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Berger, Kristi L. ; Sarrazin, Christoph ; Nelson, David R. ; Scherer, Joseph ; Sha, Nanshi ; Marquis, Martin ; Côté-Martin, Alexandra ; Vinisko, Richard ; Stern, Jerry O. ; Mensa, Federico J. ; Kukolj, George
Background & Aim: The resistance profile of anti-hepatitis C virus (HCV) agents used in combination is important to guide optimal treatment regimens. We evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants among HCV genotype (GT)-1a and -1b-infected patients treated with faldaprevir (HCV protease inhibitor), deleobuvir (HCV polymerase non-nucleoside inhibitor), and ribavirin in multiple clinical studies.
Methods: HCV NS3/4A and NS5B population sequencing (Sanger method) was performed on all baseline plasma samples (n = 1425 NS3; n = 1556 NS5B) and on post-baseline plasma samples from patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b). Persistence and time to loss of resistance-associated variants (RAVs) was estimated using Kaplan–Meier analysis.
Results: Faldaprevir RAVs (NS3 R155 and D168) and deleobuvir RAVs (NS5B 495 and 496) were rare (<1%) at baseline. Virologic response to faldaprevir/deleobuvir/ribavirin was not compromised by common baseline NS3 polymorphisms (e.g. Q80K in 17.5% of GT-1a) or by NS5B A421V, present in 20% of GT-1a. In GT-1b, alanine at NS5B codon 499 (present in 15% of baseline sequences) was associated with reduced response. Treatment-emergent RAVs consolidated previous findings: NS3 R155 and D168 were key faldaprevir RAVs; NS5B A421 and P495 were key deleobuvir RAVs. Among on-treatment virologic breakthroughs, RAVs emerged in both NS3 and NS5B (>90%). Virologic relapse was associated with RAVs in both NS3 and NS5B (53% GT-1b; 52% GT-1b); some virologic relapses had NS3 RAVs only (47% GT-1a; 17% GT-1b). Median time to loss of GT-1b NS5B P495 RAVs post-treatment (5 months) was less than that of GT-1b NS3 D168 (8.5 months) and GT-1a R155 RAVs (11.5 months).
Conclusion: Faldaprevir and deleobuvir RAVs are more prevalent among virologic failures than at baseline. Treatment response was not compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499 at baseline (wild-type in GT-1a, polymorphism in GT-1b) may reduce response to this deleobuvir-based regimen.
Kyvernitakis, Ioannis ; Maul, Holger ; Rath, Werner ; Kraft, Katrina ; Kuon, Ruben ; Hamza, Amr ; Reuschel, Edith ; Filsinger, Barbara ; Abele, Harald ; Abele, Harald ; Garnier, Yves ; Bahlmann, Franz ; Schleußner, Ekkehard ; Berger, Richard
This position paper describes clinically important, practical aspects of cervical pessary treatment. Transvaginal ultrasound is standard for the assessment of cervical length and selection of patients who may benefit from pessary treatment. Similar to other treatment modalities, the clinical use and placement of pessaries requires regular training. This training is essential for proper pessary placement in patients in emergency situations to prevent preterm delivery and optimize neonatal outcomes. Consequently, pessaries should only be applied by healthcare professionals who are not only familiar with the clinical implications of preterm birth as a syndrome but are also trained in the practical application of the devices. The following statements on the clinical use of pessary application and its removal serve as an addendum to the recently published German S2-consensus guideline on the prevention and treatment of preterm birth.
Adler, Clemens ; Ahammed, Zubayer ; Allgower, Chris ; Amonett, John ; Anderson, Bryon D. ; Anderson, Mike ; Averichev, Georgy S. ; Balewski, Jan ; Barannikova, Olga ; Barnby, Lee Stuart ; Baudot, Jérome ; Bekele, Selemon ; Belaga, Victoria Vladimirovna ; Bellwied, Rene ; Berger, Jens ; Bichsel, Hans ; Bland, Leslie C. ; Blyth, Charles O. ; Bonner, Billy E. ; Bossingham, R. ; Boucham, Abdelkrim ; Brandin, Andrei V. ; Cadman, R. V. ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Cardenas, Andrés ; Carroll, J. ; Castillo Castellanos, Javier Ernesto ; Castro, M. ; Cebra, Daniel A. ; Chattopadhyay, Subhasis ; Chen, M. L. ; Chen, Y. ; Chernenko, Sergey P. ; Cherney, Michael Gerard ; Chikanian, Alexei ; Choi, B. ; Christie, William ; Coffin, Jean Pierre ; Conin, Laurent ; Cormier, Thomas Michael ; Cramer, John G. ; Crawford, Henry J. ; DeMello, M. ; Deng, W. S. ; Derevschikov, Anatoly A. ; Didenko, Lidia ; Draper, James E. ; Dunin, V. B. ; Dunlop, James C. ; Eckardt, Volker ; Efimov, Leonid G. ; Emelianov, V. ; Engelage, Jon M. ; Eppley, Geary Wareham ; Erazmus, Barbara Ewa ; Fachini, Patricia ; Finch, Evan ; Fisyak, Yuri V. ; Flierl, Dominik Bernhard ; Foley, K. J. ; Fu, J. ; Gagunashvili, N. ; Gans, J. ; Gaudichet, L. ; Germain, Marie ; Geurts, Frank ; Ghazikhanian, Vahe ; Grabski, J. ; Grachov, Oleg A. ; Greiner, D. ; Grigoriev, Vladislav A. ; Guedon, M. ; Gushin, E. ; Hallman, Timothy J. ; Hardtke, David H. ; Harris, John W. ; Heffner, Michael D. ; Heppelmann, Steven Francis ; Herston, T. ; Hippolyte, Boris ; Hirsch, Andrew S. ; Hjort, Eric ; Hoffmann, Gerald W. ; Horsley, M. ; Huang, Huan Zhong ; Humanic, Thomas J. ; Hümmler, Holm Gero ; Igo, George J. ; Ishihara, A. ; Ivanshin, Yu. I. ; Jacobs, Peter Martin ; Jacobs, William W. ; Janik, Michał ; Johnson, I. ; Jones, Peter Graham ; Judd, Eleanor G. ; Kaneta, Kaneta ; Kaplan, Morton ; Keane, Declan ; Kisiel, Adam Ryszard ; Klay, Jennifer Lynn ; Klein, Spencer Robert ; Klyachko, A. ; Konstantinov, A. S. ; Kotchenda, L. ; Kovalenko, A. D. ; Kramer, M. ; Kravtsov, Peter ; Krueger, Keith William ; Kuhn, Christian Claude ; Kulikov, Anatoly I. ; Kunde, Gerd J. ; Kunz, Christopher Lee ; Kutuev, R. Kh. ; Kuznetsov, A. A. ; Lakehal-Ayat, L. ; Lamas-Valverde, Jose ; Lamont, Matthew A. C. ; Landgraf, Jeffery M. ; Lange, S. ; Lansdell, Curtis Patrick Leon ; Lasiuk, Brian ; Laue, Frank ; Lebedev, Alexei ; LeCompte, T. ; Lednický, Richard ; Leontiev, V. M. ; Leszczynski, P. ; LeVine, Micheal J. ; Li, Q. ; Li, Q. ; Lindenbaum, Sam J. ; Lisa, Michael A. ; Ljubicic, Tonko A. ; Llope, William Joseph ; LoCurto, G. ; Long, H. ; Longacre, Ronald S. ; Lopez-Noriega, M. ; Love, William A. ; Lynn, David ; Majka, Richard Daniel ; Maliszewski, A. ; Margetis, Spyridon ; Martin, L. ; Marx, Jay N. ; Matis, Howard S. ; Matulenko, Yuri A. ; McShane, Tom S. ; Meissner, F. ; Melnick, Yu. ; Meščanin, Aleksei P. ; Messer, Matthias ; Miller, M. L. ; Milosevich, Z. ; Minaev, Nikolai G. ; Mitchell, J. ; Moiseenko, V. A. ; Moltz, D. ; Moore, C. F. ; Morozov, V. ; de Moura, M. M. ; Munhoz, Marcelo Gameiro ; Mutchler, G. S. ; Nelson, John M. ; Nevski, P. ; Nikitin, Vladimir A. ; Nogach, Larisa V. ; Norman, B. ; Nurušev, Sandibek B. ; Odyniec, Grazyna Janina ; Ogawa, Akio ; Okorokov, Vitaly A. ; Oldenburg, Markus D. ; Olson, Douglas L. ; Paic, Guy ; Pandey, S. U. ; Panebratsev, Yuri ; Panitkin, Sergei Yurievich ; Pavlinov, A. I. ; Pawlak, Tomasz Jan ; Perevoztchikov, V. ; Peryt, Wiktor Stanislaw ; Petrov, V. A. ; Pinganaud, W. ; Platner, E. ; Pluta, Jan Marian ; Porile, Norbert T. ; Porter, Jeffrey Brent ; Poskanzer, Arthur M. ; Potrebenikova, E. ; Prindle, Duncan J. ; Pruneau, Claude A. ; Radomski, S. ; Rai, Gulshan ; Ravel, Olivier ; Ray, Robert L. ; Razin, Sergej V. ; Reichhold, Dennis Michael ; Reid, Jeffrey G. ; Retiere, Fabrice ; Ridiger, Alexey ; Ritter, Hans Georg ; Roberts, Jabus B. ; Rogachevski, O. V. ; Romero, Juan L. ; Roy, Christelle Sophie ; Russ, D. ; Rykov, Vladimir L. ; Sakrejda, Iwona ; Sandweiss, Jack H. ; Saulys, A. C. ; Savin, Igor A. ; Schambach, Joachim ; Scharenberg, Rolf Paul ; Schweda, Kai ; Schmitz, Norbert ; Schroeder, Lee S. ; Schüttauf, Andreas ; Seger, Janet Elizabeth ; Seliverstov, D. ; Seyboth, Peter ; Shahaliev, Ehtiram ; Shestermanov, Konstantin E. ; Shimanskii, S. S. ; Shvetcov, V. S. ; Skoro, Goran P. ; Smirnov, Nikolai ; Snellings, Raimond ; Sowinski, James ; Spinka, Harold. M. ; Srivastava, Brijesh Kumar ; Stephenson, Edward J. ; Stock, Reinhard ; Stolpovsky, Alexander ; Strichanov, Michail Nikolaevič ; Stringfellow, Blair ; Ströbele, Herbert ; Struck, Christof ; Suaide, Alexandre Alarcon do Passo ; Sugarbaker, Evan R. ; Suire, Christophe Pierre ; Šumbera, Michal ; Symons, Timothy James MacNeil ; Toledo, Alejandro Szanto de ; Szarwas, Piotr ; Takahashi, Jun ; Tang, Aihong ; Thomas, James H. ; Tikhomirov, V. ; Trainor, Thomas A. ; Trentalange, Stephen ; Tokarev, Mikhail V. ; Tonjes, Marguerite Belt ; Trofimov, V. ; Tsai, Oleg D. ; Turner, K. ; Ullrich, Thomas ; Underwood, David G. ; Van Buren, Gene ; VanderMolen, A. M. ; Vanyashin, A. ; Vasilevski, I. M. ; Vasiliev, Alexander Nikolaevich ; Vigdor, Steven E. ; Voloshin, Sergei ; Wang, F. ; Ward, H. ; Watson, J. W. ; Wells, R. ; Wenaus, T. ; Westfall, Gary D. ; Whitten, Charles A. ; Wieman, Howard ; Willson, Robert ; Wissink, Scott W. ; Witt, Richard ; Xu, N. ; Xu, Z. ; Yakutin, A. E. ; Yamamoto, E. ; Yang, J. ; Yepes, Pablo P. ; Yokosawa, A. ; Yurevich, Vladimir Yurevich ; Zanevski, Y. V. ; Zborovský, Imrich ; Zhang, W. M. ; Zoulkarneev, R. ; Zubarev, A. N.
We report first results on elliptic flow of identified particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR TPC at RHIC. The elliptic flow as a function of transverse momentum and centrality differs significantly for particles of different masses. This dependence can be accounted for in hydrodynamic models, indicating that the system created shows a behavior consistent with collective hydrodynamical flow. The fit to the data with a simple model gives information on the temperature and flow velocities at freeze-out.