prognostic value of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 and should study pathophysiologic mechanisms.

Published
2021
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4. Do Children with Immune Thrombocytopenia Have Cerebral Microbleeds?

Author

Alice C J Hart, Ana Maria Cabrera, Camelia Vladescu, Sobia Mustafa, Richard Syzdlo, Rocel C. Saputil, Michelle MH Tan, Amna Malik, David Sharp, Pedro Vicente, Albert Busza, Michael Laffan, Anastasia Gontsarova, Adam Waldman, and Nichola Cooper

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

5. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial

Author

Pauline Amuge, Abbas Lugemwa, Ben Wynne, Hilda A Mujuru, Avy Violari, Cissy M Kityo, Moherndran Archary, Ebrahim Variava, Ellen White, Rebecca M Turner, Clare Shakeshaft, Shabinah Ali, Kusum J Nathoo, Lorna Atwine, Afaaf Liberty, Dickson Bbuye, Elizabeth Kaudha, Rosie Mngqibisa, Modehei Mosala, Vivian Mumbiro, Annet Nanduudu, Rogers Ankunda, Lindiwe Maseko, Adeodata R Kekitiinwa, Carlo Giaquinto, Pablo Rojo, Diana M Gibb, Anna Turkova, Deborah Ford, Amina Farhana Mehar (nee Abdulla), Pattamukkil Abraham, Elaine Abrams, Judith Acero, Gerald Muzorah Agaba, Grace Ahimbisibwe, Barbara Ainebyoona, Winnie Akobye, Yasmeen Akhalwaya, Nazim Akoojee, Shabinah S. Ali, Catherine Andrea, Maria Angeles Muñoz Fernandez, Diana Antonia Rutebarika, Suvaporn Anugulruengkitt, Tsitsi Apollo, Ronelle Arendze, Juliet Ategeka, Eunice Atim, Abdel Babiker, Sarah Babirye, Enock Babu, Edward Bagirigomwa, Angella Baita, David Balamusani, Patsy Baliram, David Baliruno, Colin Ball, Henry Balwa, Alasdair Bamford, Srini Bandi, Dominique Barker, Linda Barlow-Mosha, Shazia Begum, Osee Behuhuma, Sarah Bernays, Rogers Besigye, Maria Bester, Joyline Bhiri, Davide Bilardi, Kristien Bird, Pauline Bollen, Chiara Borg, Anne-Marie Borges Da Silva, Jackie Brown, Elena Bruno, Torsak Bunupuradah, David Burger, Nomzamo Buthelezi, Mutsa Bwakura-Dangarembizi, Africanus Byaruhanga, Joanna Calvert, Petronelle Casey, Haseena Cassim, Sphiwee Cebekhulu, Sanuphong Chailert, Suwalai Chalermpantmetagul, Wanna Chamjamrat, Man Chan, Precious Chandiwana, Thannapat Chankun, Sararut Chanthaburanun, Nuttawut Chanto, Ennie Chidziva, Minenhle Chikowore, Joy Chimanzi, Dujrudee Chinwong, Stuart Chitongo, Moses Chitsamatanga, Joshua Choga, Duangrat Chutima, Polly Clayden, Alexandra Coelho, Angela Colbers, Alexandra Compagnucci, Ana Constança Mendes, Magda Conway, Mark F. Cotton, Jane Crawley, Tim R. Cressey, Jacky Crisp, Ana Cristina Matos, Sumaya Dadan, Jacqui Daglish, Siva Danaviah, Tseleng Daniel, Anita De Rossi, Sukanda Denjanta, Els Dobbels, Maria Dowie, Prosper Dube, Benedictor Dube, Nimisha Dudakia, Alice Elwana, Cristina Epalza, David Eram, Juan Erasmus, Peter Erim, Luis Escosa Garcia, Zaakirah Essack, Carolina Estepa, Monica Etima, Alexandre Fernandes, Maite Fernandez, Felicity Fitzgerald, Jacquie Flynn, Claudia Fortuny Guasch, Caroline Foster, George Fourie, Yolandie Fourie, Sophie Foxall, Derusha Frank, Kate Gandhi, India Garcia, Kathleen Gartner, Joshua Gasa, Gugu Gasa, Diana M. Gibb, Coral Gomez Rico, Daniel Gomez-Pena, Secrecy Gondo, Anna Goodman, Maria Gorreti Nakalema, Winnie Gozhora, Pisut Greetanukroh, Biobanco Gregorio Maranon, Tiziana Grossele, Shamiso Gwande, Tapiwa Gwaze, Tsitsi Gwenzi, James Hakim, Emmanuel Hakiza, Abdul Hamid Kaka, Ashley Harley, Mornay Isaacs, Richard Isabirye, Wilber Ishemunyoro, Tom Jacobs, Lungile Jafta, Nasir Jamil, Anita Janse Janse van Rensburg, Vinesh Jeaven, Maria José Mellado Peña, Gonzague Jourdain, Katabalwa Juliet, Thidarat Jumpimai, Raungwit Junkaew, Thidarat Jupimai, Winfred Kaahwa, Mildred Kabasonga, Olivia Kaboggoza, Rose Jacqueline Kadhuba, Ampika Kaewbundit, Kanyanee Kaewmamueng, Bosco Kafufu, Brenda Kakayi, Phakamas Kamboua, Suparat Kanjanavanit, Gladys Kasangaki, Naruporn Kasipong, Miriam Kasozi, Hajira Kataike, Chrispus Katemba, Nkata Kekane, Adeodata R. Kekitiinwa, Edridah Keminyeto, Woottichai Khamduang, Warunee Khamjakkaew, Jiraporn Khamkon, Sasipass Khannak, Orapin Khatngam, Tassawan Khayanchoomnoom, Busi Khumalo, Mirriam Khunene, Suwimon Khusuwan, Phionah Kibalama, Robinah Kibenge, Anthony Kirabira, Cissy M. Kityo, Lameck Kiyimba, Nigel Klein, Soraya Klinprung, Robin Kobbe, Olivia Kobusingye, Josephine Kobusungye, Areerat Kongponoi, Christoph Königs, Olivier Koole, Christelle Kouakam, Nitinart Krueduangkam, Namthip Kruenual, Nuananong Kunjaroenrut, Raymonds Kyambadde, Priscilla Kyobutungi, Flavia Kyomuhendo, Erinah Kyomukama, Reshma Lakha, Cleopatra Langa, Laddawan Laomanit, Emily Lebotsa, Prattana Leenasirimakul, Lawrence Lekku, Sarah Lensen, Valériane Leroy, Jin Li, Juthamas Limplertjareanwanich, Emma Little, Ezra Lutalo, Jose Luis Jimenez, Hermione Lyall, Candice MacDonald, Gladness Machache, Penelope Madlala, Tryphina Madonsela, Nomfundo Maduna, Joel Maena, Apicha Mahanontharit, Collin Makanga, Candice Makola, Shafic Makumbi, Lucille Malgraaf, Angelous Mamiane, Felicia Mantkowski, Wendy Mapfumo, Laura Marques, Agnes Mary Mugagga, Tshepiso Masienyane, Ruth Mathiba, Farai Matimba, Sajeeda Mawlana, Emmanuel Mayanja, Fatima Mayat, Ritah Mbabazi, Nokuthula Mbadaliga, Faith Mbasani, Kathleen McClaughlin, Helen McIlleron, Watchara Meethaisong, Patricia Mendez Garcia, Annet Miwanda, Carlota Miranda, Siphiwe Mkhize, Kgosimang Mmolawa, Fatima Mohamed, Tumelo Moloantoa, Maletsatsi Monametsi, Samuel Montero, Cecilia L. Moore, Rejoice Mosia, Columbus Moyo, Mumsy Mthethwa, Shepherd Mudzingwa, Tawona Mudzviti, Hilda Mujuru, Emmanuel Mujyambere, Trust Mukanganiki, Cynthia Mukisa Williams, Mark Mulder, Disan Mulima, Alice Mulindwa, Zivai Mupambireyi, Alba Murciano Cabeza, Herbert Murungi, Dorothy Murungu, Sandra Musarurwa, Victor Musiime, Alex V. Musiime, Maria Musisi, Philippa Musoke, Barbara Musoke Nakirya, Godfrey Musoro, Sharif Musumba, Sobia Mustafa, Shirley Mutsai, Phyllis Mwesigwa Rubondo, Mariam Naabalamba, Immaculate Nagawa, Allemah Naidoo, Shamim Nakabuye, Sarah Nakabuye, Sarah Nakalanzi, Justine Nalubwama, Annet Nalugo, Stella Nalusiba, Clementine Namajja, Sylvia Namanda, Paula Namayanja, Esther Nambi, Rachael Kikabi Namuddu, Stella Namukwaya, Florence Namuli, Josephine Namusanje, Rosemary Namwanje, Anusha Nanan-kanjee, Charity Nankunda, Joanita Nankya Baddokwaya, Maria Nannungi, Winnie Nansamba, Kesdao Nanthapisal, Juliet Nanyonjo, Sathaporn Na-Rajsima, Claire Nasaazi, Helena Nascimento, Eleni Nastouli, Wipaporn Natalie Songtaweesin, Kusum Nathoo, Ian Natuhurira, Rashidah Nazzinda, Thabisa Ncgaba, Milly Ndigendawani, Makhosonke Ndlovu, Georgina Nentsa, Chaiwat Ngampiyaskul, Ntombenhle Ngcobo, Nicole Ngo Giang Huong, Pia Ngwaru, Ruth Nhema, Emily Ninsiima, Gloria Ninsiima, Misheck Nkalo Phiri, Antoni Noguera Julian, Monica Nolan, Thornthun Noppakaorattanamanee, Muzamil Nsibuka Kisekka, Eniola Nsirim, Rashina Nundlal, Rosita Nunes, Lungile Nyantsa, Mandisa Nyati, Sean O'Riordan, Paul Ocitti Labeja, Denis Odoch, Rachel Oguntimehin, Martin Ojok, Geoffrey Onen, Wilma Orange, Pradthana Ounchanum, Benson Ouma, Andreia Padrao, Deborah Pako, Anna Parker, Malgorzata Pasko-Szcech, Reena Patel, Rukchanok Peongjakta, Turian Petpranee, Tasmin Phillips, Jackie Philps, Laura Picault, Sonja Pieterse, Helena Pinheiro, Supawadee Pongprapass, Anton Pozniak, Andrew Prendergast, Luis Prieto Tato, Patcharee Puangmalai, Thanyawee Puthanakit, Modiehi Rakgokong, Helena Ramos, Nastassja Ramsagar, Cornelius Rau, Yoann Riault, Pablo Rojo Conejo, Basiimwa Roy Clark, Eddie Rubanga, Baker Rubinga, Chutima Ruklao, Pattira Runarassamee, Chalermpong Saenjum, Chayakorn Saewtrakool, Yacine Saidi, Talia Sainz Costa, Chutima Saisaengjan, Rebecca Sakwa, Tatiana Sarfati, Noshalaza Sbisi, Dihedile Scheppers, Stephan Schultze-Strasser, Ulf Schulze-Sturm, Karen Scott, Janet Seeley, Robert Serunjogi, Leora Sewnarain, Subashinie Sidhoo, Mercy Shibemba, Delane Shingadia, Sheleika Singh, Wasna Sirirungsi, Sibongile Sithebe, Theresa Smit, Kurt Smith, Marlize Smuts, Moira Spyer, Worathip Sripaoraya, Ussanee Srirompotong, Warunee Srisuk, Mark Ssenyonga, Patamawadee Sudsaard, Praornsuda Sukrakanchana, Pathanee Tearsansern, Carla Teixeira, Kanchana Than-in-at, Thitiwat Thapwai, Yupawan Thaweesombat, Jutarat Thewsoongnoen, Rodolphe Thiébaut, Margaret Thomason, Laura Thrasyvoulou, Khanungnit Thungkham, Judith Tikabibamu, Gloria Tinago, Ketmookda Trairat, Gareth Tudor-Williams, Mercy Tukamushaba, Deogratiuos Tukwasibwe, Julius Tumusiime, Joana Tuna, Rebecca Turner, Arttasid Udomvised, Aasia Vadee, Hesti Van Huyssteen, Nadine Van Looy, Yvonne Vaughan-Gordon, Giulio Vecchia, Richard Vowden, Hylke Waalewijn, Rebecca Wampamba, Steve Welch, Ian Weller, Sibusisiwe Weza, Ian White, Kaja Widuch, Helen Wilkes, Sookpanee Wimonklang, Pacharaporn Yingyong, Zaam Zinda Nakawungu, and Peter Zuidewind

Subjects
Adult, Epidemiology, Pyridones, Anti-HIV Agents, Immunology, HIV Infections, 3-Ring, Piperazines, Heterocyclic Compounds, Virology, Oxazines, Humans, Protease Inhibitors, Child, Preschool, Infant, Newborn, Infant, Bayes Theorem, Viral Load, Newborn, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Child, Preschool, Heterocyclic Compounds, 3-Ring, Treatment Outcome
Abstract

Contains fulltext : 283099.pdf (Publisher’s version ) (Open Access) BACKGROUND: Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg. METHODS: ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of care and comprises two cohorts (children weighing ≥14 kg and

Published
2022

6. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Author

Anna Turkova, Hylke Waalewijn, Man K Chan, Pauline D J Bollen, Mutsa F Bwakura-Dangarembizi, Adeodata R Kekitiinwa, Mark F Cotton, Abbas Lugemwa, Ebrahim Variava, Grace Miriam Ahimbisibwe, Ussanee Srirompotong, Vivian Mumbiro, Pauline Amuge, Peter Zuidewind, Shabinah Ali, Cissy M Kityo, Moherndran Archary, Rashida A Ferrand, Avy Violari, Diana M Gibb, David M Burger, Deborah Ford, Angela Colbers, Amina Farhana Mehar (nee Abdulla), Pattamukkil Abraham, Elaine Abrams, Judith Acero, Gerald Muzorah Agaba, Grace Ahimbisibwe, Barbara Ainebyoona, Winnie Akobye, Yasmeen Akhalwaya, Nazim Akoojee, Shabinah S. Ali, Catherine Andrea, Maria Angeles Muñoz Fernandez, Rogers Ankunda, Diana Antonia Rutebarika, Suvaporn Anugulruengkitt, Tsitsi Apollo, Ronelle Arendze, Juliet Ategeka, Eunice Atim, Lorna Atwine, Abdel Babiker, Sarah Babirye, Enock Babu, Edward Bagirigomwa, Angella Baita, David Balamusani, Patsy Baliram, David Baliruno, Colin Ball, Henry Balwa, Alasdair Bamford, Srini Bandi, Dominique Barker, Linda Barlow-Mosha, Dickson Bbuye, Shazia Begum, Osee Behuhuma, Sarah Bernays, Rogers Besigye, Maria Bester, Joyline Bhiri, Davide Bilardi, Kristien Bird, Pauline Bollen, Chiara Borg, Anne-Marie Borges Da Silva, Jackie Brown, Elena Bruno, Torsak Bunupuradah, David Burger, Nomzamo Buthelezi, Mutsa Bwakura-Dangarembizi, Africanus Byaruhanga, Joanna Calvert, Petronelle Casey, Haseena Cassim, Sphiwee Cebekhulu, Sanuphong Chailert, Suwalai Chalermpantmetagul, Wanna Chamjamrat, Man Chan, Precious Chandiwana, Thannapat Chankun, Sararut Chanthaburanun, Nuttawut Chanto, Ennie Chidziva, Minenhle Chikowore, Joy Chimanzi, Dujrudee Chinwong, Stuart Chitongo, Moses Chitsamatanga, Joshua Choga, Duangrat Chutima, Polly Clayden, Alexandra Coelho, Alexandra Compagnucci, Ana Constança Mendes, Magda Conway, Mark F. Cotton, Jane Crawley, Tim R. Cressey, Jacky Crisp, Ana Cristina Matos, Sumaya Dadan, Jacqui Daglish, Siva Danaviah, Tseleng Daniel, Anita De Rossi, Sukanda Denjanta, Els Dobbels, Maria Dowie, Prosper Dube, Benedictor Dube, Nimisha Dudakia, Alice Elwana, Cristina Epalza, David Eram, Juan Erasmus, Peter Erim, Luis Escosa Garcia, Zaakirah Essack, Carolina Estepa, Monica Etima, Alexandre Fernandes, Maite Fernandez, Felicity Fitzgerald, Jacquie Flynn, Claudia Fortuny Guasch, Caroline Foster, George Fourie, Yolandie Fourie, Sophie Foxall, Derusha Frank, Kate Gandhi, India Garcia, Kathleen Gartner, Joshua Gasa, Gugu Gasa, Carlo Giaquinto, Diana M. Gibb, Coral Gomez Rico, Daniel Gomez-Pena, Secrecy Gondo, Anna Goodman, Maria Gorreti Nakalema, Winnie Gozhora, Pisut Greetanukroh, Biobanco Gregorio Maranon, Tiziana Grossele, Shamiso Gwande, Tapiwa Gwaze, Tsitsi Gwenzi, James Hakim, Emmanuel Hakiza, Abdul Hamid Kaka, Ashley Harley, Mornay Isaacs, Richard Isabirye, Wilber Ishemunyoro, Tom Jacobs, Lungile Jafta, Nasir Jamil, Anita Janse Janse van Rensburg, Vinesh Jeaven, Maria José Mellado Peña, Gonzague Jourdain, Katabalwa Juliet, Thidarat Jumpimai, Raungwit Junkaew, Thidarat Jupimai, Winfred Kaahwa, Mildred Kabasonga, Olivia Kaboggoza, Rose Jacqueline Kadhuba, Ampika Kaewbundit, Kanyanee Kaewmamueng, Bosco Kafufu, Brenda Kakayi, Phakamas Kamboua, Suparat Kanjanavanit, Gladys Kasangaki, Naruporn Kasipong, Miriam Kasozi, Hajira Kataike, Chrispus Katemba, Elizabeth Kaudha, Nkata Kekane, Adeodata R. Kekitiinwa, Edridah Keminyeto, Woottichai Khamduang, Warunee Khamjakkaew, Jiraporn Khamkon, Sasipass Khannak, Orapin Khatngam, Tassawan Khayanchoomnoom, Busi Khumalo, Mirriam Khunene, Suwimon Khusuwan, Phionah Kibalama, Robinah Kibenge, Anthony Kirabira, Cissy M. Kityo, Lameck Kiyimba, Nigel Klein, Soraya Klinprung, Robin Kobbe, Olivia Kobusingye, Josephine Kobusungye, Areerat Kongponoi, Christoph Königs, Olivier Koole, Christelle Kouakam, Nitinart Krueduangkam, Namthip Kruenual, Nuananong Kunjaroenrut, Raymonds Kyambadde, Priscilla Kyobutungi, Flavia Kyomuhendo, Erinah Kyomukama, Reshma Lakha, Cleopatra Langa, Laddawan Laomanit, Emily Lebotsa, Prattana Leenasirimakul, Lawrence Lekku, Sarah Lensen, Valériane Leroy, Jin Li, Afaaf Liberty, Juthamas Limplertjareanwanich, Emma Little, Ezra Lutalo, Jose Luis Jimenez, Hermione Lyall, Candice MacDonald, Gladness Machache, Penelope Madlala, Tryphina Madonsela, Nomfundo Maduna, Joel Maena, Apicha Mahanontharit, Collin Makanga, Candice Makola, Shafic Makumbi, Lucille Malgraaf, Angelous Mamiane, Felicia Mantkowski, Wendy Mapfumo, Laura Marques, Agnes Mary Mugagga, Lindiwe Maseko, Tshepiso Masienyane, Ruth Mathiba, Farai Matimba, Sajeeda Mawlana, Emmanuel Mayanja, Fatima Mayat, Ritah Mbabazi, Nokuthula Mbadaliga, Faith Mbasani, Kathleen McClaughlin, Helen McIlleron, Watchara Meethaisong, Patricia Mendez Garcia, Annet Miwanda, Carlota Miranda, Siphiwe Mkhize, Kgosimang Mmolawa, Rosie Mngqibisa, Fatima Mohamed, Tumelo Moloantoa, Maletsatsi Monametsi, Samuel Montero, Cecilia L. Moore, Rejoice Mosia, Columbus Moyo, Mumsy Mthethwa, Shepherd Mudzingwa, Tawona Mudzviti, Hilda Mujuru, Emmanuel Mujyambere, Trust Mukanganiki, Cynthia Mukisa Williams, Mark Mulder, Disan Mulima, Alice Mulindwa, Zivai Mupambireyi, Alba Murciano Cabeza, Herbert Murungi, Dorothy Murungu, Sandra Musarurwa, Victor Musiime, Alex V. Musiime, Maria Musisi, Philippa Musoke, Barbara Musoke Nakirya, Godfrey Musoro, Sharif Musumba, Sobia Mustafa, Shirley Mutsai, Phyllis Mwesigwa Rubondo, Mariam Naabalamba, Immaculate Nagawa, Allemah Naidoo, Shamim Nakabuye, Sarah Nakabuye, Sarah Nakalanzi, Justine Nalubwama, Annet Nalugo, Stella Nalusiba, Clementine Namajja, Sylvia Namanda, Paula Namayanja, Esther Nambi, Rachael Kikabi Namuddu, Stella Namukwaya, Florence Namuli, Josephine Namusanje, Rosemary Namwanje, Anusha Nanan-kanjee, Annet Nanduudu, Charity Nankunda, Joanita Nankya Baddokwaya, Maria Nannungi, Winnie Nansamba, Kesdao Nanthapisal, Juliet Nanyonjo, Sathaporn Na-Rajsima, Claire Nasaazi, Helena Nascimento, Eleni Nastouli, Wipaporn Natalie Songtaweesin, Kusum Nathoo, Ian Natuhurira, Rashidah Nazzinda, Thabisa Ncgaba, Milly Ndigendawani, Makhosonke Ndlovu, Georgina Nentsa, Chaiwat Ngampiyaskul, Ntombenhle Ngcobo, Nicole Ngo Giang Huong, Pia Ngwaru, Ruth Nhema, Emily Ninsiima, Gloria Ninsiima, Misheck Nkalo Phiri, Antoni Noguera Julian, Monica Nolan, Thornthun Noppakaorattanamanee, Muzamil Nsibuka Kisekka, Eniola Nsirim, Rashina Nundlal, Rosita Nunes, Lungile Nyantsa, Mandisa Nyati, Sean O'Riordan, Paul Ocitti Labeja, Denis Odoch, Rachel Oguntimehin, Martin Ojok, Geoffrey Onen, Wilma Orange, Pradthana Ounchanum, Benson Ouma, Andreia Padrao, Deborah Pako, Anna Parker, Malgorzata Pasko-Szcech, Reena Patel, Rukchanok Peongjakta, Turian Petpranee, Tasmin Phillips, Jackie Philps, Laura Picault, Sonja Pieterse, Helena Pinheiro, Supawadee Pongprapass, Anton Pozniak, Andrew Prendergast, Luis Prieto Tato, Patcharee Puangmalai, Thanyawee Puthanakit, Modiehi Rakgokong, Helena Ramos, Nastassja Ramsagar, Cornelius Rau, Yoann Riault, Pablo Rojo Conejo, Basiimwa Roy Clark, Eddie Rubanga, Baker Rubinga, Chutima Ruklao, Pattira Runarassamee, Chalermpong Saenjum, Chayakorn Saewtrakool, Yacine Saidi, Talia Sainz Costa, Chutima Saisaengjan, Rebecca Sakwa, Tatiana Sarfati, Noshalaza Sbisi, Dihedile Scheppers, Stephan Schultze-Strasser, Ulf Schulze-Sturm, Karen Scott, Janet Seeley, Robert Serunjogi, Leora Sewnarain, Clare Shakeshaft, Subashinie Sidhoo, Mercy Shibemba, Delane Shingadia, Sheleika Singh, Wasna Sirirungsi, Sibongile Sithebe, Theresa Smit, Kurt Smith, Marlize Smuts, Moira Spyer, Worathip Sripaoraya, Warunee Srisuk, Mark Ssenyonga, Patamawadee Sudsaard, Praornsuda Sukrakanchana, Pathanee Tearsansern, Carla Teixeira, Kanchana Than-in-at, Thitiwat Thapwai, Yupawan Thaweesombat, Jutarat Thewsoongnoen, Rodolphe Thiébaut, Margaret Thomason, Laura Thrasyvoulou, Khanungnit Thungkham, Judith Tikabibamu, Gloria Tinago, Ketmookda Trairat, Gareth Tudor-Williams, Mercy Tukamushaba, Deogratiuos Tukwasibwe, Julius Tumusiime, Joana Tuna, Rebecca Turner, Arttasid Udomvised, Aasia Vadee, Hesti Van Huyssteen, Nadine Van Looy, Yvonne Vaughan-Gordon, Giulio Vecchia, Richard Vowden, Rebecca Wampamba, Steve Welch, Ian Weller, Sibusisiwe Weza, Ellen White, Ian White, Kaja Widuch, Helen Wilkes, Sookpanee Wimonklang, Ben Wynne, Pacharaporn Yingyong, and Zaam Zinda Nakawungu

Subjects
Male, Adolescent, Pyridones, Epidemiology, Immunology, Infant, HIV Infections, 3-Ring, Piperazines, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Child, Child, Preschool, Female, Heterocyclic Compounds, 3-Ring, Humans, Oxazines, Rifampin, Uganda, HIV-1, Tuberculosis, Heterocyclic Compounds, Virology, Preschool
Abstract

Contains fulltext : 282959.pdf (Publisher’s version ) (Open Access) BACKGROUND: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. METHODS: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to

Published
2022

8. Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Author

Federico Martinón-Torres, Antonio Salas, Irene Rivero-Calle, Miriam Cebey-López, Jacobo Pardo-Seco, Jethro A Herberg, Navin P Boeddha, Daniela S Klobassa, Fatou Secka, Stephane Paulus, Ronald de Groot, Luregn J Schlapbach, Gertjan J Driessen, Suzanne T Anderson, Marieke Emonts, Werner Zenz, Enitan D Carrol, Michiel Van der Flier, Michael Levin, Lachlan Coin, Stuart Gormley, Shea Hamilton, Jethro Herberg, Bernardo Hourmat, Clive Hoggart, Myrsini Kaforou, Vanessa Sancho-Shimizu, Victoria Wright, Amina Abdulla, Paul Agapow, Maeve Bartlett, Evangelos Bellos, Hariklia Eleftherohorinou, Rachel Galassini, David Inwald, Meg Mashbat, Stefanie Menikou, Sobia Mustafa, Simon Nadel, Rahmeen Rahman, Clare Thakker, Sumit Bokhandi, Sue Power, Heather Barham, Nazima Pathan, Jenna Ridout, Deborah White, Sarah Thurston, Saul Faust, Sanjay Patel, Jenni McCorkell, Patrick Davies, Lindsey Crate, Helen Navarra, Stephanie Carter, Raghu Ramaiah, Rekha Patel, Catherine Tuffrey, Andrew Gribbin, Sharon McCready, Mark Peters, Katie Hardy, Fran Standing, Lauren O'Neill, Eugenia Abelake, Akash Deep, Eniola Nsirim, Andrew Pollard, Louise Willis, Zoe Young, C Royad, Sonia White, Peter Marc Fortune, Phil Hudnott, Antonio Salas Ellacuriaga, Fernando Álvez González, Ruth Barral-Arca, María José Curras-Tuala, Natalia García, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Andrea Grela Beiroa, Antonio Justicia Grande, Pilar Leboráns Iglesias, Alba Elena Martínez Santos, Nazareth Martinón-Torres, José María Martinón Sánchez, Beatriz Morillo Gutiérrez, Belén Mosquera Pérez, Pablo Obando Pacheco, Sara Pischedda, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Sonia Serén Fernández, María del Sol Porto Silva, Ana Vega, Lucía Vilanova Trillo, Susana Beatriz Reyes, María Cruz León León, Álvaro Navarro Mingorance, Xavier Gabaldó Barrios, Eider Oñate Vergara, Andrés Concha Torre, Ana Vivanco, Reyes Fernández, Francisco Giménez Sánchez, Miguel Sánchez Forte, Pablo Rojo, Jesús Ruiz Contreras, Alba Palacios, Cristina Epalza Ibarrondo, Elizabeth Fernández Cooke, Marisa Navarro, Cristina Álvarez Álvarez, María José Lozano, Eduardo Carreras, Sonia Brió Sanagustín, Olaf Neth, María del Carmen Martínez Padilla, Luis Manuel Prieto Tato, Sara Guillén, Laura Fernández Silveira, David Moreno, A. Marceline van Furth, Michiel van der Flier, Navin Prekash Boeddha, Gertjan JA Driessen, Jan A Hazelzet, Taco W Kuijpers, Dasja Pajkrt, Elisabeth AM Sanders, Diederik van de Beek, Arie van der Ende, Ria LA Philipsen, Abdul OA Adeel, Meike A Breukels, Danielle MC Brinkman, Carla CMM de Korte, Esther de Vries, Wouter J de Waal, Roel Dekkers, Anouk Dings-Lammertink, Rienus A Doedens, Albertine E Donker, Mieke Dousma, Tina E Faber, G Peter JM Gerrits, Jan AM Gerver, Jojanneke Heidema, Jenneke Homan-van der Veen, Monique AM Jacobs, Nicolaas JG Jansen, Pawel Kawczynski, Kristine Klucovska, Martin CJ Kneyber, Yvonne Koopman-Keemink, Veerle J Langenhorst, José Leusink, Bettina F Loza, Istvan T Merth, Carien J Miedema, Chris Neeleman, Jeroen G Noordzij, Charles C Obihara, A Lidy T van Overbeek - van Gils, Geriska H Poortman, Steph T Potgieter, Joke Potjewijd, Philippe PR Rosias, Tom Sprong, Gavin W ten Tussher, Boony J Thio, Gerdien A Tramper-Stranders, Marcel van Deuren, Henny van der Meer, Andre JM van Kuppevelt, Anne-Marie van Wermeskerken, Wim A Verwijs, Tom FW Wolfs, Luregn Jan Schlapbach, Philipp Agyeman, Christoph Aebi, Christoph Berger, Eric Giannoni, Martin Stocker, Klara M Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Paul Hasters, Christa Relly, Walter Baer, Enitan Carrol, Stéphane Paulus, Hannah Frederick, Rebecca Jennings, Joanne Johnston, Rhian Kenwright, Colin G Fink, Elli Pinnock, Rachel Sarah Agbeko, Kalifa A Bojang, Isatou Sarr, Ngange Kebbeh, Gibbi Sey, Momodou Saidykhan, Fatoumata Cole, Gilleh Thomas, Martin Antonio, Daniela Sabine Klobassa, Alexander Binder, Nina Alexandra Schweintzger, Manfred Sagmeister, Hinrich Baumgart, Markus Baumgartner, Uta Behrends, Ariane Biebl, Robert Birnbacher, Jan-Gerd Blanke, Carsten Boelke, Kai Breuling, Jürgen Brunner, Maria Buller, Peter Dahlem, Beate Dietrich, Ernst Eber, Johannes Elias, Josef Emhofer, Rosa Etschmaier, Sebastian Farr, Ylenia Girtler, Irina Grigorow, Konrad Heimann, Ulrike Ihm, Zdenek Jaros, Hermann Kalhoff, Wilhelm Kaulfersch, Christoph Kemen, Nina Klocker, Bernhard Köster, Benno Kohlmaier, Eleni Komini, Lydia Kramer, Antje Neubert, Daniel Ortner, Lydia Pescollderungg, Klaus Pfurtscheller, Karl Reiter, Goran Ristic, Siegfried Rödl, Andrea Sellner, Astrid Sonnleitner, Matthias Sperl, Wolfgang Stelzl, Holger Till, Andreas Trobisch, Anne Vierzig, Ulrich Vogel, Christina Weingarten, Stefanie Welke, Andreas Wimmer, Uwe Wintergerst, Daniel Wüller, Andrew Zaunschirm, Ieva Ziuraite, Veslava Žukovskaja, Posfay Barbe, Klara, Pediatrics, Huisarts & Ziekenhuis, Tranzo, Scientific center for care and wellbeing, ARD - Amsterdam Reproduction and Development, AII - Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, ANS - Neuroinfection & -inflammation, Neurology, Medical Microbiology and Infection Prevention, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), The European Society for Paediatric Infectious Diseases, Meningitis Research Foundation, Imperial College Healthcare NHS Trust- BRC Funding, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), University of Zurich, and Martinón-Torres, Federico

Subjects
Male, Pediatrics, RJ101, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Severity of Illness Index, Cohort Studies, 0302 clinical medicine, Cost of Illness, Developmental and Educational Psychology, 030212 general & internal medicine, Prospective Studies, Sepsis/epidemiology, Prospective cohort study, Child, media_common, ddc:618, Bacterial Infections, Europe, Child, Preschool, Cohort, Female, Algorithms, Cohort study, medicine.medical_specialty, 610 Medicine & health, Europe/epidemiology, Sepsis, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 030225 pediatrics, Severity of illness, medicine, media_common.cataloged_instance, Humans, 2735 Pediatrics, Perinatology and Child Health, European union, Preschool, Disease burden, 3204 Developmental and Educational Psychology, business.industry, Infant, Newborn, Infant, medicine.disease, Newborn, Pneumonia, 10036 Medical Clinic, Pediatrics, Perinatology and Child Health, business, Bacterial Infections/epidemiology
Abstract

Background Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; pInterpretation Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients.

Published
2018

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