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1,057 results on '"Kalil, Andre C."'

2. Evaluating Demographic Representation in Clinical Trials: Use of the Adaptive Coronavirus Disease 2019 Treatment Trial (ACTT) as a Test Case.

Author

Ortega-Villa, Ana M, Hynes, Noreen A, Levine, Corri B, Yang, Katherine, Wiley, Zanthia, Jilg, Nikolaus, Wang, Jing, Whitaker, Jennifer A, Colombo, Christopher J, Nayak, Seema U, Kim, Hannah Jang, Iovine, Nicole M, Ince, Dilek, Cohen, Stuart H, Langer, Adam J, Wortham, Jonathan M, Atmar, Robert L, El Sahly, Hana M, Jain, Mamta K, Mehta, Aneesh K, Wolfe, Cameron R, Gomez, Carlos A, Beresnev, Tatiana, Mularski, Richard A, Paules, Catharine I, Kalil, Andre C, Branche, Angela R, Luetkemeyer, Annie, Zingman, Barry S, Voell, Jocelyn, Whitaker, Michael, Harkins, Michelle S, Davey, Richard T, Grossberg, Robert, George, Sarah L, Tapson, Victor, Short, William R, Ghazaryan, Varduhi, Benson, Constance A, Dodd, Lori E, Sweeney, Daniel A, and Tomashek, Kay M

Subjects
ACTT, COVID-19 clinical trials, representation evaluation, Clinical Research, Infectious Diseases, Prevention, Clinical Trials and Supportive Activities, Good Health and Well Being
Abstract

BackgroundClinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined.MethodsWe evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots.ResultsUS ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets.ConclusionsAlthough surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

Published
2023

3. Baricitinib Treatment of Coronavirus Disease 2019 Is Associated With a Reduction in Secondary Infections

Author

Sweeney, Daniel A, Tuyishimire, Bonifride, Ahuja, Neera, Beigel, John H, Beresnev, Tatiana, Cantos, Valeria D, Castro, Jose G, Cohen, Stuart H, Cross, Kaitlyn, Dodd, Lori E, Erdmann, Nathan, Fung, Monica, Ghazaryan, Varduhi, George, Sarah L, Grimes, Kevin A, Hynes, Noreen A, Julian, Kathleen G, Kandiah, Sheetal, Kim, Hannah Jang, Levine, Corri B, Lindholm, David A, Lye, David C, Maves, Ryan C, Oh, Myoung-Don, Paules, Catharine, Rapaka, Rekha R, Short, Willam R, Tomashek, Kay M, Wolfe, Cameron R, and Kalil, Andre C

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Clinical Trials and Supportive Activities, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, baricitinib, COVID-19, secondary infections, Clinical sciences, Medical microbiology
Abstract

We performed a secondary analysis of the National Institutes of Health-sponsored Adaptive COVID-19 Treatment Trial (ACTT-2) randomized controlled trial and found that baricitinib was associated with a 50% reduction in secondary infections after controlling for baseline and postrandomization patient characteristics. This finding provides a novel mechanism of benefit for baricitinib and supports the safety profile of this immunomodulator for the treatment of coronavirus disease 2019.

Published
2023

5. A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol

Author

Arns, Beatriz, Horvath, Jaqueline Driemeyer C., Rech, Gabriela Soares, Sesin, Guilhermo Prates, Agani, Crepin Aziz Jose Oluwafoumi, da Rosa, Bruna Silveira, dos Santos, Tiago Marcon, Brochier, Liliane Spencer Bittencourt, Cavalcanti, Alexandre Biasi, Tomazini, Bruno Martins, Pereira, Adriano Jose, Veiga, Viviane Cordeiro, Nascimento, Giovana Marssola, Kalil, Andre C., and Zavascki, Alexandre P.

Published
2024
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7. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

Author

Wolfe, Cameron R, Tomashek, Kay M, Patterson, Thomas F, Gomez, Carlos A, Marconi, Vincent C, Jain, Mamta K, Yang, Otto O, Paules, Catharine I, Palacios, Guillermo M Ruiz, Grossberg, Robert, Harkins, Michelle S, Mularski, Richard A, Erdmann, Nathaniel, Sandkovsky, Uriel, Almasri, Eyad, Pineda, Justino Regalado, Dretler, Alexandra W, de Castilla, Diego Lopez, Branche, Angela R, Park, Pauline K, Mehta, Aneesh K, Short, William R, McLellan, Susan LF, Kline, Susan, Iovine, Nicole M, El Sahly, Hana M, Doernberg, Sarah B, Oh, Myoung-Don, Huprikar, Nikhil, Hohmann, Elizabeth, Kelley, Colleen F, Holodniy, Mark, Kim, Eu Suk, Sweeney, Daniel A, Finberg, Robert W, Grimes, Kevin A, Maves, Ryan C, Ko, Emily R, Engemann, John J, Taylor, Barbara S, Ponce, Philip O, Larson, LuAnn, Melendez, Dante Paolo, Seibert, Allan M, Rouphael, Nadine G, Strebe, Joslyn, Clark, Jesse L, Julian, Kathleen G, de Leon, Alfredo Ponce, Cardoso, Anabela, de Bono, Stephanie, Atmar, Robert L, Ganesan, Anuradha, Ferreira, Jennifer L, Green, Michelle, Makowski, Mat, Bonnett, Tyler, Beresnev, Tatiana, Ghazaryan, Varduhi, Dempsey, Walla, Nayak, Seema U, Dodd, Lori E, Beigel, John H, Kalil, Andre C, and ACTT-4 Study Group

Subjects
ACTT-4 Study Group, Humans, Oxygen, Sulfonamides, Azetidines, Pyrazoles, Purines, Dexamethasone, Treatment Outcome, Double-Blind Method, Adolescent, Adult, Middle Aged, Female, Male, SARS-CoV-2, COVID-19 Drug Treatment, Clinical Trials and Supportive Activities, Lung, Clinical Research, Prevention, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract

BackgroundBaricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.MethodsIn this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168.FindingsBetween Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012).InterpretationIn hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered.FundingNational Institute of Allergy and Infectious Diseases.

Published
2022

9. Universal Risk Factors for Mortality in Bloodstream Infections (UNIFORM): a systematic review and Delphi survey

Author

Bonten, Marc, Carmeli, Yehuda, Carrara, Elena, Chambers, Henry F., Davis, Joshua S., Daikos, George L., de Kraker, Marlieke, Durante-Mangoni, Emanuele, Huttner, Angela, Kalil, Andre C., Kaye, Keith, Lee, Todd C., Leibovici, Leonard, Palacios-Baena, Zaira R., Paterson, David, Paul, Mical, Gentil, Pilar Retamar, Baño, Jesus Rodríiguez, Scudeller, Luigia, Tacconelli, Evelina, Thwaites, Guy, Tong, Steven, Varon, Ben, Yahav, Dafna, de Kraker, Marlieke E.A., and Rodríguez-Baño, Jesús

Published
2024
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10. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials

Author

Hermine, Olivier, Mariette, Xavier, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Resche-Rigon, Matthieu, Tharaux, Pierre-Louis, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Porcher, Raphaël, Pourchet-Martinez, Valerie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Raked, Nabil, Mameri, Lakhdar, Montlahuc, Claire, Biard, Lucie, Alary, St.phanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Charreteur, Robin, Dupre, Céline, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madelaine, Claire, D'Ortenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Pavot, Arthur, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Pavy, Stephan, Nocturne, Gaétane, Bitoun, Samuel, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stephane, Baudry, Elodie, Verny, Christiane, Lefevre, Edouard, Zaidan, Mohamad, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Grimaldi, Lamiae, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Soléne, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Le Tiec, Clotilde, Verstuyft, Céline, Roques, Anne-Marie, Georgin-Lavialle, Sophie, Senet, Patricia, Pialoux, Gilles, Soria, Angele, Parrot, Antoine, François, Helene, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadege, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefévre, Guillaume, Gottenberg, Jacques-Eric, Hansmann, Yves, Blanc, Frédéric, Ohlmann-Caillard, Sophie, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurelien, Heger, Bob, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Mertes, Paul-Michel, Noll, Eric, Oberlin, Mathieu, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Weill, François, Meyer, Nicolas, Andres, Emmanuel, Demonsant, Eric, Tayebi, Hakim, Nisand, Gabriel, Brin, Stéphane, Sublon, Cédric, Becker, Guillaume, Hutt, Anne, Martin, Tristan, Bayer, Sophie, Metzger, Catherine, Mekinian, Arsene, Abisror, Noémie, Adedjouma, Amir, Bollens, Diane, Bonneton, Marion, Bourcicaux, Nathalie, Bourrier, Anne, Thibault Chiarabiani, Maria Chauchard, Chopin, Doroth.e, Cohen, Jonathan, Devred, Ines, Donadille, Bruno, Fain, Olivier, Hariri, Geoffrey, Jachiet, Vincent, Ingliz, Patrick, Garnier, Marc, Gatfosse, Marc, Ghrenassia, Etienne, Gobert, Delphine, Krause le Garrec, Jessica, Landman, Cecilia, Lavillegrand, Jean Remy, Lefebvre, Benedicte, Mahevas, Thibault, Mazerand, Sandie, Meynard, Jean Luc, Morgand, Marjolaine, Ouaz.ne, Zineb, Pacanowski, Jerome, Riviere, S.bastien, Seksik, Philippe, Sokol, Harry, Soliman, Heithem, Valin, Nadia, Urbina, Thomas, McAvoy, Chloé, Miranda, Maria Pereira, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Nguyen, Anne Daguenel, Girault, Elise, Mayala-Kanda, Cl.mentine, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean-Sébastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Pennet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Denis, Jesuthasan, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Val.rie, Tréhan, Anne, Vigna, Véronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charléne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, Xavier, Ghosn, Jade, Bachelard, Antoine, Rachline, Anne, Isernia, Valentina, Bao-chau, Phung, Vallois, Dorothée, Sautereau, Aurelie, Neukrich, Catherine, Dossier, Antoine, Borie, Raphaël, Crestani, Bruno, Ducrocq, Gregory, Steg, Philippe Gabriel, Dieude, Philippe, Papo, Thomas, Marcault, Estelle, Chaudhry, Marhaba, Da Silveira, Charléne, Metois, Annabelle, Mahenni, Ismahan, Meziani, Meriam, Nilusmas, Cyndie, Le Gac, Sylvie, Ndiaye, Awa, Louni, Fran.oise, Chansombat, Malikhone, Julia, Zelie, Chalal, Solaya, Chalal, Lynda, Kramer, Laura, Le Grand, Jeniffer, Ouifiya, Kafif, Piquard, Valentine, Tubiana, Sarah, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anais, Zarrouk, Virginie, de Lastours, Victoire, Uzzan, Matthieu, Gamany, Naura, Claveirole, Agathe, Navid, Alexandre, Fouque, Tiffanie, Cohen, Yonathan, Lupo, Maya, Gilles, Constance, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, de Castro, Nathalie, Clément, Melissa, Darmon, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lenglin, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asma, Mariotte, Eric, Martin de Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault de Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Lebras, Karine Celli, Chabert, Julien, Djaghout, Lamia, Fauvaux, Catherine, Jegu, Anne Lise, Kozakiewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madelaine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, Sène, Damien, Burlacu, Ruxandra, Chousterman, Benjamin, Mégarbanne, Bruno, Richette, Pascal, Riveline, Jean-Pierre, Frazier, Aline, Vicaut, Eric, Berton, Laure, Hadjam, Tassadit, Vazquez-Ibarra, Miguel Alejandro, Jourdaine, Clément, Tran, Olivia, Jouis, Véronique, Jacob, Aude, Smati, Julie, Renaud, Stéphane, Pernin, Claire, Suarez, Lydia, Semerano, Luca, Abad, Sébastien, nainous, Ruben B., Bonnet, Nicolas, Comparon, Celine, Cohen, Yves, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Gille, Thomas, Giroux-Leprieur, Benedicte, Goupil de Bouille, Jeanne, Nunes, Hilario, Oziel, Johanna, Roulot, Dominique, Sese, Lucile, ClaireTantet, Uzunhan, Yurdagul, Bloch-Queyrat, Coralie, Levy, Vincent, Messani, Fadhila, Rahaoui, Mohammed, Petit, Myléne, Brahmi, Sabrina, Rathoin, Vanessa, Rigal, Marthe, Costedoat-Chalumeau, Nathalie, Luong, Liem Binh, Hamou, Zakaria Ait, Benghanem, Sarah, Blanche, Philippe, Carlier, Nicolas, Chaigne, Benjamin, Gauzit, Remy, Joumaa, Hassan, Jozwiak, Mathieu, Lachétre, Marie, Lafoeste, Hélène, Launay, Odie, Legendre, Paul, Marey, Jonathan, Morbieu, Caroline, Palmieri, Lola-Jade, Szwebel, Tali-Anne, Abdoul, Hendy, Bruneau, Alexandra, Beclin-Clabaux, Audrey, Larrieu, Charly, Montanari, Pierre, Dufour, Eric, Clarke, Ada, Le Bourlout, Catherine, Marin, Nathalie, Menage, Nathalie, Saleh-Mghir, Samira, Cisse, Mamadou Salif, Cheref, Kahina, Guerin, Corinne, Zerbit, Jérémie, Michel, Marc, Gallien, Sébastien, Crickx, Etienne, Le Vavasseur, Benjamin, Kempf, Emmanuelle, Jaffal, Karim, Vindrios, William, Oniszczuk, Julie, Guillaud, Constance, Lim, Pascal, Fois, Elena, Melica, Giovanna, Matignon, Marie, Jalabert, Maud, Lelièvre, Jean-Daniel, Schmitz, David, Bourhis, Marion, Belazouz, Sylia, Languille, Laetitia, Boucle, Caroline, Cita, Nelly, Didier, Agnés, Froura, Fahem, Ledudal, Katia, Sadaoui, Thiziri, Thiemele, Alaki, Le Febvre De Bailly, Delphine, Verlinde, Muriel Carvhalo, Mayaux, Julien, Cacoub, Patrice, Saadoun, David, Vautier, Mathieu, Bugaut, Héléne, Benveniste, Olivier, Allenbach, Yves, Leroux, Gaëlle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Chloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Goncalo, Ferfar, Yasmina, Corvol, Jean-Christophe, Louapre, C.line, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aicha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sebastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Charbonnier, Fanny, Aguilar, Claire, Alby-Laurent, Fanny, Burger, Carole, Campos-Vega, Clara, Chavarot, Nathalie, Fournier, Benjamin, Rouzaud, Claire, Vimpére, Damien, Elie, Caroline, Bakouboula, Prissile, Choupeaux, Laure, Granville, Sophie, Issorat, Elodie, Broissand, Christine, Alyanakian, Marie-Alexandra, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Héléne, Duclos-vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Kounis, Ilias, Tamazirt, Sonia, Rudant, Eric, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Christophe, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Netzer, Florence, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Héléne, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Chan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Marquis, Eric, Benoit, Philippe, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Helene, Mourad, Jean-Jacques, Sacco, Emmanuelle, Renet, Sophie, Ader, F., Yazdanpanah, Y., Mentre, F., Peiffer-Smadja, N., Lescure, F.X., Poissy, J., Bouadma, L., Timsit, J.F., Lina, B., Morfin-Sherpa, F., Bouscambert, M., Gaymard, A., Peytavin, G., Abel, L., Guedj, J., Andrejak, C., Burdet, C., Laouenan, C., Belhadi, D., Dupont, A., Alfaiate, T., Basli, B., Chair, A., Laribi, S., Level, J., Schneider, M., Tellier, M.C., Dechanet, A., Costagliola, D., Terrier, B., Ohana, M., Couffin-Cadiergues, S., Esperou, H., Delmas, C., Saillard, J., Fougerou, C., Moinot, L., Wittkop, L., Cagnot, C., Le Mestre, S., Lebrasseur-Longuet, D., Petrov-Sanchez, V., Diallo, A., Mercier, N., Icard, V., Leveau, B., Tubiana, S., Hamze, B., Gelley, A., Noret, M., D’Ortenzio, E., Puechal, O., Semaille, C., Welte, T., Paiva, J.A., Halanova, M., Kieny, M.P., Balssa, E., Birkle, C., Gibowski, S., Landry, E., Le Goff, A., Moachon, L., Moins, C., Wadouachi, L., Paul, C., Levier, A., Bougon, D., Djossou, F., Epelboin, L., Dellamonica, J., Marquette, C.H., Robert, C., Gibot, S., Senneville, E., Jean-Michel, V., Zerbib, Y., Chirouze, C., Boyer, A., Cazanave, C., Gruson, D., Malvy, D., Andreu, P., Quenot, J.P., Terzi, N., Faure, K., Chabartier, C., Le Moing, V., Klouche, K., Ferry, T., F, Valour, Gaborit, B., Canet, E., Le Turnier, P., Boutoille, D., Bani-Sadr, F., Benezit, F., Revest, M., Cameli, C., Caro, A., Um Tegue, MJ Ngo, Le Tulzo, Y., Laviolle, B., Laine, F., Thiery, G., Meziani, F., Hansmann, Y., Oulehri, W., Tacquard, C., Vardon-Bounes, F., Riu-Poulenc, B., Murris-Espin, M., Bernard, L., Garot, D., Hinschberger, O., Martinot, M., Bruel, C., Pilmis, B., Bouchaud, O., Loubet, P., Roger, C., Monnet, X., Figueiredo, S., Godard, V., Mira, J.P., Lachatre, M., Kerneis, S., Aboab, J., Sayre, N., Crockett, F., Lebeaux, D., Buffet, A., Diehl, J.L., Fayol, A., Hulot, J.S., Livrozet, M., Dessap, A Mekontso, Ficko, C., Stefan, F., Le Pavec, J., Mayaux, J., Ait-Oufella, H., Molina, J.M., Pialoux, G., Fartoukh, M., Textoris, J., Brossard, M., Essat, A., Netzer, E., Riault, Y., Ghislain, M., Beniguel, L., Genin, M., Gouichiche, L., Betard, C., Belkhir, L., Altdorfer, A., Centro, V Fraipont, Braz, S., Ribeiro, JM Ferreira, Alburqueque, R Roncon, Berna, M., Alexandre, M., Lamprecht, B., Egle, A., Greil, R., Joannidis, M., Patterson, Thomas F., Ponce, Philip O., Taylor, Barbara S., Patterson, Jan E., Bowling, Jason E., Javeri, Heta, Kalil, Andre C., Larson, LuAnn, Hewlett, Angela, Mehta, Aneesh K., Rouphael, Nadine G., Saklawi, Youssef, Scanlon, Nicholas, Traenkner, Jessica J., Trible, Ronald P., Jr., Walter, Emmanuel B., Ivey, Noel, Holland, Thomas L., Ruiz-Palacios, Guillermo M., Ponce de León, Alfredo, Rajme, Sandra, Hsieh, Lanny, Amin, Alpesh N., Watanabe, Miki, Lee, Helen S., Kline, Susan, Billings, Joanne, Noren, Brooke, Kim, Hyun, Bold, Tyler D., Tapson, Victor, Grein, Jonathan, Sutterwala, Fayyaz, Iovine, Nicole, Beattie, Lars K., Wakeman, Rebecca Murray, Shaw, Matthew, Jain, Mamta K., Mocherla, Satish, Meisner, Jessica, Luque, Amneris, Sweeney, Daniel A., Benson, Constance A., Ali, Farhana, Atmar, Robert L., El Sahly, Hana M., Whitaker, Jennifer, Falsey, Ann R., Branche, Angela R., Rozario, Cheryl, Pineda, Justino Regalado, Martinez-Orozco, José Arturo, Lye, David Chien, Ong, Sean WX., Chia, Po Ying, Young, Barnaby E., Sandkovsky, Uriel, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Cantos, Valeria D., Kelley, Colleen F., Rebolledo Esteinou, Paulina A., Kandiah, Sheetal, Doernberg, Sarah B., Crouch, Pierre-Cedric B., Jang, Hannah, Luetkemeyer, Anne F., Dwyer, Jay, Cohen, Stuart H., Thompson, George R., 3rd, Nguyen, Hien H., Finberg, Robert W., Wang, Jennifer P., Perez-Velazquez, Juan, Wessolossky, Mireya, Jackson, Patrick E.H., Bell, Taison D., West, Miranda J., Taiwo, Babafemi, Krueger, Karen, Perez, Johnny, Pearson, Triniece, Paules, Catharine I., Julian, Kathleen G., Ahmad, Danish, Hajduczok, Alexander G., Arguinchona, Henry, Arguinchona, Christa, Erdmann, Nathaniel, Goepfert, Paul, Ahuja, Neera, Frank, Maria G., Wyles, David, Young, Heather, Oh, Myoung-don, Park, Wan Beom, Kang, Chang Kyung, Marconi, Vincent, Moanna, Abeer, Cribbs, Sushma, Harrison, Telisha, Kim, Eu Suk, Jung, Jongtak, Song, Kyoung-Ho, Kim, Hong Bin, Tan, Seow Yen, Shafi, Humaira, Chien, Jaime, Fong, Raymond KC., Murray, Daniel D., Lundgren, Jens, Nielsen, Henrik, Jensen, Tomas, Zingman, Barry S., Grossberg, Robert, Riska, Paul F., Yang, Otto O., Ahn, Jenny, Arias, Rubi, Rapaka, Rekha R., Hauser, Naomi, Campbell, James D., Short, William R., Tebas, Pablo, Baron, Jillian T., McLellan, Susan L.F., Blanton, Lucas S., Seashore, Justin B., Creech, C. Buddy, Rice, Todd W., Walker, Shannon, Thomsen, Isaac P., Lopez de Castilla, Diego, Van Winkle, Jason W., Riedo, Francis X., Pada, Surinder Kaur, Wang, Alvin DY., Lin, Li, Harkins, Michelle, Mertz, Gregory, Sosa, Nestor, Ann Chai, Louis Yi, Tambyah, Paul Anantharajah, Tham, Sai Meng, Archuleta, Sophia, Yan, Gabriel, Lindholm, David A., Markelz, Ana Elizabeth, Mende, Katrin, Mularski, Richard, Hohmann, Elizabeth, Torres-Soto, Mariam, Jilg, Nikolaus, Maves, Ryan C., Utz, Gregory C., George, Sarah L., Hoft, Daniel F., Brien, James D., Paredes, Roger, Mateu, Lourdes, Loste, Cora, Kumar, Princy, Thornton, Sarah, Mohanraj, Sharmila, Hynes, Noreen A., Sauer, Lauren M., Colombo, Christopher J., Schofield, Christina, Colombo, Rhonda E., Chambers, Susan E., Novak, Richard M., Wendrow, Andrea, Gupta, Samir K., Lee, Tida, Lalani, Tahaniyat, Holodniy, Mark, Chary, Aarthi, Huprikar, Nikhil, Ganesan, Anuradha, Ohmagari, Norio, Mikami, Ayako, Price, D. Ashley, Duncan, Christopher J.A., Dierberg, Kerry, Neumann, Henry J., Taylor, Stephanie N., Lacour, Alisha, Masri, Najy, Swiatlo, Edwin, Widmer, Kyle, Neaton, James D., Bessesen, Mary, Stephens, David S., Burgess, Timothy H., Uyeki, Timothy M., Walker, Robert, Marks, G. Lynn, Osinusi, Anu, Cao, Huyen, Cardoso, Anabela, de Bono, Stephanie, Schlichting, Douglas E., Chung, Kevin K., Ferreira, Jennifer L., Green, Michelle, Makowski, Mat, Wierzbicki, Michael R., Conrad, Tom M., El-Khorazaty, Jill Ann, Hill, Heather, Bonnett, Tyler, Gettinger, Nikki, Engel, Theresa, Lewis, Teri, Wang, Jing, Beigel, John H., Tomashek, Kay M., Ghazaryan, Varduhi, Beresnev, Tatiana, Nayak, Seema, Dodd, Lori E., Dempsey, Walla, Nomicos, Effie, Lee, Marina, Pikaart-Tautges, Rhonda, Elsafy, Mohamed, Jurao, Robert, Koo, Hyung, Proschan, Michael, Yokum, Tammy, Arega, Janice, Florese, Ruth, Voell, Jocelyn D., Davey, Richard, Serrano, Ruth C., Wiley, Zanthia, Phadke, Varun K., Goepfert, Paul A., Gomez, Carlos A., Sofarelli, Theresa A., Certain, Laura, Imlay, Hannah N., Wolfe, Cameron R., Ko, Emily R., Engemann, John J., Felix, Nora Bautista, Wan, Claire R., Elmor, Sammy T., Bristow, Laurel R., Harkins, Michelle S., Iovine, Nicole M., Elie-Turenne, Marie-Carmelle, Tapson, Victor F., Choe, Pyoeng Gyun, Mularski, Richard A., Rhie, Kevin S., Hussein, Rezhan H., Ince, Dilek, Winokur, Patricia L., Takasaki, Jin, Saito, Sho, McConnell, Kimberly, Wyles, David L., Sarcone, Ellen, Grimes, Kevin A., Perez, Katherine, Janak, Charles, Whitaker, Jennifer A., Rebolledo, Paulina A., Gharbin, John, Lambert, Allison A., Zea, Diego F., Bainbridge, Emma, Hostler, David C., Hostler, Jordanna M., Shahan, Brian T., Ling, Evelyn, Go, Minjoung, Hubbard, Fleesie A., Chakrabarty, Melony, Laguio-Vila, Maryrose, Walsh, Edward E., Guirgis, Faheem, Marconi, Vincent C., Madar, Christian, Borgetti, Scott A., Levine, Corri, Nock, Joy, Candiotti, Keith, Rozman, Julia, Dangond, Fernando, Hyvert, Yann, Seitzinger, Andrea, Cross, Kaitlyn, Pettibone, Stephanie, Nayak, Seema U., Deye, Gregory A., Siempos, Ilias I., Belhadi, Drifa, Veiga, Viviane Cordeiro, Cavalcanti, Alexandre Biasi, Branch-Elliman, Westyn, Papoutsi, Eleni, Gkirgkiris, Konstantinos, Xixi, Nikoleta A., and Kotanidou, Anastasia

Published
2024
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11. Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial

Author

Kalil, Andre C, Mehta, Aneesh K, Patterson, Thomas F, Erdmann, Nathaniel, Gomez, Carlos A, Jain, Mamta K, Wolfe, Cameron R, Ruiz-Palacios, Guillermo M, Kline, Susan, Pineda, Justino Regalado, Luetkemeyer, Anne F, Harkins, Michelle S, Jackson, Patrick EH, Iovine, Nicole M, Tapson, Victor F, Oh, Myoung-don, Whitaker, Jennifer A, Mularski, Richard A, Paules, Catharine I, Ince, Dilek, Takasaki, Jin, Sweeney, Daniel A, Sandkovsky, Uriel, Wyles, David L, Hohmann, Elizabeth, Grimes, Kevin A, Grossberg, Robert, Laguio-Vila, Maryrose, Lambert, Allison A, de Castilla, Diego Lopez, Kim, EuSuk, Larson, LuAnn, Wan, Claire R, Traenkner, Jessica J, Ponce, Philip O, Patterson, Jan E, Goepfert, Paul A, Sofarelli, Theresa A, Mocherla, Satish, Ko, Emily R, de Leon, Alfredo Ponce, Doernberg, Sarah B, Atmar, Robert L, Maves, Ryan C, Dangond, Fernando, Ferreira, Jennifer, Green, Michelle, Makowski, Mat, Bonnett, Tyler, Beresnev, Tatiana, Ghazaryan, Varduhi, Dempsey, Walla, Nayak, Seema U, Dodd, Lori, Tomashek, Kay M, Beigel, John H, members, ACTT-3 study group, Hewlett, Angela, Taylor, Barbara S, Bowling, Jason E, Serrano, Ruth C, Rouphael, Nadine G, Wiley, Zanthia, Phadke, Varun K, Certain, Laura, Imlay, Hannah N, Engemann, John J, Walter, Emmanuel B, Meisner, Jessica, Rajme, Sandra, Billings, Joanne, Kim, Hyun, Martinez-Orozco, Jose A, Felix, Nora Bautista, Elmor, Sammy T, Bristow, Laurel R, Mertz, Gregory, Sosa, Nestor, Bell, Taison D, West, Miranda J, Elie-Turenne, Marie-Carmelle, Grein, Jonathan, Sutterwala, Fayyaz, Choe, Pyoeng Gyun, Kang, Chang Kyung, Sahly, Hana M El, Rhie, Kevin S, Hussein, Rezhan H, Winokur, Patricia L, Mikami, Ayako, Saito, Sho, Benson, Constance A, McConnell, Kimberly, Berhe, Mezgebe, Dishner, Emma, Frank, Maria G, Sarcone, Ellen, Crouch, Pierre-Cedric B, Jang, Hannah, and Jilg, Nikolaus

Subjects
Rehabilitation, Clinical Trials and Supportive Activities, Lung, Clinical Research, Infectious Diseases, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Adenosine Monophosphate, Adult, Aged, Alanine, Antiviral Agents, Double-Blind Method, Female, Humans, Interferon beta-1a, Japan, Male, Mexico, Middle Aged, Oxygen, Oxygen Saturation, Republic of Korea, SARS-CoV-2, Singapore, Treatment Outcome, United States, COVID-19 Drug Treatment, ACTT-3 study group members, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract

BackgroundFunctional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19.MethodsWe did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 μg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475.FindingsBetween Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group.InterpretationInterferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo.FundingThe National Institute of Allergy and Infectious Diseases (USA).

Published
2021

12. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

Author

Kalil, Andre C, Patterson, Thomas F, Mehta, Aneesh K, Tomashek, Kay M, Wolfe, Cameron R, Ghazaryan, Varduhi, Marconi, Vincent C, Ruiz-Palacios, Guillermo M, Hsieh, Lanny, Kline, Susan, Tapson, Victor, Iovine, Nicole M, Jain, Mamta K, Sweeney, Daniel A, El Sahly, Hana M, Branche, Angela R, Regalado Pineda, Justino, Lye, David C, Sandkovsky, Uriel, Luetkemeyer, Anne F, Cohen, Stuart H, Finberg, Robert W, Jackson, Patrick EH, Taiwo, Babafemi, Paules, Catharine I, Arguinchona, Henry, Erdmann, Nathaniel, Ahuja, Neera, Frank, Maria, Oh, Myoung-Don, Kim, Eu-Suk, Tan, Seow Y, Mularski, Richard A, Nielsen, Henrik, Ponce, Philip O, Taylor, Barbara S, Larson, LuAnn, Rouphael, Nadine G, Saklawi, Youssef, Cantos, Valeria D, Ko, Emily R, Engemann, John J, Amin, Alpesh N, Watanabe, Miki, Billings, Joanne, Elie, Marie-Carmelle, Davey, Richard T, Burgess, Timothy H, Ferreira, Jennifer, Green, Michelle, Makowski, Mat, Cardoso, Anabela, de Bono, Stephanie, Bonnett, Tyler, Proschan, Michael, Deye, Gregory A, Dempsey, Walla, Nayak, Seema U, Dodd, Lori E, and Beigel, John H

Subjects
Rehabilitation, Clinical Trials and Supportive Activities, Lung, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Adenosine Monophosphate, Adult, Aged, Alanine, Antiviral Agents, Azetidines, COVID-19, Double-Blind Method, Drug Therapy, Combination, Female, Hospital Mortality, Hospitalization, Humans, Janus Kinase Inhibitors, Male, Middle Aged, Oxygen Inhalation Therapy, Purines, Pyrazoles, Respiration, Artificial, Sulfonamides, Treatment Outcome, COVID-19 Drug Treatment, ACTT-2 Study Group Members, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundSevere coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.MethodsWe conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.ResultsA total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003).ConclusionsBaricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

Published
2021

13. Infectious Diseases Society of America Position Paper: Recommended Revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Sepsis Quality Measure

Author

Rhee, Chanu, Chiotos, Kathleen, Cosgrove, Sara E, Heil, Emily L, Kadri, Sameer S, Kalil, Andre C, Gilbert, David N, Masur, Henry, Septimus, Edward J, Sweeney, Daniel A, Strich, Jeffrey R, Winslow, Dean L, and Klompas, Michael

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Sepsis, Hematology, Prevention, Infectious Diseases, Infection, Inflammatory and immune system, Good Health and Well Being, Aged, Anti-Bacterial Agents, Communicable Diseases, Humans, Medicare, Quality Indicators, Health Care, Reproducibility of Results, Shock, Septic, United States, sepsis, septic shock, SEP-1, severe sepsis, IDSA, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

The Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1's complex "time zero" definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA's core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

Published
2021

14. Performance Analysis of the National Early Warning Score and Modified Early Warning Score in the Adaptive COVID-19 Treatment Trial Cohort.

Author

Colombo, Christopher J, Colombo, Rhonda E, Maves, Ryan C, Branche, Angela R, Cohen, Stuart H, Elie, Marie-Carmelle, George, Sarah L, Jang, Hannah J, Kalil, Andre C, Lindholm, David A, Mularski, Richard A, Ortiz, Justin R, Tapson, Victor, and Liang, C Jason

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Patient Safety, Clinical Research, Infectious Diseases, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Modified Early Warning Score, National Early Warning Score, age, coronavirus disease 2019, prognostic scores, severe acute respiratory syndrome coronavirus 2, Clinical sciences
Abstract

We sought to validate prognostic scores in coronavirus disease 2019 including National Early Warning Score, Modified Early Warning Score, and age-based modifications, and define their performance characteristics.DesignWe analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected daily during the trial, Modified Early Warning Score was calculated, and age applied to both scores. We assessed prognostic value for the end points of recovery, mechanical ventilation, and death for score at enrollment, average, and slope of score over the first 48 hours.SettingA multisite international inpatient trial.PatientsA total of 1,062 adult nonpregnant inpatients with severe coronavirus disease 2019 pneumonia.InterventionsAdaptive COVID-19 Treatment Trial 1 randomized participants to receive remdesivir or placebo. The prognostic value of predictive scores was evaluated in both groups separately to assess for differential performance in the setting of remdesivir treatment.Measurements and main resultsFor mortality, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.60-0.68), and improved with addition of age (c-index, 0.66-0.74). For recovery, baseline National Early Warning Score and Modified Early Warning Score demonstrated somewhat better prognostic ability (c-index, 0.65-0.69); however, National Early Warning Score+age and Modified Early Warning Score+age further improved performance (c-index, 0.68-0.71). For deterioration, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.59-0.69) and improved with addition of age (c-index, 0.63-0.70). All prognostic performance improvements due to addition of age were significant (p < 0.05).ConclusionsIn the Adaptive COVID-19 Treatment Trial 1 cohort, National Early Warning Score and Modified Early Warning Score demonstrated moderate prognostic performance in patients with severe coronavirus disease 2019, with improvement in predictive ability for National Early Warning Score+age and Modified Early Warning Score+age. Area under receiver operating curve for National Early Warning Score and Modified Early Warning Score improved in patients receiving remdesivir versus placebo early in the pandemic for recovery and mortality. Although these scores are simple and readily obtainable in myriad settings, in our data set, they were insufficiently predictive to completely replace clinical judgment in coronavirus disease 2019 and may serve best as an adjunct to triage, disposition, and resourcing decisions.

Published
2021

16. Remdesivir for the Treatment of Covid-19 — Final Report

Author

Beigel, John H, Tomashek, Kay M, Dodd, Lori E, Mehta, Aneesh K, Zingman, Barry S, Kalil, Andre C, Hohmann, Elizabeth, Chu, Helen Y, Luetkemeyer, Annie, Kline, Susan, Lopez de Castilla, Diego, Finberg, Robert W, Dierberg, Kerry, Tapson, Victor, Hsieh, Lanny, Patterson, Thomas F, Paredes, Roger, Sweeney, Daniel A, Short, William R, Touloumi, Giota, Lye, David Chien, Ohmagari, Norio, Oh, Myoung-Don, Ruiz-Palacios, Guillermo M, Benfield, Thomas, Fätkenheuer, Gerd, Kortepeter, Mark G, Atmar, Robert L, Creech, C Buddy, Lundgren, Jens, Babiker, Abdel G, Pett, Sarah, Neaton, James D, Burgess, Timothy H, Bonnett, Tyler, Green, Michelle, Makowski, Mat, Osinusi, Anu, Nayak, Seema, and Lane, H Clifford

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Clinical Trials and Supportive Activities, Clinical Research, Rehabilitation, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Good Health and Well Being, Adenosine Monophosphate, Administration, Intravenous, Adult, Aged, Alanine, Antiviral Agents, Betacoronavirus, COVID-19, Coronavirus Infections, Double-Blind Method, Extracorporeal Membrane Oxygenation, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Oxygen Inhalation Therapy, Pandemics, Pneumonia, Viral, Respiration, Artificial, SARS-CoV-2, Time Factors, Young Adult, COVID-19 Drug Treatment, ACTT-1 Study Group Members, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundAlthough several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.ResultsA total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P

Published
2020

22. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial

Author

Wahid, Lana, Walter, Emmanuel B., Belur, Akhila G., Dreyer, Grace, Patterson, Jan E., Bowling, Jason E., Dixon, Danielle O., Hewlett, Angela, Odrobina, Robert, Pupaibool, Jakrapun, Mocherla, Satish, Lazarte, Suzana, Cayabyab, Meilani, Hussein, Rezhan H., Golamari, Reshma R., Krill, Kaleigh L., Rajme, Sandra, Riska, Paul F., Zingman, Barry S., Mertz, Gregory, Sosa, Nestor, Goepfert, Paul A., Berhe, Mezgebe, Dishner, Emma, Fayed, Mohamed, Hubel, Kinsley, Martinez-Orozco, José Arturo, Bautista Felix, Nora, Elmor, Sammy T., Bechnak, Amer Ryan, Saklawi, Youssef, Van Winkle, Jason W., Zea, Diego F., Laguio-Vila, Maryrose, Walsh, Edward E., Falsey, Ann R., Carvajal, Karen, Hyzy, Robert C., Hanna, Sinan, Olbrich, Norman, Traenkner, Jessica J., Kraft, Colleen S., Tebas, Pablo, Baron, Jillian T, Levine, Corri, Nock, Joy, Billings, Joanne, Kim, Hyun, Elie-Turenne, Marie-Carmelle, Whitaker, Jennifer A., Luetkemeyer, Anne F., Dwyer, Jay, Bainbridge, Emma, Gyun Choe, Pyoeng, Kyung Kang, Chang, Jilg, Nikolaus, Cantos, Valeria D, Bhamidipati, Divya R., Nithin Gopalsamy, Srinivasa, Chary, Aarthi, Jung, Jongtak, Song, Kyoung-Ho, Kim, Hong Bin, Benson, Constance A., McConnell, Kimberly, Wang, Jennifer P., Wessolossky, Mireya, Perez, Katherine, Eubank, Taryn A, Berjohn, Catherine, Utz, Gregory C., Jackson, Patrick E.H., Bell, Taison D., Haughey, Heather M., Moanna, Abeer, Cribbs, Sushma, Harrison, Telisha, Colombo, Christopher J., Schofield, Christina, Colombo, Rhonda E., Tapson, Victor F., Grein, Jonathan, Sutterwala, Fayyaz, Ince, Dilek, Winokur, Patricia L., Fung, Monica, Jang, Hannah, Wyles, David, Frank, Maria G., Sarcone, Ellen, Neumann, Henry, Viswanathan, Anand, Hochman, Sarah, Mulligan, Mark, Eckhardt, Benjamin, Carmody, Ellie, Ahuja, Neera, Nadeau, Kari, Svec, David, Macaraeg, Jeffrey C., Morrow, Lee, Quimby, Dave, Bessesen, Mary, Nicholson, Lindsay, Adams, Jill, Kumar, Princy, Lambert, Allison A., Arguinchona, Henry, Alicic, Radica Z., Saito, Sho, Ohmagari, Norio, Mikami, Ayako, Chien Lye, David, Hong Lee, Tau, Ying Chia, Po, Hsieh, Lanny, Amin, Alpesh N., Watanabe, Miki, Candiotti, Keith A., Castro, Jose G., Antor, Maria A., Lee, Tida, Lalani, Tahaniyat, Novak, Richard M., Wendrow, Andrea, Borgetti, Scott A., George, Sarah L., Hoft, Daniel F., Brien, James D., Cohen, Stuart H., Thompson, George R., 3rd, Chakrabarty, Melony, Guirgis, Faheem, Davey, Richard T., Voell, Jocelyn, Strich, Jeffrey R., Lindholm, David A., Mende, Katrin, Wellington, Trevor R., Rapaka, Rekha R., Husson, Jennifer S., Levine, Andrea R., Yen Tan, Seow, Shafi, Humaira, Chien, Jaime M F, Hostler, David C., Hostler, Jordanna M., Shahan, Brian T., Adams, David H., Osinusi, Anu, Cao, Huyen, Burgess, Timothy H., Rozman, Julia, Chung, Kevin K., Nieuwoudt, Christina, El-Khorazaty, Jill A., Hill, Heather, Pettibone, Stephanie, Gettinger, Nikki, Engel, Theresa, Lewis, Teri, Wang, Jing, Deye, Gregory A., Nomicos, Effie, Pikaart-Tautges, Rhonda, Elsafy, Mohamed, Jurao, Robert, Koo, Hyung, Proschan, Michael, Yokum, Tammy, Arega, Janice, Florese, Ruth, Wolfe, Cameron R, Tomashek, Kay M, Patterson, Thomas F, Gomez, Carlos A, Marconi, Vincent C, Jain, Mamta K, Yang, Otto O, Paules, Catharine I, Palacios, Guillermo M Ruiz, Grossberg, Robert, Harkins, Michelle S, Mularski, Richard A, Erdmann, Nathaniel, Sandkovsky, Uriel, Almasri, Eyad, Pineda, Justino Regalado, Dretler, Alexandra W, de Castilla, Diego Lopez, Branche, Angela R, Park, Pauline K, Mehta, Aneesh K, Short, William R, McLellan, Susan L F, Kline, Susan, Iovine, Nicole M, El Sahly, Hana M, Doernberg, Sarah B, Oh, Myoung-don, Huprikar, Nikhil, Hohmann, Elizabeth, Kelley, Colleen F, Holodniy, Mark, Kim, Eu Suk, Sweeney, Daniel A, Finberg, Robert W, Grimes, Kevin A, Maves, Ryan C, Ko, Emily R, Engemann, John J, Taylor, Barbara S, Ponce, Philip O, Larson, LuAnn, Melendez, Dante Paolo, Seibert, Allan M, Rouphael, Nadine G, Strebe, Joslyn, Clark, Jesse L, Julian, Kathleen G, de Leon, Alfredo Ponce, Cardoso, Anabela, de Bono, Stephanie, Atmar, Robert L, Ganesan, Anuradha, Ferreira, Jennifer L, Green, Michelle, Makowski, Mat, Bonnett, Tyler, Beresnev, Tatiana, Ghazaryan, Varduhi, Dempsey, Walla, Nayak, Seema U, Dodd, Lori E, Beigel, John H, and Kalil, Andre C

Published
2022
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24. Implementation of a Virtual Interprofessional ICU Learning Collaborative: Successes, Challenges, and Initial Reactions From the Structured Team-Based Optimal Patient-Centered Care for Virus COVID-19 Collaborators

Author

Zec, Simon, Zorko Garbajs, Nika, Dong, Yue, Gajic, Ognjen, Kordik, Christina, Harmon, Lori, Bogojevic, Marija, Singh, Romil, Sun, Yuqiang, Bansal, Vikas, Vu, Linh, Cawcutt, Kelly, Litell, John M., Redmond, Sarah, Fitzpatrick, Eleanor, Kooda, Kirstin J., Biehl, Michelle, Dangayach, Neha S., Kaul, Viren, Chae, June M., Leppin, Aaron, Siuba, Mathew, Kashyap, Rahul, Walkey, Allan J., Niven, Alexander S., Martinez, Anthony, Meadows, Dean, Stinnett, Helen, Allison, Michael, Adeyemi, Olubukola, Herbert, Terry, Weinhouse, Gerald L., Patil, Namrata, Hacobian, Gaspar, Rangelov, Kamen, Parker, Jillian, Smith, Michael P., Smith, Rachel, Deery, Eliza, Harper, Andrea, Davis, Emily, Arteaga, Grace M., Fleegel, Jennifer L., Duncan, Julie M., Graner, Kevin K., Schultz, Tammy J., Giri, Abhishek, Gill, Ashley, Mielke, Catherine L., Sanghavi, Devang, Clark, Jonathan K., Shimp, Julie, Marshall, Lisa, Spiros, Michael, Kaur, Nirmaljot, Kiley, Sean P., Yarrarapu, Siva Naga, Keister, Teresa, Stroope, Gage, Stark, Jackie, Poehler, Jessica, Pablo, Juan, Garces, Domecq, Jain, Nitesh Kumar, Khan, Syed Anjum, Koritala, Thoyaja, La Nou, Abigail, Hall, Christina, Christensen, Cindy, Holbrook, Kirsten, Toufar, Sara, Normand, Sarah, Spitzner, Amy, Quinn, Carissa, Xia, Christina, Behrns, Holly D., Barreto, Erin, Elmer, Jennifer, Chalmers, Sarah, Cooper, Macy, Harthan, Aaron, Martinez, Edmundo A., Bandy, Jennifer A., Sanford, John, Guiliani, Jackie A., Kupferschmid, Megan, Pariyadath, Anand, Vitielliss, Brandy, Temas, Daniel, Heavner, Smith F., Frary, Amanda, Akhter, Murtaza, Rahman, Rania, Mulrow, Mary, Cooper, Tracy, Litell, John M., Chae, June Mee, Cawcutt, Kelly, Kooda, Kirstin J., Biehl, Michelle, Dangayach, Neha S., Redmond, Sarah, Kaul, Viren, Siuba, Matthew, Holley, Aaron B., Kon, Alexander A., Avadhani, Amita, Dzierba, Amy L., Kalil, Andre C., Cawcutt, Kelly, DePriest, Ashley D., Peters, Bradley, Pun, Brenda T., Bennett, Courtney E., Kriner, Eric, DeMartino, Erin S., Strong, Erin, Netzer, Giora, Martin, Greg S., Zimmerman, Jerry J., Taylor, Julia, Korzick, Karen A., Fischkoff, Katherine, Kaplan, Lewis J., Ostermann, Marlies, Gaeta, Mary Susan, Marshall, Mary Faith, Ahmed, Nahreen, Nyquist, Paul Alan, Nawathe, Pooja A., John, Preeti R., and Syed, Uzma

Published
2023
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25. Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-blind, randomised, placebo-controlled, phase 3 trial

Author

Hewlett, Angela, Taylor, Barbara S, Bowling, Jason E, Serrano, Ruth C, Rouphael, Nadine G, Wiley, Zanthia, Phadke, Varun K, Certain, Laura, Imlay, Hannah N, Engemann, John J, Walter, Emmanuel B, Meisner, Jessica, Rajme, Sandra, Billings, Joanne, Kim, Hyun, Martinez-Orozco, Jose A, Bautista Felix, Nora, Elmor, Sammy T, Bristow, Laurel R, Mertz, Gregory, Sosa, Nestor, Bell, Taison D, West, Miranda J, Elie-Turenne, Marie-Carmelle, Grein, Jonathan, Sutterwala, Fayyaz, Gyun Choe, Pyoeng, Kyung Kang, Chang, El Sahly, Hana M, Rhie, Kevin S, Hussein, Rezhan H, Winokur, Patricia L, Mikami, Ayako, Saito, Sho, Benson, Constance A, McConnell, Kimberly, Berhe, Mezgebe, Dishner, Emma, Frank, Maria G, Sarcone, Ellen, Crouch, Pierre-Cedric B, Jang, Hannah, Jilg, Nikolaus, Perez, Katherine, Janak, Charles, Cantos, Valeria D, Rebolledo, Paulina A, Gharbin, John, Zingman, Barry S, Riska, Paul F, Falsey, Ann R, Walsh, Edward E, Branche, Angela R, Arguinchona, Henry, Arguinchona, Christa, Van Winkle, Jason W, Zea, Diego F, Jung, Jongtak, Song, Kyoung-Ho, Kim, Hong Bin, Dwyer, Jay, Bainbridge, Emma, Hostler, David C, Hostler, Jordanna M, Shahan, Brian T, Hsieh, Lanny, Amin, Alpesh N, Watanabe, Miki, Short, William R, Tebas, Pablo, Baron, Jillian T, Ahuja, Neera, Ling, Evelyn, Go, Minjoung, Yang, Otto O, Ahn, Jenny, Arias, Rubi, Rapaka, Rekha R, Hubbard, Fleesie A, Campbell, James D, Cohen, Stuart H, Thompson, George R, 3rd, Chakrabarty, Melony, Taylor, Stephanie N, Masri, Najy, Lacour, Alisha, Lee, Tida, Lalani, Tahaniyat, Lindholm, David A, Markelz, Ana Elizabeth, Mende, Katrin, Colombo, Christopher J, Schofield, Christina, Colombo, Rhonda E, Guirgis, Faheem, Holodniy, Mark, Chary, Aarthi, Bessesen, Mary, Hynes, Noreen A, Sauer, Lauren M, Marconi, Vincent C, Moanna, Abeer, Harrison, Telisha, Lye, David C, Ong, Sean W X, Ying Chia, Po, Huprikar, Nikhil, Ganesan, Anuradha, Madar, Christian, Novak, Richard M, Wendrow, Andrea, Borgetti, Scott A, George, Sarah L, Hoft, Daniel F, Brien, James D, McLellan, Susan L F, Levine, Corri, Nock, Joy, Yen Tan, Seow, Shafi, Humaira, Chien, Jaime M F, Candiotti, Keith, Finberg, Robert W, Wang, Jennifer P, Wessolossky, Mireya, Utz, Gregory C, Chambers, Susan E, Stephens, David S, Burgess, Timothy H, Rozman, Julia, Hyvert, Yann, Seitzinger, Andrea, Osinusi, Anu, Cao, Huyen, Chung, Kevin K, Conrad, Tom M, Cross, Kaitlyn, El-Khorazaty, Jill A, Hill, Heather, Pettibone, Stephanie, Wierzbicki, Michael R, Gettinger, Nikki, Engel, Theresa, Lewis, Teri, Wang, Jing, Deye, Gregory A, Nomicos, Effie, Pikaart-Tautges, Rhonda, Elsafy, Mohamed, Jurao, Robert, Koo, Hyung, Proschan, Michael, Davey, Richard, Yokum, Tammy, Arega, Janice, Florese, Ruth, Kalil, Andre C, Mehta, Aneesh K, Patterson, Thomas F, Erdmann, Nathaniel, Gomez, Carlos A, Jain, Mamta K, Wolfe, Cameron R, Ruiz-Palacios, Guillermo M, Kline, Susan, Regalado Pineda, Justino, Luetkemeyer, Anne F, Harkins, Michelle S, Jackson, Patrick E H, Iovine, Nicole M, Tapson, Victor F, Oh, Myoung-don, Whitaker, Jennifer A, Mularski, Richard A, Paules, Catharine I, Ince, Dilek, Takasaki, Jin, Sweeney, Daniel A, Sandkovsky, Uriel, Wyles, David L, Hohmann, Elizabeth, Grimes, Kevin A, Grossberg, Robert, Laguio-Vila, Maryrose, Lambert, Allison A, Lopez de Castilla, Diego, Kim, EuSuk, Larson, LuAnn, Wan, Claire R, Traenkner, Jessica J, Ponce, Philip O, Patterson, Jan E, Goepfert, Paul A, Sofarelli, Theresa A, Mocherla, Satish, Ko, Emily R, Ponce de Leon, Alfredo, Doernberg, Sarah B, Atmar, Robert L, Maves, Ryan C, Dangond, Fernando, Ferreira, Jennifer, Green, Michelle, Makowski, Mat, Bonnett, Tyler, Beresnev, Tatiana, Ghazaryan, Varduhi, Dempsey, Walla, Nayak, Seema U, Dodd, Lori, Tomashek, Kay M, and Beigel, John H

Published
2021
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27. Treatment of patients hospitalized for COVID-19 with remdesivir is associated with lower likelihood of 30-day readmission: a retrospective observational study

Author

Mozaffari, Essy, primary, Chandak, Aastha, additional, Gottlieb, Robert L, additional, Chima-Melton, Chidinma, additional, Kalil, Andre C, additional, Sarda, Vishnudas, additional, Der-Torossian, Celine, additional, Oppelt, Thomas, additional, Berry, Mark, additional, and Amin, Alpesh N, additional

Published
2024
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34. Universal Risk Factors for Mortality in Bloodstream Infections (UNIFORM): a systematic review and Delphi survey

Author

Varon, Ben, primary, Palacios-Baena, Zaira R., additional, de Kraker, Marlieke E.A., additional, Rodríguez-Baño, Jesús, additional, Leibovici, Leonard, additional, Paul, Mical, additional, Bonten, Marc, additional, Carmeli, Yehuda, additional, Carrara, Elena, additional, Chambers, Henry F., additional, Davis, Joshua S., additional, Daikos, George L., additional, Kraker, Marlieke de, additional, Durante-Mangoni, Emanuele, additional, Huttner, Angela, additional, Kalil, Andre C., additional, Kaye, Keith, additional, Lee, Todd C., additional, Paterson, David, additional, Gentil, Pilar Retamar, additional, Baño, Jesus Rodríiguez, additional, Scudeller, Luigia, additional, Tacconelli, Evelina, additional, Thwaites, Guy, additional, Tong, Steven, additional, Varon, Ben, additional, and Yahav, Dafna, additional

Published
2024
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35. A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol

Author

Arns, Beatriz, primary, Horvath, Jaqueline Driemeyer C., additional, Rech, Gabriela Soares, additional, Sesin, Guilhermo Prates, additional, Agani, Crepin Aziz Jose Oluwafoumi, additional, da Rosa, Bruna Silveira, additional, dos Santos, Tiago Marcon, additional, Brochier, Liliane Spencer Bittencourt, additional, Cavalcanti, Alexandre Biasi, additional, Tomazini, Bruno Martins, additional, Pereira, Adriano Jose, additional, Veiga, Viviane Cordeiro, additional, Nascimento, Giovana Marssola, additional, Kalil, Andre C., additional, and Zavascki, Alexandre P., additional

Published
2023
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36. Less is more: critically ill status is not a carte blanche for unlimited antibiotic use

Author

Kalil, Andre C. and Timsit, Jean-Francois

Subjects
Communicable diseases, Hospital patients, Health care industry
Abstract

Author(s): Andre C. Kalil [sup.1], Jean-Francois Timsit [sup.2] [sup.3] Author Affiliations: (1) grid.266813.8, 0000 0001 0666 4105, Department of Internal Medicine, Division of Infectious Disease, University of Nebraska Medical Center, [...]

Published
2020
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38. Improving Sepsis Outcomes in the Era of Pay-for-Performance and Electronic Quality Measures: A Joint IDSA/ACEP/PIDS/SHEA/SHM/SIDP Position Paper.

Author

Rhee, Chanu, Strich, Jeffrey R, Chiotos, Kathleen, Classen, David C, Cosgrove, Sara E, Greeno, Ron, Heil, Emily L, Kadri, Sameer S, Kalil, Andre C, Gilbert, David N, Masur, Henry, Septimus, Edward J, Sweeney, Daniel A, Terry, Aisha, Winslow, Dean L, Yealy, Donald M, and Klompas, Michael

Subjects
MORTALITY prevention, MEDICARE, HOSPITAL care, TREATMENT effectiveness, BLOOD plasma substitutes, SEPTIC shock, SEPSIS, LABOR incentives, PAY for performance, COMORBIDITY
Abstract

The Centers for Medicare & Medicaid Services (CMS) introduced the Severe Sepsis/Septic Shock Management Bundle (SEP-1) as a pay-for-reporting measure in 2015 and is now planning to make it a pay-for-performance measure by incorporating it into the Hospital Value-Based Purchasing Program. This joint IDSA/ACEP/PIDS/SHEA/SHM/SIPD position paper highlights concerns with this change. Multiple studies indicate that SEP-1 implementation was associated with increased broad-spectrum antibiotic use, lactate measurements, and aggressive fluid resuscitation for patients with suspected sepsis but not with decreased mortality rates. Increased focus on SEP-1 risks further diverting attention and resources from more effective measures and comprehensive sepsis care. We recommend retiring SEP-1 rather than using it in a payment model and shifting instead to new sepsis metrics that focus on patient outcomes. CMS is developing a community-onset sepsis 30-day mortality electronic clinical quality measure (eCQM) that is an important step in this direction. The eCQM preliminarily identifies sepsis using systemic inflammatory response syndrome (SIRS) criteria, antibiotic administrations or diagnosis codes for infection or sepsis, and clinical indicators of acute organ dysfunction. We support the eCQM but recommend removing SIRS criteria and diagnosis codes to streamline implementation, decrease variability between hospitals, maintain vigilance for patients with sepsis but without SIRS, and avoid promoting antibiotic use in uninfected patients with SIRS. We further advocate for CMS to harmonize the eCQM with the Centers for Disease Control and Prevention's (CDC) Adult Sepsis Event surveillance metric to promote unity in federal measures, decrease reporting burden for hospitals, and facilitate shared prevention initiatives. These steps will result in a more robust measure that will encourage hospitals to pay more attention to the full breadth of sepsis care, stimulate new innovations in diagnosis and treatment, and ultimately bring us closer to our shared goal of improving outcomes for patients. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Improving Sepsis Outcomes in the Era of Pay-for-Performance and Electronic Quality Measures: A Joint IDSA/ACEP/PIDS/SHEA/SHM/SIDP Position Paper

Author

Rhee, Chanu, primary, Strich, Jeffrey R, additional, Chiotos, Kathleen, additional, Classen, David C, additional, Cosgrove, Sara E, additional, Greeno, Ron, additional, Heil, Emily L, additional, Kadri, Sameer S, additional, Kalil, Andre C, additional, Gilbert, David N, additional, Masur, Henry, additional, Septimus, Edward J, additional, Sweeney, Daniel A, additional, Terry, Aisha, additional, Winslow, Dean L, additional, Yealy, Donald M, additional, and Klompas, Michael, additional

Published
2023
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40. Remdesivir Is Associated With Reduced Mortality in COVID-19 Patients Requiring Supplemental Oxygen Including Invasive Mechanical Ventilation Across SARS-CoV-2 Variants

Author

Mozaffari, Essy, primary, Chandak, Aastha, additional, Gottlieb, Robert L, additional, Chima-Melton, Chidinma, additional, Read, Stephanie H, additional, Lee, EunYoung, additional, Der-Torossian, Celine, additional, Gupta, Rikisha, additional, Berry, Mark, additional, Hollemeersch, Stijn, additional, and Kalil, Andre C, additional

Published
2023
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41. Molecular Targets for Therapy

Author

Kalil, Andre C., Opal, Steven M., Rounds, Sharon I.S., Series editor, Dixon, Anne, Series editor, Schnapp, Lynn M., Series editor, Ward, Nicholas S., editor, and Levy, Mitchell M., editor

Published
2017
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43. Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients

Author

Timsit, Jean-François, Sonneville, Romain, Kalil, Andre C., Bassetti, Matteo, Ferrer, Ricard, Jaber, Samir, and Lanternier, Fanny

Subjects
Pfizer Inc., Transplantation of organs, tissues, etc. -- Health aspects, Mortality -- France, Diseases -- Risk factors, Immunotherapy -- Health aspects, Bacterial infections -- Risk factors, Medical colleges -- Health aspects, Epidemiology -- Health aspects, Organ transplant recipients -- Health aspects, Septic shock -- Risk factors, Acute respiratory distress syndrome -- Risk factors, Virus diseases -- Risk factors, Health care industry
Abstract

Purpose Prognosis of solid organ transplant (SOT) recipients has improved, mainly because of better prevention of rejection by immunosuppressive therapies. However, SOT recipients are highly susceptible to conventional and opportunistic infections, which represent a major cause of morbidity, graft dysfunction and mortality. Methods Narrative review. Results We cover the current epidemiology and main aspects of infections in SOT recipients including risk factors such as postoperative risks and specific risks for different transplant recipients, key points on anti-infective prophylaxis as well as diagnostic and therapeutic approaches. We provide an up-to-date guide for management of the main syndromes that can be encountered in SOT recipients including acute respiratory failure, sepsis or septic shock, and central nervous system infections as well as bacterial infections with multidrug-resistant strains, invasive fungal diseases, viral infections and less common pathogens that may impact this patient population. Conclusion We provide state-of the art review of available knowledge of critically ill SOT patients with infections., Author(s): Jean-François Timsit [sup.1] [sup.2], Romain Sonneville [sup.3] [sup.4], Andre C. Kalil [sup.5], Matteo Bassetti [sup.6], Ricard Ferrer [sup.7], Samir Jaber [sup.8], Fanny Lanternier [sup.9] [sup.10], Charles-Edouard Luyt [sup.11] [sup.12], [...]

Published
2019
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44. Reply to Hassoun et al

Author

Sweeney, Daniel A., Klompas, Michael, Muscedere, John, Metersky, Mark L., and Kalil, Andre C.

Published
2017

45. Reply to Daniels et al.

Author

Palmer, Lucy B., Sweeney, Daniel A., Metersky, Mark L., and Kalil, Andre C.

Published
2017

46. Remdesivir Reduced Mortality in Immunocompromised Patients Hospitalized for Coronavirus Disease 2019 Across Variant Waves: Findings From Routine Clinical Practice

Author

Mozaffari, Essy, primary, Chandak, Aastha, additional, Gottlieb, Robert L, additional, Chima-Melton, Chidinma, additional, Read, Stephanie H, additional, Jiang, Heng, additional, Chiang, Mel, additional, Lee, EunYoung, additional, Gupta, Rikisha, additional, Berry, Mark, additional, and Kalil, Andre C, additional

Published
2023
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48. Management of Ventilator-Associated Pneumonia

Author

Metersky, Mark L. and Kalil, Andre C.

Abstract

Two recent major guidelines on diagnosis and treatment of ventilator-associated pneumonia (VAP) recommend consideration of local antibiotic resistance patterns and individual patient risks for resistant pathogens when formulating an initial empiric antibiotic regimen. One recommends against invasive diagnostic techniques with quantitative cultures to determine the cause of VAP; the other recommends either invasive or noninvasive techniques. Both guidelines recommend short-course therapy be used for most patients with VAP. Although neither guideline recommends use of procalcitonin as an adjunct to clinical judgment when diagnosing VAP, they differ with respect to use of serial procalcitonin to shorten the length of antibiotic treatment.

Published
2024
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50. Remdesivir Reduced Mortality in Immunocompromised Patients Hospitalized for COVID-19 Across Variant Waves: Findings From Routine Clinical Practice.

Author

Mozaffari, Essy, Chandak, Aastha, Gottlieb, Robert L, Chima-Melton, Chidinma, Read, Stephanie H, Jiang, Heng, Chiang, Mel, Lee, EunYoung, Gupta, Rikisha, Berry, Mark, and Kalil, Andre C

Subjects
COVID-19, CONFIDENCE intervals, IMMUNOCOMPROMISED patients, ANTIVIRAL agents, RISK assessment, COMPARATIVE studies, KAPLAN-Meier estimator, DESCRIPTIVE statistics, PHYSICIAN practice patterns
Abstract

Background Immunocompromised patients are at high risk of severe coronavirus disease 2019 (COVID-19) and death, yet treatment strategies for immunocompromised patients hospitalized for COVID-19 reflect variations in clinical practice. In this comparative effectiveness study, we investigated the effect of remdesivir treatment on inpatient mortality among immunocompromised patients hospitalized for COVID-19 across all variants of concern (VOC) periods. Methods Data for immunocompromised patients hospitalized for COVID-19 between December 2020 and April 2022 were extracted from the US PINC AITM Healthcare Database. Patients who received remdesivir within 2 days of hospitalization were matched 1:1 using propensity score matching to patients who did not receive remdesivir. Additional matching criteria included admission month, age group, and hospital. Cox proportional hazards models were used to examine the effect of remdesivir on risk of 14- and 28-day mortality during VOC periods. Results A total of 19 184 remdesivir patients were matched to 11 213 non-remdesivir patients. Overall, 11.1% and 17.7% of remdesivir patients died within 14 and 28 days, respectively, compared with 15.4% and 22.4% of non-remdesivir patients. Remdesivir was associated with a reduction in mortality at 14 (hazard ratio [HR], 0.70; 95% confidence interval,.62–.78) and 28 days (HR, 0.75; 95% CI,.68–.83). The survival benefit remained significant during the pre-Delta, Delta, and Omicron periods. Conclusions Prompt initiation of remdesivir in immunocompromised patients hospitalized for COVID-19 is associated with significant survival benefit across all variant waves. These findings provide much-needed evidence relating to the effectiveness of a foundational treatment for hospitalized COVID-19 patients among a high-risk population. [ABSTRACT FROM AUTHOR]

Published
2023
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