205 results on '"Grund, Birgit"'
Search Results
2. Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery.
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Douin, David J, Siegel, Lianne, Grandits, Greg, Phillips, Andrew, Aggarwal, Neil R, Baker, Jason, Brown, Samuel M, Chang, Christina C, Goodman, Anna L, Grund, Birgit, Higgs, Elizabeth S, Hough, Catherine L, Murray, Daniel D, Paredes, Roger, Parmar, Mahesh, Pett, Sarah, Polizzotto, Mark N, Sandkovsky, Uriel, Self, Wesley H, Young, Barnaby E, Babiker, Abdel G, Davey, Victoria J, Kan, Virginia, Gelijns, Annetine C, Matthews, Gail, Thompson, B Taylor, Lane, H Clifford, Neaton, James D, Lundgren, Jens D, and Ginde, Adit A
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Humans ,Antibodies ,Monoclonal ,Treatment Outcome ,Aftercare ,Patient Discharge ,Aged ,COVID-19 ,SARS-CoV-2 ,monoclonal antibodies ,outcomes assessment ,Clinical Trials and Supportive Activities ,Clinical Research ,Good Health and Well Being ,Medical and Health Sciences ,Respiratory System - Abstract
Rationale: Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Objectives: Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery. Methods: We used pooled data from three clinical trials of neutralizing monoclonal antibodies to compare: 1) the hospital discharge approach; 2) the TICO (Therapeutics for Inpatients with COVID-19) trials sustained recovery approach; and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-ICU setting without organ failure or major extrapulmonary manifestations of COVID-19. We defined discordance as a difference between time to recovery. Measurements and Main Results: Discordance between the hospital discharge and comprehensive approaches occurred in 170 (20%) of 850 enrolled participants, including 126 hospital readmissions and 24 deaths after initial hospital discharge. Discordant participants were older (median age, 68 vs. 59 years; P
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- 2022
3. Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19
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Barkauskas, Christina, Mylonakis, Eleftherios, Poulakou, Garyfallia, Young, Barnaby E, Vock, David M, Siegel, Lianne, Engen, Nicole, Grandits, Greg, Mosaly, Nilima R, Vekstein, Andrew M, Rogers, Ralph, Shehadeh, Fadi, Kaczynski, Matthew, Mylona, Evangelia K, Syrigos, Konstantinos N, Rapti, Vasiliki, Lye, David C, Hui, Diong Shiau, Leither, Lindsay, Knowlton, Kirk U, Jain, Mamta K, Marines-Price, Rubria, Osuji, Alice, Overcash, J Scott, Kalomenidis, Ioannis, Barmparessou, Zafeiria, Waters, Michael, Zepeda, Karla, Chen, Peter, Torbati, Sam, Kiweewa, Francis, Sebudde, Nicholus, Almasri, Eyad, Hughes, Alyssa, Bhagani, Sanjay R, Rodger, Alison, Sandkovsky, Uriel, Gottlieb, Robert L, Nnakelu, Eriobu, Trautner, Barbara, Menon, Vidya, Lutaakome, Joseph, Matthay, Michael, Robinson, Philip, Protopapas, Konstantinos, Koulouris, Nikolaos, Kimuli, Ivan, Baduashvili, Amiran, Braun, Dominique L, Günthard, Huldrych F, Ramachandruni, Srikanth, Kidega, Robert, Kim, Kami, Hatlen, Timothy J, Phillips, Andrew N, Murray, Daniel D, Jensen, Tomas O, Padilla, Maria L, Accardi, Evan X, Shaw-Saliba, Katy, Dewar, Robin L, Teitelbaum, Marc, Natarajan, Ven, Laverdure, Sylvain, Highbarger, Helene C, Rehman, M Tauseef, Vogel, Susan, Vallée, David, Crew, Page, Atri, Negin, Schechner, Adam J, Pett, Sarah, Hudson, Fleur, Badrock, Jonathan, Touloumi, Giota, Brown, Samuel M, Self, Wesley H, North, Crystal M, Ginde, Adit A, Chang, Christina C, Kelleher, Anthony, Nagy-Agren, Stephanie, Vasudeva, Shikha, Looney, David, Nguyen, Hien H, Sánchez, Adriana, Weintrob, Amy C, Grund, Birgit, Sharma, Shweta, Reilly, Cavan S, Paredes, Roger, Bednarska, Agnieszka, Gerry, Norman P, Babiker, Abdel G, Davey, Victoria J, Gelijns, Annetine C, Higgs, Elizabeth S, Kan, Virginia, Matthews, Gail, and Thompson, B Taylor
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Clinical Research ,Clinical Trials and Supportive Activities ,Lung ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Adult ,Designed Ankyrin Repeat Proteins ,Double-Blind Method ,Humans ,Recombinant Fusion Proteins ,SARS-CoV-2 ,Treatment Outcome ,COVID-19 Drug Treatment ,ACTIV-3/TICO Study Group ,Clinical Sciences ,Public Health and Health Services - Abstract
BackgroundEnsovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.ObjectiveTo investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.DesignDouble-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978).SettingMultinational, multicenter trial.ParticipantsAdults hospitalized with COVID-19.InterventionIntravenous ensovibep, 600 mg, or placebo.MeasurementsEnsovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90.ResultsAn independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR
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- 2022
4. Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial
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Group, ACTIV-3 Therapeutics for Inpatients with COVID-19 Study, Self, Wesley H, Sandkovsky, Uriel, Reilly, Cavan S, Vock, David M, Gottlieb, Robert L, Mack, Michael, Golden, Kevin, Dishner, Emma, Vekstein, Andrew, Ko, Emily R, Der, Tatyana, Franzone, John, Almasri, Eyad, Fayed, Mohamed, Filbin, Michael R, Hibbert, Kathryn A, Rice, Todd W, Casey, Jonathan D, Hayanga, J Awori, Badhwar, Vinay, Leshnower, Bradley G, Sharifpour, Milad, Knowlton, Kirk U, Peltan, Ithan D, Bakowska, Elizieta, Kowalska, Justyna, Bowdish, Michael E, Sturek, Jeffrey M, Rogers, Angela J, Files, D Clark, Mosier, Jarrod M, Gong, Michelle N, Douin, David J, Hite, R Duncan, Trautner, Barbara W, Jain, Mamta K, Gardner, Edward M, Khan, Akram, Jensen, Jens-Ulrik, Matthay, Michael A, Ginde, Adit A, Brown, Samuel M, Higgs, Elizabeth S, Pett, Sarah, Weintrob, Amy C, Chang, Christina C, Murrary, Daniel D, Günthard, Huldrych F, Moquete, Ellen, Grandits, Greg, Engen, Nicole, Grund, Birgit, Sharma, Shweta, Cao, Huyen, Gupta, Rajesh, Osei, Suzette, Margolis, David, Zhu, Qing, Polizzotto, Mark N, Babiker, Abdel G, Davey, Victoria J, Kan, Virginia, Thompson, B Taylor, Gelijns, Annetine C, Neaton, James D, Lane, H Clifford, Jundgren, Jens D, Tierney, John, Barrett, Kevin, Herpin, Betsey R, Smolskis, Mary C, Voge, Susan E, McNay, Laura A, Cahill, Kelly, Crew, Page, Kirchoff, Matthew, Sardana, Ratna, Raim, Sharon Segal, Chiu, Joseph, Hensley, Lisa, Lorenzo, Josua, Mock, Rebecca, Shaw-Saliba, Katy, Zuckerman, Judith, Adam, Stacey J, Currier, Judy, Read, Sarah, Hughes, Eric, Amos, Laura, Carlsen, Amy, Carter, Anita, Davis, Bionca, Denning, Eileen, DuChene, Alain, Harrison, Merrie, Kaiser, Payton, Koopmeiners, Joseph, Meger, Sue, and Murray, Thomas
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Clinical Trials and Supportive Activities ,Lung ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Antibodies ,Monoclonal ,Antibodies ,Monoclonal ,Humanized ,Antibodies ,Neutralizing ,Double-Blind Method ,Female ,Humans ,Male ,Middle Aged ,SARS-CoV-2 ,Treatment Outcome ,COVID-19 Drug Treatment ,ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study Group ,Clinical Sciences ,Medical Microbiology ,Public Health and Health Services ,Microbiology - Abstract
BackgroundWe aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.MethodsIn this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.FindingsBetween Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.InterpretationNeither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.FundingUS National Institutes of Health and Operation Warp Speed.
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- 2022
5. Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study
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Sahner, David, Tierney, John, Vogel, Susan E., Herpin, Betsey R., Smolskis, Mary C., McKay, Laura A., Cahill, Kelly, Crew, Page, Sardana, Ratna, Raim, Sharon Segal, Hensely, Lisa, Lorenzo, Johsua, Mock, Rebecca, Zuckerman, Judith, Atri, Negin, Miller, Mark, Vallee, David, Chung, Lucy, Kang, Nayon, Barrett, Kevin, Adam, Stacey J., Read, Sarah, Draghia-Akli, Ruxandra, Currier, Judy, Hughes, Eric, Harrigan, Rachel H., Amos, Laura, Carlsen, Amy, Carter, Anita, Collins, Gary, Davis, Bionca, Denning, Eileen, DuChene, Alain, Eckroth, Kate, Engen, Nicole, Frase, Alex, Gandits, Greg, Grund, Birgit, Harrison, Merrie, Hurlbut, Nancy, Kaiser, Payton, Koopmeiners, Joseph, Larson, Gregg, Meger, Sue, Mistry, Shweta Sharma, Murray, Thomas, Nelson, Ray, Quan, Kien, Quan, Siu Fun, Reilly, Cavan, Siegel, Lianne, Thompson, Greg, Vock, David, Walski, Jamie, Gelijns, Annetine C., Moskowitz, Alan J., Bagiella, Emilia, Moquete, Ellen, O'Sullivan, Karen, Marks, Mary E., Accardi, Evan, Kinzel, Emily, Burris, Sarah, Bedoya, Gabriela, Gupta, Lola, Overbey, Jessica R., Santos, Milerva, Gillinov, Marc A., Miller, Marissa A., Taddei-Peters, Wendy C., Fenton, Kathleen, Sandkovsky, Uriel, Gottlieb, Robert L., Mack, Michael, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Bettacchi, Christopher, Golden, Kevin, Duhaime, Erin, Ryan, Madison, Tallmadge, Catherine, Estrada, Lorie, Jones, Felecia, Villa, Samatha, Wang, Samatha, Robert, Raven, Coleman, Tanquinisha, Clariday, Laura, Baker, Rebecca, Hurutado-Rodriguez, Mariana, Iram, Nazia, Fresnedo, Michelle, Davis, Allyson, Leonard, Kiara, Ramierez, Noelia, Thammavong, Jon, Duque, Krizia, Turner, Emma, Fisher, Tammy, Robinson, Dianna, Ransom, Desirae, Maldonado, Nicholas, Lusk, Erica, Killian, Aaron, Palacious, Adriana, Solis, Edilia, Jerrow, Janet, Watts, Matthew, Whitacre, Heather, Cothran, Elizabeth, Smith, Peter K., Barkauskas, Christina E., Vekstein, Andrew M., Ko, Emily R., Dreyer, Grace R., Stafford, Neil, Brooks, Megan, Der, Tatyana, Witte, Marie, Gamarallage, Ruwan, Franzone, John, Ivey, Noel, Lumsden, Rebecca H., Mosaly, Nilima, Mourad, Ahmaad, Holland, Thomas L., Motta, Mary, Lane, Kathleen, McGowan, Lauren M., Stout, Jennifer, Aloor, Heather, Bragg, Kennesha M., Toledo, Barvina, McLendon-Arvik, Beth, Bussadori, Barbara, Hollister, Beth A., Griffin, Michelle, Giangiacomo, Dana M., Rodriguez, Vicente, Bokhart, Gordon, Eichman, Sharon M., Parrino, Patrick E., Spindel, Stephen, Bansal, Aditya, Baumgarten, Katherine, Hand, Johnathan, Vonderhaar, Derek, Nossaman, Bobby, Sylvia Laudun, Ames, DeAnna, Broussard, Shane, Hernandez, Nilmo, Isaac, Geralyn, Dinh, Huan, Zheng, Yiling, Tran, Sonny, McDaniel, Hunter, Crovetto, Nicolle, Perin, Emerson, Costello, Briana, Manian, Prasad, Sohail, M. Rizwan, Postalian, Alexander, Hinsu, Punit, Watson, Carolyn, Chen, James, Fink, Melyssa, Sturgis, Lydia, Walker, Kim, Mahon, Kim, Parenti, Jennifer, Kappenman, Casey, Knight, Aryn, Sturek, Jeffrey M., Barros, Andrew, Enfield, Kyle B., Kadl, Alexandra, Green, China J., Simon, Rachel M., Fox, Ashley, Thornton, Kara, Adams, Amy, Badhwar, Vinay, Sharma, Sunil, Peppers, Briana, McCarthy, Paul, Krupica, Troy, Sarwari, Arif, Reece, Rebecca, Fornaresico, Lisa, Glaze, Chad, Evans, Raquel, Di, Fang, Carlson, Shawn, Aucremanne, Tanja, Tennant, Connie, Sutton, Lisa Giblin, Buterbaugh, Sabrina, Williams, Roger, Bunner, Robin, Traverse, Jay H., Rhame, Frank, Huelster, Joshua, Kethireddy, Rajesh, Davies, Irena, Salamanca, Julianne, Majeski, Christine, Skelton, Paige, Zarambo, Maria, Sarafolean, Andrea, Bowdish, Michael E., Borok, Zea, Wald-Dickler, Noah, Hutcheon, Douglass, Towfighi, Amytis, Lee, Mary, Lewis, Meghan R., Spellberg, Brad, Sher, Linda, Sharma, Aniket, Olds, Anna P., Justino, Chris, Loxano, Edward, Romero, Chris, Leong, Janet, Rodina, Valentina, Quesada, Christine, Hamilton, Luke, Escobar, Jose, Leshnower, Brad, Bender, William, Sharifpour, Milad, Miller, Jeffrey, Farrington, Woodrow, Baio, Kim T., McBride, Mary, Fielding, Michele, Mathewson, Sonya, Porte, Kristina, Maton, Missy, Ponder, Chari, Haley, Elisabeth, Spainhour, Christine, Rogers, Susan, Tyler, Derrick, Madathil, Ronson J., Rabin, Joseph, Levine, Andrea, Saharia, Kapil, Tabatabai, Ali, Lau, Christine, Gammie, James S., Peguero, Maya-Loren, McKernan, Kimberly, Audette, Mathew, Fleischmann, Emily, Akbari, Kreshta, Lee, Myounghee, Chi, Andrew, Salehi, Hanna, Pariser, Alan, Nyguyen, Phuong Tran, Moore, Jessica, Gee, Adrienne, Vincent, Shelika, Zuckerman, Richard A., Iribarne, Alexander, Metzler, Sara, Shipman, Samantha, Johnson, Haley, Newton, Crystallee, Parr, Doug, Miller, Leslie, Schelle, Beth, McLean, Sherry, Rothbaum, Howard R., Alvarez, Michael S., Kalan, Shivam P., Germann, Heather H., Hendershot, Jennifer, Moroney, Karen, Herring, Karen, Cook, Sharri, Paul, Pam, Walker-Ignasiak, Rebecca, North, Crystal, Oldmixon, Cathryn, Ringwood, Nancy, Muzikansky, Ariela, Morse, Richard, Fitzgerald, Laura, Morin, Haley D., Brower, Roy G., Reineck, Lora A., Bienstock, Karen, Steingrub, Jay H., Hou, Peter K., Steingrub, Jay S., Tidswell, Mark A., Kozikowski, Lori-Ann, Kardos, Cynthia, DeSouza, Leslie, Romain, Sarah, Thornton-Thompson, Sherell, Talmor, Daniel, Shapiro, Nathan, Andromidas, Konstantinos, Banner-Goodspeed, Valerie, Bolstad, Michael, Boyle, Katherine L., Cabrera, Payton, deVilla, Arnaldo, Ellis, Joshua C., Grafals, Ana, Hayes, Sharon, Higgins, Conor, Kurt, Lisa, Kurtzman, Nicholas, Redman, Kimberly, Rosseto, Elinita, Scaffidi, Douglas, Filbin, Michael R., Hibbert, Kathryn A., Parry, Blair, Margolin, Justin, Hillis, Brooklynn, Hamer, Rhonda, Brait, Kelsey, Beakes, Caroline, McKaig, Brenna, Kugener, Eleonore, Jones, Alan E., Galbraith, James, Nandi, Utsav, Peacock, Rebekah, Hendey, Gregory, Kangelaris, Kirsten, Ashktorab, Kimia, Gropper, Rachel, Agrawal, Anika, Yee, Kimberley J., Jauregui, Alejandra E., Zhuo, Hanjing, Almasri, Eyad, Fayed, Mohamed, Hubel, Kinsley A., Hughes, Alyssa R., Garcia, Rebekah L., Lim, George W., Chang, Steven Y., Lin, Michael Y., Vargas, Julia, Sihota, Hena, Beutler, Rebecca, Agarwal, Trisha, Wilson, Jennifer G., Vojnik, Rosemary, Perez, Cynthia, McDowell, Jordan H., Roque, Jonasel, Wang, Henry, Huebinger, Ryan M., Patel, Bela, Vidales, Elizabeth, Albertson, Timothy, Hardy, Erin, Harper, Richart, Moss, Marc A., Baduashvili, Amiran, Chauhan, Lakshmi, Douin, David J., Martinez, Flora, Finck, Lani L., Bastman, Jill, Howell, Michelle, Higgins, Carrie, McKeehan, Jeffrey, Finigan, Jay, Stubenrauch, Peter, Janssen, William J., Griesmer, Christine, VerBurg, Olivia, Hyzy, Robert C., Park, Pauline K., Nelson, Kristine, McSparron, Jake I., Co, Ivan N., Wang, Bonnie R., Jimenez, Jose, Olbrich, Norman, McDonough, Kelli, Jia, Shijing, Hanna, Sinan, Gong, Michelle N., Richardson, Lynne D., Nair, Rahul, Lopez, Brenda, Amosu, Omowunmi, Offor, Obiageli, Tzehaie, Hiwet, Nkemdirim, William, Boujid, Sabah, Mosier, Jarrod M., Hypes, Cameron, Campbell, Elizabeth Salvagio, Bixby, Billie, Gilson, Boris, Lopez, Anitza, Bime, Christian, Parthasarathy, Sairam, Cano, Ariana M., Hite, R. Duncan, Terndrup, Thomas E., Wiedemann, Herbert P., Hudock, Kristin, Tanzeem, Hammad, More, Harshada, Martinkovic, Jamie, Sellers, Susan, Houston, Judy, Burns, Mary, Kiran, Simra, Roads, Tammy, Kennedy, Sarah, Duggal, Abhijit, Thiruchelvam, Nirosshan, Ashok, Kiran, King, Alexander H., Mehkri, Omar, Dugar, Siddharth, Sahoo, Debasis, Yealy, Donald M., Angus, Derek C., Weissman, Alexandra J., Vita, Tina M., Berryman, Emily, Hough, Catherine L., Khan, Akram, Krol, Olivia F., Mills, Emmanuel, Kinjal, Mistry, Briceno, Genesis, Reddy, Raju, Hubel, Kinsley, Jouzestani, Milad K., McDougal, Madeline, Deshmukh, Rupali, Johnston, Nicholas J., Robinson, Bryce H., Gundel, Staphanie J., Katsandres, Sarah C., Chen, Peter, Torbati, Sam S., Parimon, Tanyalak, Caudill, Antonina, Mattison, Brittany, Jackman, Susan E., Chen, Po-En, Bayoumi, Emad, Ojukwu, Cristabelle, Fine, Devin, Weissberg, Gwendolyn, Isip, Katherine, Choi-Kuaea, Yunhee, Mehdikhani, Shaunt, Dar, Tahir B., Fleury Augustin, Nsole Biteghe, Tran, Dana, Dukov, Jennifer Emilow, Matusov, Yuri, Choe, June, Hindoyan, Niree A., Wynter, Timothy, Pascual, Ethan, Clapham, Gregg J., Herrera, Lisa, Caudill, Antonia, O’Mahony, D. Shane, Nyatsatsang, Sonam T., Wilson, David M., Wallick, Julie A., Duven, Alexandria M., Fletcher, Dakota D., Miller, Chadwick, Files, D. Clark, Gibbs, Kevin W., Flores, Lori S., LaRose, Mary E., Landreth, Leigha D., Palacios, D. Rafael, Parks, Lisa, Hicks, Madeline, Goodwin, Andrew J., Kilb, Edward F., Lematty, Caitlan T., Patti, Kerilyn, Grady, Abigail, Rasberry, April, Morris, Peter E., Sturgill, Jamie L., Cassity, Evan P., Dhar, Sanjay, Montgomery-Yates, Ashley A., Pasha, Sarah N., Mayer, Kirby P., Pharm.D., Brittany Bissel, Trott, Terren, Rehman, Shahnaz, de Wit, Marjolein, Mason, Jessica, Bledsoe, Joseph, Knowlton, Kirk U., Brown, Samuel, Lanspa, Michael, Leither, Lindsey, Pelton, Ithan, Armbruster, Brent P., Montgomery, Quinn, Kumar, Naresh, Fergus, Melissa, Imel, Karah, Palmer, Ghazal, Webb, Brandon, Klippel, Carolyn, Jensen, Hannah, Duckworth, Sarah, Gray, Andrew, Burke, Tyler, Knox, Dan, Lumpkin, Jenna, Aston, Valerie T., Applegate, Darrin, Serezlic, Erna, Brown, Katie, Merril, Mardee, Harris, Estelle S., Middleton, Elizabeth A., Barrios, Macy A.G., Greer, Jorden, Schmidt, Amber D., Webb, Melissa K., Paine, Roert, Callahan, Sean J., Waddoups, Lindsey J., Yamane, Misty B., Self, Wesley H., Rice, Todd W., Casey, Jonathan D., Johnson, Jakea, Gray, Christopher, Hays, Margaret, Roth, Megan, Menon, Vidya, Kasubhai, Moiz, Pillai, Anjana, Daniel, Jean, Sittler, Daniel, Kanna, Balavenkatesh, Jilani, Nargis, Amaro, Francisco, Santana, Jessica, Lyakovestsky, Aleksandr, Madhoun, Issa, Desroches, Louis Marie, Amadon, Nicole, Bahr, Alaa, Ezzat, Imaan, Guerrero, Maryanne, Padilla, Joane, Fullmer, Jessie, Singh, Inderpreet, Ali Shah, Syed Hamad, Narang, Rajeev, Mock, Polly, Shadle, Melissa, Hernandez, Brenda, Welch, Kevin, Payne, Andrea, Ertl, Gabriela, Canario, Daniel, Barrientos, Isabel, Goss, Danielle, DeVries, Mattie, Folowosele, Ibidolapo, Garner, Dorothy, Gomez, Mariana, Price, Justin, Bansal, Ekta, Wong, Jim, Faulhaber, Jason, Fazili, Tasaduq, Yeary, Brian, Ndolo, Ruth, Bryant, Christina, Smigeil, Bridgette, Robinson, Philip, Najjar, Rana, Jones, Patrice, Nguyen, Julie, Chin, Christina, Taha, Hassan, Najm, Salah, Smith, Christopher, Moore, Jason, Nassar, Talal, Gallinger, Nick, Christian, Amy, Mauer, D’Amber, Phipps, Ashley, Waters, Michael, Zepeda, Karla, Coslet, Jordan, Landazuri, Rosalynn, Pineda, Jacob, Uribe, Nicole, Garcia, Jose Ruiz, Barbabosa, Cecilia, Sandler, Kaitlyn, Overcash, J. Scott, Marquez, Adrienna, Chu, Hanh, Lee, Kia, Quillin, Kimberly, Garcia, Andrea, Lew, Pauline, Rogers, Ralph, Shehadeh, Fadi, Mylona, Evangelia K., Kaczynski, Matthew, Tran, Quynh-Lam, Benitez, Gregorio, Mishra, Biswajit, Felix, Lewis Oscar, Vafea, Maria Tsikala, Atalla, Eleftheria, Davies, Robin, Hedili, Salma, Monkeberg, Maria Andrea, Tabler, Sandra, Harrington, Britt, Meegada, Sreenath, Koripalli, Venkata Sandeep, Muddana, Prithvi, Jain, Lakshay, Undavalli, Chaitanya, Kavya, Parasa, Ibiwoye, Mofoluwaso, Akilo, Hameed, Lovette, Bryce D., Wylie, Jamie-Crystal, Smith, Diana M., Poon, Kenneth, Eckardt, Paula, Heysu, Rubio-Gomez, Sundararaman, Nithya, Alaby, Doris, Sareli, Candice, Sánchez, Adriana, Popielski, Laura, Kambo, Amy, Viens, Kimberley, Turner, Melissa, Vjecha, Michael J., Weintrob, Amy, Brar, Indira, Markowitz, Norman, Pastor, Erika, Corpuz, Roweena, Alangaden, George, McKinnon, John, Ramesh, Mayur, Herc, Erica, Yared, Nicholas, Lanfranco, Odaliz Abreu, Rivers, Emanuel, Swiderek, Jennifer, Gupta, Ariella Hodari, Pabla, Pardeep, Eliya, Sonia, Jazrawi, Jehan, Delor, Jeremy, Desai, Mona, Cook, Aaron, Jaehne, Anja Kathrina, Gill, Jasreen Kaur, Renaud, Sheri, Sarveswaran, Siva, Gardner, Edward, Scott, James, Bianchini, Monica, Melvin, Casey, Kim, Gina, Wyles, David, Kamis, Kevin, Miller, Rachel, Douglas, Ivor, Haukoos, Jason, Hicks, Carrie, Lazarte, Susana, Marines-Price, Rubria, Osuji, Alice, Agbor Agbor, Barbine Tchamba, Petersen, Tianna, Kamel, Dena, Hansen, Laura, Garcia, Angie, Cha, Christine, Mozaffari, Azadeh, Hernandez, Rosa, Cutrell, James, Kim, Mina, DellaValle, Natalie, Gonzales, Sonia, Somboonwit, Charurut, Oxner, Asa, Guerra, Lucy, Hayes, Michael, Nguyen, Thi, Tran, Thanh, Pinto, Avenette, Hatlen, Timothy, Anderson, Betty, Zepeda-Gutierrez, Ana, Martin, Dannae, Temblador, Cindi, Cuenca, Avon, Tanoviceanu, Roxanne, Prieto, Martha, Guerrero, Mario, Daar, Eric, Correa, Ramiro, Hartnell, Gabe, Wortmann, Glenn, Doshi, Saumil, Moriarty, Theresa, Gonzales, Melissa, Garman, Kristin, Baker, Jason V., Frosch, Anne, Goldsmith, Rachael, Driver, Brian, Frank, Christine, Leviton, Tzivia, Prekker, Matthew, Jibrell, Hodan, Lo, Melanie, Klaphake, Jonathan, Mackedanz, Shari, Ngo, Linh, Garcia-Myers, Kelly, Kunisaki, Ken M., Wendt, Chris, Melzer, Anne, Wetherbee, Erin, Drekonja, Dimitri, Pragman, Alexa, Hamel, Aimee, Thielen, Abbie, Hassler, Miranda, Walquist, Mary, Augenbraun, Michael, George, Jensen, Demeo, Lynette, Mishko, Motria, Thomas, Lorraine, Tatem, Luis, Dehovitz, Jack, Abassi, Mahsa, Leuck, Anne-Marie, Rao, Via, Pullen, Matthew, Luke, Darlette, LaBar, Derek, Christiansen, Theresa, Howard, Diondra, Biswas, Kousick, Harrington, Cristin, Garcia, Amanda, Bremer, Tammy, Burke, Tara, Koker, Brittany, Davis-Karim, Anne, Pittman, David, Vasudeva, Shikha S., Johnstone, Jaylynn R., Agnetti, Kate, Davis, Ruby, Trautner, Barbara, Hines-Munson, Casey, Van, John, Dillon, Laura, Wang, Yiqun, Nagy-Agren, Stephanie, Vasudeva, Shikha, Ochalek, Tracy, Caldwell, Erin, Humerickhouse, Edward, Boone, David, McGraw, William, Looney, David J., Mehta, Sanjay R., Johns, Scott Thompson, St. John, Melissa, Raceles, Jacqueline, Sear, Emily, Funk, Stephen, Cesarini, Rosa, Fang, Michelle, Nicalo, Keith, Drake, Wonder, Jones, Beatrice, Holtman, Teresa, Nguyen, Hien H., Maniar, Archana, Johnson, Eric A., Nguyen, Lam, Tran, Michelle T., Barrett, Thomas W., Johnston, Tera, Huggins, John T., Beiko, Tatsiana Y., Hughes, Heather Y., McManigle, William C., Tanner, Nichole T., Washburn, Ronald G., Ardelt, Magdalena, Tuohy, Patricia A., Mixson, Jennifer L., Hinton, Charles G., Thornley, Nicola, Allen, Heather, Elam, Shannon, Boatman, Barry, Baber, Brittany J., Ryant, Rudell, Roller, Brentin, Nguyen, Chinh, Mikail, Amani Morgan, Research, Marivic Hansen, Lichtenberger, Paola, Baracco, Gio, Ramos, Carol, Bjork, Lauren, Sueiro, Melyssa, Tien, Phyllis, Freasier, Heather, Buck, Theresa, Nekach, Hafida, Holodniy, Mark, Chary, Aarthi, Lu, Kan, Peters, Theresa, Lopez, Jessica, Tan, Susanna Yu, Lee, Robert H., Asghar, Aliya, Karyn Isip, Tasadduq Karim, Le, Katherine, Nguyen, Thao, Wong, Shinn, Raben, Dorthe, Murray, Daniel D., Jensen, Tomas O., Peters, Lars, Aagaard, Bitten, Nielsen, Charlotte B., Krapp, Katharina, Nykjær, Bente Rosdahl, Olsson, Christina, Kanne, Katja Lisa, Grevsen, Anne Louise, Joensen, Zillah Maria, Bruun, Tina, Bojesen, Ane, Woldbye, Frederik, Normand, Nick E., Esman, Frederik V.L., Benfield, Thomas, Clausen, Clara Lundetoft, Hovmand, Nichlas, Israelsen, Simone Bastrup, Iversen, Katrine, Leding, Caecilie, Pedersen, Karen Brorup, Thorlacius-Ussing, Louise, Tinggaard, Michaela, Tingsgard, Sandra, Krohn-Dehli, Louise, Pedersen, Dorthe, Villadsen, Signe, Staehr Jensen, Jens-Ulrik, Overgaard, Rikke, Rastoder, Ema, Heerfordt, Christian, Hedsund, Caroline, Ronn, Christian Phillip, Kamstrup, Peter Thobias, Hogsberg, Dorthe Sandbaek, Bergsoe, Christina, Søborg, Christian, Hissabu, Nuria M.S., Arp, Bodil C., Ostergaard, Lars, Staerke, Nina Breinholt, Yehdego, Yordanos, Sondergaard, Ane, Johansen, Isik S., Pedersen, Andreas Arnholdt, Knudtzen, Fredrikke C., Larsen, Lykke, Hertz, Mathias A., Fabricius, Thilde, Holden, Inge K., Lindvig, Susan O., Helleberg, Marie, Gerstoft, Jan, Kirk, Ole, Jensen, Tomas Ostergaard, Madsen, Birgitte Lindegaard, Pedersen, Thomas Ingemann, Harboe, Zitta Barrella, Roge, Birgit Thorup, Hansen, Thomas Michael, Glesner, Matilde Kanstrup, Lofberg, Sandra Valborg, Nielsen, Ariella Denize, Leicht von Huth, Sebastian, Nielsen, Henrik, Thisted, Rikke Krog, Petersen, Kristine Toft, Juhl, Maria Ruwald, Podlekareva, Daria, Johnsen, Stine, Andreassen, Helle Frost, Pedersen, Lars, Clara Ellinor Lindnér, Cecilia Ebba, Wiese, Lothar, Knudsen, Lene Surland, Skrøder Nytofte, Nikolaj Julian, Havmøller, Signe Ravn, Expósito, Maria, Badillo, José, Martínez, Ana, Abad, Elena, Chamorro, Ana, Figuerola, Ariadna, Mateu, Lourdes, España, Sergio, Lucero, Maria Constanza, Santos, José Ramón, Lladós, Gemma, Lopez, Cristina, Carabias, Lydia, Molina-Morant, Daniel, Loste, Cora, Bracke, Carmen, Siles, Adrian, Fernández-Cruz, Eduardo, Di Natale, Marisa, Padure, Sergiu, Gomez, Jimena, Ausin, Cristina, Cervilla, Eva, Balastegui, Héctor, Sainz, Carmen Rodríguez, Lopez, Paco, Carbone, Javier, Escobar, Mariam, Balerdi, Leire, Legarda, Almudena, Roldan, Montserrat, Letona, Laura, Muñoz, José, Camprubí, Daniel, Arribas, Jose R., Sánchez, Rocio Montejano, Díaz-Pollán, Beatriz, Stewart, Stefan Mark, Garcia, Irene, Borobia, Alberto, Mora-Rillo, Marta, Estrada, Vicente, Cabello, Noemi, Nuñez-Orantos, M.J., Sagastagoitia, I., Homen, J.R., Orviz, E., Montalvá, Adrián Sánchez, Espinosa-Pereiro, Juan, Bosch-Nicolau, Pau, Salvador, Fernando, Burgos, Joaquin, Morales-Rull, Jose Luis, Moreno Pena, Anna Maria, Acosta, Cristina, Solé-Felip, Cristina, Horcajada, Juan P., Sendra, Elena, Castañeda, Silvia, López-Montesinos, Inmaculada, Gómez-Junyent, Joan, Gonzáles, Carlota Gudiol, Cuervo, Guilermo, Pujol, Miquel, Carratalà, Jordi, Videla, Sebastià, Günthard, Huldrych, Braun, Dominique L., West, Emily, M’Rabeth-Bensalah, Khadija, Eichinger, Mareile L., Grüttner-Durmaz, Manuela, Grube, Christina, Zink, Veronika, pharmacist, Goes pharmacist, Josefine, Fätkenheuer, Gerd, Malin, Jakob J., Tsertsvadze, Tengiz, Abutidze, Akaki, Chkhartishvili, Nikoloz, Metchurtchlishvili, Revaz, Endeladze, Marina, Paciorek, Marcin, Bursa, Dominik, Krogulec, Dominika, Pulik, Piotr, Ignatowska, Anna, Horban, Andrzej, Bakowska, Elzbieta, Kowaska, Justyna, Bednarska, Agnieszka, Jurek, Natalia, Skrzat-Klapaczynska, Agata, Bienkowski, Carlo, Hackiewicz, Malgorzata, Makowiecki, Michal, Platowski, Antoni, Fishchuk, Roman, Kobrynska, Olena, Levandovska, Khrystyna, Kirieieva, Ivanna, Kuziuk, Mykhailo, Naucler, Pontus, Perlhamre, Emma, Mazouch, Lotta, Kelleher, Anthony, Polizzotto, Mark, Carey, Catherine, Chang, Christina C., Hough, Sally, Virachit, Sophie, Davidson, Sarah, Bice, Daniel J., Ognenovska, Katherine, Cabrera, Gesalit, Flynn, Ruth, Young, Barnaby E., Chia, Po Ying, Lee, Tau Hong, Lin, Ray J., Lye, David C., Ong, Sean W.X., Puah, Ser Hon, Yeo, Tsin Wen, Diong, Shiau Hui, Ongko, Juwinda, Yeo, He Ping, Eriobu, Nnakelu, Kwaghe, Vivian, Zaiyad, Habib, Idoko, Godwin, Uche, Blessing, Selvamuthu, Poongulali, Kumarasamy, Nagalingeswaran, Beulah, Faith Ester, Govindarajan, Narayan, Mariyappan, Kowsalya, Losso, Marcelo H., Abela, Cecilia, Moretto, Renzo, Belloc, Carlos G., Ludueña, Jael, Amar, Josefina, Toibaro, Javier, Macias, Laura Moreno, Fernandez, Lucia, Frare, Pablo S., Chaio, Sebastian R., Pachioli, Valeria, Timpano, Stella M., Sanchez, Marisa del Lujan, de Paz Sierra, Mariana, Stanek, Vanina, Belloso, Waldo, Cilenti, Flavia L., Valentini, Ricardo N., Stryjewski, Martin E., Locatelli, Nicolas, Soler Riera, Maria C., Salgado, Clara, Baeck, Ines M., Di Castelnuovo, Valentina, Zarza, Stella M., Hudson, Fleur, Parmar, Mahesh K.B., Goodman, Anna L., Dphil, Badrock, Jonathan, Gregory, Adam, Goodall, Katharine, Harris, Nicola, Wyncoll, James, Bhagani, S., Rodger, A., Luntiel, A., Patterson, C., Morales, J., Witele, E., Preston, A.-M., Nandani, A., Price, D.A., Hanrath, Aiden, Nell, Jeremy, Patel, Bijal, Hays, Carole, Jones, Geraldine, Davidson, Jade, Bawa, T., Mathews, M., Mazzella, A., Bisnauthsing, K., Aguilar-Jimenez, L., Borchini, F., Hammett, S., Touloumi, Giota, Pantazis, Nikos, Gioukari, Vicky, Souliou, Tania, Antoniadou, A., Protopapas, K., Kavatha, D., Grigoropoulou, S., Oikonomopoulo, C., Moschopoulos, C., Koulouris, N.G., Tzimopoulos, K., Koromilias, A., Argyraki, K., Lourida, P., Bakakos, P., Kalomenidis, I., Vlachakos, V., Barmparessou, Z., Balis, E., Zakynthinos, S., Sigala, I., Gianniou, N., Dima, E., Magkouta, S., Synolaki, E., Konstanta, S., Vlachou, M., Stathopoulou, P., Panagopoulos, P., Petrakis, V., Papazoglou, D., Tompaidou, E., Isaakidou, E., Poulakou, G., Rapti, V., Leontis, K., Nitsotolis, T., Athanasiou, K., Syrigos, K., Kyriakoulis, K., Trontzas, I., Arfara-Melanini, M., Kolonis, V., Kityo, Cissy, Mugerwa, Henry, Kiweewa, Francis, Kimuli, Ivan, Lukaakome, Joseph, Nsereko, Christoher, Lubega, Gloria, Kibirige, Moses, Nakahima, William, Wangi, Deus, Aguti, Evelyne, Generous, Lilian, Massa, Rosemary, Nalaki, Margaret, Magala, Felix, Nabaggala, Phiona Kaweesi, Kidega, Robert, Faith, Oryem Daizy, Florence, Apio, Emmanuel, Ocung, Beacham, Mugoonyi Paul, Geoffrey, Amone, Nakiboneka, Dridah, Apiyo, Paska, Kirenga, Bruce, Atukunda, Angella, Muttamba, Winters, Remmy, Kyeyume, Segawa, Ivan, Pheona, Nsubuga, Kigere, David, Mbabazi, Queen Lailah, Boersalino, Ledra, Nyakoolo, Grace, Fred, Aniongo, Alupo, Alice, Ebong, Doryn, Monday, Edson, Nalubwama, Ritah Norah, Kainja, Milton, Ambrose, Munu, Kwehayo, Vanon, Nalubega, Mary Grace, Ongoli, Augustine, Obbo, Stephen, Sebudde, Nicholus, Alaba, Jeniffer, Magombe, Geoffrey, Tino, Harriet, Obonya, Emmanuel, Lutaakome, Joseph, Kitonsa, Jonathan, Onyango, Martin, Naboth, Tukamwesiga, Naluyinda, Hadijah, Nanyunja, Regina, Irene, Muttiibwa, Jane, Biira, Wimfred, Kyobejja, Leonard, Ssemazzi, Deus, Tkiinomuhisha, Babra, Namasaba, Taire, Paul, Nabankema, Evelyn, Ogavu, Joseph, Mugerwa, Oscar, Okoth, Ivan, Mwebaze, Raymond, Mugabi, Timothy, Makhoba, Anthony, Arikiriza, Phiona, Theresa, Nabuuma, Nakayima, Hope, Frank, Kisuule, Ramgi, Patrícia, Pereira, Kássia, Osinusi, Anu, Cao, Huyen, Klekotka, Paul, Price, Karen, Nirula, Ajay, Osei, Suzette, Tipple, Craig, Wills, Angela, Peppercorn, Amanda, Watson, Helen, Gupta, Rajesh, Alexander, Elizabeth, Mogalian, Erik, Lin, Leo, Ding, Xiao, Margolis, David, Yan, Li, Girardet, Jean-Luc, Ma, Ji, Hong, Zhi, Zhu, Quing, Seegobin, Seth, Gibbs, Michael, Latchman, Mickel, Hasior, Katarzyna, Bouquet, Jerome, Wei, Jianxin, Streicher, Katie, Schmelzer, Albert, Brooks, Dennis, Butcher, Jonny, Tonev, Dimitar, Arbetter, Douglas, Damstetter, Philippe, Legenne, Philippe, Stumpp, Michael, Goncalves, Susana, Ramanathan, Krishnan, Chandra, Richa, Baseler, Beth, Teitelbaum, Marc, Schechner, Adam, Holley, H. Preston, Jankelevich, Shirley, Becker, Nancy, Dolney, Suzanne, Hissey, Debbie, Simpson, Shelly, Kim, Mi Ha, Beeler, Joy, Harmon, Liam, Asomah, Mabel, Jato, Yvonne, Stottlemyer, April, Tang, Olivia, Vanderpuye, Sharon, Yeon, Lindsey, Buehn, Molly, Eccard-Koons, Vanessa, Frary, Sadie, MacDonald, Leah, Cash, Jennifer, Hoopengardner, Lisa, Linton, Jessica, Schaffhauser, Marylu, Nelson, Michaela, Spinelli-Nadzam, Mary, Proffitt, Calvin, Lee, Christopher, Engel, Theresa, Fontaine, Laura, Osborne, C.K., Hohn, Matt, Galcik, Michael, Thompson, DeeDee, Kopka, Stacey, Shelley, Denise M., Mendez, Gregg, Brown, Shawn, Albert, Sara, Balde, Abby, Baracz, Michelle, Bielica, Mona, Billouin-Frazier, Shere, Choudary, Jay, Dixon, Mary, Eyler, Carolyn, Frye, Leanne, Gertz, Jensen, Giebeig, Lisa, Gulati, Neelam, Hankinson, Liz, Hogarty, Debi, Huber, Lynda, Krauss, Gary, Lake, Eileen, Manandhar, Meryan, Rudzinski, Erin, Sandrus, Jen, Suders, Connie, Natarajan, Ven, Rupert, Adam W., Baseler, Michael, Lynam, Danielle, Imamichi, Tom, Laverdure, Sylvain, McCormack, Ashley, Paudel, Sharada, Cook, Kyndal, Haupt, Kendra, Khan, Ayub, Hazen, Allison, Badralmaa, Yunden, Smith, Kenneth, Patel, Bhakti, Kubernac, Amanda, Kubernac, Robert, Hoover, Marie L., Solomon, Courtney, Rashid, Marium, Murphy, Joseph, Brown, Craig, DuChateau, Nadine, Ellis, Sadie, Flosi, Adam, Fox, Lisa, Johnson, Les, Nelson, Rich, Stojanovic, Jelena, Treagus, Amy, Wenner, Christine, Williams, Richard, Jensen, Tomas O, Murray, Thomas A, Grandits, Greg A, Jain, Mamta K, Shaw-Saliba, Kathryn, Matthay, Michael A, Baker, Jason V, Dewar, Robin L, Goodman, Anna L, Hatlen, Timothy J, Highbarger, Helene C, Lallemand, Perrine, Leshnower, Bradley G, Looney, David, Moschopoulos, Charalampos D, Murray, Daniel D, Mylonakis, Eleftherios, Rehman, M Tauseef, Rupert, Adam, Stevens, Randy, Turville, Stuart, Wick, Katherine, Lundgren, Jens, and Ko, Emily R
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- 2024
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6. Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial
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Group, The ITAC Study, Polizzotto, Mark N, Nordwall, Jacqueline, Babiker, Abdel G, Phillips, Andrew, Vock, David M, Eriobu, Nnakelu, Kwaghe, Vivian, Paredes, Roger, Mateu, Lourdes, Ramachandruni, Srikanth, Narang, Rajeev, Jain, Mamta K, Lazarte, Susana M, Baker, Jason V, Frosch, Anne EP, Poulakou, Garyfallia, Syrigos, Konstantinos N, Arnoczy, Gretchen S, McBride, Natalie A, Robinson, Philip A, Sarafian, Farjad, Bhagani, Sanjay, Taha, Hassan S, Benfield, Thomas, Liu, Sean TH, Antoniadou, Anastasia, Jensen, Jens Ulrik Stæhr, Kalomenidis, Ioannis, Susilo, Adityo, Hariadi, Prasetyo, Jensen, Tomas O, Morales-Rull, Jose Luis, Helleberg, Marie, Meegada, Sreenath, Johansen, Isik S, Canario, Daniel, Fernández-Cruz, Eduardo, Metallidis, Simeon, Shah, Amish, Sakurai, Aki, Koulouris, Nikolaos G, Trotman, Robin, Weintrob, Amy C, Podlekareva, Daria, Hadi, Usman, Lloyd, Kathryn M, Røge, Birgit Thorup, Saito, Sho, Sweerus, Kelly, Malin, Jakob J, Lübbert, Christoph, Muñoz, Jose, Cummings, Matthew J, Losso, Marcelo H, Turner, Dan, Shaw-Saliba, Kathryn, Dewar, Robin, Highbarger, Helene, Lallemand, Perrine, Rehman, Tauseef, Gerry, Norman, Arlinda, Dona, Chang, Christina C, Grund, Birgit, Holbrook, Michael R, Holley, Horace P, Hudson, Fleur, McNay, Laura A, Murray, Daniel D, Pett, Sarah L, Shaughnessy, Megan, Smolskis, Mary C, Touloumi, Giota, Wright, Mary E, Doyle, Mittie K, Popik, Sharon, Hall, Christine, Ramanathan, Roshan, Cao, Huyen, Mondou, Elsa, Willis, Todd, Thakuria, Joseph V, Yel, Leman, Higgs, Elizabeth, Kan, Virginia L, Lundgren, Jens D, Neaton, James D, and Lane, H Clifford
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Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Emerging Infectious Diseases ,Clinical Research ,Vaccine Related ,Clinical Trials and Supportive Activities ,Lung ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adenosine Monophosphate ,Alanine ,Antibodies ,Neutralizing ,Antiviral Agents ,COVID-19 ,COVID-19 Vaccines ,Double-Blind Method ,Female ,Hospitalization ,Humans ,Inpatients ,Internationality ,Male ,Middle Aged ,Treatment Outcome ,Vaccines ,Inactivated ,ITAC (INSIGHT 013) Study Group ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundPassive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited.MethodsIn this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581.FindingsFrom Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77-1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66-1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14-4·29); for patients who were antibody negative, the OR was 0·51 (0·29-0·90; pinteraction=0·001).InterpretationWhen administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry.FundingUS National Institutes of Health.
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- 2022
7. Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19
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Kuriakose, Safia, Singh, Kanal, Pau, Alice K, Daar, Eric, Gandhi, Rajesh, Tebas, Pablo, Evans, Laura, Gulick, Roy M, Lane, H Clifford, Masur, Henry, Aberg, Judith A, Adimora, Adaora A, Baker, Jason, Kreuziger, Lisa Baumann, Bedimo, Roger, Belperio, Pamela S, Cantrill, Stephen V, Coopersmith, Craig M, Davis, Susan L, Dzierba, Amy L, Gallagher, John J, Glidden, David V, Grund, Birgit, Hardy, Erica J, Hinkson, Carl, Hughes, Brenna L, Johnson, Steven, Keller, Marla J, Kim, Arthur Y, Lennox, Jeffrey L, Levy, Mitchell M, Li, Jonathan Z, Martin, Greg S, Naggie, Susanna, Pavia, Andrew T, Seam, Nitin, Simpson, Steven Q, Swindells, Susan, Tien, Phyllis, Waghmare, Alpana A, Wilson, Kevin C, Yazdany, Jinoos, Zachariah, Philip, Campbell, Danielle M, Harrison, Carly, Burgess, Timothy, Francis, Joseph, Sheikh, Virginia, Uyeki, Timothy M, Walker, Robert, Brooks, John T, Ortiz, Laura Bosque, Davey, Richard T, Doepel, Laurie K, Eisinger, Robert W, Han, Alison, Higgs, Elizabeth S, Nason, Martha C, Crew, Page, Lerner, Andrea M, Lund, Claire, and Worthington, Christopher
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Biomedical and Clinical Sciences ,Clinical Sciences ,Health Services ,Clinical Research ,Generic health relevance ,Good Health and Well Being ,Advisory Committees ,COVID-19 ,Child ,Data Interpretation ,Statistical ,Drug Approval ,Evidence-Based Medicine ,Female ,Humans ,Interprofessional Relations ,National Institutes of Health (U.S.) ,Pandemics ,Practice Guidelines as Topic ,Pregnancy ,SARS-CoV-2 ,Stakeholder Participation ,United States ,COVID-19 Drug Treatment ,NIH COVID-19 Treatment Guidelines Panel ,Medical and Health Sciences ,General & Internal Medicine ,Clinical sciences - Abstract
The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.
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- 2021
8. Convalescent Plasma for the Treatment of COVID-19: Perspectives of the National Institutes of Health COVID-19 Treatment Guidelines Panel
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Pau, Alice K, Aberg, Judith, Baker, Jason, Belperio, Pamela S, Coopersmith, Craig, Crew, Page, Glidden, David V, Grund, Birgit, Gulick, Roy M, Harrison, Carly, Kim, Arthur, Lane, H Clifford, Masur, Henry, Sheikh, Virginia, Singh, Kanal, Yazdany, Jinoos, and Tebas, Pablo
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Emerging Infectious Diseases ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,COVID-19 ,Humans ,Immunization ,Passive ,National Institutes of Health (U.S.) ,Plasma ,SARS-CoV-2 ,United States ,COVID-19 Serotherapy ,National Institutes of Health COVID-19 Treatment Guidelines Panel ,Medical and Health Sciences ,General & Internal Medicine ,Clinical sciences - Abstract
In the United States, the efficacy and safety of convalescent plasma for treating coronavirus disease 2019 (COVID-19) is currently being tested in randomized placebo-controlled clinical trials. Treatment of individual patients with COVID-19 with convalescent plasma outside such trials is also now permitted through U.S. Food and Drug Administration Emergency Use Authorization. Here, members of the National Institutes of Health COVID-19 Treatment Guidelines Panel provide their views regarding use of convalescent plasma for treating COVID-19.
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- 2021
9. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial
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Tierney, John, Vogel, Susan E., McNay, Laura A., Cahill, Kelly, Crew, Page, Sardana, Ratna, Segal Raim, Sharo, Shaw-Saliba, Katy, Atri, Negin, Miller, Mark, Vallee, David, Chung, Lucy, Delph, Yvette, Adam, Stacey J., Read, Sarah, Draghia-Akli, Ruxandra, Harrigan, Rachel, Carlsen, Amy, Carter, Anita, DuChene, Alain, Eckroth, Kate, Frase, Alex, Harrison, Merrie, Meger, Sue, Quan, Kien, Quan, Siu Fun, Reilly, Cavan, Thompson, Greg, Walski, Jamie, Moskowitz, Alan J., Bagiella, Emilia, Moquete, Ellen, O'Sullivan, Karen, Marks, Mary E., Accardi, Evan, Kinzel, Emily, Bedoya, Gabriela, Gupta, Lopa, Overbey, Jessica R., Padillia, Maria L., Santos, Milerva, Gillinov, Marc A., Miller, Marissa A., Taddei-Peters, Wendy C., Fenton, Kathleen, Smith, Peter K., Vekstein, Andrew M., Ko, Emily R., Al-Hegelan, Mashael S., McGowan, Lauren M., Motta, Mary, Howell, Shauna, Bent, Francine, Kalager, Rachel, Chan, Emmanuel, Aloor, Heather L., Griffin, S. Michelle, Covington, Anna, McLendon-Arvik, Beth, Bussadori, Barbara, Miller-Bell, Mary, Sampey, Cathy, Gaver, Vincent, Hollister, Beth A., Giangiacomo, Dana M., Pauley, Alena, Patel, Aashay, Classon, Chris, Frazier, Madison, Osborne, Robyn, Conlon, Debbi H., Joshi, Marybeth, Gottlieb, Robert L., Mack, Michael, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Bettacchi, Christopher, Golden, Kevin, Duhaime, Erin, Ryan, Madison, Tallmadge, Catherine, Estrada, Lorie, Jones, Felecia, Villa, Samantha, Wang, Samantha, Robert, Raven, Coleman, Tanquinisha, Clariday, Laura, Baker, Rebecca, Hurutado-Rodriguez, Mariana, Iram, Nazia, Fresnedo, Michelle, Davis, Allyson, Leonard, Kiara, Ramierez, Noelia, Thammavong, Jon, Duque, Krizia, Turner, Emma, Fisher, Tammy, Robinson, Dianna, Ransom, Desirae, Maldonado, Nicholas, Lusk, Erica, Killian, Aaron, Palacios, Adriana, Solis, Edilia, Jerrow, Janet, Watts, Matthew, Whitacre, Heather, Cothran, Elizabeth, Bender, William, Miller, Jeffrey, Nugent, Katherine, Farrington, Woodrow, Baio, Kim T., McBride, Mary K., Fielding, Michele, Mathewson, Sonya, Porte, Kristina, Haley, Elizabeth, Rogers, Susan, Tyler, Derrick, Perin, Emerson, Costello, Briana, Postalian, Alexander, Sohail, Rizwan, Hinsu, Punit, Watson, Carolyn, Kappenman, Casey, Chen, James, Walker, Kim, Fink, Melyssa, Phillip, Gabrielle, Mahon, Kim, Sturgis, Lydia, Maher, Patrick, Rogers, Linda, Ng, Nicole, Marshall, Jason, Bassily-Marcus, Adel, Cohen, Ivy, Ramoo, Shamini, Malhotra, Aryan, Kessler, Jonathan, Goetz, Rebekah, Badhwar, Vinay, Hayanga, Jeremiah, Giblin Sutton, Lisa, Williams, Roger, Berry Bartolo, Elizabeth, Walker, Dmitry, Bunner, Robin, Glaze, Chad, Aucremanne, Tanja, Bishop, James, Kelley, Macey, Peterson, Autumn, Sauerborn, Erica, Reckart, Robin, Miller, Brittany, Mittel, Aaron, Darmanian, Anita, Rosen, Amanda, Madahar, Purnema, Schicchi, John, Gosek, Katarzyna, Dzierba, Amy, Wahab, Romina, Eng, Connie, Al-Saadi, Mukhtar, Zahiruddin, Faisal, Syed, Mohi, George, Michael, Patel, Varsha, Onwunyi, Chisom, Barroso da Costa, Rosa, North, Crystal, Ringwood, Nancy, Fitzgerald, Laura, Muzikansky, Ariela, Morse, Richard, Brower, Roy G., Reineck, Lora A., Bienstock, Karen, Hou, Peter, Steingrub, Jay S., Tidswell, Mark A., Kozikowski, Lori-Ann, Kardos, Cynthia, De Souza, Leslie, Talmor, Daniel, Shapiro, Nathan, Hibbert, Kathryn, Brait, Kelsey, Kone, Mamary, Hendey, Gregory, Kangelaris, Kirsten N., Ashktorab, Kimia, Gropper, Rachel, Agrawal, Anika, Timothy, Kelly, Zhou, Hanjing, Hughes, Alyssa, Garcia, Rebekah, Torres, Adrian, Hernandez-Almaraz, Maria Elena, Vojnik, Rosemary, Perez, Cynthia, McDowell, Jordan, Chang, Steven Y., Vargas, Julia, Moss, Marc, McKeehan, Jeffrey, Higgins, Carrie, Johnson, Emily, Slaughter, Suzanne, Wyles, David, Hiller, Terra, Oakes, Judy, Garcia, Ana, Gravitz, Stephanie, Lyle, Carolynn, Swanson, Diandra, Gong, Michelle Ng., Richardson, Lynnne D., Chen, Jen-Ting, Moskowitz, Ari, Mohamed, Amira, Lopez, Brenda, Amosu, Omowunmi, Tzehaie, Hiwet, Boujid, Sabah, Bixby, Billie, Lopez, Anitza A., Durley, JaVon, Gilson, Boris, Hite, R. Duncan, Wang, Henry, Wiedemann, Hebert P., Mehkri, Omar, Ashok, Kiran, King, Alexander, Brennan, Connery, Exline, Matthew C., Englert, Joshua A., Karow, Sarah, Schwartz, Elizabeth, So, Preston, So, Madison, Krol, Olivia F., Briceno Parra, Genesis I., Mills, Emmanuel Nii Lantei, Oh, Minn, Pena, Jose, Martínez, Jesús Alejandro, Jackman, Susan E., Bayoumi, Emad, Pascual, Ethan, Caudill, Antonina, Chen, Po-En, Richardson, Tabia, Clapham, Gregg J., Herrera, Lisa, Ojukwu, Cristabelle, Fine, Devin, Gomez, Millie J., Choi-Kuaea, Yunhee, Weissberg, Gwendolyn, Isip, Katherine, Mattison, Brittany, Tran, Dana, Emilov Dukov, Jennifer, Chung, Paul, Kang, Bo Ran, Escobar, Lauren, Tran, Trung, Baig, Saba, Wallick, Julie A., Duven, Alexandria M., Fletcher, Dakota D., Gundel, Stephanie, Fuentes, Megan, Newton, Maranda, Peterson, Emily, Jiang, Kelsey, Files, D. Clark, Miller, Chadwick, Lematty, Caitlin, Rasberry, April, Warden, Ashley, Bledsoe, Joseph, Knowlton, Kirk, Knox, Daniel B., Klippel, Carolyn, Armbruster, Brent P., Applegate, Darrin, Imel, Karah, Fergus, Melissa, Rahmati, Kasra, Jensen, Hannah, Aston, Valerie T., Jeppson, Joshua, Marshall, J. Hunter, Lumpkin, Jenna, Smith, Cassie, Burke, Tyler, Gray, Andrew, Paine, Robert, Callahan, Sean, Yamane, Misty, Waddoups, Lindsey, Rice, Todd W., Johnson, Jakea, Gray, Christopher, Hays, Margaret, Roth, Megan, Musick, Sarah, Miller, Karen, Semler, Matthew W., Popielski, Laura, Kambo, Amy, Viens, Kimberly, Turner, Melissa, Vjecha, Michael J., Denyer, Rachel, Khosla, Rahul, Rajendran, Bindu, Gonzales, Melissa, Moriarty, Theresa, Biswas, Kousick, Harrington, Cristin, Garcia, Amanda, Bremer, Tammy, Burke, Tara, Koker, Brittany, Pittman, David, Vasudeva, Shikha S., Anholm, James D., Specht, Lennard, Rodriguez, Aimee, Ngo, Han, Duong, Lien, Previte, Matthew, Raben, Dorthe, Nielsen, Charlotte B., Friis Larsen, Jakob, Peters, Lars, Matthews, Gail, Kelleher, Anthony, Polizzotto, Mark, Carey, Catherine, Chang, Christina, Dharan, Nila, Hough, Sally, Virachit, Sophie, Davidson, Sarah, Bice, Daniel J., Ognenovska, Katherine, Cabrera, Gesalit, Flynn, Ruth, Abdelghany, Mazin, Baseler, Beth, Teitelbaum, Marc, Holley, H. Preston, Jankelevich, Shirley, Adams, Amy, Becker, Nancy, Doleny, Suzanne, Hissey, Debbie, Simpson, Shelly, Kim, Mi Ha, Beeler, Joy, Harmon, Liam, Vanderpuye, Sharon, Yeon, Lindsey, Frye, Leanna, Rudzinski, Erin, Buehn, Molly, Eccard-Koons, Vanessa, Frary, Sadie, MacDonalad, Leah, Cash, Jennifer, Hoopengardner, Lisa, Linton, Jessica, Nelson, Michaela, Spinelli-Nadzam, Mary, Proffitt, Calvin, Lee, Christopher, Engel, Theresa, Fontaine, Laura, Osborne, CK, Hohn, Matt, Galcik, Michael, Thompson, DeeDee, Sandrus, Jen, Manchard, Jon, Giri, Jiwan, Kopka, Stacy, Chang, Weizhong, Sherman, Brad T., Rupert, Adam W., Highbarger, Helene, Baseler, Michael, Lallemand, Perrine, Rehman, Tauseef, Imamichi, Tom, Laverdure, Sylvain, Paudel, Sharada, Cook, Kyndal, Haupt, Kendra, Hazen, Allison, Badralmaa, Yunden, Highbarger, Jeroen, McCormack, Ashley, Gerry, Norman P., Smith, Kenneth, Patel, Bhakti, Domeraski, Nadia, Hoover, Marie L., DuChateau, Nadine, Flosi, Adam, Nelson, Rich, Stojanovic, Jelena, Wenner, Christine, Brown, Samuel M, Barkauskas, Christina E, Grund, Birgit, Sharma, Shweta, Phillips, Andrew N, Leither, Lindsay, Peltan, Ithan D, Lanspa, Michael, Gilstrap, Daniel L, Mourad, Ahmad, Lane, Kathleen, Beitler, Jeremy R, Serra, Alexis L, Garcia, Ivan, Almasri, Eyad, Fayed, Mohamed, Hubel, Kinsley, Harris, Estelle S, Middleton, Elizabeth A, Barrios, Macy A G, Mathews, Kusum S, Goel, Neha N, Acquah, Samuel, Mosier, Jarrod, Hypes, Cameron, Salvagio Campbell, Elizabeth, Khan, Akram, Hough, Catherine L, Wilson, Jennifer G, Levitt, Joseph E, Duggal, Abhijit, Dugar, Siddharth, Goodwin, Andrew J, Terry, Charles, Chen, Peter, Torbati, Sam, Iyer, Nithya, Sandkovsky, Uriel S, Johnson, Nicholas J, Robinson, Bryce R H, Matthay, Michael A, Aggarwal, Neil R, Douglas, Ivor S, Casey, Jonathan D, Hache-Marliere, Manuel, Georges Youssef, J, Nkemdirim, William, Leshnower, Brad, Awan, Omar, Pannu, Sonal, O'Mahony, Darragh Shane, Manian, Prasad, Awori Hayanga, J W, Wortmann, Glenn W, Tomazini, Bruno M, Miller, Robert F, Jensen, Jens-Ulrik, Murray, Daniel D, Bickell, Nina A, Zatakia, Jigna, Burris, Sarah, Higgs, Elizabeth S, Natarajan, Ven, Dewar, Robin L, Schechner, Adam, Kang, Nayon, Arenas-Pinto, Alejandro, Hudson, Fleur, Ginde, Adit A, Self, Wesley H, Rogers, Angela J, Oldmixon, Cathryn F, Morin, Haley, Sanchez, Adriana, Weintrob, Amy C, Cavalcanti, Alexandre Biasi, Davis-Karim, Anne, Engen, Nicole, Denning, Eileen, Taylor Thompson, B, Gelijns, Annetine C, Kan, Virginia, Davey, Victoria J, Lundgren, Jens D, Babiker, Abdel G, Neaton, James D, and Lane, H Clifford
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- 2023
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10. Health Utility Estimates and Their Application to HIV Prevention in the United States: Implications for Cost-Effectiveness Modeling and Future Research Needs.
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Whitham, Hilary, Hutchinson, Angela, Shrestha, Ram, Kuppermann, Miriam, Grund, Birgit, Shouse, R, and Sansom, Stephanie
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CEA ,HIV ,QALYs ,cost-effectiveness analyses ,health state utilities ,human immunodeficiency virus ,quality-adjusted life years - Abstract
Objectives. Health utility estimates from the current era of HIV treatment, critical for cost-effectiveness analyses (CEA) informing HIV health policy, are limited. We examined peer-reviewed literature to assess the appropriateness of commonly referenced utilities, present previously unreported quality-of-life data from two studies, and discuss future implications for HIV-related CEA. Methods. We searched a database of cost-effectiveness analyses specific to HIV prevention efforts from 1999 to 2016 to identify the most commonly referenced sources for health utilities and to examine practices around using and reporting health utility data. Additionally, we present new utility estimates from the Centers of Disease Control and Preventions Medical Monitoring Project (MMP) and the INSIGHT Strategies for Management of Anti-Retroviral Therapy (SMART) trial. We compare data collection time frames, sample characteristics, assessment methods, and key estimates. Results. Data collection for the most frequently cited utility estimates ranged from 1985 to 1997, predating modern HIV treatment. Reporting practices around utility weights are poor and lack details on participant characteristics, which may be important stratifying factors for CEA. More recent utility estimates derived from MMP and SMART were similar across CD4+ count strata and had a narrower range than pre-antiretroviral therapy (ART) utilities. Conclusions. Despite the widespread use of ART, cost-effectiveness analysis of HIV prevention interventions frequently apply pre-ART health utility weights. Use of utility weights reflecting the current state of the US epidemic are needed to best inform HIV research and public policy decisions. Improved practices around the selection, application, and reporting of health utility data used in HIV prevention CEA are needed to improve transparency.
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- 2020
11. Interim monitoring in a treatment strategy trial with a composite primary endpoint
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Kang, Minhee, Grund, Birgit, Hunsberger, Sally, Glidden, David, and Volberding, Paul
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Biomedical and Clinical Sciences ,Clinical Sciences ,Sexually Transmitted Infections ,Patient Safety ,Clinical Research ,Rare Diseases ,Cancer ,Infectious Diseases ,Clinical Trials and Supportive Activities ,HIV/AIDS ,6.1 Pharmaceuticals ,Clinical Trials Data Monitoring Committees ,Disease Progression ,Endpoint Determination ,HIV Infections ,Humans ,Research Design ,Sarcoma ,Kaposi ,Interim monitoring ,Futility ,Composite endpoint ,Treatment strategy trial ,Medical and Health Sciences ,General Clinical Medicine ,Public Health ,Biomedical and clinical sciences ,Health sciences - Abstract
When a clinical trial has a composite endpoint and a comparison of treatment strategies with multiple intervention components, interim data reviews by a data safety and monitoring board (DSMB) can be challenging as the data evolve on multiple fronts. We illustrate with a study in the treatment of Kaposi sarcoma (KS), an HIV-associated cancer with a multi-faceted disease presentation. The study, ACTG-A5264/AMC-067, was a 1:1 randomized trial to compare two strategies: immediate initiation of etoposide with antiretroviral therapy (ART), or ART with delayed etoposide upon disease progression. The outcome was a composite endpoint that included the following events, ordered from worst to best in the following three categories: (1) KS progression at 48 weeks, death, initiation of alternate KS treatment, loss to study follow-up; (2) stable KS; and (3) partial or complete KS response at 48 weeks. We present the interim results on the composite endpoint and the individual components, where components favored different study arms at an interim review. To facilitate interim data monitoring for complex trials, we recommend clear communications between the study team and the DSMB prior to the initiation of the trial on the need for a composite endpoint, the intentions behind the defined strategies, and relative importance of individual components of the composite endpoint. We also recommend flexibility in the timing of data reviews by the DSMB to interpret emerging data in multiple dimensions. Clinicaltrials.govNCT01352117.
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- 2019
12. Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial
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Ginde, Adit A., Paredes, Roger, Murray, Thomas A., Engen, Nicole, Grandits, Greg, Vekstein, Andrew, Ivey, Noel, Mourad, Ahmad, Sandkovsky, Uriel, Gottlieb, Robert L., Berhe, Mezgebe, Jain, Mamta K., Marines-Price, Rubria, Agbor Agbor, Barbine Tchamba, Mateu, Lourdes, España-Cueto, Sergio, Lladós, Gemma, Mylonakis, Eleftherios, Rogers, Ralph, Shehadeh, Fadi, Filbin, Michael R., Hibbert, Kathryn A., Kim, Kami, Tran, Thanh, Morris, Peter E., Cassity, Evan P., Trautner, Barbara, Pandit, Lavannya M., Knowlton, Kirk U., Leither, Lindsay, Matthay, Michael A., Rogers, Angela J., Drake, Wonder, Jones, Beatrice, Poulakou, Garyfallia, Syrigos, Konstantinos N., Fernández-Cruz, Eduardo, Natale, Marisa Di, Almasri, Eyad, Balerdi-Sarasola, Leire, Bhagani, Sanjay R., Boyle, Katherine L., Casey, Jonathan D., Chen, Peter, Douin, David J., Files, D. Clark, Günthard, Huldrych F., Hite, R. Duncan, Hyzy, Robert C., Khan, Akram, Kibirige, Moses, Kidega, Robert, Kiweewa, Francis, Jensen, Jens-Ulrik, Leshnower, Bradley G., Lutaakome, Joseph K., Manian, Prasad, Menon, Vidya, Morales-Rull, Jose Luis, O'Mahony, D. Shane, Overcash, J. Scott, Ramachandruni, Srikant, Steingrub, Jay S., Taha, Hassan S., Waters, Michael, Young, Barnaby E., Phillips, Andrew N., Murray, Daniel D., Jensen, Tomas O., Padilla, Maria L., Sahner, David, Shaw-Saliba, Katy, Dewar, Robin L., Teitelbaum, Marc, Natarajan, Ven, Rehman, M. Tauseef, Pett, Sarah, Hudson, Fleur, Touloumi, Giota, Brown, Samuel M., Self, Wesley H., Chang, Christina C., Sánchez, Adriana, Weintrob, Amy C., Hatlen, Timothy, Grund, Birgit, Sharma, Shweta, Reilly, Cavan S., Garbes, Pedro, Esser, Mark T., Templeton, Alison, Babiker, Abdel G., Davey, Victoria J., Gelijns, Annetine C., Higgs, Elizabeth S., Kan, Virginia, Matthews, Gail, Thompson, B. Taylor, Neaton, James D., Lane, H. Clifford, and Lundgren, Jens D.
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- 2022
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13. Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial
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Self, Wesley H., Sandkovsky, Uriel, Reilly, Cavan S., Vock, David M., Gottlieb, Robert L., Mack, Michael, Golden, Kevin, Dishner, Emma, Vekstein, Andrew, Ko, Emily R., Der, Tatyana, Franzone, John, Almasri, Eyad, Fayed, Mohamed, Filbin, Michael R., Hibbert, Kathryn A., Rice, Todd W., Casey, Jonathan D., Hayanga, J. Awori, Badhwar, Vinay, Leshnower, Bradley G., Sharifpour, Milad, Knowlton, Kirk U., Peltan, Ithan D., Bakowska, Elizieta, Kowalska, Justyna, Bowdish, Michael E., Sturek, Jeffrey M., Rogers, Angela J., Files, D. Clark, Mosier, Jarrod M., Gong, Michelle N., Douin, David J., Hite, R. Duncan, Trautner, Barbara W., Jain, Mamta K., Gardner, Edward M., Khan, Akram, Jensen, Jens-Ulrik, Matthay, Michael A., Ginde, Adit A., Brown, Samuel M., Higgs, Elizabeth S., Pett, Sarah, Weintrob, Amy C., Chang, Christina C., Murrary, Daniel D., Günthard, Huldrych F., Moquete, Ellen, Grandits, Greg, Engen, Nicole, Grund, Birgit, Sharma, Shweta, Cao, Huyen, Gupta, Rajesh, Osei, Suzette, Margolis, David, Zhu, Qing, Polizzotto, Mark N., Babiker, Abdel G., Davey, Victoria J., Kan, Virginia, Thompson, B. Taylor, Gelijns, Annetine C., Neaton, James D., Lane, H. Clifford, Jundgren, Jens D., Tierney, John, Barrett, Kevin, Herpin, Betsey R., Smolskis, Mary C., Voge, Susan E., McNay, Laura A., Cahill, Kelly, Crew, Page, Kirchoff, Matthew, Sardana, Ratna, Raim, Sharon Segal, Chiu, Joseph, Hensley, Lisa, Lorenzo, Josua, Mock, Rebecca, Shaw-Saliba, Katy, Zuckerman, Judith, Adam, Stacey J., Currier, Judy, Read, Sarah, Hughes, Eric, Amos, Laura, Carlsen, Amy, Carter, Anita, Davis, Bionca, Denning, Eileen, DuChene, Alain, Harrison, Merrie, Kaiser, Payton, Koopmeiners, Joseph, Meger, Sue, Murray, Thomas, Quan, Kien, Quan, Siu Fun, Thompson, Greg, Walski, Jamie, Wentworth, Deborah, Moskowitz, Alan J., Bagiella, Emilia, O'Sullivan, Karen, Marks, Mary E., Accardi, Evan, Kinzel, Emily, Bedoya, Gabriela, Gupta, Lopa, Overbey, Jessica R., Padillia, Maria L., Santos, Milerva, Gillinov, Marc A., Miller, Marissa A., Taddei-Peters, Wendy C., Fenton, Kathleen, Berhe, Mezgebe, Haley, Clinton, Bettacchi, Christopher, Duhaime, Erin, Ryan, Madison, Burris, Sarah, Jones, Felecia, Villa, Samantha, Want, Samantha, Robert, Raven, Coleman, Tanquinisha, Clariday, Laura, Baker, Rebecca, Hurutado-Rodriguez, Marian, Iram, Nazia, Fresnedo, Michelle, Davis, Allyson, Leonard, Kiara, Ramierez, Noelia, Thammavong, Jon, Duque, Krizia, Turner, Emma, Fisher, Tammy, Robinson, Dianna, Ransom, Desirae, Lusk, Erica, Killian, Aaron, Palacious, Adriana, Solis, Edilia, Jerrow, Janet, Watts, Matthew, Whitacre, Heather, Cothran, Elizabeth, Smith, Peter K., Barkauskas, Christina E., Dreyer, Grace R., Witte, Marie, Mosaly, Nilima, Mourad, Ahmad, Holland, Thomas L., Lane, Kathleen, Bouffler, Andrew, McGowan, Lauren M., Motta, Marry, Tipton, Gregory, Stallings, Ben, Stout, Gennifer, McLendon-Arvik, Beth, Hollister, Beth A., Giangiacomo, Dana M., Sharma, Sunil, Pappers, Brian, McCarthy, Paul, Krupica, Troy, Sarwari, Arif, Reece, Rebecca, Fornaresio, Lisa, Glaze, Chad, Evans, Raquel, Preamble, Katarina, Sutton, Lisa Giblin, Buterbaugh, Sabrina, Bartolo, Elizabeth Berry, Williams, Roger, Bunner, Robin, Bender, William, Miller, Jeffrey, Baio, Kim T., McBride, Mary K., Fielding, Michele, Mathewson, Sonya, Porte, Kristina, Maton, Missy, Ponder, Chari, Haley, Elizabeth, Spainhour, Christine, Rogers, Susan, Tyler, Derrick, Wald-Dickler, Noah, Hutcheon, Douglass, Towfighi, Amytis, Lee, May M., Lewis, Meghan R., Spellberg, Brad, Sher, Linda, Sharma, Aniket, Olds, Anna P., Justino, Chris, Lozano, Edward, Romero, Chris, Leong, Janet, Rodina, Valentina, Possemato, Tammie, Escobar, Jose, Chiu, Charlene, Weissman, Kevin, Barros, Andrew, Enfield, Kyle B., Kadl, Alexandra, Green, China J., Simon, Rachel M., Fox, Ashley, Thornton, Kara, Parrino, Patrick E., Spindel, Stephen, Bansal, Aditya, Baumgarten, Katherine, Hand, Jonathan, Vonderhaar, Derek, Nossaman, Bobby, Laudun, Sylvia, Ames, DeAnna, Broussard, Shane, Hernandez, Nilmo, Isaac, Geralyn, Dinh, Huan, Zheng, Yiling, Tran, Sonny, McDaniel, Hunter, Crovetto, Nicolle, Miller, Leslie, Schelle, Beth, McLean, Sherry, Rothbaum, Howard R., Alvarez, Michael S., Kalan, Shivam P., Germann, Heather H., Hendershot, Jennifer, Maroney, Karen, Herring, Karen, Cook, Sharri, Paul, Pam, Madathil, Ronson J., Rabin, Joseph, Levine, Andrea, Saharia, Kapil, Tabatabai, Ali, Lau, Christine, Gammie, James S., Peguero, Maya-Loren, McKernan, Kimberley, Audette, Matthew, Fleischmann, Emily, Akbari, Freshta, Lee, Maia, Lee, Myounghee, Chi, Andrew, Salehi, Hanna, Pariser, Alan, Nguyen, Phuong Tran, Moore, Jessica, Gee, Adrienne, Vincent, Shelika, Zuckerman, Richard A., Iribarne, Alexander, Metzler, Sara, Shipman, Samantha, Caccia, Taylor, Johnson, Haley, Newton, Crystallee, Parr, Doug, Rodriguez, Vicente, Bokhart, Gordon, Eichman, Sharon M., North, Crystal, Oldmixon, Cathryn, Ringwood, Nancy, Fitzgerald, Laura, Morin, Haley D., Muzikansky, Ariela, Morse, Richard, Brower, Roy G., Reineck, Lora A., Aggarwal, Neil R., Bienstock, Karen, Hou, Peter, Steingrub, Jay, Tidswell, Mark A., Kozikowski, Lori-Ann, Kardos, Cynthia, DeSouza, Leslie, Thornton-Thompson, Sherell, Talmor, Daniel, Shapiro, Nathan, Banner-Goodspeed, Valerie, Boyle, Katherine L., Hayes, Sharon, Jones, Alan E., Galbraith, James, Nandi, Utsav, Peacock, Rebekah K., Parry, Blair Alden, Margolin, Justin D., Brait, Kelsey, Beakes, Caroline, Kangelaris, Kirsten N., Yee, Kimberly J., Ashktorab, Kimia, Jauregui, Alejandra E., Zhuo, Hanjing, Hendey, Gregory, Hubel, Kinsley A., Hughes, Alyssa R., Garcia, Rebekah L., Wilson, Jennifer G., Vojnik, Rosemary, Roque, Jonasel, Perez, Cynthia, Lim, George W., Chang, Steven Y., Beutler, Rebecca, Agarwal, Trisha, Vargas, Julia, Moss, Marc, Baduashvili, Amiran, Chauhan, Lakshmi, Finck, Lani L., Howell, Michelle, Hyzy, Robert C., Park, Pauline K., Nelson, Kristine, McSparron, Jake I., Co, Ivan N., Wang, Bonnie R., Jia, Shijing, Sullins, Barbara, Hanna, Sinan, Olbrich, Norman, Richardson, Lynne D., Nair, Rahul, Offor, Obiageli, Lopez, Brenda, Amosu, Omowunmi, Tzehaie, Hiwet, Terndrup, Thomas E., Wiedemann, Herbert P., Duggal, Abhijit, Thiruchelvam, Nirosshan, Ashok, Kiran, King, Alexander H., Mehkri, Omar, Hudock, Kristin, Kiran, Simra, More, Harshada, Roads, Tammy, Martinkovic, Jamie, Kennedy, Sarah, Robinson, Bryce H., Hough, Catherine L., Krol, Olivia F., Kinjal, Mistry, Mills, Emmanuel, McDougal, Madeline, Deshmukh, Rupali, Chen, Peter, Torbati, Sam S., Matusov, Yuri, Choe, June, Hindoyan, Niree A., Jackman, Susan E., Bayoumi, Emad, Wynter, Timothy, Caudill, Antonina, Pascual, Ethan, Clapham, Gregg J., Herrera, Lisa, Ojukwu, Cristabelle, Mehdikhani, Shaunt, O'Mahony, D. Shane, Nyatsatsang, Sonam T., Wilson, David M., Wallick, Julie A., Miller, Chadwick, Gibbs, Keven W., Flores, Lori S., LaRose, Mary E., Landreth, Leigha D., Morris, Peter E., Sturgill, Jamie L., Cassity, Evan P., Dhar, Sanjay, Montgomery-Yates, Ashley A., Pasha, Sara N., Mayer, Kirby P., Bissel, Brittany, Bledsoe, Joseph, Brown, Samuel, Lanspa, Michael, Leither, Lindsey, Armbruster, Brent P., Montgomery, Quinn, Applegate, Darrin, Kumar, Naresh, Fergus, Melissa, Serezlic, Erna, Imel, Karah, Palmer, Ghazal, Webb, Brandon, Aston, Valerie T., Johnson, Jakea, Gray, Christopher, Hays, Margaret, Roth, Megan, Sánchez, Adriana, Popielski, Laura, Rivasplata, Heather, Turner, Melissa, Vjecha, Michael, Petersen, Tianna, Kamel, Dena, Hansen, Laura, Lucas, Claudia Sanchez, DellaValle, Natalie, Gonzales, Sonia, Scott, James, Wyles, David, Douglas, Ivor, Haukoos, Jason, Kamis, Kevin, Robinson, Caitlin, Baker, Jason V., Frosch, Anne, Goldsmith, Rachael, Jibrell, Hodan, Lo, Melanie, Klaphake, Jonathan, Mackedanz, Shari, Ngo, Linh, Garcia-Myers, Kelly, Markowitz, Norman, Pastor, Erika, Ramesh, Mayur, Brar, Indira, Rivers, Emanuel, Kumar, Princy, Menna, Maximiliano, Biswas, Kousick, Harrington, Cristin, Delp, Alex, Pandit, Lavannya, Hines-Munson, Casey, Van, John, Dillon, Laura, Want, Yiqun, Lichtenberger, Paola, Baracco, Gio, Ramos, Carol, Bjork, Lauren, Sueiro, Melyssa, Tien, Phyllis, Freasier, Heather, Buck, Theresa, Nekach, Hafida, Nagy-Agren, Stephanie, Vasudeva, Shikha, Ochalek, Tracy, Roller, Brentin, Nguyen, Chinh, Mikail, Amani, Raben, Dorthe, Jensen, Tomas O., Aagaard, Bitten, Nielsen, Charlotte B., Krapp, Katharina, Nykjær, Bente Rosdahl, Kanne, Katja Lisa, Grevsen, Anne Louise, Joensen, Zillah Maria, Bruun, Tina, Bojesen, Ane, Woldbye, Frederik, Normand, Nick E., Esmann, Frederik V.L., Clausen, Clara Lundetoft, Hovmand, Nichlas, Pedersen, Karen Brorup, Thorlacius-Ussing, Louise, Tinggaard, Michaela, Høgsberg, Dorthe S., Rastoder, Ema, Kamstrup, Thobias, Bergsøe, Christina Marisa, Østergaard, Lars, Stærke, Nina Breinholt, Johansen, Isik S., Knudtzen, Fredrikke C., Larsen, Lykke, Hertz, Mathias A., Fabricius, Thilde, Helleberg, Marie, Gerstoft, Jan, Jensen, Tomas Østergaard, Lindegaard, Birgitte, Pedersen, Thomas Ingemann, Røge, Birgit Thorup, Løfberg, Sandra Valborg, Hansen, Thomas Michael, Nielsen, Ariella Denize, von Huth, Sebastian Leicht, Nielsen, Henrik, Thisted, Rikke Krog, Podlekareva, Daria, Johnsen, Stine, Andreassen, Helle Frost, Pedersen, Lars, Lindnér, Cecilia Ebba Clara Ellinor, Wiese, Lothar, Knudsen, Lene Surland, Nytofte, Nikolaj Julian Skrøder, Havmøller, Signe Ravn, Paredes, Roger, Exposito, Maria, Fernández-Cruz, Eduardo, Muñoz, José, Arribas, Jose R., Estrada, Vicente, Horcajada, Juan P., Burgos, Joaquin, Morales-Rull, Jose Luis, Braun, Dominique L., West, Emily, M'Rabeth-Bensalah, Khadija, Eichinger, Mareile L., Grüttner-Durmaz, Manuela, Grube, Christina, Zink, Veronika, Horban, Andrzej, Bednarska, Agnieszka, Jurek, Natalia, Fätkenheuer, Gerd, Malinm, Jakob J., Matthews, Gail, Kelleher, Anthony, Cabrera, Gesalit, Carey, Catherine, Hough, Sally, Virachit, Sophie, Zhong, Amy, Young, Barnaby E., Chia, Po Ying, Lee, Tau Hong, Lin, Ray J., Lye, David, Ong, Sean, Puah, Ser Hon, Yeo, Tsin Wen, Diong, Shiau Hui, Ongko, Juwinda, Hudson, Fleur, Parmar, Mahesh KB, Goodman, Anna, Badrock, Jonathan, Gregory, Adam, Harris, Nicola, Touloumi, Giota, Pantaz, Nikos, Gioukari, Vicky, Lutaakome, Joseph, Kityo, Cissy M., Mugerwa, Henry, Kiweewa, Francis, Osinusi, Anu, Tipple, Craig, Willis, Angela, Peppercorn, Amanda, Watson, Helen, Alexander, Elizabeth, Mogalian, Erik, Lin, Leo, Ding, Xiao, Yan, Li, Girardet, Jean-Luc, Ma, Ji, Hong, Zhi, Adams, Amy, Albert, Sara, Balde, Abby, Baracz, Michelle, Baseler, Beth, Becker, Nancy, Bielica, Mona, Billouin-Frazier, Shere, Cash, Jennifer, Choudhary, Jay, Dolney, Suzanne, Dixon, Mary, Eyler, Carolyn, Frye, Leanna, Galcik, Michael, Gertz, Jensen, Giebeig, Lisa, Gulati, Neelam, Hankinson, Liz, Hissey, Debbie, Hogarty, Debi, Hohn, Matt, Holley, H Preston, Hoopengardner, Lisa, Huber, Lynda, Jankelevich, Shirley, Krauss, Gary, Lake, Eileen, Linton, Jessica, MacDonald, Leah, Manandhar, Meryan, Spinelli-Nadzam, Mary, Oluremi, Charles, Proffitt, Calvin, Rudzinski, Erin, Sandrus, Jen, Schaffhauser, Marylu, Schechner, Adam, Suders, Connie, Gerry, Norman P., Smith, Kenneth, Solomon, Courtney, Kubernac, Amanda, Rashid, Marium, Patel, Bhakti, Kubernac, Robert, Murphy, Joseph, Hoover, Marie L., Brown, Craig, DuChateau, Nadine, Flosi, Adam, Johnson, Les, Treagus, Amy, and Wenner, Christine
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- 2022
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14. Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial
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Polizzotto, Mark N., Nordwall, Jacqueline, Babiker, Abdel G., Phillips, Andrew, Vock, David M., Eriobu, Nnakelu, Kwaghe, Vivian, Paredes, Roger, Mateu, Lourdes, Ramachandruni, Srikanth, Narang, Rajeev, Jain, Mamta K., Lazarte, Susana M., Baker, Jason V., Frosch, Anne E.P., Poulakou, Garyfallia, Syrigos, Konstantinos N., Arnoczy, Gretchen S., McBride, Natalie A., Robinson, Philip A., Sarafian, Farjad, Bhagani, Sanjay, Taha, Hassan S., Benfield, Thomas, Liu, Sean T.H., Antoniadou, Anastasia, Jensen, Jens Ulrik Stæhr, Kalomenidis, Ioannis, Susilo, Adityo, Hariadi, Prasetyo, Jensen MD, Tomas O., Morales-Rull, Jose Luis, Helleberg, Marie, Meegada, Sreenath, Johansen, Isik S., Canario, Daniel, Fernández-Cruz, Eduardo, Metallidis, Simeon, Shah, Amish, Sakurai, Aki, Koulouris, Nikolaos G., Trotman, Robin, Weintrob, Amy C., Podlekareva, Daria, Hadi, Usman, Lloyd, Kathryn M., Røge, Birgit Thorup, Saito, Sho, Sweerus, Kelly, Malin, Jakob J., Lübbert, Christoph, Muñoz, Jose, Cummings, Matthew J., Losso, Marcelo H., Turner, Dan, Shaw-Saliba, Kathryn, Dewar, Robin, Highbarger, Helene, Lallemand, Perrine, Rehman, Tauseef, Gerry, Norman, Arlinda, Dona, Chang, Christina C., Grund, Birgit, Holbrook, Michael R., Holley, Horace P., Hudson, Fleur, McNay, Laura A., Murray, Daniel D., Pett, Sarah L., Shaughnessy, Megan, Smolskis, Mary C., Touloumi, Giota, Wright, Mary E., Doyle, Mittie K., Popik, Sharon, Hall, Christine, Ramanathan, Roshan, Cao, Huyen, Mondou, Elsa, Willis, Todd, Thakuria, Joseph V., Yel, Leman, Higgs, Elizabeth, Kan, Virginia L., Lundgren, Jens D., Neaton, James D., and Lane, H. Clifford
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- 2022
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15. No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts
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Wright, Edwina J, Grund, Birgit, Robertson, Kevin R, Cysique, Lucette, Brew, Bruce J, Collins, Gary L, Poehlman-Roediger, Mollie, Vjecha, Michael J, Penalva de Oliveira, Augusto César, Standridge, Barbara, Carey, Cate, Avihingsanon, Anchalee, Florence, Eric, Lundgren, Jens D, Arenas-Pinto, Alejandro, Mueller, Nicolas J, Winston, Alan, Nsubuga, Moses S, Lal, Luxshimi, and Price, Richard W
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Infectious Diseases ,HIV/AIDS ,Clinical Research ,Neurosciences ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,AIDS Dementia Complex ,Adult ,Anti-Retroviral Agents ,CD4 Lymphocyte Count ,Female ,HIV Infections ,Humans ,Longitudinal Studies ,Male ,Secondary Prevention ,Treatment Outcome ,antiretroviral treatment ,central nervous system ,HAND ,HIV ,neurocognitive impairment ,INSIGHT START Neurology Substudy Group ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology - Abstract
ObjectiveTo compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with more than 500 CD4 cells/μl.DesignRandomized trial.MethodsThe START parent study randomized participants to commence immediate versus deferred ART until CD4 less than 350 cells/μl. The START Neurology substudy used eight neuropsychological tests, at baseline, months 4, 8, 12 and annually, to compare groups for changes in test performance. Test results were internally standardized to z-scores. The primary outcome was the average of the eight test z-scores (QNPZ-8). Mean changes in QNPZ-8 from baseline were compared by intent-to-treat using longitudinal mixed models. Changes from baseline to specific time points were compared using ANCOVA models.ResultsThe 592 participants had a median age of 34 years; median baseline CD4 count was 629 cells/μl; the mean follow-up was 3.4 years. ART was used for 94 and 32% of accrued person-years in the immediate and deferred groups, respectively. There was no difference between the immediate and deferred ART groups in QNPZ-8 change through follow-up [-0.018 (95% CI -0.062 to 0.027, P = 0.44)], or at any visit. However, QNPZ-8 scores increased in both arms during the first year, by 0.22 and 0.24, respectively (P
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- 2018
16. Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy
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Grund, Birgit, Baker, Jason V, Deeks, Steven G, Wolfson, Julian, Wentworth, Deborah, Cozzi-Lepri, Alessandro, Cohen, Calvin J, Phillips, Andrew, Lundgren, Jens D, and Neaton, James D
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Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,HIV/AIDS ,Clinical Research ,Infectious Diseases ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,Infection ,Good Health and Well Being ,Adult ,Antiretroviral Therapy ,Highly Active ,Biomarkers ,C-Reactive Protein ,Endpoint Determination ,Female ,Fibrin Fibrinogen Degradation Products ,HIV Seropositivity ,Humans ,Interleukin-6 ,Kaplan-Meier Estimate ,Male ,Middle Aged ,Morbidity ,Risk Reduction Behavior ,INSIGHT SMART/ESPRIT/SILCAAT Study Group ,General Science & Technology - Abstract
BackgroundDespite effective antiretroviral treatment (ART), HIV-positive individuals are at increased risk of serious non-AIDS conditions (cardiovascular, liver and renal disease, and cancers), perhaps due in part to ongoing inflammation and/or coagulation. To estimate the potential risk reduction in serious non-AIDS conditions or death from any cause that might be achieved with treatments that reduce inflammation and/or coagulation, we examined associations of interleukin-6 (IL-6), D-dimer, and high-sensitivity C-reactive protein (hsCRP) levels with serious non-AIDS conditions or death in 3 large cohorts.MethodsIn HIV-positive adults on suppressive ART, associations of IL-6, D-dimer, and hsCRP levels at study entry with serious non-AIDS conditions or death were studied using Cox regression. Hazard ratios (HR) adjusted for age, gender, study, and regression dilution bias (due to within-person biomarker variability) were used to predict risk reductions in serious non-AIDS conditions or death associated with lower "usual" levels of IL-6 and D-dimer.ResultsOver 4.9 years of mean follow-up, 260 of the 3766 participants experienced serious non-AIDS conditions or death. IL-6, D-dimer and hsCRP were each individually associated with risk of serious non-AIDS conditions or death, HR = 1.45 (95% CI: 1.30 to 1.63), 1.28 (95% CI: 1.14 to 1.44), and 1.17 (95% CI: 1.09 to 1.26) per 2x higher biomarker levels, respectively. In joint models, IL-6 and D-dimer were independently associated with serious non-AIDS conditions or death, with consistent results across the 3 cohorts and across serious non-AIDS event types. The association of IL-6 and D-dimer with serious non-AIDS conditions or death was graded and persisted throughout follow-up. For 25% lower "usual" IL-6 and D-dimer levels, the joint biomarker model estimates a 37% reduction (95% CI: 28 to 46%) in the risk of serious non-AIDS conditions or death if the relationship is causal.ConclusionsBoth IL-6 and D-dimer are independently associated with serious non-AIDS conditions or death among HIV-positive adults with suppressed virus. This suggests that treatments that reduce IL-6 and D-dimer levels might substantially decrease morbidity and mortality in patients on suppressive ART. Clinical trials are needed to test this hypothesis.
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- 2016
17. Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19.
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Jensen, Tomas O, Grandits, Greg A, Jain, Mamta K, Murray, Thomas A, Grund, Birgit, Shaw-Saliba, Kathryn, Matthay, Michael A, Abassi, Mahsa, Ardelt, Magdalena, Baker, Jason V, Chen, Peter, Dewar, Robin L, Goodman, Anna L, Hatlen, Timothy J, Highbarger, Helene C, Holodniy, Mark, Lallemand, Perrine, Laverdure, Sylvain, Leshnower, Bradley G, and Looney, David
- Abstract
Background Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. Methods Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. Results Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%–27%; P <.001), and a steeper rate of decline through the first 5 days (P <.001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. Conclusions Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. Clinical Trials Registration NCT04501978. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial
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Brown, Samuel M, primary, Barkauskas, Christina E, additional, Grund, Birgit, additional, Sharma, Shweta, additional, Phillips, Andrew N, additional, Leither, Lindsay, additional, Peltan, Ithan D, additional, Lanspa, Michael, additional, Gilstrap, Daniel L, additional, Mourad, Ahmad, additional, Lane, Kathleen, additional, Beitler, Jeremy R, additional, Serra, Alexis L, additional, Garcia, Ivan, additional, Almasri, Eyad, additional, Fayed, Mohamed, additional, Hubel, Kinsley, additional, Harris, Estelle S, additional, Middleton, Elizabeth A, additional, Barrios, Macy A G, additional, Mathews, Kusum S, additional, Goel, Neha N, additional, Acquah, Samuel, additional, Mosier, Jarrod, additional, Hypes, Cameron, additional, Salvagio Campbell, Elizabeth, additional, Khan, Akram, additional, Hough, Catherine L, additional, Wilson, Jennifer G, additional, Levitt, Joseph E, additional, Duggal, Abhijit, additional, Dugar, Siddharth, additional, Goodwin, Andrew J, additional, Terry, Charles, additional, Chen, Peter, additional, Torbati, Sam, additional, Iyer, Nithya, additional, Sandkovsky, Uriel S, additional, Johnson, Nicholas J, additional, Robinson, Bryce R H, additional, Matthay, Michael A, additional, Aggarwal, Neil R, additional, Douglas, Ivor S, additional, Casey, Jonathan D, additional, Hache-Marliere, Manuel, additional, Georges Youssef, J, additional, Nkemdirim, William, additional, Leshnower, Brad, additional, Awan, Omar, additional, Pannu, Sonal, additional, O'Mahony, Darragh Shane, additional, Manian, Prasad, additional, Awori Hayanga, J W, additional, Wortmann, Glenn W, additional, Tomazini, Bruno M, additional, Miller, Robert F, additional, Jensen, Jens-Ulrik, additional, Murray, Daniel D, additional, Bickell, Nina A, additional, Zatakia, Jigna, additional, Burris, Sarah, additional, Higgs, Elizabeth S, additional, Natarajan, Ven, additional, Dewar, Robin L, additional, Schechner, Adam, additional, Kang, Nayon, additional, Arenas-Pinto, Alejandro, additional, Hudson, Fleur, additional, Ginde, Adit A, additional, Self, Wesley H, additional, Rogers, Angela J, additional, Oldmixon, Cathryn F, additional, Morin, Haley, additional, Sanchez, Adriana, additional, Weintrob, Amy C, additional, Cavalcanti, Alexandre Biasi, additional, Davis-Karim, Anne, additional, Engen, Nicole, additional, Denning, Eileen, additional, Taylor Thompson, B, additional, Gelijns, Annetine C, additional, Kan, Virginia, additional, Davey, Victoria J, additional, Lundgren, Jens D, additional, Babiker, Abdel G, additional, Neaton, James D, additional, Lane, H Clifford, additional, Tierney, John, additional, Vogel, Susan E., additional, McNay, Laura A., additional, Cahill, Kelly, additional, Crew, Page, additional, Sardana, Ratna, additional, Segal Raim, Sharo, additional, Shaw-Saliba, Katy, additional, Atri, Negin, additional, Miller, Mark, additional, Vallee, David, additional, Chung, Lucy, additional, Delph, Yvette, additional, Adam, Stacey J., additional, Read, Sarah, additional, Draghia-Akli, Ruxandra, additional, Harrigan, Rachel, additional, Carlsen, Amy, additional, Carter, Anita, additional, DuChene, Alain, additional, Eckroth, Kate, additional, Frase, Alex, additional, Harrison, Merrie, additional, Meger, Sue, additional, Quan, Kien, additional, Quan, Siu Fun, additional, Reilly, Cavan, additional, Thompson, Greg, additional, Walski, Jamie, additional, Moskowitz, Alan J., additional, Bagiella, Emilia, additional, Moquete, Ellen, additional, O'Sullivan, Karen, additional, Marks, Mary E., additional, Accardi, Evan, additional, Kinzel, Emily, additional, Bedoya, Gabriela, additional, Gupta, Lopa, additional, Overbey, Jessica R., additional, Padillia, Maria L., additional, Santos, Milerva, additional, Gillinov, Marc A., additional, Miller, Marissa A., additional, Taddei-Peters, Wendy C., additional, Fenton, Kathleen, additional, Smith, Peter K., additional, Vekstein, Andrew M., additional, Ko, Emily R., additional, Al-Hegelan, Mashael S., additional, McGowan, Lauren M., additional, Motta, Mary, additional, Howell, Shauna, additional, Bent, Francine, additional, Kalager, Rachel, additional, Chan, Emmanuel, additional, Aloor, Heather L., additional, Griffin, S. Michelle, additional, Covington, Anna, additional, McLendon-Arvik, Beth, additional, Bussadori, Barbara, additional, Miller-Bell, Mary, additional, Sampey, Cathy, additional, Gaver, Vincent, additional, Hollister, Beth A., additional, Giangiacomo, Dana M., additional, Pauley, Alena, additional, Patel, Aashay, additional, Classon, Chris, additional, Frazier, Madison, additional, Osborne, Robyn, additional, Conlon, Debbi H., additional, Joshi, Marybeth, additional, Gottlieb, Robert L., additional, Mack, Michael, additional, Berhe, Mezgebe, additional, Haley, Clinton, additional, Dishner, Emma, additional, Bettacchi, Christopher, additional, Golden, Kevin, additional, Duhaime, Erin, additional, Ryan, Madison, additional, Tallmadge, Catherine, additional, Estrada, Lorie, additional, Jones, Felecia, additional, Villa, Samantha, additional, Wang, Samantha, additional, Robert, Raven, additional, Coleman, Tanquinisha, additional, Clariday, Laura, additional, Baker, Rebecca, additional, Hurutado-Rodriguez, Mariana, additional, Iram, Nazia, additional, Fresnedo, Michelle, additional, Davis, Allyson, additional, Leonard, Kiara, additional, Ramierez, Noelia, additional, Thammavong, Jon, additional, Duque, Krizia, additional, Turner, Emma, additional, Fisher, Tammy, additional, Robinson, Dianna, additional, Ransom, Desirae, additional, Maldonado, Nicholas, additional, Lusk, Erica, additional, Killian, Aaron, additional, Palacios, Adriana, additional, Solis, Edilia, additional, Jerrow, Janet, additional, Watts, Matthew, additional, Whitacre, Heather, additional, Cothran, Elizabeth, additional, Bender, William, additional, Miller, Jeffrey, additional, Nugent, Katherine, additional, Farrington, Woodrow, additional, Baio, Kim T., additional, McBride, Mary K., additional, Fielding, Michele, additional, Mathewson, Sonya, additional, Porte, Kristina, additional, Haley, Elizabeth, additional, Rogers, Susan, additional, Tyler, Derrick, additional, Perin, Emerson, additional, Costello, Briana, additional, Postalian, Alexander, additional, Sohail, Rizwan, additional, Hinsu, Punit, additional, Watson, Carolyn, additional, Kappenman, Casey, additional, Chen, James, additional, Walker, Kim, additional, Fink, Melyssa, additional, Phillip, Gabrielle, additional, Mahon, Kim, additional, Sturgis, Lydia, additional, Maher, Patrick, additional, Rogers, Linda, additional, Ng, Nicole, additional, Marshall, Jason, additional, Bassily-Marcus, Adel, additional, Cohen, Ivy, additional, Ramoo, Shamini, additional, Malhotra, Aryan, additional, Kessler, Jonathan, additional, Goetz, Rebekah, additional, Badhwar, Vinay, additional, Hayanga, Jeremiah, additional, Giblin Sutton, Lisa, additional, Williams, Roger, additional, Berry Bartolo, Elizabeth, additional, Walker, Dmitry, additional, Bunner, Robin, additional, Glaze, Chad, additional, Aucremanne, Tanja, additional, Bishop, James, additional, Kelley, Macey, additional, Peterson, Autumn, additional, Sauerborn, Erica, additional, Reckart, Robin, additional, Miller, Brittany, additional, Mittel, Aaron, additional, Darmanian, Anita, additional, Rosen, Amanda, additional, Madahar, Purnema, additional, Schicchi, John, additional, Gosek, Katarzyna, additional, Dzierba, Amy, additional, Wahab, Romina, additional, Eng, Connie, additional, Al-Saadi, Mukhtar, additional, Zahiruddin, Faisal, additional, Syed, Mohi, additional, George, Michael, additional, Patel, Varsha, additional, Onwunyi, Chisom, additional, Barroso da Costa, Rosa, additional, North, Crystal, additional, Ringwood, Nancy, additional, Fitzgerald, Laura, additional, Muzikansky, Ariela, additional, Morse, Richard, additional, Brower, Roy G., additional, Reineck, Lora A., additional, Bienstock, Karen, additional, Hou, Peter, additional, Steingrub, Jay S., additional, Tidswell, Mark A., additional, Kozikowski, Lori-Ann, additional, Kardos, Cynthia, additional, De Souza, Leslie, additional, Talmor, Daniel, additional, Shapiro, Nathan, additional, Hibbert, Kathryn, additional, Brait, Kelsey, additional, Kone, Mamary, additional, Hendey, Gregory, additional, Kangelaris, Kirsten N., additional, Ashktorab, Kimia, additional, Gropper, Rachel, additional, Agrawal, Anika, additional, Timothy, Kelly, additional, Zhou, Hanjing, additional, Hughes, Alyssa, additional, Garcia, Rebekah, additional, Torres, Adrian, additional, Hernandez-Almaraz, Maria Elena, additional, Vojnik, Rosemary, additional, Perez, Cynthia, additional, McDowell, Jordan, additional, Chang, Steven Y., additional, Vargas, Julia, additional, Moss, Marc, additional, McKeehan, Jeffrey, additional, Higgins, Carrie, additional, Johnson, Emily, additional, Slaughter, Suzanne, additional, Wyles, David, additional, Hiller, Terra, additional, Oakes, Judy, additional, Garcia, Ana, additional, Gravitz, Stephanie, additional, Lyle, Carolynn, additional, Swanson, Diandra, additional, Gong, Michelle Ng., additional, Richardson, Lynnne D., additional, Chen, Jen-Ting, additional, Moskowitz, Ari, additional, Mohamed, Amira, additional, Lopez, Brenda, additional, Amosu, Omowunmi, additional, Tzehaie, Hiwet, additional, Boujid, Sabah, additional, Bixby, Billie, additional, Lopez, Anitza A., additional, Durley, JaVon, additional, Gilson, Boris, additional, Hite, R. Duncan, additional, Wang, Henry, additional, Wiedemann, Hebert P., additional, Mehkri, Omar, additional, Ashok, Kiran, additional, King, Alexander, additional, Brennan, Connery, additional, Exline, Matthew C., additional, Englert, Joshua A., additional, Karow, Sarah, additional, Schwartz, Elizabeth, additional, So, Preston, additional, So, Madison, additional, Krol, Olivia F., additional, Briceno Parra, Genesis I., additional, Mills, Emmanuel Nii Lantei, additional, Oh, Minn, additional, Pena, Jose, additional, Martínez, Jesús Alejandro, additional, Jackman, Susan E., additional, Bayoumi, Emad, additional, Pascual, Ethan, additional, Caudill, Antonina, additional, Chen, Po-En, additional, Richardson, Tabia, additional, Clapham, Gregg J., additional, Herrera, Lisa, additional, Ojukwu, Cristabelle, additional, Fine, Devin, additional, Gomez, Millie J., additional, Choi-Kuaea, Yunhee, additional, Weissberg, Gwendolyn, additional, Isip, Katherine, additional, Mattison, Brittany, additional, Tran, Dana, additional, Emilov Dukov, Jennifer, additional, Chung, Paul, additional, Kang, Bo Ran, additional, Escobar, Lauren, additional, Tran, Trung, additional, Baig, Saba, additional, Wallick, Julie A., additional, Duven, Alexandria M., additional, Fletcher, Dakota D., additional, Gundel, Stephanie, additional, Fuentes, Megan, additional, Newton, Maranda, additional, Peterson, Emily, additional, Jiang, Kelsey, additional, Files, D. Clark, additional, Miller, Chadwick, additional, Lematty, Caitlin, additional, Rasberry, April, additional, Warden, Ashley, additional, Bledsoe, Joseph, additional, Knowlton, Kirk, additional, Knox, Daniel B., additional, Klippel, Carolyn, additional, Armbruster, Brent P., additional, Applegate, Darrin, additional, Imel, Karah, additional, Fergus, Melissa, additional, Rahmati, Kasra, additional, Jensen, Hannah, additional, Aston, Valerie T., additional, Jeppson, Joshua, additional, Marshall, J. Hunter, additional, Lumpkin, Jenna, additional, Smith, Cassie, additional, Burke, Tyler, additional, Gray, Andrew, additional, Paine, Robert, additional, Callahan, Sean, additional, Yamane, Misty, additional, Waddoups, Lindsey, additional, Rice, Todd W., additional, Johnson, Jakea, additional, Gray, Christopher, additional, Hays, Margaret, additional, Roth, Megan, additional, Musick, Sarah, additional, Miller, Karen, additional, Semler, Matthew W., additional, Popielski, Laura, additional, Kambo, Amy, additional, Viens, Kimberly, additional, Turner, Melissa, additional, Vjecha, Michael J., additional, Denyer, Rachel, additional, Khosla, Rahul, additional, Rajendran, Bindu, additional, Gonzales, Melissa, additional, Moriarty, Theresa, additional, Biswas, Kousick, additional, Harrington, Cristin, additional, Garcia, Amanda, additional, Bremer, Tammy, additional, Burke, Tara, additional, Koker, Brittany, additional, Pittman, David, additional, Vasudeva, Shikha S., additional, Anholm, James D., additional, Specht, Lennard, additional, Rodriguez, Aimee, additional, Ngo, Han, additional, Duong, Lien, additional, Previte, Matthew, additional, Raben, Dorthe, additional, Nielsen, Charlotte B., additional, Friis Larsen, Jakob, additional, Peters, Lars, additional, Matthews, Gail, additional, Kelleher, Anthony, additional, Polizzotto, Mark, additional, Carey, Catherine, additional, Chang, Christina, additional, Dharan, Nila, additional, Hough, Sally, additional, Virachit, Sophie, additional, Davidson, Sarah, additional, Bice, Daniel J., additional, Ognenovska, Katherine, additional, Cabrera, Gesalit, additional, Flynn, Ruth, additional, Abdelghany, Mazin, additional, Baseler, Beth, additional, Teitelbaum, Marc, additional, Holley, H. Preston, additional, Jankelevich, Shirley, additional, Adams, Amy, additional, Becker, Nancy, additional, Doleny, Suzanne, additional, Hissey, Debbie, additional, Simpson, Shelly, additional, Kim, Mi Ha, additional, Beeler, Joy, additional, Harmon, Liam, additional, Vanderpuye, Sharon, additional, Yeon, Lindsey, additional, Frye, Leanna, additional, Rudzinski, Erin, additional, Buehn, Molly, additional, Eccard-Koons, Vanessa, additional, Frary, Sadie, additional, MacDonalad, Leah, additional, Cash, Jennifer, additional, Hoopengardner, Lisa, additional, Linton, Jessica, additional, Nelson, Michaela, additional, Spinelli-Nadzam, Mary, additional, Proffitt, Calvin, additional, Lee, Christopher, additional, Engel, Theresa, additional, Fontaine, Laura, additional, Osborne, CK, additional, Hohn, Matt, additional, Galcik, Michael, additional, Thompson, DeeDee, additional, Sandrus, Jen, additional, Manchard, Jon, additional, Giri, Jiwan, additional, Kopka, Stacy, additional, Chang, Weizhong, additional, Sherman, Brad T., additional, Rupert, Adam W., additional, Highbarger, Helene, additional, Baseler, Michael, additional, Lallemand, Perrine, additional, Rehman, Tauseef, additional, Imamichi, Tom, additional, Laverdure, Sylvain, additional, Paudel, Sharada, additional, Cook, Kyndal, additional, Haupt, Kendra, additional, Hazen, Allison, additional, Badralmaa, Yunden, additional, Highbarger, Jeroen, additional, McCormack, Ashley, additional, Gerry, Norman P., additional, Smith, Kenneth, additional, Patel, Bhakti, additional, Domeraski, Nadia, additional, Hoover, Marie L., additional, DuChateau, Nadine, additional, Flosi, Adam, additional, Nelson, Rich, additional, Stojanovic, Jelena, additional, and Wenner, Christine, additional
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- 2023
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19. Risk of Suicidal Behavior With Use of Efavirenz : Results from the Strategic Timing of Antiretroviral Treatment Trial
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INSIGHT START study group, Arenas-Pinto, Alejandro, Grund, Birgit, Sharma, Shweta, Martinez, Esteban, Cummins, Nathan, Fox, Julie, Klingman, Karin L., Sedlacek, Dalibor, Collins, Simon, Flynn, Patricia M., Chasanov, William M., Kedem, Eynat, Katlama, Christine, Sierra-Madero, Juan, Afonso, Claudia, Brouwers, Pim, and Cooper, David A.
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- 2018
20. Which HIV-infected adults with high CD4 T-cell counts benefit most from immediate initiation of antiretroviral therapy? A post-hoc subgroup analysis of the START trial
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Molina, Jean-Michel, Grund, Birgit, Gordin, Fred, Williams, Ian, Schechter, Mauro, Losso, Marcello, Law, Matthew, Ekong, Ernest, Mwelase, Noluthando, Skoutelis, Athanasios, Wiselka, Martin J, Vandekerckhove, Linos, Benfield, Thomas, Munroe, David, Lundgren, Jens D, and Neaton, James D
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- 2018
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21. Improved neurocognitive test performance in both arms of the SMART study: impact of practice effect.
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Grund, Birgit, Wright, Edwina J, Brew, Bruce J, Price, Richard W, Roediger, Mollie P, Bain, Margaret P, Hoy, Jennifer F, Shlay, Judith C, Vjecha, Michael J, Robertson, Kevin R, and INSIGHT SMART Study Group
- Subjects
INSIGHT SMART Study Group ,Humans ,HIV Infections ,AIDS Dementia Complex ,Anti-Retroviral Agents ,Learning ,Neuropsychological Tests ,Adult ,Middle Aged ,Female ,Male ,HIV ,Test-retest ,Practice effect ,Learning effect ,Neurocognitive performance ,Neuropsychological tests ,Virology ,Clinical Sciences ,Medical Microbiology ,Neurosciences - Abstract
We evaluated factors associated with improvement in neurocognitive performance in 258 HIV-infected adults with baseline CD4 lymphocyte counts above 350 cells/mm³ randomized to intermittent, CD4-guided antiretroviral therapy (ART) (128 participants) versus continuous therapy (130) in the Neurology substudy of the Strategies for Management of Antiretroviral Therapy trial. Participants were enrolled in Australia, North America, Brazil, and Thailand, and neurocognitive performance was assessed by a five-test battery at baseline and month 6. The primary outcome was change in the quantitative neurocognitive performance z score (QNPZ-5), the average of the z scores of the five tests. Associations of the 6-month change in test scores with ART use, CD4 cell counts, HIV RNA levels, and other factors were determined using multiple regression models. At baseline, median age was 40 years, median CD4 cell count was 513 cells/mm³, 88 % had plasma HIV RNA ≤ 400 copies/mL, and mean QNPZ-5 was -0.68. Neurocognitive performance improved in both treatment groups by 6 months; QNPZ-5 scores increased by 0.20 and 0.13 in the intermittent and continuous ART groups, respectively (both P < 0.001 for increase and P = 0.26 for difference). ART was used on average for 3.6 and 5.9 out of the 6 months in the intermittent and continuous ART groups, respectively, but the increase in neurocognitive test scores could not be explained by ART use, changes in CD4, or plasma HIV RNA, which suggests a practice effect. The impact of a practice effect after 6 months emphasizes the need for a control group in HIV studies that measure intervention effects using neurocognitive tests similar to ours.
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- 2013
22. Systemic Inflammation, Coagulation, and Clinical Risk in the START Trial
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Baker, Jason V, Sharma, Shweta, Grund, Birgit, Rupert, Adam, Metcalf, Julia A, Schechter, Mauro, Munderi, Paula, Aho, Inka, Emery, Sean, Babiker, Abdel, Phillips, Andrew, Lundgren, Jens D, Neaton, James D, and Lane, H Clifford
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- 2017
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23. Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV
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Murray, Daniel D., primary, Grund, Birgit, additional, MacPherson, Cameron R., additional, Ekenberg, Christina, additional, Zucco, Adrian G., additional, Reekie, Joanne, additional, Dominguez-Dominguez, Lourdes, additional, Leung, Preston, additional, Fusco, Dahlene, additional, Gras, Julien, additional, Gerstoft, Jan, additional, Helleberg, Marie, additional, Borges, Álvaro H., additional, Polizzotto, Mark N., additional, and Lundgren, Jens D., additional
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- 2022
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24. LB2305. Long Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection: Findings from the Extended Follow-up of the START Trial
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Babiker, Abdel G, primary, Lundgren, Jens, additional, Sharma, Shweta, additional, Grund, Birgit, additional, Phillips, Andrew, additional, Kan, Virginia L, additional, Matthews, Gail, additional, Klingman, Karin L, additional, and Neaton, James D, additional
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- 2022
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25. Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial
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Holland, Thomas L., primary, Ginde, Adit A., additional, Paredes, Roger, additional, Murray, Thomas A., additional, Engen, Nicole, additional, Grandits, Greg, additional, Vekstein, Andrew, additional, Ivey, Noel, additional, Mourad, Ahmad, additional, Sandkovsky, Uriel, additional, Gottlieb, Robert L., additional, Berhe, Mezgebe, additional, Jain, Mamta K., additional, Marines-Price, Rubria, additional, Agbor Agbor, Barbine Tchamba, additional, Mateu, Lourdes, additional, España-Cueto, Sergio, additional, Lladós, Gemma, additional, Mylonakis, Eleftherios, additional, Rogers, Ralph, additional, Shehadeh, Fadi, additional, Filbin, Michael R., additional, Hibbert, Kathryn A., additional, Kim, Kami, additional, Tran, Thanh, additional, Morris, Peter E., additional, Cassity, Evan P., additional, Trautner, Barbara, additional, Pandit, Lavannya M., additional, Knowlton, Kirk U., additional, Leither, Lindsay, additional, Matthay, Michael A., additional, Rogers, Angela J., additional, Drake, Wonder, additional, Jones, Beatrice, additional, Poulakou, Garyfallia, additional, Syrigos, Konstantinos N., additional, Fernández-Cruz, Eduardo, additional, Di Natale, Marisa, additional, Almasri, Eyad, additional, Balerdi-Sarasola, Leire, additional, Bhagani, Sanjay R., additional, Boyle, Katherine L., additional, Casey, Jonathan D., additional, Chen, Peter, additional, Douin, David J., additional, Files, D. Clark, additional, Günthard, Huldrych F., additional, Hite, R. Duncan, additional, Hyzy, Robert C., additional, Khan, Akram, additional, Kibirige, Moses, additional, Kidega, Robert, additional, Kimuli, Ivan, additional, Kiweewa, Francis, additional, Jensen, Jens-Ulrik, additional, Leshnower, Bradley G., additional, Lutaakome, Joseph K., additional, Manian, Prasad, additional, Menon, Vidya, additional, Morales-Rull, Jose Luis, additional, O'Mahony, D. Shane, additional, Overcash, J. Scott, additional, Ramachandruni, Srikant, additional, Steingrub, Jay S., additional, Taha, Hassan S., additional, Waters, Michael, additional, Young, Barnaby E., additional, Phillips, Andrew N., additional, Murray, Daniel D., additional, Jensen, Tomas O., additional, Padilla, Maria L., additional, Sahner, David, additional, Shaw-Saliba, Katy, additional, Dewar, Robin L., additional, Teitelbaum, Marc, additional, Natarajan, Ven, additional, Rehman, M. Tauseef, additional, Pett, Sarah, additional, Hudson, Fleur, additional, Touloumi, Giota, additional, Brown, Samuel M., additional, Self, Wesley H., additional, Chang, Christina C., additional, Sánchez, Adriana, additional, Weintrob, Amy C., additional, Hatlen, Timothy, additional, Grund, Birgit, additional, Sharma, Shweta, additional, Reilly, Cavan S., additional, Garbes, Pedro, additional, Esser, Mark T., additional, Templeton, Alison, additional, Babiker, Abdel G., additional, Davey, Victoria J., additional, Gelijns, Annetine C., additional, Higgs, Elizabeth S., additional, Kan, Virginia, additional, Matthews, Gail, additional, Thompson, B. Taylor, additional, Neaton, James D., additional, Lane, H. Clifford, additional, and Lundgren, Jens D., additional
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- 2022
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26. Randomized Trial of Vaccines for Zaire Ebola Virus Disease
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Kieh, Mark, Richert, Laura, Beavogui, Abdoul H., Grund, Birgit, Leigh, Bailah, D’ortenzio, Eric, Doumbia, Seydou, Lhomme, Edouard, Sow, Samba, Vatrinet, Renaud, Roy, Céline, Kennedy, Stephen B., Faye, Sylvain, Lees, Shelley, Millimouno, Niouma P., Camara, Alseny M., Samai, Mohamed, Deen, Gibrilla F., Doumbia, Moussa, Espérou, Hélène, Pierson, Jerome, Watson-Jones, Deborah, Diallo, Alpha, Wentworth, Deborah, Mclean, Chelsea, Simon, Jakub, Wiedemann, Aurélie, Dighero-Kemp, Bonnie, Hensley, Lisa, Lane, Clifford, Levy, Yves, Piot, Peter, Greenwood, Brian, Chêne, Geneviève, Neaton, James, Yazdanpanah, Yazdan, CHU de Bordeaux Pellegrin [Bordeaux], Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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[SDV]Life Sciences [q-bio] ,General Medicine - Abstract
Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease.We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4.A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14.No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.).
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- 2022
27. Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial
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ACTIV-3/TICO Study Group, Barkauskas, Christina, Mylonakis, Eleftherios, Poulakou, Garyfallia, Young, Barnaby E, Vock, David M, Siegel, Lianne, Engen, Nicole, Grandits, Greg, Mosaly, Nilima R, Vekstein, Andrew M, Rogers, Ralph, Shehadeh, Fadi, Kaczynski, Matthew, Mylona, Evangelia K, Syrigos, Konstantinos N, Rapti, Vasiliki, Lye, David C, Hui, Diong Shiau, Leither, Lindsay, Knowlton, Kirk U, Jain, Mamta K, Marines-Price, Rubria, Osuji, Alice, Overcash, J Scott, Kalomenidis, Ioannis, Barmparessou, Zafeiria, Waters, Michael, Zepeda, Karla, Chen, Peter, Torbati, Sam, Kiweewa, Francis, Sebudde, Nicholus, Almasri, Eyad, Hughes, Alyssa, Bhagani, Sanjay R, Rodger, Alison, Sandkovsky, Uriel, Gottlieb, Robert L, Nnakelu, Eriobu, Trautner, Barbara, Menon, Vidya, Lutaakome, Joseph, Matthay, Michael, Robinson, Philip, Protopapas, Konstantinos, Koulouris, Nikolaos, Kimuli, Ivan, Baduashvili, Amiran, Braun, Dominique L, Günthard, Huldrych F, Ramachandruni, Srikanth, Kidega, Robert, Kim, Kami, Hatlen, Timothy J, Phillips, Andrew N, Murray, Daniel D, Jensen, Tomas O, Padilla, Maria L, Accardi, Evan X, Shaw-Saliba, Katy, Dewar, Robin L, Teitelbaum, Marc, Natarajan, Ven, Laverdure, Sylvain, Highbarger, Helene C, Rehman, M Tauseef, Vogel, Susan, Vallée, David, Crew, Page, Atri, Negin, Schechner, Adam J, Pett, Sarah, Hudson, Fleur, Badrock, Jonathan, Touloumi, Giota, Brown, Samuel M, Self, Wesley H, North, Crystal M, Ginde, Adit A, Chang, Christina C, Kelleher, Anthony, Nagy-Agren, Stephanie, Vasudeva, Shikha, Looney, David, Nguyen, Hien H, Sánchez, Adriana, Weintrob, Amy C, Grund, Birgit, Sharma, Shweta, Reilly, Cavan S, Paredes, Roger, Bednarska, Agnieszka, Gerry, Norman P, Babiker, Abdel G, Davey, Victoria J, Gelijns, Annetine C, Higgs, Elizabeth S, Kan, Virginia, and Matthews, Gail
- Subjects
Adult ,SARS-CoV-2 ,Recombinant Fusion Proteins ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,Medical and Health Sciences ,COVID-19 Drug Treatment ,Treatment Outcome ,Good Health and Well Being ,Double-Blind Method ,Clinical Research ,6.1 Pharmaceuticals ,General & Internal Medicine ,Humans ,Designed Ankyrin Repeat Proteins ,ACTIV-3/TICO Study Group ,Lung - Abstract
BackgroundEnsovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.ObjectiveTo investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.DesignDouble-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978).SettingMultinational, multicenter trial.ParticipantsAdults hospitalized with COVID-19.InterventionIntravenous ensovibep, 600 mg, or placebo.MeasurementsEnsovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90.ResultsAn independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n=247) or placebo (n=238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P=0.68; OR>1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR>1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR 
- Published
- 2022
28. Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia
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Kennedy, Stephen B., Bolay, Fatorma, Kieh, Mark, Grandits, Greg, Badio, Moses, Ballou, Ripley, Eckes, Risa, Feinberg, Mark, Follmann, Dean, Grund, Birgit, Gupta, Swati, Hensley, Lisa, Higgs, Elizabeth, Janosko, Krisztina, Johnson, Melvin, Kateh, Francis, Logue, James, Marchand, Jonathan, Monath, Thomas, Nason, Martha, Nyenswah, Tolbert, Roman, François, Stavale, Eric, Wolfson, Julian, Neaton, James D., and Lane, Clifford H.
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- 2017
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29. Improved quality of life with immediate versus deferred initiation of antiretroviral therapy in early asymptomatic HIV infection
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Lifson, Alan R., Grund, Birgit, Gardner, Edward M., Kaplan, Richard, Denning, Eileen, Engen, Nicole, Carey, Catherine L., Chen, Fabian, Dao, Sounkalo, Florence, Eric, Sanz, Jesus, and Emery, Sean
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- 2017
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30. Hazard Regression
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Grund, Birgit, Yang, Lijian, Härdle, Wolfgang, Hlávka, Zděnk, and Klinke, Sigbert
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- 2000
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31. Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.
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Lundgren, Jens D., Babiker, Abdel G., Sharma, Shweta, Grund, Birgit, Phillips, Andrew N., Matthews, Gail, Kan, Virginia L., Aagaard, Bitten, Abo, Inka, Alston, Beverly, Arenas-Pinto, Alejandro, Avihingsanon, Anchalee, Badal-Faesen, Sharlaa, Brites, Carlos, Carey, Cate, Casseb, Jorge, Clarke, Amanda, Collins, Simon, Corbelli, Giulio Maria, and Dao, Sounkalo
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HIV prevention ,HIV infections ,HIV-positive persons ,CONFIDENCE intervals ,VIRAL load ,ANTIRETROVIRAL agents ,HIGHLY active antiretroviral therapy ,CD4 lymphocyte count ,STATISTICAL sampling ,EARLY medical intervention ,PROPORTIONAL hazards models ,LONGITUDINAL method - Abstract
Background: For people with HIV and CD4
+ counts >500 cells/mm³, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm³. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. Methods: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts >500 cells/mm³ to immediate treatment initiation after random assignment (n=2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. Results: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm³ in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm³. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm³. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). Conclusions: Among adults with CD4+ counts >500 cells/mm³, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.) In people with HIV and CD4+ counts >500 cells/mm³, immediate initiation of ART reduced serious AIDS and SNA risk, the primary end point, compared with deferring ART until CD4+ counts were <350 cells/mm³. Beginning in 2016 after the deferred group was advised to initiate ART, 89 immediate and 113 deferred group participants experienced a primary end point. Persistent excess risk of the primary end point remained in the deferred compared to the immediate ART group. [ABSTRACT FROM AUTHOR]- Published
- 2023
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32. Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV.
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Murray, Daniel D., Grund, Birgit, MacPherson, Cameron R., Ekenberg, Christina, Zucco, Adrian G., Reekie, Joanne, Dominguez-Dominguez, Lourdes, Leung, Preston, Fusco, Dahlene, Gras, Julien, Gerstoft, Jan, Helleberg, Marie, Borges, Álvaro H., Polizzotto, Mark N., and Lundgren, Jens D.
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- 2023
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33. Tixagevimab/Cilgavimab for Treatment of Hospitalised COVID-19 Patients: A Randomised, Double-Blind, Phase 3 Trial
- Author
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Holland, Thomas L., primary, Ginde, Adit A., additional, Paredes, Roger, additional, Murray, Thomas A., additional, Engen, Nicole, additional, Grandits, Greg, additional, Vekstein, Andrew, additional, Ivey, Noel, additional, Mourad, Ahmad, additional, Sandkovsky, Uriel, additional, Gottlieb, Robert L., additional, Berhe, Mezgebe, additional, Jain, Mamta, additional, Marines-Price, Rubria, additional, Tchamba Agbor Agbor, Barbine, additional, Mateu, Lourdes, additional, Espana-Cueto, Sergio, additional, Llados, Gemma, additional, Mylonakis, Eleftherios, additional, Rogers, Ralph, additional, Shehadeh, Fadi, additional, Filbin, Michael R., additional, Hibbert, Kathryn A., additional, Kim, Kami, additional, Tran, Thanh, additional, Morris, Peter E., additional, Cassity, Evan P., additional, Trautner, Barbara, additional, Pandit, Lavannya M., additional, Knowlton, Kirk U., additional, Leither, Lindsay, additional, Matthay, Michael A., additional, Rogers, Angela J., additional, Drake, Wonder, additional, Jones, Beatrice, additional, Poulakou, Garyfallia, additional, Syrigos, Konstantinos N., additional, Fernandez-Cruz, Eduardo, additional, Di Natale, Marisa, additional, Almasri, Eyad, additional, Balerdi-Sarasola, Leire, additional, Bhagani, Sanjay R., additional, Boyle, Katherine L., additional, Casey, Jonathan D., additional, Chen, Peter, additional, Douin, David J., additional, Files, D. Clark, additional, Günthard, Huldrych F., additional, Hite, R. Duncan, additional, Hyzy, Robert C., additional, Khan, Akram, additional, Kibirige, Moses, additional, Kidega, Robert, additional, Kimuli, Ivan, additional, Kiweewa, Francis, additional, Jensen, Jens Ulrik Stæhr, additional, Leshnower, Bradley G., additional, Lutaakome, Joseph K., additional, Manian, Prasad, additional, Menon, Vidya, additional, Morales-Rull, Jose Luis, additional, O'Mahony, Darragh, additional, Overcash, J. Scott, additional, Ramachandruni, Srikant, additional, Steingrub, Jay S., additional, Taha, Hassan S., additional, Waters, Michael, additional, Young, Barnaby E., additional, Phillips, Andrew N., additional, Murray, Daniel D., additional, Jensen, Tomas O., additional, Padilla, Maria L., additional, Sahner, David, additional, Shaw-Saliba, Katy, additional, Dewar, Robin L., additional, Teitelbaum, Marc, additional, Natarajan, Ven, additional, Rehman, M. Tauseef, additional, Pett, Sarah, additional, Hudson, Fleur, additional, Touloumi, Giota, additional, Brown, Samuel M., additional, Self, Wesley H., additional, Chang, Christina C., additional, Sanchez, Adriana, additional, Weintrob, Amy C., additional, Hatlen, Timothy, additional, Grund, Birgit, additional, Sharma, Shweta, additional, Reilly, Cavan S., additional, Garbes, Pedro, additional, Esser, Mark T., additional, Templeton, Alison, additional, Babiker, Abdel G., additional, Davey, Victoria J., additional, Gelijns, Annetine C., additional, Higgs, Elizabeth S., additional, Kan, Virginia, additional, Matthews, Gail, additional, Thompson, B. Taylor, additional, Neaton, James D., additional, Lane, H. Clifford, additional, and Lundgren, Jens, additional
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- 2022
- Full Text
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34. Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3)
- Author
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Murray, Daniel D, primary, Babiker, Abdel G, additional, Baker, Jason V, additional, Barkauskas, Christina E, additional, Brown, Samuel M, additional, Chang, Christina C, additional, Davey, Victoria J, additional, Gelijns, Annetine C, additional, Ginde, Adit A, additional, Grund, Birgit, additional, Higgs, Elizabeth, additional, Hudson, Fleur, additional, Kan, Virginia L, additional, Lane, H Clifford, additional, Murray, Thomas A, additional, Paredes, Roger, additional, Parmar, Mahesh KB, additional, Pett, Sarah, additional, Phillips, Andrew N, additional, Polizzotto, Mark N, additional, Reilly, Cavan, additional, Sandkovsky, Uriel, additional, Sharma, Shweta, additional, Teitelbaum, Marc, additional, Thompson, B Taylor, additional, Young, Barnaby E, additional, Neaton, James D, additional, and Lundgren, Jens D, additional
- Published
- 2021
- Full Text
- View/download PDF
35. [Choosing a Kernel Regression Estimator]: Comment
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Grund, Birgit and Hardle, Wolfgang
- Published
- 1991
36. On the Minimisation of L p Error in Mode Estimation
- Author
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Grund, Birgit and Hall, Peter
- Published
- 1995
37. sj-pdf-1-ctj-10.1177_17407745211049829 – Supplemental material for Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3)
- Author
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Murray, Daniel D, Babiker, Abdel G, Baker, Jason V, Barkauskas, Christina E, Brown, Samuel M, Chang, Christina C, Davey, Victoria J, Gelijns, Annetine C, Ginde, Adit A, Grund, Birgit, Higgs, Elizabeth, Hudson, Fleur, Kan, Virginia L, Lane, H Clifford, Murray, Thomas A, Paredes, Roger, Parmar, Mahesh KB, Pett, Sarah, Phillips, Andrew N, Polizzotto, Mark N, Reilly, Cavan, Sandkovsky, Uriel, Sharma, Shweta, Teitelbaum, Marc, Thompson, B Taylor, Young, Barnaby E, Neaton, James D, and Lundgren, Jens D
- Subjects
FOS: Clinical medicine ,160807 Sociological Methodology and Research Methods ,111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified ,FOS: Sociology - Abstract
Supplemental material, sj-pdf-1-ctj-10.1177_17407745211049829 for Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) by Daniel D Murray, Abdel G Babiker, Jason V Baker, Christina E Barkauskas, Samuel M Brown, Christina C Chang, Victoria J Davey, Annetine C Gelijns, Adit A Ginde, Birgit Grund, Elizabeth Higgs, Fleur Hudson, Virginia L Kan, H Clifford Lane, Thomas A Murray, Roger Paredes, Mahesh KB Parmar, Sarah Pett, Andrew N Phillips, Mark N Polizzotto, Cavan Reilly, Uriel Sandkovsky, Shweta Sharma, Marc Teitelbaum, B Taylor Thompson, Barnaby E Young, James D Neaton and Jens D Lundgren in Clinical Trials
- Published
- 2021
- Full Text
- View/download PDF
38. sj-docx-3-ctj-10.1177_17407745211049829 – Supplemental material for Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3)
- Author
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Murray, Daniel D, Babiker, Abdel G, Baker, Jason V, Barkauskas, Christina E, Brown, Samuel M, Chang, Christina C, Davey, Victoria J, Gelijns, Annetine C, Ginde, Adit A, Grund, Birgit, Higgs, Elizabeth, Hudson, Fleur, Kan, Virginia L, Lane, H Clifford, Murray, Thomas A, Paredes, Roger, Parmar, Mahesh KB, Pett, Sarah, Phillips, Andrew N, Polizzotto, Mark N, Reilly, Cavan, Sandkovsky, Uriel, Sharma, Shweta, Teitelbaum, Marc, Thompson, B Taylor, Young, Barnaby E, Neaton, James D, and Lundgren, Jens D
- Subjects
FOS: Clinical medicine ,160807 Sociological Methodology and Research Methods ,111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified ,FOS: Sociology - Abstract
Supplemental material, sj-docx-3-ctj-10.1177_17407745211049829 for Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) by Daniel D Murray, Abdel G Babiker, Jason V Baker, Christina E Barkauskas, Samuel M Brown, Christina C Chang, Victoria J Davey, Annetine C Gelijns, Adit A Ginde, Birgit Grund, Elizabeth Higgs, Fleur Hudson, Virginia L Kan, H Clifford Lane, Thomas A Murray, Roger Paredes, Mahesh KB Parmar, Sarah Pett, Andrew N Phillips, Mark N Polizzotto, Cavan Reilly, Uriel Sandkovsky, Shweta Sharma, Marc Teitelbaum, B Taylor Thompson, Barnaby E Young, James D Neaton and Jens D Lundgren in Clinical Trials
- Published
- 2021
- Full Text
- View/download PDF
39. sj-pdf-2-ctj-10.1177_17407745211049829 – Supplemental material for Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3)
- Author
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Murray, Daniel D, Babiker, Abdel G, Baker, Jason V, Barkauskas, Christina E, Brown, Samuel M, Chang, Christina C, Davey, Victoria J, Gelijns, Annetine C, Ginde, Adit A, Grund, Birgit, Higgs, Elizabeth, Hudson, Fleur, Kan, Virginia L, Lane, H Clifford, Murray, Thomas A, Paredes, Roger, Parmar, Mahesh KB, Pett, Sarah, Phillips, Andrew N, Polizzotto, Mark N, Reilly, Cavan, Sandkovsky, Uriel, Sharma, Shweta, Teitelbaum, Marc, Thompson, B Taylor, Young, Barnaby E, Neaton, James D, and Lundgren, Jens D
- Subjects
FOS: Clinical medicine ,160807 Sociological Methodology and Research Methods ,111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified ,FOS: Sociology - Abstract
Supplemental material, sj-pdf-2-ctj-10.1177_17407745211049829 for Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) by Daniel D Murray, Abdel G Babiker, Jason V Baker, Christina E Barkauskas, Samuel M Brown, Christina C Chang, Victoria J Davey, Annetine C Gelijns, Adit A Ginde, Birgit Grund, Elizabeth Higgs, Fleur Hudson, Virginia L Kan, H Clifford Lane, Thomas A Murray, Roger Paredes, Mahesh KB Parmar, Sarah Pett, Andrew N Phillips, Mark N Polizzotto, Cavan Reilly, Uriel Sandkovsky, Shweta Sharma, Marc Teitelbaum, B Taylor Thompson, Barnaby E Young, James D Neaton and Jens D Lundgren in Clinical Trials
- Published
- 2021
- Full Text
- View/download PDF
40. Considerations for Endpoint Selection When Designing HIV Clinical Trials
- Author
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Hullsiek, Katherine Huppler and Grund, Birgit
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- 2012
- Full Text
- View/download PDF
41. Predictors for the initial CD4+ decline after antiretroviral treatment interruption in the SMART study
- Author
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Grund, Birgit
- Abstract
Poster entitled: Predictors for the initial CD4+ decline after antiretroviral treatment interruption in the SMART study.Grund, B., Babiker, A., Baxter, J., Cohen, C., Gatell, J., Hoy, J., Neuhaus, J., Oka, S., La Rosa, A., Staszewski, S., Touloumi, G., for the SMART study group
- Published
- 2020
- Full Text
- View/download PDF
42. Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3)
- Author
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Murray, Daniel D., primary, Babiker, Abdel G., additional, Baker, Jason V., additional, Barkauskas, Christina E., additional, Brown, Samuel M., additional, Chang, Christina C., additional, Davey, Victoria J., additional, Gelijns, Annetine C., additional, Ginde, Adit A., additional, Grund, Birgit, additional, Higgs, Elizabeth, additional, Hudson, Fleur, additional, Kan, Virginia L., additional, Lane, H. Clifford, additional, Murray, Thomas A., additional, Paredes, Roger, additional, Parmar, Mahesh K.B., additional, Pett, Sarah, additional, Phillips, Andrew N., additional, Polizzotto, Mark N., additional, Reilly, Cavan, additional, Sandkovsky, Uriel, additional, Sharma, Shweta, additional, Teitelbaum, Marc, additional, Thompson, B. Taylor, additional, Young, Barnaby E., additional, Neaton, James D., additional, and Lundgren, Jens D., additional
- Published
- 2020
- Full Text
- View/download PDF
43. Semiparametric lack-of-fit tests in an additive hazard regression model
- Author
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Grund, Birgit and Polzehl, Jörg
- Published
- 2001
- Full Text
- View/download PDF
44. Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial.
- Author
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Lundgren, Jens D., Grund, Birgit, Barkauskas, Christina E., Holland, Thomas L., Gottlieb, Robert L., Sandkovsky, Uriel, Brown, Samuel M., Knowlton, Kirk U., Self, Wesley H., Files, D. Clark, Jain, Mamta K., Benfield, Thomas, Bowdish, Michael E., Leshnower, Bradley G., Baker, Jason V., Jensen, Jens-Ulrik, Gardner, Edward M., Ginde, Adit A., Harris, Estelle S., and Johansen, Isik S.
- Subjects
- *
COVID-19 , *MONOCLONAL antibodies , *RANDOMIZED controlled trials , *HOSPITAL patients , *GINGER , *COVID-19 vaccines , *NEUTRALIZATION tests - Abstract
Background: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment.Objective: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high.Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978).Setting: Multicenter trial.Patients: Hospitalized patients with COVID-19 without end-organ failure.Intervention: Bamlanivimab (7000 mg) or placebo.Measurements: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections).Results: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs.Limitation: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed.Conclusion: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting.Primary Funding Source: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
45. Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).
- Author
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Murray, Daniel D, Babiker, Abdel G, Baker, Jason V, Barkauskas, Christina E, Brown, Samuel M, Chang, Christina C, Davey, Victoria J, Gelijns, Annetine C, Ginde, Adit A, Grund, Birgit, Higgs, Elizabeth, Hudson, Fleur, Kan, Virginia L, Lane, H Clifford, Murray, Thomas A, Paredes, Roger, Parmar, Mahesh KB, Pett, Sarah, Phillips, Andrew N, and Polizzotto, Mark N
- Subjects
DRUG efficacy ,SARS-CoV-2 ,COVID-19 ,CLINICAL trials ,ANTIVIRAL agents ,MEDICAL protocols - Abstract
Background/aims: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public–private partnership initiated the Therapeutics for Inpatients with COVID-19. Therapeutics for Inpatients with COVID-19 is a multi-arm, multi-stage platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate antiviral therapeutic agents for adults hospitalized with COVID-19. Five agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed. Methods: Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. Therapeutics for Inpatients with COVID-19 utilizes a multi-arm, multi-stage design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full sample size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo, the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and Data and Safety Monitoring Board schedule was developed for the study of potential therapeutic agents with limited in-human data in hospitalized patients with COVID-19. Results: As of 8 August 2021, five agents have entered the Therapeutics for Inpatients with COVID-19 master protocol and a total of 1909 participants have been randomized to one of these agents or matching placebo. There were a number of challenges faced by the study team that needed to be overcome in order to successfully implement Therapeutics for Inpatients with COVID-19 across a global network of sites. These included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and samples without overburdening clinical staff and obtaining regulatory approvals across a global network of sites. Conclusion: Through a robust multi-network partnership, the Therapeutics for Inpatients with COVID-19 protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required to achieve the full potential of this approach in dealing with a global outbreak. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
46. Interim monitoring in a treatment strategy trial with a composite primary endpoint
- Author
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Kang, Minhee, primary, Grund, Birgit, additional, Hunsberger, Sally, additional, Glidden, David, additional, and Volberding, Paul, additional
- Published
- 2019
- Full Text
- View/download PDF
47. The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters
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Martinez, Esteban, Visnegarwala, Fehmida, Grund, Birgit, Thomas, Avis, Gibert, Cynthia, Shlay, Judith, Drummond, Fraser, Pearce, Daniel, Edwards, Simon, Reiss, Peter, El-Sadr, Wafaa, and Carr, Andrew
- Published
- 2010
- Full Text
- View/download PDF
48. Continuous antiretroviral therapy decreases bone mineral density
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Grund, Birgit, Peng, Grace, Gibert, Cynthia L, Hoy, Jennifer F, Isaksson, Rachel L, Shlay, Judith C, Martinez, Esteban, Reiss, Peter, Visnegarwala, Fehmida, and Carr, Andrew D
- Published
- 2009
- Full Text
- View/download PDF
49. Asymptomatic myocardial ischaemia in HIV-infected adults
- Author
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Carr, Andrew, Grund, Birgit, Neuhaus, Jacqueline, El-Sadr, Wafaa M, Grandits, Gregory, Gibert, Cynthia, and Prineas, Ronald J
- Published
- 2008
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50. Hazard Regression
- Author
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Grund, Birgit, primary and Yang, Lijian, additional
- Published
- 2000
- Full Text
- View/download PDF
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