232 results on '"Caccavo A."'
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2. Neubau des Pumpspeicherwerks Forbach
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Hans‐Joachim Stech, Robert Achatz, Peter Strasser, Karsten Thermann, Gabriella Caccavo, Ulrich Gommel, and Ingo Kamuf
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Geotechnical Engineering and Engineering Geology ,Civil and Structural Engineering - Published
- 2022
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3. Pediatric Drug Safety Surveillance: A 10-Year Analysis of Adverse Drug Reaction Reporting Data in Calabria, Southern Italy
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Christian Leporini, Caterina De Sarro, Caterina Palleria, Iolanda Caccavo, Brunella Piro, Rita Citraro, and Giovambattista De Sarro
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Male ,Pharmacology ,Adolescent ,Databases, Factual ,Drug-Related Side Effects and Adverse Reactions ,Infant, Newborn ,Infant ,Toxicology ,Pharmacovigilance ,Italy ,Child, Preschool ,Adverse Drug Reaction Reporting Systems ,Humans ,Pharmacology (medical) ,Child - Abstract
The paucity of pediatric clinical trials has led to many medicines frequently prescribed to children without a license for use in pediatrics, resulting in an increased risk of adverse drug reactions. Pharmacovigilance databases remain, among others, a valuable tool for evaluating pediatric drug safety in the real-life setting.We aimed to characterize pediatric adverse drug reactions reported in the Italian Pharmacovigilance database coming from the Calabria region (Southern Italy) over 10 years.All Individual Case Safety Reports (ICSRs) concerning individuals aged under 18 years were extracted from 2010 to 2019. Duplicate and vaccine ICSRs were excluded. The remaining ICSRs were analyzed with respect to patients' demographic data, suspected drugs, and category of adverse drug reactions across different age groups.Among 6529 selected ICSRs, 395 pediatric ICSRs corresponding to 556 adverse drug reactions were analyzed. From 2010 to 2015, an increasing number of ICSRs were observed, but the reporting rate decreased after 2015. The highest proportion of ICSRs concerned children and adolescents. Around 52% of ICSRs involved boys: a trend observed in all age groups excluding newborns. Sixty ICSRs were serious and among them, 75% required hospitalization mainly in children and adolescents. Most of the ICSRs were issued by physicians (64.1%), followed by other healthcare professionals (22.5%) and pharmacists (9.9%). Anti-infective agents for systemic use and skin disorders were, respectively, the most frequently reported drug group and adverse drug reaction category.This study provides an overview of adverse drug reactions reported in the pediatric population of the Calabria region and emphasizes the need for strengthening the surveillance in specific age subgroups and on given drugs in relation to their pattern of use.
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- 2022
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4. New generation of LCPM and left atrial strain: a promising predictor of atrio-ventricular synchrony in leadless pacemaker pacing
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F Troisi, V P Caccavo, P Guida, N Vitulano, F Quadrini, A Di Monaco, L Sgarra, and M Grimaldi
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Funding Acknowledgements Type of funding sources: None. Introduction Leadless cardiac pacemakers (LCPMs) are a new alternative to traditional transvenous pacemaker. They recently have evolved from a single chamber VVI-R pacemaker to devices that can provide atrio-ventricular synchrony (AVS) in patient with sinus rhythm through an 3-axis accelerometer, detecting atrial contractions. To date, Micra AV Transcatheter Pacing System (Medtronic) is the only LCPM on the market that provides AVS. Purpose Many efforts have been made to identify clinical predictors of a good A4 signal amplitude, that determines the ability of the Micra-AV to pace while maintaining AVS (1). Our exploratory study investigates the utility of Left Atrial strain (LAs) for this purpose. Methods Data was extracted from the Cardiac Interventional Registry implemented at our hospital and approved by local ethic committee. Six patients, implanted with Micra-AV (72±13 years), underwent to a complete echocardiography focused on left atrium (LA). Morphological (LA diameters, 2d LA volume and 2d LA area) and functional (EA ratio and LAs study) parameters were assessed. An echocardiography core laboratory studied LAs (Figure A), using a dedicated software (Philips, Epiq 7-Auto Strain Tomtec Application): LA Reservoir Strain (LAsr), LA Conduit Strain (LAscd) and LA Contraction Strain (LAsct) were measured (2). All patients after implantation had a complete electronic control of leadless pacemaker to assess A4 wave amplitude. Results We found that A4 wave amplitude was inversely correlated to 2D-LA volume (Spearman's coefficient rho=-0.96; p=0.003), while it was positively related to LAsr (rho=0.81; p=0.05) and LAsct absolute value (Figure B). In the last years, in addition to the traditional echocardiographic parameters, LA was studied with a new functional parameter, LAs (3). The MARVEL2 study showed that A4 amplitude is fundamental to ensure a high AVS percentage; it was directly related to a parameter defined generically "atrial strain" (4). It is known that LAs is a complex parameter that indicates how the left atrium works overall. Today, thanks to the technological developments of the new echocardiographic software, it can be evaluated more precisely in its components. According to our preliminary data the components that predict A4 amplitude are specifically LAsr and LAsct: we found higher value of A4 in patients that have grater absolute value of these LAs parameters. LAsr is related to the atrial filling and depends on atrial stiffness and fibrosis, LAsct is an indicator of LA ability to empty, thus contributing to the final stage of ventricular diastolic filling. These are simple measurable parameters of LA functional capacity and they seem capable of predicting the possibility of a good AVS in LCPM pacing. Conclusion Patient selection is crucial to obtain good clinical outcomes. In this context, echocardiographic parameters and particularly the LAs study look promising to make a correct choice.
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- 2023
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5. Efficacy of antibacterial envelope use in cardiac implantable electronic device infection prevention: insights from real world data
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M Ziacchi, M Biffi, S Iacopino, M De Silvestro, P Marchese, F Miscio, V P Caccavo, G Zanotto, A Dello Russo, L Donazzan, and G Boriani
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Funding Acknowledgements Type of funding sources: None. Background Infections of Cardiac implantable electronic device (CIED) are rare but serious complications impacting patients and the whole heath care system. Recently, a significative reduction in major CIED infections within 12 months of the procedure has been showed by the use of an absorbable antibiotic-eluting envelope. The aim of the analysis is to evaluate the impact of the use of the envelope on infection-related clinical events (including pocket hematoma, infection, and systemic infection) reduction in a real word patient population Methods Data on patients underwent CIED implantation or replacement were collected prospectively in the framework of One HospitalClinicalService project. Patients were divided into two groups according to the utilization of an absorbable antibiotic-eluting envelope or the non-usage of the envelope. Results Out of 1819 patients, 872 (47.9%) were implanted with an absorbable antibiotic-eluting envelope and denoted as the Envelope group. Accordingly, 947 (52.1%) patients were categorized as the control group. As compared to control, patients with envelope had higher thrombo-embolic risk, higher BMI, lower LV ejection fraction and in general had more comorbidities. During a mean follow-up of 1.4 year, the incidence rate per 100 patients-months of infective related events were significantly greater in the control compared to the Envelope group (2.85% vs 1.26%, p< 0.001). The 48-month cumulative incidence of infective related events was 6.7% in the control and 2.9% in the Envelope group (HR:0.47; 95%CI: 0.27-0.95, p= 0.032). Fig1 When considering a subgroup of 1170 patients matched by PADIT score, the incidence of infective related events was 1.0 % (6/585) in the envelope and 3.8% (22/585) in the envelope and control group, respectively, p=0.002. Conclusions In our analysis, the use of envelope in the general CIED population was effective to reduce the risk of systemic or pocket infection, or pocket hematoma
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- 2023
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6. Reflexões e Narrativas Pedagógicas
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Anelize Pires Reynozo da Silva, Simone de Oliveira Coelho, Fernanda Bittencourt Novato Porto, Marcele Martins Pereira, Michele da Costa Pinheiro, Isabella Freire Ribeiro Rocha, Rosiane de Oliveira da Fonseca Santos, Amanda Oliveira Rabelo, Bárbara da Silva Leôncio, Romulo Caccavo, Flávio Pereira Rosa, Thais Vianna Maia, Rafael Romano, Leonardo Avelino Povoas, Fátima Kzam Damaceno de Lacerda, Glória da Penha Cândido Martins, Gleice Martins de Oliveira da Silva, Norma Suely Batista de Souza, Felipe Carestiato Cariello, Anderson Miguel dos Santos da Paz, Clayton Torres Felizardo, Maria Beatriz Dias da Silva Maia Porto, Kemily Toledo-Quiroga, Ingrid Carla Aldicéia Oliveira do Nascimento, Tatiana de Araújo, Marcia Garcia Gianfaldoni, Maria Alcina Porfírio dos Santos, Ranlig Carvalho de Medeiros, and Tatiana Ferreira de Lima
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Reflexões e Narrativas Pedagógicas – Volume 2 (Série Formação Docente) é a continuidade de uma série que trata da formação docente em seus múltiplos aspectos. Nosso desejo é seguir contribuindo e potencializando, de forma democrática e gratuita, os debates no campo da Educação, apresentando por meio desta nova coletânea, artigos que discutem questões fundamentais em diferentes áreas do conhecimento.
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- 2023
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7. P454 ARRHYTHMIC RISK AND REPOLARIZATION ALTERATIONS ON THE ECG UNCOVERED BY AN ISOPRENALINE TEST
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V Perniciaro, V Caccavo, A Di Monaco, G Katsouras, F Quadrini, I Romanazzi, L Sgarra, F Troisi, F Mangini, and M Grimaldi
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Cardiology and Cardiovascular Medicine - Abstract
A 62–year–old man came to our attention for a syncopal episode that occurred during a competitive race, without prodromes, lasting a few seconds, with total, spontaneous regression and without issues. On ECG sinus bradycardia, HR 46/min and QRS fragmented in V1. During monitoring were documented many polymorphic premature ventricular complex (PVC) and polymorphic nonsustained ventricular tachycardia (NSVT). Coronary angiography showed normal coronary arteries. The Isoprenaline test was performed (intravenous infusion of Isoprenaline 0.2 mg in 100 ml of physiological solution at variable speed until obtaining a HR increase of at least 20% compared to baseline). As HR increased, a clear epsilon wave in V1 became evident. Also documented numerous polymorphic PVC and polymorphic NSVT. Cardiac magnetic resonance (MRI) was performed with documentation of findings suggestive of primary cardiomyopathy with biventricular phenotypic expression with a clear left prevalence. All these elements placed the patient at high arrhythmic risk. An implantable cardiac defibrillator was then performed. The isoprenaline–induced increase in heart rate made the epsilon wave manifest, which is an expression of an extremely delayed depolarization caused by the fibroadipose replacement of portions of the myocardium (as documented by cardiac MRI). It was also possible to exclude a J–wave syndrome in which the alterations are of repolarization and are due to the epi–endocardial electrical gradient which increases and becomes more evident at lower heart rates. The test with isoprenaline has therefore allowed us to distinguish depolarization disorders from repolarization disorders and to direct us towards the former.
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- 2023
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8. P418 WHEN THE GAME IS HARD…. IT‘S BETTER TO COOPERATE! THE INTEGRATED MANAGEMENT OF THE ELECTROPHYSIOLOGIST AND HEMODYNAMIST WHO RESOLVES THE COMPLICATION
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V Perniciaro, V Caccavo, A Di Monaco, G Katsouras, F Quadrini, L Sgarra, F Troisi, T Langialonga, and M Grimaldi
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Cardiology and Cardiovascular Medicine - Abstract
A 66–year–old woman came to our attention to undergo ablation of monomorphic, frequent and repetitive premature ventricular complex, symptomatic and refractory antiarrhythmic therapy. Mapping of the arrhythmia showed precocity both on the anterolateral segment of the coronary sinus and on the anterolateral mitral annulus (corresponding to the point first identified in the coronary sinus). However, earliness on the anterolateral segment of the coronary sinus was better; radiofrequency was then applied there (maximum power of 30 Watts for 120 seconds). After a few minutes, blood pressure drop and echocardiogram showed tamponade pericardial effusion. Pericardiocentesis was performed and part of the drained blood recovered by connecting an 8F long introducer (inserted in the pericardium) to the introducer in the right femoral vein, thus stabilizing the patient‘s hemodynamics. The coronary sinus was selectively cannulated with an Agilis deflectable long introducer (advanced to the vessel ostium using a deflectable decapular electrocatheter as a guide) thus visualizing the lesion on the vessel wall site of ablation. A guiding catheter for the right coronary artery was inserted into the coronary sinus and a guidewire was advanced to the distal part of the vessel. The lesion was effectively treated by placing a 5 mm by 21 mm covered stent. After approximately one hour of monitoring, the pericardial drainage was removed. There were no recurrences of arrhythmia or pericardial effusion during observation in the ICU or at follow–up. In this complex case, the integrated management of the electrophysiologist and the hemodynamist successfully resolved the complication without resorting to cardiac surgery.
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- 2023
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9. Small mammals from the <scp>C</scp> aatinga: A dataset for the <scp>B</scp> razilian semiarid biome
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Anna Ludmilla da Costa‐Pinto, Ricardo S. Bovendorp, Adriana Bocchiglieri, Aldo Caccavo, Ana Cláudia Delciellos, Ana Cláudia Malhado, Ana Karolina Rodrigues de Almeida, Caryne Braga, Diogo Loretto, Edeltrudes Maria Valadares Calaça Câmara, Fernando Heberson Menezes, Gabby Guilhon, Gabriela Paise, Gisela Sobral, Iardley Cícero Gomes Varjão, Jéssica Viviane Amorim Ferreira, Leandro da Silva Oliveira, Lena Geise, Luiz Cezar Machado Pereira, Matheus Rocha Jorge Corrêa, Patricia Avello Nicola, Patricia Gonçalves Guedes, Rafael Gustavo Becker, Rebeca Mascarenhas Fonseca Barreto, Shirley Seixas Pereira da Silva, Vinicius Santana Orsini, and Richard James Ladle
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Ecology, Evolution, Behavior and Systematics - Abstract
The Caatinga is an exclusively Brazilian biome, and is the largest and most biodiverse Seasonal Tropical Dry Forest in the world. Despite that, the mammalian fauna, especially small mammals, is the least studied of all Brazilian biomes. In order to fill gaps and provide detailed information on small mammals (Didelphimorphia, Rodentia) in the Caatinga biome, we compiled reliable records focusing on richness, composition and some biometric data. These records came from mammal collections, papers, theses, books, and unpublished data, prioritizing records with vouchers housed in scientific collections. We compiled a total of 3133 records from 816 locations, resulting in a richness of 47 native species (12 marsupials and 35 rodents, plus three exotic rodents, Rattus rattus, Rattus norvegicus, and Mus musculus). This dataset includes records of three new species for the biome and its transition zone: the rodents Calomys mattevii, Holochilus oxe, and Nectomys squamipes. Of the total number of records, 1808 (57.71%) are from consulting activities, 95 (3.03%) are from zoonoses studies and 104 (3.32%) are from the National Plague Service (SNP). All nine Brazilian states with territory in the Caatinga have sampling data for small mammals, but the number of records and localities are unevenly distributed, with the state of Rio Grande do Norte having the lowest number of records and locations sampled. Our dataset is the first of its kind for the Caatinga biome and has considerable potential value for studies of habitat use, landscape ecology, macroecology, biogeography, and conservation. There are no copyright restrictions on the data. Please cite this data paper when the data are used in publications. We also request that researchers and teachers inform us of how they are using the data.
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- 2022
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10. Effects of Below-Ground Microbial Biostimulant
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Pierluigi, Forlano, Stefania Mirela, Mang, Vittoria, Caccavo, Paolo, Fanti, Ippolito, Camele, Donatella, Battaglia, and Vincenzo, Trotta
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Agrochemicals are generally used in agriculture to maximize yields and product quality, but their overuse can cause environmental pollution and human health problems. To reduce the off-farm input of chemicals, numerous biostimulant products based on beneficial symbiont plant fungi are receiving a great deal of attention. The evolution of plant diseases and the performance of insects are influenced by plant chemical defences, both of which are, in turn, influenced by below-ground symbionts. Direct and indirect plant defences mediated by belowground symbionts against plant diseases and insect herbivores were demonstrated in greenhouses experiments. However, little attention has been paid to the use of
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- 2022
11. Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab
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Emil Hagström, P. Gabriel Steg, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Nicolas Danchin, Rafael Diaz, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Evangelos Liberopoulos, Nikolaus Marx, Jennifer McGinniss, Garen Manvelian, Robert Pordy, Michel Scemama, Harvey D. White, Andreas M. Zeiher, Gregory G. Schwartz, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S Nieminen, Vakhtang Chumburidze, Pablo Carlos, Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J Dalby, José Tuñón, H. Asita de Silva, Ulf Landmesser, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B Schiavi, Marcelo Garrido, Andrés F Alvarisqueta, Sonia A Sassone, Anselmo P Bordonava, Alberto E Alves De Lima, Jorge M Schmidberg, Ernesto A Duronto, Orlando C Caruso, Leonardo P Novaretto, Miguel Angel Hominal, Oscar R Montaña, Alberto Caccavo, Oscar A Gomez Vilamajo, Alberto J Lorenzatti, Luis R Cartasegna, Gustavo A Paterlini, Ignacio J Mackinnon, Guillermo D Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R Codutti, Horacio O Jure, Julio OE Bono, Adrian D Hrabar, Julio A Vallejos, Rodolfo A Ahuad Guerrero, Federico Novoa, Cristian A Patocchi, Cesar J Zaidman, Maria E Giuliano, Ricardo D Dran, Marisa L Vico, Gabriela S Carnero, Pablo N Guzman, Juan C Medrano Allende, Daniela F Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H Waites, Nicholas Collins, Allan Soward, Chris LS Hii, James Shaw, Margaret A Arstall, John Horowitz, Daniel Ninio, James F Rogers, David Colquhoun, Romulo E Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J Lehman, Constantine Aroney, Steven GM Coverdale, Paul J Garrahy, Gregory Starmer, Mark Sader, Patrick A Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias CM Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Azra Durak-Nalbantic, Mehmed Kulić, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C Nicolau, Flavio E Giorgeto, Ricardo P Silva, Lilia Nigro Maia, Rafael Rech, Paulo RF Rossi, Maria José AG Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler ON de Santos, Fernando Neuenschwander, Luiz C Bodanese, Yorghos L Michalaros, Freddy G Eliaschewitz, Maria H Vidotti, Paulo E Leaes, Roberto V Botelho, Sergio Kaiser, Euler Roberto F Fernandes Manenti, Dalton B Precoma, Jose C Moura Jorge, Pedro Silva, Jose A Silveira, Wladmir Saporito, Jose A Marin Neto, Gilson S Feitosa, Luiz Eduardo F Ritt, Juliana A de Souza, Fernando Costa, Weimar KSB Souza, Helder JL Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V Todorov, Fedya P Nikolov, Elena S Velcheva, Maria L Tzekova, Haralambi O Benov, Stanislav L Petranov, Haralin S Tumbev, Nina S Shehova-Yankova, Dimitar T Markov, Dimitar H Raev, Mihail N Mollov, Kostadin N Kichukov, Katya A Ilieva- Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M Mincheva, Petar V Lazov, Bojidar I Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi’An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian’An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C Luna Botia, Rodrigo Botero Lopez, Dora I Molina De Salazar, Alberto J Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I Barrera Silva, Henry J Garcia Lozada, Julian A Coronel Arroyo, Jose L Accini Mendoza, Ricardo L Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A Urina Triana, Angela M Fernandez Trujillo, Maja Strozzi, Siniša Car, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H Poulsen, Bent Raungaard, Peter Clemmensen, Lia E Bang, Ole May, Morten Bøttcher, Jens D Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S Kristensen, Piotr Maria Walichiewicz, Jens D Lomholdt, Ib C Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Saila Vikman, Heikki Huikuri, Juhani Airaksinen, Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Ph. Gabriel Steg, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun- Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk 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Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B Pothineni, Minguel R Monteiro, Aziz Khan, Shamanna S Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C Fulwani, Dr. Aparna Patange, Patil Sachin, Vijay K Chopra, Naresh K Goyal, Rituparna Shinde, Gajendra V Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karnaand Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Jabir Abdullkutty, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel 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Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hyo-Soo Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B Liew, Wan Mohd 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McClanahan, Roe, Matthew T., Blicharski, Tomasz, Bystryk, Leszek, Szpajer, Michal, Korol, Marek, Czerski, Tomasz, Gniot, Jacek, Lubinski, Andrzej, Gorny, Jerzy, Franek, Edward, Raczak, Grzegorz, Vogel, Robert, Szwed, Hanna, Monteiro, Pedro, Mesquita Bastos, Jose, Pereira, Helder H., Morais, Joao, Seixo, Filipe, Mendonça, Carlos, Botelho, Ana, Caetano, Francisca, Minescu, Bogdan, Chaitman, Bernard, Istratoaie, Octavian, Tesloianu, Dan N., Dorobantu, Maria, Cristian, Gabriel, Dumitrescu, Silviu, Podoleanu, Cristian Gc, Constantinescu, Mircea Ca, Bengus, Cristina M., Militaru, Constantin, Rosu, Doina, Kelsey, Sheryl F., Parepa, Irinel R., Matei, Adrian V., Alexandru, Tom M., Malis, Mihaela, Coman, Ioan, Shvarts, Yury, Orlikova, Olga, Kobalava, Zhanna, Barbarash, Olga L., Markov, Valentin, Olsson, Anders G., Lyamina, Nadezhda, Gordienko, Alexander, Zrazhevsky, Konstantin, Vishnevsky, Alexander Y., Gurevich, Victor, Stryuk, Raisa, Lomakin, Nikita V., Bokarev, Igor, Khlevchuk, Tatiana, Shalaev, Sergey, Rouleau, Jean-Lucien, Khaisheva, Larisa, Chizhov, Petr, Viktorova, Inna, Osokina, Natalya, Shchekotov, Vladimir, Akatova, Evgenia, Chumakova, Galina, Libov, Igor, Voevoda, Mikhail I., Tretyakova, Tatyana V., Simoons, Maarten L., Baranov, Evgeny, Shustov, Sergey, Yakushin, Sergey, Gordeev, Ivan, Khasanov, Niiaz, Reshetko, Olga, Sotnikova, Tatiana, Molchanova, Olga, Nikolaev, Konstantin, Gapon, Liudmila, Alexander, Karen, Baranova, Elena, Kosmachova, Elena, Karpov, Yuriy, Karpov, Yuri, Povzun, Anton, Egorova, Liudmila, Tyrenko, Vadim V., Ivanov, Igor G., Ilya, Masterov, Kanorsky, Sergey, Meloni, Chiara, Simic, Dragan, Ivanovic, Nikola, Davidovic, Goran, Tasic, Nebojsa, Asanin, Milika R., Stojic, Stevo, Apostolovic, Svetlana R., Ilic, Stevan, Tosic, Biljana Putnikovic, Stankovic, Aleksandar, Rosenson, Robert, Arandjelovic, Aleksandra, Radovanovic, Slavica, Todic, Branislava, Ristic, Arsen D., Balinovac, Jovan, Dincic, Dragan V., Seferovic, Petar, Karadzic, Ana, Dodic, Slobodan, Dimkovic, Sinisa, Sijbrands, Eric J. G., Jakimov, Tamara, Poh, Kian-Keong, Yee Ong, Hean, Tang I-Shing, Justin, Micko, Karol, Nociar, Jan, Pella, Daniel, Fulop, Peter, Hranai, Marian, Palka, Juraj, Tricoci, Pierluigi, Mazur, Juraj, Majercák, Ivan, Dzupina, Andrej, Fazekas, František, Gonsorcik, Jozef, Bugan, Viliam, Murin, Jan, Selecky, Juraj, Kamensky, Gabriel, Strbova, Jaroslava, Alexander, John H., Smik, Rudolf, Dukat, Andrej, Olexa, Peter, Žuran, Ivan, Poklukar, Janez, Šuligoj, Nataša Černič, Cevc, Matija, Fras, Zlatko, Cyster, Henry P., Ranjith, Naresh, Armaganijan, Luciana, Corbett, Clive, Bayat, Junaid, Makoali Makotoko, Ellen, du Toit Theron, Hendrik, Kapp, Ilse E., de V Basson, Matthys M., Lottering, Hanlie, Van Aswegen, Dina, Van Zyl, Louis J., Sebastian, Peter J., Bagai, Akshay, Pillay, Thayabran, Saaiman, Jan A., Commerford, Patrick J., Cassimjee, Soraya, Riaz, Garda, Ebrahim, Iftikhar O., Sarvan, Mahomed, Mynhardt, Joseph H., Dalby, Anthony J., Reuter, Helmuth, Bahit, Maria Cecilia, Moodley, Rajendran, Vida, Manuel, Fillat, Angel R. Cequier, Peris, Vicente Bodí, Jimenez, Francisco Fuentes, Marín, Francisco, Cruz Fernández, Jose M., Hidalgo Urbano, Rafael Jesus, Gil-Extremera, Blas, Toledo, Pablo, Brennan, J. Matthew, Worner Diz, Fernando, Garcia-Dorado, David, Iñiguez, Andres, Gonzalez-Juanatey, Jose R., Portales, Javier Fernandez, Murillo, Fernando Civeira, Pericas, Laia Matas, Zamorano, Jose Luis, De Mora Martin, Manuel, Cortada, Jordi Bruguera, Clifton, Shaun, Alonso Martin, Joaquin J., Serrano Antolin, Jose Maria, De Berrazueta Fernández, José R., Vázquez de Prada, José Antonio, Díaz Fernández, Jose Francisco, García Lledó, José Alberto, Cosín Sales, Juan, Rodriguez, Javier Botas, Tragant, Gabriel Gusi, Benedicto, Amparo, DeVore, Adam D., Gonzalez-Juanatey, Carlos, Camprubí Potau, Mercedes, Perez, Ignacio Plaza, De La Tassa, César Morís, Rincon, Pablo Loma-Osorio, Recena, Javier Balaguer, Escudier, Juan M., Payeras, Antonio Coca, Orcajo, Norberto Alonso, Constantine, Godwin, Deloatch, Shalonda, Haniffa, Ruvaiz, Tissera, Nirmali, Amarasekera, Stanley, Ponnamperuma, Chandrike, Fernando, Nimali, Fernando, Kaputella, Jayawardena, Jayanthimala, Wijeyasingam, Santharaj, Ranasinghe, Gotabhaya, Ekanayaka, Ruvan, Dickey, Sheila, Mendis, Sepalika, Senaratne, Vajira, Mayurathan, Gnanamoorthy, Rajapaksha, Ajantha, Sirisena, Thilak, Herath, Jagath I., Amarasena, Naomali, Berglund, Stefan, Rasmanis, Gundars, Hagström, Emil, Dombrowski, Keith, Vedin, Ola, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjörn, Ducrocq, Grégory, Moccetti, Tiziano, Müller, Christian, Mach, Francois, Binde, Ronald, Landmesser, Ulf, Gämperli, Oliver, Chiang, Chern-En, Tsai, Wei-Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Eapen, Zubin, Liu, Ming-En, Hwang, Juey-Jen, Yin, Wei-Hsian, Hsieh, I.-Chang, Hsieh, Ming-Jer, Hsiang Lin, Wei, Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Endsley, Patricia, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Sritara, Piyamitr, Wongpraparut, Nattawut, Sastravaha, Krisada, Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Chotnoparatpat, Paiboon, Eppinger, Arleen, Camsari, Ahmet, Kultursay, Hakan, Guneri, Sema, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Harrison, Robert W., Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, Hess, Connie Ng, Stanislavchuk, Mykola, Kyiak, Yulian, Karpenko, Yuriy, Malynovsky, Yaroslav, Klantsa, Andriy, Kutniy, Oles, Amosova, Ekaterina, Tashchuk, Viktor, Leshchuk, Oleh, Parkhomenko, Alexander, Hlatky, Mark A., Rishko, Mykola, Kopytsya, Mykola, Yagensky, Andriy, Vatutin, Mykola, Bagriy, Andriy, Barna, Olga M., Ushakov, Olexiy, Dzyak, Georgiy, Goloborodko, Borys, Rudenko, Anatolii, Jordan, Joseph Dedrick, Zheleznyy, Volodymyr, Trevelyan, Jasper, Zaman, Azfar, Lee, Kaeng, Moriarty, Andrew, Aggarwal, Rajesh K., Clifford, Piers, Wong, Yuk-ki, Iqbal, Syed Mr, Subkovas, Eduardas, Knowles, Joshua W., Braganza, Denise, Sarkar, David, Storey, Robert, Griffiths, Huw, Mcclure, Sam, Muthusamy, Rangasamy, Smith, Simon, Kurian, John, Levy, Terry, Barr, Craig, Kolls, Bradley J., Kadr, Honer, Gerber, Robert, Simaitis, Audrius, Soran, Handrean, Brodison, Adrian, Ayaz, Mohammad, Cheema, Muhammad, Oliver, Richard, Thackray, Simon, Mudawi, Telal, Kong, David F., Rahma, Gohar, Sultan, Ayyaz, Reynolds, Timothy, Sharman, David, Spriging, David, Butler, Rob, Wilkinson, Peter, Lip, Gregory Yh, Ossei-Gerning, Nicholas, Vardi, Gil, Leonardi, Sergio, Baldari, Duccio, Brabham, David, Treasure Ii, Charles, Dahl, Charles, Palmer, Bruce, Wiseman, Alan, Khan, Abul, Puri, Sanjeev, Mohart, Ann Elizabeth, Ince, Carlos, Lillis, Linda, Flores, Enrique, Wright, Scott, Cheng, Shi-Chi, Rosenberg, Michael, Rogers, William, Kosinski, Edward, Forgosh, Les, Waltman, Jonathan, Shoukfeh, Mohammad, Dagher, Georges, Lopes, Renato D., Cambier, Patrick, Lieber, Ira, Kumar, Priya, East, Cara, Krichmar, Perry, Hasan, Mian, White, Lindsey, Knickelbine, Thomas, Haldis, Thomas, Gillespie, Eve, Maron, David J., Amidon, Thomas, Suh, David, Arif, Imran, Abdallah, Mouhamad, Akhter, Faiq, Carlson, Eric, D'Urso, Michael, El-Ahdab, Fadi, Nelson, William, Moriarty, Katie, Mahaffey, Kenneth W., Harris, Barry, Cohen, Steven, Carter, Luther, Doty, Daniel, Sabatino, Kenneth, Haddad, Tariq, Rao, Sunder, Mulkay, Angel, Jovin, Ion, Klancke, Kim, Marcus, Jill, Malhotra, Vinay, Devarapalli, Sai K., Koren, Michael, Chandna, Harish, Dodds Iii, George, Goraya, Tauqir, Bengston, James, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Mathews, Robin, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, Fenton, Sarah, Singh, Narendra, Mehta, Rajendra H., Shah, Anil V., Moriarty, Patrick M., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Richard, Kerensky, Keating, Friederike, Kondo, Nicholas I., Mentz, Robert J., Shetty, Sanjay, Levite, Howard, Waider, Winfried, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Kumar, Anil, Hattler, Brack, Do, Rose, Moreira, Humberto Graner, Link, Chad, Bortnick, Anna, Kinzfogl Iii, George, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Patel, Chetan B., Abbas, Jalal, White, Matthew, Islam, Othman, Subherwal, Sumeet, Ranadive, Nandkishore, Vakili, Babak, Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Pereira, Sabrina Bernardez, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Horwitz, Phillip, Zahr, Firas, Ponce, George, Jafar, Zubair, Perkins, Lynn, Mcgarvey, Joseph, Panchal, Vipul, Voyce, Stephen, Blok, Thomas, Sheldon, William, Azizad, Masoud M., Schmalfuss, Carsten, Picone, Mark, Pederson, Robert, Herzog, William, Povsic, Thomas J., Friedman, Keith, Lindsey, Jason, Timothy, Eichenlaub, Leonard, Parilak, Lepor, Norman, El Shahawy, Mahfouz, Weintraub, Howard, Irimpen, Anand, Alonso, Alvaro, May, Wade, Puymirat, Etienne, Christopher, Daniels, Galski, Thomas, Chu, Alan, Mody, Freny, Ramin, Ebrahimi, Hodes, Zachary, Rossi, Joseph, Rose, Gregory, Fairlamb, James, Lambert, Charles, Raisinghani, Ajit, Abbate, Antonio, Vetrovec, George, King, Marilyn, Carey, Charles, Gerber, Jaime, Younis, Liwa, Park, Hyeun Tom, Vidovich, Mladen, Knutson, Thomas, Jones, William Schuyler, Friedman, Dennis, Chaleff, Fred, Loussararian, Arthur, Rozeman, Phillip, Kimmelstiel, Carey, Kuvin, Jeffrey, Silver, Kevin, Foster, Malcolm, Tonnessen, Glen, Espinoza, Andrey, Shah, Bimal R., Amlani, Mohamadali, Wali, Andreas, Malozzi, Christopher, Jong, Geert T., Massey, Clara, Wattanakit, Keattiyoat, O'Donnell, Philip J., Singal, Dinesh, Jaffrani, Naseem, Banuru, Sridhar, Sherwood, Matthew W., Fisher, Daniel, Xenakis, Mark, Perlmutter, Neal, Bhagwat, Ravi, Strader, James, Blonder, Ronald, Akyea-Djamson, Ayim, Labroo, Ajay, Lee, Kwan, Marais, H. John, Stringfellow, Kenya, Claxton, Edmund, Weiss, Robert, Kathryn, Rohr, Berk, Martin, Rossi, Peter, Joshi, Parag, Khera, Amit, Khaira, Ajit S., Kumkumian, Greg, Lupovitch, Steven, Sujjavanich, Darin, Purow, Joshua, Welka, Stephen, Hoffman, David, Fischer, Stuart, Soroka, Eugene, Eagerton, Donald, Pancholy, Samir, Ray, Michael, Erenrich, Norman, Farrar, Michael, Toma, Mustafa, Pollock, Stewart, French, William J., Diamantis, Steve, Guy, Douglas, Gimple, Lawrence, Neustel, Mark, Schwartz, Steven, Pereira, Edward, Albert, Seals, Spriggs, Douglas, Trotter, Charlene, Strain, Janet, Mittal, Suneet, Vo, Anthony, Chane, Majed, Hall, Jason, Vijay, Nampalli, Lotun, Kapildeo, Lester, F. Martin, Nahhas, Ahed, Pope, Theodore, van Diepen, Sean F. P., Nager, Paul, Vohra, Rakesh, Sharma, Mukesh, Bashir, Riyaz, Ahmed, Hinan, Berlowitz, Michael, Fishberg, Robert, Barrucco, Robert, Yang, Eric, Radin, Michael, Wilson, Matthew D., Sporn, Daniel, Stapleton, Dwight, Eisenberg, Steven, Landzberg, Joel, Mcgough, Martin, Turk, Samir, Schwartz, Michael, Sundram, P. Sandy, Jain, Diwakar, Zainea, Mark, Tze-Kay Yan, Andrew, Bayron, Carlos, Karlsberg, Ronald, Dohad, Suhail, Lui, Henry, Keen, William, Westerhausen, Donald, Khurana, Sandeep, Agarwal, Himanshu, Birchem, Jessica, Penny, William, Schiavi, Lilia B., Chang, Mark, Murphy, Sherrill, Henry, John, Schifferdecker, Branislav, Gilbert, John M., Chalavarya, Gopal, Eaton, Charles, Schmedtje, John F., Christenson, Stuart, Dotani, Imran, Garrido, Marcelo, Denham, Douglas, Macdonell, Alexander, Gibson, Paul, Rahman, Aref, Al Joundi, Tammam, Assi, Nizar, Conrad, Gary, Kotha, Purushotham, Love, Michael, Giesler, Gregory, Alvarisqueta, Andrés F., Rubenstein, Howard, Gamil, Dawood, Akright, Laura, Krawczyk, Justine, Cobler, Joanne, Wells, Terry, Welker, James, Foster, Robert, Gilmore, Richard, Anderson, Jay, Sassone, Sonia A., Jacoby, Douglas, Harris, Bill, Gardner, Geraldine, Dandillaya, Ramprasad, Vora, Kishor, Kostis, John, Hunter, John, Laxson, David, Ball, Eric, Bordonava, Anselmo P., Egydio, Flavia, Kawakami, Anelise, Oliveira, Janaina, Goodman, Shaun G., Wozniak, Julianna, Alves De Lima, Alberto E., Matthews, Alexander, Ratky, Caroline, Valiris, Janine, Berdan, Lisa, Hepditch, Anita, Quintero, Kirby, Rorick, Tyrus, Westbrook, Melissa, Danchin, Nicolas, Schmidberg, Jorge M., Bezault, Madeleine, Drouet, Elodie, Simon, Tabassome, White, Harvey D., Alsweiler, Caroline, Sinnaeve, Peter, Luyten, Anne, Aylward, Philip E., Butters, Julie, Griffith, Liddy, Duronto, Ernesto A., Shaw, Michelle, Grunberg, Lena, Szarek, Michael, Islam, Shahidul, Brégeault, Marie-France, Bougon, Nathalie, Faustino, Douglas, Fontecave, Sylvie, Murphy, Judith, Caruso, Orlando C., Tamby, Jean-Francois, Verrier, Melanie, Agnetti, Veronique, Andersen, Dorthe, Badreddine, Emmy, Bekkouche, Mhamed, Bouancheau, Cecile, Brigui, Imane, Brocklehurst, Maddy, Cianciarulo, Joseph, Novaretto, Leonardo P., Devaul, Dawn, Domokos, Szilvia, Gache, Cecile, Gobillot, Caroline, Guillou, Severine, Healy, Jan, Heath, Megan, Jaiwal, Gayatri, Javierre, Carine, Labeirie, Julien, Hominal, Miguel Angel, Monier, Myriam, Morales, Ulises, Mrabti, Asmaa, Mthombeni, Bicky, Okan, Betim, Smith, Lucile, Sheller, Jennifer, Sopena, Sebastien, Pellan, Valerie, Benbernou, Fadela, Montaña, Oscar R., Bengrait, Nafissa, Lamoureux, Maud, Kralova, Katarina, Scemama, Michel, Bejuit, Raphael, Coulange, Anthony, Berthou, Christelle, Repincay, Jérôme, Lorenzato, Christelle, Etienne, Alexis, Caccavo, Alberto, Gouet, Valerie, Lecorps, Guillaume, Loizeau, Virginie, Normand, Mickael, Ourliac, Anne, Rondel, Christelle, Adamo, Antony, Beltran, Pascale, Barraud, Pauline, Dubois-Gache, Helene, Gomez Vilamajo, Oscar A., Halle, Benjamin, Metwally, Lamia, Mourgues, Maxime, Sotty, Marc, Vincendet, Marion, Cotruta, Raluca, Chengyue, Zhu, Fournie-Lloret, Dominique, Morrello, Christine, Perthuis, Aurelie, Lorenzatti, Alberto J., Picault, Patrick, Zobouyan, Isabelle, Colhoun, Helen M., Dempsey, Michael A., McClanahan, Mark A., Cartasegna, Luis R., Paterlini, Gustavo A., Mackinnon, Ignacio J., Caime, Guillermo D., Amuchastegui, Marcos, Salomone, Oscar, Codutti, Oscar R., Jure, Horacio O., Bono, Julio Oe, Hrabar, Adrian D., Vallejos, Julio A., Ahuad Guerrero, Rodolfo A., Novoa, Federico, Patocchi, Cristian A., Zaidman, Cesar J., Giuliano, Maria E., Schwartz, Gregory G., Dran, Ricardo D., Vico, Marisa L., Carnero, Gabriela S., Guzman, Pablo N., Medrano Allende, Juan C., Garcia Brasca, Daniela F., Bustamante Labarta, Miguel H., Nani, Sebastian, Blumberg, Eduardo Ds, Colombo, Hugo R., Bhatt, Deepak L., Liberman, Alberto, Fuentealba, Victorino, Luciardi, Hector L., Waisman, Gabriel D., Berli, Mario A., Garcia Duran, Ruben O., Cestari, Horacio G., Luquez, Hugo A., Giordano, Jorge A., Saavedra, Silvia S., Bittner, Vera A., Zapata, Gerardo, Costamagna, Osvaldo, Llois, Susana, Waites, Jonathon H., Collins, Nicholas, Soward, Allan, Hii, Chris Ls, Shaw, James, Diaz, Rafael, Arstall, Margaret A., Horowitz, John, Ninio, Daniel, Rogers, James F., Colquhoun, David, Oqueli Flores, Romulo E., Roberts-Thomson, Philip, Raffel, Owen, Lehman, Sam J., Aroney, Constantine, Coverdale, Steven Gm, Garrahy, Paul J., Starmer, Gregory, Sader, Mark, Carroll, Patrick A., Dick, Ronald, Zweiker, Robert, Hoppe, Uta, Drexel, Heinz, Huber, Kurt, Harrington, Robert A., Berger, Rudolf, Delle-Karth, Georg, Frey, Bernhard, Weidinger, Franz, Faes, Dirk, Hermans, Kurt, Pirenne, Bruno, Leone, Attilio, Hoffer, Etienne, Jukema, J. 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Michael A, and McClanahan, Mark A
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Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ,Anticholesteremic Agents/adverse effects ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,prevention & control ,heart disease risk factors ,diagnosis [Cardiovascular Diseases] ,Antibodies, Monoclonal, Humanized ,PCSK9 inhibitors, acute coronary syndrome, apolipoproteins B, LDL cholesterol ,Antibodies ,acute coronary syndrome ,LDL ,drug therapy [Atherosclerosis] ,Risk Factors ,Physiology (medical) ,therapeutic use [Hydroxymethylglutaryl-CoA Reductase Inhibitors] ,Monoclonal ,Humans ,Cardiac and Cardiovascular Systems ,Humanized ,Cardiovascular Diseases/diagnosis ,Apolipoproteins B ,Kardiologi ,diagnosis [Acute Coronary Syndrome] ,Anticholesteremic Agents ,PCSK9 inhibitors ,apolipoproteins B ,cholesterol, LDL ,cholesterol ,Atherosclerosis/drug therapy ,Cholesterol, LDL ,Atherosclerosis ,Acute Coronary Syndrome/diagnosis ,drug therapy ,Cholesterol ,Treatment Outcome ,Cardiovascular Diseases ,Heart Disease Risk Factors ,epidemiology ,adverse effects [Anticholesteremic Agents] ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine - Abstract
Circulation : an official journal of the American Heart Association / ed.-in-chief Ephraim Donosco 146(9), 657-672 (2022). doi:10.1161/CIRCULATIONAHA.121.057807, Published by Ovid, [Erscheinungsort nicht ermittelbar]
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- 2022
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12. Systematics of the rodent genusNeacomysThomas (Cricetidae: Sigmodontinae): two new species and a discussion on carotid patterns
- Author
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Marcelo Weksler and Aldo Caccavo
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0106 biological sciences ,Systematics ,0303 health sciences ,Species complex ,Sigmodontinae ,Ecology ,biology ,Holotype ,biology.organism_classification ,Neacomys ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,Genus ,Evolutionary biology ,Genetics ,Animal Science and Zoology ,Taxonomy (biology) ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Nature and Landscape Conservation ,Cricetidae - Abstract
The taxonomy of the oryzomyine genus Neacomys currently is in a state of flux: systematic studies in the last 20 years increased its diversity from four to 16 species, with an additional several undescribed phylogenetic lineages. Despite this progress, morphological variation and species limits remain poorly known for several species groups and complexes within the genus, such as N. tenuipes, N. musseri, and N. dubosti. Here we analyze the variation of morphological characters and morphometric patterns of two new candidate species of Neacomys for northern Venezuela and Pará state, Brazil, that are characterized by the presence of derived carotid circulation, a rare character state for the genus. Analyzed material included holotypes, type series, and/or topotypes of almost all described species of Neacomys, including type series of N. musseri, the holotype of N. tenuipes, and sequenced specimens of N. xingu. Qualitative comparison showed that 25 characters are informative for the distinction of the two new forms, and morphometric analyses corroborated the morphological separation of the new species. Results also point that N. tenuipes might represent a species complex. The new forms are sympatric with other species, including N. tenuipes and N. xingu, and can be identified by a suite of morphological characters, including the presence of a derived carotid pattern and, for the Pará form, by a unique morphology of the first upper molar. We review the occurrence of carotid circulation patterns within Sigmodontinae and discuss its use for the systematics of the subfamily. Further studies involving the new Neacomys species will contribute to understanding the biogeographic patterns and evolutionary trends within this distinct and diverse genus.
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- 2021
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13. Does stress mess with rodents’ heads? Influence of habitat amount and genetic factors in mandible fluctuating asymmetry in South American water rats ( Nectomys squamipes , Sigmodontinae) from Brazilian Atlantic rainforest remnants
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Luana S. Maroja, Hudson de Macedo Lemos, Aldo Caccavo, and Pablo Rodrigues Gonçalves
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0106 biological sciences ,Population ,Zoology ,010603 evolutionary biology ,01 natural sciences ,Fluctuating asymmetry ,03 medical and health sciences ,Genetic variation ,developmental changes ,education ,QH540-549.5 ,Ecology, Evolution, Behavior and Systematics ,Original Research ,030304 developmental biology ,Nature and Landscape Conservation ,human impacts ,0303 health sciences ,education.field_of_study ,Habitat fragmentation ,Ecology ,biology ,Nectomys squamipes ,habitat availability ,biology.organism_classification ,Habitat destruction ,Habitat ,rodents ,Inbreeding - Abstract
Loss of developmental stability can lead to deviations from bilateral symmetry (i.e. Fluctuating Asymmetry ‐ FA), and is thought to be caused by environmental and genetic factors associated with habitat loss and stress. Therefore, levels of FA might be a valuable tool to monitor wild populations if FA serves as an indicator of exposure to stress due to impacts of habitat loss and fragmentation. In studies examining FA and habitat fragmentation, FA levels are often explained by loss of genetic variation, though few studies have addressed FA’s use as indicator of environmental impact. Here, we investigated whether habitat loss, genetic variation, and/or inbreeding affect the developmental instability in Brazilian Atlantic forest populations of a Neotropical water rat (Nectomys squamipes). We sampled individuals from eight sites within Atlantic forest remnants with different amounts of available forest habitat and assessed FA levels with geometric morphometric techniques using adult mandibles. We used observed heterozygosity (Ho) and inbreeding coefficient (Fis), from seven microsatellite markers, as a proxy of genetic variation at individual and population levels. Populations were not significantly different for shape or size FA levels. Furthermore, interindividual variation in both shape and size FA levels and interpopulational differences in size FA levels were best explained by chance. However, habitat amount was negatively associated with both interpopulational variance and average shape FA levels. This association was stronger in populations living in areas with, We used geometric morphometric data to asses whether fluctuating asymmetry (FA) on mandibles of Neotropical water rats (Nectomys squamipes) from eight sites within Brazilian Atlantic forest remnants would be related to habitat amount, genetic diversity, and/or inbreeding on individual and populational level. FA might be a valuable tool to monitor wild populations, as it might serve as an indicator of exposure to stress due to impacts of habitat loss and fragmentation. We used observed heterozygosity and inbreeding coefficient from seven microsatellite markers, as a proxy of genetic variation. We found that habitat availability rather than genetic or biological factors was negatively associated with both inter‐populational variance and average shape FA levels, which are higher in populations living in areas with
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- 2021
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14. Effect of Long-Term Proton Pump Inhibitor Use on Blood Vitamins and Minerals: A Primary Care Setting Study
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Giuseppe Losurdo, Natale Lino Bruno Caccavo, Giuseppe Indellicati, Francesca Celiberto, Enzo Ierardi, Michele Barone, and Alfredo Di Leo
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General Medicine - Abstract
Background and objectives. Long-term proton pump inhibitor (PPI) use is frequently encountered in primary care. Its effect on micronutrient absorption is known, as vitamin B12, calcium or vitamin D insufficiency may occur in such patients. Materials and methods. We recruited patients using a PPI (pantoprazole) for >12 months. The control group was represented by subjects attending the general practitioner not taking any PPI in the last 12 months. We excluded subjects using nutritional supplements or with diseases interfering with micronutrient blood levels. All subjects underwent blood sampling with full blood count, iron, ferritin, vitamin D, calcium, sodium, potassium, phosphate, zinc and folate. Results. We recruited 66 subjects: 30 in the PPI group and 36 in the control group. Long-term pantoprazole users had lower red blood cell count but similar hemoglobin. We did not find any significant difference in blood iron, ferritin, vitamin B12 and folate. Vitamin D deficit was observed more frequently in the PPI group (100%) than in controls (30%, p < 0.001), with blood levels lower in pantoprazole consumers. No differences in calcium, sodium and magnesium were observed. Pantoprazole users had lower phosphate levels than controls. Finally, a non-significant trend for zinc deficiency was found in PPI users. Conclusions. Our study confirms that chronic PPI users may encounter alterations in some micronutrients involved in bone mineral homeostasis. The effect on zinc levels deserves further investigation.
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- 2023
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15. A New Productive Approach and Formulative Optimization for Curcumin Nanoliposomal Delivery Systems
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Raffaella De Piano, Diego Caccavo, Gaetano Lamberti, Katrien Remaut, Hanne Seynaeve, and Anna Angela Barba
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nutraceuticals ,simil-microfluidic technology ,anticancer ,antioxidant activity ,curcumin ,nanoliposomes ,nanotechnologies ,Pharmaceutical Science - Abstract
The use of natural resources and the enhancing of technologies are outlining the strategies of modern scientific-technological research for sustainable health products manufacturing. In this context, the novel simil-microfluidic technology, a mild production methodology, is exploited to produce liposomal curcumin as potential powerful dosage system for cancer therapies and for nutraceutical purposes. Through simil-microfluidic technology, based on interdiffusion phenomena of a lipid-ethanol phase in an aqueous flow, massive productions of liposomes at nanometric scale can be obtained. In this work, studies on liposomal production with useful curcumin loads were performed. In particular, process issues (curcumin aggregations) were elucidated and formulation optimization for curcumin load was performed. The main achieved result has been the definition of operative conditions for nanoliposomal curcumin production with interesting loads and encapsulation efficiencies.
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- 2023
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16. OC.16.6 EFFECT OF LONG TERM PROTON PUMP INHIBITOR USE ON BLOOD VITAMIN AND MINERALS: A PRIMARY CARE SETTING STUDY
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G. Indellicati, G. Losurdo, M.L. Martino, F. Celiberto, N.L.B. Caccavo, M. Barone, and A. Di Leo
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Hepatology ,Gastroenterology - Published
- 2023
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17. Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets
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Caccavo, Diego, Iannone, Marco, Angela BARBA, Anna, and Lamberti, Gaetano
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Applied Mathematics ,General Chemical Engineering ,General Chemistry ,Industrial and Manufacturing Engineering - Published
- 2023
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18. Grain yield, yield components and nitrogen economy of irrigated second-crop common Buckwheat (Fagopyrum esculentum Moench) in a cold-temperate region
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Diego Hernán Rotili, Antonio Guglielmini, Matías Caccavo, Sandra Antequera, Carlos María Rocca, and Daniel Julio Miralles
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Soil Science ,Plant Science ,Agronomy and Crop Science - Published
- 2023
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19. [Results of a surveillance strategy with SARS-CoV-2 antigen testing]
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Juan, Benger, María E, Esandi, Valentina, Viego, Alberto, Caccavo, Angelina S, Firpo, Miranda, Bru, Joaquín, Funes, and Ana, Rodríguez
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SARS-CoV-2 ,Quarantine ,COVID-19 ,Humans ,COVID-19 Serological Testing ,Retrospective Studies - Abstract
The objective was to describe the results of a surveillance strategy based on the use of SARS-CoV-2 rapid antigen detection tests. A retrospective cohort study was held between December 2020 and March 2021, which included suspected cases of COVID-19 evaluated by rapid antigen tests at a public hospital, with confirmatory molecular tests in negative cases. Positive cases and their close contacts were followed up by telephone. The scope, acceptability, follow-up coverage and positivity rate of the strategy were estimated, as well as indicators of viral transmissibility (probability of generating transmission, number of secondary infections generated, secondary attack rate, and overdispersion index). Its association with diagnostic tests results was analyzed by multivariate models. Of 1706 patients tested by rapid antigen tests, 526 were positive and 1180 were negative (65 tested positive by molecular tests); 579 confirmed cases could be contacted and 1669 close contacts were identified (85% of these contacts had full follow-up); 398 contacts tested positive during their quarantine (secondary attack rate of 27.9%). Of the 579 contacted cases, 205 (35%) reported symptomatic transmission, with an average of 0.91 secondary cases per infector. Transmission overdispersion was observed. Positive cases confirmed by rapid antigen tests had a higher chance of generating secondary cases, a higher number of secondary cases per infector and a higher secondary attack rate than those confirmed by molecular tests. In conclusion, the rapid antigen tests strategy showed high acceptability and coverage, and accelerated the diagnosis and identification of individuals with the highest contagiousness.El objetivo fue describir los resultados de la implementación de una estrategia de vigilancia con el uso de test rápidos de detección de antígeno de SARS-CoV-2. Se realizó un estudio de cohorte retrospectiva entre diciembre de 2020 y marzo de 2021, que incluyó casos sospechosos de COVID-19 evaluados en un hospital público mediante test rápidos y, en los negativos, por test moleculares. Se realizó seguimiento telefónico de los casos positivos y sus contactos estrechos. Se estimaron indicadores de implementación y de transmisibilidad viral (probabilidad de generar transmisión, cantidad de contagios secundarios generados, tasa de ataque secundaria e índice de sobredispersión). Se analizó su asociación con el resultado del test diagnóstico por modelos multivariados. De 1706 pacientes analizados con test rápidos de detección de antígeno, 526 resultaron positivos y 1180 negativos (65 fueron positivos por test moleculares). Se contactaron 579 casos confirmados e identificaron 1669 contactos estrechos (85% con seguimiento completo); 398 contactos fueron positivos durante su cuarentena (tasa de ataque secundaria de 27.9%). De los 579 casos, 205 (35%) reportaron contagios sintomáticos, con un promedio de 0.91 casos secundarios por infector. Se observó sobredispersión de la transmisión. Los positivos confirmados por test rápido tuvieron mayores chances de generar casos secundarios, más casos secundarios por infector y mayor tasa de ataque que los confirmados por test molecular. En conclusión, la estrategia con test rápido de detección de antígeno tuvo una aceptabilidad y cobertura elevada y aceleró el diagnóstico e identificación de los individuos con mayor contagiosidad.
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- 2022
20. Folates dysmetabolism promotes atrial cardiomyopathy/fibrillation through a cardiac-bone marrow networking involving endothelial progenitor cell dysfunction and erythropoiesis diversion
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L Sgarra, VP Caccavo, G Katsouras, A Di Monaco, F Quadrini, N Vitulano, F Troisi, A Solimando, S Cicco, C Nacci, MA Potenza, V Desantis, A Vacca, M Montagnani, and M Grimaldi
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): dedicated cardiovascular research foud Background Recent advances support the concept that pre-persistent Atrial Fibrillation (AF) does not explain the wholeness of embolic strokes, suggesting the recently postulated hypothesis of a broad Atrial Cardiomyopathy (AC). In contrast to its worldwide distribution and its very inclusive definition, pathogenic mechanisms underlying AC are still largely unknown. Folate cycle disorders (FCD) are a yet underrated dysmetabolism only partly explained by methylene tetrahydrofolate reductase (MTHFR)-inherited defects. On a translational basis, FCD could hinder both endothelial and circulating endothelial progenitor cell (EPCs) functioning, therefore providing one-shot explanation to both atrial stasis (increasing atrial fibrosis and generating atrial hypocontractility) and endothelial dysfunction (ED). If such cardiac-bone marrow networking would be verified, a fundamental pathogenic mechanism of AC and subsequent AF would be unraveled. Purpose This study aims to enquire for the hypothesis that: 1) atrial fibrosis (AFib) would relate to FCD (intended as both: a)MTHFR C677T inherited mutations and b)bone-marrow function disorders, here referring to erythropoiesis diversions) and 2) AF patients would show dysfunctional EPCs. Methods We studied 59 consecutive patients admitted to the Cardiology Unit of the General Hospital "F.Miulli", with preserved EF, subjected to AF ablation. AFib was quantified by relative % of low-voltage ( Results Baseline characteristics did not differ between Sample and Control groups (Fig. 1 – Left Table). % of Afib significantly differs between C677T MTHFR homozigosis patients (n=15) with respect to non-C677T MTHFR homozygosis patients (n=44) (Fig.1 – Right graph. - p < 0,02). Once univariate analysis was performed, subsequent multivariate analysis highlights highest fit once merged RBC, RDW-SD and folates values were inputed: Goodness of fit was proper, modelling good (Fig.2 – superior graph. - R2=0,39; p=0,0001). Either RBC, RDW-SD and folates coefficient reached significance (p < 0,0001; p < 0,01; p < 0,05 respectively). Number of EPCs significantly differs between AF patients and matched controls (Fig 2 – inferior graph. – p < 0,001). Conclusions Our findings support the hypothesis that genetically determined folates dysmetabolism (MTHFR dysfunction) promotes AFib via a complex cardiac-bone marrow networking involving circulating EPCs and unraveled by erythropoiesis diversions. Such results suggest a pathogenic role of folate cycle disorders in the AC development.
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- 2022
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21. Leadless transcatheter pacemaker: Indications, implantation technique and peri-procedural patient management in the Italian clinical practice
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Pietro Palmisano, Saverio Iacopino, Stefano De Vivo, Carlo D'Agostino, Luca Tomasi, Umberto Startari, Matteo Ziacchi, Ennio Carmine Luigi Pisanò, Vincenzo Ezio Santobuono, Vincenzo Paolo Caccavo, Giuseppe Sgarito, Mariano Rillo, Antonino Nicosia, and Giulio Zucchelli
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Male ,Pacemaker, Artificial ,Time Factors ,Treatment Outcome ,Humans ,Female ,Equipment Design ,Prospective Studies ,Cardiology and Cardiovascular Medicine ,Pericardial Effusion - Abstract
Safety and efficacy of leadless pacemakers (L-PM) have been demonstrated in multiple clinical trials, but real-world data on patient selection, implantation technique, and peri-procedural patient management in a clinical practice setting are lacking.Consecutive patients undergoing L-PM implantation in 14 Italian centers were followed in a prospective, multicentre, observational project. Data on baseline patient characteristics, clinical indications, implantation procedure, and peri-procedural patient management were collected. The rate and nature of device-related complications were also recorded.A total of 782 L-PM patients (68.4% male, 75.6 ± 12.4 years) were included in the analysis. The main patients-related reason leading to the choice of implanting a L-PM rather than a conventional PM was the high-risk of device infection (29.5% of cases). The implantation success rate was 99.2%. The median duration of the procedure was 46 min. In 90% of patients the device was implanted in the septum. Of patients on oral anticoagulant therapy (OAT) (n = 498) the implantation procedure was performed without interrupting (17.5%) or transiently interrupting OAT without heparin bridging (60.6%). During a median follow-up of 20 months major device-related complications occurred in 7 patients (0.9%): vascular access-site complications in 3 patients, device malfunction in 2 patients, pericardial effusion/cardiac tamponade in one patient, device migration in one patient.In the real world setting of Italian clinical practice L-PM is often reserved for patients at high-risk of infection. The implantation success rate was very high and the risk of major complications was low. Peri-procedural management of OAT was consistent with available scientific evidence.
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- 2022
22. Effects of
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Vittoria, Caccavo, Pierluigi, Forlano, Stefania Mirela, Mang, Paolo, Fanti, Maria, Nuzzaci, Donatella, Battaglia, and Vincenzo, Trotta
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Fungi belonging to the genus
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- 2022
23. Metastatic rhabdomyosarcoma: Evidence of the impact of radiotherapy on survival. A retrospective single-center experience
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Andrea Ferrari, Luca Bergamaschi, Stefano Chiaravalli, Virginia Livellara, Giovanna Sironi, Olga Nigro, Nadia Puma, Giovanna Gattuso, Carlo Morosi, Patrizia Gasparini, Roberta Caccavo, Emilia Pecori, Ombretta Alessandro, Sabina Vennarini, Lorenza Gandola, Maura Massimino, and Michela Casanova
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Adult ,Neoplasms, Second Primary ,Hematology ,Prognosis ,Combined Modality Therapy ,Disease-Free Survival ,Young Adult ,Treatment Outcome ,Oncology ,Pediatrics, Perinatology and Child Health ,Antineoplastic Combined Chemotherapy Protocols ,Rhabdomyosarcoma ,Humans ,Child ,Retrospective Studies - Abstract
The prognosis for patients with metastatic rhabdomyosarcoma (RMS) remains largely unsatisfactory despite the adoption of intensive multimodal therapy. To assess the role of different treatments adopted over the years, we retrospectively analyzed a cohort of patientslt;21 years old with metastatic RMS, treated from 1990 to 2020 at a referral center for pediatric sarcomas.Patients were treated using a multimodal approach that included surgery, radiotherapy, and chemotherapy (both high-dose chemotherapy and maintenance therapy in some cases). The type of radiotherapy administered was categorized as radical (to all sites of disease); partial (to at least one, but not all sites of disease); or none. A landmark analysis was used to examine the impact of radiotherapy on survival, that is, patients who had an event before day 221 were excluded from the analysis.The series included 80 patients. Event-free survival (EFS) and overall survival (OS) rates at 5 years were 17.3% and 21.3%, respectively. Survival was significantly associated with radiotherapy to metastatic sites, and with the radiotherapy category. In particular, 5-year EFS and OS rates were 70.6% and 76.0% for patients given radical radiotherapy, and 4.8% and 10.7%, respectively, for those given partial radiotherapy or none. Using the Cox multivariable analysis, OS correlated significantly with radiotherapy category.While confirming the poor overall outcome of patients with metastatic RMS, this study identified radiotherapy-when given to all sites of disease (including metastases)-as the main variable influencing survival.
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- 2022
24. Adaptive immunity in different CT patterns of active tuberculosis and possible variability according to patients' geographic provenience
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Giulia Scioscia, Donato Lacedonia, Ernesto Giuffreda, Incoronata Caccavo, Carla Maria Irene Quarato, Piera Soccio, Pasquale Tondo, Ennio Vincenzo Sassani, Dalila Pescatore, and Maria Pia Foschino Barbaro
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General Medicine - Abstract
BackgroundIt is still unclear if low lymphocyte levels are directly related to immunological modifications induced by the TB infection or if they depend on the general pre-existing health impairment of affected patients. Our aim was to detect eventual differences in the immunological status of patients with pulmonary TB compared to an age and sex-matched group of hospitalized patients with other bacterial community-acquired pneumonia (CAP). In addition, we tried to assess an association between alterations in the peripheral lymphocyte subsets and the development of different CT patterns of active TB and to discover differences in the immunological status and in the radiological patterns of TB presentation between patients of different geographic proveniences.MethodsThis observational study included 48 patients with TB and 48 sex- and age-matched patients affected by other bacterial CAP. The presence of HIV/AIDS, other immunocompromising conditions, and confounding chronic pulmonary comorbidities was excluded. Flow cytometry was performed on all the enrolled subjects at admission, before starting the appropriate antibiotic therapy. Patients with TB also underwent a computed tomography (CT) scan.ResultsPatients with TB showed a decrease in the absolute count of all the lymphocyte subsets compared to the CAP group. Only the reduction in the percentage of CD4+ T-lymphocytes was significant, while the percentage of CD8+ T-lymphocytes was significantly increased. Patients presenting exudative forms with atypical locations of TB showed a significant reduction in the absolute count and percentage of CD19+ B-lymphocytes compared to those affected by productive TB forms with the typical location. Despite being younger, our black Sub-Saharan Africans showed a significant reduction in the CD4+ T-lymphocytes compartment and a higher prevalence of atypical and exudative forms of TB compared with white Europeans.ConclusionTuberculosis itself may alter peripheral blood lymphocyte subsets compared to other CAP. An impaired CD19+ B-lymphocyte compartment may result in an abnormal exudative response in atypical locations and a suboptimal bacterial control. Other constitutive or environmental causes may influence immunological differences found in patients with TB, particularly in case of different geographic origins. Anyhow, flow cytometry may be of great value in evaluating the immune function of these patients.
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- 2022
25. Bullying entre alunos do Ensino Superior: um estudo com graduandos do curso de Educação Física
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Rafael Valladão, Raphael Martins Gonçalves de Lima, Romulo Caccavo, Mauricio Fidelis, Sergio Ferreira Tavares, and Thais Vianna Maia
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Intervention (counseling) ,Psychology ,Physical education ,Clinical psychology - Abstract
O bullying é a interdição do corpo mediada por signos culturais que pautam atitudes agressivas, intencionais e repetidas. Nas aulas de Educação Física ainda ocorre exclusão daqueles que não se enquadram nos padrões corporais considerados ideais. Foi investigada a presença, ou não, do bullying entre estudantes do curso de Educação Física em relação aos seus colegas. A pesquisa foi qualitativa e de campo; foi aplicado aos alunos do primeiro e segundo período de Educação Física da Universidade Castelo Branco um questionário (pré-intervenção), realizada uma palestra com um aluno com deficiência que sofre bullying e, três meses após, aplicado novamente o mesmo questionário para verificar se houve mudanças de comportamentos e atitudes (pós-intervenção). Na pré-intervenção, responderam ao questionário 8 homens e 7 mulheres: 7 homens não sofreram bullying, 1 sofreu e as 7 mulheres não sofreram; 5 homens e 6 mulheres não praticaram bullying, 3 homens e 1 mulher praticaram; 4 homens e 6 mulheres já viram acontecer, enquanto 4 homens e 1 mulher afirmaram nunca ter visto. Na pós-intervenção, dos 8 homens e 7 mulheres que foram entrevistados: 4 homens e 5 mulheres não sofreram bullying, 4 homens e 2 mulheres já sofreram; 5 homens e 4 mulheres não praticaram bullying, 3 homens e 3 mulheres já praticaram; 6 homens e 6 mulheres já viram acontecer, enquanto 2 homens e 1 mulher nunca viram. Concluímos que a maioria dos alunos não tinham entendimento das consequências do bullying, mas, após a intervenção, puderam reconhecer as práticas que cometiam contra seus colegas.
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- 2020
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26. The benefits to climate science of including early-career scientists as reviewers
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M. Casado, G. Gremion, P. Rosenbaum, J. A. Caccavo, K. Aho, N. Champollion, S. L. Connors, A. Dahood, A. Fernandez, M. Lizotte, K. Mintenbeck, E. Poloczanska, and G. Fugmann
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0106 biological sciences ,Sociology of scientific knowledge ,010504 meteorology & atmospheric sciences ,business.industry ,Process (engineering) ,media_common.quotation_subject ,lcsh:Geography. Anthropology. Recreation ,Climate change ,Climate science ,Public relations ,010603 evolutionary biology ,01 natural sciences ,lcsh:G ,Feeling ,Workforce ,lcsh:Q ,Early career ,lcsh:Science ,Psychology ,Set (psychology) ,business ,0105 earth and related environmental sciences ,media_common - Abstract
Early-career scientists (ECSs) are a large part of the workforce in science. While they produce new scientific knowledge that they share in publications, they are rarely invited to participate in the peer-review process. Barriers to the participation of ECSs as peer reviewers include, among other things, their lack of visibility to editors, inexperience in the review process and lack of confidence in their scientific knowledge. Participation of ECSs in group reviews, e.g. for regional or global assessment reports, provides an opportunity for ECSs to advance their skill set and to contribute to policy-relevant products. Here, we present the outcomes of a group peer review of the First Order Draft of the Intergovernmental Panel on Climate Change (IPCC) Special Report on the Ocean and Cryosphere in a Changing Climate (SROCC). Overall, PhD students spent more time on the review than those further advanced in their careers and provided a similar proportion of substantive comments. After the review, participants reported feeling more confident in their skills, and 86 % were interested in reviewing individually. By soliciting and including ECSs in the peer-review process, the scientific community would not only reduce the burden carried by more established scientists but also permit their successors to develop important professional skills relevant to advancing climate science and influencing policy.
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- 2020
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27. Anionic hydrogels: equilibrium behaviour modelling
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DE PIANO, Raffaella, Caccavo, Diego, Barba, Anna Angela, and Lamberti, Gaetano
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- 2022
28. Feasibility of semi-recumbent bicycle exercise Doppler echocardiography for the evaluation of the right heart and pulmonary circulation unit in different clinical conditions: the RIGHT heart international NETwork (RIGHT-NET)
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Ferrara F., Gargani L., Naeije R., Rudski L., Armstrong W. F., Wierzbowska-Drabik K., Argiento P., Bandera F., Cademartiri F., Citro R., Cittadini A., Cocchia R., Contaldi C., D'Alto M., D'Andrea A., Grunig E., Guazzi M., Kolias T. J., Limongelli G., Marra A. M., Mauro C., Moreo A., Ranieri B., Saggar R., Salzano A., Stanziola A. A., Vriz O., Vannan M., Kasprzak J. D., Bossone E., Capuano F., Benvenga R., Bellino M., Radano I., Marra A., D'Assante R., Rega S., Mazzola M., Raciti M., Dellegrottaglie S., De Luca N., Rozza F., Russo V., Di Salvo G., Ghio S., Guida S., Eichstaedt C. A., Labate V., La Gerche A., Pacileo G., Verrengia M., Kovacs G., Douschan P., Casadei F., De Chiara B., Ostenfeld E., Pedrizzetti G., Pieri F., Mori F., Moggi-Pignone A., Pratali L., Pugliese N., Selton-Suty C., Huttin O., Venner C., Serra W., Tafuni F., Stanziola A., Martino M., Caccavo G., Szabo I., Varga A., Agoston G., Voilliot D., Mobasseri S., Flueckiger P., Liu S., Ferrara, F., Gargani, L., Naeije, R., Rudski, L., Armstrong, W. F., Wierzbowska-Drabik, K., Argiento, P., Bandera, F., Cademartiri, F., Citro, R., Cittadini, A., Cocchia, R., Contaldi, C., D'Alto, M., D'Andrea, A., Grunig, E., Guazzi, M., Kolias, T. J., Limongelli, G., Marra, A. M., Mauro, C., Moreo, A., Ranieri, B., Saggar, R., Salzano, A., Stanziola, A. A., Vriz, O., Vannan, M., Kasprzak, J. D., Bossone, E., Capuano, F., Benvenga, R., Bellino, M., Radano, I., Marra, A., D'Assante, R., Rega, S., Mazzola, M., Raciti, M., Dellegrottaglie, S., De Luca, N., Rozza, F., Russo, V., Di Salvo, G., Ghio, S., Guida, S., Eichstaedt, C. A., Labate, V., La Gerche, A., Pacileo, G., Verrengia, M., Kovacs, G., Douschan, P., Casadei, F., De Chiara, B., Ostenfeld, E., Pedrizzetti, G., Pieri, F., Mori, F., Moggi-Pignone, A., Pratali, L., Pugliese, N., Selton-Suty, C., Huttin, O., Venner, C., Serra, W., Tafuni, F., Stanziola, A., Martino, M., Caccavo, G., Szabo, I., Varga, A., Agoston, G., Voilliot, D., Mobasseri, S., Flueckiger, P., and Liu, S.
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Adult ,medicine.medical_specialty ,Pulmonary Circulation ,Adolescent ,Ventricular Dysfunction, Right ,Atrial Pressure ,Population ,Right heart ,Predictive Value of Test ,Regurgitation (circulation) ,030204 cardiovascular system & hematology ,Doppler echocardiography ,Pulmonary hypertension ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,medicine.artery ,medicine ,Ventricular outflow tract ,Humans ,Radiology, Nuclear Medicine and imaging ,education ,Cardiac imaging ,Exercise Doppler echocardiography ,Aged ,Aged, 80 and over ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Echocardiography, Doppler ,Bicycling ,Feasibility Studie ,030228 respiratory system ,Pulmonary artery ,Cardiology ,cardiovascular system ,Ventricular Function, Right ,Right ventricle ,Feasibility Studies ,Female ,Cardiology and Cardiovascular Medicine ,business ,Human - Abstract
Exercise Doppler echocardiography (EDE) is a well-validated tool in ischemic and valvular heart diseases. However, its use in the assessment of the right heart and pulmonary circulation unit (RH-PCU) is limited. The aim of this study is to assess the semi-recumbent bicycle EDE feasibility for the evaluation of RH-PCU in a large multi-center population, from healthy individuals and elite athletes to patients with overt or at risk of developing pulmonary hypertension (PH). From January 2019 to July 2019, 954 subjects [mean age 54.2 ± 16.4years, range 16–96, 430 women] underwent standardized semi-recumbent bicycle EDE with an incremental workload of 25 watts every 2min, were prospectively enrolled among 7 centers participating to the RIGHT Heart International NETwork (RIGHT-NET). EDE parameters of right heart structure, function and pressures were obtained according to current recommendations. Right ventricular (RV) function at peak exercise was feasible in 903/940 (96%) by tricuspid annular plane systolic excursion (TAPSE), 667/751 (89%) by tissue Doppler-derived tricuspid lateral annular systolic velocity (S′) and 445/672 (66.2%) by right ventricular fractional area change (RVFAC). RV—right atrial pressure gradient [RV–RA gradient = 4 × tricuspid regurgitation velocity2 (TRV)] was feasible in 894/954 patients (93.7%) at rest and in 816/954 (85.5%) at peak exercise. The feasibility rate in estimating pulmonary artery pressure improved to more than 95%, if both TRV and/or right ventricular outflow tract acceleration time (RVOT AcT) were considered. In high specialized echocardiography laboratories semi-recumbent bicycle EDE is a feasible tool for the assessment of the RH-PCU pressure and function.
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- 2021
29. Evaluación del impacto de la cuarentena por la pandemia de COVID-19 en la transmisión perinatal del VIH en Buenos Aires, Argentina
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María Laura Samaniego, Andrea Scardigno, Mónica González Alcántara, Diego Cecchini, Irene Foradori, Constanza Johnston, María José Rolón, Maria Teresa Rodriguez Brieschke, Patricia Coll, Silvia Perez Macri, Marina G Martinez, Maria Fernanda Consalvo, Jamile Ballivian, Claudia Scalise, Alejandro Hakim, Silvina Vulcano, Juliana Caccavo, Damián Serrano, Silvina Ivalo, Manuela Bulló, Mara De Bernardi, Verónica Rossi, Marcela Ortiz de Zarate, Florencia Verdi Brusati, Claudia Rodriguez, and Adriana Duran
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General Engineering - Abstract
Objetivos: Evaluar la influencia de la cuarentena por COVID-19 en variables epidemiológicas clave con respecto a la prevención de la transmisión materno infantil (TMI) del VIH en Ciudad de Buenos Aires (CABA). Métodos: Análisis retrospectivo de los datos agregados de TMI de las principales maternidades de CABA. El año pandémico (2020) se comparó con los años no pandémicos 2018-2019. Resultados: Se observó una reducción del total de nacimientos en 2020 en comparación con 2019 y 2018 (11640 vs. 14031 y 15978, respectivamente). La proporción de nacidos vivos en madres VIH+ (MEV) fue 0,88% en 2020 sin diferencia con 2019 y 2018 (0,94% y 0,93%), p> 0,05 para todas las comparaciones. Entre las MEV, el diagnóstico intraparto fue del 2,9% para 2020, sin diferencias con 2019 (2,25%) y 2018 (9,3%), p> 0,05 (todas las comparaciones); el 8,8% comenzó el tratamiento antirretroviral con >28 semanas de edad gestacional en 2020 frente al 16% y el 18,05% en 2018 y 2019 (p> 0,05, todas las comparaciones). La prevalencia de la carga viral indetectable en el momento del parto fue del 67% en 2020 frente al 64% en 2018 y del 65,4% en 2019 (p> 0,05, todas las comparaciones). La transmisión perinatal fue 0% en 2020 vs 1.33% en 2018 y 2.25% 2019 (p> 0.05, todas las comparaciones) Conclusiones: En la primera ola de la pandemia de COVID 19 no se observó ningún impacto perjudicial en la proporción de MEV asistidas, diagnóstico intraparto de VIH, inicio tardío del TARV y TMI en CABA.
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- 2021
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30. Identification of quantitative trait loci for survival in the mutant dynactin p150Glued mouse model of motor neuron disease
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Guillermo M. Alexander, Terry D. Heiman-Patterson, Frank Bearoff, Roger B. Sher, Laura Hennessy, Shannon Terek, Nicole Caccavo, Gregory A. Cox, Vivek M. Philip, and Elizabeth A. Blankenhorn
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Mice, Inbred C57BL ,Disease Models, Animal ,Mice ,Superoxide Dismutase-1 ,Multidisciplinary ,Superoxide Dismutase ,Amyotrophic Lateral Sclerosis ,Quantitative Trait Loci ,Animals ,Humans ,Mice, Transgenic ,Dynactin Complex ,Motor Neuron Disease - Abstract
Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disorder. Although most cases of ALS are sporadic, 5–10% of cases are familial, with mutations associated with over 40 genes. There is variation of ALS symptoms within families carrying the same mutation; the disease may develop in one sibling and not in another despite the presence of the mutation in both. Although the cause of this phenotypic variation is unknown, it is likely related to genetic modifiers of disease expression. The identification of ALS causing genes has led to the development of transgenic mouse models of motor neuron disease. Similar to families with familial ALS, there are background-dependent differences in disease phenotype in transgenic mouse models of ALS suggesting that, as in human ALS, differences in phenotype may be ascribed to genetic modifiers. These genetic modifiers may not cause ALS rather their expression either exacerbates or ameliorates the effect of the mutant ALS causing genes. We have reported that in both the G93A-hSOD1 and G59S-hDCTN1 mouse models, SJL mice demonstrated a more severe phenotype than C57BL6 mice. From reciprocal intercrosses between G93A-hSOD1 transgenic mice on SJL and C57BL6 strains, we identified a major quantitative trait locus (QTL) on mouse chromosome 17 that results in a significant shift in lifespan. In this study we generated reciprocal intercrosses between transgenic G59S-hDCTN1 mice on SJL and C57BL6 strains and identified survival QTLs on mouse chromosomes 17 and 18. The chromosome 17 survival QTL on G93A-hSOD1 and G59S-hDCTN1 mice partly overlap, suggesting that the genetic modifiers located in this region may be shared by these two ALS models despite the fact that motor neuron degeneration is caused by mutations in different proteins. The overlapping region contains eighty-seven genes with non-synonymous variations predicted to be deleterious and/or damaging. Two genes in this segment, NOTCH3 and Safb/SAFB1, have been associated with motor neuron disease. The identification of genetic modifiers of motor neuron disease, especially those modifiers that are shared by SOD1 and dynactin-1 transgenic mice, may result in the identification of novel targets for therapies that can alter the course of this devastating illness.
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- 2022
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31. 25 Hydroxyvitamin D Levels are Negatively and Independently Associated with Fat Mass in a Cohort of Healthy Overweight and Obese Subjects
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Silvia Paradiso, Tommaso Martino, Claudio Pecorella, Giovanni De Pergola, Domenico Caccavo, Roberta Zupo, Vincenzo Triggiani, and Franco Silvestris
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Adult ,Male ,0301 basic medicine ,obesity ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Body water ,030209 endocrinology & metabolism ,Overweight ,Article ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,Immunology and Allergy ,Vitamin D ,Adiposity ,Aged ,Obesity, Metabolically Benign ,030109 nutrition & dietetics ,25-hydroxyvitamin D levels ,business.industry ,Insulin ,fat mass ,Organ Size ,Middle Aged ,medicine.disease ,Obesity ,adipose tissue ,blood pressure levels ,Endocrinology ,Body Composition ,Female ,medicine.symptom ,business ,Body mass index - Abstract
Background:Obesity is associated with lower serum vitamin D (25(OH)D) levels through several mechanisms. The aim of the study was to examine the possibility of a negative association between fat mass and 25(OH)D levels in a cohort of otherwise healthy overweight and obese subjects, independently of age, sex, blood pressure levels and anthropometric and metabolic parameters.Materials and Methods:147 overweight and obese subjects (106 women and 41 men), aged between 18 and 69 years, were enrolled into the study. All of them did not show any clinically evident metabolic or chronic diseases (i.e. hypertension, diabetes mellitus, renal failure, etc.) and did not use any kind of drug. Serum fasting levels of 25(OH)D, insulin, glucose, uric acid and lipids (triglycerides, total, HDL and LDL cholesterol) were measured. The season in which the blood samples were collected was autumn. Insulin resistance was assessed by using the Homeostasis Model Assessment (HOMA-IR). Body composition parameters (Fat Mass [FM], Fat Free Mass [FFM], body cell mass [BCM], Total Body Water [TBW]) were measured by electrical Bioimpedance Analysis (BIA). Lastly, demographic, anthropometric and clinical parameters (age, Body Mass Index [BMI], Waist Circumference [WC], Systolic (SBP) and Diastolic (DBP) blood pressure) were also assessed.Results:25(OH)D levels were significantly and negatively correlated with BMI (P Conclusion:This study clearly shows that 25(OH)D circulating levels are progressively lower with the increase of fat mass, independently of sex, body fat distribution, blood pressure and insulin and metabolic parameters. These data strongly show that adipose tissue accumulation per se is absolutely the main factor responsible factor for lower 25(OH)D levels in obese subjects, possibly through sequestration of fat soluble 25(OH)D in fat mass.
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- 2019
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32. Mesial hyperdontia in Sigmodontinae (Rodentia: Cricetidae), with comments on the evolution of the anteroconid in Myomorpha
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Marcelo Weksler and Aldo Caccavo
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0106 biological sciences ,0301 basic medicine ,Sigmodontinae ,biology ,Ecology (disciplines) ,Zoology ,Hyperdontia ,biology.organism_classification ,medicine.disease ,010603 evolutionary biology ,01 natural sciences ,Myomorpha ,03 medical and health sciences ,030104 developmental biology ,stomatognathic system ,medicine ,Animal Science and Zoology ,Ecology, Evolution, Behavior and Systematics ,Cricetidae - Abstract
Supernumerary teeth are common dental anomalies reported in rodents, mainly occurring distally to molars. We report the first case of mesial hyperdontia in wild-caught sigmodontine: a simplified tooth anterior to the right first lower molar in Neacomys amoenus. It affected the first molar morphology, which exhibits an underdeveloped mesial region with a reduced anterior conulid, a similar pattern observed in early known myomorph fossils, including lineages that still possess the last premolar. However, only lineages without premolar display an elongated first lower molar with a large anteroconid, as observed in extant Myomorpha. During the odontogenesis in myomorphs, the posteriormost vestigial diastemal tooth bud, located at the same locus of the last lower premolar, has its development arrested and merges with the cap of the first molar. This process might have contributed to the development of an increased anteroconid in this lineage. The abnormal Neacomys’ atavistic phenotype corroborates the hypothesis that the absorption of the primordium of the last lower premolar had played an important role in the development of first molar’s mesial region. Additionally, it also might have promoted the evolutionary transition from a reduced conulid into an enlarged anteroconid, as deduced from the fossil record and developmental evidence
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- 2019
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33. Características de los pacientes mayores de 75 años en el Registro ARGEN-IAM-ST
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Juan Gagliardi, Adrián Charask, Cecilia Cassano, Alberto Caccavo, Yanina Castillo Costa, and Karina Moreno
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Gynecology ,medicine.medical_specialty ,education.field_of_study ,Smoking habit ,business.industry ,Population ,Female sex ,Anterior myocardial infarction ,medicine.disease ,Lower incidence ,Heart failure ,Diabetes mellitus ,medicine ,education ,business ,Dyslipidemia - Abstract
espanolIntroduccion: Los adultos mayores representan una poblacion cada vez mas numerosa en la practica clinica.Objetivos: Conocer las caracteristicas clinicas y evolucion de los adultos mayores que se internan por infarto en Argentina.Material y metodos: Se analizaron los pacientes de acuerdo con la edad mayor o menor de 75 anos incluidos en el registroARGEN-IAM-ST.Resultados: De 1714 pacientes ingresados, 233 (13,6%) tenian una edad ≥ 75 anos. Se observo en estos una mayor prevalenciade sexo femenino, de hipertension arterial, menor de tabaquismo y similar de diabetes, dislipidemia, infarto agudo de miocardiode localizacion anterior y tiempo de evolucion al ingreso. Recibieron menos tratamiento de reperfusion y evolucionaronmas frecuentemente con insuficiencia cardiaca (el 31% vs. a 14%; p EnglishBackground: Older adults represent a growing population in clinical practice.Objectives: The aim of this study was to learn the clinical characteristics and outcome of older adults hospitalized with myocardialinfarction in Argentina.Methods: Patients included in the ARGEN-IAM-ST registry were analyzed depending on whether they were older or youngerthan 75 years of age.Results: Among the 1,714 patients included in the registry, 233 (13.6%) were aged 75 years or older. These patients hadgreater prevalence of female sex and hypertension and lower incidence of smoking habits, while the prevalence of diabetes,dyslipidemia, anterior myocardial infarction and time from onset of symptoms was similar. They were less likely to receivereperfusion therapy and progression to heart failure (31% vs. 14%; p
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- 2019
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34. Effect of binder and load solubility properties on HPMC granules produced by wet granulation process
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Matteo D'Amore, Gaetano Lamberti, Annalisa Dalmoro, Veronica De Simone, Diego Caccavo, and Anna Angela Barba
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Diffusion ,Pharmaceutical Science ,02 engineering and technology ,Granulation liquid composition ,030226 pharmacology & pharmacy ,Wet granulation process ,Hydroxypropyl methylcellulose ,Vitamin solubility ,Vitamin diffusion ,Polymer erosion ,Dosage form ,03 medical and health sciences ,chemistry.chemical_compound ,Granulation ,0302 clinical medicine ,Solubility ,chemistry.chemical_classification ,Ethanol ,Chemistry ,Polymer ,021001 nanoscience & nanotechnology ,Chemical engineering ,Distilled water ,Yield (chemistry) ,0210 nano-technology - Abstract
Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.
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- 2019
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35. Right Ventricular Functional Reserve in Early-Stage Idiopathic Pulmonary Fibrosis
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Antonello D’Andrea, Anna Agnese Stanziola, Rajan Saggar, Rajeev Saggar, Simona Sperlongano, Marianna Conte, Michele D’Alto, Francesco Ferrara, Luna Gargani, Patrizio Lancellotti, Eduardo Bossone, Robert Naeije, William F. Armstrong, Theodore John Kolias, Luigi Caliendo, Rosangela Cocchia, Rodolfo Citro, Michele Bellino, Ilaria Radano, Antonio Cittadini, Paola Argiento, Andreina Carbone, Santo Dellegrottaglie, Nicola De Luca, Montuori Maria Grazia, Francesco Rozza, Valentina Russo, Giovanni Di Salvo, Stefano Ghio, Ekkerard Grunig, Alberto Marra, Marco Guazzi, Francesco Bandera, Valentina Labate, André La Gerche, Giuseppe Limongelli, Giuseppe Pacileo, Marina Verrengia, Jaroslaw D. Kasprzak, Karina Wierzbowska Drabik, Gabor Kovacs, Antonella Moreo, Francesca Casadei, Benedetta De Chiara, Ellen Ostenfeld, Francesco Pieri, Lorenza Pratali, Christine Selton-Suty, Olivier Huttin, Clément Venner, Walter Serra, Anna Stanziola, Maria Martino, Giovanna Caccavo, István Szabó, Albert Varga, Gergely Agoston, Darmien Voilliot, Olga Vriz, Domenico Galzerano, Marco Scalese, and Luca Carannante
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Pulmonary and Respiratory Medicine ,Spirometry ,medicine.medical_specialty ,Speckle tracking echocardiography ,Doppler echocardiography ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,Idiopathic pulmonary fibrosis ,0302 clinical medicine ,Internal medicine ,medicine ,Stress Echocardiography ,030212 general & internal medicine ,Pulmonary wedge pressure ,medicine.diagnostic_test ,business.industry ,respiratory system ,medicine.disease ,Pulmonary hypertension ,respiratory tract diseases ,medicine.anatomical_structure ,030228 respiratory system ,Vascular resistance ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background The most important determinant of long-term survival in patients with idiopathic pulmonary fibrosis is the right ventricular (RV) adaptation to the increased pulmonary vascular resistance. Our aim was to explore RV contractile reserve during stress echocardiography in early-stage IPF. Methods Fifty early-stage patients with IPF and 50 healthy control patients underwent rest and stress echocardiography, including RV two-dimensional speckle tracking echocardiography. At peak exertion, blood gas analysis and spirometry were also assessed. Results At rest, RV diameters were mildly increased in IPF; however, although RV conventional systolic function indexes were similar between the IPF and control groups, RV global longitudinal strain and RV lateral wall longitudinal strain (LWLS) were significantly reduced in the IPF cohort. During physical exercise, patients with IPF showed a reduced exercise tolerance with lower maximal workload (P o 2; P Conclusions RV myocardial dysfunction is already present at rest in early-stage IPF and worsens during exertion as detected by two-dimensional speckle-tracking echocardiography. The RV altered contractile reserve appears to be related to reduced exercise tolerability and impaired pulmonary hemodynamic.
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- 2019
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36. Programa de acompañamiento por pares para personas con diagnóstico reciente de infección por VIH: Experiencia PPP
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Luciana Faraone, Nadia Roussilian, Sandra Rodríguez, Edgardo G. Bottaro, María Rosa Cascasi, Beatriz Lauge, Daniela D’Alessandro, Juliana Caccavo, Maria Teresa Rodriguez Brieschke, María del Carmen Espiño, Mónica Pasarón, María Magdalena Ilamendi, Mara De Bernardi, Sylvia Errea, Agustina Soncini, Pablo Gustavo Scapellato, and Alvaro Otreras
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medicine.medical_specialty ,Exact test ,business.industry ,Internal medicine ,General Engineering ,medicine ,Human immunodeficiency virus (HIV) ,Outpatient clinic ,Intervention group ,Peer support ,medicine.disease_cause ,business ,Viral load - Abstract
Introducción: Para mejorar la retención en el sistema de salud de las personas que viven con VIH (PVVIH) con diagnóstico reciente y promover su adherencia se implementó el programa de acompañamiento de pares “Positivos para Positivos” (PPP). Material y métodos: Se entrenó a PVVIH con excelente adherencia y se les ofreció integrar PPP. Entre 06/2014 y 08/2018 cada individuo con diagnóstico reciente de infección VIH fue invitado a contactar con PPP. Se evaluó prospectivamente la evolución de los pacientes durante un año y se analizaron variables vinculadas a adherencia. Se compararon sus resultados con lo observado entre PVVIH con diagnóstico reciente sin apoyo de pares. Se analizó mediante tablas de 2x2 y la prueba exacta de Fisher (EpiInfo7.2.2.6). Resultados: Se incluyeron 158 PVVIH (40 grupo intervención y 118 grupo control). En el grupo intervención hubo más pacientes que iniciaron TARGA [100% vs 87,3%; RR 1,15 (IC95 1,07-1,23); p=0,024]. Tras excluir a los derivados y fallecidos tempranamente quedaron 37 y 112 pacientes respectivamente. En el grupo intervención se observó mejor control clínico [94,6% vs 75,9%; RR 4,2 (IC95 1,08-16,6); p=0,015] y menos abandono de seguimiento [8,1% vs 25,9%; RR 0,3 (IC95 0,11-0,98); p=0,02]. Entre quienes iniciaron TARGA y tuvieron al menos una consulta con el servicio de Infectología (37 grupo intervención y 97 grupo control) se registraron más pacientes con alta tasa de retiro de TARGA de farmacia [51,4% vs 18,6%; RR 2,77 (IC95 1,64–4,66); p=0,0003]; mayor alcance de CV
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- 2021
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37. Effects of Trichoderma harzianum Strain T22 on the Arthropod Community Associated with Tomato Plants and on the Crop Performance in an Experimental Field
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Vittoria Caccavo, Pierluigi Forlano, Stefania Mang, Paolo Fanti, Maria Nuzzaci, Donatella Battaglia, and Vincenzo Trotta
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Insect Science ,fungi ,Trichoderma ,field experiment ,QBSar ,plant pathogens ,tomato aphids ,Chaetocnema tibialis ,Tetranychus urticae ,leaf miner ,integrated pest management ,food and beverages - Abstract
Fungi belonging to the genus Trichoderma have received much attention in recent years due to their beneficial effects on crop health and their use as pest control agents. Trichoderma activates direct plant defenses against phytophagous arthropods and reinforces indirect plant defense through the attraction of predators. Although the plant defenses against insect herbivores were demonstrated in laboratory experiments, little attention has been paid to the use of Trichoderma spp. in open field conditions. In the present study, we investigated the effects of the inoculation of the commercial Trichoderma harzianum strain T22 on the arthropod community associated with tomato plants and on the crop performance in an experimental field located in South Italy. Our results showed that inoculation with T. harzianum could alter the arthropod community and reduce the abundance of specific pests under field conditions with respect to the sampling period. The present study also confirmed the beneficial effect of T. harzianum against plant pathogens and on tomato fruit. The complex tomato–arthropod–microorganism interactions that occurred in the field are discussed to enrich our current information on the possibilities of using Trichoderma as a green alternative agent in agriculture.
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- 2022
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38. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease
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Lincoff, A. Michael, Nicholls, Stephen J., Riesmeyer, Jeffrey S., Barter, Philip J., Brewer, H. Bryan, Fox, Keith A. A., Gibson, C. Michael, Granger, Christopher, Menon, Venu, Montalescot, Gilles, Rader, Daniel, Tall, Alan R., McErlean, Ellen, Wolski, Kathy, Ruotolo, Giacomo, Vangerow, Burkhard, Weerakkody, Govinda, Goodman, Shaun G., Conde, Diego, McGuire, Darren K., Nicolau, Jose C., Leiva-Pons, Jose L., Pesant, Yves, Li, Weimin, Kandath, David, Kouz, Simon, Tahirkheli, Naeem, Mason, Denise, Nissen, Steven E. Del Valle M, Finnell JB, Standley J, Poi K, Croaning J, Tong YC, Guerra JL, Guasparini G, Hubert C, Ardissino D, Betteridge J, Borghi C, Bruckert E, Chiang CE, Cinteza M, Dalby AJ, Erlinge D, Fernandez-Ortiz A, Ge J, Gottlieb S, Goudev A, Gratsiansky N, Huber K, Ilavská A, Jeong MH, Jukema JW, Katus H, Keltai M, Krum H, Nielsen H, Ogawa H, Ongen Z, Parkhomenko A, Raugaliene R, Renkin J, Rynkiewicz A, Steinhubl S, White H, Widimsky P, Zhu J, Armstrong P, Ridker P, Mahaffey K, Steg G, Wittes J, Bhargava A, Chenier M, Coleman C, Cremer P, Jellis C, Lahoud R, Lappe J, Min D, Monteleone P, Newton D, Stegman B, Senn T, Katzan I, Sharma J, Uchino K, Vora N, Brown K, Fabec D, Piper P, Preston S, Colombo T, Pagel-Langenickel I, Penev P, Maixing A, Crowley K, Sarkar S, Torosyan N, Castano L, Tran D, Dena V, Blain L, Keenan G, Slade K, Quinlan E, Edwards R, Ren H, Glenny J, Maffei L, Albisu Di Gennaro J, Caccavo A, Prado A, Colombo H, Luquez H, Lobo Marquez L, Hammett C, Blombery P, Colquhoun D, Amerena J, Howes L, Cooke D, Simpson R, Horowitz J, Sullivan D, Proietto J, Yeo W, Hirschl M, Hanusch U, Drexel H, Brodmann M, Wollaert B, De Wolf L, Delforge M, Vanwelden J, Peeters A, Siqueira Bodart J, Montenegro R, Franken M, Eliaschewitz F, Parvanova Z, Raev D, Mincheva V, Kichukov K, Stoyanov M, Apostolova E, Tzekova M, Dimov B, Lazov P, Devedzhiev T, Dion D, Poirier P, Lavoie JP, Lonn E, Shukla D, Chehayeb R, Nault P, Gaudet D, Tardif JC, Beaudry Y, Bakbak A, Wong B, St-Maurice F, Labonte R, Polasek P, Sweet M, Bhargava R, Nawaz S, Pandey S, Tishler S, Peterson S, O’Keefe D, Genest J, Syan R, Leiter L, Li H, Ma W, Ma C, Xu D, Li X, Hala T, Machova V, Smejkalova O, Vodnansky P, Reichert P, Velimsky T, Matuska J, Machkova M, Jerabek O, Kuchar J, Rasmussen T, Lindgren L, Alexandersen P, Bang L, Brønnum-Schou J, Valter I, Soots M, Lanno R, Rosenthal S, Cottin Y, Elbaz M, Lafitte S, Silvain J, Coste P, Rangé G, Gosse P, Morel O, Berrouschot J, Bourhaial H, Toursarkissian N, Appel KF, Rieker W, Stellbrink C, Münzel T, Geisler T, Kadel C, Giannitsis E, Trenk D, vom Dahl J, Dorsel T, Singer O, Schäufele T, Natour M, Ozaki R, Lau E, Chan K, Yeung V, Yu C, Lakatos F, Zólyomi S, Vangel S, Merkely B, Szakal I, Sipos A, Laszloczky A, Kis E, Szocs A, Szántai G, Faludi P, Kancz S, Oroszlan T, Hamoud S, Francis A, Chorin E, Leibowitz D, Kracoff O, Weisz G, Schiff E, Bitzur R, Hussein O, Di Lorenzo L, Visona A, Mos L, De Luca G, Salvioni A, Rubba P, Imberti D, Bucci M, Saku K, Sueyoshi A, Ohshima K, Kazatani Y, Shimizu M, Fujii K, Higa N, Kawamitsu K, Shimomura H, Hoshizaki H, Tashiro H, Baden M, Ueda O, Tanabe J, Momiyama Y, Hosokawa S, Takahashi N, Kimura K, Fujinaga H, Masutani M, Kuramochi T, Higashikata T, Ichikawa S, Yamagishi M, Sakota S, Sakuragi S, Suzuki M, Taguchi S, Nakamura T, Ozaki Y, Tsujita K, Yasuda S, Ando K, Fujimoto K, Tanabe K, Fukunaga M, Kavaliauskiene R, Motiejuniene L, Slapikas R, Jarasuniene D, De los Rios Ibarra M, Alcocer Gamba M, Nevarez Ruiz L, Fajardo-Campos P, Llamas Esperon G, Violante Ortiz R, Stobschinski de Alba C, Guizar Sanchez C, Guerra Lopez A, Montano E, Miracle S, Fanghanel G, Lenderink T, Troquay R, Van Leendert R, van Eck J, Hamer B, Ronner E, Karalis I, Lok D, Magro M, Westendorp I, Stroes E, De Melker E, Verhave G, Plomp J, Bronzwaer P, Wiersma J, Kooy A, Herrman JP, Imholz B, de Groot M, Devlin G, Elliott J, Benatar J, Harding S, Hart H, Young C, Mirek-Bryniarska E, Gniot J, Broncel M, Kozina M, Kus W, Sciborski R, Lesnik J, Kawka-Urbanek T, Krzyzanowski M, Okopien B, Wierzbicka K, Dyczek A, Ochean V, Copaci I, Matei C, Pruna C, Constantinescu M, Minescu B, Stamate C, Boldueva S, Markov V, Alexeeva N, Chizhov P, Supryadkina T, Petrochenkova N, Zrazhevsky K, Barbarash O, Gurevich V, Hranai M, Gergel V, Dzupina A, Uhliar R, Vinanska D, Fazekas F, Bugan W, Saaiman J, Nortje H, Theron H, Bernhardi D, Ramlachan P, Van-Zyl L, Basson M, Venter T, Kim D, Han S, Park G, Hwang K, Rhee M, Cho B, Jeong J, Hong B, Chang 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Ando, K, Fujimoto, K, Tanabe, K, Fukunaga, M, Kavaliauskiene, R, Motiejuniene, L, Slapikas, R, Jarasuniene, D, De los Rios Ibarra, M, Alcocer Gamba, M, Nevarez Ruiz, L, Fajardo-Campos, P, Llamas Esperon, G, Violante Ortiz, R, Stobschinski de Alba, C, Guizar Sanchez, C, Guerra Lopez, A, Montano, E, Miracle, S, Fanghanel, G, Lenderink, T, Troquay, R, Van Leendert, R, van Eck, J, Hamer, B, Ronner, E, Karalis, I, Lok, D, Magro, M, Westendorp, I, Stroes, E, De Melker, E, Verhave, G, Plomp, J, Bronzwaer, P, Wiersma, J, Kooy, A, Herrman, Jp, Imholz, B, de Groot, M, Devlin, G, Elliott, J, Benatar, J, Harding, S, Hart, H, C, Young, Mirek-Bryniarska, E, Gniot, J, Broncel, M, Kozina, M, Kus, W, Sciborski, R, Lesnik, J, Kawka-Urbanek, T, Krzyzanowski, M, Okopien, B, Wierzbicka, K, Dyczek, A, Ochean, V, Copaci, I, Matei, C, Pruna, C, Constantinescu, M, Minescu, B, Stamate, C, Boldueva, S, Markov, V, Alexeeva, N, Chizhov, P, Supryadkina, T, Petrochenkova, N, Zrazhevsky, K, Barbarash, O, Gurevich, V, Hranai, M, Gergel, V, Dzupina, A, Uhliar, R, Vinanska, D, Fazekas, F, Bugan, W, Saaiman, J, Nortje, H, Theron, H, Bernhardi, D, Ramlachan, P, Van-Zyl, L, Basson, M, Venter, T, Kim, D, Han, S, Park, G, Hwang, K, Rhee, M, Cho, B, Jeong, J, Hong, B, Chang, K, Garcia Puig, J, Fuentes Jiménez, F, Nieto Iglesias LJ, Pintó Sala, X, Gamez, Jm, Sánchez Álvarez, J, Hernandez García JM, Olsson, A, Mooe, T, Tengmark, Bo, Lindholm, Cj, Hansen, O, Tyden, P, Moccetti, T, Binder, R, Ueng, K, Lai, W, Shyu, K, Hsieh, I, Sheu, W, Chen, J, Altunkeser, B, Erkan, A, Karpenko, O, Kaydashev, I, Yagensky, A, Kovalenko, V, Brunskill, J, Barr, C, Cecil, J, Cahill, T, A Gorog D, Bakhai, A, Coulson, W, Gorog, D, Loftus, I, Haddad, T, Hotchkiss, D, Isserman, S, Janik, M, Weinstein, D, Wilson, S, Butman, S, Hearne, S, Khan, F, Nadar, V, Zelman, R, R, Benton, E, Flore, Kahn, B, Soni, A, Asbill, B, Singal, D, Dy, J, Foucauld, J, Crenshaw, B, Rogers, W, Aslam, A, Lieber, I, Shah, P, Durr, S, Spencer, R, Mahal, S, 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Shah, S, Geohas, C., Lincoff, A. Michael, Nicholls, Stephen J., Riesmeyer, Jeffrey S., Barter, Philip J., Brewer, H. Bryan, Fox, Keith A. A., Gibson, C. Michael, Granger, Christopher, Menon, Venu, Montalescot, Gille, Rader, Daniel, Tall, Alan R., Mcerlean, Ellen, Wolski, Kathy, Ruotolo, Giacomo, Vangerow, Burkhard, Weerakkody, Govinda, Goodman, Shaun G., Conde, Diego, Mcguire, Darren K., Nicolau, Jose C., Leiva-Pons, Jose L., Pesant, Yve, Li, Weimin, Kandath, David, Kouz, Simon, Tahirkheli, Naeem, Mason, Denise, Nissen, Steven E., Del Valle M, Young, C, Nieto Iglesias, Lj, Hernandez García, Jm, A Gorog, D, Benton, R, Flores, E, Z Jafar, M, and Salazar, J
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Male ,0301 basic medicine ,Cardiovascular Outcome ,Cholesterol Ester Transfer Protein ,Myocardial Ischemia ,030204 cardiovascular system & hematology ,Coronary artery disease ,cholesteryl ester transfer protein inhibitor ,Benzodiazepines ,chemistry.chemical_compound ,0302 clinical medicine ,Cardiovascular Disease ,Anticholesteremic Agent ,Intracranial Arteriosclerosi ,Treatment Failure ,Evacetrapib ,Peripheral Vascular Diseases ,Benzodiazepine ,biology ,Medicine (all) ,Anticholesteremic Agents ,Diabetes Mellitu ,General Medicine ,Middle Aged ,Intracranial Arteriosclerosis ,High-Risk Vascular Disease ,Editorial ,Cardiovascular Diseases ,Cardiology ,Female ,lipids (amino acids, peptides, and proteins) ,Human ,Risk ,medicine.medical_specialty ,Acute coronary syndrome ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,Cholesterylester transfer protein ,Diabetes Mellitus ,Journal Article ,medicine ,Humans ,Aged ,Cholesterol ,Vascular disease ,business.industry ,Cholesterol, HDL ,Biomarker ,Cholesterol, LDL ,medicine.disease ,Cholesterol Ester Transfer Proteins ,Surgery ,030104 developmental biology ,Peripheral Vascular Disease ,chemistry ,biology.protein ,business ,Biomarkers ,Lipoprotein - Abstract
BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).
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- 2017
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39. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial
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Negron Miguel, S, Sanabria Perez, E, Carrion Chambilla, J, Chavez Ayala, C, Castillo Leon, R, Vargas Gonzales, R, Hernandez Zuniga, J, Camacho Cosavalente, L, Bravo Mannucci, J, Heredia Landeo, J, Llerena Navarro, N, Roldan Concha, Y, Rodriguez Chavez, V, Anchante Hernandez, H, Zea Nunez, C, Mogrovejo Ramos, W, Ferrolino, A, Sy, R, Tirador, L, Matiga, G, Coching, R, Bernan, A, Rogelio, G, Morales, D, Tan, E, Sulit, D, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewoda, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Saminski, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Miklaszewicz, B, Kubica, J, Andrzej Lipko, J, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Raczak, G, Szwed, H, Monteiro, P, Mesquita Bastos, J, Pereira, H, Martins, D, Seixo, F, Mendonca, C, Botelho, A, Caetano, F, Minescu, B, Istratoaie, O, Tesloianu, D, Cristian, G, Dumitrescu, S, Podoleanu, C, Constantinescu, M, Bengus, C, Militaru, C, Rosu, D, Parepa, I, Matei, A, Alexandru, T, Malis, M, Coman, I, Stanescu-Cioranu, R, Dimulescu, D, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, O, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, A, Gurevich, V, Stryuk, R, Lomakin, N, Bokarev, I, Khlevchuk, T, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Shchekotov, V, Akatova, E, Chumakova, G, Libov, I, Voevoda, M, Tretyakova, T, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Povzun, A, Egorova, L, Tyrenko, V, Ivanov, I, Ilya, M, Kanorsky, S, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, M, Stojic, S, Apostolovic, S, Ilic, S, Putnikovic Tosic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Todic, B, Balinovac, J, Dincic, D, Seferovic, P, Karadzic, A, Dodic, S, Dimkovic, S, Jakimov, T, Poh, K, Ong, H, Tang I-Shing, J, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Zuran, I, Poklukar, J, Cernic Suligoj, N, Cevc, M, Cyster, H, Ranjith, N, Corbett, C, Bayat, J, Makotoko, E, du Toit Theron, H, Kapp, I, de V Basson, M, Lottering, H, Van Aswegen, D, Van Zyl, L, Sebastian, P, Pillay, T, Saaiman, J, Commerford, P, Cassimjee, S, Riaz, G, Ebrahim, I, Sarvan, M, Mynhardt, J, Reuter, H, Moodley, R, Vida, M, Cequier Fillat, A, Bodi Peris, V, Fuentes Jimenez, F, Marin, F, Cruz Fernandez, J, Hidalgo Urbano, R, Gil-Extremera, B, Toledo, P, Worner Diz, F, Garcia-Dorado, D, Iniguez, A, Gonzalez-Juanatey, J, Fernandez Portales, J, Civeira Murillo, F, Matas Pericas, L, Zamorano, J, De Mora Martin, M, Bruguera Cortada, J, Alonso Martin, J, Serrano Antolin, J, De Berrazueta Fernandez, J, Vazquez de Prada, J, Diaz Fernandez, J, Garcia Lledo, J, Cosin Sales, J, Botas Rodriguez, J, Gusi Tragant, G, Benedicto, A, Gonzalez-Juanatey, C, Camprubi Potau, M, Plaza Perez, I, De La Tassa, C, Loma-Osorio Rincon, P, Balaguer Recena, J, Escudier, J, Payeras, A, Alonso Orcajo, N, Valdivielso, P, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Ponnamperuma, C, Fernando, N, Fernando, K, Jayawardena, J, Wijeyasingam, S, Ranasinghe, G, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, J, Amarasena, N, Berglund, S, Rasmanis, G, Vedin, O, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Agergaard Jensen, S, Torstensson, I, Ahremark, U, Sundelin, T, Moccetti, T, Muller, C, Mach, F, Binde, R, Tsai, W, Ueng, K, Lai, W, Liu, M, Hwang, J, Yin, W, Hsieh, I, Hsieh, M, Kuo, J, Huang, T, Fang, C, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Chotnoparatpat, P, Camsari, A, Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, O, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, R, Clifford, P, Wong, Y, Iqbal, S, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Smith, S, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Ayaz, M, Cheema, M, Oliver, R, Thackray, S, Mudawi, T, Rahman, G, Sultan, A, Sharman, D, Sprigings, D, Butler, R, Wilkinson, P, Lip, G, Halcox, J, Gallagher, S, Ossei-Gerning, N, Vardi, G, Baldari, D, Brabham, D, Treasure II, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, A, Ince, C, Flores, E, Wright, S, Cheng, S, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Cambier, P, Lieber, I, Kumar, P, East, C, Krichmar, P, Hasan, M, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Amidon, T, Suh, D, Arif, I, Abdallah, M, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Moriarty, K, Harris, B, Cohen, S, Carter, L, Doty, D, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, S, Koren, M, Chandna, H, Dodds III, G, Goraya, T, Bengston, J, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Fenton, S, Singh, N, Shah, A, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Richard, K, Keating, F, Kondo, N, Shetty, S, Levite, H, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Izzo, M, Kumar, A, Hattler, B, Do, R, Link, C, Bortnick, A, Kinzfogl III, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, W, Thew, S, Abbas, J, White, M, Islam, O, Subherwal, S, Ranadive, N, Vakili, B, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Zahr, F, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, M, Schmalfuss, C, Picone, M, Pederson, R, Herzog, W, Friedman, K, Lindsey, J, Nowins, R, Timothy, E, Leonard, P, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, Alonso, A, May, W, Christopher, D, Galski, T, Chu, A, Mody, F, Ramin, E, Hodes, Z, Rossi, J, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, Vetrovec, G, King, M, Carey, C, Gerber, J, Younis, L, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Kuvin, J, Silver, K, Foster, M, Tonnessen, G, Espinoza, A, Amlani, M, Wali, A, Malozzi, C, Jong, G, Massey, C, Wattanakit, K, O'Donnell, P, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Blonder, R, Akyea-Djamson, A, Labroo, A, Marais, H, Claxton, E, Weiss, R, Kathryn, R, Berk, M, Joshi, P, Khera, A, Khaira, A, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Erenrich, N, Farrar, M, Pollock, S, French, W, Diamantis, S, Guy, D, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Albert, S, Spriggs, D, Strain, J, Mittal, S, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, F, Nahhas, A, Pope, T, Nager, P, Vohra, R, Sharma, M, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Stapleton, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, P, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Dohad, S, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Henry, J, Schifferdecker, B, Gilbert, J, Chalavarya, G, Eaton, C, Schmedtje, J, Christenson, S, Dotani, I, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Assi, N, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Gamil, D, Akright, L, Krawczyk, J, Cobler, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bregeault, M, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Chengyue, Z, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, Dempsey, M, Mcclanahan, M, ODYSSEY OUTCOMES Comm Investigato, and Ege Üniversitesi
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Male ,BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences ,STATIN THERAPY ,blood-glucose ,Endocrinology, Diabetes and Metabolism ,GUIDELINES ,PCSK9 ,0302 clinical medicine ,Endocrinology ,GENETIC-VARIANTS ,Cardiovascular Disease ,Diabetes Complication ,Aged Antibodies, Monoclonal, Humanized / therapeutic use* Cardiovascular Diseases / blood Cardiovascular Diseases / prevention & control* Diabetes Complications / blood Diabetes Complications / prevention & control* Female Humans Male Middle Aged Substances ,Clinical endpoint ,Medicine ,guidelines ,030212 general & internal medicine ,Prediabetes ,Myocardial infarction ,myocardial-infarction ,genetic-variants ,statin therapy ,risk ,pcsk9 ,association ,liraglutide ,evolocumab ,RISK ,BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti ,BLOOD-GLUCOSE ,ASSOCIATION ,Middle Aged ,Cardiovascular Diseases ,Female ,Life Sciences & Biomedicine ,Human ,medicine.medical_specialty ,Acute coronary syndrome ,PCSK9 inhibitor ,acute coronary syndrome ,lipoprotein(a) ,low-density lipoprotein cholesterol ,030209 endocrinology & metabolism ,Antibodies, Monoclonal, Humanized ,Diabetes Complications ,Endocrinology & Metabolism ,03 medical and health sciences ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,Humans ,Aged ,Alirocumab ,diabetes, PCSK9, hyperlipidemia ,Science & Technology ,ODYSSEY OUTCOMES Committees and Investigators ,business.industry ,Unstable angina ,EVOLOCUMAB ,medicine.disease ,MYOCARDIAL-INFARCTION ,LIRAGLUTIDE ,Human medicine ,business - Abstract
Doi, Yasuji/0000-0002-8368-0827; galvani, marcello/0000-0001-5897-667X; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Sherwood, Matthew/0000-0002-4305-5883; Malynovsky, Yaroslav V/0000-0002-9118-1104; Viktorova, vic-inna@mail.ru I.A./0000-0001-8728-2722; bastos, jose/0000-0002-9526-3123; Yang, Eric H/0000-0003-4889-7454; Rudenko, Anatoliy Viktorovich/0000-0003-1099-1613; Novotny, Vojtech/0000-0003-3521-9945; Nikolaev, Konstantin/0000-0003-4601-6203; Reshetko, Olga/0000-0003-3107-7636; Leonardi, Sergio/0000-0002-4800-6132; Muenzel, Thomas/0000-0001-5503-4150; Ushakov, Alexei V/0000-0002-7020-4442; Tse, Hung Fat/0000-0002-9578-7808; Podoleanu, Cristian/0000-0001-9987-2519; Raffel, Owen C/0000-0001-5470-7050; Khasanov, Niiaz/0000-0002-7760-0763; Chumakova, Galina A/0000-0002-2810-6531; Ersanli, Murat/0000-0003-1847-3087; cornel, jan hein/0000-0002-1006-2112; Abbate, Antonio/0000-0002-1930-785X; Racca, Vittorio/0000-0002-4465-3789; Urina-Triana, Miguel A/0000-0001-6003-4622; Rasputina, Lesia/0000-0003-1230-4039; Racca, Vittorio/0000-0002-4465-3789; Reis, Gilmar/0000-0002-4847-1034; Sandhu, Manjinder/0000-0003-2538-2079; Keskin, Kudret/0000-0002-9049-1530; PAREPA, IRINEL/0000-0002-7571-9015; Manakshe, Gajendra/0000-0002-4983-4271; Nicolau, Jose C/0000-0002-9680-3689; Strelnieks, Aldis/0000-0003-3493-2562; Budaj, Andrzej/0000-0002-6395-2098; Marin, Francisco/0000-0001-7246-7708; Wongpraparut, Nattawut/0000-0002-1541-3313; Yuan, Zuyi/0000-0002-4141-0298; Jeong, Myung Ho/0000-0003-2424-810X; Mostovoy, Yuriy/0000-0002-7041-1230; Pepine, Carl/0000-0002-6011-681X; Lopez-Jaramillo, Patricio/0000-0002-9122-8742; Garcia-Lledo, Alberto/0000-0002-8986-2584; Tesloianu, Nicolae-Dan/0000-0002-1007-3022; Kosmacheva, Elena/0000-0001-8600-0199; Kunz Sebba Barroso Souza, Weimar/0000-0002-1265-1930; Katz, Amos/0000-0003-0422-934X; Tunon, Jose/0000-0002-1373-0999; Acevedo, Monica/0000-0002-7989-6633; Hove, Jens/0000-0002-5600-5623; Yakushin, Sergey/0000-0001-7202-742X; Gonzalez Juanatey, Jose Ramon/0000-0001-9681-3388; Lyamina, Nadezhda/0000-0001-6939-3234; Aylward, Philip/0000-0002-5358-8552; Apostolovic, Svetlana/0000-0001-9015-297X; Airaksinen, Juhani/0000-0002-0193-568X; Nahhas, Prof. Dr. Ahmed/0000-0002-2887-8187; Barbarash, Olga/0000-0002-4642-3610, WOS: 000475553300016, PubMed: 31272931, Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1: 1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0.65-1.30 mmol/L. in this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA(1c) or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. the primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials. gov, number NCT01663402. Findings At study baseline, 5444 patients (28.8%) had diabetes, 8246 (43.6%) had prediabetes, and 5234 (27.7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2.20-2.28 mmol/L), after 4 months' treatment with alirocumab (0.80 mmol/L), or after 4 months' treatment with placebo (2.25-2.28 mmol/L). in the placebo group, the incidence of the primary endpoint over a median of 2.8 years was greater in patients with diabetes (16.4%) than in those with prediabetes (9.2%) or normoglycaemia (8.5%); hazard ratio (HR) for diabetes versus normoglycaemia 2.09 (95% CI 1.78-2.46, p, Sanofi; Regeneron Pharmaceuticals, Sanofi and Regeneron Pharmaceuticals.
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- 2019
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40. Mechanics and drug release from poroviscoelastic hydrogels: Experiments and modeling
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Gaetano Lamberti, Diego Caccavo, and Anna Angela Barba
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Materials science ,Polymers ,Pharmaceutical Science ,02 engineering and technology ,030226 pharmacology & pharmacy ,Viscoelasticity ,Diffusion ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Theophylline ,Poroviscoelasticity ,Agarose ,Molecule ,Water transport ,Viscosity ,Modeling ,Water ,Hydrogels ,General Medicine ,Mechanics ,021001 nanoscience & nanotechnology ,Chemical energy ,Drug Liberation ,chemistry ,Drug delivery ,Self-healing hydrogels ,Drug release ,0210 nano-technology ,Porosity ,Biotechnology - Abstract
Hydrogels are peculiar soft materials formed by a 3D polymeric network surrounded by water molecules. In these systems the mechanical and the chemical energy are well balanced and an applied external stimulus (mechanical or chemical) can cause a distinctive response, where the contributions of the mechanics and the mass transport are combined to form a "poroviscoelastic" behavior. In this work the poroviscoelastic behavior of the agarose gels has been investigated, from the experimental and modeling points of view, by applications of external mechanical stimuli. The pure gel, brought in the non-equilibrium condition, showed that the combined effect of mechanical viscoelasticity and water transport were essential to reach the new equilibrium condition. Furthermore, the agarose gel loaded with a model drug, theophylline, showed that the mechanical stimulus can enhance the drug release from the system by stretching the polymeric chains, modifying the mesh size and therefore the drug diffusion coefficient.
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- 2020
41. A multidisciplinary approach to understanding the population structure of an exploited Southern Ocean top predator, the Antarctic toothfish, to improve sustainability and marine spatial planning
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Jilda Caccavo, Camila Mazzoni, and Thomas Brey
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The Antarctic toothfish (Dissostichus mawsoni), commonly known as Chilean Sea Bass, has a critical role in Southern ecosystems as a top fish predator. Simultaneously, it represents the most lucrative Antarctic fishery.Its fishery is managed by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR), which introduced the world’s largest Marine Protected Area (MPA) in the Ross Sea region of the Southern Ocean in 2016.Since 2013, scientists at the Alfred Wegener Institute in Germany have been proposing the creation of an even more expansive MPA in the Weddell Sea region of the Southern Ocean, in order to protect unique ecosystems in this region, which has largely escaped the exploitation seen in the Ross Sea, due to its historic inaccessibility. However, CCAMLR, whose 25-member country composition functions by consensus, has failed to arrive at unanimous support for the various forms of a Weddell Sea MPA (WSMPA) proposed over recent years.A remaining impediment to the design and acceptance of a WSMPA, is a near total lack of knowledge of the life history and population structure of Antarctica toothfish in the Weddell Sea. Much of the data regarding connectivity and ontogenic movement of Antarctic toothfish derive from the Ross Sea, given the presence of an active fishery there since 1997. Based on the hypotheses that have arisen from the Ross Sea (which remain contentious), a possible life cycle of Antarctic toothfish comprises juvenile development on nutrient rich continental shelf areas, followed by passive transport via gyre systems to offshore sea mounts, where spawning occurs, prior to completion of the cycle as fish are passively transported back towards the coast.The combination of population genetics and otolith chemistry, methodologies which define population structure via metrics of relatedness and provenance respectively, offers the possibility to fill many of the existing knowledge gaps with regards to Antarctic toothfish life history connectivity in the Weddell Sea region of the Southern Ocean. The integration of hydrographic data on water mass movement which informs both the passive transport of Antarctic toothfish at various life stages, as well as the location of important prey sources, is an integral third point of consideration, completing the development of life history connectivity hypotheses testable via the aforementioned metrics.Tissue samples from the present study derive from otoliths (fish ear bones), which are a standard tissue extract by CCAMLR observers on Antarctic fishing vessels, historically collected for age determination. Otoliths provide both a source of DNA for genetics work, via tissue traces dried on the otolith exterior, as well as a source for chemistry analysis, via trace element analysis of otolith ring layers from the nucleus (earliest) to edge (latest) elemental depositions.The aim of the present study is to utilize this readily available tissue source (otoliths) in order to apply both aforementioned methodologies, with the ultimate aim to test between hypotheses of single or multiple populations within the Weddell Sea, while also contextualizing those Weddell Sea population(s) within the greater Southern Ocean distribution of Antarctic toothfish.
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- 2020
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42. Témoignage d’une expérience d’enseignement de l’histoire en italien en lycée international
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Marco Caccavo
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General Medicine - Abstract
Nous temoignons de l’utilisation de la bande dessinee comme support en classe d’histoire en lycee international, en section italienne, et, d’une maniere generale, comme media pedagogique qui s’adresse a tout public travaillant l’histoire en langue etrangere (DNL, CLIL). Nous montrerons comment le roman graphique permet l’acquisition de competences a la fois linguistiques et culturelles, mais aussi le reinvestissement des connaissances acquises dans une production graphique qui developpe l’autonomie et la creativite de l’eleve.
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- 2018
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43. HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties
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Matteo D'Amore, Anna Angela Barba, Gaetano Lamberti, Diego Caccavo, Veronica De Simone, and Annalisa Dalmoro
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Vitamin ,Chemical Phenomena ,Compressive Strength ,Polymers and Plastics ,Kinetics ,Portable water purification ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Granulation ,chemistry.chemical_compound ,Hypromellose Derivatives ,Wet granulation process ,Hydroxypropyl methylcellulose ,Granules ,Vitamin B12 ,Release properties ,Materials Chemistry ,Particle Size ,Porosity ,Mechanical Phenomena ,Chromatography ,Calorimetry, Differential Scanning ,Organic Chemistry ,Water ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Vitamin B 12 ,chemistry ,0210 nano-technology - Abstract
Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various fields such as pharmaceuticals, biomaterials, agriculture, food, water purification. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45–2 mm in size, was fully characterized. Results showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45–2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.
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- 2018
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44. Prevalence of comorbidities in patients with obstructive sleep apnea syndrome, overlap syndrome and obesity hypoventilation syndrome
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Alberto Capozzolo, Maria Aliani, Donato Lacedonia, Annarita Depalo, Mauro Carone, Incoronata Caccavo, Maria Pia Foschino Barbaro, Crescenzio Gallo, Giulia Patricelli, Roberto Sabato, and Giovanna Elisiana Carpagnano
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Pediatrics ,medicine.medical_specialty ,Vital Capacity ,Excessive daytime sleepiness ,Comorbidity ,030204 cardiovascular system & hematology ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Sleep Disorders, Circadian Rhythm ,Forced Expiratory Volume ,Obesity Hypoventilation Syndrome ,Diabetes Mellitus ,Prevalence ,medicine ,Humans ,Immunology and Allergy ,Obesity ,Undifferentiated Connective Tissue Diseases ,Genetics (clinical) ,Aged ,Retrospective Studies ,Metabolic Syndrome ,Obesity hypoventilation syndrome ,Sleep Apnea, Obstructive ,business.industry ,Sleep apnea ,Overlap syndrome ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Obstructive sleep apnea ,030228 respiratory system ,Hypertension ,Female ,Metabolic syndrome ,medicine.symptom ,business - Abstract
Introduction Sleep-disordered breathing causes a burden to the sufferer, the health care system and the society. Most studies have focused on obstructive sleep apnea (OSA); however, the prevalence of comorbidities in patients affected by overlap syndrome (OS) and obesity hypoventilation syndrome (OHS) has not been carefully evaluated. Study objectives The principal aim of this study was to identify the presence of comorbidities in patients suffering from OSA, OS, OHS and the differences in three groups of patients. Another purpose was to verify if sleepiness is associated with a greater prevalence of comorbidities. Methods A retrospective analysis in 989 adults referred for sleep diagnostic testing to our sleep center was performed. Patients were classified in OSA (721), OS (123) and OHS (145). Results The prevalence of comorbidities was higher in patients affected by OS and was the highest in the OHS group, while the prevalence of arterial hypertension is the highest in patients affected by OS. The probability of having more than two comorbidities follows the same trend. Excessive daytime sleepiness was associated with an increased rate of arterial hypertension, diabetes mellitus and the presence of multimorbidity in each group of patients. Conclusions The presence and the association of comorbidities seem to be higher in patients suffering from OSA, OS and OHS. Subjects suffering of OHS present a high prevalence of main diseases despite their younger age compared with others patients with SDB. Sleepiness may have a role, at least in a subset of these patients, into the development of comorbidities.
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- 2018
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45. Mammal collections in Brazil
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Elisandra Chiquito, Aldo Caccavo, Carolina Santos, Thiago Semedo, Anna Ludmilla Costa-Pinto, Diego Astúa, Alexandra Maria Bezerra, Claudia Regina Silva, Edú Guerra, Pablo Gonçalves, Sérgio Luiz Althoff, Tatiane Trigo, and Alexandre Percequillo
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Advances in our knowledge on the planet biodiversity have been largely dependent upon biological collections, and today they continue to be the cornerstone of several disciplines. Recently, the Brazilian Society of Mammalogists established the Mammal Collections Committee (CCM-SBMz) aiming to collect, organize and share information on the mammalian collections in Brazil, as well as support their management. As a first step, our goal here is to provide a diagnosis of mammal collections in Brazil, and the CCM-SBMz contacted 100 collections and successfully registered 71, distributed in all five Brazilian regions. These collections house ca. 372,200 specimens, with 60% of these concentrated in three institutions: MNRJ, MZUSP, and MPEG. The material more commonly deposited are voucher specimens. The database is completely digitized or in process of digitization in most collections, however, this information is not widely available online. The geographic coverage of the collections is mainly regional or national. In number of specimens, Rodentia is the most frequent order in the collections, followed by Carnivora. At the family level, Didelphidae, Cricetidae, and Felidae are the more frequent taxa. This study shows that Brazil houses an important volume of mammalian specimens. However, considering the country’s continental size and high mammal diversity, these numbers are still far from a sufficient representation of the Brazilian mammalian diversity. The results summarize the first efforts of the CCM-SBMz and the committee will continue monitoring the mammal collections in Brazil, as well as working to help the management and growth of collections.
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- 2021
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46. Effect of Colchicine vs Usual Care Alone on Intubation and 28-Day Mortality in Patients Hospitalized With COVID-19
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Rafael, Diaz, Andrés, Orlandini, Noelia, Castellana, Alberto, Caccavo, Pablo, Corral, Gonzalo, Corral, Carolina, Chacón, Pablo, Lamelas, Fernando, Botto, María Luz, Díaz, Juan Manuel, Domínguez, Andrea, Pascual, Carla, Rovito, Agustina, Galatte, Franco, Scarafia, Omar, Sued, Omar, Gutierrez, Sanjit S, Jolly, José M, Miró, John, Eikelboom, Mark, Loeb, Aldo Pietro, Maggioni, Deepak L, Bhatt, Salim, Yusuf, and Adriana P, Steren
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Adult ,Inflammation ,Male ,SARS-CoV-2 ,Research ,Anti-Inflammatory Agents ,COVID-19 ,Standard of Care ,General Medicine ,Middle Aged ,Respiration, Artificial ,Hospitalization ,Online Only ,Infectious Diseases ,Adrenal Cortex Hormones ,Intubation, Intratracheal ,Humans ,Female ,Colchicine ,Original Investigation ,Aged - Abstract
Key Points Question Does colchicine prevent intubation and mortality in hospitalized patients with COVID-19 pneumonia? Findings In this randomized clinical trial of 1279 patients hospitalized with COVID-19, patients allocated to receive colchicine plus usual care or to usual care alone demonstrated no significant difference in the coprimary outcome of mechanical ventilation or 28-day mortality. Meaning This randomized clinical trial found that colchicine did not significantly reduce the need for mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia., This randomized clinical trial assesses the efficacy of colchicine in preventing mechanical ventilation and mortality in hospitalized patients with COVID-19 pneumonia., Importance Hospitalized patients with COVID-19 pneumonia have high rates of morbidity and mortality. Objective To assess the efficacy of colchicine in hospitalized patients with COVID-19 pneumonia. Design, Setting, and Participants The Estudios Clínicos Latino América (ECLA) Population Health Research Institute (PHRI) COLCOVID trial was a multicenter, open-label, randomized clinical trial performed from April 17, 2020, to March 28, 2021, in adults with confirmed or suspected SARS-CoV-2 infection followed for up to 28 days. Participants received colchicine vs usual care if they were hospitalized with COVID-19 symptoms and had severe acute respiratory syndrome or oxygen desaturation. The main exclusion criteria were clear indications or contraindications for colchicine, chronic kidney disease, and negative results on a reverse transcription–polymerase chain reaction test for SARS-CoV-2 before randomization. Data were analyzed from June 20 to July 25, 2021. Interventions Patients were assigned in a 1:1 ratio to usual care or usual care plus colchicine. Colchicine was administered orally in a loading dose of 1.5 mg immediately after randomization, followed by 0.5 mg orally within 2 hours of the initial dose and 0.5 mg orally twice a day for 14 days or discharge, whichever occurred first. Main Outcomes and Measures The first coprimary outcome was the composite of a new requirement for mechanical ventilation or death evaluated at 28 days. The second coprimary outcome was death at 28 days. Results A total of 1279 hospitalized patients (mean [SD] age, 61.8 [14.6] years; 449 [35.1%] women and 830 [64.9%] men) were randomized, including 639 patients in the usual care group and 640 patients in the colchicine group. Corticosteroids were used in 1171 patients (91.5%). The coprimary outcome of mechanical ventilation or 28-day death occurred in 160 patients (25.0%) in the colchicine group and 184 patients (28.8%) in the usual care group (hazard ratio [HR], 0.83; 95% CI, 0.67-1.02; P = .08). The second coprimary outcome, 28-day death, occurred in 131 patients (20.5%) in the colchicine group and 142 patients (22.2%) in the usual care group (HR, 0.88; 95% CI, 0.70-1.12). Diarrhea was the most frequent adverse effect of colchicine, reported in 68 patients (11.3%). Conclusions and Relevance This randomized clinical trial found that compared with usual care, colchicine did not significantly reduce mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia. Trial Registration ClinicalTrials.gov Identifier: NCT04328480
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- 2021
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47. Erratum to: Systematics of the rodent genus Neacomys Thomas (Cricetidae: Sigmodontinae): two new species and a discussion on carotid patterns
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Aldo Caccavo and Marcelo Weksler
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Ecology ,Genetics ,Animal Science and Zoology ,Ecology, Evolution, Behavior and Systematics ,Nature and Landscape Conservation - Published
- 2021
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48. Evaluación económica comparativa sobre terapias de reemplazo renal en Argentina, Costa Rica y Uruguay
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Mauricio Beltrán, Alfonso Rosales, Martín Esteche, Carlos Azofeifa, María Paula Esquivel, Santiago Torales, Eliana Leguizamo, Santiago Hasdeu, Francisco Caccavo, José Berardo, Jordan Salazar, Alexandre Lemgruber, Manuel Cerdas, and Oscar Gianneo
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Costa Rica ,medicine.medical_treatment ,RC955-962 ,Argentina ,kidney transplantation ,costo efectividad ,Argentina, Costa Rica ,Peritoneal dialysis ,Arctic medicine. Tropical medicine ,fatores epidemiológicos ,medicine ,transplante de rim ,Investigación Original ,Enfermedad renal crónica ,trasplante renal ,Dialysis ,Renal inssufficiency, chronic ,diálise ,cost effectiveness ,business.industry ,Incidence (epidemiology) ,diálisis ,Public Health, Environmental and Occupational Health ,Uruguai ,epidemiologic factors ,medicine.disease ,Insuficiência renal crónica ,Donation ,Medicine ,Uruguay ,dialysis ,custo-efetividade ,Hemodialysis ,Public aspects of medicine ,RA1-1270 ,business ,factores epidemiológicos ,Demography ,Kidney disease - Abstract
Evaluate differences in the cost and prevalence of renal replacement therapies (RRTs) such as transplants, peritoneal dialysis, and hemodialysis in Argentina, Costa Rica, and Uruguay, based on cost-effective dissemination strategies.Costs and prevalence obtained from the main financers and providers in each country; analysis of cost-effectiveness using a Markov model with a five-year horizon, evaluating resource allocation strategies for their incremental cost-effectiveness ratio expressed as quality-adjusted years of life.There is observed dispersion among countries in terms of access to and beneficial value of RRTs, affecting their prevalence and monetary breakeven point. From the cost standpoint, it is more efficient to promote transplants and peritoneal dialysis, and to discourage hemodialysis, although the availability of each RRT in each country required a specific evaluation.Promoting transplants saves costs, but the variable breakeven points make it necessary to determine different cost-effectiveness thresholds for each country. In Argentina and Uruguay, RRTs would be more cost-effective with an increase in the number of patients in peritoneal dialysis and higher donation rates for transplants. In Costa Rica (where there is a high transplant rate and large budgetary margin), the use of dialysis is aligned with demand and with the incidence of patients with terminal chronic kidney disease.Avaliar as diferenças de custos e prevalência das terapias de substituição renal (TSR) como o transplante, a diálise peritoneal e a hemodiálise na Argentina, na Costa Rica e no Uruguai, mediante estratégias de difusão custo-efetivas.Foram avaliados custos e prevalência dos principais financiadores e prestadores por país, e realizada análise de custo-efetividade mediante modelo de Markov para 5 anos, avaliando estratégias de alocação de recursos expressas pela razão de custo-efetividade incremental por ano de vida ajustado por qualidade.Foi observada, entre os países, dispersão no acesso e nos valores prestacionais de TSR, afetando sua prevalência e o ponto de equilíbrio monetário. Do ponto de vista dos custos, é mais eficiente promover a realização de transplantes e de diálise peritoneal e desestimular a indicação de hemodiálise, embora a disponibilidade de cada TSR por país tenha exigido avaliações específicas.Promover a realização de transplantes economiza custos, embora os pontos de equilíbrio variáveis requeiram a determinação de diferentes limiares de custo-efetividade por país. Na Argentina e no Uruguai, a administração de TSR melhoraria sua eficiência se a quantidade de pacientes em diálise peritoneal e as taxas de doação para transplantes aumentassem. Na Costa Rica (onde há taxas elevadas de transplantes e margem orçamentária), a incorporação de técnicas dialíticas é ajustada por demanda e incidência de pacientes com DRCT.
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- 2021
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49. Engineering approaches in siRNA delivery
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Sara Cascone, Roberto Andrea Abbiati, Mario Grassi, Michela Abrami, Anna Angela Barba, Gianluca Chiarappa, Vincenzo La Carrubba, Gabriele Grassi, Giovanna Tomaiuolo, Diego Caccavo, Francesco Carfì Pavia, Davide Manca, Gaetano Lamberti, Giulio Ghersi, Valerio Brucato, Stefano Guido, Barba, Anna Angela, Cascone, Sara, Caccavo, Diego, Lamberti, Gaetano, Chiarappa, Gianluca, Abrami, Michela, Grassi, Gabriele, Grassi, Mario, Tomaiuolo, Giovanna, Guido, Stefano, Brucato, Valerio, Carfì Pavia, Francesco, Ghersi, Giulio, La Carrubba, Vincenzo, Abbiati, Roberto Andrea, Manca, Davide, Barba, A., Cascone, S., Caccavo, D., Lamberti, G., Chiarappa, G., Abrami, M., Grassi, G., Grassi, M., Tomaiuolo, G., Guido, S., Brucato, V., Carfì Pavia, F., Ghersi, G., La Carrubba, V., Abbiati, R., Manca, D., Anna Angela, Barba, Sara, Cascone, Diego, Caccavo, Gaetano, Lamberti, Giovanna, Tomaiuolo, Stefano, Guido, Valerio, Brucato, Francesco, Carfìpavia, Giulio, Ghersi, Vincenzo, Lacarrubba, Robertoandrea, Abbiati, and Davide, Manca
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0301 basic medicine ,siRNAs, Delivery vectors, in vitro models, Mathematical modeling, Physical modeling ,Delivery vectors ,In vitro models ,Mathematical modeling ,Physical modeling ,SiRNAs ,3003 ,Pharmaceutical Science ,Nanotechnology ,02 engineering and technology ,Computational biology ,Biology ,03 medical and health sciences ,Drug Delivery Systems ,Humans ,siRNAs ,in vitro models ,RNA, Small Interfering ,Settore ING-IND/34 - Bioingegneria Industriale ,Hydrogels ,Models, Theoretical ,021001 nanoscience & nanotechnology ,Delivery vector ,Clinical Practice ,Hydrogel ,030104 developmental biology ,in vitro model ,siRNA ,0210 nano-technology ,Blood stream ,Drug Delivery System ,Clearance ,Human - Abstract
siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectorsâ production processes and siRNAs vectorsâ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectorsâ fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.
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- 2016
50. Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness
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Spyropoulos A. C., Ageno W., Albers G. W., Elliott C. G., Halperin J. L., Hiatt W. R., Maynard G. A., Steg P. G., Weitz J. I., Suh E., Spiro T. E., Barnathan E. S., Raskob G. E., Douketis J., Turpie A. G., Schulman S., Kearon C., Linkins L. A., Schellong S., Bauer K., Geerts W., Roberts R., Casais P., Gallus A., Karrasch J., Eichinger-Hasenauer S., Krivenchuk V., Hadzovic-Dzuvo A., Trbojevic S., Lopes R., Mincheva V., Carrier M., Dennis R., Tudoric N., Spinar J., Nielsen H., Marandi T., Shaburishvili T., Beyer-Westendorf J., Vardas P., Boda Z., Brenner B., Piovella F., Krievins D., Petrauskiene B., Dejanova-Ilijevska V., Virgen Carrillo L. R., Middeldorp S., Castillo Leon R. P., Torbicki A., Saraiva de Sousa M., Dorobantu M., Militaru C., Yavelov I., Vuckovic B., Reuter H., Basson M., Monreal M., Kucukoglu S., Parkhomenko A., Alikhan R., Rosenberg D., Yusen R., Khorana A., Tapson V., Pollack C., Hazelrigg M., Jure H., Alvarisqueta A., Cartasegna L., Hominal M., Cursack G., Alzogaray M., Maillo M., Parody M., Caccavo A., Dran R. D., Muntaner J. A., Casas M., Schmidberg J., Sarjanovich R., Gabito A., Garrido M., Amuchastegui M., Fernandez A., Loureyro J., Giumelli C., Heazlewood V., Colquhoun D., White H., Sabet A., Bowler S., Carroll P., Khalafallah A., Baker R., Hedger S., Simpson F. G., Jackson D., Chong B., Siostrzonek P., Gary T., Hoppe U., Dosta N., Prystrom A., Gorokhovsky S., Yanushko V., Skrahin A., Kulik A., Maslianski B., Yakubtsevich R., Timkin I., Moguchaya O., Tanaskovic N., Miljkovic S., Stojkovic S., Kovacevic-Preradovic T., Jovic D., Basagic E., Radjen M., Mutapcic M., Rizvanovic-Vojic E., Galic K., Terzic I., Pojskic B., Stevanovic D., Cehajic M., Rech R., Annichino-Bizzacchi J., Stelmach R., Blanco D., Castro I., Backes L. M., Saraiva J. F., Ramacciotti E., de Barros e Silva P. G. M., Reis G., Moreira Vieira E., Leaes P., Zimmermann S., Van Bellen B., Precoma D., Luiz Silvestrini T., Hernandes M. E., Kyoleyan M., Kalinova T., Tiholov R., Petrov I., Mihov A., Chompalova B., Velikov C., Pencheva G., Atanasov P., Raev D., Kinova E., Peltegov V., Marchev S., Siulemezova S., Ayryanova I. D., Grigorov M., Naydenova I., Koteva N., Dimov B., Runev N., Getov D., Metev H., Donchev K., Taseva M., Hadzhieva A., Benov H., Stoyanov M., Tisheva-Gospodinova S., Mihaylova N., Abadzhiev S., Atzev B., Georgiev R., Mollov M., Stoikov A., Mazhdrakov G., Karastanev K., Dube F., Roth S., Mansour S., Wu C., Dolan S., Pesant Y., Pietrangelo M., Dresser G., Kahn S., Kruisselbrink R., Cadena Bonfanti A., Botero R., Quintero Ossa A., Poveda C. M., Cedano J., Gomez Isaza L., Villaquiran Torres C., Gomez Mesa J., Vargas Alonso R., Espinosa D., Rodriguez J. M., Sanchez G., Accini Mendoza J. L., Gomez Florez C. C., Cuervo Millan F., Pesek K., Horvat D., Fuckar K., Ruzic A., Ostricki B., Knezevic A., Breitenfeld T., Laganovic M., Samodol A., Sikic J., Starcevic B., Babic Z., Samarzija M., Milas K., Votocek S., Kvapil M., Kolman P., Bindas P., Simon V., Adamek T., Svobodova J., Gergely L., Lastuvka J., Macel I., Navratil K., Gregor P., Lacnak B., Janousek J., Kellnerova I., Hulinsky V., Matusek Z., Prucek L., Dunaj M., Pirchala M., Vencour D., Pavolko M., Gorican K., Fiksa J., Tuxen C., Meyer C., Suppli Ulrik C., Uuetoa T., Otarishvili N., Khintibidze I., Emukhvari N., Kipiani Z., Gochitashvili D., Mamatsashvili M., Megreladze I., Paposhvili K., Agladze R., Eradze Z., Chelidze K., Lominadze S., Chukhrukidze A., Chumburidze V., Metreveli S., Danelia V., Orjonikidze S., Kobulia B., Nikolaishvili G., Gvenetadze R., Melia A., Tsinamdzgvrishvili B., Sekhniashvili M., Sikharulidze I., Meuser M., Licka M., Rauch-Kroehnert U., Graf K., Brachmann J., Akin I., Toumbis M., Vassilikos V., Konstantinides S., Steiropoulos P., Gogos C., Andrikopoulos G., Parthenakis F., Karydi P., Tsivgoulis G., Mertzanos G., Olympios C., Karapanayiotides T., Paraskevopoulou E., Kifnidis K., Hahalis G., Skoutelis A., Vadikolias K., Nyirati G., Nagy L., Matoltsy A., Komoly S., Lippai J., Kiss K., Toth K., Pozsegovits K., Kiraly C., Bereczki D., Zolyomi S., Szakal I., Pall D., Futo L., Forster T., Lovasz O., Papp A., Kiraly Z., Pozsonyi Z., Hajko E., Kristof P., Lakatos F., Ples Z., Kirschner R., Lupkovics G., Timar G., Pinter I., Kristof T., Kis E., Kovacs A., Jakab G., Palinkas A., Muller G., Turi T., Horvath C., Kondakor I., Csanyi A., Frankfurter Z., Gurzo M., Gafter-Gvili A., Kuchuk M., Azzam Z., Elis A., Halabi M., Hussein O., Blum A., Tsoran-Rosenthal I., Lishner M., Hochberg-Klein S., Caraco Y., Atar S., Elias N., Gavish D., Butnaru A., Cosmi F., Garbelotto R., Giorgi Pierfranceschi M., Simioni L., Gronda E., Pesci A., D'Angelo A., Fedele F., Ghirarduzzi A., Piovaccari G., Lembo G., Ria L., Monaco G. L., Brunelli C., Tosetto A., Capucci A., Zanatta N., Pistolesi M., Mazzi V., Testa S., Scherillo M., Di Biase M., Antonicelli R., Lodigiani C., Nassiacos D., Viksne I., Lapkovska Z., Rancane G., Sime I., Pontaga N., Eglite R., Puzule S., Smolova R., Butkiene Z., Bagdonas A., Raugaliene R., Norkiene S., Norviliene R., Basijokiene V., Stonkus S., Griskeviciene V., Miskiniene A., Norvaisiene R., Skripkauskiene I., Jovkovska-Kaeva B., Kochovska-Kamchevska N., Antovski A., Nechevska L., Celeska V., Ilievska-Poposka B., Kostojchinoska M., Donchovska S., Kedev S., Kuzmanovski I., Bushletikj O., Stojchev S., Bakrachevski N., Kuzmanovska B., Angusheva T., Llamas Esperon G., Valdez Lopez H., Medina Pech C., Cortes Hernandez M., Virgen Carrillo L., Gans S., Smulders S., Swart H., Boersma W., Goosens M., Hovens M., Semplonius G., Sohne M., Lema Osores J., Salas Perez M. D., Rodriguez A., Rios Oliva C., Cotrina R., Berrospi Argandona P., Toce Yanez L., Chavez Ayala C., Mirek-Bryniarska E., Goch A., Skucha W., Skorski M., Miekus P., Szyszka A., Piotrowski G., Gniot J., Czerski T., Debich P., Zaluska R., Bebenek W., Wozakowska-Kaplon B., Sciborski R., Ilkowski J., Wojnowski P., Uscinska E., Gaciong Z., Bonek R., Sobkowicz B., Berkowski P., Bejgier K., Polonski L., Kosior D., Lata S., Kolodziej P., Gessek J., Kachel T., Talalaj M., Musial J., Lewczuk J., Krysiak W., Kucharski L., Wysokinski A., Minc P., Martinez J., Gregorio T., Almeida F., Monteiro P., Stanciulescu G., Mercea C. D., Iosipescu L. C., Ciobotaru V., Crisu D., Burca M., Tudoran M., Savu A., Negrean V., Cojocaru C., Minescu B., Popa V., Blajan D., Nastase-Melicovici D., Fruntelata A., Barbulescu S., Lukinyh L., Akhunova S., Vishneva E., Semenova I., Nikolaev K. Y., Shaydyuk O., Nilk R., Shalnev V., Apartsin K., Goloshchekin B. M., Shpagina L., Khlevchuk T., Arkhipov M., Malygin A., Shvarts Y., Khaisheva L., Popov D., Kobalava Z., Lipchenko A., Shapovalova Y., Zrazhevsky K., Greshnova I., Maslova N., Karabenenko A., Shogenov Z., Budankova E., Barbarash O., Uspenskiy Y., Kosmacheva E., Berns S., Kostenko V., Zateyshchikov D., Vishnevsky A., Boldueva S., Podzolkov V., Sergeeva E., Grinshtein Y., Khrustalev O., Bugrova O., Repin A., Andreev D., Petrovic P., Boskovic Matic T., Apostolovic S., Lazic Z., Stankovic D., Stankovic A., Mitov V., Sofronic D., Kopitovic I., Zdravkovic V., Joksimovic Z., Lazovic N., Petrovic-Stanojevic N., Ilic A., Vujadinovic O., Pencic-Popovic B., Andjelkovic N., Sekularac N., Hinic S., Radjen G., Zivkovic A., Putnikovic B., Ivanov I., Babic R., Van Zyl L., Hobson B., Engelbrecht J., Mitha I., Siebert H., Jacobson B., Breedt J., Prozesky H., Ntsekhe M., Bayat J., Ellis G., Tarr G., Adler D., Van Dyk C., Ismail S. M., Spargo C. E., Abdool-Gaffar M., Saaiman J., Venter K., Lorente Aroca M. L., Fernandez Portales F., Pedrajas Navas J., Rodriguez Botaro A., Santa Cruz Siminiani A., Lopez Reyes R., Bisbe i Company J., Piedecausa Selfa M., Velasco Garrido J., Sobrino-Martinez J., Munoz Delgado G., Sala Llinas E., Blanco Coronado J., Almenar Bonet L., Vida Gutierrez M., Sanchez Lora F., Sanchez Martinez R., Calderon E. J., Villalta Blanch J., De la Hera Galarza J. M., Bustamante Ruiz A., Garcia-Fuster M. J., Ripoll Vera T., Alvarez-Sala Walter L., Todoli Parra J. A., Diaz Fernandez J., Bosa Ojeda F., Pellicer-Ciscar C., Jara Palomares L., Quiles Granado J., Trigo Bautista A., Ruiz Bustillo S., Ordi Ros J., Tolosa-Vilella C., Marin Ortuno F., Garcia Sanchez F., Barba Martin R., Segovia Cubero J., Cuervas-Mons Martinez V., Galan Montejano M., Lopez Meseguer M., Sener Comert S., Koksal N., Tertemiz K., Ernam D., Dursun A. B., Yildiz O., Rudenko L., Abrahamovych O., Goloborodko A., Holovchenko N., Kulyk A., Yagensky A., Batushkin V., Zolotaikina V., Kozyolkin O., Faynyk A., Maslovskyy V., Petrovskyy R., Koshlia V., Chopey I., Burmak I., Malynovsky Y., Voronkov L., Karpenko O., Dziublyk O., Godlevska O., Borovyk V., Bezrodna L., Serik S., Ovsyannikova N., Vynnychenko L., Kopytsya M., Rudkovskiy V., Grishyna O., Vyshnyvetskyy I., Prystupa L., Tseluyko V., Perepeliuk M., Koval O., Sychov O., Church A., Goudie A., Elliott M., Ferguson C., Welker J., Kao C. K., Bhagwat R., Serota H., Bozorgchami H., Nambiar R., Spilseth S., Bhagwath G., Syed F., Morrow L., Updegrove J., Bercz P., Kambo V., Henderson D., Wright P., Dang N., Nadar V., Jaffrani N., El-Shahawy M., Grossman C. H., Pearle J., Weinstein D., Galanis T. P., Gazmuri R., Kastelic R., Martinez R., Laman D., Macchiavelli A., Kmetzo J., Thurm C., Kayembe T., Chandrashekhar Y., Bassetti D., Jaoude P., Williams H., Dewhurst R., Naqvi S., Burr J., Rodriguez-Cintron W., Jeanfreau R., Kosinski E., Ndukwu I. M., Sotolongo C., Daboul N., Wilmer C., Simon P., Tak T., Rees C., Gupta N., Lerner R., Graffagnino C., Reed R. M., Alford C. M., Mody F., Wellmon B., Hamroff G., Rajan R., Kaatz S., OMÜ, Spyropoulos, A, Ageno, W, Albers, G, Elliott, C, Halperin, J, Hiatt, W, Maynard, G, Steg, P, Weitz, J, Suh, E, Spiro, T, Barnathan, E, Raskob, G, Douketis, J, Turpie, A, Schulman, S, Kearon, C, Linkins, L, Schellong, S, Bauer, K, Geerts, W, Roberts, R, Casais, P, Gallus, A, Karrasch, J, Eichinger-Hasenauer, S, Krivenchuk, V, Hadzovic-Dzuvo, A, Trbojevic, S, Lopes, R, Mincheva, V, Carrier, M, Dennis, R, Tudoric, N, Spinar, J, Nielsen, H, Marandi, T, Shaburishvili, T, Beyer-Westendorf, J, Vardas, P, Boda, Z, Brenner, B, Piovella, F, Krievins, D, Petrauskiene, B, Dejanova-Ilijevska, V, Virgen Carrillo, L, Middeldorp, S, Castillo Leon, R, Torbicki, A, Saraiva de Sousa, M, Dorobantu, M, Militaru, C, Yavelov, I, Vuckovic, B, Reuter, H, Basson, M, Monreal, M, Kucukoglu, S, Parkhomenko, A, Alikhan, R, Rosenberg, D, Yusen, R, Khorana, A, Tapson, V, Pollack, C, Hazelrigg, M, Jure, H, Alvarisqueta, A, Cartasegna, L, Hominal, M, Cursack, G, Alzogaray, M, Maillo, M, Parody, M, Caccavo, A, Dran, R, Muntaner, J, Casas, M, Schmidberg, J, Sarjanovich, R, Gabito, A, Garrido, M, Amuchastegui, M, Fernandez, A, Loureyro, J, Giumelli, C, Heazlewood, V, Colquhoun, D, White, H, Sabet, A, Bowler, S, Carroll, P, Khalafallah, A, Baker, R, Hedger, S, Simpson, F, Jackson, D, Chong, B, Siostrzonek, P, Gary, T, Hoppe, U, Dosta, N, Prystrom, A, Gorokhovsky, S, Yanushko, V, Skrahin, A, Kulik, A, Maslianski, B, Yakubtsevich, R, Timkin, I, Moguchaya, O, Tanaskovic, N, Miljkovic, S, Stojkovic, S, Kovacevic-Preradovic, T, Jovic, D, Basagic, E, Radjen, M, Mutapcic, M, Rizvanovic-Vojic, E, Galic, K, Terzic, I, Pojskic, B, Stevanovic, D, Cehajic, M, Rech, R, Annichino-Bizzacchi, J, Stelmach, R, Blanco, D, Castro, I, Backes, L, Saraiva, J, Ramacciotti, E, de Barros e Silva, P, Reis, G, Moreira Vieira, E, Leaes, P, Zimmermann, S, Van Bellen, B, Precoma, D, Luiz Silvestrini, T, Hernandes, M, Kyoleyan, M, Kalinova, T, Tiholov, R, Petrov, I, Mihov, A, Chompalova, B, Velikov, C, Pencheva, G, Atanasov, P, Raev, D, Kinova, E, Peltegov, V, Marchev, S, Siulemezova, S, Ayryanova, I, Grigorov, M, Naydenova, I, Koteva, N, Dimov, B, Runev, N, Getov, D, Metev, H, Donchev, K, Taseva, M, Hadzhieva, A, Benov, H, Stoyanov, M, Tisheva-Gospodinova, S, Mihaylova, N, Abadzhiev, S, Atzev, B, Georgiev, R, Mollov, M, Stoikov, A, Mazhdrakov, G, Karastanev, K, Dube, F, Roth, S, Mansour, S, Wu, C, Dolan, S, Pesant, Y, Pietrangelo, M, Dresser, G, Kahn, S, Kruisselbrink, R, Cadena Bonfanti, A, Botero, R, Quintero Ossa, A, Poveda, C, Cedano, J, Gomez Isaza, L, Villaquiran Torres, C, Gomez Mesa, J, Vargas Alonso, R, Espinosa, D, Rodriguez, J, Sanchez, G, Accini Mendoza, J, Gomez Florez, C, Cuervo Millan, F, Pesek, K, Horvat, D, Fuckar, K, Ruzic, A, Ostricki, B, Knezevic, A, Breitenfeld, T, Laganovic, M, Samodol, A, Sikic, J, Starcevic, B, Babic, Z, Samarzija, M, Milas, K, Votocek, S, Kvapil, M, Kolman, P, Bindas, P, Simon, V, Adamek, T, Svobodova, J, Gergely, L, Lastuvka, J, Macel, I, Navratil, K, Gregor, P, Lacnak, B, Janousek, J, Kellnerova, I, Hulinsky, V, Matusek, Z, Prucek, L, Dunaj, M, Pirchala, M, Vencour, D, Pavolko, M, Gorican, K, Fiksa, J, Tuxen, C, Meyer, C, Suppli Ulrik, C, Uuetoa, T, Otarishvili, N, Khintibidze, I, Emukhvari, N, Kipiani, Z, Gochitashvili, D, Mamatsashvili, M, Megreladze, I, Paposhvili, K, Agladze, R, Eradze, Z, Chelidze, K, Lominadze, S, Chukhrukidze, A, Chumburidze, V, Metreveli, S, Danelia, V, Orjonikidze, S, Kobulia, B, Nikolaishvili, G, Gvenetadze, R, Melia, A, Tsinamdzgvrishvili, B, Sekhniashvili, M, Sikharulidze, I, Meuser, M, Licka, M, Rauch-Kroehnert, U, Graf, K, Brachmann, J, Akin, I, Toumbis, M, Vassilikos, V, Konstantinides, S, Steiropoulos, P, Gogos, C, Andrikopoulos, G, Parthenakis, F, Karydi, P, Tsivgoulis, G, Mertzanos, G, Olympios, C, Karapanayiotides, T, Paraskevopoulou, E, Kifnidis, K, Hahalis, G, Skoutelis, A, Vadikolias, K, Nyirati, G, Nagy, L, Matoltsy, A, Komoly, S, Lippai, J, Kiss, K, Toth, K, Pozsegovits, K, Kiraly, C, Bereczki, D, Zolyomi, S, Szakal, I, Pall, D, Futo, L, Forster, T, Lovasz, O, Papp, A, Kiraly, Z, Pozsonyi, Z, Hajko, E, Kristof, P, Lakatos, F, Ples, Z, Kirschner, R, Lupkovics, G, Timar, G, Pinter, I, Kristof, T, Kis, E, Kovacs, A, Jakab, G, Palinkas, A, Muller, G, Turi, T, Horvath, C, Kondakor, I, Csanyi, A, Frankfurter, Z, Gurzo, M, Gafter-Gvili, A, Kuchuk, M, Azzam, Z, Elis, A, Halabi, M, Hussein, O, Blum, A, Tsoran-Rosenthal, I, Lishner, M, Hochberg-Klein, S, Caraco, Y, Atar, S, Elias, N, Gavish, D, Butnaru, A, Cosmi, F, Garbelotto, R, Giorgi Pierfranceschi, M, Simioni, L, Gronda, E, Pesci, A, D'Angelo, A, Fedele, F, Ghirarduzzi, A, Piovaccari, G, Lembo, G, Ria, L, Monaco, G, Brunelli, C, Tosetto, A, Capucci, A, Zanatta, N, Pistolesi, M, Mazzi, V, Testa, S, Scherillo, M, Di Biase, M, Antonicelli, R, Lodigiani, C, Nassiacos, D, Viksne, I, Lapkovska, Z, Rancane, G, Sime, I, Pontaga, N, Eglite, R, Puzule, S, Smolova, R, Butkiene, Z, Bagdonas, A, Raugaliene, R, Norkiene, S, Norviliene, R, Basijokiene, V, Stonkus, S, Griskeviciene, V, Miskiniene, A, Norvaisiene, R, Skripkauskiene, I, Jovkovska-Kaeva, B, Kochovska-Kamchevska, N, Antovski, A, Nechevska, L, Celeska, V, Ilievska-Poposka, B, Kostojchinoska, M, Donchovska, S, Kedev, S, Kuzmanovski, I, Bushletikj, O, Stojchev, S, Bakrachevski, N, Kuzmanovska, B, Angusheva, T, Llamas Esperon, G, Valdez Lopez, H, Medina Pech, C, Cortes Hernandez, M, Gans, S, Smulders, S, Swart, H, Boersma, W, Goosens, M, Hovens, M, Semplonius, G, Sohne, M, Lema Osores, J, Salas Perez, M, Rodriguez, A, Rios Oliva, C, Cotrina, R, Berrospi Argandona, P, Toce Yanez, L, Chavez Ayala, C, Mirek-Bryniarska, E, Goch, A, Skucha, W, Skorski, M, Miekus, P, Szyszka, A, Piotrowski, G, Gniot, J, Czerski, T, Debich, P, Zaluska, R, Bebenek, W, Wozakowska-Kaplon, B, Sciborski, R, Ilkowski, J, Wojnowski, P, Uscinska, E, Gaciong, Z, Bonek, R, Sobkowicz, B, Berkowski, P, Bejgier, K, Polonski, L, Kosior, D, Lata, S, Kolodziej, P, Gessek, J, Kachel, T, Talalaj, M, Musial, J, Lewczuk, J, Krysiak, W, Kucharski, L, Wysokinski, A, Minc, P, Martinez, J, Gregorio, T, Almeida, F, Monteiro, P, Stanciulescu, G, Mercea, C, Iosipescu, L, Ciobotaru, V, Crisu, D, Burca, M, Tudoran, M, Savu, A, Negrean, V, Cojocaru, C, Minescu, B, Popa, V, Blajan, D, Nastase-Melicovici, D, Fruntelata, A, Barbulescu, S, Lukinyh, L, Akhunova, S, Vishneva, E, Semenova, I, Nikolaev, K, Shaydyuk, O, Nilk, R, Shalnev, V, Apartsin, K, Goloshchekin, B, Shpagina, L, Khlevchuk, T, Arkhipov, M, Malygin, A, Shvarts, Y, Khaisheva, L, Popov, D, Kobalava, Z, Lipchenko, A, Shapovalova, Y, Zrazhevsky, K, Greshnova, I, Maslova, N, Karabenenko, A, Shogenov, Z, Budankova, E, Barbarash, O, Uspenskiy, Y, Kosmacheva, E, Berns, S, Kostenko, V, Zateyshchikov, D, Vishnevsky, A, Boldueva, S, Podzolkov, V, Sergeeva, E, Grinshtein, Y, Khrustalev, O, Bugrova, O, Repin, A, Andreev, D, Petrovic, P, Boskovic Matic, T, Apostolovic, S, Lazic, Z, Stankovic, D, Stankovic, A, Mitov, V, Sofronic, D, Kopitovic, I, Zdravkovic, V, Joksimovic, Z, Lazovic, N, Petrovic-Stanojevic, N, Ilic, A, Vujadinovic, O, Pencic-Popovic, B, Andjelkovic, N, Sekularac, N, Hinic, S, Radjen, G, Zivkovic, A, Putnikovic, B, Ivanov, I, Babic, R, Van Zyl, L, Hobson, B, Engelbrecht, J, Mitha, I, Siebert, H, Jacobson, B, Breedt, J, Prozesky, H, Ntsekhe, M, Bayat, J, Ellis, G, Tarr, G, Adler, D, Van Dyk, C, Ismail, S, Spargo, C, Abdool-Gaffar, M, Saaiman, J, Venter, K, Lorente Aroca, M, Fernandez Portales, F, Pedrajas Navas, J, Rodriguez Botaro, A, Santa Cruz Siminiani, A, Lopez Reyes, R, Bisbe i Company, J, Piedecausa Selfa, M, Velasco Garrido, J, Sobrino-Martinez, J, Munoz Delgado, G, Sala Llinas, E, Blanco Coronado, J, Almenar Bonet, L, Vida Gutierrez, M, Sanchez Lora, F, Sanchez Martinez, R, Calderon, E, Villalta Blanch, J, De la Hera Galarza, J, Bustamante Ruiz, A, Garcia-Fuster, M, Ripoll Vera, T, Alvarez-Sala Walter, L, Todoli Parra, J, Diaz Fernandez, J, Bosa Ojeda, F, Pellicer-Ciscar, C, Jara Palomares, L, Quiles Granado, J, Trigo Bautista, A, Ruiz Bustillo, S, Ordi Ros, J, Tolosa-Vilella, C, Marin Ortuno, F, Garcia Sanchez, F, Barba Martin, R, Segovia Cubero, J, Cuervas-Mons Martinez, V, Galan Montejano, M, Lopez Meseguer, M, Sener Comert, S, Koksal, N, Tertemiz, K, Ernam, D, Dursun, A, Yildiz, O, Rudenko, L, Abrahamovych, O, Goloborodko, A, Holovchenko, N, Kulyk, A, Yagensky, A, Batushkin, V, Zolotaikina, V, Kozyolkin, O, Faynyk, A, Maslovskyy, V, Petrovskyy, R, Koshlia, V, Chopey, I, Burmak, I, Malynovsky, Y, Voronkov, L, Karpenko, O, Dziublyk, O, Godlevska, O, Borovyk, V, Bezrodna, L, Serik, S, Ovsyannikova, N, Vynnychenko, L, Kopytsya, M, Rudkovskiy, V, Grishyna, O, Vyshnyvetskyy, I, Prystupa, L, Tseluyko, V, Perepeliuk, M, Koval, O, Sychov, O, Church, A, Goudie, A, Elliott, M, Ferguson, C, Welker, J, Kao, C, Bhagwat, R, Serota, H, Bozorgchami, H, Nambiar, R, Spilseth, S, Bhagwath, G, Syed, F, Morrow, L, Updegrove, J, Bercz, P, Kambo, V, Henderson, D, Wright, P, Dang, N, Nadar, V, Jaffrani, N, El-Shahawy, M, Grossman, C, Pearle, J, Weinstein, D, Galanis, T, Gazmuri, R, Kastelic, R, Martinez, R, Laman, D, Macchiavelli, A, Kmetzo, J, Thurm, C, Kayembe, T, Chandrashekhar, Y, Bassetti, D, Jaoude, P, Williams, H, Dewhurst, R, Naqvi, S, Burr, J, Rodriguez-Cintron, W, Jeanfreau, R, Kosinski, E, Ndukwu, I, Sotolongo, C, Daboul, N, Wilmer, C, Simon, P, Tak, T, Rees, C, Gupta, N, Lerner, R, Graffagnino, C, Reed, R, Alford, C, Mody, F, Wellmon, B, Hamroff, G, Rajan, R, and Kaatz, S
- Subjects
Male ,medicine.medical_specialty ,Aftercare ,Aged ,Double-Blind Method ,Drug Administration Schedule ,Factor Xa Inhibitors ,Female ,Hemorrhage ,Humans ,Kaplan-Meier Estimate ,Middle Aged ,Patient Discharge ,Rivaroxaban ,Treatment Outcome ,Venous Thromboembolism ,Venous Thrombosis ,Hospitalization ,Medicine (all) ,030204 cardiovascular system & hematology ,Placebo ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Medical illness ,Internal medicine ,Hospital discharge ,Medicine ,Venous Thrombosi ,030212 general & internal medicine ,Thromboprophylaxis ,business.industry ,General Medicine ,medicine.disease ,Venous thrombosis ,Increased risk ,rivaroxaban ,thromboprophylaxis ,medical illness ,business ,Venous thromboembolism ,Factor Xa Inhibitor ,Human ,medicine.drug - Abstract
Zateyshchikov, Dmitry A/0000-0001-7065-2045; Vyshnyvetskyy, Ivan/0000-0001-7228-3052; Bustillo, Sonia Ruiz/0000-0002-6074-914X; Maslovskyi, Valentyn/0000-0001-5184-1799; Ruzic, Alen/0000-0001-5031-2975; Nikolaev, Konstantin/0000-0003-4601-6203; Musial, Jacek/0000-0002-8994-0036; Malynovsky, Yaroslav V/0000-0002-9118-1104; Tsivgoulis, Georgios/0000-0002-0640-3797; Maslovskyi, Valentyn/0000-0001-5184-1799; Grinshtein, Yury/0000-0001-8847-235X; Shpagina, Lyubov/0000-0003-0871-7551; Yildiz, Oznur/0000-0002-5379-6829; Marchev, Sotir/0000-0001-9250-510X; Weitz, Jeffrey/0000-0002-1092-7550; Apartsin, Konstantin A/0000-0003-0577-9001; Reis, Gilmar/0000-0002-4847-1034; Baker, Ross/0000-0002-2728-6788; Koziolkin, Olexandr/0000-0001-9878-5798; Barbarash, Olga/0000-0002-4642-3610; Sala-Llinas, Ernest/0000-0002-6499-1638; Gallus, Alexander/0000-0001-7347-9989; lodigiani, corrado/0000-0002-9152-9385; Kosmacheva, Elena/0000-0001-8600-0199; Ramacciotti, Eduardo/0000-0002-5735-1333; Khorana, Alok/0000-0002-9509-0998; Giorgi-Pierfranceschi, Matteo/0000-0002-7988-9652; Torbicki, Adam/0000-0003-3475-8832; Abragamovic, Orest/0000-0001-6862-6809; Jara-Palomares, Luis/0000-0002-4125-3376; Prozesky, Hans/0000-0001-9715-3449; Andreev, Denis/0000-0002-0276-7374; Cuervas-Mons Martinez, Valentin/0000-0003-3086-9463; Apostolovic, Svetlana/0000-0001-9015-297X; Gregorio, Tiago/0000-0002-0131-9430; Sanchez Martinez, Rosario/0000-0003-0408-3029; Antonicelli, Roberto/0000-0002-5921-1828; Konstantinides, Stavros/0000-0001-6359-7279; Karapanayiotides, Theodoros/0000-0002-2357-7967; Repin, Alexey/0000-0001-7123-0645 WOS: 000445020900006 PubMed: 30145946 BACKGROUND Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. METHODS In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma n-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. RESULTS Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). CONCLUSIONS Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. Janssen Research and Development; Daiichi SankyoDaiichi Sankyo Company Limited; Portola; Boehringer IngelheimBoehringer Ingelheim; JanssenJohnson & Johnson USAJanssen Biotech Inc; BayerBayer AG; BMS PfizerPfizer; Aspen; Sanofi; University of Cincinnati and Spectrum Health; PfizerPfizer; ATLAS Group (Colorado Prevention Center); Johnson JohnsonJohnson & Johnson USA; Ortho-McNeil-JanssenJohnson & Johnson USAJanssen Biotech Inc; Bayer/JanssenJohnson & Johnson USAJanssen Biotech IncBayer AG; MerckMerck & Company; AmgenAmgen Supported by Janssen Research and Development.r Dr. Spyropoulos reports receiving advisory board fees from Daiichi Sankyo and Portola, grant support, consulting fees, and advisory board fees from Boehringer Ingelheim and Janssen, consulting fees and advisory board fees from Bayer, and a stipend from ATLAS Group (Colorado Prevention Center); Dr. Ageno, receiving grant support and advisory board fees from Bayer and BMS Pfizer and advisory board fees from Portola, Daiichi Sankyo, Aspen, Boehringer Ingelheim, and Sanofi; Dr. Albers, receiving consulting fees from Bayer; Dr. Elliott, receiving fees for serving on a steering committee from Bayer and lecture fees from the University of Cincinnati and Spectrum Health; Dr. Halperin, receiving consulting fees from Boehringer Ingelheim, Daiichi Sankyo, Pfizer, ATLAS Group (Colorado Prevention Center), Johnson & Johnson, and Ortho-McNeil-Janssen; Dr. Hiatt, receiving grant support from Janssen and Bayer; Dr. Steg, receiving grant support and fees for serving on a steering committee from Bayer/Janssen, grant support and lecture fees from Merck, grant support, consulting fees, lecture fees, and fees for serving as cochair of the ODYSSEY outcomes trial and the SCORED trial from Sanofi, grant support and fees for serving as chair of the CLARIFY registry from Servier, consulting fees and fees for serving on the executive steering committee for the REDUCE IT trial from Amarin, consulting fees and lecture fees from Amgen, consulting fees, lecture fees, and fees for critical event committee work from Bristol-Myers Squibb, fees for serving on the executive steering committee of the REDUAL PCI trial from Boehringer Ingelheim, fees for critical event committee work from Pfizer, consulting fees and fees for serving on the executive steering committee for the PARADISE MI trial from Novartis, consulting fees from Regeneron and Lilly, and consulting fees and fees for serving as cochair of the THEMIS trial from AstraZeneca; Dr. Weitz, receiving consulting fees and honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer and Portola; Dr. Suh and Dr. Barnathan, being employed by Janssen Research and Development and owning stock in Johnson & Johnson; Dr. Spiro, being employed by and owning shares in Bayer U.S.; and Dr. Raskob, receiving consulting fees from Bayer, BMS, Boehringer Ingelheim, Eli Lilly, Portola, and Novartis and consulting fees and honoraria from Daiichi Sankyo and Pfizer. No other potential conflict of interest relevant to this article was reported.
- Published
- 2018
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