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4. Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries

Author

Kakaraskoska Boceska, Biljana, Vilken, Tuba, Xavier, Basil Britto, Kostyanev, Tomislav, Lin, Qiang, Lammens, Christine, Ellis, Sally, O’Brien, Seamus, da Costa, Renata Maria Augusto, Cook, Aislinn, Russell, Neal, Bielicki, Julia, Riddell, Amy, Stohr, Wolfgang, Walker, Ann Sarah, Berezin, Eitan Naaman, Roilides, Emmanuel, De Luca, Maia, Romani, Lorenza, Ballot, Daynia, Dramowski, Angela, Wadula, Jeannette, Lochindarat, Sorasak, Boonkasidecha, Suppawat, Namiiro, Flavia, Ngoc, Hoang Thi Bich, Tran, Minh Dien, Cressey, Tim R., Preedisripipat, Kanchana, Berkley, James A., Musyimi, Robert, Zarras, Charalampos, Nana, Trusha, Whitelaw, Andrew, da Silva, Cely Barreto, Jaglal, Prenika, Ssengooba, Willy, Saha, Samir K., Islam, Mohammad Shahidul, Mussi-Pinhata, Marisa Marcia, Carvalheiro, Cristina Gardonyi, Piddock, Laura J. V., Heath, Paul T., Malhotra-Kumar, Surbhi, Sharland, Michael, Glupczynski, Youri, and Goossens, Herman

Published
2024
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6. Cross-border differences in the prevalence and risk factors for carriage of antimicrobial resistance in children attending daycare centers: a point prevalence study in the Netherlands and Belgium

Author

Dequeker, Sara, van Hensbergen, Mitch, den Heijer, Casper D. J., Dhaeze, Wouter, Raven, Stijn F. H., Ewalts-Hakkoer, Helen, Tolsma, Paulien, Willemsen, Ina, van Drunen-Kamp, Karine J., van der Slikke-Verstraten, Krista, Goossens, Herman, Kluytmans-van den Bergh, Marjolein F. Q., and Hoebe, Christian J. P. A.

Published
2024
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7. Simvastatin in Critically Ill Patients with Covid-19.

Author

Hills, Thomas, Lorenzi, Elizabeth, Berry, Lindsay, Shyamsundar, Murali, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Aryal, Diptesh, Au, Carly, Beane, Abigail, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Burrell, Aidan, Buxton, Meredith, Calfee, Carolyn, Cecconi, Maurizio, Cheng, Allen, Cove, Matthew, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goligher, Ewan, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Harrison, David, Hashmi, Madiha, Higgins, Alisa, Huang, David, Ichihara, Nao, Jayakumar, Deva, Kruger, Peter, Lamontagne, François, Lampro, Lamprini, Lawler, Patrick, Marshall, John, Mason, Alexina, McGlothlin, Anna, McGuinness, Shay, McQuilten, Zoe, McVerry, Bryan, Mouncey, Paul, Murthy, Srinivas, Neal, Matthew, Nichol, Alistair, OKane, Cecilia, Parke, Rachael, Parker, Jane, Rabindrarajan, Ebenezer, Reyes, Luis, Rowan, Kathryn, Saito, Hiroki, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Shankar-Hari, Manu, Sinha, Pratik, Thompson, B, Turgeon, Alexis, Turner, Anne, van de Veerdonk, Frank, Weis, Sebastian, Young, Ian, Zarychanski, Ryan, McArthur, Colin, Angus, Derek, Berry, Scott, Derde, Lennie, Webb, Steve, Gordon, Anthony, McAuley, Daniel, and Lewis, Roger

Subjects
Humans, Bayes Theorem, COVID-19, COVID-19 Drug Treatment, Critical Illness, Hospital Mortality, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Treatment Outcome
Abstract

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was

Published
2023

8. The global point prevalence survey of antimicrobial consumption and resistance (Global-PPS): First results of antimicrobial prescribing in a children hospital in Nigeria

Author

Aghogorvia Titilayo M, Ola-Bello Olafoyekemi I, Mabogunje Cecilia, Versporten Ann, Pauwels Ines, Goossens Herman, Aina Olugbenga, Roberts Alero A, Akinjole Janet O, and Oduyebo Oyinlola O

Subjects
antimicrobial, stewardship, resistance, children, global-pps, Medicine
Abstract

Background: Antimicrobial stewardship is vital for our hospital practice but it requires a knowledge of antibiotic prescribing practices, which is currently lacking. This survey aimed to assess the antimicrobial prescribing practices in our hospital. Method: To obtain baseline information on antimicrobial prescribing practices, a uniform and standardized method for surveillance of antibiotic use in hospitals was employed. A point prevalence survey (PPS) was conducted in all the wards of the Massey Street Children’s hospital in June 2019. The PPS included all i n p a t i e n t s r e c e i v i n g a n antimicrobial on the day of survey. Data collected included age, gender, antimicrobial agents, microbiological data, and compliance to guidelines, documentation of reasons and stop/ review date of prescription. The denominator was the number of eligible patients. A web-based application developed by the University of Antwerp was used for data-entry, validation and reporting. Results: Sixty-seven children were eligible, of which 62 (92%) CC –BY 4.0 received 128 antimicrobials. Fifty- seven (85%) were on multiple antimicrobial therapies, and route of administration was parenteral in 86%. All prescriptions were empiric. Reasons for prescribing were documented in 121(94.5%) therapies in case notes; Stop/review dates were not documented in 126(98.4%). The most frequently prescribed antibiotics we r e c e f u r o x i m e ( 1 8 % ) , Ampicillin-sulbactam (15%) and gentamicin (12%). Antibiotic guidelines were not available. Most common diagnoses were sepsis (42%), pneumonia (15%) and malaria (9%). Conclusion: This survey revealed v e r y h i g h a n t i m i c r o b i a l prescribing rates in the hospital and the need to assess it appropriateness. We disclosed areas to improve antibiotic prescribing: antibiotic prescribing according to guidelines and low reporting of a stop/review date. There is a need to create awareness for evidence based antibiotic guidelines.

Published
2024

9. Antimicrobial prescribing patterns in patients with COVID-19 in Russian multi-field hospitals in 2021: Results of the Global-PPS Project

Author

Avdeev, Sergey, Rachina, Svetlana, Belkova, Yuliya, Kozlov, Roman, Versporten, Ann, Pauwels, Ines, Goossens, Herman, Bochanova, Elena, Elokhina, Elena, Portnjagina, Ulyana, Reshetko, Olga, Sychev, Igor, Strelkova, Darya, Evgeny, Dovgan, Lyudmila, Fedina, Yulia, Kim, Svyatoslav, Korolkov, Evgenia, Kurtz, Anastasia, Kuznetsova, Artur, Levitan, Konstantin, Lutsevich, Tatiana, Lutsevich, Larisa, Popova, Ekaterina, Privalova, Valentin, Prokopovich, Sofia, Rogacheva, and Inna, Ryzhenkova

Published
2022

11. Immunogenicity, reactogenicity, and safety of a second booster with BNT162b2 or full-dose mRNA-1273: A randomized VACCELERATE trial in adults aged ≥75 years (EU-COVAT-1-AGED Part B)

Author

Stemler, Jannik, Yeghiazaryan, Lusine, Stephan, Christoph, Mohn, Kristin Greve-Isdahl, Carcas-Sansuan, Antonio-José, Rodriguez, Esperanza Romero, Moltó, José, Mitxeltorena, Itziar Vergara, Welte, Tobias, Zablockienė, Birutė, Akova, Murat, Bethe, Ullrich, Heringer, Sarah, Salmanton-García, Jon, Jeck, Julia, Tischmann, Lea, Zarrouk, Marouan, Cüppers, Arnd, Biehl, Lena M., Grothe, Jan, Mellinghoff, Sibylle C., Nacov, Julia A., Neuhann, Julia M., Sprute, Rosanne, Frías-Iniesta, Jesús, Negi, Riya, Gaillard, Colette, Saini, Gurvin, León, Alejandro García, Mallon, Patrick W.G., Lammens, Christine, Hotterbeekx, An, Loens, Katherine, Malhotra-Kumar, Surbhi, Goossens, Herman, Kumar-Singh, Samir, König, Franz, Posch, Martin, Koehler, Philipp, and Cornely, Oliver A.

Published
2024
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12. Global-PPS targets for antimicrobial stewardship in paediatric patients at hospitals in Sanandaj, Western Iran, compared with Southeast Asian and European hospitals

Author

Verhamme, Katia, Vanneste, Lorenz, Jansens, Hilde, Konopnicki, Deborah, Hufnagel, Markus, chadalavada, vineela, Schweitzer, Valentijn, Reyes, Mari Rose A. De Los, Garcia, Jemelyn U., Bo, Rhenalyn, Andres, Joy, Morga, Janelle B., Bonaobra, Joan, Quisil, Darel Gresan, Muñasquer, Estella, Javier, Zenaida M., Ariola – Ramos, Mary Shiela J., Salvio, Lilibeth G., Vergara, Aubrey V., Jison, Catherine T., Cerrada, Joan E., Macasero, Michelle L., Pabalinas, John Marz Richmond B., Mayo, Isolde, Toledo, Keshia Kate S., Layora, Desteen Abegail M., Valenzuela, Keith Bryan S., Hufano, Ma. Charmain M., Sabado, Anna Andrea S., Tizon, Susana, Ancieto, Ralph, Yago, Julie S., Somera, Katrina M., Jurao, Ludovico L., Torio, Ma Kristina U., Gler, Ma. Tarcela S., Betito, Gina de Guzman, Villadore, Lozel, Pedron, Dan Micko F., Nava, Ralph, Ceraos, Anthony, Mendoza, Myrna, Ecarma, Raquel, Dela Cruz, Buenafe A., Espeleta, Elsa M., Afaga, Liezel C., Espiritu, Joynes N., Callos, Marie Paz S., Villasis, Jannsen, Monzon, Olivia, Padua, Jay Ron O., Medrano, Kara Marie Venice P., Yabut, Agnes, Palomo, Ma. Regina A., Araneta, Teresita Cherie, Fontanilla, Stephen Rae G., Mendoza, Maria Jonelyn C., P, Mia Lovella, Aparece, Nomi, Yala, Expedito, Paez, Vivinia, Tamayo, Ellen Marie, Henson, Karl Evans R., Rayos, Katrina, Rellamas, Mona Clare, rguil, Yuriko A, Parreno, Maria Luna, Ayson, Mary Jane Dolores, Chan, Marchi D., Gentil, PILAR Retamar, Riddell, Anna, Soltani, Jafar, Behzadi, Shirin, Pauwels, Ines, Goossens, Herman, and Versporten, Ann

Published
2024
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13. Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA)

Author

Serna, Almudena de la, Monteau, Sophie, Palomo, Virginia, Soriano, Elena, Gutierrez, David, Moreno, Elisa, Sojo-Dorado, Jesus, Morales, Isabel, Maldonado, Natalia, Santis, Lucia Valiente de, Ciezar, Antonio Plata, Ruiz Mesa, Juan Diego, Diaz, Beatriz Sobrino, Gomez, Ignacio Marquez, Camacho, Ines Perez, Cano, Angela, Frutos-Adame, Azahara, Guzman-Puche, Julia, Gracia-Ahufinger, Irene, Perez-Nadales, Elena, Torre-Gimenez, Julian, Pyrpasopoulou, Athina, Iosifidis, Elias, Chorafa, Elsa, Radovanovic, Ivana, Petrovic, Sladjana, Cvetkovi, Slavica, Melentijevic, Srdjan-Sanja, Bicmen, Can, Senol, Gunes, Tubau, Fe, Camara, Jordi, Daniel Gumucio, Victor, Bassoulis, Dimitris, Deliolanis, John, Pitiriga, Vassiliki Ch., Triarides, Nikolaos, Argiti, Efstathia, Legakis, Nikolaos J., Margarita, Kyriakidou, Gijón-Cordero, Desirée, Ruiz-Garbajosa, Patricia, Rossolini, Gian Maria, Nica, Maria, Talapan, Daniela, Medić, Deana, Prijić, Sanja Maričić, Caballero, Mireia Cantero, Ramírez, Lina M Parra, Bilgin, Hüseyin, Dalekos, George N., Stefos, Aggelos, Spyridis, Nikolaos, Michos, Athanasios, De Rosa, Francesco Giuseppe, Cavallo, Rossana, Petrosillo, Nicola, Dicaro, Antonio, Landini, Maria Paola, degli Atti, Marta Luisa Ciofi, Masanovic, Mileva, Matkovic, Dusan, Tsiodras, Sotirios, Blasi, Francesco, pasquale, Marta Di, Viscoli, Claudio, Vata, Andrei, Dorneanu, Olivia, Kapisyzi, Perlat, Vince, Adriana, Tsigou, Evdoxia, Maltezos, Efstratios, Komnos, Apostolos, Gogos, Charalampos, Franzetti, Fabio, Antonelli, Massimo, Lupse, Mihaela, Corneci, Dan, Tomescu, Dana, Georgescu, Anca, Bukarica, Ljiljana, Mitrović, Goran, Krstić, Nataša Lukić, Kurti, Arsim, Reuter, Sandra, Díaz-Pollán, Beatriz, Sabater, Julia Origüen, Muñoz, Patricia, Azap, Alpay, ancak, Banu, Sahin, Arife, Akalin, Halis, Paniagua-García, María, Bravo-Ferrer, Jose M., Pérez-Galera, Salvador, Kostyanev, Tomislav, de Kraker, Marlieke E.A., Feifel, Jan, Palacios-Baena, Zaira R., Schotsman, Joost, Cantón, Rafael, Daikos, George L., Carevic, Biljana, Dragovac, Gorana, Tan, Lionel K., Raka, Lul, Hristea, Adriana, Viale, Pierluigi, Akova, Murat, Cano, Ángela, Reguera, Jose María, Bartoloni, Alessandro, Florescu, Simin-Aysel, Benea, Serban, Asensio, Ángel, Korten, Volkan, Grundmann, Hajo, Goossens, Herman, Bonten, Marc J., Gutiérrez-Gutiérrez, Belén, and Rodríguez-Baño, Jesús

Published
2024
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14. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Author

Goligher, Ewan C, Bradbury, Charlotte A, McVerry, Bryan J, Lawler, Patrick R, Berger, Jeffrey S, Gong, Michelle N, Carrier, Marc, Reynolds, Harmony R, Kumar, Anand, Turgeon, Alexis F, Kornblith, Lucy Z, Kahn, Susan R, Marshall, John C, Kim, Keri S, Houston, Brett L, Derde, Lennie PG, Cushman, Mary, Tritschler, Tobias, Angus, Derek C, Godoy, Lucas C, McQuilten, Zoe, Kirwan, Bridget-Anne, Farkouh, Michael E, Brooks, Maria M, Lewis, Roger J, Berry, Lindsay R, Lorenzi, Elizabeth, Gordon, Anthony C, Ahuja, Tania, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Contreras, Aira, Costantini, Todd W, de Brouwer, Sophie, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Eng, Heather F, Escobedo, Jorge, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Froess, Joshua D, Fu, Zhuxuan, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, Girard, Timothy D, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Haniffa, Rashan, Hegde, Sheila M, Hendrickson, Carolyn M, Higgins, Alisa M, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Huang, David T, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei, King, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, Kutcher, Matthew E, Laffan, Michael A, Lamontagne, Francois, and Le Gal, Grégoire

Subjects
Clinical Trials and Supportive Activities, Clinical Research, Comparative Effectiveness Research, Cardiovascular, Good Health and Well Being, Aged, Anticoagulants, COVID-19, Critical Illness, Female, Hemorrhage, Heparin, Hospital Mortality, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Respiration, Artificial, Thrombosis, Treatment Failure, COVID-19 Drug Treatment, REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.MethodsIn an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.ResultsThe trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio

Published
2021

15. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Author

Lawler, Patrick R, Goligher, Ewan C, Berger, Jeffrey S, Neal, Matthew D, McVerry, Bryan J, Nicolau, Jose C, Gong, Michelle N, Carrier, Marc, Rosenson, Robert S, Reynolds, Harmony R, Turgeon, Alexis F, Escobedo, Jorge, Huang, David T, Bradbury, Charlotte A, Houston, Brett L, Kornblith, Lucy Z, Kumar, Anand, Kahn, Susan R, Cushman, Mary, McQuilten, Zoe, Slutsky, Arthur S, Kim, Keri S, Gordon, Anthony C, Kirwan, Bridget-Anne, Brooks, Maria M, Higgins, Alisa M, Lewis, Roger J, Lorenzi, Elizabeth, Berry, Scott M, Berry, Lindsay R, Aday, Aaron W, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Costantini, Todd W, de Brouwer, Sophie, Derde, Lennie PG, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, García-Madrona, Sebastian, Girard, Timothy D, Godoy, Lucas C, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Hamburg, Naomi M, Haniffa, Rashan, Hanna, George, Hanna, Nicholas, Hegde, Sheila M, Hendrickson, Carolyn M, Hite, R Duncan, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Iyer, Vivek N, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei L, King, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, and Krishnan, Vidya

Subjects
Cardiovascular, Clinical Trials and Supportive Activities, Clinical Research, Hematology, Transplantation, Good Health and Well Being, Adult, Aged, Anticoagulants, COVID-19, Female, Hemorrhage, Heparin, Heparin, Low-Molecular-Weight, Hospital Mortality, Humans, Male, Middle Aged, Survival Analysis, Thrombosis, COVID-19 Drug Treatment, ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.MethodsIn this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.ResultsThe trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.ConclusionsIn noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

Published
2021

16. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.

Author

REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Goligher, Ewan C, Bradbury, Charlotte A, McVerry, Bryan J, Lawler, Patrick R, Berger, Jeffrey S, Gong, Michelle N, Carrier, Marc, Reynolds, Harmony R, Kumar, Anand, Turgeon, Alexis F, Kornblith, Lucy Z, Kahn, Susan R, Marshall, John C, Kim, Keri S, Houston, Brett L, Derde, Lennie PG, Cushman, Mary, Tritschler, Tobias, Angus, Derek C, Godoy, Lucas C, McQuilten, Zoe, Kirwan, Bridget-Anne, Farkouh, Michael E, Brooks, Maria M, Lewis, Roger J, Berry, Lindsay R, Lorenzi, Elizabeth, Gordon, Anthony C, Ahuja, Tania, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Contreras, Aira, Costantini, Todd W, de Brouwer, Sophie, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Eng, Heather F, Escobedo, Jorge, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Froess, Joshua D, Fu, Zhuxuan, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, Girard, Timothy D, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Haniffa, Rashan, Hegde, Sheila M, Hendrickson, Carolyn M, Higgins, Alisa M, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Huang, David T, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei, King, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, and Kutcher, Matthew E

Subjects
REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Humans, Thrombosis, Critical Illness, Hemorrhage, Heparin, Anticoagulants, Treatment Failure, Respiration, Artificial, Hospital Mortality, Logistic Models, Odds Ratio, Aged, Middle Aged, Female, Male, COVID-19, Clinical Research, Cardiovascular, Clinical Trials and Supportive Activities, Comparative Effectiveness Research, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundThrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.MethodsIn an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.ResultsThe trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio

Published
2021

17. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.

Author

ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Lawler, Patrick R, Goligher, Ewan C, Berger, Jeffrey S, Neal, Matthew D, McVerry, Bryan J, Nicolau, Jose C, Gong, Michelle N, Carrier, Marc, Rosenson, Robert S, Reynolds, Harmony R, Turgeon, Alexis F, Escobedo, Jorge, Huang, David T, Bradbury, Charlotte A, Houston, Brett L, Kornblith, Lucy Z, Kumar, Anand, Kahn, Susan R, Cushman, Mary, McQuilten, Zoe, Slutsky, Arthur S, Kim, Keri S, Gordon, Anthony C, Kirwan, Bridget-Anne, Brooks, Maria M, Higgins, Alisa M, Lewis, Roger J, Lorenzi, Elizabeth, Berry, Scott M, Berry, Lindsay R, Aday, Aaron W, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Costantini, Todd W, de Brouwer, Sophie, Derde, Lennie PG, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, García-Madrona, Sebastian, Girard, Timothy D, Godoy, Lucas C, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Hamburg, Naomi M, Haniffa, Rashan, Hanna, George, Hanna, Nicholas, Hegde, Sheila M, Hendrickson, Carolyn M, Hite, R Duncan, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Iyer, Vivek N, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei L, and King, Andrew J

Subjects
ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Humans, Thrombosis, Hemorrhage, Heparin, Heparin, Low-Molecular-Weight, Anticoagulants, Hospital Mortality, Survival Analysis, Adult, Aged, Middle Aged, Female, Male, COVID-19, Hematology, Clinical Trials and Supportive Activities, Transplantation, Clinical Research, Cardiovascular, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundThrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.MethodsIn this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.ResultsThe trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.ConclusionsIn noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

Published
2021

18. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

Author

Arabi, Yaseen M, Gordon, Anthony C, Derde, Lennie PG, Nichol, Alistair D, Murthy, Srinivas, Beidh, Farah Al, Annane, Djillali, Swaidan, Lolowa Al, Beane, Abi, Beasley, Richard, Berry, Lindsay R, Bhimani, Zahra, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen, De Jong, Menno, Detry, Michelle A, Duffy, Eamon J, Estcourt, Lise J, Fitzgerald, Mark, Fowler, Rob, Girard, Timothy D, Goligher, Ewan C, Goossens, Herman, Haniffa, Rashan, Higgins, Alisa M, Hills, Thomas E, Horvat, Christopher M, Huang, David T, King, Andrew J, Lamontagne, Francois, Lawler, Patrick R, Lewis, Roger, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Malakouti, Salim, McAuley, Daniel F, McGlothlin, Anna, Mcguinness, Shay, McVerry, Bryan J, Montgomery, Stephanie K, Morpeth, Susan C, Mouncey, Paul R, Orr, Katrina, Parke, Rachael, Parker, Jane C, Patanwala, Asad E, Rowan, Kathryn M, Santos, Marlene S, Saunders, Christina T, Seymour, Christopher W, Shankar-Hari, Manu, Tong, Steven YC, Turgeon, Alexis F, Turner, Anne M, Van de Veerdonk, Frank Leo, Zarychanski, Ryan, Green, Cameron, Berry, Scott, Marshall, John C, McArthur, Colin, Angus, Derek C, and Webb, Steven A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Comparative Effectiveness Research, Clinical Research, Clinical Trials and Supportive Activities, Good Health and Well Being, Adult, Antiviral Agents, Bayes Theorem, Critical Illness, Drug Combinations, Humans, Hydroxychloroquine, Lopinavir, Ritonavir, SARS-CoV-2, COVID-19 Drug Treatment, Adaptive platform trial, Intensive care, Pneumonia, Pandemic, COVID-19, Lopinavir-ritonavir, REMAP-CAP Investigators, Public Health and Health Services, Emergency & Critical Care Medicine, Clinical sciences
Abstract

PurposeTo study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsCritically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable.ResultsWe randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively).ConclusionAmong critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.

Published
2021

19. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

Author

Gordon, Anthony, Mouncey, Paul, Al-Beidh, Farah, Rowan, Kathryn, Nichol, Alistair, Arabi, Yaseen, Annane, Djillali, Beane, Abi, van Bentum-Puijk, Wilma, Berry, Lindsay, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buzgau, Adrian, Cheng, Allen, Detry, Michelle, Duffy, Eamon, Estcourt, Lise, Fitzgerald, Mark, Goossens, Herman, Haniffa, Rashan, Higgins, Alisa, Hills, Thomas, Horvat, Christopher, Lamontagne, Francois, Lawler, Patrick, Leavis, Helen, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Marshall, John, Mayr, Florian, McAuley, Daniel, McGlothlin, Anna, McGuinness, Shay, McVerry, Bryan, Montgomery, Stephanie, Morpeth, Susan, Murthy, Srinivas, Orr, Katrina, Parke, Rachael, Parker, Jane, Patanwala, Asad, Pettilä, Ville, Rademaker, Emma, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Shankar-Hari, Manu, Sligl, Wendy, Turgeon, Alexis, Turner, Anne, van de Veerdonk, Frank, Zarychanski, Ryan, Green, Cameron, Lewis, Roger, Angus, Derek, McArthur, Colin, Berry, Scott, Webb, Steve, and Derde, Lennie

Subjects
Adult, Aged, Antibodies, Monoclonal, Humanized, COVID-19, Critical Illness, Female, Hospital Mortality, Humans, Intensive Care Units, Male, Middle Aged, Odds Ratio, Receptors, Interleukin-6, Respiration, Artificial, COVID-19 Drug Treatment
Abstract

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).

Published
2021

20. The Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia (REMAP-CAP) Study: Rationale and Design

Author

Angus, Derek C, Berry, Scott, Lewis, Roger J, Al-Beidh, Farah, Arabi, Yaseen, van Bentum-Puijk, Wilma, Bhimani, Zahra, Bonten, Marc, Broglio, Kristine, Brunkhorst, Frank, Cheng, Allen C, Chiche, Jean-Daniel, De Jong, Menno, Detry, Michelle, Goossens, Herman, Gordon, Anthony, Green, Cameron, Higgins, Alisa M, Hullegie, Sebastiaan J, Kruger, Peter, Lamontagne, Francois, Litton, Edward, Marshall, John, McGlothlin, Anna, McGuinness, Shay, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, O'Neill, Genevieve K, Parke, Rachael, Parker, Jane, Rohde, Gernot, Rowan, Kathryn, Turner, Anne, Young, Paul, Derde, Lennie, McArthur, Colin, and Webb, Steven A

Subjects
Influenza, Cancer, Clinical Research, Lung, Clinical Trials and Supportive Activities, Vaccine Related, Pneumonia & Influenza, Comparative Effectiveness Research, Patient Safety, Infectious Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Anti-Bacterial Agents, Antiviral Agents, Betacoronavirus, COVID-19, Community-Acquired Infections, Coronavirus Infections, Evidence-Based Medicine, Humans, Influenza, Human, Pandemics, Pneumonia, Pneumonia, Viral, Point-of-Care Systems, SARS-CoV-2, randomized clinical trial, Bayesian adaptive platform trial, master protocol, community-acquired pneumonia, coronavirus disease 2019, Bayesian adaptive, platform trial
Abstract

There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled "a randomized embedded multifactorial adaptive platform." The design has five key features: 1) randomization, allowing robust causal inference; 2) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability; 3) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups; 4) response-adaptive randomization with preferential assignment to those interventions that appear most favorable; and 5) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within four treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority, and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies, and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) was approved and enrolling patients in 52 intensive care units in 13 countries on 3 continents. In February, it transitioned into pandemic mode with several design adaptations for coronavirus disease 2019. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas.Clinical trial registered with www.clinicaltrials.gov (NCT02735707).

Published
2020

21. The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design.

Author

Angus, Derek C, Berry, Scott, Lewis, Roger J, Al-Beidh, Farah, Arabi, Yaseen, van Bentum-Puijk, Wilma, Bhimani, Zahra, Bonten, Marc, Broglio, Kristine, Brunkhorst, Frank, Cheng, Allen C, Chiche, Jean-Daniel, De Jong, Menno, Detry, Michelle, Goossens, Herman, Gordon, Anthony, Green, Cameron, Higgins, Alisa M, Hullegie, Sebastiaan J, Kruger, Peter, Lamontagne, Francois, Litton, Edward, Marshall, John, McGlothlin, Anna, McGuinness, Shay, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, O'Neill, Genevieve K, Parke, Rachael, Parker, Jane, Rohde, Gernot, Rowan, Kathryn, Turner, Anne, Young, Paul, Derde, Lennie, McArthur, Colin, and Webb, Steven A

Subjects
Humans, Community-Acquired Infections, Pneumonia, Viral, Coronavirus Infections, Pneumonia, Anti-Bacterial Agents, Antiviral Agents, Evidence-Based Medicine, Point-of-Care Systems, Influenza, Human, Pandemics, Betacoronavirus, COVID-19, SARS-CoV-2, Bayesian adaptive, community-acquired pneumonia, coronavirus disease 2019, master protocol, platform trial, randomized clinical trial, Bayesian adaptive platform trial, Respiratory System, Clinical Sciences
Abstract

There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled "a randomized embedded multifactorial adaptive platform." The design has five key features: 1) randomization, allowing robust causal inference; 2) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability; 3) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups; 4) response-adaptive randomization with preferential assignment to those interventions that appear most favorable; and 5) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within four treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority, and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies, and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) was approved and enrolling patients in 52 intensive care units in 13 countries on 3 continents. In February, it transitioned into pandemic mode with several design adaptations for coronavirus disease 2019. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas.Clinical trial registered with www.clinicaltrials.gov (NCT02735707).

Published
2020

22. Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

Author

de la Serna, Almudena, Monteau, Sophie, Palomo, Virginia, Soriano, Elena, Gutierrez, David, Moreno, Elisa, Palacios, Zaira, Morales, Isabel, Maldonado, Natalia, Ciezar, Antonio Plata, Ruiz Mesa, Juan Diego, Diaz, Beatriz Sobrino, Gomez, Ignacio Marquez, Camacho, Ines Perez, Frutos-Adame, Azahara, Guzman-Puche, Julia, Gracia-Ahufinger, Irene, Perez-Nadales, Elena, Torre-Gimenez, Julian, Pyrpasopoulou, Athina, Iosifidis, Elias, Chorafa, Elsa, Radovanovic, Ivana, Petrovic, Sladjana, Cvetkovi, Slavica, Melentijevic, Srdjan-Sanja, Bicmen, Can, Senol, Gunes, Tubau, Fe, Camara, Jordi, Gumucio, Victor Daniel, Bassoulis, Dimitris, Deliolanis, John, Pitiriga, Vassiliki Ch., Triarides, Nikolaos, Argiti, Efstathia, Legakis, Nikolaos J., Margarita, Kyriakidou, Gijón-Cordero, Desirée, Ruiz-Garbajosa, Patricia, Bartoloni, Alessandro, Rossolini, Gian Maria, Florescu, Simin-Aysel, Nica, Maria, Benea, Serban, Talapan, Daniela, Medić, Deana, Prijić, Sanja Maričić, Caballero, Mireia Cantero, Parra Ramírez, Lina M., Korten, Volkan, Bilgin, Hüseyin, Dalekos, George N., Stefos, Aggelos, Spyridis, Nikolaos, Michos, Athanasios, De Rosa, Francesco Giuseppe, Cavallo, Rossana, Petrosillo, Nicola, Dicaro, Antonio, Landini, Maria Paola, Ciofi degli Atti, Marta Luisa, Masanovic, Mileva, Matkovic, Dusan, Tsiodras, Sotirios, Blasi, Francesco, Di pasquale, Marta, Viscoli, Claudio, Vata, Andrei, Dorneanu, Olivia, Kapisyzi, Perlat, Vince, Adriana, Tsigou, Evdoxia, Maltezos, Efstratios, Komnos, Apostolos, Gogos, Charalampos, Franzetti, Fabio, Antonelli, Massimo, Lupse, Mihaela, Corneci, Dan, Tomescu, Dana, Georgescu, Anca, Bukarica, Ljiljana, Mitrović, Goran, Krstić, Nataša Lukić, Kurti, Arsim, Díaz-Pollán, Beatriz, Sabater, Julia Origüen, Muñoz, Patricia, Azap, Alpay, Sancak, Banu, Sahin, Arife, Akalin, Halis, Pérez-Galera, Salvador, Bravo-Ferrer, Jose M., Paniagua, María, Kostyanev, Tomislav, de Kraker, Marlieke E.A., Feifel, Jan, Sojo-Dorado, Jesús, Schotsman, Joost, Cantón, Rafael, Daikos, George L., Carevic, Biljana, Dragovac, Gorana, Tan, Lionel K., Raka, Lul, Hristea, Adriana, Viale, Pierluigi, Akova, Murat, Reguera, Jose María, Valiente de Santis, Lucía, Torre-Cisneros, Julián, Cano, Ángela, Roilides, Emmanuel, Radulovic, Lili, Kirakli, Cenk, Shaw, Evelyn, Falagas, Matthew E., Pintado, Vicente, Goossens, Herman, Bonten, Marc J., Gutiérrez-Gutiérrez, Belén, and Rodriguez-Baño, Jesús

Published
2023
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24. Challenges of data sharing in European Covid-19 projects: A learning opportunity for advancing pandemic preparedness and response

Author

Tacconelli, Evelina, Gorska, Anna, Carrara, Elena, Davis, Ruth Joanna, Bonten, Marc, Friedrich, Alex W., Glasner, Corinna, Goossens, Herman, Hasenauer, Jan, Abad, Josep Maria Haro, Peñalvo, José L., Sanchez-Niubo, Albert, Sialm, Anastassja, Scipione, Gabriella, Soriano, Gloria, Yazdanpanah, Yazdan, Vorstenbosch, Ellen, and Jaenisch, Thomas

Published
2022
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25. Did aetiology matter in illness duration and complications in patients presenting in primary care with acute respiratory tract infections early in the COVID-19 pandemic: An observational study in nine countries.

Author

Venekamp, Roderick P., Eijkemans, Marinus J.C., Zuithoff, Nicolaas P.A., Böhmer, Femke, Chlabicz, Slawomir, Colliers, Annelies, García-Sangenís, Ana, Malania, Lile, Pauer, Jozsef, Tomacinschii, Angela, Verheij, Theo J., Goossens, Herman, Vellinga, Akke, Butler, Christopher C., and van der Velden, Alike W.

Published
2024
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28. Profiling of humoral immune responses to norovirus in children across Europe

Author

Villabruna, Nele, Izquierdo-Lara, Ray W., Schapendonk, Claudia M. E., de Bruin, Erwin, Chandler, Felicity, Thao, Tran Thi Nhu, Westerhuis, Brenda M., van Beek, Janko, Sigfrid, Louise, Giaquinto, Carlo, Goossens, Herman, Bielicki, Julia A., Kohns Vasconcelos, Malte, Fraaij, Pieter L. A., Koopmans, Marion P. G., and de Graaf, Miranda

Published
2022
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30. Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial

Author

Chastre, Jean, François, Bruno, Bourgeois, Marc, Komnos, Apostolos, Ferrer, Ricard, Rahav, Galia, De Schryver, Nicolas, Lepape, Alain, Koksal, Iftihar, Luyt, Charles-Edouard, Sánchez-García, Miguel, Torres, Antoni, Eggimann, Philippe, Koulenti, Despoina, Holland, Thomas L., Ali, Omar, Shoemaker, Kathryn, Ren, Pin, Sauser, Julien, Ruzin, Alexey, Tabor, David E., Akhgar, Ahmad, Wu, Yuling, Jiang, Yu, DiGiandomenico, Antonio, Colbert, Susan, Vandamme, Drieke, Coenjaerts, Frank, Malhotra-Kumar, Surbhi, Timbermont, Leen, Oliver, Antonio, Barraud, Olivier, Bellamy, Terramika, Bonten, Marc, Goossens, Herman, Reisner, Colin, Esser, Mark T., and Jafri, Hasan S.

Published
2022
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31. Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS)

Author

Russell, Neal J., Stöhr, Wolfgang, Plakkal, Nishad, Cook, Aislinn, Berkley, James A., Adhisivam, Bethou, Agarwal, Ramesh, Ahmed, Nawshad Uddin, Balasegaram, Manica, Ballot, Daynia, Bekker, Adrie, Berezin, Eitan Naaman, Bilardi, Davide, Boonkasidecha, Suppawat, Carvalheiro, Cristina G., Chami, Neema, Chaurasia, Suman, Chiurchiu, Sara, Colas, Viviane Rinaldi Favarin, Cousens, Simon, Cressey, Tim R., de Assis, Ana Carolina Dantas, Dien, Tran Minh, Ding, Yijun, Dung, Nguyen Trong, Dong, Han, Dramowski, Angela, DS, Madhusudhan, Dudeja, Ajay, Feng, Jinxing, Glupczynski, Youri, Goel, Srishti, Goossens, Herman, Hao, Doan Thi Huong, Khan, Mahmudul Islam, Huertas, Tatiana Munera, Islam, Mohammad Shahidul, Jarovsky, Daniel, Khavessian, Nathalie, Khorana, Meera, Kontou, Angeliki, Kostyanev, Tomislav, Laoyookhon, Premsak, Lochindarat, Sorasak, Larsson, Mattias, Luca, Maia De, Malhotra-Kumar, Surbhi, Mondal, Nivedita, Mundhra, Nitu, Musoke, Philippa, Mussi-Pinhata, Marisa M., Nanavati, Ruchi, Nakwa, Firdose, Nangia, Sushma, Nankunda, Jolly, Nardone, Alessandra, Nyaoke, Borna, Obiero, Christina W., Owor, Maxensia, Ping, Wang, Preedisripipat, Kanchana, Qazi, Shamim, Qi, Lifeng, Ramdin, Tanusha, Riddell, Amy, Romani, Lorenza, Roysuwan, Praewpan, Saggers, Robin, Roilides, Emmanuel, Saha, Samir K., Sarafidis, Kosmas, Tusubira, Valerie, Thomas, Reenu, Velaphi, Sithembiso, Vilken, Tuba, Wang, Xiaojiao, Wang, Yajuan, Yang, Yonghong, Zunjie, Liu, Ellis, Sally, Bielicki, Julia A., Walker, A. Sarah, Heath, Paul T., and Sharland, Mike

Subjects
Infants -- Patient outcomes, Sepsis -- Diagnosis -- Care and treatment, Antibiotics -- Dosage and administration, Hospital patients -- Care and treatment, Market trend/market analysis, Biological sciences
Abstract

Background There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. Methods and findings Hospitalized infants A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-'Low' Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3-'Medium' Watch), 18.0% (n = 566) started a carbapenem (Group 4-'High' Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. Conclusion Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. Trial registration ClinicalTrials.gov, (NCT03721302)., Author(s): Neal J. Russell 1,*, Wolfgang Stöhr 2, Nishad Plakkal 3, Aislinn Cook 1, James A. Berkley 4,5,6, Bethou Adhisivam 3, Ramesh Agarwal 7, Nawshad Uddin Ahmed 8, Manica Balasegaram [...]

Published
2023
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34. Antimicrobial resistance research in a post-pandemic world: Insights on antimicrobial resistance research in the COVID-19 pandemic

Author

Rodríguez-Baño, Jesús, Rossolini, Gian Maria, Schultsz, Constance, Tacconelli, Evelina, Murthy, Srinivas, Ohmagari, Norio, Holmes, Alison, Bachmann, Till, Goossens, Herman, Canton, Rafael, Roberts, Adam P., Henriques-Normark, Birgitta, Clancy, Cornelius J., Huttner, Benedikt, Fagerstedt, Patriq, Lahiri, Shawon, Kaushic, Charu, Hoffman, Steven J., Warren, Margo, Zoubiane, Ghada, Essack, Sabiha, Laxminarayan, Ramanan, and Plant, Laura

Published
2021
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37. Multi-Criteria Decision Analysis to prioritize hospital admission of patients affected by COVID-19 in low-resource settings with hospital-bed shortage

Author

Durante Mangoni, E., Florio, L.L., Zampino, R., Mele, F., Gentile, I., Pinchera, B., Coppola, N., Pisaturo, M., Luzzati, R., Petrosillo, N., Nicastri, E., Corpolongo, A., Cataldo, M.A., D’Abramo, A., Maffongelli, G., Scorzolini, L., Palazzolo, C., Boumis, E., Pan, A., D’Arminio Monforte, A., Bai, F., Antinori, S., De Rosa, F.G., Corcione, S., Lupia, T., Pinna, S.M., Scabini, S., Canta, F., Belloro, S., Bisoffi, Z., Angheben, A., Gobbi, F., Turcato, E., Ronzoni, N., Moro, L., Calabria, S., Rodari, P., Bertoli, G., Marasca, G., Puoti, M., Gori, A., Bandera, A., Mangioni, D., Rizzi, M., Castelli, F., Montineri, A., Coco, C.A., Maresca, M., Frasca, M., Aquilini, D., Vincenzi, M., Lambertenghi, L., De Rui, M.E., Razzaboni, E., Cattaneo, P., Visentin, A., Erbogasto, A., Dalla Vecchia, I., Coledan, I., Vecchi, M., Be, G., Motta, L., Zaffagnini, A., Auerbach, N., Del Bravo, P., Azzini, A.M., Righi, E., Carrara, E., Savoldi, A., Sibani, M., Lattuada, E., Carolo, G., Cordioli, M., Soldani, F., Pezzani, M.D., Avallone, S., Bruno, R., Ricciardi, A., Saggese, M.P., Malerba, G., De Nardo, Pasquale, Gentilotti, Elisa, Mazzaferri, Fulvia, Cremonini, Eleonora, Hansen, Paul, Goossens, Herman, and Tacconelli, Evelina

Published
2020
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41. Did aetiology matter in illness duration and complications in patients presenting in primary care with acute respiratory tract infections early in the COVID-19 pandemic: An observational study in nine countries

Author

HAG Onderzoek, Infection & Immunity, Child Health, Biostatistiek Onderzoek, CTM & Statistical consultation, Other research (not in main researchprogram), HAG Infectieziekten, Ecraid, JC onderzoeksprogramma Infectieziekten, Venekamp, Roderick P, Eijkemans, Marinus J C, Zuithoff, Nicolaas P A, Böhmer, Femke, Chlabicz, Slawomir, Colliers, Annelies, García-Sangenís, Ana, Malania, Lile, Pauer, Jozsef, Tomacinschii, Angela, Verheij, Theo J, Goossens, Herman, Vellinga, Akke, Butler, Christopher C, van der Velden, Alike W, HAG Onderzoek, Infection & Immunity, Child Health, Biostatistiek Onderzoek, CTM & Statistical consultation, Other research (not in main researchprogram), HAG Infectieziekten, Ecraid, JC onderzoeksprogramma Infectieziekten, Venekamp, Roderick P, Eijkemans, Marinus J C, Zuithoff, Nicolaas P A, Böhmer, Femke, Chlabicz, Slawomir, Colliers, Annelies, García-Sangenís, Ana, Malania, Lile, Pauer, Jozsef, Tomacinschii, Angela, Verheij, Theo J, Goossens, Herman, Vellinga, Akke, Butler, Christopher C, and van der Velden, Alike W

Published
2024

42. Cross-border differences in the prevalence and risk factors for carriage of antimicrobial resistance in children attending daycare centers: a point prevalence study in the Netherlands and Belgium

Author

Infection & Immunity, Epi Infectieziekten Team 1, JC onderzoeksprogramma Infectieziekten, Dequeker, Sara, van Hensbergen, Mitch, den Heijer, Casper D.J., Dhaeze, Wouter, Raven, Stijn F.H., Ewalts-Hakkoer, Helen, Tolsma, Paulien, Willemsen, Ina, van Drunen-Kamp, Karine J., van der Slikke-Verstraten, Krista, Goossens, Herman, Kluytmans-van den Bergh, Marjolein F.Q., Hoebe, Christian J.P.A., on behalf of the i-4-1-Health Study Group, Infection & Immunity, Epi Infectieziekten Team 1, JC onderzoeksprogramma Infectieziekten, Dequeker, Sara, van Hensbergen, Mitch, den Heijer, Casper D.J., Dhaeze, Wouter, Raven, Stijn F.H., Ewalts-Hakkoer, Helen, Tolsma, Paulien, Willemsen, Ina, van Drunen-Kamp, Karine J., van der Slikke-Verstraten, Krista, Goossens, Herman, Kluytmans-van den Bergh, Marjolein F.Q., Hoebe, Christian J.P.A., and on behalf of the i-4-1-Health Study Group

Published
2024

43. Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA)

Author

Julius Centrum, Ecraid, Epi Infectieziekten, Infection & Immunity, Epidemiology of Sepsis & Inflammation in Critically Ill Patients, JC onderzoeksprogramma Infectious Diseases, Paniagua-García, María, Bravo-Ferrer, Jose M, Pérez-Galera, Salvador, Kostyanev, Tomislav, de Kraker, Marlieke E A, Feifel, Jan, Palacios-Baena, Zaira R, Schotsman, Joost, Cantón, Rafael, Daikos, George L, Carevic, Biljana, Dragovac, Gorana, Tan, Lionel K, Raka, Lul, Hristea, Adriana, Viale, Pierluigi, Akova, Murat, Cano, Ángela, Reguera, Jose María, Bartoloni, Alessandro, Florescu, Simin-Aysel, Benea, Serban, Bukarica, Ljiljana, Asensio, Ángel, Korten, Volkan, Grundmann, Hajo, Goossens, Herman, Bonten, Marc J, Gutiérrez-Gutiérrez, Belén, Rodríguez-Baño, Jesús, COMBACTE-CARE-EURECA Team, Julius Centrum, Ecraid, Epi Infectieziekten, Infection & Immunity, Epidemiology of Sepsis & Inflammation in Critically Ill Patients, JC onderzoeksprogramma Infectious Diseases, Paniagua-García, María, Bravo-Ferrer, Jose M, Pérez-Galera, Salvador, Kostyanev, Tomislav, de Kraker, Marlieke E A, Feifel, Jan, Palacios-Baena, Zaira R, Schotsman, Joost, Cantón, Rafael, Daikos, George L, Carevic, Biljana, Dragovac, Gorana, Tan, Lionel K, Raka, Lul, Hristea, Adriana, Viale, Pierluigi, Akova, Murat, Cano, Ángela, Reguera, Jose María, Bartoloni, Alessandro, Florescu, Simin-Aysel, Benea, Serban, Bukarica, Ljiljana, Asensio, Ángel, Korten, Volkan, Grundmann, Hajo, Goossens, Herman, Bonten, Marc J, Gutiérrez-Gutiérrez, Belén, Rodríguez-Baño, Jesús, and COMBACTE-CARE-EURECA Team

Published
2024

44. A microbiological and genomic perspective of globally collected Escherichia coli from adults hospitalized with invasive E. coli disease

Author

Epi Infectieziekten, Infection & Immunity, Epidemiology of Sepsis & Inflammation in Critically Ill Patients, JC onderzoeksprogramma Infectious Diseases, Epi Infectieziekten Team 1, MMB Medische Staf, Arconada Nuin, Enya, Vilken, Tuba, Xavier, Basil Britto, Doua, Joachim, Morrow, Brian, Geurtsen, Jeroen, Go, Oscar, Spiessens, Bart, Sarnecki, Michal, Poolman, Jan, Bonten, Marc, Ekkelenkamp, Miquel, Lammens, Christine, Goossens, Herman, Glupczynski, Youri, Van Puyvelde, Sandra, COMBACTE-NET Consortium/EXPECT Study Group, Epi Infectieziekten, Infection & Immunity, Epidemiology of Sepsis & Inflammation in Critically Ill Patients, JC onderzoeksprogramma Infectious Diseases, Epi Infectieziekten Team 1, MMB Medische Staf, Arconada Nuin, Enya, Vilken, Tuba, Xavier, Basil Britto, Doua, Joachim, Morrow, Brian, Geurtsen, Jeroen, Go, Oscar, Spiessens, Bart, Sarnecki, Michal, Poolman, Jan, Bonten, Marc, Ekkelenkamp, Miquel, Lammens, Christine, Goossens, Herman, Glupczynski, Youri, Van Puyvelde, Sandra, and COMBACTE-NET Consortium/EXPECT Study Group

Published
2024

45. Risk factors for bloodstream infections due to carbapenem-resistant Enterobacterales: a nested case-control-control study

Author

Epi Infectieziekten, Infection & Immunity, Epidemiology of Sepsis & Inflammation in Critically Ill Patients, JC onderzoeksprogramma Infectious Diseases, Zhou, Hongyu, Buetti, Niccolò, Pérez-Galera, Salvador, Bravo-Ferrer, Jose, Gutiérrez-Gutiérrez, Belén, Paniagua-García, María, Feifel, Jan, Sauser, Julien, Kostyanev, Tomi, Canton, Rafael, Tan, Lionel K, Basoulis, Dimitris, Pintado, Vicente, Roilides, Emmanuel, Dragovac, Gorana, Torre-Cisneros, Julian, Mediç, Deana, Akova, Murat, Goossens, Herman, Bonten, Marc, Harbarth, Stephan, Rodriguez-Baño, Jesus, De Kraker, Marlieke E A, COMBACTE- EURECA project team, Epi Infectieziekten, Infection & Immunity, Epidemiology of Sepsis & Inflammation in Critically Ill Patients, JC onderzoeksprogramma Infectious Diseases, Zhou, Hongyu, Buetti, Niccolò, Pérez-Galera, Salvador, Bravo-Ferrer, Jose, Gutiérrez-Gutiérrez, Belén, Paniagua-García, María, Feifel, Jan, Sauser, Julien, Kostyanev, Tomi, Canton, Rafael, Tan, Lionel K, Basoulis, Dimitris, Pintado, Vicente, Roilides, Emmanuel, Dragovac, Gorana, Torre-Cisneros, Julian, Mediç, Deana, Akova, Murat, Goossens, Herman, Bonten, Marc, Harbarth, Stephan, Rodriguez-Baño, Jesus, De Kraker, Marlieke E A, and COMBACTE- EURECA project team

Published
2024

46. Epidemiology and molecular typing of multidrug-resistant bacteria in tertiary hospitals and nursing homes in Flanders, Belgium

Author

UMC Utrecht Holding, Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Medische Microbiologie, MMB, Ecraid, van Kleef-van Koeveringe, Stefanie, Matheeussen, Veerle, Schuermans, Annette, De Koster, Sien, Perales Selva, Natascha, Jansens, Hilde, De Coninck, Dieter, De Bruyne, Katrien, Mensaert, Klaas, Kluytmans-van den Bergh, Marjolein, Kluytmans, Jan, Goossens, Herman, Dhaeze, Wouter, Leroux-Roels, Isabel, UMC Utrecht Holding, Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Medische Microbiologie, MMB, Ecraid, van Kleef-van Koeveringe, Stefanie, Matheeussen, Veerle, Schuermans, Annette, De Koster, Sien, Perales Selva, Natascha, Jansens, Hilde, De Coninck, Dieter, De Bruyne, Katrien, Mensaert, Klaas, Kluytmans-van den Bergh, Marjolein, Kluytmans, Jan, Goossens, Herman, Dhaeze, Wouter, and Leroux-Roels, Isabel

Published
2024

47. Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection

Author

Wheatley, Rachel, Diaz Caballero, Julio, Kapel, Natalia, de Winter, Fien H. R., Jangir, Pramod, Quinn, Angus, del Barrio-Tofiño, Ester, López-Causapé, Carla, Hedge, Jessica, Torrens, Gabriel, Van der Schalk, Thomas, Xavier, Basil Britto, Fernández-Cuenca, Felipe, Arenzana, Angel, Recanatini, Claudia, Timbermont, Leen, Sifakis, Frangiscos, Ruzin, Alexey, Ali, Omar, Lammens, Christine, Goossens, Herman, Kluytmans, Jan, Kumar-Singh, Samir, Oliver, Antonio, Malhotra-Kumar, Surbhi, and MacLean, Craig

Published
2021
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49. Evaluation of GeneXpert PA assay compared to genomic and (semi-)quantitative culture methods for direct detection of Pseudomonas aeruginosa in endotracheal aspirates

Author

van der Schalk, Thomas Ewout, Coppens, Jasmine, Timbermont, Leen, Turlej-Rogacka, Agata, Van Heirstraeten, Liesbet, Berkell, Matilda, Yu, Li, Lammens, Christine, Xavier, Basil Britto, Matheeussen, Veerle, Ieven, Margareta, McCarthy, Michael, Jorens, Philippe G., Ruzin, Alexey, Esser, Mark T., Kumar-Singh, Samir, Goossens, Herman, and Malhotra-Kumar, Surbhi

Published
2021
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50. Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries

Author

Irwin, Adam, Akula, Akhila, Bamford, Alasdair, Chang, Amanda, da Silva, Andre, Whitelaw, Andrew, Dramowski, Angela, Vasudevan, Anil Kumar, Sharma, Anita, Justicia, Antonio, Chikkappa, Ashok, Slowinska-Jarzabek, Barbara, Rippberger, Bianca, Zhao, Changan, Tersigni, Chiara, Cheng, Chinglan, Harkensee, Christian, Jing, Chuamei, Zhu, Chunmei, Li, Chunyan, Tagliabue, Claudia, Epalza, Cristina, Jacqueline, Daglish, Tian, Daiyin, Jinka, Dasaratha, Gkentzi, Despoina, Dharmapalan, Dhanya, Benadof, Dona, Papadimitriou, Eleni, Iosifidis, Elias, Roilides, Emmanuel, Yarci, Erbu, Majda-Stanisławska, Ewa, Gowin, Ewelina, Chappell, Faye, Torres, Federico Martinon, Collett-White, Francis, Liu, Gang, Lu, Gen, Syrogiannopoulos, George, Pitsava, Georgia, Alvarez-Uria, Gerardo, Renk, Hana, Mahmood, Hana, Saxen, Harri, Finlayson, Heather, Green, Helen, Rabie, Helena, Kandraju, Hemasree, Zhang, Hong, Okokon, Ita, Cross, Jack, Herberg, Jethro, Li, Jianping, Zhang, Jiaosheng, Deng, Jikui, Liu, Jing, Qian, Jing, Yang, Jinhong, Sicińska, Joanna, Hübner, Johannes, Fukuoka, Kahoru, Yao, Kaihu, Cheung, Kaman, Ojeda, Karla, Kaffe, Katerina, Kreitmeyer, Katharina, Doerholt, Katja, Grimwood, Keith, Ledoare, Kirsty, Vazouras, Konstantinos, Shen, Kunling, Tang, Lanfang, Zhang, Lehai, Lin, Li, Ashkenazi-Hoffnung, Liat, Wu, Lijuan, Wang, Lijun, Teston, Lilian, Galli, Luisa, Speirs, Lynne, Tsolia, Maria, Hufnagel, Markus, Knuf, Markus, Duse, Marzia, Ding, Mingjie, Rozic, Mojca, Premru, Mueller, O'Connell, Natasha, Rieber, Nikolaus, Spyridis, Nikos, Tunga, Onkaraiah, Conejo, Pablo Rojo, McMaster, Paddy, Lumbiganon, Pagakrong, Pansa, Paola, D'Argenio, Patrizia, Moriarty, Paul, Nikolic, Petra, Wang, Ping, Paopongsawan, Pongsatorn, Cao, Qing, Deng, Qiulian, Laxminarayan, Ramanan, Kanithi, Ravishankar, Jimenez, Rodolfo, Cao, Sancheng, Singh, Sanjeev, Rees, Sarah, Praveen, Saroey, Kekomaki, Satu, Hackett, Scott, Ashkenazi, Shai, Chang, Si Min, Drysdale, Simon, Koning, Sonia, Subramanian, Sreeram, Murki, Srinivas, Vergnano, Stefania, Gandra, Sumanth, Esposito, Susanna, Anugulruengkitt, Suvaporn, Puthanakit, Thanyawee, Behrends, Uta, Papaevangelous, Vana, Jian, Victoria, Li, Wei, Zhao, Wei, Wang, Wei, Zhang, Wenshuang, Mu, Xiaoping, Dong, Xiaoyie, Jiang, Xiyuan, Chen, Xu, Wang, Yi, Zheng, Yuejie, Horikoshi, Yuho, Aboderin, Aaron, Olayinka, Adebola, Dedeic-Ljubovic, Amela, McCorry, Ann, Enimil, Anthony, Neubert, Antje, solano, antonio, Pignatari, Antonio, Poojary, Aruna, Kambaralieva, Baktygul, McCullagh, Bernadette, Carevi, Biljana, Van Herendael, Bruno, Gormley, Cairine, Carvajal, Camila, Ramírez, Carlos, Fitzgerald, David, Sabuda, Deana, Konopnicki, Deborah, Lacej, Denada, Pierard, Denis, Rios, Edgar, Marshall, Emily, Firre, Eric, van Elzakker, Erika, Shaqiri, Erjona, Darwish Elhajji, Feras, Gawrys, Gerard, Markovic, Goran, Kunsihima, Hiroyuki, Chen, Hui Hiong, Sviestina, Inese, Pristas, Irina, Hoxha, Iris, Korinteli, Irma, Mareković, Ivana, Soltani, Jafar, Labarca, Jaime, AlSalman, Jameela, Horvatic, Jasminka, Frimpong, Juliet Ampomah, Pagava, Karaman, Kei, Kasahara, Okinaka, Keiji, Iregbu, Kenneth, Ghazaryan, Lilit, Raka, Lul, Gessner-Wharton, Mallory, Aldeyab, Mamoon, Cooper, Mandelin, del Castillo, Marcelo, Hojman, Martin, Hudson, Melissa, Alshehri, Mohamed, Ling, Moi Lin, Greer, Nickie, Oduyebo, Oyinlola, Buijtels, Patricia, TEROL BARRERO, PEDRO, Zarb, Peter, Schelstraete, PEtra, Nwajiobi-Princewill, Princewill Ifeanyi Philip, Khanna, Priya, Quiros, Rodolfo, Simovic, Sanja, Thompson, Sarah, Chan, Si Min, Burokiene, Sigita, Rachina, Svetlana, Usonis, Vytautas, Cornistein, Wanda, Holemans, Xavier, Gu, Yoshiaki, Brothers, Adam, Hersh, Adam, Fernandez, Alfred, Tribble, Alison, Hurst, Amanda, Green, Andrea, Hammer, Benjamin, Lee, Betty P, Kuzmic, Brenik, Shapiro, Craig, Boge, Craig, Haslam, David, Berman, David, Naeem, Fouzia, Johnson, George, Schwenk, Hayden, Orr, Hillary, Maples, Holly, Olsen, Jared, Gerber, Jeffrey, Girotto, Jennifer, Zweiner, Jennifer, Goldman, Jennifer, Gillon, Jessica, Tansmore, Jessica, Manaloor, John, Courter, Joshua, Mongkolrattanothai, Kanokporn, Patel, Karisma, Merkel, Kathryn, Namtu, Katie, Flett, Kelly, Lee, Kelly, Nichols, Kristen, Klein, Kristin, Handy, Lori, Castagnini, Luis, Mazade, Marc, Heger, Margaret, Fernandez, Marisol, Chang, Michael, Crawford, Michelle, Nelson, Miranda, Bennett, Nicholas, Jaggi, Preeti, Hamdy, Rana, Banerjee, Ritu, Olivero, Rosemary, Patel, Sameer, Arnold, Sandra, Ogrin, Sara, Jones, Sarah, Parker, Sarah, Kubes, Sarah, Hymes, Saul, Weissman, Scott, Chan, Shannon, Henderson, Sheryl, Metjian, Talene, Hsia, Yingfen, Lee, Brian R, Versporten, Ann, Yang, Yonghong, Bielicki, Julia, Jackson, Charlotte, Newland, Jason, Goossens, Herman, Magrini, Nicola, and Sharland, Mike

Published
2019
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