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Tendencias recientes en cáncer de próstata en España
Recent trends in prostate cancer in Spain
L. Cayuelaa, G. Lendínez-Canob, M. Chávez-Condec, S. Rodríguez-Domínguezd,
Autor para correspondencia
susana.rodriguez.dominguez@gmail.com

Autor para correspondencia.
, A. Cayuelae
a Departamento de Medicina Interna, Hospital Severo Ochoa, Leganés, España
b Unidad de Urología Oncología, UGC Urología-Nefrología, Hospital Universitario Virgen del Rocío, Sevilla, España
c Unidad de Gestión Clínica de Oncología, Hospital Universitario Nuestra Señora de Valme, Sevilla, España
d Centro de Salud Pino Montano A, Distrito Sanitario Sevilla, Sevilla, España
e Unidad de Salud Pública, Prevención y Promoción de la Salud, Área de Gestión Sanitaria Sur de Sevilla, Sevilla, España
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">A nivel mundial&#44; el incremento observado en el n&#250;mero de casos de c&#225;ncer de pr&#243;stata &#40;CP&#41; en los &#250;ltimos a&#241;os reflejar&#237;a en parte el envejecimiento y el crecimiento de la poblaci&#243;n<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a>&#46; En 2018&#44; se estim&#243; que hubo casi 1&#44;3<span class="elsevierStyleHsp" style=""></span>millones de casos incidentes &#40;segunda neoplasia diagnosticada con mayor frecuencia&#41; y 358&#46;989 muertes &#40;la quinta causa principal de muerte por c&#225;ncer&#41; en hombres<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">El CP es el c&#225;ncer m&#225;s com&#250;n en los hombres europeos y representa aproximadamente el 20&#37; de todos los casos de c&#225;ncer nuevos diagnosticados&#46; En Europa&#44; las tasas de mortalidad estandarizadas por edad var&#237;an mucho&#59; las tasas m&#225;s altas se observan en los pa&#237;ses del norte &#40;Noruega&#44; Dinamarca y Suecia&#41; y este &#40;Lituania&#44; Eslovaquia&#44; Letonia y Estonia&#41; y las m&#225;s bajas en el oeste &#40;Francia&#44; Luxemburgo&#44; B&#233;lgica y Austria&#41; y el sur &#40;Italia&#44; Espa&#241;a&#44; Malta y Grecia&#41;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Un estudio en 76 pa&#237;ses<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">3</span></a> ha observado diferencias en las tendencias recientes &#40;&#250;ltimos 5 a&#241;os de datos disponibles&#41; en las tasas de incidencia y mortalidad por CP&#46; Las tasas de incidencia&#44; despu&#233;s de aumentar durante muchos a&#241;os&#44; disminuyeron en 5 pa&#237;ses o se estabilizaron en 35&#59; en contraste&#44; las tasas continuaron aumentando en 4 pa&#237;ses de Europa del Este y Asia&#46; Las tasas de mortalidad aumentaron en 3 pa&#237;ses&#44; se mantuvieron estables en 59 y disminuyeron en 14&#46; En general&#44; las tendencias decrecientes se limitaron a los pa&#237;ses desarrollados&#44; con tasas que disminuyeron entre un promedio del 5&#37; en Irlanda&#44; Francia y Australia y del 2&#37; en Alemania y el Reino Unido&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">En Espa&#241;a &#40;2018&#41;&#44; aunque el CP es el segundo c&#225;ncer m&#225;s diagnosticado en los hombres en todo el mundo&#44; ocupa el primer lugar<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a>&#46; Las tasas de incidencia aumentaron en Espa&#241;a durante el per&#237;odo 1975-1990 en un 1&#44;3&#37; por a&#241;o y aceleraron su aumento &#40;7&#44;3&#37; por a&#241;o&#41; durante el per&#237;odo 1990-2004<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a>&#46; Recientemente&#44; las tasas de incidencia parecen haberse estabilizado en Navarra<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">5</span></a>&#46; Las tasas de mortalidad por CP experimentaron un ligero aumento durante el per&#237;odo 1951-1970&#59; desde entonces hasta mediados de la d&#233;cada de los 80&#44; las tasas se estabilizaron y se mantuvieron estables hasta mediados de la d&#233;cada de los 90&#44; cuando comenzaron a disminuir tanto a nivel nacional como por comunidades aut&#243;nomas<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">6&#8211;9</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Teniendo en cuenta lo anterior&#44; planteamos actualizar la informaci&#243;n sobre incidencia&#44; supervivencia y mortalidad por CP y evaluar las tendencias recientes en Espa&#241;a&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todos</span><p id="par0030" class="elsevierStylePara elsevierViewall">Las defunciones por CP se han obtenido del Instituto Nacional de Estad&#237;stica &#40;INE&#41;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a>&#46; Los casos incidentes de CP se han obtenido de las bases de datos <span class="elsevierStyleItalic">Cancer incidence in five continents</span> &#40;CI5&#41;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">11</span></a> y <span class="elsevierStyleItalic">European Cancer Information System</span> &#40;ECIS&#41;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a> y corresponden a 14 registros de c&#225;ncer de base poblacional espa&#241;oles&#46; Los c&#243;digos utilizados han sido&#58; 185 y C61 de las revisiones 9&#46;<span class="elsevierStyleSup">a</span> y 10&#46;<span class="elsevierStyleSup">a</span> de la Clasificaci&#243;n Internacional de Enfermedades y causas de muerte &#40;CIE&#41;&#46; Los denominadores &#40;estimaciones de poblaci&#243;n a 1 de julio de cada a&#241;o&#44; por grupos de edad&#41; se han obtenido del INE y del ECIS&#46; Se han calculado las tasas espec&#237;ficas por grupos de edad&#44; crudas y estandarizadas directas &#40;poblaci&#243;n est&#225;ndar mundial&#41; y se expresan como tasas por 100&#46;000 varones-a&#241;o<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">13</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Para el an&#225;lisis de tendencias se usaron modelos de regresi&#243;n <span class="elsevierStyleItalic">joinpoint</span><a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">14</span></a>&#46; El prop&#243;sito de estos modelos es doble&#58; identificar el momento en que se producen los cambios significativos en la tendencia y estimar la magnitud del aumento o el descenso observado en cada intervalo&#46; De esta manera se expresaron en los resultados los a&#241;os &#40;per&#237;odo&#41; que componen cada tendencia&#44; as&#237; como el porcentaje de cambio anual &#40;PCA&#41; para cada una de ellas&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Para la estimaci&#243;n de dichos modelos se usaron las tasas estandarizadas y sus errores est&#225;ndar&#44; y para los modelos por grupos de edad se utilizaron las defunciones o los casos incidentes y las poblaciones bajo un modelo de distribuci&#243;n de Poisson&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Fijamos el m&#237;nimo n&#250;mero de datos en la tendencia lineal en ambos extremos del per&#237;odo en 3&#46; Se busc&#243; un m&#225;ximo de 3 puntos de inflexi&#243;n en cada regresi&#243;n&#44; para lo cual el programa busca el modelo m&#225;s sencillo que se ajuste a los datos mediante la t&#233;cnica de m&#237;nimos cuadrados ponderados&#44; estimando luego su significaci&#243;n estad&#237;stica por medio de permutaciones Monte Carlo&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Para cuantificar la tendencia a lo largo de todo el per&#237;odo&#44; calculamos el cambio porcentual anual medio &#40;PCAM&#41; como un promedio geom&#233;trico ponderado de los PCA del modelo <span class="elsevierStyleItalic">joinpoint</span>&#46; Esto representa una medida resumen de la tendencia durante el per&#237;odo de estudio&#46; Si un PCAM se encuentra por completo dentro de un &#250;nico segmento&#44; el PCAM ser&#225; igual al PCA para ese segmento&#46; Para determinar la direcci&#243;n y la magnitud de las tendencias recientes&#44; los PCAM tambi&#233;n se evaluaron durante los &#250;ltimos 5 a&#241;os disponibles&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Al describir los resultados del an&#225;lisis de tendencias&#44; los t&#233;rminos &#171;aumenta&#187; o &#171;disminuye&#187; indican significaci&#243;n estad&#237;stica &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; mientras que los resultados no significativos se informan como &#171;estables&#187;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Para todos los c&#225;lculos y an&#225;lisis se us&#243; el software &#171;Joinpoint Regression Program&#187;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">15</span></a>&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Resultados</span><p id="par0065" class="elsevierStylePara elsevierViewall">A lo largo del per&#237;odo de estudio&#44; el n&#250;mero de muertes por CP aument&#243; en Espa&#241;a &#40;de 3&#46;120 muertes en 1980 a 5&#46;841 en 2018&#41;&#44; ocupando en 2018 el tercer lugar como causa de muerte por c&#225;ncer tras el c&#225;ncer de pulm&#243;n y el de colon&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a> se muestran las tasas estandarizadas &#40;poblaci&#243;n est&#225;ndar mundial&#41; por 100&#46;000 hombres-a&#241;o y las tendencias <span class="elsevierStyleItalic">joinpoint</span> de incidencia y mortalidad por CP en Espa&#241;a 1980-2018&#46; Las tasas de mortalidad cambiaron durante el per&#237;odo de estudio de 12&#44;9 en 1980 a 7&#44;9 en el a&#241;o 2018&#44; con un PCAM de &#8722;1&#44;2&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Sin embargo&#44; el an&#225;lisis <span class="elsevierStyleItalic">joinpoint</span> identific&#243; 3 per&#237;odos de tiempo&#58; un per&#237;odo inicial de aumento estad&#237;sticamente significativo &#40;1980-1998&#59; PCA&#58; 0&#44;6&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; y 2 per&#237;odos de disminuci&#243;n en las tasas &#40;1998-2008&#59; PCA&#58; &#8211;3&#44;3&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 y 2008-2018&#59; PCA&#58; &#8722;2&#44;4&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Las tasas de incidencia se incrementaron de forma significativa&#44; pasando de 16&#44;4 en 1980 a 61&#44;3 en 2014&#46; El an&#225;lisis <span class="elsevierStyleItalic">joinpoint</span> muestra 3 per&#237;odos&#58; 2 iniciales de incrementos significativos &#40;1980-1990&#59; 3&#44;5&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 y 1990-2004&#59; 8&#44;4&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; seguidos de uno final en el que las tasas se estabilizan &#40;2004-2014&#59; &#8722;0&#44;5&#37;&#44; no significativo&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se muestran&#44; para los a&#241;os 1980 y 2018&#44; las tasas espec&#237;ficas por grupos de edad y estandarizadas &#40;poblaci&#243;n est&#225;ndar mundial&#41; por 100&#46;000 hombres-a&#241;o y resultados del an&#225;lisis <span class="elsevierStyleItalic">joinpoint</span> para la mortalidad por CP en Espa&#241;a &#40;1980-2018&#41;&#46; Para todos los grupos de edad se observa una tendencia reciente &#40;2014-2018&#41; descendente significativa&#44; el PCAM oscil&#243; entre &#8722;3&#44;5&#37; en el grupo de 80-84 a&#241;os y &#8722;1&#44;9&#37; en el grupo de 55-59 a&#241;os&#46; El an&#225;lisis <span class="elsevierStyleItalic">joinpoint</span> muestra 2 per&#237;odos en todos los grupos de edad por debajo de los 85 a&#241;os&#58; uno inicial en el que las tasas aumentan de forma significativa &#40;grupos de 55-59 y 80-84 a&#241;os&#41; o permanecen estables &#40;resto de grupos de edad&#41; seguido de un per&#237;odo de descenso significativo&#46; El grupo de 85&#43;<span class="elsevierStyleHsp" style=""></span>a&#241;os muestra 3 per&#237;odos&#58; uno inicial en el que las tasas permanecen estables &#40;1980-1990&#41;&#44; otro de marcado incremento &#40;1990-1998&#59; 4&#44;1&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; y uno final en el que las tasas descienden de forma significativa &#40;1998-2018&#59; &#8722;2&#44;6&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a> se muestran&#44; para los a&#241;os 1980 y 2014&#44; las tasas espec&#237;ficas por grupos de edad y estandarizadas &#40;poblaci&#243;n est&#225;ndar mundial&#41; por 100&#46;000 hombres-a&#241;o y resultados del an&#225;lisis <span class="elsevierStyleItalic">joinpoint</span> para incidencia de CP en Espa&#241;a &#40;1980-2014&#41;&#46; Para todos los grupos de edad por encima de los 69 a&#241;os se observa una tendencia reciente &#40;2010-2014&#41; descendente significativa&#44; el PCAM oscil&#243; entre &#8722;1&#44;8&#37; en el grupo de 70-74 a&#241;os y &#8722;7&#44;4&#37; en el grupo de 85&#43;<span class="elsevierStyleHsp" style=""></span>a&#241;os&#46; En el resto de los grupos de edad las tasas permanecen estables&#44; excepto el grupo de 55-59 a&#241;os en el que las tasas tambi&#233;n disminuyen de forma significativa &#40;&#8722;4&#44;4&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; El an&#225;lisis <span class="elsevierStyleItalic">joinpoint</span> muestra 3 per&#237;odos en todos los grupos de edad por debajo de los 75 a&#241;os&#58; uno inicial en el que las tasas aumentan de forma significativa &#40;grupos de 60-64 y 65-69 a&#241;os&#41; o permanecen estables &#40;resto de grupos de edad&#41;&#44; un segundo per&#237;odo de marcado incremento significativo &#40;desde finales de los 80 y principios de los 90&#41; y un tercero en el que las tasas se estabilizan o descienden &#40;grupos de 55-59 y 70-74 a&#241;os&#41; desde principios de los 2000&#46; En los mayores de 74 a&#241;os se observan 2 per&#237;odos significativos&#58; uno inicial de incremento en las tasas seguido de otro de descenso significativo de las mismas&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discusi&#243;n</span><p id="par0085" class="elsevierStylePara elsevierViewall">Las tendencias recientes &#40;&#250;ltimos 5 a&#241;os&#41; muestran que las tasas de mortalidad han disminuido y que las tasas de incidencia se han estabilizado e incluso descendido en algunos grupos de edad&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">El aumento en las tasas de incidencia durante la d&#233;cada de los 80 &#40;3&#44;5&#37; anual&#41; podr&#237;a ser debido a varios factores&#46; El aumento del uso de la resecci&#243;n transuretral&#44; desde mediados de los 70&#44; para tratar la hiperplasia benigna de pr&#243;stata<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">16</span></a> y la detecci&#243;n temprana junto con el aumento de las tasas de prostatectom&#237;a radical para las formas localizadas&#44; que comenz&#243; antes de la introducci&#243;n de la determinaci&#243;n del ant&#237;geno prost&#225;tico espec&#237;fico &#40;PSA&#41;&#44; habr&#237;an influido en dicho incremento&#46; Desde la d&#233;cada de los 80&#44; el sistema de atenci&#243;n primaria de salud en Espa&#241;a mejor&#243;&#44; facilitando el diagn&#243;stico de CP en las zonas rurales&#44; por lo que tambi&#233;n podr&#237;a haber contribuido al aumento observado<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Desde principios de la d&#233;cada de los 90 la tendencia ascendente se hace m&#225;s pronunciada &#40;8&#44;4&#37; anual&#41; y de forma m&#225;s llamativa en los menores de 70 a&#241;os&#44; en los que la incidencia aumenta entre un 10&#44;1&#37; y un 16&#44;7&#37;&#46; Este incremento en la incidencia&#44; similar al observado en otros pa&#237;ses<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a>&#44; coincidi&#243; con la introducci&#243;n del PSA y podr&#237;a ser debido al adelanto diagn&#243;stico <span class="elsevierStyleItalic">&#40;lead-time&#41;</span> de tumores que se hubieran diagnosticado posteriormente&#44; al sobrediagn&#243;stico<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a> o a una exposici&#243;n potencialmente mayor a factores de riesgo desconocidos<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a>&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Aparte de los pocos factores de riesgo no modificables establecidos&#58; edad&#44; antecedentes familiares de CP y etnia&#44; no existen factores de riesgo modificables bien establecidos para el CP<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a>&#46; El riesgo de CP aumenta con la edad&#44; especialmente despu&#233;s de los 50 a&#241;os &#40;<a class="elsevierStyleCrossRefs" href="#tbl0005">tablas 1 y 2</a>&#41;&#46; Por lo tanto&#44; el envejecimiento de la poblaci&#243;n tambi&#233;n puede haber influido en el aumento observado en la incidencia&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">En Espa&#241;a&#44; como en otros pa&#237;ses europeos&#44; el CP es una enfermedad con un pron&#243;stico relativamente bueno&#46; La supervivencia relativa del CP para los casos diagnosticados en Espa&#241;a durante 1990-1994 fue del 65&#37; a 5 a&#241;os<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">22</span></a>&#44; incremento del 11&#37;&#44; respecto a los casos diagnosticados durante 1985-1989<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">23</span></a>&#46; La supervivencia neta estandarizada por edad a 5 a&#241;os aument&#243; del 73&#44;7&#37; en 1995-1999 al 87&#44;1&#37; en 2005-2009<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a> y alcanz&#243; el 89&#44;8&#37; en 2008-2013<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a>&#46; El adelanto diagn&#243;stico y los efectos del sobrediagn&#243;stico por la detecci&#243;n oportunista mediante el PSA probablemente condujeron a una mayor supervivencia&#46; Pese a ello&#44; el aumento del uso de la prostatectom&#237;a radical y la disponibilidad de terapias hormonales tambi&#233;n habr&#237;an podido influir<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">26&#44;27</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">El continuo descenso de las tasas de mortalidad por CP &#40;espec&#237;ficas por grupos de edad y estandarizadas&#41; podr&#237;a reflejar la mejora en los tratamientos &#40;cirug&#237;a&#44; hormonoterapia y radioterapia&#41; as&#237; como un mayor acceso a dichos tratamientos<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">28</span></a>&#46; La contribuci&#243;n del aumento de las pruebas de PSA en la disminuci&#243;n de las tasas de mortalidad por CP no est&#225; clara<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">29</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Nuestro estudio tiene ciertas fortalezas y limitaciones&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Una fortaleza de este estudio es el uso de datos de incidencia y mortalidad basados en fuentes de alta calidad para examinar las tasas y tendencias recientes de incidencia y mortalidad por CP&#46; Adem&#225;s&#44; los datos a largo plazo permiten comprender c&#243;mo las modificaciones en las recomendaciones del uso del PSA podr&#237;an haber afectado las tasas de incidencia y mortalidad&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Los datos de mortalidad son la &#250;nica fuente de datos disponible que satisface los criterios de continuidad y globalidad a nivel nacional<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">30</span></a>&#46; Adem&#225;s&#44; las estad&#237;sticas de mortalidad&#44; basadas en los certificados de defunci&#243;n&#44; se consideran v&#225;lidas para estimar la magnitud y tendencia del c&#225;ncer en Espa&#241;a<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">31&#44;32</span></a>&#46; Aunque durante el per&#237;odo de estudio se utilizaron 2 clasificaciones diferentes&#44; CIE-9 y CIE-10&#44; las tendencias no se han visto afectadas<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">A pesar de todo&#44; los datos de mortalidad por CP parecen ser la &#250;nica estad&#237;stica descriptiva no sesgada durante el per&#237;odo de estudio&#46; Una gran proporci&#243;n de diagn&#243;sticos anticipados &#40;<span class="elsevierStyleItalic">lead-time</span> y sobrediagn&#243;stico a nivel poblacional&#41; podr&#237;an haber inflado los datos de incidencia al aumentar el n&#250;mero de casos latentes diagnosticados en hombres asintom&#225;ticos y sesgar&#237;an tambi&#233;n las estad&#237;sticas de supervivencia basadas en la poblaci&#243;n&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Conclusi&#243;n&#58; Las tendencias recientes &#40;&#250;ltimos 5 a&#241;os&#41; muestran que las tasas de mortalidad han disminuido y que las tasas de incidencia se han estabilizado e incluso descendido en algunos grupos de edad&#46; Pese a ello&#44; este tipo de c&#225;ncer sigue siendo un importante problema de salud p&#250;blica en Espa&#241;a&#44; principalmente debido al envejecimiento de la poblaci&#243;n&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflicto de intereses</span><p id="par0140" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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          "titulo" => "Abstract"
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            0 => array:2 [
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          "titulo" => "Conflicto de intereses"
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        9 => array:1 [
          "titulo" => "Bibliograf&#237;a"
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    "fechaRecibido" => "2020-03-31"
    "fechaAceptado" => "2020-05-07"
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            0 => "C&#225;ncer de pr&#243;stata"
            1 => "Mortalidad"
            2 => "Incidencia"
            3 => "Tendencia"
            4 => "Epidemiolog&#237;a"
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "Prostate cancer"
            1 => "Mortality"
            2 => "Incidence"
            3 => "Trend"
            4 => "Epidemiology"
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      ]
    ]
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    "resumen" => array:2 [
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evaluar las tendencias recientes de incidencia&#44; supervivencia y mortalidad por c&#225;ncer de pr&#243;stata en Espa&#241;a utilizando datos actualizados&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Sujetos y m&#233;todo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Las defunciones por c&#225;ncer de pr&#243;stata se han obtenido del Instituto Nacional de Estad&#237;stica &#40;INE&#41;&#46; Los casos incidentes se han obtenido de las bases de datos <span class="elsevierStyleItalic">Cancer incidence in five continents &#40;CI5&#41;</span> y <span class="elsevierStyleItalic">European Cancer Information System</span>&#46; Para el an&#225;lisis de tendencias se usaron modelos de regresi&#243;n <span class="elsevierStyleItalic">joinpoint</span>&#46; En los resultados se muestran los a&#241;os &#40;per&#237;odo&#41; que componen cada tendencia&#44; as&#237; como el porcentaje de cambio anual &#40;PCA&#41; para cada una de ellas&#46; La direcci&#243;n y magnitud de las tendencias recientes &#40;&#250;ltimos 5 a&#241;os disponibles&#41; se evaluaron mediante los porcentajes de cambio anual medio &#40;PCAM&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Las tasas de incidencia aumentaron de forma significativa&#44; pasando de 16&#44;4 en 1980 a 61&#44;3 en 2014&#46; El an&#225;lisis <span class="elsevierStyleItalic">joinpoint</span> muestra 3 per&#237;odos&#58; 2 iniciales de incrementos significativos &#40;1980-1990&#59; 3&#44;5&#37; y 1990-2004&#59; 8&#44;4&#37;&#41; seguidos de uno final en el que las tasas se estabilizan &#40;2004-2014&#59; &#8722;0&#44;5&#37;&#44; no significativo&#41;&#46; Las tasas de mortalidad descienden pasando de 12&#44;9 en 1980 a 7&#44;9 en el a&#241;o 2018&#44; con un PCAM de &#8722;1&#44;2&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Sin embargo&#44; el an&#225;lisis <span class="elsevierStyleItalic">joinpoint</span> identific&#243; 3 per&#237;odos de tiempo&#58; un per&#237;odo inicial de aumento estad&#237;sticamente significativo &#40;1980-1998&#59; PCA&#58; 0&#44;6&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; y 2 per&#237;odos de disminuci&#243;n en las tasas &#40;1992-2008&#59; PCA&#58; &#8211;3&#44;3&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 y 2008-2018&#59; PCA&#58; &#8722;2&#44;4&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusi&#243;n</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Las tendencias recientes &#40;&#250;ltimos 5 a&#241;os&#41; muestran que las tasas de mortalidad han disminuido y que las tasas de incidencia se han estabilizado e incluso descendido en algunos grupos de edad&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Sujetos y m&#233;todo"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusi&#243;n"
          ]
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      ]
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To assess recent trends in prostate cancer incidence&#44; survival and mortality in Spain using updated data&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Subjects and method</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Prostate cancer mortality data have been obtained from the National Institute of Statistics &#40;INE&#41;&#46; Incidence cases have been obtained from the databases Cancer Incidence in Five Continents &#40;CI5&#41; and European Cancer Information System&#46; Joinpoint regression models were used for trend analysis&#46; The results show the duration &#40;years&#41; of each trend&#44; as well as the Annual Percent Change &#40;APC&#41; for each of them&#46; The direction and magnitude of recent trends &#40;last 5 years available&#41; were evaluated using the percentages of Average Annual Percent Change &#40;AAPC&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Incidence rates increased significantly from 16&#46;4 in 1980 to 61&#46;3 in 2014&#46; The joinpoint analysis shows three periods&#58; two initial periods of significant rise &#40;1980-1990&#59; 3&#46;5&#37; and 1990-2004&#59; 8&#46;4&#37;&#41; followed by a final one in which rates stabilize &#40;2004-2014&#59; &#8722;0&#46;5&#37;&#44; non-significant&#41;&#46; Mortality rates drop from 12&#46;9 in 1980 to 7&#46;9 in 2018&#44; with an AAPC of &#8722;1&#46;2&#37; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; However&#44; the joinpoint analysis identified three time periods&#58; an initial period of statistically significant rise &#40;1980-1998&#59; APC&#58; 0&#46;6&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; and two periods of decreasing rates &#40;1992-2008&#59; APC&#58; &#8722;3&#46;3&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 and 2008-2018&#59; APC&#58; &#8722;2&#46;4&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusion</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Recent trends &#40;last 5 years&#41; show that mortality rates have decreased and incidence rates have stabilized or even decreased in some age groups&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0025"
            "titulo" => "Objective"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Subjects and method"
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            "identificador" => "abst0035"
            "titulo" => "Results"
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            "identificador" => "abst0040"
            "titulo" => "Conclusion"
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        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
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        "descripcion" => array:1 [
          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Tasas estandarizadas &#40;poblaci&#243;n est&#225;ndar mundial&#41; por 100&#46;000 hombres-a&#241;o y tendencias <span class="elsevierStyleItalic">joinpoint</span>&#46; Mortalidad e incidencia por c&#225;ncer de pr&#243;stata&#44; Espa&#241;a 1980-2018&#46;</p>"
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            "identificador" => "at1"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">PCA&#58; porcentaje de cambio anual&#59; PCAM&#58; porcentaje de cambio anual medio&#59; TEw&#58; tasas estandarizadas por 100&#46;000 hombres-a&#241;o &#40;poblaci&#243;n est&#225;ndar mundial&#41;&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t  " colspan="16" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mortalidad</th></tr><tr title="table-row"><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t" scope="col">Edad&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tendencia 1</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tendencia 2</th><th class="td" title="\n
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                  \t\t\t\t  " colspan="3" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tendencia 3</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1980&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1980-2018&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2014-2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Per&#237;odo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Per&#237;odo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Per&#237;odo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">50-54&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8722;1&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8722;3&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1980-1995&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1995-2018&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1993-2018&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tendencia 3</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1980&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1980-2014</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2010-2014</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Per&#237;odo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Per&#237;odo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Per&#237;odo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PCA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50-54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1980-1992&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1992-2004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2004-2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55-59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">134&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;4&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1980-1985&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;7&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1985-2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2007-2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;4&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60-64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">345&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1980-1990&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1990-2004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2004-2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65-69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">491&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1980-1991&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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