array:23 [
  "pii" => "S225488741300101X"
  "issn" => "22548874"
  "doi" => "10.1016/j.rceng.2013.07.002"
  "estado" => "S300"
  "fechaPublicacion" => "2013-11-01"
  "aid" => "777"
  "copyright" => "Elsevier España, S.L.. All rights reserved"
  "copyrightAnyo" => "2013"
  "documento" => "article"
  "crossmark" => 0
  "subdocumento" => "fla"
  "cita" => "Rev Clin Esp. 2013;213:363-9"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 535
    "formatos" => array:2 [
      "HTML" => 532
      "PDF" => 3
    ]
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0014256513001641"
      "issn" => "00142565"
      "doi" => "10.1016/j.rce.2013.04.009"
      "estado" => "S300"
      "fechaPublicacion" => "2013-11-01"
      "aid" => "777"
      "copyright" => "Elsevier España, S.L."
      "documento" => "article"
      "crossmark" => 0
      "subdocumento" => "fla"
      "cita" => "Rev Clin Esp. 2013;213:363-9"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 1509
        "formatos" => array:2 [
          "HTML" => 1131
          "PDF" => 378
        ]
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Original</span>"
        "titulo" => "Carga de la enfermedad atribuible al hipotiroidismo subcl&#237;nico en la poblaci&#243;n espa&#241;ola"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "363"
            "paginaFinal" => "369"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Burden of illness attributable to subclinical hypothyroidism in the Spanish population"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0015"
            "etiqueta" => "Figura 3"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr3.jpeg"
                "Alto" => 933
                "Ancho" => 1574
                "Tamanyo" => 145824
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Carga de enfermedad &#40;a&#241;os de vida con discapacidad m&#225;s a&#241;os de vida perdidos por muerte&#41; del hipotiroidismo subcl&#237;nico en la poblaci&#243;n espa&#241;ola&#46; Los valores 0 indican que el riesgo de episodios entre pacientes con hipotiroidismo subcl&#237;nico y los pacientes eutiroideos es el mismo &#40;no hay diferencias estad&#237;sticas significativas&#41;&#46; No se incluyen estos episodios al no poderse atribuir al hipotiroidismo subcl&#237;nico&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "S&#46; Donnay, J&#46;A&#46; Balsa, J&#46; &#193;lvarez, C&#46; Crespo, F&#46; P&#233;rez-Alc&#225;ntara, C&#46; Polanco"
            "autores" => array:6 [
              0 => array:2 [
                "nombre" => "S&#46;"
                "apellidos" => "Donnay"
              ]
              1 => array:2 [
                "nombre" => "J&#46;A&#46;"
                "apellidos" => "Balsa"
              ]
              2 => array:2 [
                "nombre" => "J&#46;"
                "apellidos" => "&#193;lvarez"
              ]
              3 => array:2 [
                "nombre" => "C&#46;"
                "apellidos" => "Crespo"
              ]
              4 => array:2 [
                "nombre" => "F&#46;"
                "apellidos" => "P&#233;rez-Alc&#225;ntara"
              ]
              5 => array:2 [
                "nombre" => "C&#46;"
                "apellidos" => "Polanco"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S225488741300101X"
          "doi" => "10.1016/j.rceng.2013.07.002"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225488741300101X?idApp=WRCEE"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256513001641?idApp=WRCEE"
      "url" => "/00142565/0000021300000008/v1_201310250818/S0014256513001641/v1_201310250818/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2254887413001021"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2013.07.003"
    "estado" => "S300"
    "fechaPublicacion" => "2013-11-01"
    "aid" => "760"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "fla"
    "cita" => "Rev Clin Esp. 2013;213:370-6"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 249
      "formatos" => array:2 [
        "HTML" => 239
        "PDF" => 10
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Hospitalizations due to severe hypoglycemia in patients with diabetes mellitus in Spain"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "370"
          "paginaFinal" => "376"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Hospitalizaciones por hipoglucemia grave en pacientes con diabetes mellitus en Espa&#241;a"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 2239
              "Ancho" => 1603
              "Tamanyo" => 249124
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Percentage of hospitals in each Autonomous Community &#40;AC&#41; in which the information was obtained using 1 of 3 sources &#40;MBDS&#44; Website&#44; and the rest of the National of Health System &#91;NHS&#93;&#41;&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "L&#46; Lindner, R&#46; Garc&#237;a-S&#225;nchez, C&#46; Alvarez, L&#46; Beteg&#243;n, X&#46; Badia"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Lindner"
            ]
            1 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "Garc&#237;a-S&#225;nchez"
            ]
            2 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "Alvarez"
            ]
            3 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Beteg&#243;n"
            ]
            4 => array:2 [
              "nombre" => "X&#46;"
              "apellidos" => "Badia"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0014256513001239"
        "doi" => "10.1016/j.rce.2013.02.015"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256513001239?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887413001021?idApp=WRCEE"
    "url" => "/22548874/0000021300000008/v1_201310250817/S2254887413001021/v1_201310250817/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Burden of illness attributable to subclinical hypothyroidism in the Spanish population"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "363"
        "paginaFinal" => "369"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "S&#46; Donnay, J&#46;A&#46; Balsa, Julia &#193;lvarez, C&#46; Crespo, F&#46; P&#233;rez-Alc&#225;ntara, C&#46; Polanco"
        "autores" => array:6 [
          0 => array:3 [
            "nombre" => "S&#46;"
            "apellidos" => "Donnay"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">1</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "J&#46;A&#46;"
            "apellidos" => "Balsa"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">2</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Julia"
            "apellidos" => "&#193;lvarez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">3</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "C&#46;"
            "apellidos" => "Crespo"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">4</span>"
                "identificador" => "aff0020"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">5</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "F&#46;"
            "apellidos" => "P&#233;rez-Alc&#225;ntara"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">5</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
          5 => array:4 [
            "nombre" => "C&#46;"
            "apellidos" => "Polanco"
            "email" => array:1 [
              0 => "carlos&#46;crespo&#64;oblikue&#46;com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">6</span>"
                "identificador" => "aff0030"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">¿</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:6 [
          0 => array:3 [
            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital Universitario Fundaci&#243;n Alcorc&#243;n&#44; Madrid&#44; Spain"
            "etiqueta" => "1"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital Universitario Infanta Sof&#237;a&#44; Madrid&#44; Spain"
            "etiqueta" => "2"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital Universitario Pr&#237;ncipe de Asturias&#44; Alcal&#225; de Henares&#44; Madrid&#44; Spain"
            "etiqueta" => "3"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Departamento de Estad&#237;stica&#44; Universidad de Barcelona&#44; Barcelona&#44; Spain"
            "etiqueta" => "4"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Oblikue Consulting&#44; Barcelona&#44; Spain"
            "etiqueta" => "5"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Econom&#237;a de la Salud&#44; Business Excellence &#38; Strategy Realization&#44; Merck S&#46;L&#46;&#44; Madrid&#44; Spain"
            "etiqueta" => "6"
            "identificador" => "aff0030"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Carga de la enfermedad atribuible al hipotiroidismo subcl&#237;nico en la poblaci&#243;n espa&#241;ola"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1363
            "Ancho" => 1589
            "Tamanyo" => 102554
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Number of patients with subclinical hypothyroidism&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0005"></elsevierMultimedia></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Background</span><p id="par0025" class="elsevierStylePara elsevierViewall">Subclinical hypothyroidism &#40;SH&#41; is defined as the coexistence in asymptomatic<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> patients of high levels of thyrotropin&#44; also known as thyroid-stimulating hormone &#40;TSH&#41; and normal levels of thyroid hormone&#46; The initiation of replacement therapy with levothyroxine in patients with severe SH &#40;TSH levels<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#41; is justified by the high rate of progression to clinical hypothyroidism &#40;CH&#41;&#44; which is approximately 2&#8211;5&#37; annually&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> By contrast&#44; replacement therapy in patients with TSH levels &#60;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;L is only recommended during pregnancy and for patients with symptoms of hypothyroidism or goiter and who have a positive autoimmune test or high cardiovascular risk &#40;particularly for patients younger than 65 years&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">CH is associated with an increase in risk factors for developing coronary diseases&#44; including hypercholesterolemia&#44; high blood pressure and increased homocysteine levels&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Moreover&#44; SH &#40;especially in adults younger than 65 years&#41; and CH have been linked to an increased risk of mortality&#44; resulting from increased frequency of cardiovascular episodes&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The burden of disease&#44; whose unit of measure is disability-adjusted life years &#40;DALYs&#41;&#44; is an indicator measuring the loss of health in a population due to both fatal and nonfatal consequences&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Studies on the burden of disease allow us to monitor&#44; compare and plan the impact of health interventions among the various diseases&#46; The studies accomplish this goal by reducing the various effects to the same magnitude&#44; such as the time lost due to premature death and the time lived with good health or without disability&#46; The aim of this study was to determine the burden of disease of SH in Spain&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Materials and methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">The calculation of the burden of disease was performed according to the methodology described by Murray and L&#243;pez in the study <span class="elsevierStyleItalic">Global Burden of Disease</span> developed by the World Health Organization&#44; the World Bank and Harvard University&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The DALYs attributable to SH were calculated by adding the life lost due to premature death &#40;years of life lost &#91;YLL&#93;&#41; to the functional and well-being losses resulting from disability and poor health &#40;years lost due to disability &#91;YLD&#93;&#41;&#58; DALY<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>YLL<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>YLD&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We limited the analysis to the direct and significant relationship observed between SH and the presence of coronary artery disease in patients with high TSH levels &#40;Hazard Ratio &#91;HR&#93;&#44; 1&#46;89 for TSH levels 10&#8211;19&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The relationship between SH and coronary artery disease is derived from a meta-analysis that collected data on 55&#44;287 adults from the U&#46;S&#46;&#44; Europe&#44; Australia&#44; Japan and Brazil&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In this study&#44; a certain relationship between SH and cardiac mortality was also observed&#44; although it was not to possible to determine the relationship with overall mortality&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Years of life lost</span><p id="par0050" class="elsevierStylePara elsevierViewall">Although the study by Rodondi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> associated SH as a precursor of cardiac episodes&#44; there is no specific diagnostic code for calculating mortality due to SH&#46; Therefore&#44; to calculate the YLL due to SH&#44; we estimated the mean life expectancy in patients with cardiac episodes and calculated the number of patients with SH who had cardiac episodes and&#47;or died due to these episodes&#58;<elsevierMultimedia ident="eq0005"></elsevierMultimedia></p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">d</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">i</span></span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>number of deaths in each age group&#59; <span class="elsevierStyleItalic">e</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">i</span></span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>life expectancy at the time of death for each age group&#46;</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Life expectancy</span><p id="par0060" class="elsevierStylePara elsevierViewall">Based on a registry of deaths according to cause&#44; we identified patients who died from circulatory system diseases according to age and gender &#40;codes&#58; CIE 9 MC I00-I99&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> We then applied the overall life expectancy by age and gender to these patients&#44; thereby obtaining the mean life expectancy of patients with circulatory system disease&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Number of deaths and cardiac episodes</span><p id="par0065" class="elsevierStylePara elsevierViewall">For the reference population&#44; we used the short-term population projection of the National Institute of Statistics&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> applying to it a 6&#37; prevalence of SH for the general population &#40;TSH levels<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>4&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#41;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> extracted from international studies&#46; Using the distribution according to TSH levels&#44; approximately 70&#46;5&#37; of the patients with SH had TSH levels of 4&#46;5&#8211;6&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#44; 19&#46;5&#37; had TSH levels of 7&#8211;9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L and the remainder &#40;10&#37;&#41; had levels of 10&#8211;19&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> equivalent to prevalence rates of 4&#46;2&#37;&#44; 1&#46;2&#37; and 0&#46;6&#37;&#44; respectively&#46; Therefore&#44; to achieve an adjusted calculation of the proportion of coronary episodes and mortality in the Spanish population that could have been avoidable if the patients had not been exposed to the SH risk factor&#44; we used the formula by Miettinen for the Population Attributable Fraction &#40;PAF&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a> This formula facilitates unbiased calculations of the population attributable risk in the presence of confounders&#44; assuming that there is no interaction between the exposure variables&#44;<elsevierMultimedia ident="eq0010"></elsevierMultimedia>where <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">c</span></span> is the prevalence and <span class="elsevierStyleItalic">HR</span> is the Hazard Ratio&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The prevalence of patients exposed and not exposed for the calculation of the population attributable fraction was obtained from the meta-analysis by Rodondi et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> which observed that 2&#46;31&#37; and 1&#46;29&#37; of cardiac deaths correspond to patients with TSH levels of 7&#8211;9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L and &#62;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#44; respectively&#44; while 1&#46;57&#37; of the coronary episodes correspond to patients with TSH levels &#62;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#46; To avoid biases in the calculation of the burden of disease&#44; we took a conservative position and only attributed hypothyroidism to those episodes that were significant in the study by Rodondi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Therefore&#44; we only included HRs adjusted for age and gender corresponding to coronary mortality in patients with TSH levels of 7&#8211;9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;42&#41;&#44; and &#62;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;L &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;58&#41; and HRs of coronary episodes in patients with TSH levels &#62;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;L &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;89&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Thus&#44; starting with the mortality according to coronary cause and multiplying by the PAF of hypothyroidism&#44; we determined the cardiac mortality associated with hypothyroidism&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Years lived with disability</span><p id="par0075" class="elsevierStylePara elsevierViewall">Similar to the calculation for SH-associated mortality &#40;applying the specific PAF of hypothyroidism to cardiac episodes of the registry of diagnoses at hospital discharge of the Minimum Basic Data Set&#41;&#44; we calculated the cardiac episodes resulting from SH&#46; Due to the fact that we detected mainly ischemic heart disease in the meta-analysis used to estimate the PAF&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> we conservatively calculated only the YLD corresponding to these types of discharges &#40;codes&#58; CIE 9 MC 410&#8211;414&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">To calculate the YLD&#44; we estimated the time disabled for each cardiac episode based on the 2008 survey of disability&#44; personal autonomy and conditions of dependence&#44; adjusting for age based on the hospital discharge registry<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a>&#58;<elsevierMultimedia ident="eq0015"></elsevierMultimedia><span class="elsevierStyleItalic">N</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">i</span></span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>population susceptible to contracting the disease in each age group&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">i</span></span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>annual incidence rate of the disease in each age group&#59; <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">i</span></span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>duration of the disease &#40;in years&#41; in each age group&#59; <span class="elsevierStyleItalic">D</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>degree of disability assigned to each disease&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">To calculate the disability associated with cardiac episodes&#44; we used the disease burden data&#44; assigning 0 to an ideal health state and 1 to death&#46; Specifically&#44; we applied a disability value of 0&#46;105 for chest angina&#44; 0&#46;395 for myocardial infarction and 0&#46;191 for all other ischemic heart diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Sensitivity analysis</span><p id="par0090" class="elsevierStylePara elsevierViewall">To confirm the robustness of the results&#44; we analyzed them at a 95&#37; confidence interval &#40;CI&#41; for the PAF&#46; The results were calculated using the substitution method&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> which assumes that the variability in the calculation of the prevalence is negligible in comparison with the variability in the calculation of the relative risk&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">To contextualize the result in DALYs&#44; we estimated the proportion of cardiovascular DALYs &#40;618&#44;200 years&#41; that could be attributed to SH&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Economic burden</span><p id="par0100" class="elsevierStylePara elsevierViewall">In addition to calculating the burden of disease&#44; we estimated the economic burden of SH&#44; i&#46;e&#46; the associated costs due to the morbidity and mortality of the disease&#44; using the &#8220;human capital&#8221; method&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> This method&#39;s main assumption is equivalence between the value that an individual may produce and the remuneration they receive&#46; To transform years into monetary units&#44; we used the mean annual earnings by worker in 2008&#44; applying the lost working years according to age and gender&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results</span><p id="par0105" class="elsevierStylePara elsevierViewall">Taking into account that the population in Spain rose to 46&#44;118&#44;733 inhabitants and applying a 6&#37; prevalence in the general population&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> we calculated that there are 2&#44;767&#44;124 people with SH&#46; We estimated&#44; therefore&#44; that Spain has 1&#44;949&#44;820 individuals with SH with TSH levels of 4&#46;5&#8211;6&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#44; 538&#44;988 people with TSH levels of 7&#8211;9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L and approximately 278&#44;317 people with TSH levels of 10&#8211;19&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L and normal thyroid hormone levels &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Thus&#44; by taking into account the 1&#44;709&#44;778 ischemic cardiac episodes in Spain&#44; 120&#44;057 deaths by circulatory diseases and an overall mortality of 384&#44;933 at 1 year and applying the specific PAF of SH&#44; we determined that 12&#44;608 cardiac episodes &#40;0&#46;74&#37;&#59; 95&#37; CI 0&#46;34&#8211;1&#46;01&#37;&#41; and 1388 cardiac deaths &#40;1&#46;16&#37;&#59; 95&#37; CI 0&#46;18&#8211;1&#46;85&#37;&#41; are potentially attributable to SH each year &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Years of life lost</span><p id="par0115" class="elsevierStylePara elsevierViewall">The mean number of YLL due to circulatory system diseases was 9&#46;45 years &#40;11&#46;03 in men and 8&#46;13 years in women&#41;&#59; for the remaining causes&#44; the mean YLL was 14&#46;09 years &#40;14&#46;83 in men and 12&#46;68 years in women&#41;&#46; This equals a total of 7743 YLL for the group with TSH levels of 7&#8211;9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L and 5381 YLL in the group with severe SH &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Years lived with disability</span><p id="par0120" class="elsevierStylePara elsevierViewall">The mean disability was 0&#46;212 and the mean time of disability was 5&#46;88 years&#44; with an estimated total of 17&#44;426 YLD &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; A total of 94&#46;1&#37; of years lost due to disability was observed in patients with severe SH&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Years of life adjusted by disability</span><p id="par0125" class="elsevierStylePara elsevierViewall">The DALYs associated with SH were 30&#44;550 years&#44; which equals approximately 4&#46;9&#37; &#40;1&#46;6&#8211;7&#46;3&#37;&#41; of cardiovascular DALYs&#46; Seventy-one percent of the overall DALYs &#40;95&#37; CI&#58; 68&#8211;91&#37;&#41; were due to severe SH&#46; For the group with TSH levels of 7&#8211;9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#44; the YLL represented 88&#37; of the relative weight&#59; by contrast&#44; for the group with TSH levels of 10&#8211;19&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#44; the YLD represented the greater weight &#40;75&#37;&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Economic burden</span><p id="par0130" class="elsevierStylePara elsevierViewall">Taking into account that the average annual salary for men and women in 2008 was 24&#44;203 &#8364; and 18&#44;911 &#8364;&#44; respectively&#44; we determined that the mean indirect cost per patient was 39&#44;979 &#8364; for men and 8406 &#8364; for women&#44; by applying the work years lost due to death of cardiovascular origin&#46; Thus&#44; the total cost resulting from hypothyroidism rose to 39&#44;625&#44;176 &#8364; for the group with TSH levels of 7&#8211;9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L and to 27&#44;540&#44;333 &#8364; for the group with TSH levels of 10&#8211;19&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Discussion</span><p id="par0135" class="elsevierStylePara elsevierViewall">Approximately 2&#46;7 million people in Spain have SH&#46; This group suffers approximately 12&#44;608 cardiac episodes and 1388 cardiac deaths annually&#46; At the socioeconomic level&#44; these results represent approximately 30&#44;500 DALYs &#40;5&#37; of the cardiovascular DALYs in Spain&#41; and an associated cost of 67&#46;2 million euros&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The lack of symptoms presented by most patients with SH may result in a situation of underdiagnosis of up to 79&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> For this reason&#44; the diagnosis of SH will increase due partly to the increased availability of simple and economic diagnostic methods&#46; This underdiagnosis entails a considerable burden of cardiovascular DALYs&#46; However&#44; controversy still exists as to whether SH should be treated&#44; especially with TSH levels &#60;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;24&#8211;26</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Epidemiological studies confirming the association of SH and CH with an increased prevalence of cardiovascular episodes and mortality<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> have shown the need to perform an analysis of the efficacy of screening and the burden of disease in order to plan for and control this disease&#46; In this context&#44; our study provides new information by assessing coronary episodes attributable to SH using a theoretical formula&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The burden of SH is similar&#44; in terms of DALY and YLL&#44; to that shown by Parkinson&#39;s disease &#40;30&#44;200 DALYs and 8&#46;5 YLL&#41; and is similar&#44; in terms of DALYs&#44; to pancreatic cancer &#40;37&#44;900 DALYs&#41;&#44; lymphoma &#40;33&#44;700 DALYs&#41;&#44; lower respiratory pathway diseases &#40;32&#44;700 DALYs&#41; and nutritional deficiencies &#40;30&#44;100 DALYs&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> One of the limitations of the &#8220;burden of disease&#8221; variable is that it places an apparently asymptomatic process such as SH at the same level as highly debilitating diseases&#46; This occurs because noncommunicable diseases have a higher burden&#44; as they can last throughout life&#44; and their effects steadily worsen as the patient ages&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">One of the limitations of studies on the burden of disease is that they only analyze the consequences that result in mortality or disability&#44; despite the fact that CH has been shown to affect quality of life&#46; Other possible abnormalities not assessed include the reduced intelligence quotient in offspring of women affected by untreated gestational hypothyroidism&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">The main limitation of our study is that we have attributed cardiovascular episodes and mortality to SH using a meta-analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Although there could be different risks in each country&#44; we believe that the HRs on the risks for euthyroid patients allow for extrapolation to Spain&#46; Similarly&#44; we believe that the set of conservative measures in our study&#44; such as attributing only the significant estimators&#44; and the fact that this meta-analysis included individual data from 55&#44;287 patients&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> has helped reduce these limitations in our study&#46; Moreover&#44; even though the HR of people with TSH levels between 10 and 19&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L with respect to euthyroid individuals is greater than that observed in those who have TSH levels of 7&#8211;9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L&#44; we observed that the attributable fraction&#44; the cardiac mortality and the burden of disease were higher in the second group due to their greater prevalence&#46; These results could support the initiation of replacement therapy in patients with SH with TSH levels of 7&#8211;9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L when they present a high cardiovascular risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> Nevertheless&#44; our results should be taken with caution&#59; we do not have cross-sectional epidemiological studies in the Spanish population or a sufficient level of evidence to support the treatment of SH to prevent cardiovascular morbidity and mortality&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study shows &#40;from a theoretical point of view&#41; the calculated socioeconomic burden for SH&#44; which may establish the advisability of performing SH screening&#44; at least for patients belonging to risk groups &#40;pregnant women&#44; women older than 60 years&#44; patients with type 1 diabetes mellitus or other autoimmune diseases and individuals with a history of or relatives with thyroid disease&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Funding</span><p id="par0170" class="elsevierStylePara elsevierViewall">This study was funded by <span class="elsevierStyleGrantSponsor" id="gs0005">Merck S&#46;L</span>&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Authors&#47;collaborators</span><p id="par0175" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0180" class="elsevierStylePara elsevierViewall">Concept and design of the manuscript&#58; Dr&#46; Carlos Polanco&#44; Dr&#46; Sergio Donnay&#44; Dr&#46; Julia &#193;lvarez&#44; Dr&#46; Jos&#233; Antonio Balsa&#44; Dr&#46; Carlos Crespo and Dr&#46; Ferran P&#233;rez-Alc&#225;ntara&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0185" class="elsevierStylePara elsevierViewall">Data collection&#58; Dr&#46; Sergio Donnay&#44; Dr&#46; Julia &#193;lvarez and Dr&#46; Jos&#233; Antonio Balsa&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3</span><p id="par0190" class="elsevierStylePara elsevierViewall">Data analysis and interpretation&#58; Dr&#46; Sergio Donnay&#44; Dr&#46; Julia &#193;lvarez&#44; Dr&#46; Jos&#233; Antonio Balsa&#44; Dr&#46; Carlos Crespo and Dr&#46; Ferran P&#233;rez-Alc&#225;ntara&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4</span><p id="par0195" class="elsevierStylePara elsevierViewall">Drafting&#44; review and approval of the submitted manuscript&#58; Dr&#46; Carlos Polanco&#44; Dr&#46; Sergio Donnay&#44; Dr&#46; Julia &#193;lvarez&#44; Dr&#46; Jos&#233; Antonio Balsa&#44; Dr&#46; Carlos Crespo and Dr&#46; Ferran P&#233;rez-Alc&#225;ntara&#46;</p></li></ul></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflicts of interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors affirm the independence from the sponsoring and funding organization in the analysis of the results and the preparation of the conclusions&#46; Dr&#46; S&#46; Donnay&#44; Dr&#44; J&#46; &#193;lvarez and Dr&#46; J&#46;A&#46; Balsa received honoraria for their participation in the project&#46; Dr&#46; F&#46; P&#233;rez-Alc&#225;ntara and Dr&#46; C&#46; Crespo work in an independent consulting firm that received funding from Merck S&#46;L&#46; Dr&#46; C&#46; Polanco is an employee of Merck S&#46;L&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:13 [
        0 => array:2 [
          "identificador" => "xres285283"
          "titulo" => array:5 [
            0 => "Abstract"
            1 => "Introduction"
            2 => "Patients and methods"
            3 => "Results"
            4 => "Conclusion"
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec268543"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xres285284"
          "titulo" => array:5 [
            0 => "Resumen"
            1 => "Introducci&#243;n"
            2 => "pacientes y m&#233;todos"
            3 => "Resultados"
            4 => "Conclusi&#243;n"
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec268544"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Background"
        ]
        5 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Materials and methods"
        ]
        6 => array:3 [
          "identificador" => "sec0025"
          "titulo" => "Years of life lost"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Life expectancy"
            ]
            1 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Number of deaths and cardiac episodes"
            ]
            2 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Years lived with disability"
            ]
            3 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Sensitivity analysis"
            ]
            4 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Economic burden"
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0055"
          "titulo" => "Results"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Years of life lost"
            ]
            1 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Years lived with disability"
            ]
            2 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Years of life adjusted by disability"
            ]
            3 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Economic burden"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Discussion"
        ]
        9 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Funding"
        ]
        10 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Authors&#47;collaborators"
        ]
        11 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Conflicts of interest"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-02-13"
    "fechaAceptado" => "2013-04-21"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec268543"
          "palabras" => array:6 [
            0 => "Burden of illness"
            1 => "Hypothyroidism"
            2 => "Subclinical hypothyroidism"
            3 => "Disability-adjusted life year"
            4 => "Years of life lost"
            5 => "Years lost due to disability"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec268544"
          "palabras" => array:6 [
            0 => "Carga de enfermedad"
            1 => "Hipotiroidismo"
            2 => "Hipotiroidismo subcl&#237;nico"
            3 => "A&#241;os de vida ajustados por discapacidad"
            4 => "A&#241;os de vida perdidos"
            5 => "A&#241;os de salud perdidos por discapacidad"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Subclinical hypothyroidism &#40;SH&#41; has been associated recently to cardiovascular diseases&#46; However&#44; the loss of health it entails remains unknown&#46; This study has assessed the burden of illness attributable to SH in Spain&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Based on the Spanish prevalence data found in international studies&#44; a theoretical model was developed to estimate the Disability Adjusted Life Years &#40;DALYs&#41;&#44; years of life lost &#40;YLL&#41; and years lost due to disability &#40;YLD&#41; associated with SH&#46; Prevalence of risk factors&#44; coronary mortality risk and coronary event risk associated with SH were obtained from a review of the literature&#46; An analysis was conducted according to the World Health Organization methodology approach for these studies&#44; using official Spanish sources &#40;hospital discharge records&#44; minimum basic set data &#91;MBSD&#93;&#44; inpatient mortality records&#44; etc&#46;&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In Spain&#44; approximately 2&#44;767&#44;124 people have SH&#44; specifically 1&#44;949&#44;820 with levels of TSH between 4&#46;5 and 6&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L &#40;70&#46;5&#37;&#41;&#44; 538&#44;988 with levels between 7 and 9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L &#40;19&#46;5&#37;&#41;&#44; and 278&#44;317 between 10 and 19&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L &#40;10&#37;&#41;&#46; These subjects suffer approximately 12&#44;608 cardiac events and 1388 deaths a year attributed to their SH&#46; This represents 30&#44;550 DALYs &#40;13&#44;124 YLL and 17&#44;426 YLD&#41;&#46; Between 1&#46;6 and 7&#46;3&#37; of cardiovascular DALYs can be attributed to SH&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">SH is a silent disease which considerably increases the burden of disease&#46; Evaluation of SH&#44; at least in patients belonging to risk groups&#44; could be cost-effective&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El hipotiroidismo subcl&#237;nico &#40;HS&#41; se ha asociado a enfermedades cardiovasculares&#44; pero se desconoce la p&#233;rdida de salud que conlleva&#46; Hemos evaluado la carga de enfermedad del HS en Espa&#241;a&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A partir de la prevalencia del HS en Espa&#241;a&#44; obtenida de estudios internacionales&#44; se llev&#243; a cabo un modelo te&#243;rico que calcul&#243; los a&#241;os de vida ajustados por discapacidad &#40;AVAD&#41;&#44; los a&#241;os de vida perdidos &#40;AVP&#41; y las p&#233;rdidas de salud por discapacidad &#40;AVD&#41; asociados al HS&#46; Las prevalencias de los factores de riesgo&#44; el riesgo de mortalidad coronaria y de eventos coronarios asociados al HS se obtuvieron de una revisi&#243;n de la literatura&#46; El an&#225;lisis se llev&#243; a cabo seg&#250;n la metodolog&#237;a de la Organizaci&#243;n Mundial de la Salud&#44; utilizando fuentes oficiales espa&#241;olas &#40;registro de altas hospitalaria&#58; Conjunto M&#237;nimo B&#225;sico de Datos &#91;CMBD&#93;&#44; registro de mortalidad hospitalaria&#44;&#8230;&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En Espa&#241;a hay aproximadamente 2&#46;767&#46;124 personas con HS &#40;1&#46;949&#46;820 con niveles de TSH entre 4&#44;5 y 6&#44;9 mUI&#47;L &#91;70&#44;5&#37;&#93;&#44; 538&#46;988 con TSH entre 7 y 9&#44;9 mUI&#47;L &#91;19&#44;5&#37;&#93;&#44; y 278&#46;317 con TSH entre 10 y 19&#44;9 mUI&#47;L &#91;10&#37;&#93;&#41;&#46; Estas personas con HS podr&#237;an sufrir 12&#46;608 eventos cardiacos y 1&#46;388 muertes cardiacas anuales&#44; lo que representa 30&#46;550 AVAD &#40;13&#46;124 AVP y 17&#46;426 AVD&#41;&#46; El HS puede representar entre el 1&#44;6 y el 7&#44;3&#37; de los AVAD cardiovasculares&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El HS es una condici&#243;n silente que determina una enorme carga de enfermedad&#46; La valoraci&#243;n del HS&#44; al menos en pacientes pertenecientes a grupos de riesgo&#44; podr&#237;a ser coste-efectiva&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Donnay S&#44; et al&#46; Carga de la enfermedad atribuible al hipotiroidismo subcl&#237;nico en la poblaci&#243;n espa&#241;ola&#46; Rev Clin Esp&#46; 2013&#59;213&#58;363&#8211;369&#46;</p>"
      ]
    ]
    "multimedia" => array:8 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1363
            "Ancho" => 1589
            "Tamanyo" => 102554
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Number of patients with subclinical hypothyroidism&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 879
            "Ancho" => 1606
            "Tamanyo" => 91077
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Cardiac events and deaths attributable to subclinical hypothyroidism&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 921
            "Ancho" => 1571
            "Tamanyo" => 107519
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Burden of disease &#40;years of life with disabilities plus years of life lost due to death&#41; of subclinical hypothyroidism in the Spanish population&#46; Values of 0 indicate that the risk of episodes among patients with subclinical hypothyroidism and euthyroid patients is the same &#40;there are no statistically significant differences&#41;&#46; These episodes are not included because they could not be attributed to subclinical hypothyroidism&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; 95&#37; CI&#44; 95&#37; confidence interval&#59; TSH&#58; thyroid-stimulating hormone&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">TSH levels 4&#46;5&#8211;6&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L mean &#37; &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">TSH levels 7&#46;0&#8211;9&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L mean &#37; &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">TSH levels 10&#8211;19&#46;9<span class="elsevierStyleHsp" style=""></span>mIU&#47;L mean &#37; &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Cardiac episode&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&#46;00 &#40;0&#46;00&#8211;0&#46;64&#37;&#41;&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&#46;17 &#40;0&#46;00&#8211;0&#46;35&#37;&#41;&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&#46;28 &#40;0&#46;13&#8211;0&#46;39&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Cardiac mortality&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&#46;35 &#40;0&#46;00&#8211;0&#46;98&#37;&#41;&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&#46;35 &#40;0&#46;03&#8211;0&#46;57&#37;&#41;&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&#46;22 &#40;0&#46;05&#8211;0&#46;34&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Total mortality&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&#46;24 &#40;0&#46;00&#8211;0&#46;61&#37;&#41;&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&#46;02 &#40;0&#46;00&#8211;0&#46;23&#37;&#41;&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&#46;11 &#40;0&#46;00&#8211;0&#46;28&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab418284.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Number of cardiac episodes&#44; cardiac mortality and total mortality in patients with subclinical hypothyroidism according to various levels of TSH&#46;</p>"
        ]
      ]
      4 => array:5 [
        "identificador" => "eq0005"
        "tipo" => "MULTIMEDIAFORMULA"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "Formula" => array:5 [
          "Matematica" => "AVP&#61;&#8721;0Ldi&#8901;ei"
          "Fichero" => "si1.jpeg"
          "Tamanyo" => 1256
          "Alto" => 46
          "Ancho" => 105
        ]
      ]
      5 => array:5 [
        "identificador" => "eq0010"
        "tipo" => "MULTIMEDIAFORMULA"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "Formula" => array:5 [
          "Matematica" => "FAP&#61;Pc&#8722;PcHR"
          "Fichero" => "si2.jpeg"
          "Tamanyo" => 1530
          "Alto" => 40
          "Ancho" => 120
        ]
      ]
      6 => array:5 [
        "identificador" => "eq0015"
        "tipo" => "MULTIMEDIAFORMULA"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "Formula" => array:5 [
          "Matematica" => "AVD&#61;&#8721;0LNi&#8901;Ii&#8901;Ti&#8901;D"
          "Fichero" => "si3.jpeg"
          "Tamanyo" => 1654
          "Alto" => 30
          "Ancho" => 152
        ]
      ]
      7 => array:5 [
        "identificador" => "tb0005"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">What we know</span><p id="par0010" class="elsevierStylePara elsevierViewall">Subclinical hypothyroidism has been associated with cardiovascular disease&#44; but we do not know the loss of health that this endocrine disease entails&#46; We have evaluated the burden of disease for subclinical hypothyroidism in Spain&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">What this article provides</span><p id="par0015" class="elsevierStylePara elsevierViewall">More than 2&#46;5 million individuals in Spain are afflicted with subclinical hypothyroidism&#46; These individuals may have more than 12&#44;500 cardiac episodes&#44; 10&#37; of which are fatal&#46; This burden of disease represents a loss of more than 30&#44;000 disability-adjusted life years &#40;DALYs&#44; 5&#37; of all cardiovascular DALYs&#41;&#44; which in economic terms is equivalent to a cost of almost 67 million euros&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The Editors</p></span></span>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:30 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypothyroidism&#58; etiology&#44; diagnosis&#44; and management"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;P&#46; Almandoz"
                            1 => "H&#46; Gharib"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.mcna.2012.01.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Med Clin North Am"
                        "fecha" => "2012"
                        "volumen" => "96"
                        "paginaInicial" => "203"
                        "paginaFinal" => "221"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22443971"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Under-diagnosis of common chronic diseases&#58; prevalence and impact on human health"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;E&#46; Falagas"
                            1 => "K&#46;Z&#46; Vardakas"
                            2 => "P&#46;I&#46; Vergidis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1742-1241.2007.01423.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Clin Pract"
                        "fecha" => "2007"
                        "volumen" => "61"
                        "paginaInicial" => "1569"
                        "paginaFinal" => "1579"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17686096"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical practice guidelines for hypothyroidism in adults&#58; co-sponsored by American Association of Clinical Endocrinologists and the American Thyroid Association"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;R&#46; Garber"
                            1 => "R&#46;H&#46; Cobin"
                            2 => "H&#46; Gharib"
                            3 => "J&#46;V&#46; Hennessey"
                            4 => "I&#46; Klein"
                            5 => "J&#46;I&#46; Mechanick"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4158/EP12280.GL"
                      "Revista" => array:6 [
                        "tituloSerie" => "Endocr Pract"
                        "fecha" => "2012"
                        "volumen" => "18"
                        "paginaInicial" => "988"
                        "paginaFinal" => "1028"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23246686"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Subclinical thyroid disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;S&#46; Cooper"
                            1 => "B&#46; Biondi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(11)60276-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2012"
                        "volumen" => "379"
                        "paginaInicial" => "1142"
                        "paginaFinal" => "1154"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22273398"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypothyroidism and moderate subclinical hypothyroidism are associated with increased all-cause mortality independent of coronary heart disease risk factors&#58; a PreCIS database study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46; McQuade"
                            1 => "M&#46; Skugor"
                            2 => "D&#46;M&#46; Brennan"
                            3 => "B&#46; Hoar"
                            4 => "C&#46; Stevenson"
                            5 => "B&#46;J&#46; Hoogwerf"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1089/thy.2010.0298"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thyroid"
                        "fecha" => "2011"
                        "volumen" => "21"
                        "paginaInicial" => "837"
                        "paginaFinal" => "843"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21745107"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Subclinical hypothyroidism and the risk of coronary heart disease and mortality"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Rodondi"
                            1 => "W&#46;P&#46; den Elzen"
                            2 => "D&#46;C&#46; Bauer"
                            3 => "A&#46;R&#46; Cappola"
                            4 => "S&#46; Razvi"
                            5 => "J&#46;P&#46; Walsh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2010.1361"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2010"
                        "volumen" => "304"
                        "paginaInicial" => "1365"
                        "paginaFinal" => "1374"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20858880"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "La medida de los problemas de salud en el &#225;mbito internacional&#58; los estudios de carga de enfermedad"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Pereira"
                            1 => "J&#46; Ca&#241;&#243;n"
                            2 => "E&#46; &#193;lvarez"
                            3 => "R&#46; G&#232;nova"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Admin Sanitaria"
                        "fecha" => "2001"
                        "volumen" => "V"
                        "paginaInicial" => "441"
                        "paginaFinal" => "466"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relaci&#243;n en Espa&#241;a entre la investigaci&#243;n sanitaria financiada por el sistema nacional de salud y la carga de enfermedad en la comunidad"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "F&#46; Catal&#224; L&#243;pez"
                            1 => "E&#46; &#193;lvarez Mart&#237;n"
                            2 => "R&#46; G&#233;nova Maleras"
                            3 => "C&#46; Morant Ginestar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Esp Salud Publ"
                        "fecha" => "2009"
                        "volumen" => "83"
                        "paginaInicial" => "137"
                        "paginaFinal" => "151"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rethinking DALYs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "C&#46;J&#46;L&#46; Murray"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:6 [
                        "editores" => "C&#46;J&#46;L&#46;MurrayA&#46;L&#243;pez"
                        "paginaInicial" => "1"
                        "paginaFinal" => "98"
                        "edicion" => "vol&#46; I"
                        "serieTitulo" => "The global burden of disease"
                        "serieFecha" => "1996"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Defunciones seg&#250;n la Causa de Muerte 2009"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Instituto Nacional de Estad&#237;stica"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:2 [
                        "fecha" => "2012"
                        "editorial" => "INE"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;www&#46;ine&#46;es"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tablas de mortalidad de la poblaci&#243;n de Espa&#241;a 1991&#8211;2009&#46; Esperanza de vida por edad y sexo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Instituto Nacional de Estad&#237;stica"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:2 [
                        "fecha" => "2012"
                        "editorial" => "INE"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;www&#46;ine&#46;es"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Proyecciones de poblaci&#243;n a corto plazo&#46; 2011&#8211;2021"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Instituto Nacional de Estad&#237;stica"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:2 [
                        "fecha" => "2012"
                        "editorial" => "INE"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;www&#46;ine&#46;es"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reemplazo de la hormona tiroidea para el hipotiroidismo subcl&#237;nico &#40;Revisi&#243;n Cochrane traducida&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "H&#46;C&#46;C&#46;E&#46; Villar"
                            1 => "H&#46; Saconato"
                            2 => "O&#46; Valente"
                            3 => "A&#46;N&#46; Atallah"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:2 [
                        "titulo" => "La Biblioteca Cochrane Plus&#44; N&#250;mero 2"
                        "serieFecha" => "2008"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Proportion of disease caused or prevented by a given exposure&#44; trait or intervention"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "O&#46;S&#46; Miettinen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Epidemiol"
                        "fecha" => "1974"
                        "volumen" => "99"
                        "paginaInicial" => "325"
                        "paginaFinal" => "332"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4825599"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Estimating the population attributable risk for multiple risk factors using case&#8211;control data"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Bruzzi"
                            1 => "S&#46;B&#46; Green"
                            2 => "D&#46;P&#46; Byar"
                            3 => "L&#46;A&#46; Brinton"
                            4 => "C&#46; Schairer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Epidemiol"
                        "fecha" => "1985"
                        "volumen" => "122"
                        "paginaInicial" => "904"
                        "paginaFinal" => "914"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4050778"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Registro de diagn&#243;sticos al alta hospitalaria del Conjunto M&#237;nimo B&#225;sico de Datos &#40;CMBD&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Ministerio Sanidad&#44; servicios sociales e igualdad &#40;MSSI&#41;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2009"
                        "editorial" => "MSSI 2012"
                        "editorialLocalizacion" => "Madrid"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;www&#46;msc&#46;es"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Encuesta sobre discapacidades&#44; autonom&#237;a personal y situaciones de dependencia 2008"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Instituto Nacional de Estad&#237;stica"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:2 [
                        "fecha" => "2012"
                        "editorial" => "INE"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;www&#46;ine&#46;es"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Victorian Burden of Disease Study&#58; Morbidity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Public Health Division"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2001"
                        "editorial" => "Victorian Government&#58; Department of Human Services"
                        "editorialLocalizacion" => "Melbourne"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Confidence limits made easy&#58; interval estimation using a substitution method"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "L&#46;E&#46; Daly"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Epidemiol"
                        "fecha" => "1998"
                        "volumen" => "147"
                        "paginaInicial" => "783"
                        "paginaFinal" => "790"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9554420"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A practical guide for calculating indirect cost of disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;A&#46; Koopmanschap"
                            1 => "F&#46;F&#46; Rutten"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "PharmaEconomics"
                        "fecha" => "1996"
                        "volumen" => "10"
                        "paginaInicial" => "460"
                        "paginaFinal" => "466"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Encuesta anual de estructura salarial &#40;CNAE-2009&#41;&#46; A&#241;o 2008&#46; INE"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Instituto Nacional de Estad&#237;stica"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2012"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;www&#46;ine&#46;es"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Estimaci&#243;n de la prevalencia de hipotiroidismo en Lleida a partir de la prescripci&#243;n de hormonas tiroideas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;C&#46; Serna Arnaiz"
                            1 => "L&#46; Galv&#225;n Santiago"
                            2 => "E&#46; Gasc&#243; Eguiluz"
                            3 => "M&#46; Manrique Manrique"
                            4 => "M&#46;M&#46; Foix O&#241;a"
                            5 => "E&#46; Mart&#237;n Gracia"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Esp Salud Publ"
                        "fecha" => "2003"
                        "volumen" => "77"
                        "paginaInicial" => "405"
                        "paginaFinal" => "410"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Disfunci&#243;n tiroidea en poblaci&#243;n laboral hospitalaria"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "P&#46; Iglesias"
                            1 => "J&#46; L&#225;zaro"
                            2 => "G&#46; Velasco"
                            3 => "J&#46;J&#46; D&#237;ez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rce.2010.06.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Clin Esp"
                        "fecha" => "2010"
                        "volumen" => "210"
                        "paginaInicial" => "505"
                        "paginaFinal" => "508"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20851391"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detecci&#243;n de la disfunci&#243;n tiroidea en la poblaci&#243;n gestante&#58; est&#225; justi&#64257;cado el cribado universal"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Vila"
                            1 => "I&#46; Velasco"
                            2 => "S&#46; Gonz&#225;lez"
                            3 => "F&#46; Morales"
                            4 => "E&#46; S&#225;nchez"
                            5 => "J&#46;M&#46; Lailla"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Med Clin &#40;Barc&#41;"
                        "fecha" => "2012"
                        "volumen" => "139"
                        "numero" => "509"
                        "paginaInicial" => "e1"
                        "paginaFinal" => "e11"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Subclinical hypothyroidism is mild thyroid failure and should be treated"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;T&#46; McDermott"
                            1 => "E&#46;C&#46; Ridgway"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jcem.86.10.7959"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2001"
                        "volumen" => "86"
                        "paginaInicial" => "4585"
                        "paginaFinal" => "4590"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11600507"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The clinical significance of subclinical thyroid dysfunction"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46; Biondi"
                            1 => "D&#46;S&#46; Cooper"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/er.2006-0043"
                      "Revista" => array:6 [
                        "tituloSerie" => "Endocr Rev"
                        "fecha" => "2008"
                        "volumen" => "29"
                        "paginaInicial" => "76"
                        "paginaFinal" => "131"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17991805"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;E&#46; Haddow"
                            1 => "G&#46;E&#46; Palomaki"
                            2 => "W&#46;C&#46; Allan"
                            3 => "J&#46;R&#46; Williams"
                            4 => "G&#46;J&#46; Knight"
                            5 => "J&#46; Gagnon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM199908193410801"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1999"
                        "volumen" => "341"
                        "paginaInicial" => "549"
                        "paginaFinal" => "555"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10451459"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25&#8211;30 months"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Li"
                            1 => "Z&#46; Shan"
                            2 => "W&#46; Teng"
                            3 => "X&#46; Yu"
                            4 => "Y&#46; Li"
                            5 => "C&#46; Fan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Endocrinol &#40;Oxf&#41;"
                        "fecha" => "2010"
                        "volumen" => "72"
                        "paginaInicial" => "825"
                        "paginaFinal" => "829"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagn&#243;stico y tratamiento de la disfunci&#243;n tiroidea subcl&#237;nica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;J&#46; Corrales Hern&#225;ndez"
                            1 => "N&#46; Alonso Pedrol"
                            2 => "A&#46; Cant&#243;n Blanco"
                            3 => "J&#46;C&#46; Galofr&#233; Ferrater"
                            4 => "A&#46; P&#233;rez P&#233;rez"
                            5 => "T&#46; Lajo Morales"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Endocrinol Nutr"
                        "fecha" => "2007"
                        "volumen" => "54"
                        "paginaInicial" => "44"
                        "paginaFinal" => "52"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reconocimiento rec&#237;proco y toma de decisiones compartida con el paciente"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;M&#46; Costa-Alcaraz"
                            1 => "J&#46;C&#46; Siurana-Aparisoi"
                            2 => "C&#46; Almendro-Padilla"
                            3 => "S&#46; Garc&#237;a-Vicente"
                            4 => "R&#46; Ordov&#225;s-Casaurr&#225;n"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.rce.2011.01.025"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Clin Esp"
                        "fecha" => "2011"
                        "volumen" => "211"
                        "paginaInicial" => "581"
                        "paginaFinal" => "586"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22088666"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/22548874/0000021300000008/v1_201310250817/S225488741300101X/v1_201310250817/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "1901"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original Articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021300000008/v1_201310250817/S225488741300101X/v1_201310250817/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225488741300101X?idApp=WRCEE"
]
Share
Journal Information
Vol. 213. Issue 8.
Pages 363-369 (November 2013)
Share
Share
Download PDF
More article options
Visits
541
Vol. 213. Issue 8.
Pages 363-369 (November 2013)
Original article
Burden of illness attributable to subclinical hypothyroidism in the Spanish population
Carga de la enfermedad atribuible al hipotiroidismo subclínico en la población española
Visits
541
S. Donnay1, J.A. Balsa2, Julia Álvarez3, C. Crespo4,5, F. Pérez-Alcántara5, C. Polanco6,
Corresponding author
carlos.crespo@oblikue.com

Corresponding author.
1 Servicio de Endocrinología y Nutrición, Hospital Universitario Fundación Alcorcón, Madrid, Spain
2 Servicio de Endocrinología y Nutrición, Hospital Universitario Infanta Sofía, Madrid, Spain
3 Servicio de Endocrinología y Nutrición, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
4 Departamento de Estadística, Universidad de Barcelona, Barcelona, Spain
5 Oblikue Consulting, Barcelona, Spain
6 Economía de la Salud, Business Excellence & Strategy Realization, Merck S.L., Madrid, Spain
This item has received
Article information
Abstract
Full Text
Bibliography
Download PDF
Statistics
Figures (3)
Show moreShow less
Tables (1)
Table 1. Number of cardiac episodes, cardiac mortality and total mortality in patients with subclinical hypothyroidism according to various levels of TSH.
Abstract
Introduction

Subclinical hypothyroidism (SH) has been associated recently to cardiovascular diseases. However, the loss of health it entails remains unknown. This study has assessed the burden of illness attributable to SH in Spain.

Patients and methods

Based on the Spanish prevalence data found in international studies, a theoretical model was developed to estimate the Disability Adjusted Life Years (DALYs), years of life lost (YLL) and years lost due to disability (YLD) associated with SH. Prevalence of risk factors, coronary mortality risk and coronary event risk associated with SH were obtained from a review of the literature. An analysis was conducted according to the World Health Organization methodology approach for these studies, using official Spanish sources (hospital discharge records, minimum basic set data [MBSD], inpatient mortality records, etc.).

Results

In Spain, approximately 2,767,124 people have SH, specifically 1,949,820 with levels of TSH between 4.5 and 6.9mIU/L (70.5%), 538,988 with levels between 7 and 9.9mIU/L (19.5%), and 278,317 between 10 and 19.9mIU/L (10%). These subjects suffer approximately 12,608 cardiac events and 1388 deaths a year attributed to their SH. This represents 30,550 DALYs (13,124 YLL and 17,426 YLD). Between 1.6 and 7.3% of cardiovascular DALYs can be attributed to SH.

Conclusion

SH is a silent disease which considerably increases the burden of disease. Evaluation of SH, at least in patients belonging to risk groups, could be cost-effective.

Keywords:
Burden of illness
Hypothyroidism
Subclinical hypothyroidism
Disability-adjusted life year
Years of life lost
Years lost due to disability
Resumen
Introducción

El hipotiroidismo subclínico (HS) se ha asociado a enfermedades cardiovasculares, pero se desconoce la pérdida de salud que conlleva. Hemos evaluado la carga de enfermedad del HS en España.

pacientes y métodos

A partir de la prevalencia del HS en España, obtenida de estudios internacionales, se llevó a cabo un modelo teórico que calculó los años de vida ajustados por discapacidad (AVAD), los años de vida perdidos (AVP) y las pérdidas de salud por discapacidad (AVD) asociados al HS. Las prevalencias de los factores de riesgo, el riesgo de mortalidad coronaria y de eventos coronarios asociados al HS se obtuvieron de una revisión de la literatura. El análisis se llevó a cabo según la metodología de la Organización Mundial de la Salud, utilizando fuentes oficiales españolas (registro de altas hospitalaria: Conjunto Mínimo Básico de Datos [CMBD], registro de mortalidad hospitalaria,…).

Resultados

En España hay aproximadamente 2.767.124 personas con HS (1.949.820 con niveles de TSH entre 4,5 y 6,9 mUI/L [70,5%], 538.988 con TSH entre 7 y 9,9 mUI/L [19,5%], y 278.317 con TSH entre 10 y 19,9 mUI/L [10%]). Estas personas con HS podrían sufrir 12.608 eventos cardiacos y 1.388 muertes cardiacas anuales, lo que representa 30.550 AVAD (13.124 AVP y 17.426 AVD). El HS puede representar entre el 1,6 y el 7,3% de los AVAD cardiovasculares.

Conclusión

El HS es una condición silente que determina una enorme carga de enfermedad. La valoración del HS, al menos en pacientes pertenecientes a grupos de riesgo, podría ser coste-efectiva.

Palabras clave:
Carga de enfermedad
Hipotiroidismo
Hipotiroidismo subclínico
Años de vida ajustados por discapacidad
Años de vida perdidos
Años de salud perdidos por discapacidad

Article

These are the options to access the full texts of the publication Revista Clínica Española (English Edition)
Member
Si es usted socio de FESEMI siga los siguientes pasos:

Diríjase desde aquí a la web de la >>>FESEMI<<< e inicie sesión mediante el formulario que se encuentra en la barra superior, pulsando sobre el candado.

Una vez autentificado, en la misma web de FESEMI, en el menú superior, elija la opción deseada.

>>>FESEMI<<<

Subscriber
Subscriber

If you already have your login data, please click here .

If you have forgotten your password you can you can recover it by clicking here and selecting the option “I have forgotten my password”
Subscribe
Subscribe to

Revista Clínica Española (English Edition)

Purchase
Purchase article

Purchasing article the PDF version will be downloaded

Price 19.34 €

Purchase now
Contact
Phone for subscriptions and reporting of errors
From Monday to Friday from 9 a.m. to 6 p.m. (GMT + 1) except for the months of July and August which will be from 9 a.m. to 3 p.m.
Calls from Spain
932 415 960
Calls from outside Spain
+34 932 415 960
Email
Idiomas
Revista Clínica Española (English Edition)
Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?