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1,550 results on '"Forman, S."'

2. The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate‐to‐severe atopic dermatitis: results from a randomized double‐blind placebo‐controlled study

Author

Bissonnette, R, Maari, C, Forman, S, Bhatia, N, Lee, M, Fowler, J, Tyring, S, Pariser, D, Sofen, H, Dhawan, S, Zook, M, Zammit, DJ, Usansky, H, Denis, L, Rao, N, Song, T, Pavel, AB, and Guttman‐Yassky, E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cardiovascular, Prevention, Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Acetonitriles, Adult, Biomarkers, Dermatitis, Atopic, Dose-Response Relationship, Drug, Double-Blind Method, Down-Regulation, E-Selectin, Female, Humans, Janus Kinase Inhibitors, Janus Kinases, Male, Middle Aged, Piperidines, Placebos, Pyridazines, Severity of Illness Index, Signal Transduction, Syk Kinase, Treatment Outcome, Young Adult, Dermatology & Venereal Diseases, Clinical sciences
Abstract

BackgroundASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved in the pathogenesis of atopic dermatitis (AD) through their regulatory role on T helper (Th)1, Th2 and Th17/Th22 pathways.ObjectivesThe objectives of this study were to evaluate the efficacy, safety, pharmacokinetics and effects on systemic biomarkers of ASN002 in patients with moderate-to-severe AD. Methods A total of 36 patients with moderate-to-severe AD were randomized (3 : 1) to ASN002 or placebo in the phase Ib study. Three dosage cohorts were studied over a 28-day period (20 mg, 40 mg and 80 mg once daily).ResultsASN002 was superior to placebo for the proportion of patients achieving Eczema Area and Severity Index (EASI) 50 (20 mg 20%, P = 0·93; 40 mg 100%, P = 0·003; 80 mg 83%, P = 0·03; placebo 22%), EASI 75 (20 mg 0%, P = 0·27; 40 mg 71%, P = 0·06; 80 mg 33%, P = 0·65; placebo 22%) and in change from baseline in pruritus (20 mg -1·3 ± 2·1, P = 0·81; 40 mg -3·1 ± 2·7, P = 0·27; 80 mg -4·7 ± 2·1, P = 0·01; placebo -1·6 ± 1·8). Adverse events were generally mild and similar across all groups. ASN002 showed dose-dependent plasma exposure with low interpatient variability, significantly downregulated several serum biomarkers involved in Th1, Th2 and Th17/Th22 immunity, and decreased the atherosclerosis-associated biomarker E selectin/SELE.ConclusionsIn patients with moderate-to-severe AD, ASN002 showed strong efficacy with rapid onset of action and associated improvements in systemic inflammation.

Published
2019

3. Relating the long-term and short-term vertical deformation across a transect of the forearc in the central Mexican subduction zone

Author

Ramírez-Herrera, MT, Gaidzik, K, Forman, S, Kostoglodov, V, Bürgmann, R, and Johnson, CW

Subjects
Geochemistry & Geophysics, Geochemistry, Geology, Geophysics
Abstract

Earthquake-cycle deformation, which includes earthquake ruptures, interseismic strain, and transient slow slip events, spans spatial scales ranging from fractions of a meter to thousands of kilometers. Similarly, temporal scales range from seconds during an earthquake rupture to thousands of years of strain accumulation between earthquakes. We discuss results regarding the vertical crustal deformation associated with both slow and rapid crustal deformation across a transect of the central Mexican subduction forearc in the Guerrero seismic gap, where the Cocos plate underthrusts the North America plate. This sector of the subduction zone is characterized by a flat-slab geometry with zones of sharp bending-unbending of the slab, irregularly distributed seismicity, and exceptionally large slow slip events. We used the river network, topography, geomorphic features, and morphometry on a transect across the forearc to assess Quaternary crustal deformation. The Papagayo drainage network shows that the forearc has been uplifted since the late Cenozoic (~25 Ma), and that rates of uplift increased since the beginning of the Holocene. Uplift is not homogeneous but shows a trend of increase away from the coast. This vertical deformation is strongly influenced by subduction processes. Thus, the Papagayo River network is strongly controlled by Holocene earthquake cycle processes. This is particularly true for the southern section of the drainage basin, where E-W-striking left-lateral strike-slip faults with a vertical component offset the course of the main river. These faults are accommodating part of the oblique plate convergence at the Mexican subduction zone. We measured the height of a series of terraces and dated quartz extracts by optically stimulated luminescence, and we calculated long-term rates of uplift ranging from 0.5 to 4.9 mm/yr. We discuss associations of forearc topography, faults, and long-term crustal deformation with the Cocos slab geometry, distribution of slow slip events, and earthquake-cycle deformation.

Published
2018

4. LB1702 Lebrikizumab does not impact vaccine-induced immune responses: Results from a phase 3 study in adult patients with moderate-to-severe atopic dermatitis

Author

Soung, J., primary, Laquer, V., additional, Merola, J.F., additional, Forman, S., additional, Elmaraghy, H., additional, Meskimen, E., additional, Hu, C., additional, Natalie, C., additional, Pierce, E., additional, Torisu-Itakura, H., additional, Gil, E., additional, and Jarell, A., additional

Published
2023
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5. The woman voter's manual

Author

Forman, S. E. (Samuel Eagle), 1858-1941., National American Woman Suffrage Association Collection (Library of Congress), Catt, Carrie Chapman, 1859-1947, former owner., Shuler, Marjorie, joint author., and Forman, S. E. (Samuel Eagle), 1858-1941.

Published
1918

9. Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice:: GLORIA-AF Registry

Author

Lip G. Y. H., Kotalczyk A., Teutsch C., Diener H. -C., Dubner S. J., Halperin J. L., Ma C. -S., Rothman K. J., Marler S., Gurusamy V. K., Huisman M. V., Abban D. W., Aziz E., Kalan M. B., Abdul N., Backes L. M., Bradman D., Abud A. M., Badings E., Brautigam D., Adams F., Bagni E., Breton N., Addala S., Baker S. H., Brouwers P. J. A. M., Adragao P., Bala R., Browne K., Ageno W., Baldi A., Cortada J. B., Aggarwal R., Bando S., Bruni A., Agosti S., Banerjee S., Brunschwig C., Agostoni P., Bank A., Buathier H., Aguilar F., Esquivias G. B., Buhl A., Linares J. A., Barr C., Bullinga J., Aguinaga L., Bartlett M., Cabrera J. W., Ahmed J., Basic Kes V., Caccavo A., Aiello A., Baula G., Cai S., Ainsworth P., Behrens S., Caine S., Aiub J. R., Bell A., Calo L., Al-Dallow R., Benedetti R., Calvi V., Alderson L., Mazuecos J. B., Sanchez M. C., Velasco J. A. A., Benhalima B., Candeias R., Alexopoulos D., Bergler-Klein J., Capuano V., Manterola F. A., Berneau J. -B., Capucci A., Aliyar P., Bernstein R. A., Caputo R., Alonso D., Berrospi P., Rizo T. C., da Costa F. A. A., Berti S., Cardona F., Amado J., Berz A., da Costa Darrieux F. C., Amara W., Best E., Vera Y. C. D., Amelot M., Bettencourt P., Carolei A., Amjadi N., Betzu R., Carreno S., Ammirati F., Bhagwat R., Carvalho P., Andrade M., Bhatta L., Cary S., Andrawis N., Biscione F., Casu G., Annoni G., Bisignani G., Cavallini C., Ansalone G., Black T., Cayla G., Ariani M. K., Bloch M. J., Celentano A., Arias J. C., Bloom S., Cha T. -J., Armero S., Blumberg E., Cha K. S., Arora C., Bo M., Chae J. K., Aslam M. S., Bohmer E., Chalamidas K., Asselman M., Bollmann A., Challappa K., Audouin P., Bongiorni M. G., Chand S. P., Augenbraun C., Boriani G., Chandrashekar H., Aydin S., Boswijk D. J., Chartier L., Bott J., Chatterjee K., Ayryanova I., Bottacchi E., Ayala C. A. C., Cheema A., Davis G., Evonich R., Davy J. -M., Evseeva O., Chen L., Dayer M., Ezhov A., Chen S. -A., De Biasio M., Fahmy R., Chen J. H., De Bonis S., Fang Q., Chiang F. -T., De Caterina R., Farsad R., Chiarella F., De Franceschi T., Fauchier L., Chih-Chan L., de Groot J. R., Favale S., Cho Y. K., De Horta J., Fayard M., Choi J. -I., De La Briolle A., Fedele J. L., Choi D. J., de la Pena Topete G., Fedele F., Chouinard G., de Paola A. A. V., Fedorishina O., Chow D. H. -F., de Souza W., Fera S. R., Chrysos D., de Veer A., Ferreira L. G. G., Chumakova G., De Wolf L., Ferreira J., Valenzuela E. J. J. R. C., Decoulx E., Ferri C., Nica N. C., Deepak S., Ferrier A., Cislowski D. J., Defaye P., Ferro H., Clay A., Munoz F. D. -C., Finsen A., Clifford P., Brkljacic D. D., First B., Cohen A., Deumite N. J., Fischer S., Cohen M., Di Legge S., Fonseca C., Cohen S., Diemberger I., Almeida L. F., Colivicchi F., Dietz D., Forman S., Collins R., Dionisio P., Frandsen B., Colonna P., Dong Q., French W., Compton S., dos Santos F. R., Friedman K., Connolly D., Dotcheva E., Friese A., Conti A., Doukky R., Fruntelata A. G., Buenostro G. C., D'Souza A., Fujii S., Coodley G., Dubrey S., Fumagalli S., Cooper M., Ducrocq X., Fundamenski M., Coronel J., Dupljakov D., Furukawa Y., Corso G., Duque M., Gabelmann M., Sales J. C., Dutta D., Gabra N., Cottin Y., Duvilla N., Gadsboll N., Covalesky J., Duygun A., Galinier M., Cracan A., Dziewas R., Gammelgaard A., Crea F., Eaton C. B., Ganeshkumar P., Crean P., Eaves W., Gans C., Crenshaw J., Ebels-Tuinbeek L. A., Quintana A. G., Cullen T., Ehrlich C., Gartenlaub O., Darius H., Eichinger-Hasenauer S., Gaspardone A., Dary P., Eisenberg S. J., Genz C., Dascotte O., Jabali A. E., Georger F., Dauber I., Shahawy M. E., Georges J. -L., Davalos V., Hernandes M. E., Georgeson S., Davies R., Izal A. E., Giedrimas E., Gierba M., Haruna T., Jarmukli N., Ortega I. G., Hayek E., Jeanfreau R. J., Gillespie E., Healey J., Jenkins R. D., Giniger A., Hearne S., Sanchez C. J., Giudici M. C., Heffernan M., Jimenez J., Gkotsis A., Heggelund G., Jobe R., Glotzer T. V., Heijmeriks J. A., Joen-Jakobsen T., Gmehling J., Hemels M., Jones N., Gniot J., Hendriks I., Jorge J. C. M., Goethals P., Henein S., Jouve B., Goldbarg S., Her S. -H., Jung B. C., Goldberg R., Hermany P., Jung K. T., Goldmann B., Del Rio J. E. H., Jung W., Golitsyn S., Higashino Y., Kachkovskiy M., Gomez S., Hill M., Kafkala K., Mesa J. G., Hisadome T., Kalinina L., Gonzalez V. B., Hishida E., Kallmunzer B., Hermosillo J. A. G., Hoffer E., Kamali F., Lopez V. M. G., Hoghton M., Kamo T., Gorka H., Hong K., Kampus P., Gornick C., Hong S., Kashou H., Gorog D., Horbach S., Kastrup A., Gottipaty V., Horiuchi M., Katsivas A., Goube P., Hou Y., Kaufman E., Goudevenos I., Hsing J., Kawai K., Graham B., Huang C. -H., Kawajiri K., Greer G. S., Huckins D., Kazmierski J. F., Gremmler U., Hughes K., Keeling P., Grena P. G., Huizinga A., Saraiva J. F. K., Grond M., Hulsman E. L., Ketova G., Gronda E., Hung K. -C., Khaira A. S., Gronefeld G., Hwang G. -S., Khripun A., Gu X., Ikpoh M., Kim D. -I., Torres I. G. T., Imberti D., Kim Y. H., Guardigli G., Ince H., Kim N. H., Guevara C., Indolfi C., Kim D. K., Guignier A., Inoue S., Kim J. S., Gulizia M., Irles D., Gumbley M., Iseki H., Kim K. S., Gunther A., Israel C. N., Kim J., Ha A., Iteld B., Kinova E., Hahalis G., Iyer V., Klein A., Hakas J., Jackson-Voyzey E., Kmetzo J. J., Hall C., Jaffrani N., Kneller G. L., Han B., Jager F., Knezevic A., Han S., James M., Koh S. M. A., Hargrove J., Jang S. -W., Koide S., Hargroves D., Jaramillo N., Kollias A., Kooistra J. A., Li W., McClure J., Koons J., Li X., McCormack T., Koschutnik M., Lichy C., McGarity W., Kostis W. J., Lieber I., McIntyre H., Kovacic D., Rodriguez R. H. L., McLaurin B., Kowalczyk J., Lin H., Alvaro F., Palomino M., Koziolova N., Melandri F., Kraft P., Liu F., Meno H., Kragten J. A., Liu H., Menzies D., Krantz M., Esperon G. L., Mercader M., Krause L., Navarro N. L., Meyer C., Krenning B. J., Lo E., Meyer B. J., Krikke F., Lokshyn S., Miarka J., Kromhout Z., Lopez A., Mibach F., Krysiak W., Lopez-Sendon J. L., Michalski D., Kumar P., Filho A. M. L., Michel P., Kumler T., Lorraine R. S., Chreih R. M., Kuniss M., Luengas C. A., Luengas A., Mikdadi G., Kuo J. -Y., Luke R., Mikus M., Kuppers A., Luo M., Milicic D., Kurrelmeyer K., Lupovitch S., Militaru C., Kwak C. H., Lyrer P., Minaie S., Laboulle B., Ma C., Minescu B., Labovitz A., Ma G., Mintale I., Ter Lai W., Madariaga I., Mirault T., Lam A., Maeno K., Mirro M. J., Lam Y. Y., Magnin D., Mistry D., Lanas Zanetti F., Maid G., Miu N. V., Landau C., Mainigi S. K., Miyamoto N., Landini G., Makaritsis K., Moccetti T., Lanna Figueiredo E., Malhotra R., Mohammed A., Larsen T., Manning R., Nor A. M., Lavandier K., Manolis A., Mollerus M., LeBlanc J., Hurtado H. A. M., Molon G., Lee M. H., Mantas I., Mondillo S., Lee C. -H., Jattin F. M., Moniz P., Lehman J., Maqueda V., Mont L., Leitao A., Marchionni N., Montagud V., Lellouche N., Ortuno F. M., Montana O., Lelonek M., Santana A. M., Monti C., Lenarczyk R., Martinez J., Moretti L., Lenderink T., Maskova P., Mori K., Gonzalez S. L., Hernandez N. M., Moriarty A., Leong-Sit P., Matsuda K., Morka J., Leschke M., Maurer T., Moschini L., Ley N., Mauro C., Moschos N., Li Z., May E., Mugge A., Mayer N., Mulhearn T. J., Muresan C., Jose E. P., Precoma D. B., Muriago M., Padilla F. G. P., Prelle A., Musial W., Rios V. P., Prodafikas J., Musser C. W., Pajes G., Protasov K., Musumeci F., Pandey A. S., Pye M., Nageh T., Paparella G., Qiu Z., Nakagawa H., Paris F., Quedillac J. -M., Nakamura Y., Park H. W., Raev D., Nakayama T., Park J. S., Grado C. A. R., Nam G. -B., Parthenakis F., Rahimi S., Nanna M., Passamonti E., Raisaro A., Natarajan I., Patel R. J., Rama B., Nayak H. M., Patel J., Ramos R., Naydenov S., Patel M., Ranieri M., Nazlic J., Patrick J., Raposo N., Nechita A. C., Jimenez R. P., Rashba E., Nechvatal L., Paz A., Rauch-Kroehnert U., Negron S. A., Pengo V., Reddy R., Neiman J., Pentz W., Renda G., Neuenschwander F. C., Perez B., Reza S., Neves D., Rios A. M. P., Ria L., Neykova A., Perez-Cabezas A., Richter D., Miguel R. N., Perlman R., Rickli H., Nijmeh G., Persic V., Rieker W., Nizov A., Perticone F., Vera T. R., Campos R. N., Peters T. K., Ritt L. E., Nossan J., Petkar S., Roberts D., Novikova T., Pezo L. F., Briones I. R., Nowalany-Kozielska E., Pflucke C., Escudero A. E. R., Nsah E., Pham D. N., Pascual C. R., Fragoso J. C. N., Phillips R. T., Roman M., Nurgalieva S., Phlaum S., Romeo F., Nuyens D., Pieters D., Ronner E., Nyvad O., Pineau J., Roux J. -F., de Los Rios Ibarra M. O., Pinter A., Rozkova N., O'Donnell P., Pinto F., Rubacek M., O'Donnell M., Pisters R., Rubalcava F., Oh S., Pivac N., Russo A. M., Oh Y. S., Pocanic D., Rutgers M. P., Oh D., Podoleanu C., Rybak K., O'Hara G., Politano A., Said S., Oikonomou K., Poljakovic Z., Sakamoto T., Olivares C., Pollock S., Salacata A., Oliver R., Garcea J. P., Salem A., Ruiz R. O., Poppert H., Bodes R. S., Olympios C., Porcu M., Saltzman M. A., Omaszuk-Kazberuk A., Reino A. P., Salvioni A., Asensi J. O., Prasad N., Vallejo G. S., Fernandez M. S., Sokal A., Tu T. M., Saporito W. F., Yan Y. S. O., Tuininga Y., Sarikonda K., Sotolongo R., Turakhia M., Sasaoka T., de Souza O. F., Turk S., Sati H., Sparby J. A., Turner W., Savelieva I., Spinar J., Tveit A., Scala P. -J., Sprigings D., Tytus R., Schellinger P., Spyropoulos A. C., Valadao C., Scherr C., Stakos D., van Bergen P. F. M. M., Schmitz L., Steinwender C., van de Borne P., Schmitz K. -H., Stergiou G., van den Berg B. J., Schmitz B., Stiell I., van der Zwaan C., Schnabel T., Stoddard M., Van Eck M., Schnupp S., Stoikov A., Vanacker P., Schoeniger P., Streb W., Vasilev D., Schon N., Styliadis I., Vasilikos V., Schwimmbeck P., Su G., Vasilyev M., Seamark C., Su X., Veerareddy S., Searles G., Sudnik W., Mino M. V., Seidl K. -H., Sukles K., Venkataraman A., Seidman B., Sun X., Verdecchia P., Sek J., Swart H., Versaci F., Sekaran L., Szavits-Nossan J., Vester E. G., Serrati C., Taggeselle J., Vial H., Shah N., Takagi Y., Victory J., Shah V., Takhar A. P. S., Villamil A., Shah A., Tamm A., Vincent M., Shah S., Tanaka K., Vlastaris A., Sharma V. K., Tanawuttiwat T., Dahl J., Shaw L., Tang S., Vora K., Sheikh K. H., Tang A., Vranian R. B., Shimizu N., Tarsi G., Wakefield P., Shimomura H., Tassinari T., Wang N., Shin D. -G., Tayal A., Wang M., Shin E. -S., Tayebjee M., Wang X., Shite J., Berg J. M., Wang F., Sibilio G., Tesloianu D., Wang T., Silver F., The S. H. K., Warner A. L., Sime I., Thomas D., Watanabe K., Simmers T. A., Timsit S., Wei J., Singh N., Tobaru T., Weimar C., Siostrzonek P., Tomasik A. R., Weiner S., Smadja D., Torosoff M., Weinrich R., Smith D. W., Touze E., Wen M. -S., Snitman M., Trendafilova E., Wiemer M., Filho D. S., Tsai W. K., Wiggers P., Soda H., Tse H. F., Wilke A., Sofley C., Tsutsui H., Williams D., Williams M. L., Yan P. Y. B., Zhang P., Witzenbichler B., Yang T., Zhang J., Wong B., Yao J., Zhao S. P., Wong K. S. L., Yeh K. -H., Zhao Y., Wozakowska-Kaplon B., Yin W. H., Zhao Z., Wu S., Yotov Y., Zheng Y., Wu R. C., Zahn R., Zhou J., Wunderlich S., Zarich S., Zimmermann S., Wyatt N., Zenin S., Zini A., Wylie J., Zeuthen E. L., Zizzo S., Xu Y., Zhang H., Zong W., Xu X., Zhang D., Zukerman L. S., Yamanoue H., Zhang X., Yamashita T., Cardiology, ACS - Heart failure & arrhythmias, Lip G.Y.H., Kotalczyk A., Teutsch C., Diener H.-C., Dubner S.J., Halperin J.L., Ma C.-S., Rothman K.J., Marler S., Gurusamy V.K., Huisman M.V., Abban D.W., Aziz E., Kalan M.B., Abdul N., Backes L.M., Bradman D., Abud A.M., Badings E., Brautigam D., Adams F., Bagni E., Breton N., Addala S., Baker S.H., Brouwers P.J.A.M., Adragao P., Bala R., Browne K., Ageno W., Baldi A., Cortada J.B., Aggarwal R., Bando S., Bruni A., Agosti S., Banerjee S., Brunschwig C., Agostoni P., Bank A., Buathier H., Aguilar F., Esquivias G.B., Buhl A., Linares J.A., Barr C., Bullinga J., Aguinaga L., Bartlett M., Cabrera J.W., Ahmed J., Basic Kes V., Caccavo A., Aiello A., Baula G., Cai S., Ainsworth P., Behrens S., Caine S., Aiub J.R., Bell A., Calo L., Al-Dallow R., Benedetti R., Calvi V., Alderson L., Mazuecos J.B., Sanchez M.C., Velasco J.A.A., Benhalima B., Candeias R., Alexopoulos D., Bergler-Klein J., Capuano V., Manterola F.A., Berneau J.-B., Capucci A., Aliyar P., Bernstein R.A., Caputo R., Alonso D., Berrospi P., Rizo T.C., da Costa F.A.A., Berti S., Cardona F., Amado J., Berz A., da Costa Darrieux F.C., Amara W., Best E., Vera Y.C.D., Amelot M., Bettencourt P., Carolei A., Amjadi N., Betzu R., Carreno S., Ammirati F., Bhagwat R., Carvalho P., Andrade M., Bhatta L., Cary S., Andrawis N., Biscione F., Casu G., Annoni G., Bisignani G., Cavallini C., Ansalone G., Black T., Cayla G., Ariani M.K., Bloch M.J., Celentano A., Arias J.C., Bloom S., Cha T.-J., Armero S., Blumberg E., Cha K.S., Arora C., Bo M., Chae J.K., Aslam M.S., Bohmer E., Chalamidas K., Asselman M., Bollmann A., Challappa K., Audouin P., Bongiorni M.G., Chand S.P., Augenbraun C., Boriani G., Chandrashekar H., Aydin S., Boswijk D.J., Chartier L., Bott J., Chatterjee K., Ayryanova I., Bottacchi E., Ayala C.A.C., Cheema A., Davis G., Evonich R., Davy J.-M., Evseeva O., Chen L., Dayer M., Ezhov A., Chen S.-A., De Biasio M., Fahmy R., Chen J.H., De Bonis S., Fang Q., Chiang F.-T., De Caterina R., Farsad R., Chiarella F., De Franceschi T., Fauchier L., Chih-Chan L., de Groot J.R., Favale S., Cho Y.K., De Horta J., Fayard M., Choi J.-I., De La Briolle A., Fedele J.L., Choi D.J., de la Pena Topete G., Fedele F., Chouinard G., de Paola A.A.V., Fedorishina O., Chow D.H.-F., de Souza W., Fera S.R., Chrysos D., de Veer A., Ferreira L.G.G., Chumakova G., De Wolf L., Ferreira J., Valenzuela E.J.J.R.C., Decoulx E., Ferri C., Nica N.C., Deepak S., Ferrier A., Cislowski D.J., Defaye P., Ferro H., Clay A., Munoz F.D.-C., Finsen A., Clifford P., Brkljacic D.D., First B., Cohen A., Deumite N.J., Fischer S., Cohen M., Di Legge S., Fonseca C., Cohen S., Diemberger I., Almeida L.F., Colivicchi F., Dietz D., Forman S., Collins R., Dionisio P., Frandsen B., Colonna P., Dong Q., French W., Compton S., dos Santos F.R., Friedman K., Connolly D., Dotcheva E., Friese A., Conti A., Doukky R., Fruntelata A.G., Buenostro G.C., D'Souza A., Fujii S., Coodley G., Dubrey S., Fumagalli S., Cooper M., Ducrocq X., Fundamenski M., Coronel J., Dupljakov D., Furukawa Y., Corso G., Duque M., Gabelmann M., Sales J.C., Dutta D., Gabra N., Cottin Y., Duvilla N., Gadsboll N., Covalesky J., Duygun A., Galinier M., Cracan A., Dziewas R., Gammelgaard A., Crea F., Eaton C.B., Ganeshkumar P., Crean P., Eaves W., Gans C., Crenshaw J., Ebels-Tuinbeek L.A., Quintana A.G., Cullen T., Ehrlich C., Gartenlaub O., Darius H., Eichinger-Hasenauer S., Gaspardone A., Dary P., Eisenberg S.J., Genz C., Dascotte O., Jabali A.E., Georger F., Dauber I., Shahawy M.E., Georges J.-L., Davalos V., Hernandes M.E., Georgeson S., Davies R., Izal A.E., Giedrimas E., Gierba M., Haruna T., Jarmukli N., Ortega I.G., Hayek E., Jeanfreau R.J., Gillespie E., Healey J., Jenkins R.D., Giniger A., Hearne S., Sanchez C.J., Giudici M.C., Heffernan M., Jimenez J., Gkotsis A., Heggelund G., Jobe R., Glotzer T.V., Heijmeriks J.A., Joen-Jakobsen T., Gmehling J., Hemels M., Jones 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Perticone F., Vera T.R., Campos R.N., Peters T.K., Ritt L.E., Nossan J., Petkar S., Roberts D., Novikova T., Pezo L.F., Briones I.R., Nowalany-Kozielska E., Pflucke C., Escudero A.E.R., Nsah E., Pham D.N., Pascual C.R., Fragoso J.C.N., Phillips R.T., Roman M., Nurgalieva S., Phlaum S., Romeo F., Nuyens D., Pieters D., Ronner E., Nyvad O., Pineau J., Roux J.-F., de Los Rios Ibarra M.O., Pinter A., Rozkova N., O'Donnell P., Pinto F., Rubacek M., O'Donnell M., Pisters R., Rubalcava F., Oh S., Pivac N., Russo A.M., Oh Y.S., Pocanic D., Rutgers M.P., Oh D., Podoleanu C., Rybak K., O'Hara G., Politano A., Said S., Oikonomou K., Poljakovic Z., Sakamoto T., Olivares C., Pollock S., Salacata A., Oliver R., Garcea J.P., Salem A., Ruiz R.O., Poppert H., Bodes R.S., Olympios C., Porcu M., Saltzman M.A., Omaszuk-Kazberuk A., Reino A.P., Salvioni A., Asensi J.O., Prasad N., Vallejo G.S., Fernandez M.S., Sokal A., Tu T.M., Saporito W.F., Yan Y.S.O., Tuininga Y., Sarikonda K., Sotolongo R., Turakhia 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Zhang D., Zukerman L.S., Yamanoue H., Zhang X., and Yamashita T.

Subjects
Apixaban, Atrial fibrillation, Dabigatran, Non-vitamin K antagonists, Rivaroxaban, Pyridones, Medizin, Myocardial Infarction, Administration, Oral, Anticoagulants, Hemorrhage, General Medicine, Non-vitamin K antagonist, Stroke, Clinical Trials, Phase III as Topic, Humans, Prospective Studies, Registries, Cardiology and Cardiovascular Medicine
Abstract

Background and purpose Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013. Graphical abstract

Published
2022

10. P1296: SUPPRESSING SYNTHESIS OF THE LONG ISOFORM OF THE PROLACTIN RECEPTOR IS A TARGETED STRATEGY TO TREAT AUTOIMMUNE B-LYMPHOPROLIFERATIVE DISEASES AND B CELL MALIGNANCIES

Author

Taghi Khani, A., primary, Kumar, A., additional, Radecki, K., additional, Lee, S. J., additional, Sanchez Ortiz, A., additional, Lorenson, M., additional, Wu, X., additional, Koff, J., additional, Forman, S., additional, Gu, Z., additional, Walker, A., additional, and Swaminathan, S., additional

Published
2022
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11. PO-1171 Ten-year follow-up of tandem autologous transplantation with total marrow irradiation for myeloma

Author

Ladbury, C., primary, Rincon, A., additional, Song, J., additional, Armenian, S., additional, Liu, A., additional, Spielberger, R., additional, Popplewell, L., additional, Sahebi, F., additional, Parker, P., additional, Forman, S., additional, Snyder, D., additional, Dagis, A., additional, Frankel, P., additional, Yang, D., additional, Wong, J., additional, and Somlo, G., additional

Published
2022
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12. Allogeneic Bone Marrow Transplantation for BCR-ABL Positive Acute Lymphoblastic Leukemia

Author

Snyder, D. S., Nademanee, A. P., O’donnell, M. R., Parker, P. M., Stein, A. S., Margolin, K., Somlo, G., Molina, A., Spielberger, R., Kashyap, A., Fung, H., Vora, N., Slovak, M. L., Niland, J., Palmer, J., Negrin, R. S., Amylon, M. D., Blume, K. G., Forman, S. J., Büchner, T., editor, Hiddemann, W., editor, Wörmann, B., editor, Schellong, G., editor, Ritter, J., editor, and Creutzig, U., editor

Published
2001
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13. Comparing abrocitinib and dupilumab in the treatment of atopic dermatitis: a plain language summary.

Author

Bieber, T, Simpson, EL, Silverberg, JI, Thaçi, D, Paul, C, Pink, AE, Kataoka, Y, Chu, C-Y, DiBonaventura, M, Rojo, R, Antinew, J, Ionita, I, Sinclair, R, Forman, S, Zdybski, J, Biswas, P, Malhotra, B, Zhang, F, Valdez, H, Bieber, T, Simpson, EL, Silverberg, JI, Thaçi, D, Paul, C, Pink, AE, Kataoka, Y, Chu, C-Y, DiBonaventura, M, Rojo, R, Antinew, J, Ionita, I, Sinclair, R, Forman, S, Zdybski, J, Biswas, P, Malhotra, B, Zhang, F, and Valdez, H

Abstract

Atopic dermatitis (AD, also called atopic eczema) is a long-term skin disease that causes intensely itchy, red skin. Healthcare providers can prescribe medicated creams and ointments to reduce the signs and symptoms of AD. However, these treatments are not always enough to provide relief. A new medicine called abrocitinib, which is taken every day as a tablet, reduces part of the body's immune response that happens in AD. The clinical study described in this plain language summary, called JADE COMPARE, investigated how well and how safely 16 weeks of treatment with abrocitinib worked in adults with AD compared to placebo ('dummy treatment') and a medicine that is already approved for AD, called dupilumab. The study showed that abrocitinib was better than placebo in improving the signs and symptoms of AD after 16 weeks. In addition, patients who were taking abrocitinib 200 mg for 2 weeks experienced greater relief from itch than patients who were taking abrocitinib 100 mg, placebo, or dupilumab. More people who took abrocitinib 200 mg reported side effects than those taking abrocitinib 100 mg, placebo, or dupilumab, but most of these side effects were mild or moderate. ClinicalTrials.gov NCT number: NCT03720470.

Published
2022

20. Dapagliflozin and cardiovascular outcomes in type 2 diabetes

Author

Wiviott, S, Raz, I, Bonaca, M, Mosenzon, O, Kato, E, Cahn, A, Silverman, M, Zelniker, T, Kuder, J, Murphy, S, Bhatt, D, Leiter, L, Mcguire, D, Wilding, J, Ruff, C, Nilsson, G, Fredriksson, M, Johansson, P, Langkilde, A, Sabatine, M, Bansilal, S, Furtado, R, Fish, M, Gabovitch, D, Jevne, A, Ahern, S, Im, K, Goodrich, E, Lowe, C, Fisher, N, Gannon, J, Trindade, S, Towarowski, A, Fox, Y, Johnsson, E, Ranft, S, Faber, B, Wallander, M, Weiss, A, Buskila, A, Abola, M, Ardissino, D, Averkov, O, Aylward, P, Bode, C, Bonnici, F, Bonora, E, Budaj, A, Cernea, S, Chiang, C, Cooper, M, Dalby, A, Deerochanawong, C, Dellborg, M, Diaz, R, Dimulescu, D, Eliaschewitz, F, Goudev, A, Hadjadj, S, Herrera, M, Huo, Y, Jermendy, G, Ji, L, Kadowaki, T, Kiss, R, Kooy, A, Kumar, K, Lewis, B, Litwak, L, Lopez-Sendon, J, Ma, R, Merlini, P, Nauck, M, Nguyen, T, Nicolau, J, Ostgren, C, Ophuis, T, Padilla, F, Pais, P, Park, K, Parkhomenko, A, Ray, K, Rosenstock, J, Ruda, M, Satman, I, Shestakova, M, Smahelova, A, Spinar, J, Strojek, K, Sy, R, Tankova, T, Theroux, P, Tkac, I, Van Gaal, L, Wainstein, J, Harrington, R, Droller, M, Lee, K, Nesto, R, Tuomilehto, J, Hedlin, H, Desai, M, Sayfer, I, Alexanian, S, Awtry, E, Bentley-Lewis, R, Berger, C, Croce, K, Desai, A, Garg, R, Gelfand, E, Gignac, G, Goessling, W, Ho, C, Hochberg, E, Lane, A, Larrey, D, Leeman, D, Lewis, J, Link, M, Mcdonnell, M, Norden, A, Pande, A, Rosenberg, C, Rost, N, Ruberg, F, Schiff, E, Silverman, S, Singhal, A, Wagner, A, Wolpin, B, Aizenberg, D, Fernandez, M, Sala, J, Maffei, L, Luquez, C, Waitman, J, Rista, L, Nardone, L, Sposetti, G, Cantero, M, Alvarisqueta, A, Montana, O, Cuadrado, J, Cartasegna, L, Baccaro, C, Chertkoff, A, Sanabria, H, Vainstein, N, Amerena, J, Arya, K, D'Emden, M, Proietto, J, Moses, R, Colquhoun, D, Stranks, S, Lehman, R, Hamilton, A, Whelan, A, Simpson, R, Purnell, P, Abhayaratna, W, Hammett, C, Mckeirnan, M, Sullivan, D, Bach, L, Hughes, K, Mathieu, C, Vercammen, C, Scheen, A, Duyck, F, Cools, F, De Wolf, L, Verhaegen, A, Nobels, F, Missault, L, Crenier, L, Thoeng, J, Wollaert, B, Vandenbroucke, M, Borges, J, Turatti, L, Lima, F, dos Santos, F, Kerr Saraiva, J, Pereira, M, Pereira, A, Precoma, D, Filho, G, Reis, G, Maia, L, Bacheva, T, Temelkova-Kurktschiev, T, Maneva, S, Stoyanovska, B, Boshnyashka, R, Stoykova, Y, Georgiev, D, Tagarev, Z, Dimitrova, E, Vitkina, M, Yordanova, L, Temelkova, M, Vasileva, S, Kuneva, T, Zyumbyuleva, M, Daskalova, I, Genadieva, V, Boyanov, L, Farah, G, Lazarova, G, Georgieva, M, Krasteva, S, Slavcheva, A, Yabroudi, N, Veleva, N, Zlateva, A, Damyanova, V, Elenkova, A, Kotselova, T, Genov, K, Lyubenova, L, Temelkova, N, Harizanova, B, Zaharieva, S, Bajaj, H, Goldenberg, R, Aronson, R, Twum-Barima, D, Dumas, R, Kouz, S, Kaiser, S, Ajala, B, Cha, J, Teitelbaum, I, Chouinard, G, Woo, V, Dan Dattani, I, Mazza, G, Gaudet, D, Poirier, P, Conway, J, Dion, D, Mckeough, M, Manyari, D, Harris, S, St-Pierre, B, Yale, J, Landry, D, Gupta, M, Hramiak, I, Lau, D, 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J., Muirhead N., Zimmermann R., Galiwango P., Tobe S., Priestman B., Zinman B., Ma J., Zhao X., Wang C., Zhang A., Dong Y., Dong X., Luo M., Guo J., Zheng Z., Li Y., Liang Y., Peng D., Maderic D., Spinarova L., Raclavska L., Ludka O., Rihacek I., Karasova J., Pelikanova M., Vlasakova H., Urbancova K., Zamrazil V., Hradec J., Vlasicova H., Racicka E., Okenka L., Naplava R., Skopecek J., Palova S., Krystl T., Pistek Z., Oznerova M., Andresova A., Sarbochova R., Taborska P., Petrova I., Stanek L., Reichert P., Lorenc Z., Szabo M., Petit C., Krempf M., Boye A., Dubois S., Clavel S., Gourdy P., Elbaz M., Jazayeri S., Gouet D., Verges B., Couffinhal T., Sendeski M., Klausmann G., Appel K., Pein M., Thieme R., Schumm-Draeger P., Jacob S., Toursarkissian N., Kleinecke-Pohl U., Tschope D., Ott P., Haak T., Nauck M., Derwahl K., Bugger H., Hui G., Tsang C., Zilahi Z., Puski L., Vangel S., Fulop T., Pall K., Hidvegi T., Revesz K., Koranyi L., Kajetan M., Kerenyi Z., Penzes J., Herczeg B., Laszloczky A., Turi T., Rapi J., Pentek Z., Gaal Z., Winkler G., Percs E., Czigany A., Harcsa E., Gurzo M., Tassaly J., Horthy R., Petro G., Farago K., Muller G., Varju I., Kirschner R., Kiss I., Bakai J., Kancz S., Marton Z., Kodur R., Yajnik C., Thomas N., Ayyar V., Iyengar P., Bashkin A., Daoud D., Itzhak B., Katz A., Tsur A., Nikolsky E., Atar S., Grossman A., Klainman E., Tsalihin D., Shotan A., Turgeman Y., Ferrario M., Merlini P., Piatti P., Zenari L., Trevisan R., Bosco B., Di Lorenzo L., Mannucci E., Avogaro A., Reimers B., Trimarco B., Silvestri O., Salvioni A., Nakagawa H., Sueyoshi A., Fukuda K., Yasumoto H., Matsubayashi S., Kawajiri K., Togashi Y., Senokuchi T., Ohta Y., Yamauchi T., Node K., Alcocer Gamba M., Herrera Marmolejo M., De los Rios Ibarra M., Gonzalez Galvez G., Garcia Cantu E., Leguizamo Dimas A., Luna Ceballos R., Medina Pech C., Stobschinski de Alba C., Gonzalez Gonzalez J., Padilla Padilla F., Fanghanel Salmon G., Robles Torres F., Lopez Rosas E., Pelayo Orozco E., Banda Elizondo R., Escalona Caamano A., Frenk Baron P., Aguilar Salinas C., Mustieles Rocha C., Vidrio Velazquez M., Rodriguez Briones I., Saldate Alonso M., Velasco Sanchez R., Groenemeijer B., Ronner E., Kuijper A., Strikwerda S., Van Kempen W., Gijsbers S., Oude Ophuis A., Swart H., Hoogenberg K., Hovens M., van Hessen M., Westerink J., Kragten J., Nierop P., Bax W., Hartong S., Nieuwdorp M., Gonkel F., Al Windy N., Troquay R., Schaafsma H., Lieverse A., Knufman N., Tirador L., Guenon M., Ferrolino A., Atilano A., Aportadera M., Que M., Denopol M., Tolentino M., Jimeno C., Wee J., Mirasol R., Panelo A., Roxas D., Abola M., Palmes P., Silva A., Salvador D., Rosita R., Maravilla L., Rogelio G., Pacheco E., Tin Hay L., Prado J., Krzyzagorska E., Witek R., Miklaszewicz B., Sudnik W., Pomiecko W., Bochenek A., Fares I., Wujkowski M., Korol M., Powierza S., Goch A., Miekus P., Siegel A., Skierkowska J., Romanczuk P., Cygler J., Landa K., Szyprowska E., Stachlewski P., Czerski T., Pawlowicz L., Sowinski D., Romanowski L., Rudzki H., Skorski M., Jasiel-Wojculewicz H., Stasiewski A., Budaj A., Kania G., Mirek-Bryniarska E., Wojnowski L., Korzeniak R., Oh T., Park K., Lee M., Lee K., Jang H., Kim S., Ku B., Cha B., Son H., Lee I., Park J., Yu S., Shon H., Rhee E., Cho J., Park T., Nam J., Pintilei E., Popescu A., Nafornita V., Gutu O., Dumitrescu A., Bala C., Caceaune E., Mindrescu N., Morosanu M., Bradescu O., Munteanu M., Voitec M., Vlaiculescu M., Hancu N., Diaconu Sotropa M., Lupu S., Mateescu A., Carlan L., Marton R., Lupusoru D., Mot A., Coman A., Zaharie D., Rebrov A., Shutemova E., Bolieva L., Khalimov Y., Statsenko M., Galyavich A., Koziolova N., Shapovalova Y., Pavlysh E., Strongin L., Vertkin A., Vishneva E., Pavlova M., Khasanov N., Antsiferov M., Gavrisheva I., Sokolova N., Vorobyev S., Morugova T., Sinitsina I., Ezhov A., Kobalava Z., Belenkiy D., Supryadkina T., Kazakov Y., Oschepkova E., Dreval A., Novikova T., Vishnevsky A., Chizhov D., Akatova E., Vorokhobina N., Ivanov I., Dudinskaya E., Konstantinov V., Kanderkova D., Pavlik L., Raslova K., Paulovic V., Babikova J., Belesova K., Merciakova M., Truban J., Vargova A., Fabryova L., Slovenska M., Plasil R., Tomasova L., Kollarova D., Spodniakova D., Kosikova M., Dzuponova J., Kurcova I., Skripova D., Gabrisova A., Kalinova S., Ranjith N., Burgess L., Mitha I., Conradie M., Distiller L., Pillai P., Pillay S., Horak A., Nethononda R., van den Berg E., Nortje H., Bayat J., Corbett C., Abelson M., van Zyl L., Pillay T., Wing J., Kapp C., Hidalgo Urbano R., Gonzalez Juanatey J., Blanco Coronado J., Bruguera Cortada J., Ferreiro Gutierrez J., Quesada Simon M., Castro A., Delgado Alvarez E., Freixa R., Boada A., Larnefeldt H., Mooe T., Koskinen P., Lagerback P., Linderfalk C., Liu B., Berndtsson Blom K., Tengmark B., Lindholm C., Ostgren C., Oweling M., Albertsson P., Alvarsson M., Fant S., Berglund O., Hsia C., Chiang C., Fang C., Ueng K., Wang K., Lai W., Mamanasiri S., Wongvipaporn C., Kuanprasert S., Thongsri T., Srimahachota S., Boonyavarakul A., Suwanwalaikorn S., Tantiwong P., Sritara P., Sriwijitkamol A., Sanguanwong S., Chotinaiwattarakul C., Piyayotai D., Balci M., Orbay E., Saygili F., Oguz A., Altuntas Y., Comlekci A., Karpenko O., Tkach S., Vlasenko M., Fushtey I., Pertseva T., Reshotko D., Mostovoy Y., Vizir V., Kraiz I., Amosova K., Batushkin V., Tseluyko V., Koval O., Strang C., Bodalia B., Pieters R., Turner W., Asamoah-Owusu N., White C., Calvert J., McNally D., Jones N., McKaig G., Thompson J., Mohr S., Simpson H., Conn P., McCoye A., Rivero O., Yazdani S., Ince C., Zeitlin J., Wharton T., Platt G., Anderson R. J., Angueira-Serrano E., Lillestol M., Hanlon B., Soufer J., Garcia B., Iteld B., Venugopal C., Ahmed A., Duardo-Guerra Y., Jetty P., Miranda A., Wahlen J., Lederman S., Cohen K., Lake L., French W. J., Tahirkheli N., Baker S., Stoltz R., Wilson J., Nadar V., Brown J., Larrain G., Wiseman A., Ruoff G., Williams M., Tan A., Hartman I., Singh N., Graf R., Wakefield P., McNeill R., Byars W., Reyes Almodovar R., Jones S., Kantaros L., Hegedosh N., Graves M., Bernstein M., Falkowski S., Bialow M., Paraschos A., Dagher G., Arif A., Condit J., Chaykin L., Grunstra B., Earl J., Unks D., Srivastava S., Benson M., Huffman C., Miller G., Willis J., Bender K., Martin E., Blackmore R., Rohr K., Chilka S., Gadowski G., Fitz-Patrick D., Benjamin S., Morin D., Zias Dilena A., Acosta R., Claassen D., Miranda F., Raad G., Inzerello A., Porter J., Bhattacharya A., Gutmann J., Korpas D., Syed M., Zieve F., Raisinghani A., Alam S., Bartkowiak A., Boccalandro F., Talano J., Mercado A., Krichmar P., Oldfield C., Adams K., Gorman T., Lewis D., Shah R., Shockey G., Lefebvre G., Andrawis N., Tami L., Bittar N., Khan M. S., Rink L., Hendrix E., Wood J., Robinson J., Pavon H., Irfan M., Gonzalez E., Singal R., Shore K., Saba F., Bianco J., Erickson B., Gorson D., Puri S., Arauz-Pacheco C., Forman S., Akyea-Djamson A., Lieber I., Barker B., Desai P., Sotolongo C., Steinhoff J., Hill R., Radin M., Patel R., Lieberman S., Wenocur H., Dagogo-Jack S., Lupovitch S., Ison R., Bacharach J. M., Diogo J., Mazzella M., Greenwald J., Quadrel M., Mayer N., Datu J., McCartney M., Bruce T., Singal D., Turner J., Videau B., Fritz R., Fox D., Calatayud G., Sheldon W., Kereiakes D., Thomas J., Salacata A., McCullum K., Harris B., de Souza J., Rahman A., Blumenthal S., Narayan P., Bloch M., Augenbraun C., Bernstein R., Perlman R., Berman J., LaBryer L., Wynne A., Fish J., Zarich S., Gabra N., Popeil L., Hermany P., Barreto A., Pomposini D., Gonzalez-Campoy J. M., Langer M., Bayron C., Suneja R., Kamlet J., Wheeler K., Hurley S., Sharma S., Wefald F., Hershon K., O'Connor T., Pueblitz G., Laguerre J., Amin M., Alfonso T., Jaffrani N., Isserman S., Portnay E., Vlastaris A., Dy J., Hagan M., Noveck H., Kraft P., Andersen J., Foley B., Carr K., Gelormini J., Williams T., Landau C., Richwine R., Thakkar M., Karim A., Madhun Z., Francyk D., Lamantia J., Baker B., Zhang W., Lev V., Hasan M., Captain A., Herzog W., Friedman K., Lawson W., Desai V., Ow C., Simons R., Mandviwala M., Le T., Hack T., Zebrack J., Henderson D., DeJulia J., Mehta R., Reza S., Poonawala R., Awad A., Velasquez M., Mohiuddin S., Salazar Sharma M., Myrick G., Gottlieb D., Ovalle F., Alfieri A., Ahmed S., Bohula E., Donahoe S. M., Longshaw K., Eshaghian S., Lash J., Goldberg R. K., Fox B., Mostel E., Dobies D., Ward H., Burbano J., Puleo P., Lenhard M. J., Korn D., Thadani U., Bradley A., Kmetzo J., Heasley E., Raikhel M., Mahr N., Bittar G., Fuentes F., Raghu P., Diep T. T. B., Tran Q. K., Tran N., Nguyen D., and Nguyen V.

Abstract

BACKGROUND The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. METHODS We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to ≥60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. RESULTS We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], ≥1.3; P≥0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P = 0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P = 0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87)

Published
2019

30. Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis

Author

Bieber, T, Simpson, EL, Silverberg, JI, Thaci, D, Paul, C, Pink, AE, Kataoka, Y, Chu, C-Y, DiBonaventura, M, Rojo, R, Antinew, J, Ionita, I, Sinclair, R, Forman, S, Zdybski, J, Biswas, P, Malhotra, B, Zhang, F, Valdez, H, Bieber, T, Simpson, EL, Silverberg, JI, Thaci, D, Paul, C, Pink, AE, Kataoka, Y, Chu, C-Y, DiBonaventura, M, Rojo, R, Antinew, J, Ionita, I, Sinclair, R, Forman, S, Zdybski, J, Biswas, P, Malhotra, B, Zhang, F, and Valdez, H

Abstract

BACKGROUND: The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited. METHODS: In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16. RESULTS: A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P<0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P<0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superio

Published
2021

31. Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation: The GLORIA-AF registry

Author

Ntaios, G., Huisman, M. V., Diener, H. -C., Halperin, J. L., Teutsch, C., Marler, S., Gurusamy, V. K., Thompson, M., Lip, G. Y. H., Olshansky, B., Abban, D. W., Abdul, N., Abud, A. M., Adams, F., Addala, S., Adragao, P., Ageno, W., Aggarwal, R., Agosti, S., Agostoni, P., Aguilar, F., Linares, J. A., Aguinaga, L., Ahmed, J., Aiello, A., Ainsworth, P., Aiub, J. R., Al-Dallow, R., Alderson, L., Aldrete Velasco, J. A., Alexopoulos, D., Manterola, F. A., Aliyar, P., Alonso, D., Alves da Costa, F. A., Amado, J., Amara, W., Amelot, M., Amjadi, N., Ammirati, F., Andrade, M., Andrawis, N., Annoni, G., Ansalone, G., Ariani, M. K., Arias, J. C., Armero, S., Arora, C., Aslam, M. S., Asselman, M., Audouin, P., Augenbraun, C., Aydin, S., Ayryanova, I., Aziz, E., Backes, L. M., Badings, E., Bagni, E., Baker, S. H., Bala, R., Baldi, A., Bando, S., Banerjee, S., Bank, A., Esquivias, G. B., Barr, C., Bartlett, M., Kes, V. B., Baula, G., Behrens, S., Bell, A., Benedetti, R., Mazuecos, J. B., Benhalima, B., Bergler-Klein, J., Berneau, J. -B., Bernstein, R. A., Berrospi, P., Berti, S., Berz, A., Best, E., Bettencourt, P., Betzu, R., Bhagwat, R., Bhatta, L., Biscione, F., Bisignani, G., Black, T., Bloch, M. J., Bloom, S., Blumberg, E., Bo, M., Bohmer, E., Bollmann, A., Bongiorni, M. G., Boriani, G., Boswijk, D. J., Bott, J., Bottacchi, E., Kalan, M. B., Bradman, D., Brautigam, D., Breton, N., Brouwers, P. J. A. M., Browne, K., Cortada, J. B., Bruni, A., Brunschwig, C., Buathier, H., Buhl, A., Bullinga, J., Cabrera, J. W., Caccavo, A., Cai, S., Caine, S., Calo, L., Calvi, V., Sanchez, M. C., Candeias, R., Capuano, V., Capucci, A., Caputo, R., Rizo, T. C., Cardona, F., Carlos da Costa Darrieux, F., Duarte Vera, Y. C., Carolei, A., Carreno, S., Carvalho, P., Cary, S., Casu, G., Cavallini, C., Cayla, G., Celentano, A., Cha, T. -J., Cha, K. S., Chae, J. K., Chalamidas, K., Challappa, K., Chand, S. P., Chandrashekar, H., Chartier, L., Chatterjee, K., Chavez Ayala, C. A., Cheema, A., Chen, L., Chen, S. -A., Chen, J. H., Chiang, F. -T., Chiarella, F., Chih-Chan, L., Cho, Y. K., Choi, J. -I., Choi, D. J., Chouinard, G., Hoi-Fan Chow, D., Chrysos, D., Chumakova, G., Jose Roberto Chuquiure Valenzuela, E. J., Nica, N. C., Cislowski, D. J., Clay, A., Clifford, P., Cohen, A., Cohen, M., Cohen, S., Colivicchi, F., Collins, R., Colonna, P., Compton, S., Connolly, D., Conti, A., Buenostro, G. C., Coodley, G., Cooper, M., Coronel, J., Corso, G., Sales, J. C., Cottin, Y., Covalesky, J., Cracan, A., Crea, Filippo, Crean, P., Crenshaw, J., Cullen, T., Darius, H., Dary, P., Dascotte, O., Dauber, I., Davalos, V., Davies, R., Davis, G., Davy, J. -M., Dayer, M., De Biasio, M., De Bonis, S., De Caterina, R., De Franceschi, T., de Groot, J. R., De Horta, J., De La Briolle, A., Topete, G. D. L. P., Vicenzo de Paola, A. A., de Souza, W., de Veer, A., De Wolf, L., Decoulx, E., Deepak, S., Defaye, P., Del-Carpio Munoz, F., Brkljacic, D. D., Deumite, N. J., Di Legge, S., Diemberger, I., Dietz, D., Dionisio, P., Dong, Q., Rossi dos Santos, F., Dotcheva, E., Doukky, R., D'Souza, A., Dubrey, S., Ducrocq, X., Dupljakov, D., Duque, M., Dutta, D., Duvilla, N., Duygun, A., Dziewas, R., Eaton, C. B., Eaves, W., Ebels-Tuinbeek, L. A., Ehrlich, C., Eichinger-Hasenauer, S., Eisenberg, S. J., El Jabali, A., El Shahawy, M., Hernandes, M. E., Izal, A. E., Evonich, R., Evseeva, O., Ezhov, A., Fahmy, R., Fang, Q., Farsad, R., Fauchier, L., Favale, S., Fayard, M., Fedele, J. L., Fedele, F., Fedorishina, O., Fera, S. R., Gomes Ferreira, L. G., Ferreira, J., Ferri, C., Ferrier, A., Ferro, H., Finsen, A., First, B., Fischer, S., Fonseca, C., Almeida, L. F., Forman, S., Frandsen, B., French, W., Friedman, K., Friese, A., Fruntelata, A. G., Fujii, S., Fumagalli, S., Fundamenski, M., Furukawa, Y., Gabelmann, M., Gabra, N., Gadsboll, N., Galinier, M., Gammelgaard, A., Ganeshkumar, P., Gans, C., Quintana, A. G., Gartenlaub, O., Gaspardone, A., Genz, C., Georger, F., Georges, J. -L., Georgeson, S., Giedrimas, E., Gierba, M., Ortega, I. G., Gillespie, E., Giniger, A., Giudici, M. C., Gkotsis, A., Glotzer, T. V., Gmehling, J., Gniot, J., Goethals, P., Goldbarg, S., Goldberg, R., Goldmann, B., Golitsyn, S., Gomez, S., Mesa, J. G., Gonzalez, V. B., Gonzalez Hermosillo, J. A., Gonzalez Lopez, V. M., Gorka, H., Gornick, C., Gorog, D., Gottipaty, V., Goube, P., Goudevenos, I., Graham, B., Greer, G. S., Gremmler, U., Grena, P. G., Grond, M., Gronda, E., Gronefeld, G., Gu, X., Torres Torres, I. G., Guardigli, G., Guevara, C., Guignier, A., Gulizia, M., Gumbley, M., Gunther, A., Ha, A., Hahalis, G., Hakas, J., Hall, C., Han, B., Han, S., Hargrove, J., Hargroves, D., Harris, K. B., Haruna, T., Hayek, E., Healey, J., Hearne, S., Heffernan, M., Heggelund, G., Heijmeriks, J. A., Hemels, M., Hendriks, I., Henein, S., Her, S. -H., Hermany, P., Hernandez Del Rio, J. E., Higashino, Y., Hill, M., Hisadome, T., Hishida, E., Hoffer, E., Hoghton, M., Hong, K., Hong, S. K., Horbach, S., Horiuchi, M., Hou, Y., Hsing, J., Huang, C. -H., Huckins, D., Kathy, Hughe, Huizinga, A., Hulsman, E. L., Hung, K. -C., Hwang, G. -S., Ikpoh, M., Imberti, D., Ince, H., Indolfi, C., Inoue, S., Irles, D., Iseki, H., Israel, C. N., Iteld, B., Iyer, V., Jackson-Voyzey, E., Jaffrani, N., Jager, F., James, M., Jang, S. -W., Jaramillo, N., Jarmukli, N., Jeanfreau, R. J., Jenkins, R. D., Sanchez, C. J., Jimenez, J., Jobe, R., Joen-Jakobsen, T., Jones, N., Moura Jorge, J. C., Jouve, B., Jung, B. C., Jung, K. T., Jung, W., Kachkovskiy, M., Kafkala, K., Kalinina, L., Kallmunzer, B., Kamali, F., Kamo, T., Kampus, P., Kashou, H., Kastrup, A., Katsivas, A., Kaufman, E., Kawai, K., Kawajiri, K., Kazmierski, J. F., Keeling, P., Kerr Saraiva, J. F., Ketova, G., Khaira, A. S., Khripun, A., Kim, D. -I., Kim, Y. H., Kim, N. H., Kim, D. K., Kim, J. S., Kim, K. S., Kim, J. 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M., Mollerus, M., Molon, G., Mondillo, S., Moniz, P., Mont, L., Montagud, V., Montana, O., Monti, C., Moretti, L., Mori, K., Moriarty, A., Morka, J., Moschini, L., Moschos, N., Mugge, A., Mulhearn, T. J., Muresan, C., Muriago, M., Musial, W., Musser, C. W., Musumeci, F., Nageh, T., Nakagawa, H., Nakamura, Y., Nakayama, T., Nam, G. -B., Nanna, M., Natarajan, I., Nayak, H. M., Naydenov, S., Nazli, J., Nechita, A. C., Nechvatal, L., Negron, S. A., Neiman, J., Neuenschwander, F. C., Neves, D., Neykova, A., Miguel, R. N., Nijmeh, G., Nizov, A., Campos, R. N., Nossan, J., Novikova, T., Nowalany-Kozielska, E., Nsah, E., Nunez Fragoso, J. C., Nurgalieva, S., Nuyens, D., Nyvad, O., Odin de Los Rios Ibarra, M., O'Donnell, P., O'Donnell, M., Oh, S., Oh, Y. S., Oh, D., O'Hara, G., Oikonomou, K., Olivares, C., Oliver, R., Ruiz, R. O., Olympios, C., Anna, omaszuk-Kazberuk, Asensi, J. O., eena Padayattil, Jose, Padilla Padilla, F. G., Rios, V. P., Pajes, G., Pandey, A. S., Paparella, G., Paris, F., Park, H. W., Park, J. S., Parthenakis, F., Passamonti, E., Patel, R. J., Patel, J., Patel, M., Patrick, J., Jimenez, R. P., Paz, A., Pengo, V., Pentz, W., Perez, B., Perez Rios, A. M., Perez-Cabezas, A., Perlman, R., Persic, V., Perticone, F., Peters, T. K., Petkar, S., Pezo, L. F., Pflucke, C., Pham, D. N., Phillips, R. T., Phlaum, S., Pieters, D., Pineau, J., Pinter, A., Pinto, F., Pisters, R., Pivac, N., Pocanic, D., Podoleanu, C., Politano, A., Poljakovic, Z., Pollock, S., Garcea, J. P., Poppert, H., Porcu, M., Reino, A. P., Prasad, N., Precoma, D. B., Prelle, A., Prodafikas, J., Protasov, K., Pye, M., Qiu, Z., Quedillac, J. -M., Raev, D., Raffo Grado, C. A., Rahimi, S., Raisaro, A., Rama, B., Ramos, R., Ranieri, M., Raposo, N., Rashba, E., Rauch-Kroehnert, U., Reddy, R., Renda, G., Reza, S., Ria, L., Richter, D., Rickli, H., Rieker, W., Vera, T. R., Ritt, L. E., Roberts, D., Briones, I. R., Rodriguez Escudero, A. E., Pascual, C. 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V., Vora, K., Vranian, R. B., Wakefield, P., Wang, N., Wang, M., Wang, X., Wang, F., Wang, T., Warner, A. L., Watanabe, K., Wei, J., Weimar, C., Weiner, S., Weinrich, R., Wen, M. -S., Wiemer, M., Wiggers, P., Wilke, A., Williams, D., Williams, M. L., Witzenbichler, B., Wong, B., Lawrence Wong, K. S., Wozakowska-Kaplon, B., Wu, S., Wu, R. C., Wunderlich, S., Wyatt, N., Wylie, J. J., Xu, Y., Xu, X., Yamanoue, H., Yamashita, T., Bryan Yan, P. Y., Yang, T., Yao, J., Yeh, K. -H., Yin, W. H., Yotov, Y., Zahn, R., Zarich, S., Zenin, S., Zeuthen, E. L., Zhang, H., Zhang, D., Zhang, X., Zhang, P., Zhang, J., Zhao, S. P., Zhao, Y., Zhao, Z., Zheng, Y., Zhou, J., Zimmermann, S., Zini, A., Zizzo, S., Zong, W., Zukerman, L. S., and Crea F. (ORCID:0000-0001-9404-8846)

Abstract

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.

Published
2021

42. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes

Author

Wiviott S. D., Raz I., Bonaca M. P., Mosenzon O., Kato E. T., Cahn A., Silverman M. G., Zelniker T. A., Kuder J. F., Murphy S. A., Bhatt D. L., Leiter L. A., McGuire D. K., Wilding J. P. H., Ruff C. T., Nilsson G. I., Fredriksson M., Johansson P. A., Langkilde A. M., Sabatine M. S., Bansilal S., Furtado R., Fish M. P., Gabovitch D., Jevne A., Ahern S., Im K., Goodrich E. L., Lowe C., Fisher N., Gannon J., Trindade S., Towarowski A., Fox Y., Johnsson E., Ranft S., Faber B., Wallander M., Weiss A., Buskila A., Abola M. T. B., Ardissino D., Averkov O., Aylward P., Bode C., Bonnici F., Bonora E., Budaj A. J., Cernea S., Chiang C. E., Cooper M., Dalby A., Deerochanawong C., Dellborg M., Diaz R., Dimulescu D., Eliaschewitz F. G., Goudev A. R., Hadjadj S., Herrera M., Huo Y., Jermendy G., Ji L., Kadowaki T., Kiss R., Kooy A., Kumar K. M. P., Lewis B., Litwak L., Lopez-Sendon J., Ma R., Merlini P. A., Nauck M. A., Nguyen T. K., Nicolau J. C., Ostgren C. J., Ophuis T. O., Padilla F., Pais P., Park K. S., Parkhomenko A., Ray K., Rosenstock J., Ruda M., Satman I., Shestakova M., Smahelova A., Spinar J., Strojek K., Sy R., Tankova T., Theroux P., Tkac I., Van Gaal L., Wainstein J., Harrington R. A., Droller M. J., Lee K. L., Nesto R. W., Tuomilehto J., Hedlin H., Desai M., Sayfer I., Alexanian S., Awtry E., Bentley-Lewis R., Berger C. J., Croce K., Desai A., Garg R. K., Gelfand E., Gignac G., Goessling W., Ho C., Hochberg E., Lane A., Larrey D., Leeman D. E., Lewis J., Link M. S., McDonnell M. E., Norden A. 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K., Tran N., Nguyen D., Nguyen V., Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), VA Boston Healthcare System, Turbulence Research Laboratory [Goteborg], Chalmers University of Technology [Göteborg], Wiviott, S, Raz, I, Bonaca, M, Mosenzon, O, Kato, E, Cahn, A, Silverman, M, Zelniker, T, Kuder, J, Murphy, S, Bhatt, D, Leiter, L, Mcguire, D, Wilding, J, Ruff, C, Nilsson, G, Fredriksson, M, Johansson, P, Langkilde, A, Sabatine, M, Bansilal, S, Furtado, R, Fish, M, Gabovitch, D, Jevne, A, Ahern, S, Im, K, Goodrich, E, Lowe, C, Fisher, N, Gannon, J, Trindade, S, Towarowski, A, Fox, Y, Johnsson, E, Ranft, S, Faber, B, Wallander, M, Weiss, A, Buskila, A, Abola, M, Ardissino, D, Averkov, O, Aylward, P, Bode, C, Bonnici, F, Bonora, E, Budaj, A, Cernea, S, Chiang, C, Cooper, M, Dalby, A, Deerochanawong, C, Dellborg, M, Diaz, R, Dimulescu, D, Eliaschewitz, F, Goudev, A, Hadjadj, S, Herrera, M, Huo, Y, Jermendy, G, Ji, L, Kadowaki, T, Kiss, R, Kooy, A, Kumar, K, 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J, Moses, R, Colquhoun, D, Stranks, S, Lehman, R, Hamilton, A, Whelan, A, Simpson, R, Purnell, P, Abhayaratna, W, Hammett, C, Mckeirnan, M, Sullivan, D, Bach, L, Hughes, K, Mathieu, C, Vercammen, C, Scheen, A, Duyck, F, Cools, F, De Wolf, L, Verhaegen, A, Nobels, F, Missault, L, Crenier, L, Thoeng, J, Wollaert, B, Vandenbroucke, M, Borges, J, Turatti, L, Lima, F, dos Santos, F, Kerr Saraiva, J, Pereira, M, Pereira, A, Precoma, D, Filho, G, Reis, G, Maia, L, Bacheva, T, Temelkova-Kurktschiev, T, Maneva, S, Stoyanovska, B, Boshnyashka, R, Stoykova, Y, Georgiev, D, Tagarev, Z, Dimitrova, E, Vitkina, M, Yordanova, L, Temelkova, M, Vasileva, S, Kuneva, T, Zyumbyuleva, M, Daskalova, I, Genadieva, V, Boyanov, L, Farah, G, Lazarova, G, Georgieva, M, Krasteva, S, Slavcheva, A, Yabroudi, N, Veleva, N, Zlateva, A, Damyanova, V, Elenkova, A, Kotselova, T, Genov, K, Lyubenova, L, Temelkova, N, Harizanova, B, Zaharieva, S, Bajaj, H, Goldenberg, R, Aronson, R, Twum-Barima, D, Dumas, R, Kouz, S, Kaiser, S, Ajala, B, Cha, J, Teitelbaum, I, Chouinard, G, Woo, V, Dan Dattani, I, Mazza, G, Gaudet, D, Poirier, P, Conway, J, Dion, D, Mckeough, M, Manyari, D, Harris, S, St-Pierre, B, Yale, J, Landry, D, Gupta, M, Hramiak, I, Lau, D, Degrace, M, Gallo, R, Montigny, M, Dzongowski, P, Liutkus, J, Frechette, A, Gosselin, G, Sabbah, E, Langlois, M, Rabasa-Lhoret, R, Bedard, J, Hart, R, Dowell, A, Pandey, A, O'Keefe, D, Hill, L, Weisnagel, S, Muirhead, N, Zimmermann, R, Galiwango, P, Tobe, S, Priestman, B, Zinman, B, Ma, J, Zhao, X, Wang, C, Zhang, A, Dong, Y, Dong, X, Luo, M, Guo, J, Zheng, Z, Li, Y, Liang, Y, Peng, D, Maderic, D, Spinarova, L, Raclavska, L, Ludka, O, Rihacek, I, Karasova, J, Pelikanova, M, Vlasakova, H, Urbancova, K, Zamrazil, V, Hradec, J, Vlasicova, H, Racicka, E, Okenka, L, Naplava, R, Skopecek, J, Palova, S, Krystl, T, Pistek, Z, Oznerova, M, Andresova, A, Sarbochova, R, Taborska, P, Petrova, I, Stanek, L, Reichert, P, Lorenc, Z, Szabo, M, Petit, C, Krempf, M, Boye, A, Dubois, S, Clavel, S, Gourdy, P, Elbaz, M, Jazayeri, S, Gouet, D, Verges, B, Couffinhal, T, Sendeski, M, Klausmann, G, Appel, K, Pein, M, Thieme, R, Schumm-Draeger, P, Jacob, S, Toursarkissian, N, Kleinecke-Pohl, U, Tschope, D, Ott, P, Haak, T, Derwahl, K, Bugger, H, Hui, G, Tsang, C, Zilahi, Z, Puski, L, Vangel, S, Fulop, T, Pall, K, Hidvegi, T, Revesz, K, Koranyi, L, Kajetan, M, Kerenyi, Z, Penzes, J, Herczeg, B, Laszloczky, A, Turi, T, Rapi, J, Pentek, Z, Gaal, Z, Winkler, G, Percs, E, Czigany, A, Harcsa, E, Gurzo, M, Tassaly, J, Horthy, R, Petro, G, Farago, K, Muller, G, Varju, I, Kirschner, R, Kiss, I, Bakai, J, Kancz, S, Marton, Z, Kodur, R, Yajnik, C, Thomas, N, Ayyar, V, Iyengar, P, Bashkin, A, Daoud, D, Itzhak, B, Katz, A, Tsur, A, Nikolsky, E, Atar, S, Grossman, A, Klainman, E, Tsalihin, D, Shotan, A, Turgeman, Y, Ferrario, M, Piatti, P, Zenari, L, Trevisan, R, Bosco, B, Di Lorenzo, L, Mannucci, E, Avogaro, A, Reimers, B, Trimarco, B, Silvestri, O, Salvioni, A, Nakagawa, H, Sueyoshi, A, Fukuda, K, Yasumoto, H, Matsubayashi, S, Kawajiri, K, Togashi, Y, Senokuchi, T, Ohta, Y, Yamauchi, T, Node, K, Alcocer Gamba, M, Herrera Marmolejo, M, De los Rios Ibarra, M, Gonzalez Galvez, G, Garcia Cantu, E, Leguizamo Dimas, A, Luna Ceballos, R, Medina Pech, C, Stobschinski de Alba, C, Gonzalez Gonzalez, J, Padilla Padilla, F, Fanghanel Salmon, G, Robles Torres, F, Lopez Rosas, E, Pelayo Orozco, E, Banda Elizondo, R, Escalona Caamano, A, Frenk Baron, P, Aguilar Salinas, C, Mustieles Rocha, C, Vidrio Velazquez, M, Rodriguez Briones, I, Saldate Alonso, M, Velasco Sanchez, R, Groenemeijer, B, Ronner, E, Kuijper, A, Strikwerda, S, Van Kempen, W, Gijsbers, S, Oude Ophuis, A, Swart, H, Hoogenberg, K, Hovens, M, van Hessen, M, Westerink, J, Kragten, J, Nierop, P, Bax, W, Hartong, S, Nieuwdorp, M, Gonkel, F, Al Windy, N, Troquay, R, Schaafsma, H, Lieverse, A, Knufman, N, Tirador, L, Guenon, M, Ferrolino, A, Atilano, A, Aportadera, M, Que, M, Denopol, M, Tolentino, M, Jimeno, C, Wee, J, Mirasol, R, Panelo, A, Roxas, D, Palmes, P, Silva, A, Salvador, D, Rosita, R, Maravilla, L, Rogelio, G, Pacheco, E, Tin Hay, L, Prado, J, Krzyzagorska, E, Witek, R, Miklaszewicz, B, Sudnik, W, Pomiecko, W, Bochenek, A, Fares, I, Wujkowski, M, Korol, M, Powierza, S, Goch, A, Miekus, P, Siegel, A, Skierkowska, J, Romanczuk, P, Cygler, J, Landa, K, Szyprowska, E, Stachlewski, P, Czerski, T, Pawlowicz, L, Sowinski, D, Romanowski, L, Rudzki, H, Skorski, M, Jasiel-Wojculewicz, H, Stasiewski, A, Kania, G, Mirek-Bryniarska, E, Wojnowski, L, Korzeniak, R, Oh, T, Lee, M, Jang, H, Kim, S, Ku, B, Cha, B, Son, H, Lee, I, Park, J, Yu, S, Shon, H, Rhee, E, Cho, J, Park, T, Nam, J, Pintilei, E, Popescu, A, Nafornita, V, Gutu, O, Dumitrescu, A, Bala, C, Caceaune, E, Mindrescu, N, Morosanu, M, Bradescu, O, Munteanu, M, Voitec, M, Vlaiculescu, M, Hancu, N, Diaconu Sotropa, M, Lupu, S, Mateescu, A, Carlan, L, Marton, R, Lupusoru, D, Mot, A, Coman, A, Zaharie, D, Rebrov, A, Shutemova, E, Bolieva, L, Khalimov, Y, Statsenko, M, Galyavich, A, Koziolova, N, Shapovalova, Y, Pavlysh, E, Strongin, L, Vertkin, A, Vishneva, E, Pavlova, M, Khasanov, N, Antsiferov, M, Gavrisheva, I, Sokolova, N, Vorobyev, S, Morugova, T, Sinitsina, I, Ezhov, A, Kobalava, Z, Belenkiy, D, Supryadkina, T, Kazakov, Y, Oschepkova, E, Dreval, A, Novikova, T, Vishnevsky, A, Chizhov, D, Akatova, E, Vorokhobina, N, Ivanov, I, Dudinskaya, E, Konstantinov, V, Kanderkova, D, Pavlik, L, Raslova, K, Paulovic, V, Babikova, J, Belesova, K, Merciakova, M, Truban, J, Vargova, A, Fabryova, L, Slovenska, M, Plasil, R, Tomasova, L, Kollarova, D, Spodniakova, D, Kosikova, M, Dzuponova, J, Kurcova, I, Skripova, D, Gabrisova, A, Kalinova, S, Ranjith, N, Burgess, L, Mitha, I, Conradie, M, Distiller, L, Pillai, P, Pillay, S, Horak, A, Nethononda, R, van den Berg, E, Nortje, H, Bayat, J, Corbett, C, Abelson, M, van Zyl, L, Pillay, T, Wing, J, Kapp, C, Hidalgo Urbano, R, Gonzalez Juanatey, J, Blanco Coronado, J, Bruguera Cortada, J, Ferreiro Gutierrez, J, Quesada Simon, M, Castro, A, Delgado Alvarez, E, Freixa, R, Boada, A, Larnefeldt, H, Mooe, T, Koskinen, P, Lagerback, P, Linderfalk, C, Liu, B, Berndtsson Blom, K, Tengmark, B, Lindholm, C, Oweling, M, Albertsson, P, Alvarsson, M, Fant, S, Berglund, O, Hsia, C, Fang, C, Ueng, K, Wang, K, Lai, W, Mamanasiri, S, Wongvipaporn, C, Kuanprasert, S, Thongsri, T, Srimahachota, S, Boonyavarakul, A, Suwanwalaikorn, S, Tantiwong, P, Sritara, P, Sriwijitkamol, A, Sanguanwong, S, Chotinaiwattarakul, C, Piyayotai, D, Balci, M, Orbay, E, Saygili, F, Oguz, A, Altuntas, Y, Comlekci, A, Karpenko, O, Tkach, S, Vlasenko, M, Fushtey, I, Pertseva, T, Reshotko, D, Mostovoy, Y, Vizir, V, Kraiz, I, Amosova, K, Batushkin, V, Tseluyko, V, Koval, O, Strang, C, Bodalia, B, Pieters, R, Turner, W, Asamoah-Owusu, N, White, C, Calvert, J, Mcnally, D, Jones, N, Mckaig, G, Thompson, J, Mohr, S, Simpson, H, Conn, P, Mccoye, A, Rivero, O, Yazdani, S, Ince, C, Zeitlin, J, Wharton, T, Platt, G, Anderson, R, Angueira-Serrano, E, Lillestol, M, Hanlon, B, Soufer, J, Garcia, B, Iteld, B, Venugopal, C, Ahmed, A, Duardo-Guerra, Y, Jetty, P, Miranda, A, Wahlen, J, Lederman, S, Cohen, K, Lake, L, French, W, Tahirkheli, N, Baker, S, Stoltz, R, Wilson, J, Nadar, V, Brown, J, Larrain, G, Wiseman, A, Ruoff, G, Williams, M, Tan, A, Hartman, I, Singh, N, Graf, R, Wakefield, P, Mcneill, R, Byars, W, Reyes Almodovar, R, Jones, S, Kantaros, L, Hegedosh, N, Graves, M, Bernstein, M, Falkowski, S, Bialow, M, Paraschos, A, Dagher, G, Arif, A, Condit, J, Chaykin, L, Grunstra, B, Earl, J, Unks, D, Srivastava, S, Benson, M, Huffman, C, Miller, G, Willis, J, Bender, K, Martin, E, Blackmore, R, Rohr, K, Chilka, S, Gadowski, G, Fitz-Patrick, D, Benjamin, S, Morin, D, Zias Dilena, A, Acosta, R, Claassen, D, Miranda, F, Raad, G, Inzerello, A, Porter, J, Bhattacharya, A, Gutmann, J, Korpas, D, Syed, M, Zieve, F, Raisinghani, A, Alam, S, Bartkowiak, A, Boccalandro, F, Talano, J, Mercado, A, Krichmar, P, Oldfield, C, Adams, K, Gorman, T, Lewis, D, Shah, R, Shockey, G, Lefebvre, G, Andrawis, N, Tami, L, Bittar, N, Khan, M, Rink, L, Hendrix, E, Wood, J, Robinson, J, Pavon, H, Irfan, M, Gonzalez, E, Singal, R, Shore, K, Saba, F, Bianco, J, Erickson, B, Gorson, D, Puri, S, Arauz-Pacheco, C, Forman, S, Akyea-Djamson, A, Lieber, I, Barker, B, Desai, P, Sotolongo, C, Steinhoff, J, Hill, R, Radin, M, Patel, R, Lieberman, S, Wenocur, H, Dagogo-Jack, S, Lupovitch, S, Ison, R, Bacharach, J, Diogo, J, Mazzella, M, Greenwald, J, Quadrel, M, Mayer, N, Datu, J, Mccartney, M, Bruce, T, Singal, D, Turner, J, Videau, B, Fritz, R, Fox, D, Calatayud, G, Sheldon, W, Kereiakes, D, Thomas, J, Salacata, A, Mccullum, K, Harris, B, de Souza, J, Rahman, A, Blumenthal, S, Narayan, P, Bloch, M, Augenbraun, C, Bernstein, R, Perlman, R, Berman, J, Labryer, L, Wynne, A, Fish, J, Zarich, S, Gabra, N, Popeil, L, Hermany, P, Barreto, A, Pomposini, D, Gonzalez-Campoy, J, Langer, M, Bayron, C, Suneja, R, Kamlet, J, Wheeler, K, Hurley, S, Sharma, S, Wefald, F, Hershon, K, O'Connor, T, Pueblitz, G, Laguerre, J, Amin, M, Alfonso, T, Jaffrani, N, Isserman, S, Portnay, E, Vlastaris, A, Dy, J, Hagan, M, Noveck, H, Kraft, P, Andersen, J, Foley, B, Carr, K, Gelormini, J, Williams, T, Landau, C, Richwine, R, Thakkar, M, Karim, A, Madhun, Z, Francyk, D, Lamantia, J, Baker, B, Zhang, W, Lev, V, Hasan, M, Captain, A, Herzog, W, Friedman, K, Lawson, W, Desai, V, Ow, C, Simons, R, Mandviwala, M, Le, T, Hack, T, Zebrack, J, Henderson, D, Dejulia, J, Mehta, R, Reza, S, Poonawala, R, Awad, A, Velasquez, M, Mohiuddin, S, Salazar Sharma, M, Myrick, G, Gottlieb, D, Ovalle, F, Alfieri, A, Ahmed, S, Bohula, E, Donahoe, S, Longshaw, K, Eshaghian, S, Lash, J, Goldberg, R, Fox, B, Mostel, E, Dobies, D, Ward, H, Burbano, J, Puleo, P, Lenhard, M, Korn, D, Thadani, U, Bradley, A, Kmetzo, J, Heasley, E, Raikhel, M, Mahr, N, Bittar, G, Fuentes, F, Raghu, P, Diep, T, Tran, Q, Tran, N, Nguyen, D, and Nguyen, V

Subjects
Male, medicine.medical_specialty, dapagliflozin, placebo, [SDV]Life Sciences [q-bio], Renal function, Type 2 diabetes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glucosides, Diabetes mellitus, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Benzhydryl Compounds, Dapagliflozin, Sodium-Glucose Transporter 2 Inhibitors, ComputingMilieux_MISCELLANEOUS, Aged, Heart Failure, Canagliflozin, business.industry, [SDV.BA]Life Sciences [q-bio]/Animal biology, General Medicine, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Hospitalization, Diabetes Mellitus, Type 2, chemistry, Cardiovascular Diseases, Heart failure, Cardiology, Female, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Mace, medicine.drug
Abstract

BACKGROUND The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. METHODS We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to ≥60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. RESULTS We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], ≥1.3; P≥0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P = 0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P = 0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87), and death from any cause occurred in 6.2% and 6.6%, respectively (hazard ratio, 0.93; 95% CI, 0.82 to 1.04). Diabetic ketoacidosis was more common with dapagliflozin than with placebo (0.3%vs. 0.1%, P = 0.02), as was the rate of genital infections that led to discontinuation of the regimen or that were considered to be serious adverse events (0.9% vs. 0.1%, P≥0.001). CONCLUSIONS In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease, treatment with dapagliflozin did not result in a higher or lower rate of MACE than placebo but did result in a lower rate of cardiovascular death or hospitalization for heart failure, a finding that reflects a lower rate of hospitalization for heart failure. (Funded by AstraZeneca; DECLARETIMI 58 ClinicalTrials.gov number, NCT01730534

Published
2019

47. Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries

Author

Srinivasan, R., Forman, S., Quinlan, R.A., Ohanian, J., and Ohanian, V.

Subjects
Vasoconstriction -- Research, Vascular smooth muscle -- Research, Arteries -- Research, Epithelial cells -- Research, Cellular signal transduction -- Research, Cardiovascular research, Biological sciences
Abstract

The regulation of small artery contractility by vasoconstrictors is important for vascular function, and actin cytoskeleton remodeling is required for contraction, p38 MAPK and tyrosine kinases are implicated in actin polymerization and contraction through heat shock protein 27 (Hsp27) and the cytoskeletal protein paxillin, respectively. We evaluated the roles of downstream targets of p38 MAPK and tyrosine kinases in cytoskeletal reorganization and contraction and whether the two signaling pathways regulate contraction independent of each other. We identified the expression of the paxillin homologue hydrogen peroxide-inducible clone-5 (Hic-5) and showed its activation by norepinephrine (NE) in a Src-dependent manner. Furthermore, we demonstrated a NE-induced interaction of proline-rich tyrosine kinase-2 (PYK2) but not Src or p125 focal adhesion kinase with Hic-5. This interaction was Src dependent, suggesting that Hic-5 was a substrate for PYK2 downstream from Src. The activation of Hic-5 induced its relocalization to the cytosol. The parallel activation of Hsp27 by NE was p38 MAPK dependent and led to its dissociation from actin filaments and translocation from membrane to cytosol and increased actin polymerization. Both Hsp27 and Hic-5 activation resulted in their association within the same time frame as NE-induced contraction, and the inhibition of either p38 MAPK or Src inhibited the interaction between Hsp27 and Hic-5 and the contractile response. Furthermore, combined p38 MAPK and Src inhibition had no greater effect on contraction than individual inhibition, suggesting that the two pathways act through a common mechanism. These data show that NE-induced activation and the association of Hsp27 and Hic-5 are required for the reorganization of the actin cytoskeleton and force development in small arteries. smooth muscle; cytoskeleton; cell signaling; subcellular localization; [alpha]-adrenergic

Published
2008

50. Elevated D-Dimer Levels are Associated with Increased Risk of Mortality in COVID-19: A Systematic Review and Meta-Analysis

Author

Siddharth B Patel, Mohammed Osman, Kuldeep Shah, Dhanunjaya Lakkireddy, Mohit K. Turagam, Siddharth Shah, Jalaj Garg, Poonam Velagapudi, and Forman S Patel

Subjects
medicine.medical_specialty, Pooled variance, Increased risk, Coronavirus disease 2019 (COVID-19), Elevated D-dimer, business.industry, Meta-analysis, Internal medicine, Case fatality rate, Risk of mortality, MEDLINE, Medicine, business
Abstract

IntroductionThe 2019 novel Coronavirus (2019-nCoV), now declared a pandemic has an overall case fatality of 2–3% but it is as high as 50% in critically ill patients. D-dimer is an important prognostic tool, often elevated in patients with severe COVID-19 infection and in those who suffered death. In this systematic review, we aimed to investigate the prognostic role of D-dimer in COVID-19 infected patients.MethodsWe searched PubMed, Medline, Embase, Ovid, and Cochrane for studies reporting admission D-dimer levels in COVID-19 patients and its effect on mortality.Results18 studies (16 retrospective and 2 prospective) with a total of 3,682 patients met the inclusion criteria. The pooled mean difference (MD) suggested significantly elevated D-dimer levels in patients who died versus those survived (MD 6.13 mg/L, 95% CI 4.16 − 8.11, p ConclusionOur meta-analysis demonstrates that patients with COVID-19 presenting with elevated D-dimer levels have an increased risk of severe disease and mortality.

Published
2020

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