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2. In Vitro and In Vivo Wide-Spectrum Dual Antimycetomal Activity of Eight Essential Oils Coupled with Chemical Composition and Metabolomic Profiling

Author

Shereen O. Abd Algaffar, Prabodh Satyal, Naglaa S. Ashmawy, Annelies Verbon, Wendy W. J. van de Sande, and Sami A. Khalid

Subjects
Madurella mycetomatis, Actinomadura madurae, neglected tropical diseases, in vitro, in vivo, Galleria mellonella, Microbiology, QR1-502
Abstract

Mycetoma, a neglected infection of subcutaneous tissues, poses a significant health burden, especially in tropical regions. It is caused by fungal (eumycetoma) and bacterial (actinomycetoma) pathogens, with current treatments often providing unsatisfactory outcomes. This study aims to discover novel broad-spectrum antimicrobial agents to circumvent the lengthy and costly diagnostic procedures. Eight essential oils (EOs) from the roots and aerial parts of Geigeria alata, Lavandula angustifolia, Melaleuca alternifolia, Myristica fragrans, Pimpinella anisum, Syzigum aromaticum, and Thymus vulgaris were prepared using steam distillation. The in vitro antimycetomal activity against Madurella mycetomatis and Actinomadura madurae strains was assessed using resazurin assays. The chemical compositions of the EOs were analyzed using gas chromatography and mass spectrometry (GC–MS). Promising EOs underwent further in vivo toxicity and efficacy testing in Galleria mellonella larvae models. EOs of G. alata roots, M. fragrans, P. anisum, S. aromaticum, and T. vulgaris showed wide-spectrum dual in vitro antimycetomal activity against all tested strains, with minimum inhibitory concentrations (MICs) ranging from 0.004 to 0.125% v/v. G. alata aerial parts and L. angustifolia EOs demonstrated activity predominantly against A. madurae, while M. alternifolia EO did not inhibit any tested strains. M. fragrans and P. anisum EOs significantly enhanced the survival of M. mycetomatis-infected larvae without inducing toxicity in uninfected larvae. Notably, P. anisum EO tended to enhance the survival of A. madurae-infected larvae, ranking it as the most promising EO among those tested. The investigated EOs, particularly P. anisum, exhibited promising broad-spectrum antimycetomal activity against fungal and bacterial pathogens responsible for mycetoma. These findings highlight the potential of essential oils as a basis for developing novel antimycetomal agents, offering hope for improved treatment strategies for this neglected disease.

Published
2024
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3. Mental health and its consequences in people living with HIV: A network approach

Author

Elise M. G. Meeder, Louise E. van Eekeren, Marc J. T. Blaauw, Albert L. Groenendijk, Wilhelm A. J. W. Vos, Jan van Lunzen, Leo A. B. Joosten, Mihai G. Netea, Quirijn de Mast, Willem L. Blok, Annelies Verbon, Marvin A. H. Berrevoets, Vasiliki Matzaraki, Andre J. A. M. van der Ven, and Arnt F. A. Schellekens

Subjects
HIV, network analysis, psychiatry, quality of life, substance use, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Objectives Psychiatric symptoms occur frequently in people living with human immunodeficiency virus (PLWH), which may affect quality of life, sexual risk behavior, and adherence to antiretroviral therapy (ART). Data from large cohorts are limited, and symptoms are often analyzed in isolation. Therefore, we applied a network analysis to assess the interrelatedness of mental health indicators in a large cohort of PLWH. Methods We included 1615 PLWH on ART. Participants reported on the severity of depression, anxiety, impulsivity, substance use, quality of life, sexual risk behavior, and ART adherence. An Ising network model was constructed to analyze interrelations between mental health indicators and connections with clinical consequences. Results Our network analysis revealed that symptoms of depression, anxiety, and indicators of impulsivity were interrelated. Substance use was prevalent and strongly connected with sexual risk behavior. Quality of life was most strongly connected with symptoms of depression. Unexpectedly, ART adherence did not display connections with any of the mental health indicators. Conclusion In PLWH, the interrelatedness between symptoms of depression and anxiety and indicators of impulsivity is high. Mainly, depressive symptoms seem to impact quality of life, which warrants attention for depression in PLWH. We did not observe evidence for the common assumption that patients suffering from psychiatric symptoms are less adherent to HIV treatment.

Published
2024
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4. Infecties van de onderste luchtwegen en tuberculose

Author

Verbon, A., Wolfs, T. F. W., Callens, S. F. J., Prins, J. M., Hoepelman, prof. dr. A.I.M., editor, Kroes, prof. dr. A.C.M., editor, Lagrou, prof. dr. K., editor, Van der Hilst, prof. dr. J.C.H., editor, Wertheim, prof. dr. H.F.L., editor, Bonten, prof. dr. M.J.M., editor, van Hellemond, dr. J.J., editor, Vlieghe, prof. dr. E.R.J., editor, and van Vugt, prof. dr. M., editor

Published
2024
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5. Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Author

Barbara Wanjiru Citarella, Christiana Kartsonaki, Elsa D. Ibáñez-Prada, Bronner P. Gonçalves, Joaquin Baruch, Martina Escher, Mark G. Pritchard, Jia Wei, Fred Philippy, Andrew Dagens, Matthew Hall, James Lee, Demetrios James Kutsogiannis, Evert-Jan Wils, Marília Andreia Fernandes, Bharath Kumar Tirupakuzhi Vijayaraghavan, Prasan Kumar Panda, Ignacio Martin-Loeches, Shinichiro Ohshimo, Arie Zainul Fatoni, Peter Horby, Jake Dunning, Jordi Rello, Laura Merson, Amanda Rojek, Michel Vaillant, Piero Olliaro, Luis Felipe Reyes, S.A. Moharam, Sabriya Abdalasalam, Alaa Abdalfattah Abdalhadi, Naana Reyam Abdalla, Walaa Abdalla, Almthani Hamza Abdalrheem, Ashraf Abdalsalam, Saedah Abdeewi, Esraa Hassan Abdelgaum, Mohamed Abdelhalim, Mohammed Abdelkabir, Israa Abdelrahman, Sheryl Ann Abdukahil, Lamees Adil Abdulbaqi, Salaheddin Abdulhamid, Widyan Abdulhamid, Nurul Najmee Abdulkadir, Eman Abdulwahed, Rawad Abdunabi, Ryuzo Abe, Laurent Abel, Ahmed Mohammed Abodina, Amal Abrous, Lara Absil, Kamal Abu Jabal, Nashat Abu Salah, Abdurraouf Abusalama, Tareg Abdallah Abuzaid, Subhash Acharya, Andrew Acker, Elisabeth Adam, Safia Adem, Manuella Ademnou, Francisca Adewhajah, Diana Adrião, Anthony Afum-Adjei Awuah, Melvin Agbogbatey, Saleh Al Ageel, Aya Mustafa Ahmed, Musaab Mohammed Ahmed, Shakeel Ahmed, Zainab Ahmed Alaraji, Abdulrahman Ahmed Elhefnawy Enan, Reham Abdelhamid Ahmed Khalil, Ali Mostafa Ahmed Mohamed Abdelaziz, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Aisha, Bugila Aisha, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Chika Akwani, Eman Al Qasim, Ahmed Alajeeli, Ahmed Alali, Razi Alalqam, Aliya Mohammed Alameen, Mohammed Al-Aquily, Zinah A. Alaraji, Khalid Albakry, Safa Albatni, Angela Alberti, Osama Aldabbourosama, Tala Al-dabbous, Amer Aldhalia, Abdulkarim Aldoukali, Senthilkumar Alegesan, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Asil Alflite, Huda Alfoudri, Qamrah Alhadad, Hoda Salem Alhaddad, Maali Khalid Mohamed Abdalla Alhasan, Ahmad Nabil Alhouri, Hasan Alhouri, Adam Ali, Imran Ali, Maha TagElser Mohammed Ali, Syed Ali Abbas, Yomna Ali Abdelghafar, Naseem Ali Sheikh, Kazali Enagnon Alidjnou, Mahmoud Aljadi, Sarah Aljamal, Mohammed Alkahlout, Akram Alkaseek, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Lana Almasri, Abdulrahman Almjersah, Raja Ahmed Alqandouz, Walaa Alrfaea, Moayad Alrifaee, Rawan Alsaadi, Yousef Al-Saba'a, Entisar Alshareea, Eslam Alshenawy, Aneela Altaf, João Melo Alves, João Alves, Rita Alves, Joana Alves Cabrita, Maria Amaral, Amro Essam Amer, Nur Amira, Amos Amoako Adusei, John Amuasi, Roberto Andini, Claire Andrejak, Andrea Angheben, François Angoulvant, Sophia Ankrah, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Elizabeth A. Ashley, Muhammad Ashraf, Muhammad Sheharyar Ashraf, Abir Ben Ashur, Franklin Asiedu-Bekoe, Namra Asif, Mohammad Asim, Grace Assi, Jean Baptiste Assie, Amirul Asyraf, Fouda Atangana, Ahmed Atia, Minahel Atif, Asia Atif Abdelrhman Abdallahrs, Anika Atique, Moad Atlowly, AM Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Abdelmalek Awad Ali Mohammed, Eyvind W. Axelsen, Ared Ayad, Ahmed Ayman Hassan Helmi, Laurène Azemar, Mohammed Azizeldin, Cecile Azoulay, Hakeem Babatunde, Benjamin Bach, Delphine Bachelet, Claudine Badr, Roar Bævre-Jensen, Nadia Baig, John Kenneth Baillie, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Hibah Bileid Bakeer, Ashraf Bakri, Andriy Bal, Mohanaprasanth Balakrishnan, Irene Bandoh, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S. Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Cleide Barrigoto, Marie Bartoli, Joaquín Baruch, Romain Basmaci, Muhammad Fadhli Hassin Basri, AbdAlkarim Batool, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Abigail Beane, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Lamis Berdeweel, Delphine Bergeaud, Hazel Bergin, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Isabella Bianchi, Claudia Bianco, Sandra Bichoka, Farah Nadiah Bidin, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, Muhannud Binnawara, Zeno Bisoffi, Patrick Biston, Laurent Bitker, Mustapha Bittaye, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Debby Bogaert, Anne-Hélène Boivin, Ariel Bolanga, Isabela Bolaños, Pierre-Adrien Bolze, François Bompart, Aurelius Bonifasius, Joe Bonney, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Latsaniphone Bountthasavong, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Marielle Boyer-Besseyre, Maria Boylan, Fernando Augusto Bozza, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Dorothy Breen, Patrick Breen, David Brewster, Kathy Brickell, Tessa Broadley, Helen Brotherton, Alex Browne, Nicolas Brozzi, Sonja Hjellegjerde Brunvoll, Marjolein Brusse-Keizer, Petra Bryda, Nina Buchtele, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Donald Buri, Aidan Burrell, Ingrid G. Bustos, Denis Butnaru, André Cabie, Susana Cabral, Joana Cabrita, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Janice Caoili, Pauline Caraux-Paz, Sheila Cárcel, Filipa Cardoso, Filipe Cardoso, Nelson Cardoso, Sofia Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Gail Carson, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Masaneh Ceesay, Shelby Cerkovnik, Minerva Cervantes-Gonzalez, Muge Cevik, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Jean-Marc Chapplain, Charlotte Charpentier, Julie Chas, Muhammad Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Léo Chenard, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Danoy Chommanam, Marie-Charlotte Chopin, Yock Ping Chow, Ting Soo Chow, Nathaniel Christy, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Rolando Claure-Del Granado, Sara Clohisey, Cassidy Codan, Caitriona Cody, Jennifer Coles, Megan Coles, Gwenhaël Colin, Michael Collins, Pamela Combs, Jennifer Connolly, Marie Connor, Anne Conrad, Elaine Conway, Graham S. Cooke, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Juthaporn Cowan, Rachel Cregan, Gloria Crowl, Jonathan Crump, Claudina Cruz, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, John Arne Dahl, Darren Dahly, Umberto D'Alessandro, Peter Daley, Zaina Dalloul, Heidi Dalton, Jo Dalton, Seamus Daly, Juliana Damas, Joycelyn Dame, Cammandji Damien, Nick Daneman, Jorge Dantas, Frédérick D'Aragon, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Bianca DeBenedictis, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Romain Decours, Eve Defous, Isabelle Delacroix, Alexandre Delamou, Eric Delaveuve, Karen Delavigne, Nathalie M. Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhangar, Alpha Diallo, Souleymane Taran Diallo, Sylvain Diamantis, André Dias, Fernanda Dias Da Silva, Rodrigo Diaz, Juan Jose Diaz, Priscila Diaz, Bakary K. Dibba, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Cedric Djadda, Félix Djossou, Annemarie B. Docherty, Helen Doherty, Arjen M. Dondorp, Christl A. Donnelly, Yoann Donohue, Sean Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, Yash Doshi, Phouvieng Douangdala, James Joshua Douglas, Renee Douma, Nathalie Dournon, Joanne Downey, Mark Downing, Thomas Drake, Aoife Driscoll, Ibrahim Kwaku Duah, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Audrey Dubot-Pérès, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, III, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Ada Ebo, Marco Echeverria-Villalobos, Michael Edelstein, Siobhan Egan, Linn Margrete Eggesbø, Khadeja Ehzaz, Carla Eira, Mohammed El Sanharawi, Marwan El Sayed, Mohammed Elabid, Mohamed Bashir Elagili, Subbarao Elapavaluru, Mohammad Elbahnasawy, Sohail Elboshra, Brigitte Elharrar, Jacobien Ellerbroek, Merete Ellingjord-Dale, Hamida ELMagrahi, Mohammad Muatasm Elmubark, Loubna Elotmani, Lauren Eloundou, Philippine Eloy, Basma Elshaikhy, Tarek Elshazly, Wafa Elsokni, Aml Ahmed Eltayeb, Iqbal Elyazar, Zarief Kamel Emad, Hussein Embarek, Isabelle Enderle, Tomoyuki Endo, Gervais Eneli, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Haneen Esaadi, Mariano Esperatti, Hélène Esperou, Catarina Espírito Santo, Marina Esposito-Farese, Rachel Essaka, Lorinda Essuman, João Estevão, Manuel Etienne, Anna Greti Everding, Mirjam Evers, Isabelle Fabre, Marc Fabre, Ismaila Fadera, Asgad Osman Abdalla Fadlalla, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Mohamed Fathi, Salem Fatima, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Jorge Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Benigno Ferreira, Isabel Ferreira, Bernardo Ferreira, Sílvia Ferreira, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Thomas Flament, Tom Fletcher, Aline-Marie Florence, Letizia Lucia Florio, Brigid Flynn, Deirdre Flynn, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Karen Forrest, Simon Forsyth, Denise Foster, Giuseppe Foti, Berline Fotso, Erwan Fourn, Robert A. Fowler, Marianne Fraher, Diego Franch-Llasat, Christophe Fraser, John F. Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Craig French, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G. Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Abdou Gai, Sérgio Gaião, Linda Gail Skeie, Adham Mohamed Galal Mohamed Ramadan, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Malak Ghemmeid, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Tristan Gigante, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Gezy Giwangkancana, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jean-Christophe Goffard, Jin Yi Goh, Brigitta Golács, Jonathan Golob, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Lorenzo Grazioli, Christopher A. Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Fassou Mathias Grovogui, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Ali Hachemi, Abdurrahman Haddud, Nadir Hadri, Wael Hafez, Fakhir Raza Haidri, Fatima Mhd Rida Hajij, Sheeba Hakak, Adam Hall, Sophie Halpin, Shaher Hamdan, Abdelhafeez Hamdi, Jawad Hameed, Ansley Hamer, Raph L. Hamers, Rebecca Hamidfar, Bato Hammarström, Naomi Hammond, Terese Hammond, Lim Yuen Han, Matly Hanan, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M. Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Sulieman Hasan, Mohammad Ali Nabil Hasan, Mohd Shahnaz Hasan, Junaid Hashmi, Madiha Hashmi, Amoni Hassan, Ebtisam Hassanin, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ahmed Helmi, Ross Hendry, Martina Hennessy, Aquiles Rodrigo Henriquez-Trujillo, Maxime Hentzien, Diana Hernandez, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhlin Higgins, Rupert Higgins, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Antonia Ho, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Ikram Houas, Mabrouka Houderi, Catherine L. Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Abby Hurd, Iqbal Hussain, Aliae Mohamed Hussein, Mahmood Hussein, Fatima Ibrahim, Bashir Ibran, Samreen Ijaz, M. Arfan Ikram, Carlos Cañada Illana, Patrick Imbert, Muhammad Imran Ansari, Rana Imran Sikander, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Mariachiara Ippolito, Vera Irawany, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Mette Stausland Istre, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Hamza Jaber, Julien Jabot, Clare Jackson, Abubacarr Jagne, Stéphane Jaureguiberry, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth Noemí Jorge García, Silje Bakken Jørgensen, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Anna Jung, Hanna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Karl Trygve Kalleberg, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Armand Saloun Kamano, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Kavita Kamineni, Darshana Hewa Kandamby, Kong Yeow Kang, Darakhshan Kanwal, Dyah Kanyawati, Mohamed Karghul, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Kevin Katz, Christy Kay, Lamees Kayyali, Seán Keating, Pulak Kedia, Andrea Kelly, Aoife Kelly, Claire Kelly, Niamh Kelly, Sadie Kelly, Yvelynne Kelly, Maeve Kelsey, Kalynn Kennon, Sommay Keomany, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Shams Khail, Sarah Khaled, Imrana Khalid, Antoine Khalil, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Krish Kherajani, Michelle E. Kho, Denisa Khoo, Ryan Khoo, Saye Khoo, Muhammad Nasir Khoso, Amin Khuwaja, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Nobuya Kitamura, Eyrun Floerecke Kjetland Kjetland, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R. Knight, Robin Kobbe, Paa Kobina Forson, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Franklina Korkor Abebrese, Volkan Korten, Stephanie Kouba, Mohamed Lamine Kourouma, Karifa Kourouma, Arsène Kpangon, Karolina Krawczyk, Ali Kredan, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Anneli Krund, Pei Xuan Kuan, Ashok Kumar, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Ama Kwakyewaa Bedu-Addo, Sylvie Kwedi, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G. Laffey, Nadhem Lafhej, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Youssef Latifeh, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Cassie Lawrence, Teresa Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Ema Leal, Marta Leal Santos, Biing Horng Lee, Heng Gee Lee, Su Hwan Lee, Jennifer Lee, Todd C. Lee, Yi Lin Lee, Gary Leeming, Bénédicte Lefebvre, Laurent Lefebvre, Benjamin Lefèvre, Sylvie LeGac, Merili-Helen Lehiste, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Tanel Lepik, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Andrew Letizia, Sophie Letrou, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Kah Chuan Lim, Wei Shen Lim, Chantre Lima, Bruno Lina, Lim Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Anthony L. Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos M. Luna, Olguta Lungu, Miles Lunn, Liem Luong, Nestor Luque, Dominique Luton, Olavi Maasikas, Moïse Machado, Sara Machado, Gabriel Macheda, Mustafa Magzoub, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S. Maier, Oumou Maiga Ascofare, Mylène Maillet, Thomas Maitre, Nimisha Abdul Majeed, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Veronika Maráczi, Ceila Maria Sant′Ana Malaque, Flávio Marino, Samuel Markowicz, Ana Marques, Catherine Marquis, Laura Marsh, Brian Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Alessandra Martinelli, F. 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Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Sue Willems, Bailey Williams, Patricia J. Williams, Virginie Williams, Jessica Wittman, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Lim Saio Xian, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Elizabeth Yarad, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Abdelrahman Yehia Mahmoud Abdelaal, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Touxiong Yiaye, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Gustavo E. Zabert, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, and David Zucman

Subjects
COVID-19, Non-respiratory symptoms, Respiratory symptoms, Risk factors, Mortality, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Published
2024
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7. Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Author

Moharam, S.A., Abdalasalam, Sabriya, Abdalhadi, Alaa Abdalfattah, Abdalla, Naana Reyam, Abdalla, Walaa, Abdalrheem, Almthani Hamza, Abdalsalam, Ashraf, Abdeewi, Saedah, Abdelgaum, Esraa Hassan, Abdelhalim, Mohamed, Abdelkabir, Mohammed, Abdelrahman, Israa, Abdukahil, Sheryl Ann, Abdulbaqi, Lamees Adil, Abdulhamid, Salaheddin, Abdulhamid, Widyan, Abdulkadir, Nurul Najmee, Abdulwahed, Eman, Abdunabi, Rawad, Abe, Ryuzo, Abel, Laurent, Abodina, Ahmed Mohammed, Abrous, Amal, Absil, Lara, Jabal, Kamal Abu, Salah, Nashat Abu, Abusalama, Abdurraouf, Abuzaid, Tareg Abdallah, Acharya, Subhash, Acker, Andrew, Adam, Elisabeth, Adem, Safia, Ademnou, Manuella, Adewhajah, Francisca, Adrião, Diana, Afum-Adjei Awuah, Anthony, Agbogbatey, Melvin, Al Ageel, Saleh, Ahmed, Aya Mustafa, Ahmed, Musaab Mohammed, Ahmed, Shakeel, Alaraji, Zainab Ahmed, Elhefnawy Enan, Abdulrahman Ahmed, Ahmed Khalil, Reham Abdelhamid, Ahmed Mohamed Abdelaziz, Ali Mostafa, Ainscough, Kate, Airlangga, Eka, Aisa, Tharwat, Aisha, Ali, Aisha, Bugila, Hssain, Ali Ait, Tamlihat, Younes Ait, Akimoto, Takako, Akmal, Ernita, Akwani, Chika, Al Qasim, Eman, Alajeeli, Ahmed, Alali, Ahmed, Alalqam, Razi, Alameen, Aliya Mohammed, Al-Aquily, Mohammed, Alaraji, Zinah A., Albakry, Khalid, Albatni, Safa, Alberti, Angela, Aldabbourosama, Osama, Al-dabbous, Tala, Aldhalia, Amer, Aldoukali, Abdulkarim, Alegesan, Senthilkumar, Alessi, Marta, Alex, Beatrice, Alexandre, Kévin, Al-Fares, Abdulrahman, Alflite, Asil, Alfoudri, Huda, Alhadad, Qamrah, Alhaddad, Hoda Salem, Mohamed Abdalla Alhasan, Maali Khalid, Alhouri, Ahmad Nabil, Alhouri, Hasan, Ali, Adam, Ali, Imran, TagElser Mohammed Ali, Maha, Abbas, Syed Ali, Abdelghafar, Yomna Ali, Sheikh, Naseem Ali, Alidjnou, Kazali Enagnon, Aljadi, Mahmoud, Aljamal, Sarah, Alkahlout, Mohammed, Alkaseek, Akram, Alkhafajee, Qabas, Allavena, Clotilde, Allou, Nathalie, Almasri, Lana, Almjersah, Abdulrahman, Alqandouz, Raja Ahmed, Alrfaea, Walaa, Alrifaee, Moayad, Alsaadi, Rawan, Al-Saba'a, 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Nicolas, Carmoi, Thierry, Carney, Gayle, Carqueja, Inês, Carret, Marie-Christine, Carrier, François Martin, Carroll, Ida, Carson, Gail, Casanova, Maire-Laure, Cascão, Mariana, Casey, Siobhan, Casimiro, José, Cassandra, Bailey, Castañeda, Silvia, Castanheira, Nidyanara, Castor-Alexandre, Guylaine, Castro, Ivo, Catarino, Ana, Catherine, François-Xavier, Cattaneo, Paolo, Cavalin, Roberta, Cavalli, Giulio Giovanni, Cavayas, Alexandros, Ceccato, Adrian, Ceesay, Masaneh, Cerkovnik, Shelby, Cervantes-Gonzalez, Minerva, Cevik, Muge, Chair, Anissa, Chakveatze, Catherine, Chan, Adrienne, Chand, Meera, Chapplain, Jean-Marc, Charpentier, Charlotte, Chas, Julie, Chaudry, Muhammad Mobin, Chávez Iñiguez, Jonathan Samuel, Chen, Anjellica, Chen, Yih-Sharng, Chenard, Léo, Cheng, Matthew Pellan, Cheret, Antoine, Chiarabini, Thibault, Chica, Julian, Chidambaram, Suresh Kumar, Tho, Leong Chin, Chirouze, Catherine, Chiumello, Davide, Cho, Sung-Min, Cholley, Bernard, Chommanam, Danoy, Chopin, Marie-Charlotte, Chow, Yock Ping, Chow, Ting Soo, Christy, Nathaniel, Chua, Hiu Jian, Chua, Jonathan, Cidade, Jose Pedro, Cisneros Herreros, José Miguel, Citarella, Barbara Wanjiru, Ciullo, Anna, Clarke, Jennifer, Claure-Del Granado, Rolando, Clohisey, Sara, Codan, Cassidy, Cody, Caitriona, Coles, Jennifer, Coles, Megan, Colin, Gwenhaël, Collins, Michael, Combs, Pamela, Connolly, Jennifer, Connor, Marie, Conrad, Anne, Conway, Elaine, Cooke, Graham S., Cordel, Hugues, Corley, Amanda, Cornelis, Sabine, Cornet, Alexander Daniel, Corpuz, Arianne Joy, Cortegiani, Andrea, Corvaisier, Grégory, Couffignal, Camille, Couffin-Cadiergues, Sandrine, Courtois, Roxane, Cousse, Stéphanie, Cowan, Juthaporn, Cregan, Rachel, Crowl, Gloria, Crump, Jonathan, Cruz, Claudina, Csete, Marc, Cullen, Ailbhe, Cummings, Matthew, Curley, Gerard, Curlier, Elodie, Curran, Colleen, Custodio, Paula, da Silva Filipe, Ana, Da Silveira, Charlene, Dabaliz, Al-Awwab, Dagens, Andrew, Dahl, John Arne, Dahly, Darren, D'Alessandro, Umberto, Daley, Peter, Dalloul, Zaina, Dalton, Heidi, Dalton, Jo, Daly, Seamus, Damas, Juliana, Dame, Joycelyn, Damien, Cammandji, Daneman, Nick, Dantas, Jorge, D'Aragon, Frédérick, de Loughry, Gillian, de Mendoza, Diego, De Montmollin, Etienne, França, Rafael Freitas de Oliveira, Isabel de Pinho Oliveira, Ana, De Rosa, Rosanna, De Rose, Cristina, de Silva, Thushan, de Vries, Peter, Deacon, Jillian, Dean, David, Debard, Alexa, DeBenedictis, Bianca, Debray, Marie-Pierre, DeCastro, Nathalie, Dechert, William, Decours, Romain, Defous, Eve, Delacroix, Isabelle, Delamou, Alexandre, Delaveuve, Eric, Delavigne, Karen, Delfos, Nathalie M., Deligiannis, Ionna, Dell'Amore, Andrea, Delmas, Christelle, Delobel, Pierre, Delsing, Corine, Demonchy, Elisa, Denis, Emmanuelle, Deplanque, Dominique, Depuydt, Pieter, Descamps, Diane, Desvallées, Mathilde, Dewayanti, Santi, Dhangar, Pathik, Diallo, Alpha, Diallo, Souleymane Taran, Diamantis, Sylvain, Dias, André, Da Silva, Fernanda Dias, Diaz, Rodrigo, Diaz, Juan Jose, Diaz, Priscila, Dibba, Bakary K., Didier, Kévin, Diehl, Jean-Luc, Dieperink, Wim, Dimet, Jérôme, Dinot, Vincent, Diop, Fara, Diouf, Alphonsine, Dishon, Yael, Djadda, Cedric, Djossou, Félix, Docherty, Annemarie B., Doherty, Helen, Dondorp, Arjen M., Donnelly, Christl A., Donohue, Yoann, Donohue, Sean, Doran, Peter, Dorival, Céline, D'Ortenzio, Eric, Doshi, Yash, Douangdala, Phouvieng, Douglas, James Joshua, Douma, Renee, Dournon, Nathalie, Downey, Joanne, Downing, Mark, Drake, Thomas, Driscoll, Aoife, Duah, Ibrahim Kwaku, Fonseca, Claudio Duarte, Dubee, Vincent, Dubos, François, Dubot-Pérès, Audrey, Ducancelle, Alexandre, Duculan, Toni, Dudman, Susanne, Duggal, Abhijit, Dunand, Paul, Dunning, Jake, Duplaix, Mathilde, Durante-Mangoni, Emanuele, Durham, Lucian, III, Dussol, Bertrand, Duthoit, Juliette, Duval, Xavier, Dyrhol-Riise, Anne Margarita, Ean, Sim Choon, Ebo, Ada, Echeverria-Villalobos, Marco, Edelstein, Michael, Egan, Siobhan, Eggesbø, Linn Margrete, Ehzaz, Khadeja, Eira, Carla, El Sanharawi, Mohammed, El Sayed, Marwan, Elabid, Mohammed, Elagili, Mohamed Bashir, Elapavaluru, Subbarao, Elbahnasawy, Mohammad, Elboshra, Sohail, Elharrar, Brigitte, Ellerbroek, Jacobien, Ellingjord-Dale, Merete, ELMagrahi, Hamida, Elmubark, Mohammad Muatasm, Elotmani, Loubna, Eloundou, Lauren, Eloy, Philippine, Elshaikhy, Basma, Elshazly, Tarek, Elsokni, Wafa, Eltayeb, Aml Ahmed, Elyazar, Iqbal, Emad, Zarief Kamel, Embarek, Hussein, Enderle, Isabelle, Endo, Tomoyuki, Eneli, Gervais, Eng, Chan Chee, Engelmann, Ilka, Enouf, Vincent, Epaulard, Olivier, Esaadi, Haneen, Esperatti, Mariano, Esperou, Hélène, Santo, Catarina Espírito, Esposito-Farese, Marina, Essaka, Rachel, Essuman, Lorinda, Estevão, João, Etienne, Manuel, Everding, Anna Greti, Evers, Mirjam, Fabre, Isabelle, Fabre, Marc, Fadera, Ismaila, Abdalla Fadlalla, Asgad Osman, Faheem, Amna, Fahy, Arabella, Fairfield, Cameron J., Fakar, Zul, Fareed, Komal, Faria, Pedro, Farooq, Ahmed, Fateena, Hanan, Fathi, Mohamed, Fatima, Salem, Fatoni, Arie Zainul, Faure, Karine, Favory, Raphaël, Fayed, Mohamed, Feely, Niamh, Fernandes, Jorge, Fernandes, Marília Andreia, Fernandes, Susana, Ferrand, François-Xavier, Devouge, Eglantine Ferrand, Ferrão, Joana, Ferraz, Mário, Ferreira, Benigno, Ferreira, Isabel, Ferreira, Bernardo, Ferreira, Sílvia, Ferriere, Nicolas, Ficko, Céline, Figueiredo-Mello, Claudia, Finlayson, William, Flament, Thomas, Fletcher, Tom, Florence, Aline-Marie, Florio, Letizia Lucia, Flynn, Brigid, Flynn, Deirdre, Foley, Jean, Fomin, Victor, Fonseca, Tatiana, Fontela, Patricia, Forrest, Karen, Forsyth, Simon, Foster, Denise, Foti, Giuseppe, Fotso, Berline, Fourn, Erwan, Fowler, Robert A., Fraher, Marianne, Franch-Llasat, Diego, Fraser, Christophe, Fraser, John F., Freire, Marcela Vieira, Ribeiro, Ana Freitas, French, Craig, Friedrich, Caren, Fritz, Ricardo, Fry, Stéphanie, Fuentes, Nora, Fukuda, Masahiro, Argin, G., Gaborieau, Valérie, Gaci, Rostane, Gagliardi, Massimo, Gagnard, Jean-Charles, Gagneux-Brunon, Amandine, Gai, Abdou, Gaião, Sérgio, Skeie, Linda Gail, Galal Mohamed Ramadan, Adham Mohamed, Gallagher, Phil, Gamble, Carrol, Gani, Yasmin, Garan, Arthur, Garcia, Rebekha, Garcia-Diaz, Julia, Garcia-Gallo, Esteban, Garimella, Navya, Garot, Denis, Garrait, Valérie, Gauli, Basanta, Gavrylov, Anatoliy, Gaymard, Alexandre, Gebauer, Johannes, Geraud, Eva, Morlaes, Louis Gerbaud, Germano, Nuno, Ghemmeid, Malak, Ghisulal, Praveen Kumar, Ghosn, Jade, Giani, Marco, Gigante, Tristan, Gilroy, Elaine, Giordano, Guillermo, Girvan, Michelle, Gissot, Valérie, Giwangkancana, Gezy, Glikman, Daniel, Glybochko, Petr, Gnall, Eric, Goco, Geraldine, Goehringer, François, Goepel, Siri, Goffard, Jean-Christophe, Goh, Jin Yi, Golács, Brigitta, Golob, Jonathan, Gomez, Kyle, Gómez-Junyent, Joan, Gominet, Marie, Gonzalez, Alicia, Gordon, Patricia, Gorenne, Isabelle, Goubert, Laure, Goujard, Cécile, Goulenok, Tiphaine, Grable, Margarite, Graf, Jeronimo, Grandin, Edward Wilson, Granier, Pascal, Grasselli, Giacomo, Grazioli, Lorenzo, Green, Christopher A., Greene, Courtney, Greenhalf, William, Greffe, Segolène, Grieco, Domenico Luca, Griffee, Matthew, Griffiths, Fiona, Grigoras, Ioana, Groenendijk, Albert, Grovogui, Fassou Mathias, Gruner, Heidi, Gu, Yusing, Guedj, Jérémie, Guego, Martin, Guerguerian, Anne-Marie, Guerreiro, Daniela, Guery, Romain, Guillaumot, Anne, Guilleminault, Laurent, Guimarães de Castro, Maisa, Guimard, Thomas, Haalboom, Marieke, Haber, Daniel, Hachemi, Ali, Haddud, Abdurrahman, Hadri, Nadir, Hafez, Wael, Haidri, Fakhir Raza, Rida Hajij, Fatima Mhd, Hakak, Sheeba, Hall, Adam, Hall, Matthew, Halpin, Sophie, Hamdan, Shaher, Hamdi, Abdelhafeez, Hameed, Jawad, Hamer, Ansley, Hamers, Raph L., Hamidfar, Rebecca, Hammarström, Bato, Hammond, Naomi, Hammond, Terese, Han, Lim Yuen, Hanan, Matly, Haniffa, Rashan, Hao, Kok Wei, Hardwick, Hayley, Harrison, Ewen M., Harrison, Janet, Ekow Harrison, Samuel Bernard, Hartman, Alan, Hasan, Sulieman, Nabil Hasan, Mohammad Ali, Hasan, Mohd Shahnaz, Hashmi, Junaid, Hashmi, Madiha, Hassan, Amoni, Hassanin, Ebtisam, Hayat, Muhammad, Hayes, Ailbhe, Hays, Leanne, Heerman, Jan, Heggelund, Lars, Helmi, Ahmed, Hendry, Ross, Hennessy, Martina, Henriquez-Trujillo, Aquiles Rodrigo, Hentzien, Maxime, Hernandez, Diana, Hershey, Andrew, Hesstvedt, Liv, Hidayah, Astarini, Higgins, Eibhlin, Higgins, Rupert, Hinton, Samuel, Hiraiwa, Hiroaki, Hirkani, Haider, Hitoto, Hikombo, Ho, Antonia, Ho, Yi Bin, Hoctin, Alexandre, Hoffmann, Isabelle, Hoh, Wei Han, Hoiting, Oscar, Holt, Rebecca, Holter, Jan Cato, Horby, Peter, Horcajada, Juan Pablo, Houas, Ikram, Houderi, Mabrouka, Hough, Catherine L., Houltham, Stuart, Ming-Yang Hsu, Jimmy, Hulot, Jean-Sébastien, Hurd, Abby, Hussain, Iqbal, Hussein, Aliae Mohamed, Hussein, Mahmood, Ibrahim, Fatima, Ibran, Bashir, Ijaz, Samreen, Ikram, M. Arfan, Illana, Carlos Cañada, Imbert, Patrick, Ansari, Muhammad Imran, Sikander, Rana Imran, Inácio, Hugo, Dominguez, Carmen Infante, Ing, Yun Sii, Ippolito, Mariachiara, Irawany, Vera, Isgett, Sarah, Isidoro, Tiago, Ismail, Nadiah, Isnard, Margaux, Istre, Mette Stausland, Itai, Junji, Ivulich, Daniel, Jaafar, Danielle, Jaafoura, Salma, Jaber, Hamza, Jabot, Julien, Jackson, Clare, Jagne, Abubacarr, Jaureguiberry, Stéphane, Jaworsky, Denise, Jego, Florence, Jelani, Anilawati Mat, Jenum, Synne, Jimbo-Sotomayor, Ruth, Joe, Ong Yiaw, Jorge García, Ruth Noemí, Jørgensen, Silje Bakken, Joseph, Cédric, Joseph, Mark, Joshi, Swosti, Jourdain, Mercé, Jouvet, Philippe, Jung, Anna, Jung, Hanna, Juzar, Dafsah, Kafif, Ouifiya, Kaguelidou, Florentia, Kaisbain, Neerusha, Kaleesvran, Thavamany, Kali, Sabina, Kalleberg, Karl Trygve, Kalomoiri, Smaragdi, Ayadi Kamaluddin, Muhammad Aisar, Kamano, Armand Saloun, Che Kamaruddin, Zul Amali, Kamarudin, Nadiah, Kamineni, Kavita, Kandamby, Darshana Hewa, Kang, Kong Yeow, Kanwal, Darakhshan, Kanyawati, Dyah, Karghul, Mohamed, Karpayah, Pratap, Karsies, Todd, Kartsonaki, Christiana, Kasugai, Daisuke, Katz, Kevin, Kay, Christy, Kayyali, Lamees, Keating, Seán, Kedia, Pulak, Kelly, Andrea, Kelly, Aoife, Kelly, Claire, Kelly, Niamh, Kelly, Sadie, Kelly, Yvelynne, Kelsey, Maeve, Kennon, Kalynn, Keomany, Sommay, Kernan, Maeve, Kerroumi, Younes, Keshav, Sharma, Khail, Shams, Khaled, Sarah, Khalid, Imrana, Khalil, Antoine, Khan, Irfan, Khan, Quratul Ain, Khanal, Sushil, Khatak, Abid, Kherajani, Krish, Kho, Michelle E., Khoo, Denisa, Khoo, Ryan, Khoo, Saye, Khoso, Muhammad Nasir, Khuwaja, Amin, Kiat, Khor How, Kida, Yuri, Kiiza, Peter, Granerud, Beathe Kiland, Kildal, Anders Benjamin, Kim, Jae Burm, Kimmoun, Antoine, Kindgen-Milles, Detlef, Kitamura, Nobuya, Kjetland Kjetland, Eyrun Floerecke, Klenerman, Paul, Klont, Rob, Bekken, Gry Kloumann, Knight, Stephen R., Kobbe, Robin, Forson, Paa Kobina, Kodippily, Chamira, Vasconcelos, Malte Kohns, Koirala, Sabin, Komatsu, Mamoru, Abebrese, Franklina Korkor, Korten, Volkan, Kouba, Stephanie, Kourouma, Mohamed Lamine, Kourouma, Karifa, Kpangon, Arsène, Krawczyk, Karolina, Kredan, Ali, Krishnan, Vinothini, Krishnan, Sudhir, Kruglova, Oksana, Krund, Anneli, Kuan, Pei Xuan, Kumar, Ashok, Kumar, Deepali, Kumar, Ganesh, Kumar, Mukesh, Kuriakose, Dinesh, Kurtzman, Ethan, Kutsogiannis, Demetrios, Kutsyna, Galyna, Bedu-Addo, Ama Kwakyewaa, Kwedi, Sylvie, Kyriakoulis, Konstantinos, Lachatre, Marie, Lacoste, Marie, Laffey, John G., Lafhej, Nadhem, Lagrange, Marie, Laine, Fabrice, Lairez, Olivier, Lakhey, Sanjay, Lambert, Marc, Lamontagne, François, Langelot-Richard, Marie, Langlois, Vincent, Lantang, Eka Yudha, Lanza, Marina, Laouénan, Cédric, Laribi, Samira, Lariviere, Delphine, Lasry, Stéphane, Lath, Sakshi, Latif, Naveed, Latifeh, Youssef, Launay, Odile, Laureillard, Didier, Lavie-Badie, Yoan, Law, Andy, Lawrence, Cassie, Lawrence, Teresa, Le, Minh, Le Bihan, Clément, Le Bris, Cyril, Le Falher, Georges, Le Fevre, Lucie, Le Hingrat, Quentin, Le Maréchal, Marion, Le Mestre, Soizic, Le Moal, Gwenaël, Le Moing, Vincent, Le Nagard, Hervé, Leal, Ema, Santos, Marta Leal, Lee, Biing Horng, Lee, Heng Gee, Lee, Su Hwan, Lee, James, Lee, Jennifer, Lee, Todd C., Lee, Yi Lin, Leeming, Gary, Lefebvre, Bénédicte, Lefebvre, Laurent, Lefèvre, Benjamin, LeGac, Sylvie, Lehiste, Merili-Helen, Lelievre, Jean-Daniel, Lellouche, François, Lemaignen, Adrien, Lemee, Véronique, Lemeur, Anthony, Lemmink, Gretchen, Lene, Ha Sha, Lennon, Jenny, León, Rafael, Leone, Marc, Lepik, Tanel, Lepiller, Quentin, Lescure, François-Xavier, Lesens, Olivier, Lesouhaitier, Mathieu, Lester-Grant, Amy, Letizia, Andrew, Letrou, Sophie, Levy, Bruno, Levy, Yves, Levy-Marchal, Claire, Lewandowska, Katarzyna, L'Her, Erwan, Bassi, Gianluigi Li, Liang, Janet, Liaquat, Ali, Liegeon, Geoffrey, Lim, Kah Chuan, Lim, Wei Shen, Lima, Chantre, Lina, Bruno, Lina, Lim, Lind, Andreas, Lingad, Maja Katherine, Lingas, Guillaume, Lion-Daolio, Sylvie, Liu, Keibun, Livrozet, Marine, Lizotte, Patricia, Loforte, Antonio, Lolong, Navy, Loon, Leong Chee, Lopes, Diogo, Lopez-Colon, Dalia, Loschner, Anthony L., Loubet, Paul, Loufti, Bouchra, Louis, Guillame, Lourenco, Silvia, Lovelace-Macon, Lara, Lee Low, Lee, Lowik, Marije, Loy, Jia Shyi, Lucet, Jean Christophe, Luna, Carlos M., Lungu, Olguta, Lunn, Miles, Luong, Liem, Luque, Nestor, Luton, Dominique, Maasikas, Olavi, Machado, Moïse, Machado, Sara, Macheda, Gabriel, Magzoub, Mustafa, Mahieu, Rafael, Mahy, Sophie, Maia, Ana Raquel, Maier, Lars S., Ascofare, Oumou Maiga, Maillet, Mylène, Maitre, Thomas, Majeed, Nimisha Abdul, Malfertheiner, Maximilian, Malik, Nadia, Mallon, Paddy, Maltez, Fernando, Malvy, Denis, Manda, Victoria, Mandelbrot, Laurent, Manetta, Frank, Mankikian, Julie, Manning, Edmund, Manuel, Aldric, Maráczi, Veronika, Sant′Ana Malaque, Ceila Maria, Marino, Flávio, Markowicz, Samuel, Marques, Ana, Marquis, Catherine, Marsh, Laura, Marsh, Brian, Marshal, Megan, Marshall, John, Martelli, Celina Turchi, Martin, Dori-Ann, Martin, Emily, Martin-Blondel, Guillaume, Martinelli, Alessandra, Martinez, F. Eduardo, Martin-Loeches, Ignacio, Martinot, Martin, Martín-Quiros, Alejandro, Martins, Ana, Martins, João, Martins, Nuno, Rego, Caroline Martins, Martucci, Gennaro, Martynenko, Olga, Marwali, Eva Miranda, Marzukie, Marsilla, Maslove, David, Mason, Sabina, Masood, Sobia, Masoud, Fatma, Massoma, Moise, Masumbe, Palmer, Mat Nor, Mohd Basri, Matan, Moshe, Fernandes, Henrique Mateus, Mathew, Meghena, Mathew, Christina, Mattei, Mathieu, Maulin, Laurence, May, Juergen, Maynar, Javier, Mayxay, Mayfong, Mazzoni, Thierry, Sweeney, Lisa Mc, McArthur, Colin, McCann, Naina, McCanny, Peter, McCarthy, Aine, McCarthy, Anne, McCloskey, Colin, McConnochie, Rachael, McDermott, Sherry, McDonald, Sarah E., McElroy, Aine, McElwee, Samuel, McEvoy, Natalie, McGeer, Allison, McLean, Kenneth A., McNally, Paul, McNicholas, Bairbre, Meaney, Edel, Mear-Passard, Cécile, Mechlin, Maggie, Medombou, Nastia, Mehkri, Omar, Mele, Ferruccio, Melo, Luis, Memon, Kashif Ali, Mendes, João João, Menkiti, Ogechukwu, Menon, Kusum, Mentré, France, Mentzer, Alexander J., Mercier, Emmanuelle, Mercier, Noémie, Merckx, Antoine, Mergeay-Fabre, Mayka, Mergler, Blake, Merson, Laura, Mesquita, António, Meta, Roberta, Metwally, Osama, Meybeck, Agnès, Meyer, Dan, Meynert, Alison M., Meysonnier, Vanina, Mezidi, Mehdi, Michelanglei, Céline, Michelet, Isabelle, Mihelis, Efstathia, Mihnovit, Vladislav, Abdullah, Duha Milad, Miller, Jennene, Miranda-Maldonado, Hugo, Misnan, Nor Arisah, Eliza Mohamed, Nik Nur, Mohamed, Nouralsabah, Mohamed, Tahira Jamal, Ads, Alaa Mohamed, Mohamed Elsayed Abdelhalim, Ahmed Reda, Mohammed, Libya, Mohammed Mostafa, Shrouk Fawze, Abdelrahman Mohammedahmed, Manahil Omer, Mohammedelhassan, Omer Abdullah, Moin, Asma, Mokhtar, Walaa, Molinos, Elena, Molloy, Brenda, Mone, Mary, Monteiro, Agostinho, Montes, Claudia, Montrucchio, Giorgia, Moore, Sarah, Moore, Shona C., Cely, Lina Morales, Morgom, Marwa, Moro, Lucia, Motherway, Catherine, Motos, Ana, Mouquet, Hugo, Perrot, Clara Mouton, Moyet, Julien, Mualla, Suleiman Haitham, Muftah, Mohamed, Mufti, Aisha Kalsoom, Muh, Ng Yong, Muhaisen, Mo'nes, Muhamad, Dzawani, Mullaert, Jimmy, Müller, Fredrik, Müller, Karl Erik, Munblit, Daniel, Ali, Syed Muneeb, Munir, Nadeem, Munshi, Laveena, Murphy, Aisling, Murray, Patrick, Murris, Marlène, Murthy, Srinivas, Musaab, Himed, Mustafa, Alamin, Mustafa, Mus'ab, Mustafa, Dana, Muvindi, Himasha, Myrodia, Dimitra Melia, Mohd-Hanafiah, Farah Nadia, Nadjm, Behzad, Nagpal, Dave, Nagrebetsky, Alex, Nagybányai-Nagy, Blanka, Boudoin, Herwin Nanda, Narasimhan, Mangala, Narayanan, Nageswaran, Nasa, Prashant, Khan, Rashid Nasim, Nasrallah, Ahmad, Nassif Metri, Adel Gerges, Nazerali-Maitland, Alasdair, Neant, Nadège, Neb, Holger, Nekliudov, Nikita, Nelder, Matthew, Nelwan, Erni, Neto, Raul, Neumann, Emily, Ng, Wing Yiu, Ng, Pauline Yeung, Nghi, Anthony, Nguyen, Duc, Choileain, Orna Ni, Leathlobhair, Niamh Ni, Niba, Nerissa, Nichol, Alistair D., Nitayavardhana, Prompak, Nonas, Stephanie, Mohd Noordin, Nurul Amani, Izzati Norharizam, Nurul Faten, North, Anita, Notari, Alessandra, Noursadeghi, Mahdad, Nowinski, Adam, Nseir, Saad, Numfor, Leonard, Nurnaningsih, Nurnaningsih, Nusantara, Dwi Utomo, Nyamankolly, Elsa, Nygaard, Anders Benteson, Brien, Fionnuala O., Callaghan, Annmarie O., O'Callaghan, Annmarie, Occhipinti, Giovanna, OConnor, Derbrenn, O'Donnell, Max, Ofori-Boadu, Lawrence, Ogston, Tawnya, Ogura, Takayuki, Oh, Tak-Hyuk, O'Halloran, Sophie, O'Hearn, Katie, Ohene, Sally-Ann, Ohshimo, Shinichiro, Oliveira, João, Oliveira, Larissa, Olliaro, Piero L., Rageh Elnaggar, Cinderella Omar, Mohammed Omer, Alsarrah Ali, Ondobo, Pierre, Ong, David S.Y., Ong, Jee Yan, Oosthuyzen, Wilna, Opavsky, Anne, Openshaw, Peter, Orakzai, Saijad, Orozco-Chamorro, Claudia Milena, Ortoleva, Jamel, Elsayed Soliman, Mohamed Osama, Osatnik, Javier, O'Shea, Linda, O'Sullivan, Miriam, Othman, Eman, Othman, Siti Zubaidah, Ouamara, Nadia, Ouissa, Rachida, Owusu, Micheal, Owusu-Asare, Ama Akyampomaa, Oziol, Eric, Pagadoy, Maïder, Pages, Justine, Palacios, Amanda, Palmarini, Massimo, Panarello, Giovanna, Panda, Prasan Kumar, Paneru, Hem, Pang, Lai Hui, Panigada, Mauro, Pansu, Nathalie, Papadopoulos, Aurélie, Parke, Rachael, Parker, Melissa, Pasquier, Jérémie, Pastene, Bruno, Patauner, Fabian, Patel, Drashti, Pathmanathan, Mohan Dass, Patrão, Luís, Patricio, Patricia, Patterson, Lisa, Pattnaik, Rajyabardhan, Paul, Christelle, Paul, Mical, Paulos, Jorge, Paxton, William A., Payen, Jean-François, Peake, Sandra L., Peariasamy, Kalaiarasu, Peek, Giles J., Peelman, Florent, Peiffer-Smadja, Nathan, Peigne, Vincent, Pejkovska, Mare, Pelosi, Paolo, Peltan, Ithan D., Pereira, Rui, Perez, Daniel, Perpoint, Thomas, Pesenti, Antonio, Pestre, Vincent, Petrou, Lenka, Petrovic, Michele, Petrov-Sanchez, Ventzislava, Pettersen, Frank Olav, Peytavin, Gilles, Philips, Richard Odame, Phonemixay, Ooyanong, Phoutthavong, Soulichanya, Piagnerelli, Michael, Picard, Walter, Picone, Olivier, de Piero, Maria, Piersma, Djura, Pimentel, Carlos, Pinto, Raquel, Pires, Catarina, Piroth, Lionel, Pitaloka, Ayodhia, Piubelli, Chiara, Pius, Riinu, Piva, Simone, Plantier, Laurent, Png, Hon Shen, Poissy, Julien, Pokeerbux, Ryadh, Poli, Sergio, Pollakis, Georgios, Ponscarme, Diane, Porto, Diego Bastos, Post, Andra-Maris, Postma, Douwe F., Povoa, Pedro, Póvoas, Diana, Powis, Jeff, Prapa, Sofia, Praphasiri, Viladeth, Preau, Sébastien, Prebensen, Christian, Preiser, Jean-Charles, Prinssen, Anton, Pritchard, Mark G., Dilanthi Priyadarshani, Gamage Dona, Proença, Lucia, Pudota, Sravya, Semedi, Bambang Pujo, Pulicken, Mathew, Puplampu, Peter, Purcell, Gregory, Quesada, Luisa, Quinones-Cardona, Vilmaris, Quist-Paulsen, Else, Quraishi, Mohammed, Qutishat, Fadi, Rabaa, Maia, Rabaud, Christian, Rabindrarajan, Ebenezer, Rafael, Aldo, Rafiq, Marie, Ragab, Abdelrahman, Rahardjani, Mutia, Ullah, Arslan Rahat, Haji Ab Rahman, Ahmad Kashfi, Rahman, Rozanah Abd, Rainieri, Fernando, Rajahram, Giri Shan, Ramachandran, Pratheema, Ramakrishnan, Nagarajan, Ramalho, José, Ramli, Ahmad Afiq, Rammaert, Blandine, Ramos, Grazielle Viana, Rana, Asim, Rangappa, Rajavardhan, Ranjan, Ritika, Rapp, Christophe, Rashan, Aasiyah, Rashan, Thalha, Rasheed, Ghulam, Rasmin, Menaldi, Rätsep, Indrek, Rau, Cornelius, Ravi, Tharmini, Raza, Ali, Real, Andre, Rebaudet, Stanislas, Redl, Sarah, Reeve, Brenda, Rehman, Attaur, Rehman Khalid, Muhammad Osama, Reikvam, Dag Henrik, Reis, Renato, Rello, Jordi, Remppis, Jonathan, Remy, Martine, Ren, Hongru, Renk, Hanna, Resseguier, Anne-Sophie, Revest, Matthieu, Rewa, Oleksa, Reyes, Luis Felipe, Ribeiro, Maria Ines, Ricchiuto, Antonia, Richardson, David, Richardson, Denise, Richier, Laurent, Atikah Ahmad Ridzuan, Siti Nurul, Rios, Ana L., Rishu, Asgar, Rispal, Patrick, Risso, Karine, Rivera Nuñez, Maria Angelica, Robba, Chiara, Roberto, André, Roberts, Stephanie, Roberts, Charles, Robertson, David L., Robineau, Olivier, Roca, Anna, Roche-Campo, Ferran, Rodari, Paola, Rodeia, Simão, Roessler, Bernhard, Roger, Claire, Roger, Pierre-Marie, Rojek, Amanda, Roncon-Albuquerque, Roberto, Jr., Roriz, Mélanie, Rosa-Calatrava, Manuel, Rose, Michael, Rosenberger, Dorothea, Rossanese, Andrea, Rossetti, Matteo, Rossignol, Patrick, Roy, Carine, Roze, Benoît, Rusmawatiningtyas, Desy, Russell, Clark D., Ryan, Maeve, Ryckaert, Steffi, Holten, Aleksander Rygh, Saba, Isabela, Sadaf, Sairah, Sadat, Musharaf, Sahraei, Valla, Said, Abdurraouf, Saidani, Nadia, Sakiyalak, Pranya, Sako, Fodé Bangaly, Salah, Moamen, Salah Eldin Mohamed Abbas, Ali Alaa, Salahuddin, Nawal, Salazar, Leonardo, Saleem, Jodat, Alyasiri, Mohammed Saleh, Abu Salem, Talat Ahmed, Sales, Gabriele, Gandonniere, Charlotte Salmon, Salvator, Hélène, Samardali, Dana, Samardali, Shaden, Shaaban Aly Orabi, Yehia Samir, Sanchez, Emely, Sanchez, Olivier, Sanchez de Oliveira, Kizy, Sanchez-Miralles, Angel, Sancho-Shimizu, Vanessa, Sandhu, Gyan, Sandhu, Zulfiqar, Sandrine, Pierre-François, Săndulescu, Oana, Santos, Marlene, 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P. Sanka, Sriskandan, Shiranee, Stabler, Sarah, Staudinger, Thomas, Stecher, Stephanie-Susanne, Steinsvik, Trude, Stienstra, Ymkje, Stiksrud, Birgitte, Stolz, Eva, Stone, Amy, Streinu-Cercel, Anca, Streinu-Cercel, Adrian, Strong, Geoff, Stuart, Ami, Stuart, David, Su, Richa, Subekti, Decy, Suen, Gabriel, Suen, Jacky Y., Sukumar, Prasanth, Sultana, Asfia, Summers, Charlotte, Supic, Dubravka, Suppiah, Deepashankari, Surovcová, Magdalena, Suwarti, Atie, Svistunov, Andrey, Syahrin, Sarah, Sylverken, Augustina, Syrigos, Konstantinos, Sztajnbok, Jaques, Szuldrzynski, Konstanty, Tabrizi, Shirin, Taccone, Fabio S., Tagherset, Lysa, Taib, Shahdattul Mawarni, Taleb, Sara, Talla, Cheikh, Talsma, Jelmer, Tamisier, Renaud, Tampubolon, Maria Lawrensia, Tan, Kim Keat, Tan, Yan Chyi, Tanaka, Hiroyuki, Tanaka, Taku, Taniguchi, Hayato, Taqdees, Huda, Taqi, Arshad, Tardivon, Coralie, Kamal Mostafa, Yousef Tarek, Tarhabat, Ali, Tattevin, Pierre, Taufik, M Azhari, Tawfik, Hassan, Tee, Tze Yuan, Teixeira, João, Tejada, Sofia, Tellier, Marie-Capucine, Teoh, Sze Kye, Teotonio, Vanessa, Téoulé, François, Terrier, Olivier, Terzi, Nicolas, Tessier-Grenier, Hubert, Tey, Adrian, Mohd Thabit, Alif Adlan, Thakur, Anand, Tham, Zhang Duan, Thangavelu, Suvintheran, Theron, Elmi, Thibault, Vincent, Thiberville, Simon-Djamel, Thill, Benoît, Thirumanickam, Jananee, Thompson, Niamh, Thompson, Shaun, Thomson, Emma C., Thomson, David, Thorpe, Mathew, Thurai, Surain Raaj Thanga, Thwaites, Ryan S., Tierney, Paul, Tieroshyn, Vadim, Timashev, Peter S., Timsit, Jean-François, Tirupakuzhi Vijayaraghavan, Bharath Kumar, Tissot, Noémie, Toal, Fiona, Yang Toh, Jordan Zhien, Toki, Maria, Tonby, Kristian, Tonnii, Sia Loong, Torre, Marta, Torres, Antoni, Torres, Margarida, Santos-Olmo, Rosario Maria Torres, Torres-Zevallos, Hernando, Tounkara, Aboubacar, Towers, Michael, Traoré, Fodé Amara, Trapani, Tony, Tromeur, Cécile, Trontzas, Ioannis, Trouillon, Tiffany, Truong, Jeanne, Tual, Christelle, Tubiana, Sarah, Tuite, Helen, Turgeon, Alexis F., Turmel, Jean-Marie, Turtle, Lance C.W., Tveita, Anders, Twardowski, Pawel, Uchiyama, Makoto, Udayanga, PG Ishara, Udy, Andrew, Ullrich, Roman, Uribe, Alberto, Usman, Asad, Usuf, Effua, Uyeki, Timothy M., Vajdovics, Cristinava, Valentini, Piero, Val-Flores, Luís, Van de Velde, Stijn, van den Berge, Marcel, van der Feltz, Machteld, van der Palen, Job, van der Valk, Paul, Van Der Vekens, Nicky, Van der Voort, Peter, Van Der Werf, Sylvie, van Gulik, Laura, Van Hattem, Jarne, van Netten, Carolien, van Veen, Ilonka, Vanel, Noémie, Vanoverschelde, Henk, Varrone, Michael, Vasudayan, Shoban Raj, Vauchy, Charline, Vecham, Pavan Kumar, Veeran, Shaminee, Veislinger, Aurélie, Vencken, Sebastian, Ventura, Sara, Verbon, Annelies, Vidal, José Ernesto, Vieira, César, Vijayan, Deepak, Villar, Judit, Villeneuve, Pierre-Marc, Villoldo, Andrea, Vishwanathan, Gayatri, Visseaux, Benoit, Visser, Hannah, Vitiello, Chiara, Vongsouvath, Manivanh, Vonkeman, Harald, Vuotto, Fanny, Wahab, Suhaila Abdul, Wahab, Noor Hidayu, Wahid, Nadirah Abdul, Wainstein, Marina, Walsh, Laura, Shukeri, Wan Fadzlina Wan Muhd, Wang, Chih-Hsien, Webb, Steve, Wei, Jia, Weil, Katharina, Wen, Tan Pei, Wesam, Hassi, Wesselius, Sanne, West, T. Eoin, Wham, Murray, Whelan, Bryan, White, Nicole, Wicky, Paul Henri, Wiedemann, Aurélie, Wijaya, Surya Otto, Wille, Keith, Willems, Sue, Williams, Bailey, Williams, Patricia J., Williams, Virginie, Wils, Evert-Jan, Wittman, Jessica, Wong, Calvin, Wong, Xin Ci, Wong, Yew Sing, Wong, Teck Fung, Wright, Natalie, Xian, Lim Saio, Xynogalas, Ioannis, Binti Mohd Yakop, Siti Rohani, Yamazaki, Masaki, Yarad, Elizabeth, Yazdanpanah, Yazdan, Hing, Nicholas Yee Liang, Mahmoud Abdelaal, Abdelrahman Yehia, Yelnik, Cécile, Yeoh, Chian Hui, Yerkovich, Stephanie, Yiaye, Touxiong, Yokoyama, Toshiki, Yonis, Hodane, Yousif, Obada, Yuliarto, Saptadi, Zaaqoq, Akram, Zabbe, Marion, Zabert, Gustavo E., Zacharowski, Kai, Zahid, Masliza, Zahran, Maram, Binti Zaidan, Nor Zaila, Zambon, Maria, Zambrano, Miguel, Zanella, Alberto, Zaynah, Nurul, Zayyad, Hiba, Zoufaly, Alexander, Zucman, David, Ibáñez-Prada, Elsa D., Gonçalves, Bronner P., Baruch, Joaquin, Escher, Martina, Philippy, Fred, Kutsogiannis, Demetrios James, Vaillant, Michel, and Olliaro, Piero

Published
2024
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9. Novel Compound MMV1804559 from the Global Health Priority Box Exhibits In Vitro and In Vivo Activity against Madurella mycetomatis

Author

Jingyi Ma, Kimberly Eadie, Marij Schippers, Ahmed Fahal, Benoît Laleu, Annelies Verbon, and Wendy W. J. van de Sande

Subjects
Madurella mycetomatis, mycetoma, eumycetoma, treatment, COVID box, Global Health Priority Box, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Objectives: Eumycetoma is a neglected tropical disease (NTD) characterized by subcutaneous lesions and the formation of grains. Attempts to treat eumycetoma involve a combination of antifungal treatment and surgery, although the outcome is frequently disappointing. Therefore, there is a need to identify novel antifungal drugs to treat eumycetoma. In this respect, Medicines for Malaria Venture (MMV) has assembled libraries of compounds for researchers to use in drug discovery research against NTD. Therefore, we screened two MMVOpen compound libraries to identify novel leads for eumycetoma. Methods: A total of 400 compounds from the COVID Box and the Global Health Priority Box were screened in vitro at 100 µM and 25 µM against the most common causative agents of eumycetoma, namely Madurella mycetomatis and Falciformispora senegalensis, and the resulting IC50 and MIC50 values were obtained. Compounds with an IC50 < 8 µM were identified for possible in vivo efficacy studies using an M. mycetomatis grain model in Galleria mellonella larvae. Results: Out of the 400 compounds, 22 were able to inhibit both M. mycetomatis and F. senegalensis growth at 100 µM and 25 µM, with compounds MMV1593278, MMV020335, and MMV1804559 being selected for in vivo testing. Of these three, only the pyrazolopyrimidine derivative MMV1804559 was able to prolong the survival of M. mycetomatis-infected G. mellonella larvae. Furthermore, the grains in MMV1804559-treated larvae were significantly smaller compared to the PBS-treated group. Conclusion: MMV1804559 shows promising in vitro and in vivo activity against M. mycetomatis.

Published
2024
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12. Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19

Author

Abdukahil, heryl Ann, Abdulkadir, Nurul Najmee, Abe, Ryuzo, Abel, Laurent, Abrous, Amal, Absil, Lara, Acker, Andrew, Adachi, Shingo, Adrião, Diana, Al Ageel, Saleh, Ahmed, Shakeel, Ainscough, Kate, Airlangga, Eka, Aisa, Tharwat, Hssain, Ali Ait, Tamlihat, Younes Ait, Akimoto, Takako, Akmal, Ernita, Akwani, Chika, Al Qasim, Eman, Alalqam, Razi, Alberti, Angela, Al-dabbous, Tala, Alegesan, Senthilkumar, Alessi, Marta, Alex, Beatrice, Alexandre, Kévin, Al-Fares, Abdulrahman, Alfoudri, Huda, Ali, Imran, Alidjnou, Kazali Enagnon, Aliudin, Jeffrey, Alkhafajee, Qabas, Allavena, Clotilde, Allou, Nathalie, Alves, João, Alves, Rita, Alves, João Melo, Cabrita, Joana Alves, Amaral, Maria, Amira, Nur, Ampaw, Phoebe, Andini, Roberto, Andréjak, Claire, Angheben, Andrea, Angoulvant, François, Ansart, Séverine, Anthonidass, Sivanesen, Antonelli, Massimo, Antunes de Brito, Carlos Alexandre, Apriyana, Ardiyan, Arabi, Yaseen, Aragao, Irene, Arancibia, Francisco, Araujo, Carolline, Arcadipane, Antonio, Archambault, Patrick, Arenz, Lukas, Arlet, Jean-Benoît, Arnold-Day, Christel, Arora, Lovkesh, Arora, Rakesh, Artaud-Macari, Elise, Aryal, Diptesh, Asensio, Angel, Ashraf, Muhammad, Assie, Jean Baptiste, Asyraf, Amirul, Atif, Minahel, Atique, Anika, Auchabie, Johann, Aumaitre, Hugues, Auvet, Adrien, Azemar, Laurène, Azoulay, Cecile, Bach, Benjamin, Bachelet, Delphine, Badr, Claudine, Baillie, J. 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Jonathan Samuel, Chen, Anjellica, Chen, Yih-Sharng, Chenard, Léo, Cheng, Matthew Pellan, Cheret, Antoine, Chiarabini, Thibault, Chica, Julian, Chidambaram, Suresh Kumar, Tho, Leong Chin, Chirouze, Catherine, Chiumello, Davide, Cho, Sung-Min, Cholley, Bernard, Chopin, Marie-Charlotte, Chow, Ting Soo, Chow, Yock Ping, Chua, Hiu Jian, Chua, Jonathan, Cidade, Jose Pedro, Citarella, Barbara Wanjiru, Ciullo, Anna, Clarke, Jennifer, Claure-Del Granado, Rolando, Clohisey, Sara, Cobb, Perren J., Codan, Cassidy, Cody, Caitriona, Coelho, Alexandra, Coles, Megan, Coles, Jennifer, Colin, Gwenhaël, Collins, Michael, Colombo, Sebastiano Maria, Combs, Pamela, Connolly, Jennifer, Connor, Marie, Conrad, Anne, Conway, Elaine, Cooke, Graham S., Copland, Mary, Cordel, Hugues, Corley, Amanda, Cornelis, Sabine, Cornet, Alexander Daniel, Corpuz, Arianne Joy, Cortegiani, Andrea, Corvaisier, Grégory, Couffignal, Camille, Couffin-Cadiergues, Sandrine, Courtois, Roxane, Cousse, Stéphanie, Croonen, Sabine, Crowl, 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Rizo-Topete, Lilia, Pole, Jason D., and Johnson, David W.

Published
2023
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13. The efficacy and tolerability of latency-reversing agents in reactivating the HIV-1 reservoir in clinical studies: a systematic review

Author

Quinten Debrabander, Kathryn S. Hensley, Christina K. Psomas, Wichor Bramer, Tokameh Mahmoudi, Berend J. van Welzen, Annelies Verbon, and Casper Rokx

Subjects
Human immunodeficiency virus, Latency reactivation, Virus latency, Virus activation, Interleukins, Systematic review, Microbiology, QR1-502, Public aspects of medicine, RA1-1270
Abstract

Introduction: Understanding the clinical potency of latency-reversing agents (LRAs) on the HIV-1 reservoir is useful to deploy future strategies. This systematic review evaluated the effects of LRAs in human intervention studies. Methods: A literature search was performed using medical databases focusing on studies with adults living with HIV-1 receiving LRAs. Eligibility criteria required participants from prospective clinical studies, a studied compound hypothesised as LRA, and reactivation or tolerability assessments. Relevant demographical data, LRA reactivation capacity, reservoir size, and adverse events were extracted. A study quality assessment with analysis of bias was performed by RoB 2 and ROBINS-I tools. The primary endpoints were HIV-1 reservoir reactivation after LRA treatment quantified by cell-associated unspliced HIV-1 RNA, and LRA tolerability defined by adverse events. Secondary outcomes were reservoir size and the effect of LRAs on analytical treatment interruption (ATI) duration. Results: After excluding duplicates, 5182 publications were screened. In total 45 publications fulfilled eligibility criteria including 26 intervention studies and 16 randomised trials. The risk of bias was evaluated as high. Chromatin modulators were the main investigated LRA class in 24 studies. Participants were mostly males (90.1%). Where reported, HIV-1 subtype B was most frequently observed. Reactivation after LRA treatment occurred in 78% of studies and was observed with nearly all chromatin modulators. When measured, reactivation mostly occurred within 24 h after treatment initiation. Combination LRA strategies have been infrequently studied and were without synergistic reactivation. Adverse events, where reported, were mostly low grade, yet occurred frequently. Seven studies had individuals who discontinued LRAs for related adverse events. The reservoir size was assessed by HIV-1 DNA in 80% of studies. A small decrease in reservoir was observed in three studies on immune checkpoint inhibitors and the histone deacetylase inhibitors romidepsin and chidamide. No clear effect of LRAs on ATI duration was observed. Conclusion: This systematic review provides a summary of the reactivation of LRAs used in current clinical trials whilst highlighting the importance of pharmacovigilance. Highly heterogeneous study designs and underrepresentation of relevant patient groups are to be considered when interpreting these results. The observed reactivation did not lead to cure or a significant reduction in the size of the reservoir. Finding more effective LRAs by including well-designed studies are needed to define the required reactivation level to reduce the HIV-1 reservoir.

Published
2023
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14. Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry

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Abdukahil, Sheryl Ann, Abdulkadir, Nurul Najmee, Abe, Ryuzo, Abel, Laurent, Abrous, Amal, Absil, Lara, Acker, Andrew, Adam, Elisabeth, Adrião, Diana, Al Ageel, Saleh, Ahmed, Shakeel, Ainscough, Kate, Aisa, Tharwat, Hssain, Ali Ait, Tamlihat, Younes Ait, Akimoto, Takako, Akmal, Ernita, Akwani, Chika, Al Qasim, Eman, Alalqam, Razi, Alberti, Angela, Al-dabbous, Tala, Alegesan, Senthilkumar, Alessi, Marta, Alex, Beatrice, Alexandre, Kévin, Al-Fares, Abdulrahman, Alfoudri, Huda, Ali, Imran, Alidjnou, Kazali Enagnon, Aliudin, Jeffrey, Alkhafajee, Qabas, Allavena, Clotilde, Allou, Nathalie, Alves, João, Alves, Rita, Alves, João Melo, Cabrita, Joana Alves, Amaral, Maria, Amira, Nur, Ampaw, Phoebe, Andini, Roberto, Andréjak, Claire, Angheben, Andrea, Angoulvant, François, Ansart, Séverine, Anthonidass, Sivanesen, Antonelli, Massimo, de Brito, Carlos Alexandre Antunes, Apriyana, Ardiyan, Arabi, Yaseen, Aragao, Irene, Arancibia, Francisco, Araujo, Carolline, Arcadipane, Antonio, Archambault, Patrick, Arenz, Lukas, Arlet, Jean-Benoît, Arnold-Day, Christel, Arora, Lovkesh, Arora, Rakesh, Artaud-Macari, Elise, Aryal, Diptesh, Asensio, Angel, Ashraf, Muhammad, Assie, Jean Baptiste, Asyraf, Amirul, Atif, Minahel, Atique, Anika, Auchabie, Johann, Aumaitre, Hugues, Auvet, Adrien, Azemar, Laurène, Azoulay, Cecile, Bach, Benjamin, Bachelet, Delphine, Badr, Claudine, Baig, Nadia, Baillie, J. Kenneth, Bak, Erica, Bakakos, Agamemnon, Bakar, Nazreen Abu, Bal, Andriy, Balakrishnan, Mohanaprasanth, Balan, Valeria, Bani-Sadr, Firouzé, Barbalho, Renata, Barbosa, Nicholas Yuri, Barclay, Wendy S., Barnett, Saef Umar, Barnikel, Michaela, Barrasa, Helena, Barrelet, Audrey, Barrigoto, Cleide, Bartoli, Marie, Baruch, Joaquín, Basmaci, Romain, Basri, Muhammad Fadhli Hassin, Battaglini, Denise, Bauer, Jules, Rincon, Diego Fernando Bautista, Beane, Abigail, Bedossa, Alexandra, Hong Bee, Ker, Begum, Husna, Behilill, Sylvie, Beishuizen, Albertus, Beljantsev, Aleksandr, Bellemare, David, Beltrame, Anna, Beltrão, Beatriz Amorim, Beluze, Marine, Benech, Nicolas, Benjiman, Lionel Eric, Benkerrou, Dehbia, Bennett, Suzanne, Benny, Binny, Bento, Luís, Berdal, Jan-Erik, Bergeaud, Delphine, Bergin, Hazel, Sobrino, José Luis Bernal, Bertoli, Giulia, Bertolino, Lorenzo, Bessis, Simon, Bevilcaqua, Sybille, Bezulier, Karine, Bhatt, Amar, Bhavsar, Krishna, Bianco, Claudia, Bidin, Farah Nadiah, Singh, Moirangthem Bikram, Humaid, Felwa Bin, Kamarudin, Mohd Nazlin Bin, Bisoffi, Zeno, Bissuel, François, Bitker, Laurent, Bitton, Jonathan, Blanco-Schweizer, Pablo, Blier, Catherine, Bloos, Frank, Blot, Mathieu, Blumberg, Lucille, Boccia, Filomena, Bodenes, Laetitia, Bogaert, Debby, Boivin, Anne-Hélène, Bolaños, Isabela, Bolze, Pierre-Adrien, Bompart, François, Borges, Diogo, Borie, Raphaël, Bosse, Hans Martin, Botelho-Nevers, Elisabeth, Bouadma, Lila, Bouchaud, Olivier, Bouchez, Sabelline, Bouhmani, Dounia, Bouhour, Damien, Bouiller, Kévin, Bouillet, Laurence, Bouisse, Camile, Boureau, Anne-Sophie, Bourke, John, Bouscambert, Maude, Bousquet, Aurore, Bouziotis, Jason, Boxma, Bianca, Boyer-Besseyre, Marielle, Boylan, Maria, Bozza, Fernando Augusto, Braconnier, Axelle, Braga, Cynthia, Brandenburger, Timo, Monteiro, Filipa Brás, Brazzi, Luca, Breen, Patrick, Breen, Dorothy, Brewster, David, Brickell, Kathy, Browne, Shaunagh, Browne, Alex, Brozzi, Nicolas, Brusse-Keizer, Marjolein, Bryda, Petra, Buchtele, Nina, Buisson, Marielle, Burhan, Erlina, Burrell, Aidan, Bustos, Ingrid G., Cabie, André, Cabral, Susana, Caceres, Eder, Cadoz, Cyril, Garcês, Rui Caetano, Calligy, Kate, Calvache, Jose Andres, Camões, João, Campana, Valentine, Campbell, Paul, Campisi, Josie, Canepa, Cecilia, Cantero, Mireia, Caraux-Paz, Pauline, Cárcel, Sheila, Cardellino, Chiara Simona, Cardoso, Sofia, Cardoso, Filipe, Cardoso, Filipa, Cardoso, Nelson, Carelli, Simone, Carlier, Nicolas, Carmoi, Thierry, Carney, Gayle, Carqueja, Inês, Carret, Marie-Christine, Carrier, François Martin, Carroll, Ida, Carson, Gail, Casanova, Maire-Laure, Cascão, Mariana, Casey, Siobhan, Casimiro, José, Cassandra, Bailey, Castañeda, Silvia, Castanheira, Nidyanara, Castor-Alexandre, Guylaine, Castro, Ivo, Catarino, Ana, Catherine, François-Xavier, Cattaneo, Paolo, Cavalin, Roberta, Cavayas, Alexandros, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chakveatze, Catherine, Chan, Adrienne, Chand, Meera, Chantalat Auger, Christelle, Chapplain, Jean-Marc, Charpentier, Charlotte, Chas, Julie, Chávez Iñiguez, Jonathan Samuel, Chen, Anjellica, Chen, Yih-Sharng, Chenard, Léo, Cheng, Matthew Pellan, Cheret, Antoine, Chiarabini, Thibault, Chica, Julian, Chidambaram, Suresh Kumar, Chin Tho, Leong, Chirouze, Catherine, Chiumello, Davide, Cho, Sung-Min, Cholley, Bernard, Chopin, Marie-Charlotte, Chow, Ting Soo, Chua, Hiu Jian, Chua, Jonathan, Cidade, Jose Pedro, Cisneros Herreros, José Miguel, Citarella, Barbara Wanjiru, Ciullo, Anna, Clarke, Jennifer, Clarke, Emma, Claure-Del Granado, Rolando, Clohisey, Sara, Codan, Cassidy, Cody, Caitriona, Coelho, Alexandra, Coles, Megan, Coles, Jennifer, Colin, Gwenhaël, Collins, Michael, Colombo, Sebastiano Maria, Combs, Pamela, Connolly, Jennifer, Connor, Marie, Conrad, Anne, Conway, Elaine, Cooke, Graham S., Copland, Mary, Cordel, Hugues, Corley, Amanda, Cornelis, Sabine, Cornet, Alexander Daniel, Corpuz, Arianne Joy, Cortegiani, Andrea, Corvaisier, Grégory, Costigan, 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Jake, Duplaix, Mathilde, Durante-Mangoni, Emanuele, Durham, Lucian, III, Dussol, Bertrand, Duthoit, Juliette, Duval, Xavier, Dyrhol-Riise, Anne Margarita, Ean, Sim Choon, Echeverria-Villalobos, Marco, Egan, Siobhan, Eira, Carla, El Sanharawi, Mohammed, Elapavaluru, Subbarao, Elharrar, Brigitte, Ellerbroek, Jacobien, Eloy, Philippine, Elshazly, Tarek, Enderle, Isabelle, Endo, Tomoyuki, Eng, Chan Chee, Engelmann, Ilka, Enouf, Vincent, Epaulard, Olivier, Escher, Martina, Esperatti, Mariano, Esperou, Hélène, Santo, Catarina Espírito, Esposito-Farese, Marina, Estevão, João, Etienne, Manuel, Ettalhaoui, Nadia, Everding, Anna Greti, Evers, Mirjam, Fabre, Isabelle, Fabre, Marc, Faheem, Amna, Fahy, Arabella, Fairfield, Cameron J., Faria, Pedro, Fateena, Hanan, Fatoni, Arie Zainul, Faure, Karine, Favory, Raphaël, Fayed, Mohamed, Feely, Niamh, Feeney, Laura, Fernandes, Jorge, Fernandes, Marília Andreia, Fernandes, Susana, Ferrand, François-Xavier, Devouge, Eglantine Ferrand, Ferrão, Joana, Ferraz, Mário, Ferreira, Sílvia, Ferreira, Bernardo, Ferreira, Benigno, Ferreira, Isabel, Ferriere, Nicolas, Ficko, Céline, Figueiredo-Mello, Claudia, Fiorda, Juan, Flament, Thomas, Flateau, Clara, Fletcher, Tom, Florence, Aline-Marie, Florio, Letizia Lucia, Flynn, Deirdre, Foley, Claire, Foley, Jean, Fonseca, Tatiana, Forsyth, Simon, Foster, Denise, Foti, Giuseppe, Fourn, Erwan, Fowler, Robert A., Fraher, Marianne, Franch-Llasat, Diego, Fraser, John F., Fraser, Christophe, Freire, Marcela Vieira, Ribeiro, Ana Freitas, Fritz, Ricardo, Fry, Stéphanie, Fuentes, Nora, Fukuda, Masahiro, Gaborieau, Valérie, Gaci, Rostane, Gagliardi, Massimo, Gagnard, Jean-Charles, Gagneux-Brunon, Amandine, Gaião, Sérgio, Skeie, Linda Gail, Gallagher, Phil, Gamble, Carrol, Gani, Yasmin, Garan, Arthur, Garcia, Rebekha, Barrio, Noelia García, Garcia-Gallo, Esteban, Garot, Denis, Garrait, Valérie, Gault, Nathalie, Gavin, Aisling, Gavrylov, Anatoliy, Gaymard, Alexandre, Gebauer, Johannes, Geraud, Eva, Morlaes, Louis Gerbaud, Germano, Nuno, Ghosn, Jade, Giani, Marco, Gibson, Jess, Gigante, Tristan, Gilg, Morgane, Gilroy, Elaine, Giordano, Guillermo, Girvan, Michelle, Gissot, Valérie, Glikman, Daniel, Gnall, Eric, Goehringer, François, Goepel, Siri, Goffard, Jean-Christophe, Goh, Jin Yi, Golob, Jonathan, Gómez-Junyent, Joan, Gominet, Marie, Gonzalez, Alicia, Gordon, Patricia, Gorenne, Isabelle, Gormley, Conor, Goubert, Laure, Goujard, Cécile, Goulenok, Tiphaine, Grable, Margarite, Graf, Jeronimo, Grandin, Edward Wilson, Granier, Pascal, Grasselli, Giacomo, Green, Christopher A., Greene, Courtney, Greenhalf, William, Greffe, Segolène, Grieco, Domenico Luca, Griffee, Matthew, Griffiths, Fiona, Grigoras, Ioana, Groenendijk, Albert, Gruner, Heidi, Gu, Yusing, Guedj, Jérémie, Guego, Martin, Guellec, Dewi, Guerreiro, Daniela, Guery, Romain, Guillaumot, Anne, Guilleminault, Laurent, de Castro, Maisa Guimarães, Guimard, Thomas, Haalboom, Marieke, Haber, Daniel, Habraken, Hannah, Hachemi, Ali, Hadri, Nadir, Hakak, Sheeba, Hall, Adam, Hall, Matthew, Halpin, Sophie, Hamer, Ansley, Hamidfar, Rebecca, Hammond, Terese, Hammond, Naomi, Han, Lim Yuen, Haniffa, Rashan, Hao, Kok Wei, Hardwick, Hayley, Harrison, Ewen M., Harrison, Janet, Ekow Harrison, Samuel Bernard, Hartman, Alan, Hashmi, Junaid, Hayes, Ailbhe, Hays, Leanne, Heerman, Jan, Heggelund, Lars, Hendry, Ross, Hennessy, Martina, Henriquez-Trujillo, Aquiles, Hentzien, Maxime, Hernandez, Diana, Hernandez-Montfort, Jaime, Hershey, Andrew, Hesstvedt, Liv, Higgins, Eibhlin, Higgins, Dawn, Higgins, Rupert, Hinchion, Rita, Hinton, Samuel, Hiraiwa, Hiroaki, Hitoto, Hikombo, Ho, Antonia, Ho, Yi Bin, Hoctin, Alexandre, Hoffmann, Isabelle, Hoh, Wei Han, Hoiting, Oscar, Holt, Rebecca, Holter, Jan Cato, Horby, Peter, Horcajada, Juan Pablo, Hoshino, Koji, Houas, Ikram, Hough, Catherine L., Houltham, Stuart, Ming-Yang Hsu, Jimmy, Hulot, Jean-Sébastien, Hurd, Abby, Ijaz, Samreen, Ikram, M. 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Eduardo, Martin-Loeches, Ignacio, Martinot, Martin, Martins, João, Martins, Ana, Martins, Nuno, Rego, Caroline Martins, Martucci, Gennaro, Martynenko, Olga, Marwali, Eva Miranda, Marzukie, Marsilla, Maslove, David, Mason, Sabina, Mat Nor, Mohd Basri, Matan, Moshe, Mathieu, Daniel, Mattei, Mathieu, Maulin, Laurence, Maxwell, Michael, Maynar, Javier, Mazzoni, Thierry, Sweeney, Lisa Mc, McArthur, Colin, McCanny, Peter, McCarthy, Anne, McCarthy, Aine, McCloskey, Colin, McConnochie, Rachael, McDermott, Sherry, McDonald, Sarah E., McElroy, Aine, McElwee, Samuel, McEneany, Victoria, McEvoy, Natalie, McGeer, Allison, McKay, Chris, McKeown, Johnny, McLean, Kenneth A., McNally, Paul, McNicholas, Bairbre, McPartlan, Elaine, Meaney, Edel, Mear-Passard, Cécile, Mechlin, Maggie, Mehkri, Omar, Mele, Ferruccio, Melo, Luis, Mendes, Joao Joao, Menon, Kusum, Mentré, France, Mentzer, Alexander J., Mercier, Emmanuelle, Mercier, Noémie, Merckx, Antoine, Mergeay-Fabre, Mayka, Mergler, Blake, Merson, Laura, 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Holger, Neto, Raul, Neumann, Emily, Ng, Pauline Yeung, Ng, Wing Yiu, Nghi, Anthony, Nguyen, Duc, Choileain, Orna Ni, Leathlobhair, Niamh Ni, Nichol, Alistair D., Nitayavardhana, Prompak, Nonas, Stephanie, Mohd Noordin, Nurul Amani, Noret, Marion, Izzati Norharizam, Nurul Faten, Norman, Lisa, Noursadeghi, Mahdad, Nowinski, Adam, Nseir, Saad, Nunez, Jose I., Nyamankolly, Elsa, Brien, Fionnuala O., Callaghan, Annmarie O., O'Callaghan, Annmarie, Occhipinti, Giovanna, OConnor, Derbrenn, O'Donnell, Max, Ogston, Tawnya, Ogura, Takayuki, Oh, Tak-Hyuk, O'Halloran, Sophie, O'Hearn, Katie, Ohshimo, Shinichiro, Oliveira, João, Oliveira, Larissa, Olliaro, Piero L., Ong, David S.Y., Ong, Jee Yan, Oosthuyzen, Wilna, Opavsky, Anne, Openshaw, Peter, Orozco-Chamorro, Claudia Milena, Ortoleva, Jamel, Osatnik, Javier, O'Shea, Linda, O'Sullivan, Miriam, Othman, Siti Zubaidah, Ouamara, Nadia, Ouissa, Rachida, Oziol, Eric, Pagadoy, Maïder, Pages, Justine, Palacios, Amanda, Palmarini, Massimo, Panarello, Giovanna, Panda, Prasan Kumar, Pang, Lai Hui, Panigada, Mauro, Pansu, Nathalie, Papadopoulos, Aurélie, Parke, Rachael, Pasquier, Jérémie, Pastene, Bruno, Patauner, Fabian, Pathmanathan, Mohan Dass, Patrão, Luís, Patricio, Patricia, Patrier, Juliette, Patterson, Lisa, Paul, Christelle, Paul, Mical, Paulos, Jorge, Paxton, William A., Payen, Jean-François, Peake, Sandra L., Peariasamy, Kalaiarasu, Jiménez, Miguel Pedrera, Peek, Giles J., Peelman, Florent, Peiffer-Smadja, Nathan, Peigne, Vincent, Pejkovska, Mare, Pelosi, Paolo, Peltan, Ithan D., Pereira, Rui, Perez, Daniel, Periel, Luis, Perpoint, Thomas, Pesenti, Antonio, Pestre, Vincent, Petrou, Lenka, Petrovic, Michele, Petrov-Sanchez, Ventzislava, Pettersen, Frank Olav, Peytavin, Gilles, Pharand, Scott, Picard, Walter, Picone, Olivier, de Piero, Maria, Pierobon, Carola, Piersma, Djura, Pimentel, Carlos, Pinto, Raquel, Piquard, Valentine, Pires, Catarina, Pironneau, Isabelle, Piroth, Lionel, Piubelli, Chiara, Pius, Riinu, Plantier, Laurent, Png, Hon Shen, Poissy, Julien, Pokeerbux, Ryadh, Poli, Sergio, Pollakis, Georgios, Ponscarme, Diane, Porto, Diego Bastos, Post, Andra-Maris, Postma, Douwe F., Povoa, Pedro, Póvoas, Diana, Powis, Jeff, Prapa, Sofia, Preau, Sébastien, Prebensen, Christian, Preiser, Jean-Charles, Prinssen, Anton, Pritchard, Mark G., Proença, Lucia, Pudota, Sravya, Puéchal, Oriane, Semedi, Bambang Pujo, Purcell, Gregory, Quesada, Luisa, González, Víctor Quirós, Quist-Paulsen, Else, Quraishi, Mohammed, Qutishat, Fadi, Rabaud, Christian, Rafael, Aldo, Rafiq, Marie, Rahman, Rozanah Abd, Haji Ab Rahman, Ahmad Kashfi, Rainieri, Fernando, Rajahram, Giri Shan, Ramakrishnan, Nagarajan, Ramalho, José, Ramli, Ahmad Afiq, Rammaert, Blandine, Ramos, Grazielle Viana, Ranjan, Ritika, Rapp, Christophe, Rasmin, Menaldi, Rätsep, Indrek, Ravi, Tharmini, Real, Andre, Rebaudet, Stanislas, Redl, Sarah, Reeve, Brenda, Reid, Liadain, Reikvam, Dag Henrik, Reis, Renato, Rello, Jordi, Remppis, Jonathan, Remy, Martine, Ren, Hongru, Renk, Hanna, Resseguier, Anne-Sophie, Revest, Matthieu, Rewa, Oleksa, Reyes, Tiago, Reyes, Luis Felipe, Ribeiro, Maria Ines, Richardson, David, Richardson, Denise, Richier, Laurent, Atikah Ahmad Ridzuan, Siti Nurul, Rios, Ana L., Rishu, Asgar, Rispal, Patrick, Risso, Karine, Rizer, Nicholas, Robba, Chiara, Roberto, André, Roberts, Stephanie, Robertson, David L., Robineau, Olivier, Roche-Campo, Ferran, Rodari, Paola, Rodeia, Simão, Roessler, Bernhard, Roger, Pierre-Marie, Roger, Claire, Roilides, Emmanuel, Rojek, Amanda, Romaru, Juliette, Roncon-Albuquerque, Roberto, Jr., Roriz, Mélanie, Rosa-Calatrava, Manuel, Rose, Michael, Rosenberger, Dorothea, Rossanese, Andrea, Rossetti, Matteo, Rossignol, Bénédicte, Rossignol, Patrick, Rousset, Stella, Roy, Carine, Roze, Benoît, Russell, Clark D., Ryan, Maria, Ryan, Maeve, Ryckaert, Steffi, Holten, Aleksander Rygh, Saba, Isabela, Sadat, Musharaf, Sahraei, Valla, Saint-Gilles, Maximilien, Sakiyalak, Pranya, Salazar, Leonardo, Sales, Gabriele, Sallaberry, Stéphane, Gandonniere, Charlotte Salmon, Salvator, Hélène, Sanchez, Olivier, Sanchez, Emely, Sanchez-Miralles, Angel, Sancho-Shimizu, Vanessa, Sandhu, Gyan, Sandhu, Zulfiqar, Sandrine, Pierre-François, Sandulescu, Oana, Santos, Marlene, Sarfo-Mensah, Shirley, Sarmento Banheiro, Bruno, Sarmiento, Iam Claire E., Sarton, Benjamin, Satyapriya, Sree, Satyawati, Rumaisah, Saviciute, Egle, Savvidou, Parthena, Saw, Yen Tsen, Schaffer, Justin, Schermer, Tjard, Scherpereel, Arnaud, Schneider, Marion, Schroll, Stephan, Schwameis, Michael, Scicluna, Brendan, Scott, Janet T., Scott-Brown, James, Sedillot, Nicholas, Seitz, Tamara, Selvarajoo, Mageswari, Semaille, Caroline, Semple, Malcolm G., Senian, Rasidah Bt, Senneville, Eric, Sepulveda, Claudia, Sequeira, Filipa, Sequeira, Tânia, Neto, Ary Serpa, Balazote, Pablo Serrano, Shadowitz, Ellen, Shahidan, Syamin Asyraf, Shamsah, Mohammad, Sharjeel, Shaikh, Sharma, Pratima, Shaw, Catherine A., Shaw, Victoria, Sheenan, John Robert, Shi, Haixia, Shime, Nobuaki, Shimizu, Keiki, Shrapnel, Sally, Shum, Hoi Ping, Mohammed, Nassima Si, Siang, Ng Yong, Sibiude, Jeanne, Siddiqui, Atif, Sigfrid, Louise, Sillaots, Piret, Silva, Catarina, Silva, Rogério, Silva, Maria Joao, Lim Heng, Benedict Sim, Sin, Wai Ching, Singh, Punam, Singh, Budha Charan, Sitompul, Pompini Agustina, Sivam, Karisha, Skogen, Vegard, Smith, Sue, Smood, Benjamin, Smyth, Coilin, Smyth, Michelle, Snacken, Morgane, So, Dominic, Soh, Tze Vee, Solomon, Joshua, Solomon, Tom, Somers, Emily, Sommet, Agnès, Song, Rima, Song, Myung Jin, Song, Tae, Chia, Jack Song, Sonntagbauer, Michael, Soom, Azlan Mat, Sotto, Albert, Soum, Edouard, Sousa, Marta, Sousa, Ana Chora, Uva, Maria Sousa, Souza-Dantas, Vicente, Sperry, Alexandra, Spinuzza, Elisabetta, Sriskandan, Shiranee, Stabler, Sarah, Staudinger, Thomas, Stecher, Stephanie-Susanne, Steinsvik, Trude, Stienstra, Ymkje, Stiksrud, Birgitte, Stolz, Eva, Stone, Amy, Streinu-Cercel, Adrian, Streinu-Cercel, Anca, Stuart, Ami, Stuart, David, Su, Richa, Suen, Jacky Y., Suen, Gabriel, Sukumar, Prasanth, Sultana, Asfia, Summers, Charlotte, Supic, Dubravka, Suppiah, Deepashankari, Surovcová, Magdalena, Syahrin, Sarah, Syrigos, Konstantinos, Sztajnbok, Jaques, Szuldrzynski, Konstanty, Tabrizi, Shirin, Taccone, Fabio S., Tagherset, Lysa, Taib, Shahdattul Mawarni, Taleb, Sara, Talsma, Jelmer, Tampubolon, Maria Lawrensia, Tan, Kim Keat, Tan, Yan Chyi, Tanaka, Hiroyuki, Tanaka, Taku, Taniguchi, Hayato, Tardivon, Coralie, Tattevin, Pierre, Taufik, M. Azhari, Tawfik, Hassan, Tedder, Richard S., Tee, Tze Yuan, Teixeira, João, Tejada, Sofia, Tellier, Marie-Capucine, Teoh, Sze Kye, Teotonio, Vanessa, Téoulé, François, Terpstra, Pleun, Terrier, Olivier, Terzi, Nicolas, Tessier-Grenier, Hubert, Tey, Adrian, Mohd Thabit, Alif Adlan, Tham, Zhang Duan, Thangavelu, Suvintheran, Theron, Elmi, Thibault, Vincent, Thiberville, Simon-Djamel, Thill, Benoît, Thirumanickam, Jananee, Thompson, Shaun, Thomson, David, Thomson, Emma C., Thorpe, Mathew, Thanga Thurai, Surain Raaj, Thwaites, Ryan S., Tierney, Paul, Tieroshyn, Vadim, Timsit, Jean-François, Tissot, Noémie, Toal, Fiona, Yang Toh, Jordan Zhien, Toki, Maria, Tonby, Kristian, Tonnii, Sia Loong, Torre, Marta, Torres, Margarida, Torres, Antoni, Torres-Zevallos, Hernando, Towers, Michael, Trapani, Tony, Trioux, Théo, Tromeur, Cécile, Trontzas, Ioannis, Trouillon, Tiffany, Truong, Jeanne, Tual, Christelle, Tubiana, Sarah, Tuite, Helen, Turgeon, Alexis F., Turmel, Jean-Marie, Turtle, Lance C.W., Tveita, Anders, Twardowski, Pawel, Uchiyama, Makoto, Udy, Andrew, Ullrich, Roman, Uribe, Alberto, Usman, Asad, Uyeki, Timothy M., Vajdovics, Cristinava, Val-Flores, Luís, Valran, Amélie, Van de Velde, Stijn, van den Berge, Marcel, Van der Feltz, Machteld, van der Palen, Job, van der Valk, Paul, Van Der Vekens, Nicky, Van der Voort, Peter, Van Der Werf, Sylvie, van Gulik, Laura, Van Hattem, Jarne, van Netten, Carolien, van Someren Gréve, Frank, van Veen, Ilonka, Van Willigen, Hugo, Vanel, Noémie, Vanoverschelde, Henk, Varghese, Pooja, Varrone, Michael, Vasudayan, Shoban Raj, Vauchy, Charline, Veeran, Shaminee, Veislinger, Aurélie, Vencken, Sebastian, Ventura, Sara, Verbon, Annelies, Vidal, José Ernesto, Vieira, César, Villanueva, Joy Ann, Villar, Judit, Villeneuve, Pierre-Marc, Villoldo, Andrea, Visseaux, Benoit, Visser, Hannah, Vitiello, Chiara, Vonkeman, Harald, Vuotto, Fanny, Wahab, Noor Hidayu, Wahab, Suhaila Abdul, Wahid, Nadirah Abdul, Wainstein, Marina, Walsh, Laura, Wang, Chih-Hsien, Webb, Steve, Wei, Jia, Weil, Katharina, Wen, Tan Pei, Wesselius, Sanne, Wham, Murray, Whelan, Bryan, White, Nicole, Wicky, Paul Henri, Wiedemann, Aurélie, Wijaya, Surya Otto, Wille, Keith, Willems, Sue, Williams, Bailey, Williams, Virginie, Williams, Patricia J., Wils, Evert-Jan, Wittman, Jessica, Wong, Calvin, Wong, Xin Ci, Wong, Yew Sing, Wong, Teck Fung, Xian, Gan Ee, Xian, Lim Saio, Kuan, Pei Xuan, Xynogalas, Ioannis, Binti Mohd Yakop, Siti Rohani, Yamazaki, Masaki, Yarad, Elizabeth, Yazdanpanah, Yazdan, Liang Hing, Nicholas Yee, Yelnik, Cécile, Yeoh, Chian Hui, Yerkovich, Stephanie, Yokoyama, Toshiki, Yonis, Hodane, Yousif, Obada, Zaaqoq, Akram, Zabbe, Marion, Zacharowski, Kai, Zahid, Masliza, Zahran, Maram, Binti Zaidan, Nor Zaila, Zambon, Maria, Zambrano, Miguel, Zanella, Alberto, Zaynah, Nurul, Zayyad, Hiba, Zoufaly, Alexander, Zucman, David, Griffee, Matthew J., Bozza, Patricia T., Eddington, Devin P., Fanning, Jonathon P., Alexander, Peta M.A., and Fraser, John

Published
2023
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18. Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial

Author

Aardenburg-van Huisstede, Astrid, Ammerlaan, Heidi S.M., Boersma, Willem G., Bonten, Marc J.M., van den Bosch, Maurice A.A.J., Brinkman, Kees, Bruijning-Verhagen, Patricia C.J., van Crevel, Reinout, Delsing, Corine, ten Doesschaten, Thijs, Dofferhoff, Anton S.M., Duijkers, Ruud, Fohse, Konstantin, Grobusch, Martin P., Groenwold, Rolf H.H., de Haas, Corine, Hassing, Robert-Jan, de Hoog, Marieke L.A., Hoogerwerf, Jacobien J., Huijts, Susanne M., van Hylckama-Vlieg, Astrid, Jong, Eefje, de Jong, Hanna K., Knap, Martijn, Koekenbier, Eva L., Koenders, Michael, Kouijzer, Ilse J.E., Kramer, Henk, van de Laar, Roel, Lalmohamed, Arief, Lensen, Karel-Jan D.F., Lijfering, Willem M., van de Maat, Josephine S., Magdelijns, Fabienne, Meek, Bob, Middelburg, Rutger A., Moeniralam, Hazra S., Mooijaart, Simon P., van Munster, Barbara C., Netea, Mihai G., van Nieuwkoop, Cees, ten Oever, Jaap, Oosterheert, Jan Jelrik, Goossens, Marc Padros, Peters, Vincent, Postma, Douwe F., Pouw, Niels, Reesink, Herre J., de Regt, Marieke J.A., van der Reijden, Anneli C.J., Rosendaal, Frits R., Schaakxs, R., Slieker, Kitty, Slingerland, Robbert J., van Sluis, Nicolette L.J., Stehouwer, Coen D.A., van de Veerdonk, Frank, Verbon, Annelies, van Werkhoven, C.H. (Henri), van de Wijgert, Janneke H.H., and Werkhoven, C.H. (Henri) van

Published
2023
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19. External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Author

Abela, I., Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Bernasconi, E., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Hachfeld, A., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Jackson-Perry, D., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Kusejko, K., Labhardt, N., Leuzinger, K., de Tejada B, Martinez, Marzolini, C., Metzner, K.J., Müller, N., Nemeth, J., Nicca, D., Notter, J., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Salazar-Vizcaya, L., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Wandeler, G., Weisser, M., Yerly, S., van der Valk, M., Geerlings, S.E., Goorhuis, A., Harris, V.C., Hovius, J.W., Lempkes, B., Nellen, F.J.B., van der Poll, T., Prins, J.M., Spoorenberg, V., van Vugt, M., Wiersinga, W.J., Wit, F.W.M.N., Bruins, C., van Eden, J., Hylkema-van den Bout, I.J., van Hes, A.M.H., Pijnappel, F.J.J., Smalhout, S.Y., Weijsenfeld, A.M., Back, N.K.T., Berkhout, B., Cornelissen, M.T.E., van Houdt, R., Jonges, M., Jurriaans, S., Schinkel, C.J., Wolthers, K.C., Zaaijer, H.L., Peters, E.J.G., van Agtmael, M.A., Autar, R.S., Bomers, M., Sigaloff, K.C.E., Heitmuller, M., Laan, L.M., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., van Arkel, A., Stohr, J., Wintermans, B., Pronk, M.J.H., Ammerlaan, H.S.M., de Munnik, E.S., Deiman, B., Jansz, A.R., Scharnhorst, V., Tjhie, J., Wegdam, M.C.A., van Eeden, A., Hoornenborg, E., Nellen, J., Alers, W., Elsenburg, L.J.M., Nobel, H., van Kasteren, M.E.E., Berrevoets, M.A.H., Brouwer, A.E., de Kruijf-van de Wiel, B.A.F.M., Adams, A., Rijkevoorsel, M. Pawels-van, Buiting, A.G.M., Murck, J.L., Rokx, C., Anas, A.A., Bax, H.I., van Gorp, E.C.M., de Mendonça Melo, M., van Nood, E., Nouwen, J.L., Rijnders, B.J.A., Schurink, C.A.M., Slobbe, L., de Vries-Sluijs, T.E.M.S., Bassant, N., van Beek, J.E.A., Vriesde, M., van Zonneveld, L.M., de Groot, J., van Kampen, J.J.A., Koopmans, M.P.G., Rahamat-Langendoen, J.C., Branger, J., Douma, R.A., Cents-Bosma, A.S., Duijf-van de Ven, C.J.H.M., Schippers, E.F., van Nieuwkoop, C., Geilings, J., van Winden, S., van der Hut, G., van Burgel, N.D., Leyten, E.M.S., Gelinck, L.B.S., Mollema, F., Wildenbeest, G.S., Nguyen, T., Groeneveld, P.H.P., Bouwhuis, J.W., Lammers, A.J.J., van Hulzen, A.G.W., Kraan, S., Kruiper, M.S.M., van der Bliek, G.L., Bor, P.C.J., Debast, S.B., Wagenvoort, G.H.J., Roukens, A.H.E., de Boer, M.G.J., Jolink, H., Lambregts, M.M.C., Scheper, H., Dorama, W., van Holten, N., Claas, E.C.J., Wessels, E., Hollander, J.G. den, El Moussaoui, R., Pogany, K., Brouwer, C.J., Heida-Peters, D., Mulder, E., Smit, J.V., Struik-Kalkman, D., van Niekerk, T., Pontesilli, O., van Tienen, C., Lowe, S.H., Lashof, A.M.L. Oude, Posthouwer, D., van Wolfswinkel, M.E., Ackens, R.P., Burgers, K., Elasri, M., Schippers, J., Havenith, T.R.A., van Loo, M., van Vonderen, M.G.A., Kampschreur, L.M., van Broekhuizen, M.C., S, Faber, Al Moujahid, A., Kootstra, G.J., Delsing, C.E., van der Burg-van de Plas, M., Scheiberlich, L., Kortmann, W., van Twillert, G., Renckens, R., Wagenaar, J., Ruiter-Pronk, D., van Truijen-Oud, F.A., Stuart, J.W.T. Cohen, Hoogewerf, M., Rozemeijer, W., Sinnige, J.C., Brinkman, K., van den Berk, G.E.L., Lettinga, K.D., de Regt, M., Schouten, W.E.M., Stalenhoef, J.E., Veenstra, J., Vrouenraets, S.M.E., Blaauw, H., Geerders, G.F., Kleene, M.J., Knapen, M., Kok, M., van der Meché, I.B., Toonen, A.J.M., Wijnands, S., Wttewaal, E., Kwa, D., van de Laar, T.J.W., van Crevel, R., van Aerde, K., Dofferhoff, A.S.M., Henriet, S.S.V., Hofstede, H.J.M. ter, Hoogerwerf, J., Richel, O., Albers, M., Grintjes-Huisman, K.J.T., de Haan, M., Marneef, M., McCall, M., Burger, D., Gisolf, E.H., Claassen, M., Hassing, R.J., Beest, G. ter, van Bentum, P.H.M., Gelling, M., Neijland, Y., Swanink, C.M.A., Velderman, M. Klein, van Lelyveld, S.F.L., Soetekouw, R., van der Prijt, L.M.M., van der Swaluw, J., Kalpoe, J.S., Wagemakers, A., Vahidnia, A., Lauw, F.N., Verhagen, D.W.M., van Wijk, M., Bierman, W.F.W., Bakker, M., van Bentum, R.A., van den Boomgaard, M.A., Kleinnijenhuis, J., Kloeze, E., Middel, A., Postma, D.F., Schenk, H.M., Stienstra, Y., Wouthuyzen-Bakker, M., Boonstra, A., de Jonge, H., Maerman, M.M.M., de Weerd, D.A., van Eije, K.J., Knoester, M., van Leer-Buter, C.C., Niesters, H.G.M., T.Mudrikova, Barth, R.E., Bruns, A.H.W., Ellerbroek, P.M., Hensgens, M.P.M., Oosterheert, J.J., Schadd, E.M., Verbon, A., van Welzen, B.J., Berends, H., Santen, B.M.G. Griffioen-van, de Kroon, I., Lunel, F.M. Verduyn, Wensing, A.M.J., Zaheri, S., Boyd, A.C., Bezemer, D.O., van Sighem, A.I., Smit, C., Hillebregt, M.M.J., Woudstra, T.J., Rutkens, T., Bergsma, D., Brétin, N.M., Lelivelt, K.J., van de Sande, L., van der Vliet, K.M. Visser.S.T., Paling, F., de Groot-Berndsen, L.G.M., van den Akker, M., Alexander, R., Bakker, Y., El Berkaoui, A., Bezemer-Goedhart, M., Djoechro, E.A., Groters, M., Koster, L.E., Lodewijk, C.R.E., Lucas, E.G.A., Munjishvili, L., Peeck, B.M., Ree, C.M.J., Regtop, R., van Rijk, A.F., Ruijs-Tiggelman, Y.M.C., Schnörr, P.P., Schoorl, M.J.C., Tuijn, E.M., Veenenberg, D.P., Witte, E.C.M., Bretin, N.M., Karpov, I., Losso, M., Lundgren, J., Rockstroh, J., Aho, I., Rasmussen, L.D., Novak, P., Pradier, C., Chkhartishvili, N., Matulionyte, R., Oprea, C., Kowalska, J.D., Begovac, J., Miró, J.M., Guaraldi, G., Paredes, R., Peters, L., Larsen, J.F., Neesgaard, B., Jaschinski, N., Fursa, O., Raben, D., Kristensen, D., Fischer, A.H., Jensen, S.K., Elsing, T.W., Gardizi, M., Mocroft, A., Phillips, A., Reekie, J., Cozzi-Lepri, A., Pelchen-Matthews, A., Roen, A., Tusch, E.S., Bannister, W., Bellecave, P., Blanco, P., Bonnet, F., Bouchet, S., Breilh, D., Cazanave, C., Desjardin, S., Gaborieau, V., Gimbert, A., Hessamfar, M., Lacaze-Buzy, L., Lacoste, D., Lafon, M.E., Lazaro, E., Leleux, O., Le Marec, F., Le Moal, G., Malvy, D., Marchand, L., Mercié, P., Neau, D., Pellegrin, I., Perrier, A., Petrov-Sanchez, V., Vareil, M.O., Wittkop, L., Bernard, N., Chaussade, D. Bronnimann H., Dondia, D., Duffau, P., Faure, I., Morlat, P., Mériglier, E., Paccalin, F., Riebero, E., Rivoisy, C., Vandenhende, M.A., Barthod, L., Dauchy, F.A., Desclaux, A., Ducours, M., Dutronc, H., Duvignaud, A., Leitao, J., Lescure, M., Nguyen, D., Pistone, T., Puges, M., Wirth, G., Courtault, C., Camou, F., Greib, C., Pellegrin, J.L., Rivière, E., Viallard, J.F., Imbert, Y., Thierry-Mieg, M., Rispal, P., Caubet, O., Ferrand, H., Tchamgoué, S., Farbos, S., Wille, H., Andre, K., Caunegre, L., Gerard, Y., Osorio-Perez, F., Chossat, I., Iles, G., Labasse-Depis, M., Lacassin, F., Barret, A., Castan, B., Koffi, J., Rouanes, N., Saunier, A., Zabbe, J.B., Dumondin, G., Beraud, G., Catroux, M., Garcia, M., Giraud, V., Martellosio, J.P., Roblot, F., Pasdeloup, T., Riché, A., Grosset, M., Males, S., Bell, C. Ngo, Carpentier, C., Bellecave, Virology P., Tumiotto, C., Miremeont-Salamé, G., Arma, D., Arnou, G., Blaizeau, M.J., Camps, P., Decoin, M., Delveaux, S., Diarra, F., Gabrea, L., Lawson-Ayayi, S., Lenaud, E., Plainchamps, D., Pougetoux, A., Uwamaliya, B., Zara, K., Conte, V., Gapillout, M., Surial, Bernard, Ramírez Mena, Adrià, Roumet, Marie, Limacher, Andreas, Smit, Colette, Leleux, Olivier, Mocroft, Amanda, van der Valk, Marc, Bonnet, Fabrice, Peters, Lars, Rockstroh, Jürgen K., Günthard, Huldrych F., Berzigotti, Annalisa, Rauch, Andri, and Wandeler, Gilles

Published
2023
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20. Adherence to and usefulness of the national treatment guideline for urinary tract infections (UTI) in a risk area

Author

A. A. van Driel, M. Mulder, E. E. Stobberingh, and A. Verbon

Subjects
Treatment guidelines, Empirical prescription, Antibiotic resistance, Uncomplicated urine tract infections, Community-acquired, Agriculture, Medicine (General), R5-920
Abstract

Abstract Background To optimize antibiotic treatment and decrease antibiotic resistance, national treatment guidelines are available for urinary tract infections (UTIs) in general practice. The usefulness of these guidelines in risk areas for antimicrobial resistance such as cross border regions or areas with dense agriculture, is unknown. Methods Midstream urine samples from women with symptoms of acute UTI visiting general practitioners (GPs) in the Westland area, a dense agriculture area, were microbiologically analysed, and patient characteristics, symptoms, previous and present antibiotic treatment were collected. The National Nivel data were used as reference for antibiotic resistance. Results Of 310 women with symptoms of uncomplicated UTI, 247 (80%) had a culture proven E. coli UTI. Empirical antibiotic therapy was prescribed to 148 patients (48%) in total; in 7% of women with a negative and 52% with a positive urine culture. Having more than one symptom was associated with the prescription of antibiotics; travel history or previous antibiotic use for UTI were not. The isolated uropathogens were susceptible to the empiric antibiotic therapy in 98% of patients. Resistance to co-amoxiclav was higher (22%) than reported in the national data of 2004 (12%), 2009 (13%) and 2014 (9%), as was the prevalence of extended spectrum β-lactamase (ESBL): 3.4% in our study versus 0.1%, 1% and 2.2% in the national data respectively. Conclusion The presence of environmental and socio-demographic risk factors for antibiotic resistance did not influence the empiric choice nor susceptibility for antibiotics advised by the national guidelines in women with uncomplicated UTI.

Published
2022
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23. Liver steatosis is prevalent in lean people living with HIV and associated with exposure to antiretroviral treatment – a cross-sectional study

Author

Van Eekeren, Louise E, primary, Vadaq, Nadira, additional, Vos, Wilhelm A J W, additional, Blaauw, Marc J T, additional, Groenendijk, Albert L, additional, Van Lunzen, Jan, additional, Stalenhoef, Janneke E, additional, Berrevoets, Marvin A H, additional, Verbon, Annelies, additional, Weijers, Gert, additional, Netea, Mihai G, additional, Van Der Ven, André J A M, additional, De Mast, Quirijn, additional, Joosten, Leo A B, additional, and Tjwa, Eric T T L, additional

Published
2024
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24. The development and implementation of a guideline-based clinical decision support system to improve empirical antibiotic prescribing

Author

H. Akhloufi, H. van der Sijs, D. C. Melles, C. P. van der Hoeven, M. Vogel, J. W. Mouton, and A. Verbon

Subjects
Clinical decision support system, Reporting framework, Antibacterial, Antibiotic stewardship, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background To describe and evaluate a clinical decision support system (CDSS) for empirical antibiotic therapy using a systematic framework. Methods A reporting framework for behavior change intervention implementation was used, which includes several domains: development, evaluation and implementation. Within the development domain a description is given of the engagement of stakeholders, a rationale for how the CDSS may influence antibiotic prescribing and a detailed outline of how the system was developed. Within the evaluation domain a technical validation is performed and the interaction between potential users and the CDSS is analyzed. Within the domain of implementation a description is given on how the CDSS was tested in the real world and the strategies that were used for implementation and adoption of the CDSS. Results Development: a CDSS was developed, with the involvement of stakeholders, to assist empirical antibiotic prescribing by physicians. Evaluation: Technical problems were determined during the validation process and corrected in a new CDSS version. A usability study was performed to assess problems in the system-user interaction. Implementation: In 114 patients the antibiotic advice that was generated by the CDSS was followed. For 54 patients the recommendations were not adhered to. Conclusions This study describes the development and validation of a CDSS for empirical antibiotic therapy and shows the usefulness of the systematic framework for reporting CDSS interventions. In addition it shows that CDSS recommendations are not always adhered to which is associated with incorrect use of the system.

Published
2022
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25. Psychiatric symptoms in people living with HIV: prevalences, interactions and consequences

Author

E. M. Meeder, M. Blaauw, L. E. van Eekeren, A. Groenendijk, W. A. Vos, Q. de Mast, W. L. Blok, A. Verbon, M. A. Berrevoets, J. van Lunzen, L. Joosten, M. Netea, V. Matzaraki, A. J. van der Ven, and A. F. Schellekens

Subjects
Psychiatry, RC435-571
Abstract

Introduction People living with HIV (PLHIV) experience higher levels of mental health issues compared to the general population. Especially depression, anxiety, impulsivity and substance use occur frequently in PLHIV. This is thought to have important consequences for quality of life, sexual risk behaviour and antiretroviral treatment (ART) adherence. Both in PLHIV as well as in the general population, divergent psychiatric symptoms often co-occur, and influence one another. Objectives To assess the interrelatedness of psychiatric symptoms and their potential consequences in PLHIV. Methods Data from 1615 outpatient PLHIV using suppressive ART from the 2000HIV study (NCT03994835) were analysed. Participants reported on the severity of substance use (MATE-Q), depression and anxiety (HADS), impulsivity (BIS-11), quality of life (EQ-5D-5L), ART adherence (MASS-8) and sexual risk behaviour. For these variables, prevalence rates and mean scores were calculated. After binarizing the data, an Ising network model was constructed. Using this network, interrelations between psychiatric symptoms were assessed, the centrality of symptoms was estimated and connections with clinical consequences were explored. Results In our cohort of PLHIV, the increased prevalence of substance use was most pronounced, as shown by a prevalence rate of 28.7% for smoking, 13.6% for cannabis use, 11.1% for heavy alcohol drinking and 9.2% for ecstasy use in the past month. The network analysis revealed that symptoms of depression and anxiety were most strongly interrelated. The depressive symptom “feeling slowed down” was one of the most central symptoms, and was most strongly connected with quality of life. Substance use was associated with a higher occurrence of sexually transmitted diseases, and this relationship was mediated by a higher number of sexual partners. Notably, ART adherence did not display any connections with depression, anxiety, impulsivity or substance use. Image: Conclusions The high occurrence of substance use and its link with sexual risk behaviour, emphasizes it’s role as a potential target for prevention of HIV transmission. Contrary to general assumption, psychiatric symptoms are not associated with lower levels of ART adherence in our cohort. Treatment of depression in PLHIV might be improved by focussing on the symptom of feeling slowed down, since this symptom was most strongly connected with quality of life. Disclosure of Interest E. Meeder Grant / Research support from: ViiV Healthcare, M. Blaauw: None Declared, L. van Eekeren: None Declared, A. Groenendijk: None Declared, W. Vos: None Declared, Q. de Mast: None Declared, W. Blok: None Declared, A. Verbon: None Declared, M. Berrevoets: None Declared, J. van Lunzen Employee of: ViiV Healthcare, L. Joosten: None Declared, M. Netea: None Declared, V. Matzaraki: None Declared, A. van der Ven: None Declared, A. Schellekens: None Declared

Published
2023
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28. In Vitro and In Vivo Wide-Spectrum Dual Antimycetomal Activity of Eight Essential Oils Coupled with Chemical Composition and Metabolomic Profiling.

Author

Abd Algaffar, Shereen O., Satyal, Prabodh, Ashmawy, Naglaa S., Verbon, Annelies, van de Sande, Wendy W. J., and Khalid, Sami A.

Subjects
IN vivo toxicity testing, NUTMEG tree, GREATER wax moth, DRUG discovery, ESSENTIAL oils, GAS chromatography/Mass spectrometry (GC-MS)
Abstract

Mycetoma, a neglected infection of subcutaneous tissues, poses a significant health burden, especially in tropical regions. It is caused by fungal (eumycetoma) and bacterial (actinomycetoma) pathogens, with current treatments often providing unsatisfactory outcomes. This study aims to discover novel broad-spectrum antimicrobial agents to circumvent the lengthy and costly diagnostic procedures. Eight essential oils (EOs) from the roots and aerial parts of Geigeria alata, Lavandula angustifolia, Melaleuca alternifolia, Myristica fragrans, Pimpinella anisum, Syzigum aromaticum, and Thymus vulgaris were prepared using steam distillation. The in vitro antimycetomal activity against Madurella mycetomatis and Actinomadura madurae strains was assessed using resazurin assays. The chemical compositions of the EOs were analyzed using gas chromatography and mass spectrometry (GC–MS). Promising EOs underwent further in vivo toxicity and efficacy testing in Galleria mellonella larvae models. EOs of G. alata roots, M. fragrans, P. anisum, S. aromaticum, and T. vulgaris showed wide-spectrum dual in vitro antimycetomal activity against all tested strains, with minimum inhibitory concentrations (MICs) ranging from 0.004 to 0.125% v/v. G. alata aerial parts and L. angustifolia EOs demonstrated activity predominantly against A. madurae, while M. alternifolia EO did not inhibit any tested strains. M. fragrans and P. anisum EOs significantly enhanced the survival of M. mycetomatis-infected larvae without inducing toxicity in uninfected larvae. Notably, P. anisum EO tended to enhance the survival of A. madurae-infected larvae, ranking it as the most promising EO among those tested. The investigated EOs, particularly P. anisum, exhibited promising broad-spectrum antimycetomal activity against fungal and bacterial pathogens responsible for mycetoma. These findings highlight the potential of essential oils as a basis for developing novel antimycetomal agents, offering hope for improved treatment strategies for this neglected disease. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Characteristics and short- and long-term direct medical costs among adults with timely and delayed presentation for HIV care in the Netherlands.

Author

Stephanie Popping, Lisbeth Versteegh, Brooke E Nichols, David A M C van de Vijver, Ard van Sighem, Peter Reiss, Suzanne Geerlings, Charles A B Boucher, Annelies Verbon, and ATHENA observational cohort

Subjects
Medicine, Science
Abstract

IntroductionIn Europe, half of people living with HIV (PLWH) present late to care, with associated higher morbidity and mortality. This study aims to assess short- and long-term costs of HIV-care based on time of presentation and identify other factors contributing to higher costs in the first and fifth year after antiretroviral therapy (ART) initiation.Material and methodsWe included ATHENA cohort data which prospectively includes 98% of PLWH in the Netherlands. PLWH who initiated ART in 2013 were included and followed over five years. PLWH were divided in three categories based on CD4 cell-count at time of ART initiation: timely presentation (CD4>350cells/μL), late presentation (CD4 200-350cells/μL or >350cells/μL with AIDS-defining illness) and very late presentation (CD4ResultsFrom 1,296 PLWH, 273 (21%) presented late and 179 (14%) very late. Nearly half of those who entered HIV-care in a very late stage were of non-Dutch origin, with 21% originating from sub-Saharan Africa. The mean cost per patient in the first year was €12,902 (SD€11,098), of which about two-thirds due to ART (€8,250 (SD€3,142)). ART costs in the first and fifth year were comparable regardless of time of presentation. During the first year on treatment, non-ART medication costs were substantially higher among those with late presentation (€4,749 (SD€8,009)) and very late presentation (€15,886 (SD€ 21,834)), compared with timely presentation (€2,407(SD€4,511)). Higher non-ART costs were attributable to hospitalization and co-medication. The total non-ART costs incurred across five years on treatment were 56% and 246% higher for late and very late presentation respectively as compared to timely presentation.ConclusionVery late presentation is associated with substantial costs, with non-ART costs nearly seven times higher than for those presenting timely. Hospitalization and co-medication costs are likely to continue to drive higher costs for individuals with late presentation into the future. Programs that identify individuals earlier will therefore likely provide significant short- and long-term health cost savings.

Published
2023
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30. The 2000HIV study: Design, multi-omics methods and participant characteristics

Author

Wilhelm A. J. W. Vos, Albert L. Groenendijk, Marc J. T. Blaauw, Louise E. van Eekeren, Adriana Navas, Maartje C. P. Cleophas, Nadira Vadaq, Vasiliki Matzaraki, Jéssica C. dos Santos, Elise M. G. Meeder, Janeri Fröberg, Gert Weijers, Yue Zhang, Jingyuan Fu, Rob ter Horst, Christoph Bock, Rainer Knoll, Anna C. Aschenbrenner, Joachim Schultze, Linos Vanderkerckhove, Talent Hwandih, Elizabeth R. Wonderlich, Sai V. Vemula, Mike van der Kolk, Sterre C. P. de Vet, Willem L. Blok, Kees Brinkman, Casper Rokx, Arnt F. A. Schellekens, Quirijn de Mast, Leo A. B. Joosten, Marvin A. H. Berrevoets, Janneke E. Stalenhoef, Annelies Verbon, Jan van Lunzen, Mihai G. Netea, and Andre J. A. M. van der Ven

Subjects
multi-omics, HIV-1, non-AIDS comorbidities, cardiovascular disease, hepatic disease, COVID-19, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundEven during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets.MethodsThe 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort.ResultsOverall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine.ConclusionThe 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV.

Published
2022
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31. Improving indicator-condition guided testing for HIV in the hospital setting (PROTEST 2·0): A multicenter, interrupted time-series analysis

Author

Saskia J. Bogers, Maarten F. Schim van der Loeff, Anders Boyd, Udi Davidovich, Marc van der Valk, Kees Brinkman, Kim Sigaloff, Judith Branger, Nejma Bokhizzou, Godelieve J. de Bree, Peter Reiss, Jan E.A.M. van Bergen, Suzanne E. Geerlings, T. van Benthem, D. Bons, G.J. de Bree, P. Brokx, U. Davidovich, F. Deug, S.E. Geerlings, M. Heidenrijk, E. Hoornenborg, M. Prins, P. Reiss, A. van Sighem, M. van der Valk, J. de Wit, W. Zuilhof, N. Schat, D. Smith, M. van Agtmael, J. Ananworanich, D. Van de Beek, G.E.L. van den Berk, D. Bezemer, A. van Bijnen, J.P. Bil, W.L. Blok, S.J. Bogers, M. Bomers, A. Boyd, W. Brokking, D. Burger, K. Brinkman, N. Brinkman, M. de Bruin, S. Bruisten, L. Coyer, R. van Crevel, M. Dijkstra, Y.T. van Duijnhoven, A. van Eeden, L. Elsenburg, M.A.M. van den Elshout, E. Ersan, P.E.V. Felipa, T.B.H. Geijtenbeek, J. van Gool, A. Goorhuis, M. Groot, C.A. Hankins, A. Heijnen, M.M.J Hillebregt, M. Hommenga, J.W. Hovius, Y. Janssen, K. de Jong, V. Jongen, N.A. Kootstra, R.A. Koup, F.P. Kroon, T.J.W. van de Laar, F. Lauw, M.M. van Leeuwen, K. Lettinga, I. Linde, D.S.E. Loomans, I.M. van der Lubben, J.T. van der Meer, T. Mouhebati, B.J. Mulder, J. Mulder, F.J. Nellen, A. Nijsters, H. Nobel, E.L.M. Op de Coul, E. Peters, I.S. Peters, T. van der Poll, O. Ratmann, C. Rokx, M.F. Schim van der Loeff, W.E.M. Schouten, J. Schouten, J. Veenstra, A. Verbon, F. Verdult, J. de Vocht, H.J. de Vries, S. Vrouenraets, M. van Vugt, W.J. Wiersinga, F.W. Wit, L.R. Woittiez, S. Zaheri, P. Zantkuijl, A. Żakowicz, M.C. van Zelm, and H.M.L. Zimmermann

Subjects
HIV, HIV testing, Indicator condition, Tuberculosis, Cervical carcinoma, Cervical dysplasia, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Indicator-condition (IC) guided HIV testing is a feasible and cost-effective strategy to identify undiagnosed people living with HIV (PLHIV), but remains insufficiently implemented. We aimed to promote IC-guided HIV testing in seven ICs. Methods: Relevant departments in five hospitals of the Amsterdam region participated. HIV testing among adult patients without known HIV infection but with an IC was assessed using electronic health records during pre-intervention (January 2015–June 2020) and intervention (July 2020–June 2021) periods. The multifaceted intervention included audit and feedback. The primary endpoint was HIV testing ≤3 months before or after IC diagnosis and the effect of the intervention was evaluated using segmented Poisson regression. Findings: Data from 7986 patients were included, of whom 6730 (84·3%) were diagnosed with an IC in the pre-intervention period and 1256 (15·7%) in the intervention period. The proportion HIV tested ≤3 months before or after IC diagnosis increased from 36.8% to 47.0% (adjusted risk ratio [RR]= 1.16, 95% CI=1.03–1.30, p=0.02). For individual ICs, we observed significant increases in HIV testing among patients with cervical cancer or intraepithelial neoplasia grade 3 (adjusted RR=3.62, 95% CI=1.93–6.79) and peripheral neuropathy (adjusted RR=2.27 95% CI=1.48–3.49), but not the other ICs. Eighteen of 3068 tested patients were HIV positive (0.6%). Interpretation: Overall IC-guided testing improved after the intervention, but not for all ICs. Variations in effect by IC may have been due to variations in implemented developments, but the effect of separate elements could not be assessed. Funding: HIV Transmission Elimination Amsterdam (H-TEAM) initiative, Aidsfonds (grant number: P-42702).

Published
2022
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33. Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Author

Nick Daneman, John Marshall, Vinod Kumar, Aasiyah Rashan, Jérôme Dimet, Sylvain Diamantis, John F Fraser, Dominique Deplanque, Anne Conrad, François Lellouche, Heidi Gruner, Detlef Kindgen-Milles, Agnes Meybeck, Maxime Hentzien, Clotilde Allavena, André Cabié, Firouzé Bani-Sadr, Patrick Rossignol, Arjen M Dondorp, Rashan Haniffa, Harald Vonkeman, Lionel Piroth, Mathieu Blot, Yaseen Arabi, Marie-Pierre Debray, François Angoulvant, Marc Leone, Maria Zambon, Florentia Kaguelidou, Marc Lambert, Olivier Lairez, Tom Solomon, Carrol Gamble, Laura Marsh, David Richardson, Christiana Kartsonaki, Philippe Jouvet, Asgar Rishu, Eman Al Qasim, Rachael Parke, Srinivas Murthy, Alistair Nichol, Calum Semple, Colin McArthur, Gail Carson, Jake Dunning, Laura Merson, Peter Horby, David Maslove, Nadia Malik, Stephen R Knight, Annelies Verbon, Oana Sândulescu, Patrick Archambault, Paul McNally, Marlene Murris, Aurore Bousquet, Kenneth A McLean, Hugues Cordel, Marc Fabre, Laurence Bouillet, Melissa Parker, Xavier Duval, Amanda Corley, James Lee, Kusum Menon, Christian Rabaud, Paul Klenerman, Jean-François Timsit, Jennifer Lee, Nicolas Terzi, Saad Nseir, Gwenhaël Colin, Steve Webb, Kalynn Kennon, Caroline Mudara, Diana Hernández, Yazdan Yazdanpanah, Elias Iosifidis, Emmanuel Roilides, Yi Lin Lee, Pieter Depuydt, Jean-François Payen, Ana Martins, Samreen Ijaz, Meera Chand, Wei Shen Lim, Bruno Levy, Eric D'ortenzio, Jean-Charles Preiser, Pierre Delobel, Claudia Figueiredo-Mello, Jaques Sztajnbok, Ana Freitas Ribeiro, Tiphaine Goulenok, Bronner P Gonçalves, Arnaud Scherpereel, Chloe Donohue, Carlo Giaquinto, Karolina Nowicka, Adrien Auvet, Debby Bogaert, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Merce Jourdain, Anne McCarthy, Todd C Lee, António Mesquita, Sue Smith, Jia Wei, Jenny Lennon, Antoine Khalil, Nathalie Pansu, Victor Fomin, Audrey Barrelet, Christophe Fraser, Daniel Munblit, Robert A Fowler, William Greenhalf, François-Xavier Lescure, Nicolas Carlier, Saye Khoo, Riinu Pius, Lisa Norman, Louise Sigfrid, Sophie Halpin, Clare Jackson, Antonia Ho, Andrew Dagens, Thomas Flament, Julie Mankikian, Romain Basmaci, Peter Openshaw, Mary Copland, Brenda Reeve, William Dechert, Patricia Lizotte, Felwa Bin Humaid, Tom Fletcher, Adrien Lemaignen, Pierre Tattevin, Christelle Delmas, Hélène Espérou, Claire Lévy-Marchal, Olivier Picone, Jeanne Sibiude, Cecile Yelnik, Olivia V Swann, Michelle Girvan, Piero L Olliaro, Beatrice Alex, Benjamin Bach, Alexander J Mentzer, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, Georgios Pollakis, Vanessa Sancho-Shimizu, Shiranee Sriskandan, David Stuart, Charlotte Summers, Ryan S Thwaites, Hayley Hardwick, Wilna Oosthuyzen, Fiona Griffiths, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Marie Connor, Gary Leeming, Ross Hendry, Victoria Shaw, Jade Ghosn, Lucille Blumberg, Nicolas Benech, James Scott-Brown, Odile Launay, Todd Karsies, Yoan Lavie-Badie, Minh Le, Elise Artaud-Macari, Mylène Maillet, Huda Alfoudri, Djura Piersma, Didier Laureillard, Graham S. Cooke, Nicholas Sedillot, Anne-Sophie Boureau, Tony Trapani, Laurent Abel, Samuel Hinton, Sally Shrapnel, Heidi Dalton, Guillaume Martin-Blondel, Valérie Garrait, Isabelle Delacroix, Samantha Lissauer, Malte Kohns Vasconcelos, Oleksa Rewa, Erlina Burhan, Sara Machado, Jean-Benoît Arlet, Raphaël Borie, Kévin Bouiller, Vincent Langlois, Mélanie Roriz, Mical Paul, Vincent Dubée, Erwan L'her, Michael Rose, Luis Felipe Reyes, Anna Beltrame, Stéphanie Fry, Andrew Udy, Laurent Plantier, Jean-Christophe Goffard, Denis Malvy, Nina Jamieson, Irfan Khan, François Dubos, Jean-Sébastien Hulot, Paola Rodari, Paul Campbell, Abigail Beane, Cécile Tromeur, Paul Loubet, Marina Esposito-Farèse, France Mentré, Valérie Gaborieau, Anne-Marie Guerguerian, Cécile Goujard, Vincent Thibault, Rodrigo Díaz, Patricia Gordon, Sadie Kelly, Bertrand Dussol, Simon Forsyth, Marion Schneider, Nathalie Gault, Marielle Buisson, Yves Levy, Prasan Kumar Panda, Marjolein Brusse-Keizer, Carine Roy, Walter Picard, Tom Drake, Paul Tierney, Olivier Sanchez, Antoine Kimmoun, David Thomson, Nathan Peiffer-Smadja, Julien Poissy, Lila Bouadma, Bruno Lina, Maude Bouscambert, Alexandre Gaymard, Gilles Peytavin, Jeremie Guedj, Claire Andrejak, Cedric Laouenan, Anissa Chair, Samira Laribi, Marie-Capucine Tellier, Sandrine Couffin-Cadiergues, Soizic Le Mestre, Ventzislava Petrov-Sanchez, Alpha Diallo, NoéMie Mercier, Sarah Tubiana, Marion Noret, Oriane Puechal, Caroline Semaille, Patrick Imbert, Jonathan Remppis, Emmanuelle Mercier, Rui Pereira, Sylvie Van Der Werf, Waasila Jassat, Arsene Kpangon, Dominique Luton, Sophie Mahy, Pierre-Adrien Bolze, Sarah Moore, Adrienne Chan, Raphael Favory, Daniel Mathieu, Andrea Angheben, Andrea Rossanese, Matthew Hall, Johann Auchabie, Mohammed Quraishi, Katharina Weil, Hanna Renk, Hans Martin Bosse, Christophe Rapp, Vincent Peigne, Tae Song, Dewi Guellec, Mark G. Pritchard, Adrian Streinu-Cercel, Christl A Donnelly, François Goehringer, Elodie Curlier, Catherine Chirouze, Stéphane Jaureguiberry, Ary Serpa Neto, Jose Andres Calvache, Laurent Bitker, Hodane Yonis, Neerusha Kaisbain, Coline Jaud-Fischer, Laurent Mandelbrot, Jérémie Pasquier, Juliette Patrier, Gianluigi Li Bassi, Sheryl Ann Abdukahil, Jia Shyi Loy, Filipe Cardoso, Diptesh Aryal, Polina Bugaeva, Evert-Jan Wils, Stephanie Yerkovich, Julie Chas, Thushan de Silva, Ruth Lyons, Murray Wham, Sara Clohisey, Seán Keating, Thibault Chiarabini, Agnes Sommet, Hugues Aumaître, Sylvie LeGac, Sarah E McDonald, Jeanne Truong, Camille Couffignal, Anne-Hélène Boivin, Timo Brandenburger, Diane Descamps, Tala Al-Dabbous, Mark Joseph, Hwa Jin Cho, Desy Rusmawatiningtyas, Muhammad Rayhan, Christel Arnold-Day, Navy Lolong, Ernita Akmal, Menaldi Rasmin, Daniel Marino, Neurinda Permata Kusumastuti, Stéphane Lasry, Amanda Rojek, Sebastien Preau, Jean-Marie Turmel, Nowneet Kumar Bhat, Cynthia Braga, Pavan Kumar Vecham, Benoit Thill, Karine Faure, Denis Garot, Grégory Corvaisier, Elsa Nyamankolly, Joshua Solomon, Emma Clarke, Patricia Fontela, Eva Geraud, Eva Miranda Marwali, Aria Kekalih, Saptadi Yuliarto, Dyah Kanya Wati, Ivy Cerelia Valerie, Maureen Masha, Jolanta Popielska, Anca Streinu-Cercel, Mohan Dass Pathmanathan, Barbara Wanjiru Citarella, Heidi Jean Dalton, Nurul Najmee Abdulkadir, Lara Absil, Subhash Acharya, Diana Adrião, Younes Ait Tamlihat, Kévin Alexandre, Kazali Enagnon Alidjnou, Nathalie Allou, Rita Alves, Joana Alves Cabrita, Maria Amaral, Nur Amira, Phoebe Ampaw, Séverine Ansart, Sivanesen Anthonidass, Carlos Alexandre Brito, Ardiyan Apriyana, Carolline Araujo, Muhammad Ashraf, Jean Baptiste Assie, Amirul Asyraf, Anika Atique, AM Udara Attanyake, Laurène Azemar, Cecile Azoulay, Delphine Bachelet, Claudine Badr, J. Kenneth Baillie, Nazreen Abu Bakar, Mohanaprasanth Balakrishnan, Valeria Balan, Renata Barbalho, Wendy S. Barclay, Saef Umar Barnett, Marie Bartoli, Joaquín Baruch, Muhammad Fadhli Basri, Jules Bauer, Diego Fernando Rincon, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Marine Beluze, Lionel Eric Benjiman, Dehbia Benkerrou, Delphine Bergeaud, José Luis Sobrino, Giulia Bertoli, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Krishna Bhavsar, Farah Nadiah Bidin, Mohd Nazlin Kamarudin, François Bissuel, Jonathan Bitton, Laetitia Bodenes, Isabela Bolaños, François Bompart, Diogo Borges, Olivier Bouchaud, Sabelline Bouchez, Dounia Bouhmani, Damien Bouhour, Camile Bouisse, Jason Bouziotis, Bianca Boxma, Marielle Boyer-Besseyre, Fernando Augusto Bozza, Axelle Braconnier, Kathy Brickell, Aidan Burrell, Ingrid G Bustos, Denis Butnaru, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Valentine Campana, Pauline Caraux-Paz, Chiara Simona Cardellino, Sofia Cardoso, Filipa Cardoso, Thierry Carmoi, Marie-Christine Carret, François Martin Carrier, Maire-Laure Casanova, Mariana Cascão, José Casimiro, Nidyanara Castanheira, Guylaine Castor-Alexandre, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Minerva Cervantes-Gonzalez, Catherine Chakveatze, Christelle Chantalat Auger, Jean-Marc Chapplain, Anjellica Chen, Matthew Pellan Cheng, Antoine Cheret, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Bernard Cholley, Marie-Charlotte Chopin, Ting Soo Chow, Hiu Jian Chua, Jonathan Chua, Alexandra Coelho, Megan Coles, Pamela Combs, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Emma Costigan, Roxane Courtois, Stéphanie Cousse, Rachel Cregan, Sabine Croonen, Claudina Cruz, Juan Luis Bermúdez, Jaime Cruz Rojo, Paula Custodio, Ana Silva Filipe, Charlene Da Silveira, Juliana Damas, Corinne Daniel, Emmanuelle A Dankwa, Jorge Dantas, Etienne De Montmollin, Rafael Freitas França, Peter de Vries, Jillian Deacon, Alexa Debard, Nathalie DeCastro, Lauren Deconninck, Romain Decours, Eve Defous, Eric Delaveuve, Karen Delavigne, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Mathilde Desvallées, Santi Dewayanti, Pathik Dhanger, André Dias, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Félix Djossou, Annemarie B. Docherty, Maria Donnelly, Céline Dorival, James Joshua Douglas, Nathalie Dournon, Murray Dryden, Claudio Duarte Fonseca, Alexandre Ducancelle, Paul Dunand, Sim Choon Ean, Mohammed El Sanharawi, Brigitte Elharrar, Philippine Eloy, Isabelle Enderle, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Martina Escher, Catarina Espírito Santo, João Estevão, Manuel Etienne, Nadia Ettalhaoui, Mirjam Evers, Isabelle Fabre, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Pedro Faria, Ahmed Farooq, Hanan Fateena, Jorge Fernandes, Marília Andreia Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Bernardo Ferreira, Nicolas Ferriere, Céline Ficko, Clara Flateau, Tatiana Fonseca, Erwan Fourn, Robert A. Fowler, Marcela Vieira Freire, Rostane Gaci, Jean-Charles Gagnard, Yasmin Gani, Noelia García Barrio, Esteban Garcia-Gallo, Louis Gerbaud Morlaes, Nuno Germano, Jess Gibson, Tristan Gigante, Morgane Gilg, Guillermo Giordano, Valérie Gissot, Daniel Glikman, Petr Glybochko, Geraldine Goco, Siri Goepel, Jin Yi Goh, Marie Gominet, Bronner P. Gonçalves, Isabelle Gorenne, Laure Goubert, Pascal Granier, Christopher A. Green, Courtney Greene, Segolène Greffe, Albert Groenendijk, Anja Grosse Lordemann, Yusing Gu, Martin Guego, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Thomas Guimard, Marieke Haalboom, Daniel Haber, Hannah Habraken, Ali Hachemi, Nadir Hadri, Fakhir Haidri, Ansley Hamer, Rebecca Hamidfar, Lim Yuen Han, Kok Wei Hao, Ewen M. Harrison, Lars Heggelund, Astarini Hidayah, Rupert Higgins, Hikombo Hitoto, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Ikram Houas, Catherine L. Hough, Jimmy Ming-Yang Hsu, Arfan Ikram, Hajnal-Gabriela Illes, Hugo Inácio, Yun Sii Ing, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Danielle Jaafar, Salma Jaafoura, Julien Jabot, Pierre Jaquet, Florence Jego, Anilawati Mat Jelani, Ong Yiaw Joe, Cédric Joseph, Swosti Joshi, Dafsah Juzar, Ouifiya Kafif, Thavamany Kaleesvran, Sabina Kali, Muhammad Aisar Kamaluddin, Zul Amali Kamaruddin, Nadiah Kamarudin, Kong Yeow Kang, Pratap Karpayah, Anant Kataria, Kevin Katz, Yvelynne Kelly, Younes Kerroumi, Sharma Keshav, Coralie Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Ryan Khoo, Denisa Khoo, Khor How Kiat, Peter Kiiza, Rob Klont, Gry Kloumann Bekken, Robin Kobbe, Chamira Kodippily, Vinothini Krishnan, Ganesh Kumar, Bharath Kumar Vijayaraghavan, Demetrios Kutsogiannis, Marie Lachatre, Marie Lacoste, Marie Lagrange, Fabrice Laine, Antonio Lalueza, Marie Langelot-Richard, Marina Lanza, Delphine Lariviere, Andy Law, Teresa Lawrence, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Paul Le Turnier, Ema Leal, Marta Leal Santos, Heng Gee Lee, Biing Horng Lee, Laurent Lefebvre, Bénédicte Lefebvre, Benjamin Lefèvre, Jean-Daniel Lelievre, Véronique Lemee, Anthony Lemeur, Ha Sha Lene, Quentin Lepiller, Olivier Lesens, Mathieu Lesouhaitier, Geoffrey Liegeon, Kah Chuan Lim, Lim Lina, Guillaume Lingas, Sylvie Lion-Daolio, Marine Livrozet, Leong Chee Loon, Diogo Lopes, Anthony L. Loschner, Bouchra Loufti, Guillame Louis, Lee Lee Low, Marije Lowik, Jean Christophe Lucet, Carlos Lumbreras Bermejo, Liem Luong, Oryane Mabiala, Moïse Machado, Gabriel Macheda, Hashmi Madiha, Guillermo Maestro de la Calle, Rafael Mahieu, Thomas Maitre, Fernando Maltez, Victoria Manda, Jose M. Mandei, Edmund Manning, Aldric Manuel, Ceila Sant'Ana Malaque, Samuel Markowicz, Celina Turchi Martelli, Martin Martinot, Caroline Martins Rego, Marsilla Marzukie, Sabina Mason, Sobia Masood, Basri Mat Nor, Moshe Matan, Mathieu Mattei, Romans Matulevics, Laurence Maulin, Thierry Mazzoni, Cécile Mear-Passard, Ogechukwu Menkiti, Antoine Merckx, Mayka Mergeay-Fabre, Alison M. Meynert, Vanina Meysonnier, Amina Meziane, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Nor Arisah Misnan, Tahira Jamal Mohamed, Nik Nur Mohamed, Asma Moin, Agostinho Monteiro, Claudia Montes, Lina Morales Cely, Lucia Moro, Hugo Mouquet Ben Morton, Clara Mouton Perrot, Julien Moyet, Ng Yong Muh, Dzawani Muhamad, Jimmy Mullaert, Karl Erik Müller, Himed Musaab, Himasha Muvindi, Gugapriyaa Muyandy, Nadège Neant, Nikita Nekliudov, Raul Neto, Anthony Nghi, Duc Nguyen, Nurul Amani Noordin, Nurul Faten Norharizam, Nurnaningsih Nurnaningsih, Annmarie O'Callaghan, Katie O'Hearn, Agnieszka Oldakowska, Piero L. Olliaro, David S.Y. Ong, Jee Yan Ong, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Linda O'Shea, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Eric Oziol, Justine Pages Maïder Pagadoy, Lai Hui Pang, Aurélie Papadopoulos, Bruno Pastene, Christelle Paul, Jorge Paulos, William A. Paxton, Kalaiarasu Peariasamy, Miguel Pedrera Jiménez, Florent Peelman, Ithan D. Peltan, Daniel Perez, Thomas Perpoint, Vincent Pestre, Michele Petrovic, Scott Pharand, Carola Pierobon, Carlos Pimentel, Raquel Pinto, Catarina Pires, Isabelle Pironneau, Hon Shen Png, Ryadh Pokeerbux, Maria Pokorska-Spiewak, Diane Ponscarme, Douwe F. Postma, Diana Póvoas, Gamage Dona Priyadarshani, Vilmaris Quinones-Cardona, Víctor Quirós González, Marie Rafiq, Rozanah Abd Rahman, Ahmad Kashfi Rahman, Giri Shan Rajahram, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Thalha Rashan, Cornelius Rau, Tharmini Ravi, Stanislas Rebaudet, Sarah Redl, Attaur Rehman, Martine Remy, Hongru Ren, Anne-Sophie Resseguier, Matthieu Revest, Laurent Richier, Siti Nurul Ridzuan, Ana L Rios, Patrick Rispal, Karine Risso, David L. Robertson, Olivier Robineau, Pierre-Marie Roger, Juliette Romaru, Manuel Rosa-Calatrava, Bénédicte Rossignol, Stella Rousset, Benoît Roze, Clark D. Russell, Musharaf Sadat, Valla Sahraei, Maximilien Saint-Gilles, Stéphane Sallaberry, Charlotte Salmon Gandonniere, Hélène Salvator, Zulfiqar Sandhu, Pierre-François Sandrine, Shirley Sarfo-Mensah, Benjamine Sarton, Parthena Savvidou, Yen Tsen Saw, Janet T. Scott, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Tânia Sequeira, Pablo Serrano Balazote, Ellen Shadowitz, Syamin Asyraf Shahidan, Mohammad Shamsah, Shaikh Sharjeel, Catherine A. Shaw, Ashraf Sheharyar, Mohiuddin Shiekh, Nassima Si Mohammed, Ng Yong Siang, Benedict Sim Heng, Karisha Sivam, Morgane Snacken, Tze Vee Soh, Rima Song, Azlan Mat Soom, Albert Sotto, B. P Edouard Soum, Sanka Sri Darshana, Sarah Stabler, Ymkje Stienstra, Jacky Y. Suen, Deepashankari Suppiah, Andrey Svistunov, Sarah Syahrin, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Ewa Talarek, Kim Keat Tan, Yan Chyi Tan, Coralie Tardivon, M Azhari Taufik, Richard S. Tedder, Tze Yuan Tee, João Teixeira, Sze Kye Teoh, François Téoulé, Olivier Terrier, Hubert Tessier-Grenier, Alif Adlan Thabit, Zhang Duan Tham, Suvintheran Thangavelu, Simon-Djamel Thiberville, Jananee Thirumanickam, Emma C. Thomson, Surain Raaj Thurai, Peter S Timashev, Noémie Tissot, Jordan Zhien Toh, Sia Loong Tonnii, Marta Torre, Margarida Torres, Théo Treoux, Tiffany Trouillon, Christelle Tual, Lance C.W. Turtle, PG Ishara Udayanga, Timothy M. Uyeki, Luís Val-Flores, Amélie Valran, Marcel van den Berge, Job van der Palen, Paul van der Valk, Peter Van der Voort, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Shoban Raj Vasudayan, Charline Vauchy, Shaminee Veeran, Aurélie Veislinger, James Vickers, José Ernesto Vidal, César Vieira, Benoit Visseaux, Fanny Vuotto, Noor Hidayu Wahab, Suhaila Abdul Wahab, Nadirah Abdul Wahid, Tan Pei Wen, Sanne Wesselius, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Gan Ee Xian, Lim Saio Xian, Kuan Pei Xuan, Siti Rohani Yakop, Nicholas Yee Hing, Chian Hui Yeoh, Obada Yousif, Marion Zabbe, Masliza Zahid, Maram Zahran, Nor Zaila Zaidan, Konrad Zawadka, Nurul Zaynah, Hiba Zayyad, and David Zucman

Subjects
Pediatrics, RJ1-570
Abstract

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities.

Published
2022
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34. Exploring antimicrobial resistance to beta-lactams, aminoglycosides and fluoroquinolones in E. coli and K. pneumoniae using proteogenomics

Author

Dimard E. Foudraine, Nikolaos Strepis, Christoph Stingl, Marian T. ten Kate, Annelies Verbon, Corné H. W. Klaassen, Wil H. F. Goessens, Theo M. Luider, and Lennard J. M. Dekker

Subjects
Medicine, Science
Abstract

Abstract Antimicrobial resistance is mostly studied by means of phenotypic growth inhibition determinations, in combination with PCR confirmations or further characterization by means of whole genome sequencing (WGS). However, the actual proteins that cause resistance such as enzymes and a lack of porins cannot be detected by these methods. Improvements in liquid chromatography (LC) and mass spectrometry (MS) enabled easier and more comprehensive proteome analysis. In the current study, susceptibility testing, WGS and MS are combined into a multi-omics approach to analyze resistance against frequently used antibiotics within the beta-lactam, aminoglycoside and fluoroquinolone group in E. coli and K. pneumoniae. Our aim was to study which currently known mechanisms of resistance can be detected at the protein level using liquid chromatography–mass spectrometry (LC–MS/MS) and to assess whether these could explain beta-lactam, aminoglycoside, and fluoroquinolone resistance in the studied isolates. Furthermore, we aimed to identify significant protein to resistance correlations which have not yet been described before and to correlate the abundance of different porins in relation to resistance to different classes of antibiotics. Whole genome sequencing, high-resolution LC–MS/MS and antimicrobial susceptibility testing by broth microdilution were performed for 187 clinical E. coli and K. pneumoniae isolates. Resistance genes and proteins were identified using the Comprehensive Antibiotic Resistance Database (CARD). All proteins were annotated using the NCBI RefSeq database and Prokka. Proteins of small spectrum beta-lactamases, extended spectrum beta-lactamases, AmpC beta-lactamases, carbapenemases, and proteins of 16S ribosomal RNA methyltransferases and aminoglycoside acetyltransferases can be detected in E. coli and K. pneumoniae by LC–MS/MS. The detected mechanisms matched with the phenotype in the majority of isolates. Differences in the abundance and the primary structure of other proteins such as porins also correlated with resistance. LC–MS/MS is a different and complementary method which can be used to characterize antimicrobial resistance in detail as not only the primary resistance causing mechanisms are detected, but also secondary enhancing resistance mechanisms.

Published
2021
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35. HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals: a retrospective cohort study

Author

van der Valk, M., Geerlings, S.E., Goorhuis, A., Hovius, J.W., Lempkes, B., Nellen, F.J.B., van der Poll, T., Prins, J.M., van Vugt, M., Wiersinga, W.J., Wit, F.W.M.N., van Duinen, M., van Eden, J., Hazenberg, A., van Hes, A.M.H., Pijnappel, F.J.J., Smalhout, S.Y., Weijsenfeld, A.M., Jurriaans, S., Back, N.K.T., Zaaijer, H.L., Berkhout, B., Cornelissen, M.T.E., Schinkel, C.J., Wolthers, K.C., Peters, E.J.G., van Agtmael, M.A., Autar, R.S., Bomers, M., Sigaloff, K.C.E., Heitmuller, M., Laan, L.M., Ang, C.W., van Houdt, R., Jonges, M., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Buiting, A., Reuwer, A., Veenemans, J., Wintermans, B., Pronk, M.J.H., Ammerlaan, H.S.M., van den Bersselaar, D.N.J., de Munnik, E.S., Deiman, B., Jansz, A.R., Scharnhorst, V., Tjhie, J., Wegdam, M.C.A., van Eeden, A., Nellen, J., Brokking, W., Elsenburg, L.J.M., Nobel, H., van Kasteren, M.E.E., Berrevoets, M.A.H., Brouwer, A.E., Adams, A., van Erve, R., de Kruijf-van de Wiel, B.A.F.M., Keelan-Phaf, S., van de Ven, B., Buiting, A.G.M., Murck, J.L., de Vries-Sluijs, T.E.M.S., Bax, H.I., van Gorp, E.C.M., de Jong-Peltenburg, N.C., de Mendonça Melo, M., van Nood, E., Nouwen, J.L., Rijnders, B.J.A., Rokx, C., Schurink, C.A.M., Slobbe, L., Verbon, A., Bassant, N., van Beek, J.E.A., Vriesde, M., van Zonneveld, L.M., de Groot, J., Boucher, C.A.B., Koopmans, M.P.G., van Kampen, J.J.A., Branger, J., Douma, R.A., Cents-Bosma, A.S., Duijf-van de Ven, C.J.H.M., Schippers, E.F., van Nieuwkoop, C., van IJperen, J.M., Geilings, J., van Burgel, N.D., Leyten, E.M.S., van der Hut, G., Gelinck, L.B.S., Mollema, F., Davids-Veldhuis, S., Tearno, C., Wildenbeest, G.S., Heikens, E., Groeneveld, P.H.P., Bouwhuis, J.W., Lammers, A.J.J., Kraan, S., van Hulzen, A.G.W., Kruiper, M.S.M., van der Bliek, G.L., Bor, P.C.J., Debast, S.B., Wagenvoort, G.H.J., Kroon, F.P., de Boer, M.G.J., Jolink, H., Lambregts, M.M.C., Roukens, A.H.E., Scheper, H., Dorama, W., van Holten, N., Claas, E.C.J., Wessels, E., den Hollander, J.G., Brouwer, C.J., Smit, J.V., Struik-Kalkman, D., van Niekerk, T., El Moussaoui, R., Pogany, K., Pontesilli, O., Lowe, S.H., Oude Lashof, A.M.L., Posthouwer, D., van Wolfswinkel, M.E., Ackens, R.P., Burgers, K., Schippers, J., Weijenberg-Maes, B., van Loo, I.H.M., Havenith, T.R.A., van Vonderen, M.G.A., Kampschreur, L.M., Faber, S., Steeman-Bouma, R., Al Moujahid, A., Kootstra, G.J., Delsing, C.E., van der Burg-van de Plas, M., Scheiberlich, L., Kortmann, W., van Twillert, G., Renckens, R., Ruiter-Pronk, D., van Truijen-Oud, F.A., Cohen Stuart, J.W.T., Jansen, E.R., Hoogewerf, M., Rozemeijer, W., van der Reijden, W.A., Sinnige, J.C., Brinkman, K., van den Berk, G.E.L., Blok, W.L., Lettinga, K.D., de Regt, M., Schouten, W.E.M., Stalenhoef, J.E., Veenstra, J., Vrouenraets, S.M.E., Blaauw, H., Geerders, G.F., Kleene, M.J., Kok, M., Knapen, M., van der Meché, I.B., Mulder-Seeleman, E., Toonen, A.J.M., Wijnands, S., Wttewaal, E., Kwa, D., van Crevel, R., Dofferhoff, A.S.M., ter Hofstede, H.J.M., Hoogerwerf, J., Keuter, M., Richel, O., Albers, M., Grintjes-Huisman, K.J.T., de Haan, M., Marneef, M., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F.F., Burger, D., Gisolf, E.H., Hassing, R.J., Claassen, M., ter Beest, G., van Bentum, P.H.M., Langebeek, N., Tiemessen, R., Swanink, C.M.A., van Lelyveld, S.F.L., Soetekouw, R., van der Prijt, L.M.M., van der Swaluw, J., Bermon, N., Jansen, R., Herpers, B.L., Veenendaal, D., Verhagen, D.W.M., Lauw, F.N., van Broekhuizen, M.C., van Wijk, M., Bierman, W.F.W., Bakker, M., Kleinnijenhuis, J., Kloeze, E., Middel, A., Postma, D.F., Stienstra, Y., Wouthuyzen-Bakker, M., Boonstra, A., de Groot-de Jonge, H., van der Meulen, P.A., de Weerd, D.A., Niesters, H.G.M., van Leer-Buter, C.C., Knoester, M., Hoepelman, A.I.M., Arends, J.E., Barth, R.E., Bruns, A.H.W., Ellerbroek, P.M., Mudrikova, T., Oosterheert, J.J., Schadd, E.M., van Welzen, B.J., Aarsman, K., Griffioen-van Santen, B.M.G., de Kroon, I., van Berkel, M., van Rooijen, C.S.A.M., Schuurman, R., Verduyn-Lunel, F., Wensing, A.M.J., Reiss, P., Zaheri, S., Boyd, A.C., Bezemer, D.O., van Sighem, A.I., Smit, C., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Meijering, R., van de Sande, L., Rutkens, T., van der Vliet, S., de Groot, L., van den Akker, M., Bakker, Y., El Berkaoui, A., Bezemer, M., Brétin, N., Djoechro, E., Groters, M., Kruijne, E., Lelivelt, K.J., Lodewijk, C., Lucas, E., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Schnörr, P., Scheigrond, A., Tuijn, E., Veenenberg, L., Visser, K.M., Witte, E.C., Smit, Colette, Boyd, Anders, Rijnders, Bart J A, van de Laar, Thijs J W, Leyten, Eliane M, Bierman, Wouter F, Brinkman, Kees, Claassen, Mark A A, den Hollander, Jan, Boerekamps, Anne, Newsum, Astrid M, Schinkel, Janke, Prins, Maria, Arends, Joop E, Op de Coul, Eline L M, van der Valk, Marc, and Reiss, Peter

Published
2021
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36. Real-world effectiveness and tolerability of switching to doravirine-based antiretroviral therapy in people with HIV: a nationwide, matched, prospective cohort study

Author

Oomen, Patrick G A, Wit, Ferdinand W N M, Brinkman, Kees, Vrouenraets, Saskia M E, Mudrikova, Tania, van Welzen, Berend J, van der Valk, Marc, van Agtmael, M.A., Bomers, M., Geerlings, S.E., Goorhuis, A., Harris, V.C., Hovius, J.W., Lemkes, B., Nellen, F.J.B., Peters, E.J.G., van der Poll, T., Prins, J.M., Sigaloff, K.C.E., Spoorenberg, V., van Vugt, M., Wiersinga, W.J., Bruins, C., van Eden, J., Hylkema-van den Bout, I.J., Laan, L.M., Pijnappel, F.J.J., Smalhout, S.Y., Spelbrink, M.E., Weijsenfeld, A.M., Back, N.K.T., Cornelissen, M.T.E., van Houdt, R., Jonges, M., Jurriaans, S., Schinkel, C.J., Welkers, M.R.A., Wolthers, K.C., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., van Arkel, A., Stohr, J., Wintermans, B., Pronk, M.J.H., Ammerlaan, H.S.M., de Bree, C., de Munnik, E.S., Phaf, S., Deiman, B., Jansz, A.R., Scharnhorst, V., Tjhie, J., Wegdam, M.C.A., Nellen, J., van Eeden, A., Hoornenborg, E., de Stoppelaar, S., Alers, W., Elsenburg, L.J.M., Nobel, H., Schinkel, C.J., van Kasteren, M.E.E., Berrevoets, M.A.H., Brouwer, A.E., de Kruijf-van de Wiel, B.A.F.M., Adams, A., Pawels-van Rijkevoorsel, M., Murck, J.L., Rokx, C., Anas, A.A., Bax, H.I., van Gorp, E.C.M., de Mendonça Melo, M., van Nood, E., Nouwen, J.L., Rijnders, B.J.A., Schurink, C.A.M., Slobbe, L., de Vries-Sluijs, T.E.M.S., Bassant, N., van Beek, J.E.A., Vriesde, M., van Zonneveld, L.M., de Groot, J., van Kampen, J.J.A., Koopmans, M.P.G., Rahamat-Langendoen, J.C., Branger, J., Douma, R.A., Cents-Bosma, A.S., Mulder, M.A., Schippers, E.F., van Nieuwkoop, C., Geilings, J., van de Ven, E., van der Hut, G., van Burgel, N.D., Leyten, E.M.S., Gelinck, L.B.S., Mollema, F., Langbein, M., Wildenbeest, G.S., Nguyen, T., Groeneveld, P.H.P., Bouwhuis, J.W., Lammers, A.J.J., van Hulzen, A.G.W., Kraan, S., Kruiper, M.S.M., Debast, S.B., Wagenvoort, G.H.J., Roukens, A.H.E., de Boer, M.G.J., Jolink, H., Lambregts, M.M.C., Scheper, H., van Holten, N., van der Sluis, D., Claas, E.C.J., Wessels, E., den Hollander, J.G., El Moussaoui, R., Pogany, K., Brouwer, C.J., Heida-Peters, D., Mulder, E., Smit, J.V., Struik-Kalkman, D., van Niekerk, T., Pontesilli, O., van Tienen, C., Lowe, S.H., Oude Lashof, A.M.L., Posthouwer, D., Stoop, A., van Wolfswinkel, M.E., Ackens, R.P., Elasri, M., Houben-Pintaric, K., Schippers, J., Havenith, T.R.A., van Loo, M., van Vonderen, M.G.A., Kampschreur, L.M., Timmer, C., van Broekhuizen, M.C., Faber, S., Al Moujahid, A., Kootstra, G.J., Delsing, C.E., van der Burg-van de Plas, M., Scheiberlich, L., Kortmann, W., van Twillert, G., Renckens, R., Wagenaar, J., Ruiter-Pronk, D., Stander, B., Cohen Stuart, J.W.T., Hoogewerf, M., Rozemeijer, W., Sinnige, J.C., Brinkman, K., van den Berk, G.E.L., Lettinga, K.D., de Regt, M., Schouten, W.E.M., Stalenhoef, J.E., Blaauw, H., Geerders, G.F., Kleene, M.J., Knapen, M., Kok, M., van der Meché, I.B., Toonen, A.J.M., Wijnands, S., Wttewaal, E., Kwa, D., van de Laar, T.J.W., van Crevel, R., van Aerde, K., Dofferhoff, A.S.M., Henriet, S.S.V., ter Hofstede, H.J.M., Hoogerwerf, J., Richel, O., Albers, M., Grintjes-Huisman, K.J.T., de Haan, M., Marneef, M., McCall, M., Rahamat-Langendoen, J., Ruizendaal, E., Burger, D., Gisolf, E.H., Claassen, M., Hassing, R.J., ter Beest, G., van Bentum, P.H.M., Neijland, Y., Valette, M., Swanink, C.M.A., Klein Velderman, M., van Lelyveld, S.F.L., Soetekouw, R., van der Prijt, L.M.M., van der Swaluw, J., Kalpoe, J.S., Wagemakers, A., Vahidnia, A., Lauw, F.N., Verhagen, D.W.M., van Wijk, M., Bierman, W.F.W., Bakker, M., van Bentum, R.A., van den Boomgaard, M.A., Kleinnijenhuis, J., Kloeze, E., Middel, A., Postma, D.F., Schenk, H.M., Stienstra, Y., Wouthuyzen-Bakker, M., Boonstra, A., Maerman, M.M.M., de Weerd, D.A., van Eije, K.J., Knoester, M., van Leer-Buter, C.C., Niesters, H.G.M., Barth, R.E., Bruns, A.H.W., Ellerbroek, P.M., Hensgens, M.P.M., Oosterheert, J.J., Schadd, E.M., Verbon, A., Griffioen-van Santen, B.M.G., de Kroon, I., Schuurman, R., Verduyn Lunel, F.M., Wensing, A.M.J., van der Valk, M., Zaheri, S., Boyd, A.C., Bezemer, D.O., Jongen, V.W., van Sighem, A.I., Smit, C., Wit, F.W.M.N., Hillebregt, M.M.J., Woudstra, T.J., Rutkens, T., Bergsma, D., Brétin, N.M., Koster, L.E., Lelivelt, K.J., van de Sande, L., Schoorl, M.J.C., Visser, K.M., van der Vliet, S.T., Paling, F., van den Akker, M., Akpomukai, O.M., Alexander, R., Bakker, Y.M., Bastos Sales, L., El Berkaoui, A., Bezemer-Goedhart, M., Djoechro, E.A., Grolleman, J.M., El Hammoud, I., Khouw, M.R., Lodewijk, C.R.E., Lucas, E.G.A., van Meerveld-Derks, S., Mulder, H.W., Munjishvili, L., Ree, C.M.J., Regtop, R., van Rijk, A.F., Ruijs-Tiggelman, Y.M.C., Schnörr, P.P., van Veen, R., van Vliet-Klein Gunnewiek, W.H.G., and Witte, E.C.M.

Abstract

Currently, real-world data on doravirine are scarce. In a national prospective cohort, we assessed the effectiveness and tolerability of switching to doravirine-based antiretroviral therapy (ART) in people with HIV.

Published
2024
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37. Trends in mortality in people with HIV from 1999 to 2020: a multi-cohort collaboration

Author

Tusch, E, Ryom, L, Pelchen-Matthews, A, Mocroft, A, Elbirt, D, Oprea, C, Günthard, H, Staehelin, C, Zangerle, R, Suarez, I, Vehreschild, J, Wit, F, Menozzi, M, d'Arminio Monforte, A, Spagnuolo, V, Pradier, C, Carlander, C, Suanzes, P, Wasmuth, J, Carr, A, Petoumenos, K, Borgans, F, Bonnet, F, De Wit, S, El-Sadr, W, Neesgaard, B, Jaschinski, N, Greenberg, L, Hosein, S, Gallant, J, Vannappagari, V, Young, L, Sabin, C, Lundgren, J, Peters, L, Reekie, J, Calvo, G, Dabis, F, Kirk, O, Law, M, Monforte, A, Morfeldt, L, Reiss, P, Weber, R, Lind-Thomsen, A, Brandt, R, Hillebreght, M, Zaheri, S, Scherrer, A, Schöni-Affolter, F, Rickenbach, M, Tavelli, A, Fanti, I, Leleux, O, Mourali, J, Marec, F, Boerg, E, Thulin, E, Sundström, A, Bartsch, G, Thompsen, G, Necsoi, C, Delforge, M, Fontas, E, Caissotti, C, Dollet, K, Mateu, S, Torres, F, Blance, A, Huang, R, Puhr, R, Laut, K, Kristensen, D, Phillips, A, Kamara, D, Smith, C, Hatleberg, C, Raben, D, Matthews, C, Bojesen, A, Grevsen, A, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Smit, C, Ross, M, Fux, C, Morlat, P, Friis-Møller, N, Kowalska, J, Bohlius, J, Bower, M, Fätkenheuer, G, Grulich, A, Sjøl, A, Meidahl, P, Iversen, J, Reiss, C, Hillebregt, M, Prins, J, Kuijpers, T, Scherpbier, H, van der Meer, J, Godfried, M, van der Poll, T, Nellen, F, Geerlings, S, van Vugt, M, Pajkrt, D, Bos, J, Wiersinga, W, van der Valk, M, Goorhuis, A, Hovius, J, van Eden, J, Henderiks, A, van Hes, A, Mutschelknauss, M, Nobel, H, Pijnappel, F, Jurriaans, S, Back, N, Zaaijer, H, Berkhout, B, Cornelissen, M, Schinkel, C, Thomas, X, Ziekenhuis, A, van den Berge, M, Stegeman, A, Baas, S, de Looff, L, Versteeg, D, Ziekenhuis, C, Pronk, M, Ammerlaan, H, De Munnik, E, Jansz, A, Tjhie, J, Wegdam, M, Deiman, B, Scharnhorst, V, van der Plas, A, Weijsenfeld, A, van der Ende, M, De Vries-Sluijs, T, van Gorp, E, Schurink, C, Nouwen, J, Verbon, A, Rijnders, B, Bax, H, van der Feltz, M, Bassant, N, van Beek, J, Vriesde, M, van Zonneveld, L, de Oude-Lubbers, A, van den Berg-Cameron, H, Bruinsma-Broekman, F, de Groot, J, de Man, M, Boucher, C, Koopmans, M, van Kampen, J, Pas, S, Mc–sophia, E, Driessen, G, van Rossum, A, van der Knaap, L, Visser, E, Branger, J, Rijkeboer-Mes, A, de Ven, C, Ziekenhuis, H, Schippers, E, van Nieuwkoop, C, van IJperen, J, Geilings, J, van der Hut, G, Franck, P, van Eeden, A, Brokking, W, Groot, M, Elsenburg, L, Damen, M, Kwa, I, Groeneveld, P, Bouwhuis, J, van den Berg, J, van Hulzen, A, van der Bliek, G, Bor, P, Bloembergen, P, Wolfhagen, M, Ruijs, G, Kroon, F, de Boer, M, Bauer, M, Jolink, H, Vollaard, A, Dorama, W, van Holten, N, Claas, E, Wessels, E, den Hollander, J, Pogany, K, Roukens, A, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, Bezemer, M, van Niekerk, T, Pontesilli, O, Lowe, S, Lashof, A, Posthouwer, D, Ackens, R, Schippers, J, Vergoossen, R, Weijenberg-Maes, B, van Loo, I, Havenith, T, Leyten, E, Gelinck, L, van Hartingsveld, A, Meerkerk, C, Wildenbeest, G, Mutsaers, J, Jansen, C, Mulder, J, Vrouenraets, S, Lauw, F, van Broekhuizen, M, Paap, H, Vlasblom, D, Smits, P, Zuiderzee, M, Weijer, S, El Moussaoui, R, Bosma, A, van Vonderen, M, van Houte, D, Kampschreur, L, Dijkstra, K, Faber, S, Weel, J, Kootstra, G, Delsing, C, van der Burg-van de Plas, M, Heins, H, Lucas, E, Kortmann, W, van Twillert, G, Stuart, J, Diederen, B, Pronk, D, van Truijen-Oud, F, van der Reijden, W, Jansen, R, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Brouwer, C, Geerders, G, Hoeksema, K, Kleene, M, van der Meché, I, Spelbrink, M, Sulman, H, Toonen, A, Wijnands, S, Kwa, D, Witte, E, Koopmans, P, Keuter, M, van der Ven, A, ter Hofstede, H, Dofferhoff, A, van Crevel, R, Albers, M, Bosch, M, Grintjes-Huisman, K, Zomer, B, Stelma, F, Rahamat-Langendoen, J, Burger, D, Richter, C, Gisolf, E, Hassing, R, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, Hulshoff, N, van der 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P, Tumiotto, C, Haramburu, F, Miremeont-Salamé, G, Blaizeau, M, Decoin, M, Hannapier, C, Lenaud, E, Pougetoux, A, Delveaux, S, D’Ivernois, C, Diarra, F, Uwamaliya-Nziyumvira, B, Palmer, G, Conte, V, Sapparrart, V, Law, C, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Lau, H, Bloch, M, Baker, D, Cooper, D, O’Sullivan, M, Nolan, D, Guelfi, G, Calvo, C, Domingo, P, Sambeat, M, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaqué, A, Clumeck, N, Gennotte, A, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, M, Semaille, P, Van Laethem, Y, Neaton, C, Krum, E, Thompson, G, Wentworth, D, Luskin-Hawk, R, Telzak, E, Abrams, D, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, L, Sampson, J, Baxter, J, Gazzard, B, Horban, A, Karpov, I, Losso, M, Pedersen, C, Ristola, M, Rockstroh, J, Fischer, A, Larsen, J, Podlekareva, D, Cozzi-Lepri, A, Shepherd, L, Schultze, A, Amele, S, Kundro, M, 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F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, M, Cristaudo, A, Baldin, G, Capozzi, M, Cicalini, S, Sulekova, L, Iaiani, G, Latini, A, Mastrorosa, I, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Del Vecchio, R, Francisci, D, Giuli, C, Caramello, P, Orofino, G, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, Ialungo, A, Central, C, Dellamonica, P, Bernard, E, Courjon, J, Cua, E, De Salvador-Guillouet, F, Durant, J, Etienne, C, Ferrando, S, Mondain-Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost-Keller, B, Pugliese, P, Rio, V, Risso, K, Roger, P, Aubert, V, Bernasconi, E, Böni, J, Braun, D, Bucher, H, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Haerry, D, Hasse, B, Hirsch, H, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B, Marzolini, C, Metzner, K, Müller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Yerly, S, Valk, M, Hutchinson, J, Rupasinghe, D, Han, W, Appoyer, H, Vera, J, Broster, B, Barbour, L, Carney, D, Greenland, L, Coughlan, R, Saint-Pierre, C, Stephan, C, Bucht, M, Chokoshvili, O, Borghi, V, Casabona, J, Miro, J, Lampe, F, Burns, F, Chaloner, C, Muccini, C, Lolatto, R, Sönnerborg, A, Nowak, P, Vesterbacka, J, Mattsson, L, Carrick, D, Stigsäter, K, Kusejko, K, Schulze, N, Franke, B, Rooney, J, Mcnicholl, I, Garges, H, Campo, R, Volny-Anne, A, Dedes, N, Williams, E, Bruguera, A, Volny-Anne, R, Mendão, L, Timiryasova, A, Fursa, O, Jakobsen, M, Kraef, C, Gardizi, M, Andersen, K, Kumar, L, Elsing, T, Shahi, S, Valdenmaiier, O, Bansi-Matharu, L, Byonanebye, D, Bannister, W, Roen, A, Null, N, Tusch, Erich, Ryom, Lene, Pelchen-Matthews, Annegret, Mocroft, Amanda, Elbirt, Daniel, Oprea, Cristiana, Günthard, Huldrych F, Staehelin, Cornelia, Zangerle, Robert, Suarez, Isabelle, Vehreschild, Jörg Janne, Wit, Ferdinand, Menozzi, Marianna, d'Arminio Monforte, Antonella, Spagnuolo, Vincenzo, Pradier, Christian, Carlander, Christina, Suanzes, Paula, Wasmuth, Jan-Christian, Carr, Andrew, Petoumenos, Kathy, Borgans, Frauke, Bonnet, Fabrice, De Wit, Stephane, El-Sadr, Wafaa, Neesgaard, Bastian, Jaschinski, Nadine, Greenberg, Lauren, Hosein, Sean R, Gallant, Joel, Vannappagari, Vani, Young, Lital, Sabin, Caroline, Lundgren, Jens, Peters, Lars, Reekie, Joanne, Monforte, A d’Arminio, Brandt, R Salbøl, Wit, F W N M, Marec, F Le, Laut, K Grønborg, Sabin, C A, Phillips, A N, Kamara, D A, Smith, C J, Hatleberg, C I, Brandt, R S, Grevsen, A L, Lundgren, J D, Fux, C A, Monforte, A d'Arminio, Iversen, J S, Reiss, Central P, Prins, J M, Kuijpers, T W, Scherpbier, H J, van der Meer, J T M, Godfried, M H, Nellen, F J B, Geerlings, S E, Bos, J C, Wiersinga, W J, Hovius, J W, van Hes, A M H, Nobel, H E, Pijnappel, F J J, Back, N K T, Zaaijer, H L, Cornelissen, M T E, Schinkel, C J, Thomas, X V, Ziekenhuis, Admiraal De Ruyter, de Looff, L Hage, Ziekenhuis, Catharina, Pronk, M J H, Ammerlaan, H S M, De Munnik, E S, Jansz, A R, Wegdam, M C A, Weijsenfeld, A M, van der Ende, M E, De Vries-Sluijs, T E M S, van Gorp, E C M, Schurink, C A M, Nouwen, J L, Rijnders, B J A, Bax, H I, van Beek, J E A, van Zonneveld, L M, van den Berg-Cameron, H J, Bruinsma-Broekman, F B, de Man, M de Zeeuw, Boucher, C A B, Koopmans, M P G, van Kampen, J J A, Pas, S D, MC–Sophia, Erasmus, Driessen, G J A, van Rossum, A M C, van der Knaap, L C, de Ven, C J H M Duijf-van, Ziekenhuis, Haga, Schippers, E F, van IJperen, J M, Franck, P F H, Elsenburg, L J M, Kwa, I S, Groeneveld, P H P, Bouwhuis, J W, van den Berg, J F, van Hulzen, A G W, van der Bliek, G L, Bor, P C J, Wolfhagen, M J H M, Ruijs, G J H M, Kroon, F P, de Boer, M G J, Bauer, M P, Vollaard, A M, Claas, E C J, den Hollander, J G, Smit, J V, Lowe, S H, Lashof, A M L Oude, Ackens, R P, van Loo, I H M, Havenith, T R A, Leyten, E M S, Gelinck, L B S, Wildenbeest, G S, Mutsaers, J A E M, Jansen, C L, Mulder, J W, Vrouenraets, S M E, Lauw, F N, van Broekhuizen, M C, Vlasblom, D J, Smits, P H M, Zuiderzee, M C, Bosma, A S, van Vonderen, M G A, van Houte, D P F, Kampschreur, L M, Kootstra, G J, Delsing, C E, Stuart, J W T Cohen, Diederen, B M W, van Truijen-Oud, F A, van der Reijden, W A, van den Berk, G E L, Blok, W L, Frissen, P H J, Lettinga, K D, Schouten, W E M, Brouwer, C J, Geerders, G F, Kleene, M J, van der Meché, I B, Toonen, A J M, Koopmans, P P, van der Ven, A J A M, ter Hofstede, H J M, Dofferhoff, A S M, Bosch, M E W, Grintjes-Huisman, K J T, Zomer, B J, Stelma, F F, Gisolf, E H, Hassing, R J, van Bentum, P H M, Swanink, C M A, van Lelyveld, S F L, van der Prijt, L M M, Herpers, B L, Verhagen, D W M, Ziekenhuis, St Elisabeth, van Kasteren, M E E, Brouwer, A E, de Wiel, B A F M de Kruijf-van, Santegoets, R M W J, Marcelis, J H, Buiting, A G M, Kabel, P J, Bierman, W F W, Wilting, K R, Jonge, H de Groot-de, van der Meulen, P A, de Weerd, D A, Niesters, H G M, van Leer-Buter, C C, Hoepelman, A I M, Ellerbroek, P M, Oosterheert, J J, Arends, J E, Barth, R E, Wassenberg, M W M, Schadd, E M, van Elst-Laurijssen, D H M, van Oers-Hazelzet, E E B, Wensing, A M J, Peters, E J G, van Agtmael, M A, Laan, L M, Pettersson, A M, Vandenbroucke-Grauls, C M J E, Ang, C W, Kinderziekenhuis, Wilhelmina, Geelen, S P M, Wolfs, T F W, Bont, L J, Bezemer, D O, van Sighem, A I, Boender, T S, Rademaker, M J, Pellegrin, J L, Vareil, M O, Dauchy, F A, Receveur, M C, Vandenhende, M A, Viallard, J F, Lafon, Me, Blaizeau, M J, Boerg, Eloïse, Law, Central M, Calvo, Central G, Sambeat, M A, Gennotte, A F, Payen, M C, Neaton, Central J, El-Sadr, W M, Abrams, D I, Crane, L R, Fischer, A H, Larsen, J F, Wien, Pulmologisches Zentrum der Stadt, Mitsura, V M, Møller, N F, Nielsen, L N, Smidt, Jelena, Siseklinik, Nakkusosakond, Viard, J-P, Stellbrink, H J, Goethe, J W, Sthoeger, Z M, Monforte, A D’Arminio, Annunziata, Ospedale S Maria, Blokhina, I N, Novogrod, Nizhny, Gatell, J M, Miró, J M, Rodriguez, J M, Laporte, J M, Johnson, A M, Johnson, M A, Morfeldt, Central L, Perri, G Di, Marchetti, G C, Perno, C F, Caputo, S Lo, Capobianchi, M R, Biagio, A Di, Roldan, E Quiros, Santoro, M M, Caro, A Di, Manconi, P E, Moioli, M C, Ridolfo, A L, Martino, F Di, Cattelan, A M, Ursitti, M A, Sulekova, L Fontanelli, Plazzi, M M, Del Vecchio, R Fontana, Giuli, C Di, Orofino, G C, Roger, P M, Braun, D L, Bucher, H C, Günthard, H F, Hirsch, H H, Kouyos, R D, de Tejada, B Martinez, Metzner, K J, Scherrer, A U, Valk, Marc vd, Han, W Min, Saint-Pierre, C H U, Miro, J M, Wasmuth, J C, Vehreschild, J J, McNicholl, I, Williams, E D, Volny-Anne, R Campo Alain, Dedes, Nikos, Mendão, Luis, Jakobsen, M L, Kumar, L Ramesh, Elsing, T W, and null, null

Abstract

Background: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. Methods: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. Results: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. Conclusion: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.

Published
2024

38. Using Targeted Liquid Chromatography-Tandem Mass Spectrometry to Rapidly Detect β-Lactam, Aminoglycoside, and Fluoroquinolone Resistance Mechanisms in Blood Cultures Growing E. coli or K. pneumoniae

Author

Dimard E. Foudraine, Lennard J. M. Dekker, Nikolaos Strepis, Stan J. Nispeling, Merel N. Raaphorst, Wendy Kloezen, Piet Colle, Annelies Verbon, Corné H. W. Klaassen, Theo M. Luider, and Wil H. F. Goessens

Subjects
liquid chromatography-mass spectrometry, parallel reaction monitoring, antimicrobial resistance, blood cultures, beta-lactamases, GyrA, Microbiology, QR1-502
Abstract

New and rapid antimicrobial susceptibility/resistance testing methods are required for bacteria from positive blood cultures. In this study, a multiplex-targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed and validated for the detection of β-lactam, aminoglycoside, and fluoroquinolone resistance mechanisms in blood cultures growing Escherichia coli or Klebsiella pneumoniae complex. Selected targets were the β-lactamases SHV, TEM, OXA-1-like, CTX-M-1-like, CMY-2-like, chromosomal E. coli AmpC (cAmpC), OXA-48-like, NDM, VIM, and KPC; the aminoglycoside-modifying enzymes AAC(3)-Ia, AAC(3)-II, AAC(3)-IV, AAC(3)-VI, AAC(6′)-Ib, ANT(2′′)-I, and APH(3′)-VI; the 16S-RMTases ArmA, RmtB, RmtC, and RmtF; the quinolone resistance mechanisms QnrA, QnrB, AAC(6′)-Ib-cr; the wildtype quinolone resistance determining region of GyrA; and the E. coli porins OmpC and OmpF. The developed assay was evaluated using 100 prospectively collected positive blood cultures, and 148 negative blood culture samples spiked with isolates previously collected from blood cultures or isolates carrying less prevalent resistance mechanisms. The time to result was approximately 3 h. LC-MS/MS results were compared with whole-genome sequencing and antimicrobial susceptibility testing results. Overall, there was a high agreement between LC-MS/MS results and whole-genome sequencing results. In addition, the majority of susceptible and non-susceptible phenotypes were correctly predicted based on LC-MS/MS results. Exceptions were the predictions for ciprofloxacin and amoxicillin/clavulanic acid that matched with the phenotype in 85.9 and 63.7% of the isolates, respectively. Targeted LC-MS/MS based on parallel reaction monitoring can be applied for the rapid and accurate detection of various resistance mechanisms in blood cultures growing E. coli or K. pneumoniae complex.

Published
2022
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39. Perceptions of HIV cure and willingness to participate in HIV cure-related trials among people enrolled in the Netherlands cohort study on acute HIV infection

Author

Pien van Paassen, Maartje Dijkstra, Holly L. Peay, Casper Rokx, Annelies Verbon, Peter Reiss, Jan M. Prins, Gail E. Henderson, Stuart Rennie, Pythia T. Nieuwkerk, and Godelieve J. de Bree

Subjects
HIV cure, Acute HIV infection, Analytical treatment interruption, In-depth interviews, Perceptions, Microbiology, QR1-502, Public aspects of medicine, RA1-1270
Abstract

Background: People who initiate antiretroviral therapy (ART) during acute HIV infection are potential candidates for HIV cure-related clinical trials, as early ART reduces the size of the HIV reservoir. These trials, which may include ART interruption (ATI), might involve potential risks. We explored knowledge and perception of HIV cure and willingness to participate in cure-related trials among participants of the Netherlands Cohort Study on Acute HIV infection (NOVA study), who started antiretroviral therapy immediately after diagnosis of acute HIV infection. Methods: We conducted 20 in-depth qualitative interviews with NOVA study participants between October–December 2018. Data were analyzed thematically, using inductive and iterative coding techniques. Findings: Most participants had limited knowledge of HIV cure and understood HIV cure as complete eradication of HIV from their bodies. HIV cure was considered important to most participants, mostly due to the stigma surrounding HIV. More than half would consider undergoing brief ATI during trial participation, but only one person considered extended ATI. Viral rebound and increased infectiousness during ATI were perceived as large concerns. Participants remained hopeful of being cured during trial participation, even though they were informed that no personal medical benefit was to be expected. Interpretation: Our results highlight the need for thorough informed consent procedures with assessment of comprehension and exploration of personal motives prior to enrollment in cure-related trials. Researchers might need to moderate their expectations about how many participants will enroll in a trial with extended ATI.

Published
2022
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42. Selective cell death in HIV-1-infected cells by DDX3 inhibitors leads to depletion of the inducible reservoir

Author

Shringar Rao, Cynthia Lungu, Raquel Crespo, Thijs H. Steijaert, Alicja Gorska, Robert-Jan Palstra, Henrieke A. B. Prins, Wilfred van Ijcken, Yvonne M. Mueller, Jeroen J. A. van Kampen, Annelies Verbon, Peter D. Katsikis, Charles A. B. Boucher, Casper Rokx, Rob A. Gruters, and Tokameh Mahmoudi

Subjects
Science
Abstract

DEAD-box polypeptide 3 (DDX3) is a host protein belonging to the family of ATP-dependent RNA helicases. Here, the authors demonstrate that DDX3 inhibitors reverse HIV-1 latency and selectively induce cell death in HIV-1-infected cell lines, primary CD4+ T cells and in CD4+ T cells from cART-suppressed people living with HIV-1.

Published
2021
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43. Paracetamol modulates biofilm formation in Staphylococcus aureus clonal complex 8 strains

Author

Andi R. Sultan, Kirby R. Lattwein, Nicole A. Lemmens-den Toom, Susan V. Snijders, Klazina Kooiman, Annelies Verbon, and Willem J. B. van Wamel

Subjects
Medicine, Science
Abstract

Abstract Staphylococcus aureus biofilms are a major problem in modern healthcare due to their resistance to immune system defenses and antibiotic treatments. Certain analgesic agents are able to modulate S. aureus biofilm formation, but currently no evidence exists if paracetamol, often combined with antibiotic treatment, also has this effect. Therefore, we aimed to investigate if paracetamol can modulate S. aureus biofilm formation. Considering that certain regulatory pathways for biofilm formation and virulence factor production by S. aureus are linked, we further investigated the effect of paracetamol on immune modulator production. The in vitro biofilm mass of 21 S. aureus strains from 9 genetic backgrounds was measured in the presence of paracetamol. Based on biofilm mass quantity, we further investigated paracetamol-induced biofilm alterations using a bacterial viability assay combined with N-Acetylglucosamine staining. Isothermal microcalorimetry was used to monitor the effect of paracetamol on bacterial metabolism within biofilms and green fluorescent protein (GFP) promoter fusion technology for transcription of staphylococcal complement inhibitor (SCIN). Clinically relevant concentrations of paracetamol enhanced biofilm formation particularly among strains belonging to clonal complex 8 (CC8), but had minimal effect on S. aureus planktonic growth. The increase of biofilm mass can be attributed to the marked increase of N-Acetylglucosamine containing components of the extracellular matrix, presumably polysaccharide intercellular adhesion. Biofilms of RN6390A (CC8) showed a significant increase in the immune modulator SCIN transcription during co-incubation with low concentrations of paracetamol. Our data indicate that paracetamol can enhance biofilm formation. The clinical relevance needs to be further investigated.

Published
2021
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44. Liver Steatosis is Prevalent in Lean People With HIV and Associated With Exposure to Antiretroviral Treatment—A Cross-sectional Study.

Author

Eekeren, Louise E van, Vadaq, Nadira, Vos, Wilhelm A J W, Blaauw, Marc J T, Groenendijk, Albert L, Lunzen, Jan van, Stalenhoef, Janneke E, Berrevoets, Marvin A H, Verbon, Annelies, Weijers, Gert, Netea, Mihai G, Ven, André J A M van der, Mast, Quirijn de, Joosten, Leo A B, and Tjwa, Eric T T L

Subjects
ANTIRETROVIRAL agents, FATTY degeneration, HIV-positive persons, HEALTH facilities, HEPATIC fibrosis
Abstract

Background Steatotic liver disease is suggested to have a higher prevalence and severity in people with HIV (PHIV), including in those with a normal body mass index (BMI). In this study, we used data from the 2000HIV cohort to (1) assess the prevalence of liver steatosis and fibrosis in lean versus overweight/obese PHIV and (2) assess associations in these subgroups between steatosis and fibrosis with traditional risk factors and HIV-specific characteristics. Methods The 2000HIV study cohort comprises 1895 virally suppressed PHIV that were included between 2019 and 2021 in 4 HIV treatment centers in the Netherlands. The majority (58.5%) underwent vibration-controlled transient elastography for the assessment of liver steatosis and fibrosis. The prevalence of steatosis (controlled attenuation parameter ≥263 dB/m) and fibrosis (liver stiffness measurement ≥7.0 kPa) was estimated. Multiple factors including HIV characteristics and antiretroviral drugs were tested in a logistic regression model for association with steatosis and fibrosis. Analyses were performed separately for lean (Asian descent: BMI < 23 kg/m2, other descent: BMI < 25 kg/m2) and overweight/obese (other BMI) participants. Results Of 1050 PHIV including 505 lean and 545 overweight/obese PHIV, liver steatosis was observed in 37.7% of the overall study population, 19.7% of lean, and 54% of overweight/obese PHIV, whereas fibrosis was observed in 9.0% of the overall study population, 5.9% of lean, and 12.0% of overweight/obese PHIV. All associations with fibrosis and most associations with steatosis concerned metabolic factors such as type 2 diabetes mellitus (overall population: adjusted odds ratio [aOR] for steatosis: 2.3 [1.21-4.4], P =.011; aOR for fibrosis: 3.7 [1.82-7.53], P <.001). Furthermore, in lean PLHIV, liver steatosis was associated with CD4 and CD8 counts at enrollment, dual therapy, and history of treatment with raltegravir (aOR: 3.6 [1.53-8.47], P =.003), stavudine (aOR: 3.73 [1.69-8.2], P =.001), and indinavir (aOR: 3.86 [1.59-9.37], P =.003). These associations were not observed in overweight/obese PHIV. Conclusions Liver steatosis was highly prevalent, affecting approximately one-fifth of lean PHIV and half of overweight/obese PHIV. Fibrosis was observed in a minority. Both steatosis and fibrosis were associated with traditional metabolic risk factors. In addition, (prior) exposure to specific antiretroviral drugs was associated liver steatosis in lean, but not in overweight/obese PHIV. Implementing increased screening protocols could enhance the identification of steatotic liver disease in lean PHIV. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Perceptions of Rapid Antiretroviral Therapy Initiation Among Participants of The Netherlands Cohort Study on Acute HIV Infection.

Author

van Paassen, Pien, Dijkstra, Maartje, Peay, Holly L., Rokx, Casper, Verbon, Annelies, Reiss, Peter, Prins, Jan M., Henderson, Gail E., Rennie, Stuart, Nieuwkerk, Pythia T., and de Bree, Godelieve J.

Abstract

Starting antiretroviral therapy (ART) same-day, or as soon as possible after HIV diagnosis is advised in guidelines worldwide. Especially during acute HIV infection (AHI), rapid ART start may be more urgent because of a higher risk of transmission or symptoms of acute retroviral syndrome. During this phase, rapid ART start may have additional benefits for viral reservoir size and host immunity. We explored perceptions of rapid ART start among participants of The Netherlands Cohort Study on Acute HIV infection (NOVA study), who started ART rapidly after diagnosis of AHI. We conducted 20 in-depth qualitative interviews with NOVA study participants between October and December 2018. Data were analyzed thematically, using inductive and iterative coding techniques. Roughly half of the participants stated they felt well-informed about the importance of (rapid) ART. Starting ART rapidly was perceived positively by almost all participants, mostly because of the expected benefits on their health, and to prevent HIV transmission. Rapid ART start was seen as a way to cope with the diagnosis. However, a more negative perception was that rapid ART start confronted participants with their diagnosis, when they were still adjusting to a new situation. Our results show that among people diagnosed during AHI, rapid ART is well-accepted. These results should be encouraging to HIV care providers who encounter people with AHI in their clinical practice and to researchers who carry out cure-related studies, in which early ART is often included. The Clinical Trial Registration number is NCT05728996. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)

Author

Jeroen J. A. van Kampen, David A. M. C. van de Vijver, Pieter L. A. Fraaij, Bart L. Haagmans, Mart M. Lamers, Nisreen Okba, Johannes P. C. van den Akker, Henrik Endeman, Diederik A. M. P. J. Gommers, Jan J. Cornelissen, Rogier A. S. Hoek, Menno M. van der Eerden, Dennis A. Hesselink, Herold J. Metselaar, Annelies Verbon, Jurriaan E. M. de Steenwinkel, Georgina I. Aron, Eric C. M. van Gorp, Sander van Boheemen, Jolanda C. Voermans, Charles A. B. Boucher, Richard Molenkamp, Marion P. G. Koopmans, Corine Geurtsvankessel, and Annemiek A. van der Eijk

Subjects
Science
Abstract

Duration of infectious SARS-CoV-2 shedding is an important measure for improved disease control. Here, the authors use virus cultures of respiratory tract samples from COVID-19 patients and observe a median shedding duration of 8 days and a drop below 5% after 15,2 days post onset of symptoms.

Published
2021
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47. Predictive performance of comorbidity for 30-day and 1-year mortality in patients with bloodstream infection visiting the emergency department: a retrospective cohort study

Author

Annelies Verbon, Jelmer Alsma, Hester Lingsma, Anniek Brink, Romy Schuttevaer, William Boogers, Willian van Dijk, Jurriaan de Steenwinkel, and Stephanie Schuit

Subjects
Medicine
Abstract

Objectives To investigate whether the Charlson Comorbidity Index (CCI) predicted short-term and long-term mortality in patients with a bloodstream infection visiting the emergency department (ED) and compare it to the often-validated National Early Warning Score (NEWS).Design A retrospective cohort study.Setting A tertiary hospital in the Netherlands.Participants Adult patients attending the ED with a blood culture-proven infection between 2012 and 2017 were included. We collected the comorbidities from the CCI and the vital signs from the NEWS.Main outcomes Short-term mortality (30-day) and long-term mortality (1 year). We assessed the predictive performance by discrimination, expressed as the area under the curve (AUC).Results We included 1039 patients with a blood culture-proven infection. Mortality was 10.4% within 30 days and 27.8% within 1 year. On average patients had two comorbidities (ranging from 0 to 6). Highly prevalent comorbidities were malignancy (30.2%) and diabetes mellitus (20.5%). The predictive performance of the CCI was highest for 1-year mortality (AUC 0.696 (95%CI) (0.660 to 0.732)) and better compared with the NEWS (AUC (95% CI) 0.594 (0.555 to 0.632)). For prediction of 30-day mortality, the NEWS was superior (AUC (95% CI) 0.706 (0.656 to 0.756)) to the comorbidities of the CCI (AUC (95% CI) 0.568 (0.507 to 0.628)).Conclusions We found that presenting comorbidity (ie, the CCI) is most useful to prognosticate long-term outcome in patients with bloodstream infection in the ED. Short-term mortality is more accurately predicted by deviating vital signs (ie, the NEWS).

Published
2022
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48. Liquid Chromatography-Tandem Mass Spectrometry Analysis Demonstrates a Decrease in Porins and Increase in CMY-2 β-Lactamases in Escherichia coli Exposed to Increasing Concentrations of Meropenem

Author

Dimard E. Foudraine, Camiel N. M. Aarents, Agnes A. Wattel, Ria van Boxtel, Nikolaos Strepis, Marian T. ten Kate, Annelies Verbon, Theo M. Luider, Corné H. W. Klaassen, John Hays, Lennard J. M. Dekker, Jan Tommassen, and Wil H. F. Goessens

Subjects
meropenem, E. coli, OmpC, OmpF, CMY-2-like, liquid chromatography-mass spectrometry, Microbiology, QR1-502
Abstract

While Extended-Spectrum β-Lactamases (ESBL) and AmpC β-lactamases barely degrade carbapenem antibiotics, they are able to bind carbapenems and prevent them from interacting with penicillin-binding proteins, thereby inhibiting their activity. Further, it has been shown that Enterobacterales can become resistant to carbapenems when high concentrations of ESBL and AmpC β-lactamases are present in the bacterial cell in combination with a decreased influx of antibiotics (due to a decrease in porins and outer-membrane permeability). In this study, a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for the detection of the Escherichia coli porins OmpC and OmpF, its chromosomal AmpC β-lactamase, and the plasmid-mediated CMY-2 β-lactamase. BlaCMY–2–like positive E. coli isolates were cultured in the presence of increasing concentrations of meropenem, and resistant mutants were analyzed using the developed LC-MS/MS assay, Western blotting, and whole genome sequencing. In five strains that became meropenem resistant, a decrease in OmpC and/or OmpF (caused by premature stop codons or gene interruptions) was the first event toward meropenem resistance. In four of these strains, an additional increase in MICs was caused by an increase in CMY-2 production, and in one strain this was most likely caused by an increase in CTX-M-15 production. The LC-MS/MS assay developed proved to be suitable for the (semi-)quantitative analysis of CMY-2-like β-lactamases and porins within 4 h. Targeted LC-MS/MS could have additional clinical value in the early detection of non-carbapenemase-producing carbapenem-resistant E. coli.

Published
2022
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49. Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma.

Author

Wilson Lim, Bertrand Nyuykonge, Kimberly Eadie, Mickey Konings, Juli Smeets, Ahmed Fahal, Alexandro Bonifaz, Matthew Todd, Benjamin Perry, Kirandeep Samby, Jeremy Burrows, Annelies Verbon, and Wendy van de Sande

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common causative agents produce black grains and belong to the fungal orders Sordariales and Pleosporales. The current antifungal agents used to treat eumycetoma are itraconazole or terbinafine, however, their cure rates are low. To find novel drugs for eumycetoma, we screened 400 diverse drug-like molecules from the Pandemic Response Box against common eumycetoma causative agents as part of the Open Source Mycetoma initiative (MycetOS). 26 compounds were able to inhibit the growth of Madurella mycetomatis, Madurella pseudomycetomatis and Madurella tropicana, 26 compounds inhibited Falciformispora senegalensis and seven inhibited growth of Medicopsis romeroi in vitro. Four compounds were able to inhibit the growth of all five species of fungi tested. They are the benzimidazole carbamates fenbendazole and carbendazim, the 8-aminoquinolone derivative tafenoquine and MMV1578570. Minimal inhibitory concentrations were then determined for the compounds active against M. mycetomatis. Compounds showing potent activity in vitro were further tested in vivo. Fenbendazole, MMV1782387, ravuconazole and olorofim were able to significantly prolong Galleria mellonella larvae survival and are promising candidates to explore in mycetoma treatment and to also serve as scaffolds for medicinal chemistry optimisation in the search for novel antifungals to treat eumycetoma.

Published
2022
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