217 research outputs found
Benefits, challenges and obstacles of adaptive clinical trial designs
No full textAbstract In recent years, the use of adaptive design methods in pharmaceutical/clinical research and development has become popular due to its flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation. The flexibility and efficiency, however, increase the risk of operational biases with resulting decrease in the accuracy and reliability for assessing the treatment effect of the test treatment under investigation. In its recent draft guidance, the United States Food and Drug Administration (FDA) expresses regulatory concern of controlling the overall type I error rate at a pre-specified level of significance for a clinical trial utilizing adaptive design. The FDA classifies adaptive designs into categories of well-understood and less well-understood designs. For those less well-understood adaptive designs such as adaptive dose finding designs and two-stage phase I/II (or phase II/III) seamless adaptive designs, statistical methods are not well established and hence should be used with caution. In practice, misuse of adaptive design methods in clinical trials is a concern to both clinical scientists and regulatory agencies. It is suggested that the escalating momentum for the use of adaptive design methods in clinical trials be slowed in order to allow time for development of appropriate statistical methodologies.</p
Networks, knowledge, and knowledge networks: A critical review and research agenda
No full textInternational audienceA large and growing body of empirical research shows that social relationships and the networks these relationships constitute are influential in explaining the processes of knowledge creation, diffusion, absorption, and use. The authors refer to such networks as "knowledge networks." They advance an understanding of knowledge networks at multiple levels by conducting a systematic review and analysis of empirical research published on this topic in leading management, psychology, sociology, and economics journals. The authors develop a comprehensive framework that organizes the knowledge networks literature, which they use to review extant empirical research within and across multiple disciplines and levels of analysis. They identify points of coherence and conflict in theoretical arguments and empirical results within and across levels and identify emerging themes and promising areas for future research
Estudio de las complicaciones perianulares en la endocarditis infecciosa. Análisis de aspectos clínicos, microbiológicos, ecocardiográficos, terapéuticos y pronósticos en pacientes con abscesos perianulares y fístulas aorto-cavitarias en la endocarditis complicada.
Get PDF[spa] La endocarditis infecciosa (EI) es una enfermedad potencialmente muy grave, que puede llegar a ser mortal sin tratamiento, cuyo pronóstico ha experimentado una gran mejoría en las ultimas décadas. Este importante cambio en la historia natural de la enfermedad se ha reflejado en una progresiva disminución de la morbi-mortalidad, sobretodo gracias al uso de potentes antibióticos y al empleo de las técnicas quirúrgicas de reparación valvular. La EI es la infección del endotelio de las válvulas cardiacas por gérmenes patógenos. La elevada morbi-mortalidad de la EI se debe a la destrucción que se produce en las válvulas y los tejidos circundantes, debido a la particular anatomía valvular que impide la correcta difusión de los antibióticos al interior de las vegetaciones valvulares. La EI tenía en la era-preantibiótica una mortalidad del 100%. El gran descenso en la mortalidad se ha producido en las últimas tres décadas, con el desarrollo de la cirugía cardiaca y la posibilidad de efectuar recambios valvulares. Con la introducción de la ecocardiografía se han podido visualizar por primera vez mediante un método incruento las vegetaciones valvulares. El desarrollo de esta técnica de imagen ha sido fundamental y en la actualidad tiene un papel clave en el diagnóstico y manejo de esta entidad ya que permite estudiar con gran detalle la anatomía cardiaca. En la actualidad, la mortalidad por EI sobre válvula nativa en fase aguda oscila entre el 20% y el 30% y la supervivencia a los 10 años de seguimiento se sitúa entre el 70% y el 80%. El pronóstico de la EI depende de un gran número de variables. Las complicaciones perianulares en la endocarditis infecciosa representan la extensión de la infección más allá de las estructuras valvulares y representan una de las complicaciones más importantes en esta enfermedad. La formación de lesiones perianulares se asocia a un pronóstico desfavorable, con elevada mortalidad. La formación de fístulas aorto-cavitarias en la endocarditis sólo se ha descrito de forma ocasional en la endocarditis y, por ello, se desconocen sus características clínicas y sus factores pronósticos de mortalidad.La hipótesis del estudio es que la presencia de complicaciones graves en la EI (desarrollo de abscesos perianulares y fístulas aorto-cavitarias) detectadas por ecocardiografía se asocia a un incremento significativo de la morbi-mortalidad. El análisis de las características clínicas y pronósticas permitiría identificar los parámetros asociados a un curso desfavorable; de esta forma podrían redefinirse las líneas de actuación (fundamentalmente quirúrgicas) encaminadas a un abordaje más temprano en pacientes seleccionados, con más posibilidades de reconstrucción completa y erradicación de la infección. Identificar estas variables permitiría, en definitiva, aumentar la supervivencia a corto y medio plazo de los casos de EI complicada.Los objetivos de este estudio son: determinar las características clínicas y el pronóstico de los pacientes con abscesos perianulares íntegros y de pacientes con fistulización aorto-cavitaria en la endocarditis y determinar el impacto sobre el pronóstico de la aparición de fistulización aorto-cavitaria en la endocarditis complicada con lesiones perianulares.Se han publicado varios estudios multicéntricos con el objetivo de reclutar una gran serie de pacientes con complicaciones perianulares y poder estudiar con detalle las características clínicas de estas complicaciones y poder analizar sus factores pronósticos de mortalidad.ARTICULOS PUBLICADOSARTICULO 1:Anguera I, Quaglio G, Miró JM, Paré C, Azqueta M, Marco F, Mestres CA, Moreno A, Pomar JL, Mezzelani JL, Sanz G. Acquired aortocardiac fistulas complicating infective endocarditis. Am J Cardiol 2001;87:652-654. Impact factor (2005) : 3.14ARTICULO 2:Anguera I, Miro JM, Vilacosta I, Almirante B, Anguita M, Muñoz P, San Roman JA, de Alarcón A, Ripoll T, Navas E, Gonzalez-Juanatey C, Cabell CH, Sarriá C, Garcia-Bolao I, Fariñas MC, Leta R, Rufi G, Miralles F, Pare C, Evangelista A, Fowler Jr VG, Mestres CA, de Lazzari E, Guma JR. Aorto-cavitary fistulous tract formation in infective endocarditis. Clinical and echocardiographic features of 76 cases and risk factors for mortality. Eur Heart J 2005;26:288-297. Impact factor (2005) : 6.25ARTICULO 3: Anguera I, Miro JM, Evangelista A, Cabell CH, San Roman JA, Vilacosta, Almirante B, Ripoll T, Fariñas MC, Anguita M, Navas E, Gonzalez-Juanatey C, Garcia-Bolao I, Muñoz P, de Alarcón A, Sarriá C, Rufi G, Miralles F, Pare C, Fowler Jr VG, Mestres CA, de Lazzari E, Guma JR, Corey GR. Prognostic factors of mortality of Periannular complications in infective endocarditis. A multicenter cohort study of 351 patients with aorto-cavitary fistulae and non-ruptured periannular abscess (1992-2003). Am J Cardiol 2005 (en revisión editorial).ARTICULO 4: Anguera I, Miro JM, Cabell CH, Abrutyn E, Fowler VG, Hoen B, Olaison L, Stafford JA, Eykyn S, Habib G, Pare C, Wang A, Corey R and the ICE-MD Investigators. Characteristics of aortic periannular abscesses studied with transesophageal echocardiography. A report from the ICE-ME database. Am J Cardiol 2005;96:976-981. Impact factor (2005) : 3.14Como resultado de este estudio, puede concluirse que la fistulización aorto-cavitaria es una complicación infrecuente de la endocarditis infecciosa, que se asocia a una extensa destrucción tisular a nivel del anillo aórtico y a la presencia de abscesos perianulares. La ecocardiografía transesofágica es la técnica de elección para la detección y el estudio de las fístulas aorto-cavitarias. La aparición de insuficiencia cardiaca grave es frecuente en estos pacientes, y a pesar del tratamiento quirúrgico agresivo la mortalidad es elevada. La infección protésica, la cirugía urgente y el desarrollo de insuficiencia cardiaca son los factores pronósticos independientes de mortalidad en los pacientes con fístulas aorto-cavitarias en la endocarditis. La formación de fístulas aorto-cavitarias se asocia a un mayor grado de destrucción anular aórtica y con mayor frecuencia de desarrollo de insuficiencia cardiaca en comparación con los abscesos no fistulizados. Ambas complicaciones requieren con mucha frecuencia tratamiento quirúrgico y tienen una elevada mortalidad, pero la fistulización no constituye un factor pronóstico independiente de mortalidad, tanto a corto como a largo plazo. La formación de abscesos perianulares es frecuente en la endocarditis de localización aórtica, se asocia frecuentemente con infección estafilocócica, y tiene una elevada morbi-mortalidad. La infección estafilocócica es un factor de riesgo independiente de mortalidad en los pacientes que desarrollan abscesos perianulares a nivel aórtico.[eng] Title: "The study of periannular complications in infective endocarditis. Analysis of clinical, microbiological, echocardiographic, therapeutic and prognostic aspects of patients with non-ruptured periannular abscesses and with aorto-cavitary fistulous tract formation in IE"Infective endocarditis (IE) is a devastating disease associated with high death rates without appropriate treatment. The prognosis of IE has changed dramatically during the last three decades due to the use of potent antibiotics and the generalization of surgical therapies of valve repair. Infective endocarditis is characterized by the infection of the endothelium of cardiac valves caused by virulent organisms, and the elevated morbidity and mortality is produced by the destruction of valvular tissue and adjacent structures. In the modern era, one-year mortality of native valve IE is in the range of 20% - 30%, and 10-year survival is in the range of 70%-80%. Spread of infection in IE from valvular structures to the surrounding perivalvular tissue results in periannular complications. Periannular complications, including periannular abscess formation and aorto-cavitary fistulous (ACF) tract formation have not been adequately studied, and may place the patient at increased risk of adverse outcomes including heart failure (HF) and death. Aorto-cavitary fistulous tract formation has only been described occasionally.The main objectives of the present investigation were to investigate the clinical characteristics and the prognosis of patients with non-ruptured periannular abscesses and with aorto-cavitary fistulous tract formation in IE and to determine the prognostic impact of fistulization in patients with periannular lesions in the setting of IE.Several manuscripts including a large number of patients with periannular lesions have been published describing the clinical characteristics and prognostic factors of mortality of patients with periannular lesions in IE.Aorto-cavitary fistula is an uncommon complication of aortic IE associated with extensive aortic root destruction and presence of periannular abscesses. Transesophageal echocardiography is the diagnostic tool of choice for the detection of aorto-cavitary fistulae in both native and prosthetic valves. Despite aggressive surgical treatment, rates of heart failure and mortality are high. Prosthetic IE, urgent surgery and the development of heart failure were associated with an increased risk of death in patients with endocarditis complicated by fistulous tract formation. ACF formation in the course of IE is associated with higher rates of aortic annulus destruction and heart failure compared to non-ruptured abscess. Surgery and mortality rates for both complications were very high; however, despite the higher complications, ACF in the current era of high rates of surgical therapy was not an independent risk factor for mortality.Periannular abscess formation occurs frequently in aortic valve IE, is associated with staphylococcal etiology, and has a high morbidity and mortality. In the current era of TEE imaging and high use of surgical treatment periannular abscess formation in aortic valve IE is not an independent risk factor for mortality. Finally, S. aureus infection constitutes an independent prognostic factor for mortality in patients who develop an abscess
Am J Prev Med
Get PDFBackgroundA growing body of evidence suggests that tobacco dependence symptoms can occur soon after smoking onset and with low levels of use. However, limited data are available nationally and among non-cigarette tobacco users.PurposeTo examine the prevalence and determinants of tobacco dependence symptoms among adolescent tobacco users in the 2012 National Youth Tobacco Survey, a nationally representative, school-based survey of U.S. middle and high school students.MethodsMultivariate logistic regression was used to identify independent predictors of dependence symptoms among current users (i.e., past 30-day use) of cigarettes, cigars, or smokeless tobacco. Analyses were conducted in 2013 using SAS-callable SUDAAN, version 11 to account for the complex survey design.ResultsPrevalence of tobacco dependence symptoms ranged from 20.8% (95% CI=18.6, 23.1) of current tobacco users reporting wanting to use tobacco within 30 minutes of waking to 41.9% (95% CI=39.3, 44.5) reporting recent strong cravings. Reporting of dependence symptoms was most consistently associated with polytobacco use, higher frequency of use, earlier initiation age, and female gender. A 2\u20134-fold increase in the odds of symptom reporting was found in adolescents using tobacco products on as few as 3\u20135 days compared to those who only used it for 1\u20132 of the past 30 days.ConclusionsA substantial proportion of U.S. adolescent tobacco users, including those with low levels of use, report symptoms of tobacco dependence. These findings demonstrate the need for full implementation of evidence-based strategies to prevent both experimentation and progression to regular tobacco use among youth.20142015-10-28T00:00:00ZCC999999/Intramural CDC HHS/United States25044195PMC4624110970
Septopalatal Protraction for Correction of Nasal Septal Deformity in Cleft Palate Infants
No full text
The Human Issue, Spring 1972
No full texthttps://kent-islandora.s3.us-east-2.amazonaws.com/node/17346/87311-thumbnail.jpgPatrons/Donors/Sponsors/Advertisers- Anonymous, Mary Beacom, Campus Supply, City Bank, Kit Corey, Diana Culbertson, Mr. & Mrs. James Custer, Carol Donley, Mack Hassler, Mr. & Mrs. Sidney Jackson, Mr. & Mrs. Thomas Korllos, Guy A. Marco, Tom Maze, Henry Moulds, Louis Paskoff, Portage Travel Service, Richard Toerne, Barbara Child, DuBois Book Store, Epsilon Nu Gamma, Jake Leed, Bobby I. Smith
Contributors- Steve Cormany, Sidney Chough, Jack Ramey, Linda C. Robinson, Jeffrey White, William Hodkins, Michael Schuldiner, Lloyd L. Mills, Gary Fincke, Ralph La Charity, Carol Donley, Cathy Proctor, Jan Stankus, Peter Iversen, Jonathan Katz, J.H. Hull, Stephen Orsary, Joseph Carter, Eric Mottram, Charles V. Smith, Judy Platz, Michael Simington, Mark Andrew Phillips, Harold Hower, Hilton Landry, Frank Polite, Erin Quinn, William Quinn, Craig Lucas, Linda Like, Susan Hariss, Tom Hager, Jim Burkhart, Jeff Hammond, R.L. Shuebrook</p
Entrepreneurship, Innovation, and the Growth Mechanism of the Free-Enterprise Economies
No full textHow much credit can be given to entrepreneurship for the unprecedented innovation and growth of free-enterprise economies? In this book, some of the world's leading economists tackle this difficult and understudied question, and their responses shed new light on how free-market economies work--and what policies most encourage their growth. The contributors take as their starting point William J. Baumol's 2002 book The Free-Market Innovation Machine (Princeton), which argued that independent entrepreneurs are far more important to growth than economists have traditionally thought, and that an implicit partnership between such entrepreneurs and large corporations is critical to the success of market economies. The contributors include the editors and Robert M. Solow, Kenneth J. Arrow, Michael M. Weinstein, Douglass C. North, Barry R. Weingast, Ying Lowrey, Nathan Rosenberg, Melissa A. Schilling, Corey Phelps, Sylvia Nasar, Boyan Jovanovic, Peter L. Rousseau, Edward N. Wolff, Deepak Somaya, David J. Teece, Naomi R. Lamoreaux, Kenneth L. Sokoloff, Yochanan Shachmurove, Ralph E. Gomory, Jonathan Eaton, Samuel S. Kortum, Alan S. Blinder, Robert J. Shiller, Burton G. Malkiel, and Edmund S. Phelps.entrepreneurship, innovation, growth, free-market economies, independent entrepreneurs, partnerships, corporations
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