RESUMEN
Randomized trials showed that mTOR inhibitors prevent early development of cardiac allograft vasculopathy (CAV). However, the action of these drugs on CAV late after transplant is controversial, and their effectiveness for CAV prevention in clinical practice is poorly explored. In this observational study we included 143 consecutive heart transplant recipients who underwent serial intravascular ultrasound (IVUS), receiving either everolimus or mycophenolate as adjunctive therapy to cyclosporine. Ninety-one recipients comprised the early cohort, receiving IVUS at weeks 3-6 and year 1 after transplant, and 52 the late cohort, receiving IVUS at years 1 and 5 after transplant. Everolimus independently reduced the odds for early CAV (0.14 [0.01-0.77]; p = 0.02) but it did not appear to influence late CAV progression. High-dose statins were found to be associated with reduced CAV progression both early and late after transplant (p ≤ 0.05). Metabolic abnormalities, such as high triglycerides, were associated with late, but not with early CAV progression. By highlighting a differential effect of everolimus and metabolic abnormalities on early and late changes of graft coronary morphology, this observational study supports the hypothesis that everolimus may be effective for CAV prevention but not for CAV treatment, and that risk factors intervene in a time-dependent sequence during CAV development.
Asunto(s)
Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Rechazo de Injerto/tratamiento farmacológico , Trasplante de Corazón , Sirolimus/análogos & derivados , Adolescente , Adulto , Antineoplásicos , Biopsia , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/etiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Everolimus , Femenino , Estudios de Seguimiento , Rechazo de Injerto/complicaciones , Rechazo de Injerto/diagnóstico , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Miocardio/patología , Estudios Retrospectivos , Sirolimus/administración & dosificación , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento , Ultrasonografía Intervencional , Adulto JovenRESUMEN
This paper presents a GIS-based multi-criteria decision analysis approach for evaluating the suitability for landfill site selection in the Polog Region, Macedonia. The multi-criteria decision framework considers environmental and economic factors which are standardized by fuzzy membership functions and combined by integration of analytical hierarchy process (AHP) and ordered weighted average (OWA) techniques. The AHP is used for the elicitation of attribute weights while the OWA operator function is used to generate a wide range of decision alternatives for addressing uncertainty associated with interaction between multiple criteria. The usefulness of the approach is illustrated by different OWA scenarios that report landfill suitability on a scale between 0 and 1. The OWA scenarios are intended to quantify the level of risk taking (i.e., optimistic, pessimistic, and neutral) and to facilitate a better understanding of patterns that emerge from decision alternatives involved in the decision making process.