array:23 [
  "pii" => "S266627522200090X"
  "issn" => "26662752"
  "doi" => "10.1016/j.abdp.2022.06.001"
  "estado" => "S300"
  "fechaPublicacion" => "2022-07-01"
  "aid" => "546"
  "copyrightAnyo" => "2022"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by/4.0/"
  "subdocumento" => "fla"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "en" => array:18 [
      "pii" => "S0365059622000666"
      "issn" => "03650596"
      "doi" => "10.1016/j.abd.2021.09.009"
      "estado" => "S300"
      "fechaPublicacion" => "2022-07-01"
      "aid" => "546"
      "documento" => "article"
      "crossmark" => 1
      "licencia" => "http://creativecommons.org/licenses/by/4.0/"
      "subdocumento" => "fla"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:1 [
        "total" => 0
      ]
      "en" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
        "titulo" => "Icatibant use in Brazilian patients with hereditary angioedema &#40;HAE&#41; type 1 or 2 and HAE with normal C1-INH levels&#58; findings from the Icatibant Outcome Survey Registry Study"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "tieneResumen" => "en"
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "448"
            "paginaFinal" => "457"
          ]
        ]
        "contieneResumen" => array:1 [
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "en" => true
        ]
        "contienePdf" => array:1 [
          "en" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:8 [
            "identificador" => "fig0005"
            "etiqueta" => "Figure 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 463
                "Ancho" => 2508
                "Tamanyo" => 92579
              ]
            ]
            "detalles" => array:1 [
              0 => array:3 [
                "identificador" => "at0005"
                "detalle" => "Figure "
                "rol" => "short"
              ]
            ]
            "descripcion" => array:1 [
              "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Treatment-related time-to-event effectiveness outcomes&#46; Adapted from&#58; Maurer M&#44; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46; HAE&#44; Hereditary Angioedema&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Anete S&#46; Grumach, Marina T&#46; Henriques, Maine L&#46;D&#46; Bardou, Daniele A&#46; Pontarolli, Jaco Botha, Mariangela Correa"
            "autores" => array:7 [
              0 => array:2 [
                "nombre" => "Anete S&#46;"
                "apellidos" => "Grumach"
              ]
              1 => array:2 [
                "nombre" => "Marina T&#46;"
                "apellidos" => "Henriques"
              ]
              2 => array:2 [
                "nombre" => "Maine L&#46;D&#46;"
                "apellidos" => "Bardou"
              ]
              3 => array:2 [
                "nombre" => "Daniele A&#46;"
                "apellidos" => "Pontarolli"
              ]
              4 => array:2 [
                "nombre" => "Jaco"
                "apellidos" => "Botha"
              ]
              5 => array:2 [
                "nombre" => "Mariangela"
                "apellidos" => "Correa"
              ]
              6 => array:1 [
                "colaborador" => "for the IOS Brazil Study Group"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "pt" => array:9 [
          "pii" => "S266627522200090X"
          "doi" => "10.1016/j.abdp.2022.06.001"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "pt"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S266627522200090X?idApp=UINPBA00008Z"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622000666?idApp=UINPBA00008Z"
      "url" => "/03650596/0000009700000004/v1_202206290808/S0365059622000666/v1_202206290808/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2666275222000984"
    "issn" => "26662752"
    "doi" => "10.1016/j.abdp.2022.06.009"
    "estado" => "S300"
    "fechaPublicacion" => "2022-07-01"
    "aid" => "559"
    "copyright" => "Sociedade Brasileira de Dermatologia"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "fla"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "pt" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Artigo original</span>"
      "titulo" => "Diferencial de radia&#231;&#227;o UVB regula a express&#227;o de miRNAs no fotoenvelhecimento da pele"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "tieneResumen" => "pt"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "458"
          "paginaFinal" => "466"
        ]
      ]
      "contieneResumen" => array:1 [
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0030"
          "etiqueta" => "Figura 6"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr6.jpeg"
              "Alto" => 1971
              "Ancho" => 1675
              "Tamanyo" => 144201
            ]
          ]
          "descripcion" => array:1 [
            "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Valida&#231;&#227;o de miRNA&#8208;195a&#8208;5p utilizando RT&#8208;qPCR&#46; Os dados foram normalizados pela m&#233;dia &#177; erro padr&#227;o da m&#233;dia &#40;EPM&#41;&#46; &#42;&#42;&#42;p &#8804; 0&#44;001&#44; &#42;&#42;&#42;&#42;p &#8804; 0&#44;0001&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Yuan Fang, Lei Chen, Xin Wang, Xu Li, Wu Xiong, Xi Zhang, Yufang Zhang, Lu Han, Ke Cao, Xiang Chen, Haibo Li, Jianda Zhou"
          "autores" => array:12 [
            0 => array:2 [
              "nombre" => "Yuan"
              "apellidos" => "Fang"
            ]
            1 => array:2 [
              "nombre" => "Lei"
              "apellidos" => "Chen"
            ]
            2 => array:2 [
              "nombre" => "Xin"
              "apellidos" => "Wang"
            ]
            3 => array:2 [
              "nombre" => "Xu"
              "apellidos" => "Li"
            ]
            4 => array:2 [
              "nombre" => "Wu"
              "apellidos" => "Xiong"
            ]
            5 => array:2 [
              "nombre" => "Xi"
              "apellidos" => "Zhang"
            ]
            6 => array:2 [
              "nombre" => "Yufang"
              "apellidos" => "Zhang"
            ]
            7 => array:2 [
              "nombre" => "Lu"
              "apellidos" => "Han"
            ]
            8 => array:2 [
              "nombre" => "Ke"
              "apellidos" => "Cao"
            ]
            9 => array:2 [
              "nombre" => "Xiang"
              "apellidos" => "Chen"
            ]
            10 => array:2 [
              "nombre" => "Haibo"
              "apellidos" => "Li"
            ]
            11 => array:2 [
              "nombre" => "Jianda"
              "apellidos" => "Zhou"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0365059622000794"
        "doi" => "10.1016/j.abd.2022.01.003"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622000794?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222000984?idApp=UINPBA00008Z"
    "url" => "/26662752/0000009700000004/v1_202207280537/S2666275222000984/v1_202207280537/pt/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S2666275222000856"
    "issn" => "26662752"
    "doi" => "10.1016/j.abdp.2022.05.008"
    "estado" => "S300"
    "fechaPublicacion" => "2022-07-01"
    "aid" => "543"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "fla"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "pt" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Artigo original</span>"
      "titulo" => "Projeto ECHO na dermatite at&#243;pica na Argentina&#58; estrat&#233;gia inovadora para atingir &#225;reas carentes de conhecimento atualizado&#44; primeiro ano de experi&#234;ncia"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "tieneResumen" => "pt"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "443"
          "paginaFinal" => "447"
        ]
      ]
      "contieneResumen" => array:1 [
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => 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" => 880
              "Ancho" => 1734
              "Tamanyo" => 73466
            ]
          ]
          "descripcion" => array:1 [
            "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Distribui&#231;&#227;o dos participantes por especialidade&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Paula C&#46; Luna, Mar&#237;a Emilia Debernardi, Cristina Mariela Echeverr&#237;a, Mar&#237;a Valeria Angles, Luis D&#46; Mazzuoccolo"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "Paula C&#46;"
              "apellidos" => "Luna"
            ]
            1 => array:2 [
              "nombre" => "Mar&#237;a Emilia"
              "apellidos" => "Debernardi"
            ]
            2 => array:2 [
              "nombre" => "Cristina Mariela"
              "apellidos" => "Echeverr&#237;a"
            ]
            3 => array:2 [
              "nombre" => "Mar&#237;a Valeria"
              "apellidos" => "Angles"
            ]
            4 => array:2 [
              "nombre" => "Luis D&#46;"
              "apellidos" => "Mazzuoccolo"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0365059622000630"
        "doi" => "10.1016/j.abd.2021.09.006"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622000630?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222000856?idApp=UINPBA00008Z"
    "url" => "/26662752/0000009700000004/v1_202207280537/S2666275222000856/v1_202207280537/pt/main.assets"
  ]
  "pt" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Artigo original</span>"
    "titulo" => "Uso de icatibanto em pacientes brasileiros com angioedema heredit&#225;rio &#40;AEH&#41; tipo 1 ou 2 e AEH com n&#237;veis normais de C1&#8208;INH&#58; achados do registro do estudo <span class="elsevierStyleItalic">Icatibant Outcome Survey</span>"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "448"
        "paginaFinal" => "457"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Anete S&#46; Grumach, Marina T&#46; Henriques, Maine L&#46;D&#46; Bardou, Daniele A&#46; Pontarolli, Jaco Botha, Mariangela Correa"
        "autores" => array:7 [
          0 => array:4 [
            "nombre" => "Anete S&#46;"
            "apellidos" => "Grumach"
            "email" => array:1 [
              0 => "anete.grumach@fmabc.net"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Marina T&#46;"
            "apellidos" => "Henriques"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Maine L&#46;D&#46;"
            "apellidos" => "Bardou"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Daniele A&#46;"
            "apellidos" => "Pontarolli"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Jaco"
            "apellidos" => "Botha"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Mariangela"
            "apellidos" => "Correa"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          6 => array:1 [
            "colaborador" => "for the IOS Brazil Study Group"
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Imunologia Cl&#237;nica&#44; Faculdade de Medicina&#44; Centro Universitario Sa&#250;de ABC&#44; Santo Andr&#233;&#44; SP&#44; Brasil"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Takeda Pharmaceuticals International AG&#44; Zurique&#44; Su&#237;&#231;a"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Takeda Distribuidora Ltda&#44; S&#227;o Paulo&#44; SP&#44; Brasil"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Autor para correspond&#234;ncia&#46;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figura 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 1567
            "Ancho" => 3333
            "Tamanyo" => 317867
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Resultados de tempo para o evento&#46; As bordas inferior e superior das caixas representam os percentis 25 e 75&#44; respectivamente&#59; os <span class="elsevierStyleItalic">whiskers</span> das caixas denotam os valores m&#237;nimos e m&#225;ximos registrados&#46; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio tipo 1 ou 2&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#59; DP&#44; desvio padr&#227;o&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">O angioedema heredit&#225;rio &#40;AEH&#41; &#233; doen&#231;a gen&#233;tica rara associada a epis&#243;dios de edemas dolorosos que afetam os tecidos subcut&#226;neos e&#47;ou submucosos&#46; As crises geralmente afetam a regi&#227;o da cabe&#231;a e pesco&#231;o&#44; as extremidades e o abd&#244;men&#46; O edema lar&#237;ngeo pode ser potencialmente fatal em virtude do risco de asfixia&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">As crises de AEH recorrem com frequ&#234;ncia e gravidade imprevis&#237;veis&#44; afetando a vida pessoal e profissional dos pacientes e impondo uma pesada carga f&#237;sica e emocional aos pacientes&#44; familiares e cuidadores&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">3&#8211;5</span></a> Epis&#243;dios de edema dolorosos e potencialmente debilitantes podem afetar negativamente a produtividade do trabalho dos pacientes&#44; dificultar a realiza&#231;&#227;o de metas educacionais e levar &#224; ansiedade sobre crises futuras&#44; mesmo durante per&#237;odos sem crise&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">5&#44;6</span></a> De acordo com as diretrizes internacionais de manejo do AEH&#44; o tratamento oportuno de crises agudas e a preven&#231;&#227;o eficaz de crises futuras s&#227;o aspectos integrais do cuidado para pacientes com AEH&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">7&#44;8</span></a> O objetivo final &#233; reduzir a frequ&#234;ncia&#44; a dura&#231;&#227;o e a gravidade das crises&#44; minimizando assim a carga da doen&#231;a e ajudando a normalizar a vida di&#225;ria dos pacientes&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">3&#44;8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">O AEH tipo 1 &#40;em virtude dos baixos n&#237;veis e fun&#231;&#227;o do inibidor de C1 &#91;C1&#8208;INH&#93;&#41; ou tipo 2 &#40;em raz&#227;o da presen&#231;a de C1&#8208;INH disfuncional&#41; &#233; causado principalmente por muta&#231;&#245;es em <span class="elsevierStyleItalic">SERPING1</span>&#44; o gene que codifica o inibidor de C1 &#40;C1&#8208;INH&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">7&#44;9</span></a> C1&#8208;INH &#233; uma protease serina que desempenha papel fundamental na atividade de <span class="elsevierStyleItalic">down</span>&#8208;regula&#231;&#227;o em v&#225;rias cascatas de sinaliza&#231;&#227;o&#44; incluindo a via do complemento&#44; sistema de contato &#40;por meio da cascata calicre&#237;na&#8208;cinina&#41;&#44; via de coagula&#231;&#227;o e fibrin&#243;lise&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">10</span></a> Dentro da cascata de calicre&#237;na&#8208;cinina&#44; o C1&#8208;INH &#233; um inibidor essencial do fator XIIa e da calicre&#237;na plasm&#225;tica&#44; que s&#227;o proteases plasm&#225;ticas&#8208;chave envolvidas na produ&#231;&#227;o de bradicinina&#44; um potente vasodilatador&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">9&#44;10</span></a> A aus&#234;ncia de fun&#231;&#227;o suficiente de C1&#8208;INH leva &#224; ativa&#231;&#227;o descontrolada da via calicre&#237;na&#8208;cinina e &#224; superprodu&#231;&#227;o de bradicinina&#44; a causa subjacente de edema e incha&#231;o em pacientes com AEH tipo 1 ou 2 &#40;AEH&#8208;1&#47;2&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">9&#44;11&#44;12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A presen&#231;a de AEH em pacientes com n&#237;veis e fun&#231;&#227;o normais de C1&#8208;INH &#40;AEH NC1&#8208;INH&#41; tamb&#233;m est&#225; sendo cada vez mais identificada&#59; as vias patogen&#233;ticas ainda n&#227;o foram totalmente elucidadas&#46; V&#225;rias muta&#231;&#245;es em outros genes al&#233;m de <span class="elsevierStyleItalic">SERPING1</span> foram relatadas at&#233; o momento &#40;por exemplo&#44; <span class="elsevierStyleItalic">FXII</span>&#44; cadeia pesada de cininog&#234;nio&#8208;1&#44; plasminog&#234;nio&#44; angiopoietina&#8208;1&#41;&#44; e achados recentes sugerem que a presen&#231;a de uma variante de ganho de fun&#231;&#227;o de mioferlina pode <span class="elsevierStyleItalic">up</span>&#8208;regular a sinaliza&#231;&#227;o mediada pelo fator de crescimento endotelial vascular&#44; levando a permeabilidade vascular excessiva&#46; No entanto&#44; a muta&#231;&#227;o subjacente geralmente permanece desconhecida&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">12&#44;13</span></a> Como acredita&#8208;se que a bradicinina desempenhe papel importante na patog&#234;nese das manifesta&#231;&#245;es cl&#237;nicas do AEH NC1&#8208;INH&#44;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">11&#44;12&#44;14</span></a> terapias que interferem na produ&#231;&#227;o de bradicinina ou em atividades biol&#243;gicas mediadas pela bradicinina podem&#44; em princ&#237;pio&#44; tamb&#233;m ser eficazes em pacientes com essas formas de AEH&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">11</span></a> Nenhum ensaio cl&#237;nico controlado foi realizado at&#233; o momento nesse cen&#225;rio&#59; entretanto&#44; evid&#234;ncias de relatos de casos ou estudos observacionais mostram achados encorajadores em alguns pacientes&#44; incluindo aqueles tratados com icatibanto para crises agudas de AEH&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">15&#8211;17</span></a> Permanece uma necessidade urgente&#44; ainda n&#227;o atendida&#44; de avalia&#231;&#227;o adicional das op&#231;&#245;es de tratamento nessa popula&#231;&#227;o de pacientes&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">O <span class="elsevierStyleItalic">Icatibant Outcome Survey</span> &#40;IOS&#59; NCT01034969&#41; &#233; um estudo de registro p&#243;s&#8208;comercializa&#231;&#227;o&#44; observacional multic&#234;ntrico&#44; internacional e em andamento&#44; que monitora a seguran&#231;a e a efic&#225;cia do icatibanto&#44; um antagonista do receptor B<span class="elsevierStyleInf">2</span> da bradicinina&#44; usado no tratamento agudo de crises de angioedema&#46; O IOS foi iniciado &#40;pela Shire&#44; uma empresa Takeda&#41; em 2009&#44; e desde 30 de setembro de 2019 inscreveu 1&#46;491 pacientes de 13 pa&#237;ses&#44; incluindo 10 pa&#237;ses europeus&#44; al&#233;m de Austr&#225;lia&#44; Brasil e Israel&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">A caracteriza&#231;&#227;o formal do AEH no Brasil teve in&#237;cio em 2006&#44; com a cria&#231;&#227;o do registro brasileiro de AEH pela Rede Brasileira de Diagn&#243;stico&#44; Manejo e Tratamento de AEH&#59; o conhecimento sobre a popula&#231;&#227;o brasileira de pacientes com AEH continua a crescer&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">18</span></a> A preval&#234;ncia estimada de AEH no Brasil &#233; de 4&#46;220 pacientes &#40;com base em uma estimativa de 211 milh&#245;es de pessoas no Brasil em 2020 e uma preval&#234;ncia mundial presumida de AEH de &#8764;1&#58;50&#46;000&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">7&#44;19</span></a> As caracter&#237;sticas cl&#237;nicas e muta&#231;&#245;es gen&#233;ticas em pacientes brasileiros com AEH est&#227;o sendo cada vez mais relatados&#44; incluindo achados em pacientes com AEH&#8208;1&#47;2<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">20&#8211;22</span></a> e naqueles com AEH NC1&#8208;INH&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">16&#44;23&#8211;25</span></a> Estudos avaliando a qualidade de vida em pacientes brasileiros com AEH demonstram uma carga pesada da doen&#231;a nessa popula&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">26&#44;27</span></a> A maioria dos pacientes relatou medo cont&#237;nuo de crises potencialmente fatais e demonstrou comprometimento f&#237;sico e emocional&#59; o impacto negativo foi particularmente observado no que diz respeito &#224; vitalidade e fun&#231;&#227;o social&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A presente an&#225;lise relata achados de pacientes brasileiros &#40;recrutados no Brasil&#41; que foram inscritos no IOS at&#233; 30 de setembro de 2019&#44; incluindo dados demogr&#225;ficos&#44; caracter&#237;sticas cl&#237;nicas e resultados de tratamento em pacientes com AEH&#8208;1&#47;2 e aqueles com AEH NC1&#8208;INH&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Pacientes e resultados</span><p id="par0040" class="elsevierStylePara elsevierViewall">O IOS est&#225; em conformidade com os regulamentos e melhores pr&#225;ticas globais e locais relevantes e segue os princ&#237;pios da Declara&#231;&#227;o de Helsinque e as Diretrizes da <span class="elsevierStyleItalic">International Conference on Harmonisation &#8211; Good Clinical Practice</span>&#46; A aprova&#231;&#227;o foi concedida pelas autoridades de sa&#250;de e comit&#234;s de &#233;tica locais&#46; O consentimento informado por escrito foi fornecido por todos os pacientes &#40;ou seu representante legalmente autorizado&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">O registro IOS est&#225; aberto a todos os pacientes com AEH que receberam pelo menos uma dose de icatibanto&#46; &#201; digno de nota o fato de que&#44; diferentemente de outros pa&#237;ses do IOS&#44; os pacientes no Brasil precisavam ter idade &#8805; 18 para participar &#40;embora o icatibanto agora seja aprovado para uso em pacientes com idade &#60; 18 no Brasil&#41;&#46; De acordo com as descri&#231;&#245;es publicadas anteriormente do desenho de estudo do IOS&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">28</span></a> os dados demogr&#225;ficos dos pacientes&#44; suas caracter&#237;sticas cl&#237;nicas e hist&#243;rico de crises de AEH &#40;incluindo local&#44; frequ&#234;ncia&#44; gravidade&#44; dura&#231;&#227;o&#44; resultados do tratamento e tolerabilidade&#41; foram coletados na inscri&#231;&#227;o&#44; e as informa&#231;&#245;es relacionadas &#224;s crises de AEH foram registradas em visitas regulares de seguimento &#40;de prefer&#234;ncia a cada seis meses&#41;&#46; Os resultados tempo&#8208;at&#233;&#8208;o&#8208;evento relacionados ao tratamento avaliados foram o tempo at&#233; a primeira administra&#231;&#227;o de icatibanto &#40;dura&#231;&#227;o entre o in&#237;cio da crise e a primeira administra&#231;&#227;o de icatibanto&#41;&#59; tempo para resolu&#231;&#227;o completa &#40;dura&#231;&#227;o entre a primeira administra&#231;&#227;o de icatibanto e resolu&#231;&#227;o completa de todos os sintomas&#41; e dura&#231;&#227;o total da crise &#40;tempo entre o in&#237;cio da crise e a resolu&#231;&#227;o completa de todos os sintomas&#59; <a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Eventos adversos &#40;EAs&#41; foram categorizados de acordo com o <span class="elsevierStyleItalic">Dicion&#225;rio M&#233;dico para Classifica&#231;&#227;o de &#211;rg&#227;os do Sistema de Atividades Regulat&#243;rias e Termos Preferenciais</span>&#46; Os EAs ocorridos antes da inscri&#231;&#227;o foram registrados na entrada do paciente no IOS como parte do seu hist&#243;rico m&#233;dico&#44; enquanto os EAs ocorridos ap&#243;s a inscri&#231;&#227;o no IOS foram relatados durante as visitas de seguimento&#46; Embora o uso <span class="elsevierStyleItalic">off&#8208;label</span> tenha sido documentado no registro do IOS como parte das informa&#231;&#245;es de seguran&#231;a a serem relatadas de acordo com as normas regulat&#243;rias&#44; tais eventos n&#227;o foram considerados clinicamente significativos e&#44; como tal&#44; foram analisados separadamente da presente an&#225;lise de seguran&#231;a dos EAs&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">An&#225;lise estat&#237;stica</span><p id="par0055" class="elsevierStylePara elsevierViewall">Todas as an&#225;lises estat&#237;sticas foram realizadas com o software SAS&#174; vers&#227;o 9&#46;4 &#40;SAS Institute&#44; Cary&#44; NC&#44; Estados Unidos&#41;&#46; As medidas quantitativas dos resultados foram relatadas como n&#250;mero de observa&#231;&#245;es&#44; m&#233;dia &#40;desvio padr&#227;o &#91;DP&#93;&#41; ou mediana&#44; primeiro quartil &#40;25&#176; percentil&#41;&#44; terceiro quartil &#40;75&#176; percentil&#41;&#44; valores m&#237;nimos e m&#225;ximos&#46; As diferen&#231;as estat&#237;sticas nas caracter&#237;sticas basais entre pacientes com AEH&#8208;1&#47;2 e pacientes com AEH nC1&#8208;INH foram avaliadas usando o teste de Wilcoxon ou o teste Qui&#8208;Quadrado&#46; As avalia&#231;&#245;es dos resultados do tempo&#8208;at&#233;&#8208;o&#8208;tratamento foram realizadas usando um modelo misto para medidas repetidas com dados transformados em log<span class="elsevierStyleInf">10</span>&#46; As compara&#231;&#245;es de gravidade &#40;leve&#44; moderada <span class="elsevierStyleItalic">vs</span>&#46; grave&#44; muito grave&#41; foram realizadas utilizando um modelo misto linear generalizado de medidas repetidas&#46; Dada a natureza observacional deste registro&#44; todas as an&#225;lises foram consideradas explorat&#243;rias e os valores de p foram interpretados de maneira descritiva&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Resultados</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Caracter&#237;sticas basais</span><p id="par0060" class="elsevierStylePara elsevierViewall">Em 30 de setembro de 2019&#44; um total de 42 pacientes do Brasil estavam inscritos no registro IOS&#44; representando 2&#44;8&#37; do total de inscri&#231;&#245;es de pacientes &#40;AEH&#8208;1&#47;2&#44; n &#61; 26&#59; AEH nC1&#8208;INH&#44; n &#61; 16&#41;&#46; As caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas est&#227;o apresentadas na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a> e na <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>&#46; A maioria dos pacientes era do sexo feminino &#40;AEH&#8208;1&#47;2&#44; 84&#44;6&#37;&#59; AEH nC1&#8208;INH&#44; 100&#37;&#41;&#46; A maioria relatou hist&#243;ria familiar positiva &#40;AEH&#8208;1&#47;2&#44; 80&#44;8&#37;&#59; AEH nC1&#8208;INH&#44; 93&#44;8&#37;&#41;&#46; A mediana da idade no in&#237;cio dos sintomas foi significativamente menor em pacientes com AEH&#8208;1&#47;2 em rela&#231;&#227;o &#224;queles com AEH nC1&#8208;INH &#40;10&#44;0 <span class="elsevierStyleItalic">vs</span>&#46; 16&#44;5 anos&#59; p &#61; 0&#44;0105&#41;&#46; A mediana da idade ao diagn&#243;stico &#40;31&#44;1 <span class="elsevierStyleItalic">vs</span>&#46; 40&#44;9 anos&#59; p &#61; 0&#44;1276&#41; e a mediana do tempo entre o in&#237;cio dos sintomas e o diagn&#243;stico &#40;15&#44;0 <span class="elsevierStyleItalic">vs</span>&#46; 23&#44;8 anos&#59; p &#61; 0&#44;6680&#41; foram numericamente menores em pacientes com AEH&#8208;1&#47;2 do que naqueles com AEH nC1&#8208;INH&#44; respectivamente&#44; mas as diferen&#231;as n&#227;o foram estatisticamente significativas&#46; No momento do corte dos dados&#44; as informa&#231;&#245;es coletadas sobre a presen&#231;a ou aus&#234;ncia de muta&#231;&#245;es gen&#233;ticas espec&#237;ficas em pacientes com AEH nC1&#8208;INH estavam incompletas&#59; assim&#44; os resultados dessa an&#225;lise n&#227;o s&#227;o apresentados&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">N&#250;mero de crises e n&#250;mero de administra&#231;&#245;es de icatibanto</span><p id="par0065" class="elsevierStylePara elsevierViewall">Um total de 165 crises tratadas com icatibanto foi relatado em 18 pacientes com AEH&#8208;1&#47;2&#44; e 63 crises tratadas com icatibanto foram relatadas em 10 pacientes com AEH nC1&#8208;INH&#46; Uma administra&#231;&#227;o de icatibanto foi usada para a maioria das crises &#40;95&#44;7&#37; em pacientes com AEH&#8208;1&#47;2&#59; 96&#44;7&#37; naqueles com AEH nC1&#8208;INH&#41;&#44; conforme <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; &#201; digno de nota que a terapia de resgate concomitante com outros agentes al&#233;m do icatibanto para o tratamento de crises de AEH foi utilizada por alguns pacientes &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; Medicamentos de resgate concomitantes podem ter sido utilizados para ajudar a aliviar os sintomas da crise&#44; em vez de trat&#225;&#8208;la&#46; Por exemplo&#44; analg&#233;sicos e antiem&#233;ticos podem ter sido usados para tratar a dor&#44; n&#225;useas e v&#244;mitos que podem acompanhar crises abdominais&#44; e fluidos podem ter sido administrados como cuidados de suporte para a mesma crise&#46; Em alguns casos&#44; os pacientes utilizaram v&#225;rios medicamentos de resgate&#44; mas n&#227;o necessariamente para a mesma crise&#46; Os agentes utilizados para crises espec&#237;ficas n&#227;o foram registrados&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Ao longo de uma m&#233;dia &#40;DP&#41; de 4&#44;5 &#40;1&#44;66&#41; anos de seguimento &#40;desde a entrada no IOS at&#233; a data da extra&#231;&#227;o de dados ou descontinua&#231;&#227;o&#41; para pacientes com AEH&#8208;1&#47;2&#44; e uma m&#233;dia &#40;DP&#41; de 4&#44;3 &#40;1&#44;42&#41; anos de seguimento para pacientes com AEH nC1&#8208;INH&#44; o n&#250;mero m&#225;ximo de crises relatadas por paciente foi maior em pacientes com AEH&#8208;1&#47;2 &#40;29 crises&#41; do que naqueles com AEH nC1&#8208;INH &#40;17 crises&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Local e gravidade das crises</span><p id="par0075" class="elsevierStylePara elsevierViewall">Em pacientes com AEH&#8208;1&#47;2&#44; a maioria das crises &#40;72&#44;6&#37;&#41; afetou um &#250;nico local &#8211; mais comumente o abd&#244;men &#40;46&#44;3&#37;&#41;&#44; seguido pela pele &#40;22&#44;0&#37;&#59; <a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46; A combina&#231;&#227;o de locais mais comuns envolveu pele e abd&#244;men &#40;15&#44;2&#37;&#41;&#46; Em pacientes com AEH nC1&#8208;INH&#44; as crises tinham a mesma probabilidade de afetar um &#250;nico local ou v&#225;rios locais &#40;50&#37; cada&#41;&#46; A pele e o abd&#244;men foram os locais mais acometidos &#40;20&#37; cada&#41;&#46; A combina&#231;&#227;o de s&#237;tios mais comum envolveu pele e laringe &#40;25&#44;0&#37;&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Os pacientes com AEH nC1&#8208;INH eram mais propensos do que aqueles com AEH&#8208;1&#47;2 a apresentar crises graves ou muito graves antes do tratamento &#40;61&#44;7&#37; <span class="elsevierStyleItalic">vs</span>&#46; 48&#44;8&#37;&#44; respectivamente&#41;&#46; Entretanto&#44; essa diferen&#231;a &#40;grave <span class="elsevierStyleItalic">vs</span>&#46; muito grave&#41; n&#227;o foi significativa &#40;p &#61; 0&#44;8906&#41;&#44; assim como a diferen&#231;a na ocorr&#234;ncia de crises leves&#47;moderadas <span class="elsevierStyleItalic">vs</span>&#46; graves&#47;muito graves &#40;p &#61; 0&#44;1038&#59; <a class="elsevierStyleCrossRef" href="#fig0020">fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados de tempo&#8208;at&#233;&#8208;o&#8208;evento relacionados ao tratamento</span><p id="par0085" class="elsevierStylePara elsevierViewall">Os dados dos resultados do tratamento estavam dispon&#237;veis para at&#233; 142 crises em 17 pacientes com AEH&#8208;1&#47;2 e para at&#233; 52 crises em oito pacientes com AEH nC1&#8208;INH&#46; Todas as medianas &#40;varia&#231;&#227;o&#41; dos resultados de tempo&#8208;at&#233;&#8208;o&#8208;evento foram menores para pacientes com AEH nC1&#8208;INH &#40;<a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#44; incluindo o tempo desde o in&#237;cio da crise at&#233; a primeira administra&#231;&#227;o de icatibanto &#40;AEH nC1&#8208;INH&#44; n &#61; 47 crises&#44; 0&#44;5 &#91;0&#8208;96&#44;0&#93; horas&#59; AEH&#8208;1&#47;2&#44; n &#61; 135 crises&#44; 1&#44;0 &#91;0&#8208;94&#44;0&#93; horas&#41;&#59; tempo desde a primeira administra&#231;&#227;o de icatibanto at&#233; a resolu&#231;&#227;o completa dos sintomas &#40;AEH nC1&#8208;INH&#44; n &#61; 52 crises&#44; 1&#44;0 &#91;0&#8211;88&#44;0&#93; horas&#59; AEH&#8208;1&#47;2&#44; n &#61; 142 crises&#44; 5&#44;5 &#91;0&#8211;96&#44;0&#93; horas&#41;&#59; e dura&#231;&#227;o total da crise &#40;AEH nC1&#8208;INH&#44; n &#61; 45 crises&#44; 7&#44;0 &#91;0&#44;3&#8211;99&#44;0&#93; horas&#59; AEH&#8208;1&#47;2&#44; n &#61; 124 crises&#44; 18&#44;5 &#91;0&#44;1&#8211;100&#44;0&#93; horas&#41;&#46; &#201; importante notar que a m&#233;dia de tempo &#40;DP&#41; desde o in&#237;cio da crise at&#233; a resolu&#231;&#227;o foi significativamente menor para pacientes com AEH nC1&#8208;INH <span class="elsevierStyleItalic">vs</span>&#46; AEH&#8208;1&#47;2 &#40;9&#44;8 &#91;18&#44;7&#93; horas <span class="elsevierStyleItalic">vs</span>&#46; 19&#44;6 &#91;24&#44;0&#93; horas&#59; p &#61; 0&#44;0174&#59; <a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Seguran&#231;a</span><p id="par0090" class="elsevierStylePara elsevierViewall">Foram relatados 83 eventos em 42 pacientes&#44; a maioria classificado como leve &#40;66&#44;3&#37;&#41; ou moderado &#40;13&#44;3&#37;&#41; em gravidade e n&#227;o grave &#40;75&#44;9&#37;&#41;&#46; Nenhum dos eventos foi potencialmente fatal ou fatal&#46; Um total de 44 EAs foram relatados em 16 pacientes como possivelmente &#40;quatro eventos&#41; ou provavelmente &#40;40 eventos&#41; relacionados ao uso de icatibanto&#46; O EA mais comum relacionado ao icatibanto foi o eritema no local da inje&#231;&#227;o&#44; afetando 34&#44;6&#37; dos pacientes com AEH&#8208;1&#47;2 e 18&#44;8&#37; daqueles com AEH nC1&#8208;INH &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46; Nenhum evento inesperado ou novos sinais relacionados &#224; seguran&#231;a foram detectados&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discuss&#227;o</span><p id="par0095" class="elsevierStylePara elsevierViewall">Os achados da an&#225;lise atual fornecem uma representa&#231;&#227;o valiosa no mundo real em rela&#231;&#227;o ao uso de icatibanto no tratamento de pacientes com AEH&#8208;1&#47;2 e AEH nC1&#8208;INH no Brasil&#46; Embora apenas um local no Brasil tenha participado&#44; um n&#250;mero substancial de pacientes foi inclu&#237;do&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">As caracter&#237;sticas basais e as caracter&#237;sticas cl&#237;nicas de pacientes com AEH nC1&#8208;INH foram geralmente consistentes com achados publicados anteriormente de coortes de pacientes franceses e brasileiros com AEH nC1&#8208;INH&#44;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">16&#44;23&#44;29&#44;30</span></a> e os achados em pacientes com AEH&#8208;1&#47;2 foram consistentes com caracter&#237;sticas publicadas anteriormente em coortes brasileiras de pacientes com AEH&#8208;1&#47;2&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">18&#44;21&#44;22</span></a> Em compara&#231;&#227;o com pacientes com AEH&#8208;1&#47;2&#44; os pacientes com AEH nC1&#8208;INH tinham uma mediana de idade maior no in&#237;cio dos sintomas&#44; uma idade avan&#231;ada ao diagn&#243;stico e tempo prolongado entre o in&#237;cio dos sintomas e o diagn&#243;stico&#46; Ao longo de um per&#237;odo de seguimento semelhante para os dois grupos de pacientes&#44; os pacientes com AEH nC1&#8208;INH tiveram menos crises de AEH do que aqueles com AEH&#8208;1&#47;2&#46; Esse achado &#233; consistente com uma probabilidade maior de intervalos livres de doen&#231;a descritos anteriormente em pacientes com AEH nC1&#8208;INH&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">31</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Na presente an&#225;lise&#44; a localiza&#231;&#227;o das crises em pacientes com AEH&#8208;1&#47;2 &#40;mais comumente afetando o abd&#244;men ou a pele&#41; foi compar&#225;vel &#224;quelas relatadas anteriormente em outras coortes brasileiras de pacientes com AEH&#8208;1&#47;2&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">18&#44;22</span></a> Pacientes com AEH nC1&#8208;INH eram mais propensos a sofrer crises lar&#237;ngeas e menos propensos a sofrer crises abdominais do que os com AEH&#8208;1&#47;2&#44; consistente com relatos anteriores&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">31&#44;32</span></a> Deve&#8208;se notar&#44; no entanto&#44; que v&#225;rios achados relatados recentemente demonstram a ocorr&#234;ncia de crises abdominais em &#62; 50&#37; dos pacientes com AEH nC1&#8208;INH&#44; especialmente na presen&#231;a de muta&#231;&#245;es FXII&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">16&#44;23&#44;29</span></a> Os achados do presente estudo mostraram ainda que&#44; independentemente do tipo de AEH&#44; a maioria das crises foi efetivamente tratada com uma administra&#231;&#227;o de icatibanto&#44; como relatado anteriormente em pacientes franceses com AEH&#8208;1&#47;2&#44; bem como naqueles com AEH nC1&#8208;INH inclu&#237;dos no IOS&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">29</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Os achados positivos desta an&#225;lise de pacientes brasileiros do IOS baseiam&#8208;se na efic&#225;cia e seguran&#231;a a longo prazo do icatibanto&#44; demonstrada em mais de 10 anos de experi&#234;ncia com 1&#46;052 pacientes com AEH&#8208;1&#47;2 no registro do IOS em mar&#231;o de 2019&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">33</span></a> Naquela an&#225;lise&#44; com base em dados de 5&#46;253 crises tratadas&#44; a resolu&#231;&#227;o completa dos sintomas relacionados &#224; crise ocorreu em uma m&#233;dia de 6 horas ap&#243;s a administra&#231;&#227;o da primeira dose de icatibanto&#46; A dura&#231;&#227;o m&#233;dia total da crise foi de 9 horas&#46; De 618 pacientes com AEH&#8208;1&#47;2 expostos ao icatibanto durante o per&#237;odo de seguimento&#44; 24 relataram um total de 75 EAs que foram considerados possivelmente ou provavelmente relacionados ao uso de icatibanto&#46; Os EAs mais frequentes relacionados ao icatibanto foram eritema no local da inje&#231;&#227;o &#40;29&#44;3&#37;&#41; e astenia &#40;9&#44;3&#37;&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Estudos n&#227;o controlados mostraram resultados encorajadores do tratamento com icatibanto em pacientes com AEH nC1&#8208;INH&#44; incluindo relatos de casos e an&#225;lises retrospectivas&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">15&#44;17&#44;30&#44;34&#44;35</span></a> De fato&#44; o icatibanto est&#225; entre as op&#231;&#245;es de tratamento recomendadas pelas atuais diretrizes internacionais&#47;canadenses para o manejo de AEH no tratamento de crises agudas de AEH em pacientes com AEH nC1&#8208;INH &#40;com base no n&#237;vel de evid&#234;ncia de consenso&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">8</span></a> Os resultados da an&#225;lise atual de pacientes brasileiros do IOS enfatizam ainda mais os benef&#237;cios do icatibanto em pacientes com AEH nC1&#8208;INH&#46; Os achados mostraram uma tend&#234;ncia favor&#225;vel para efeitos mais r&#225;pidos do que em pacientes com AEH&#8208;1&#47;2&#44; incluindo mediana de tempo mais curta para atingir a resolu&#231;&#227;o e dura&#231;&#227;o mediana total de crise mais curta&#44; embora a &#250;nica diferen&#231;a estatisticamente significativa entre os dois grupos de pacientes nessa coorte tenha sido a m&#233;dia de tempo desde a primeira administra&#231;&#227;o de icatibanto at&#233; a resolu&#231;&#227;o completa dos sintomas&#46; &#201; importante notar que o menor tempo m&#233;dio desde o in&#237;cio da crise at&#233; a primeira administra&#231;&#227;o de icatibanto para pacientes com AEH nC1&#8208;INH pode ter contribu&#237;do para os melhores resultados de tempo&#8208;at&#233;&#8208;o&#8208;evento em compara&#231;&#227;o com pacientes com AEH&#8208;1&#47;2&#44; de acordo com os dados do IOS publicados anteriormente&#44; mostrando que a administra&#231;&#227;o precoce de icatibanto resulta em resolu&#231;&#227;o mais r&#225;pida das crises de AEH&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">28</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">O perfil de seguran&#231;a do icatibanto na an&#225;lise atual foi compar&#225;vel entre pacientes com AEH&#8208;1&#47;2 e aqueles com AEH nC1&#8208;INH&#59; as rea&#231;&#245;es relacionadas ao local da inje&#231;&#227;o foram os EAs mais frequentemente relatados&#46; Os achados s&#227;o consistentes com o perfil de seguran&#231;a do icatibanto relatado em estudos controlados&#8208;chave em pacientes com AEH&#8208;1&#47;2&#44;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">36&#44;37</span></a> bem como em outras an&#225;lises p&#243;s&#8208;comercializa&#231;&#227;o em pacientes do IOS e pacientes tratados com icatibanto com AEH nC1&#8208;INH em estudos n&#227;o controlados&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">29&#44;34&#44;38</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">V&#225;rias limita&#231;&#245;es s&#227;o inerentes a um desenho de estudo observacional&#44; incluindo a falta de comparador de tratamento e depend&#234;ncia da mem&#243;ria do paciente&#44; potencialmente levando a subnotifica&#231;&#227;o de crises mais leves ou relato incompleto de sintomas&#46; Al&#233;m disso&#44; todas as an&#225;lises foram <span class="elsevierStyleItalic">post hoc</span>&#44; e a amostra n&#227;o tinha poder para mostrar as diferen&#231;as&#59; dessa maneira&#44; os resultados das compara&#231;&#245;es entre os dois grupos de pacientes devem ser interpretados com cautela&#46; Entretanto&#44; apesar dessas limita&#231;&#245;es inerentes&#44; registros como o IOS s&#227;o ferramentas &#250;teis para obter informa&#231;&#245;es sobre o AEH al&#233;m das configura&#231;&#245;es de ensaios cl&#237;nicos controlados e para avaliar a efic&#225;cia e a seguran&#231;a do icatibanto por longos per&#237;odos de tempo&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Vale ressaltar que o icatibanto foi lan&#231;ado no Brasil em 2009 e &#233; aprovado pela Ag&#234;ncia Nacional de Vigil&#226;ncia Sanit&#225;ria &#40;Anvisa&#41;&#44; por&#233;m n&#227;o foi introduzido no protocolo oficial do Minist&#233;rio da Sa&#250;de do Brasil&#46; Desse modo&#44; n&#227;o h&#225; financiamento do governo atualmente para o seu uso&#59; portanto&#44; o acesso do paciente a essa terapia continua sendo um desafio&#46; Espera&#8208;se que o relato cont&#237;nuo dos achados de efic&#225;cia e seguran&#231;a do icatibanto&#44; como os feitos aqui&#44; ajude a melhorar a acessibilidade a essa medica&#231;&#227;o para o tratamento de AEH no Brasil&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclus&#245;es</span><p id="par0135" class="elsevierStylePara elsevierViewall">A caracteriza&#231;&#227;o de v&#225;rias formas de AEH em todo o mundo continua a crescer&#44; abrindo caminho para uma melhor compreens&#227;o das muta&#231;&#245;es gen&#233;ticas subjacentes&#44; dados demogr&#225;ficos dos pacientes e resultados do tratamento em v&#225;rias popula&#231;&#245;es de pacientes com AEH&#46; A presente an&#225;lise fornece suporte para a efic&#225;cia&#44; seguran&#231;a e tolerabilidade do icatibanto em pacientes brasileiros com AEH&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Suporte financeiro</span><p id="par0160" class="elsevierStylePara elsevierViewall">Anete S&#46; Grumach &#233; bolsista de produtividade CNPq&#46; &#40;309824&#47;2021&#8208;4&#41;&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Esta pesquisa foi patrocinada pela <span class="elsevierStyleItalic">Shire Human Genetic Therapies</span>&#44; Inc&#46;&#44; uma empresa Takeda&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Contribui&#231;&#227;o dos autores</span><p id="par0165" class="elsevierStylePara elsevierViewall">Anete S&#46; Grumach&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Marina T&#46; Henriques&#58; Obten&#231;&#227;o&#44; an&#225;lise e&#47;ou interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Maine L&#46; D&#46; Bardou&#58; Obten&#231;&#227;o&#44; an&#225;lise e&#47;ou interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Daniele A&#46; Pontarolli&#58; Obten&#231;&#227;o&#44; an&#225;lise e&#47;ou interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Jaco Botha&#58; Obten&#231;&#227;o&#44; an&#225;lise e&#47;ou interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Mariangela Correa&#58; Obten&#231;&#227;o&#44; an&#225;lise e&#47;ou interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflito de interesses</span><p id="par0195" class="elsevierStylePara elsevierViewall">Anete S&#46; Grumach foi palestrante ou consultora da BioCryst&#44; Biotest&#44; CSL Behring e Takeda&#46; Marina T&#46; Henriques&#44; Maine L&#46; D&#46; Bardou e Daniele A&#46; Pontarolli n&#227;o t&#234;m conflito de interesses a declarar&#46; J&#46; Botha &#233; funcion&#225;rio e possui op&#231;&#245;es de compra de a&#231;&#245;es&#47;a&#231;&#245;es da Takeda&#46; M&#46; Correa era funcion&#225;ria e possu&#237;a op&#231;&#245;es de compra de a&#231;&#245;es&#47;a&#231;&#245;es da Takeda no momento desta an&#225;lise&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:12 [
        0 => array:3 [
          "identificador" => "xres1751126"
          "titulo" => "Resumo"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Fundamento"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "M&#233;todos"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Objetivo"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Resultados"
            ]
            4 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Limita&#231;&#245;es do estudo"
            ]
            5 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Conclus&#245;es"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1542398"
          "titulo" => "Palavras&#8208;chave"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introdu&#231;&#227;o"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "M&#233;todos"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Pacientes e resultados"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "An&#225;lise estat&#237;stica"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "sec0025"
          "titulo" => "Resultados"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Caracter&#237;sticas basais"
            ]
            1 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "N&#250;mero de crises e n&#250;mero de administra&#231;&#245;es de icatibanto"
            ]
            2 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Local e gravidade das crises"
            ]
            3 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Resultados de tempo&#8208;at&#233;&#8208;o&#8208;evento relacionados ao tratamento"
            ]
            4 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Seguran&#231;a"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Discuss&#227;o"
        ]
        6 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conclus&#245;es"
        ]
        7 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Suporte financeiro"
        ]
        8 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Contribui&#231;&#227;o dos autores"
        ]
        9 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Conflito de interesses"
        ]
        10 => array:2 [
          "identificador" => "xack618630"
          "titulo" => "Agradecimentos"
        ]
        11 => array:1 [
          "titulo" => "Refer&#234;ncias"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2021-05-21"
    "fechaAceptado" => "2021-09-15"
    "PalabrasClave" => array:1 [
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras&#8208;chave"
          "identificador" => "xpalclavsec1542398"
          "palabras" => array:4 [
            0 => "Angioedema heredit&#225;rio"
            1 => "Bradicinina"
            2 => "Brasil"
            3 => "Receptor de bradicinina"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamento</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">O angioedema heredit&#225;rio pode ser causado por defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1 &#40;C1&#8208;INH&#59; AEH&#8208;1&#47;2&#41; ou pode ocorrer em pacientes com C1&#8208;INH normal &#40;AEH nC1&#8208;INH&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">O registro <span class="elsevierStyleItalic">Icatibant Outcome Survey</span> &#40;IOS&#59; NCT01034969&#41; monitora a seguran&#231;a e a efic&#225;cia do icatibanto no tratamento do angioedema agudo&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Objetivo</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Apresentar achados de pacientes brasileiros com AEH&#8208;1&#47;2 e AEH nC1&#8208;INH participantes do IOS&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos 42 pacientes &#40;AEH&#8208;1&#47;2&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#59; AEH nC1&#8208;INH&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&#46; A idade mediana no in&#237;cio dos sintomas foi significativamente menor com AEH&#8208;1&#47;2 <span class="elsevierStyleItalic">vs</span>&#46; AEH nC1&#8208;INH &#40;10&#44;0 <span class="elsevierStyleItalic">vs</span>&#46; 16&#44;5 anos&#44; respectivamente&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0105&#41;&#44; enquanto a mediana da idade no diagn&#243;stico &#40;31&#44;1 <span class="elsevierStyleItalic">vs</span>&#46; 40&#44;9 anos&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;1276&#41; e a mediana do tempo entre o in&#237;cio dos sintomas e o diagn&#243;stico &#40;15&#44;0 <span class="elsevierStyleItalic">vs</span>&#46; 23&#44;8 anos&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;6680&#41; foram numericamente menores <span class="elsevierStyleItalic">vs</span>&#46; AEH nC1&#8208;INH&#44; respectivamente&#46; Uma dose de icatibanto foi utilizada para &#62; 95&#37; das crises de AEH&#46; A mediana dos desfechos &#40;intervalo&#41; de tempo&#8208;at&#233;&#8208;o&#8208;evento foram menores para pacientes com AEH nC1&#8208;INH vs&#46; AEH&#8208;1&#47;2&#44; incluindo o tempo at&#233; a primeira administra&#231;&#227;o &#40;0&#44;5 &#91;0&#8211;96&#44;0&#93; vs&#46; 1&#44;0 &#91;0&#8211;94&#44;0&#93; hora&#44; respectivamente&#41;&#44; tempo desde a primeira administra&#231;&#227;o at&#233; a resolu&#231;&#227;o completa &#40;1&#44;0 &#91;0&#8211;88&#44;0&#93; <span class="elsevierStyleItalic">vs</span>&#46; 5&#44;5 &#91;0&#8211;96&#44;0&#93; horas&#44; respectivamente&#41; e dura&#231;&#227;o total da crise &#40;7&#44;0 &#91;0&#44;3&#8211;99&#44;0&#93; <span class="elsevierStyleItalic">vs</span>&#46; 18&#44;5 &#91;0&#44;1&#8211;100&#44;0&#93; horas&#44; respectivamente&#41;&#46; O tempo m&#233;dio &#40;DP&#41; desde o in&#237;cio da crise at&#233; a resolu&#231;&#227;o foi significativamente menor em pacientes com AEH nC1&#8208;INH <span class="elsevierStyleItalic">vs</span>&#46; AEH&#8208;1&#47;2 &#40;9&#44;8 &#91;18&#44;7&#93; <span class="elsevierStyleItalic">vs</span>&#46; 19&#44;6 &#91;24&#44;0&#93; horas&#44; respectivamente&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0174&#41;&#46; Foram relatados 83 eventos adversos &#40;EAs&#41; em 42 pacientes&#59; a maioria foi leve &#40;66&#44;3&#37;&#41; ou moderada &#40;13&#44;3&#37;&#41; e n&#227;o grave &#40;75&#44;9&#37;&#41;&#46; O EA mais comum relacionado ao icatibanto foi eritema no local da inje&#231;&#227;o &#40;AEH&#8208;1&#47;2&#44; 34&#44;6&#37;&#59; AEH nC1&#8208;INH&#44; 18&#44;8&#37;&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Este foi um estudo observacional que n&#227;o tinha um comparador de tratamento e baseou&#8208;se nas recorda&#231;&#245;es dos pacientes&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Os achados demonstram efic&#225;cia e tolerabilidade do icatibanto em pacientes brasileiros com AEH&#46;</p></span>"
        "secciones" => array:6 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Fundamento"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Objetivo"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Limita&#231;&#245;es do estudo"
          ]
          5 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Conclus&#245;es"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0045">Como citar este artigo&#58; Grumach AS&#44; Henriques MT&#44; Bardou MLD&#44; Pontarolli DA&#44; Botha J&#44; Correa M&#46; Icatibant use in Brazilian patients with hereditary angioedema &#40;HAE&#41; type&#160;1&#160;or&#160;2 and HAE with normal C1&#8208;INH levels&#58; findings from the Icatibant Outcome Survey Registry Study&#46; An Bras Dermatol&#46; 2022&#59;97&#58;448&#8211;57&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0050">Trabalho realizado na Imunologia Cl&#237;nica&#44; Faculdade de Medicina&#44; Centro Universit&#225;rio Sa&#250;de ABC&#44; Santo Andr&#233;&#44; SP&#44; Brasil&#46;</p>"
      ]
    ]
    "multimedia" => array:9 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 629
            "Ancho" => 3333
            "Tamanyo" => 145061
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Resultados da efic&#225;cia do tempo&#8208;at&#233;&#8208;o&#8208;evento relacionados ao tratamento&#46; Adaptada de&#58; Maurer M et al&#46;&#44; <a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">28</span></a>&#46; AEH&#44; angioedema heredit&#225;rio&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2790
            "Ancho" => 1675
            "Tamanyo" => 187136
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Dados demogr&#225;ficos basais&#46; &#40;a&#41; Mediana da idade no in&#237;cio dos sintomas de angioedema heredit&#225;rio &#40;p &#61; 0&#44;0105&#41;&#46; &#40;b&#41; Mediana da idade no diagn&#243;stico &#40;p &#61; 0&#44;1276&#41;&#46; &#40;c&#41; Mediana do tempo desde o in&#237;cio dos sintomas at&#233; o diagn&#243;stico &#40;diferen&#231;a entre a idade dos primeiros sintomas e a idade de diagn&#243;stico&#59; p &#61; 0&#44;6680&#41;&#46; As bordas esquerda e direita das caixas representam os percentis 25 e 75&#44; respectivamente&#59; os <span class="elsevierStyleItalic">whiskers</span> da caixa denotam os valores m&#237;nimos e m&#225;ximos registrados&#46; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1542
            "Ancho" => 2175
            "Tamanyo" => 140219
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Local mais comum de crises de angioedema heredit&#225;rio&#46; AEH&#8208;1&#47;2&#44; n &#61; 164 crises &#40;um faltando&#41;&#59; AEH nC1&#8208;INH&#44; n &#61; 60 crises &#40;tr&#234;s faltando&#41;&#46; Apenas os locais &#250;nicos e combina&#231;&#245;es de locais mais comuns s&#227;o mostrados&#59; assim&#44; os percentuais n&#227;o totalizam 100&#37;&#46; As crises que afetam a pele referem&#8208;se aos seguintes locais&#58; bra&#231;os&#44; pavilh&#245;es auriculares&#44; p&#225;lpebras&#44; face&#44; p&#233;s&#44; genitais&#44; m&#227;os&#44; pernas&#44; l&#225;bios&#44; nariz&#44; tronco&#44; outros&#44; desconhecidos&#46; Crises abdominais referem&#8208;se especificamente a crises que afetam a mucosa gastrintestinal&#46; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figura 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 992
            "Ancho" => 2175
            "Tamanyo" => 135903
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Gravidade das crises de angioedema heredit&#225;rio antes do tratamento&#46; AEH&#8208;1&#47;2&#44; n &#61; 164 crises &#40;falta uma&#41;&#59; AEH nC1&#8208;INH&#44; n &#61; 60 crises &#40;faltam tr&#234;s&#41;&#46; A gravidade da crise foi avaliada com base nas seguintes descri&#231;&#245;es&#58; Leve&#58; interfer&#234;ncia leve nas atividades di&#225;rias&#59; Moderada&#58; interfer&#234;ncia moderada nas atividades di&#225;rias e sem necessidade de outras contramedidas&#59; Grave&#58; interfer&#234;ncia grave nas atividades di&#225;rias e com ou sem outras contramedidas&#59; Muito grave&#58; interfer&#234;ncia muito grave nas atividades di&#225;rias e outras contramedidas necess&#225;rias&#46; A diferen&#231;a entre os dois grupos de pacientes na ocorr&#234;ncia de crises leves&#47;moderadas versus graves&#47;muito graves n&#227;o foi significativa &#40;p &#61; 0&#44;1038&#41;&#46; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figura 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 1567
            "Ancho" => 3333
            "Tamanyo" => 317867
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Resultados de tempo para o evento&#46; As bordas inferior e superior das caixas representam os percentis 25 e 75&#44; respectivamente&#59; os <span class="elsevierStyleItalic">whiskers</span> das caixas denotam os valores m&#237;nimos e m&#225;ximos registrados&#46; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio tipo 1 ou 2&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#59; DP&#44; desvio padr&#227;o&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabela 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">AEH</span>&#44; angioedema heredit&#225;rio&#59; <span class="elsevierStyleItalic">AEH&#8208;1&#47;2</span>&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; <span class="elsevierStyleItalic">AEH nC1&#8208;INH</span>&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#59; <span class="elsevierStyleItalic">IOS</span>&#44; <span class="elsevierStyleItalic">Icatibant Outcome Survey</span>&#59; <span class="elsevierStyleItalic">DP</span>&#44; desvio padr&#227;o&#59; SI&#44; sem informa&#231;&#245;es&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Caracter&#237;stica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH&#8208;1&#47;2&#40;n &#61; 26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH nC1&#8208;INH &#40;n &#61; 16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Geral&#40;n &#61; 42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">26 &#40;0&#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">16 &#40;0&#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">42 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Feminino&#44; n &#40;&#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">22 &#40;84&#44;6&#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">16 &#40;100&#44;0&#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">38 &#40;90&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Masculino&#44; n &#40;&#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">4 &#40;15&#44;4&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;9&#44;5&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade no in&#237;cio dos sintomas de AEH &#40;anos&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">23 &#40;3&#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">16 &#40;0&#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">39 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dia &#40;DP&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;5 &#40;9&#44;4&#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">18&#44;9 &#40;10&#44;1&#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">14&#44;0 &#40;10&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;varia&#231;&#227;o&#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">10&#44;0 &#40;0&#44;3&#8211;35&#44;0&#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">16&#44;5 &#40;3&#44;0&#8211;35&#44;0&#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">14&#44;0 &#40;0&#44;3&#8211;35&#44;0&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade no diagn&#243;stico de AEH &#40;anos&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">25 &#40;1&#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">16 &#40;0&#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">41 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dia &#40;DP&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;6 &#40;16&#44;2&#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">37&#44;6 &#40;15&#44;8&#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">33&#44;9 &#40;16&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;varia&#231;&#227;o&#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">31&#44;1 &#40;5&#44;1&#8211;68&#44;0&#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">40&#44;9 &#40;7&#44;8&#8211;62&#44;3&#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">33&#44;8 &#40;5&#44;1&#8211;68&#44;0&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tempo entre o in&#237;cio dos sintomas de AEH e o diagn&#243;stico &#40;anos&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">22 &#40;4&#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">16 &#40;0&#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">38 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dia &#40;DP&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;8 &#40;17&#44;8&#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">18&#44;8 &#40;15&#44;9&#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">18&#44;8 &#40;16&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;varia&#231;&#227;o&#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">15&#44;0 &#40;0&#8211;66&#44;9&#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">23&#44;8 &#40;0&#8211;48&#44;3&#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">16&#44;1 &#40;0&#8211;66&#44;9&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hist&#243;ria familiar de AEH</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">24 &#40;2&#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">16 &#40;0&#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">40 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; n &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;87&#44;5&#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">15 &#40;93&#44;8&#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">36 &#40;90&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&#44; n &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;12&#44;5&#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">1 &#40;6&#44;3&#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">4 &#40;10&#44;0&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade na inclus&#227;o do IOS &#40;anos&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">26 &#40;0&#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">16 &#40;0&#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">42 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dia &#40;DP&#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">41&#44;9 &#40;13&#44;0&#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">42&#44;1 &#40;13&#44;8&#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">42&#44;0 &#40;13&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;varia&#231;&#227;o&#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">39&#44;8 &#40;19&#44;0&#8211;0&#44;7&#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">42&#44;9 &#40;18&#44;3&#8211;64&#44;3&#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">41&#44;9 &#40;18&#44;3&#8211;70&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:4 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">p &#61; 0&#44;0105&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">p &#61; 0&#44;1276&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">p &#61; 0&#44;6880&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Porcentagens excluem valores faltantes&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas basais</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">AEH</span>&#44; angioedema heredit&#225;rio&#59; <span class="elsevierStyleItalic">AEH&#8208;1&#47;2</span>&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; <span class="elsevierStyleItalic">AEH nC1&#8208;INH</span>&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#59; <span class="elsevierStyleItalic">Q</span>&#44; quartil&#59; <span class="elsevierStyleItalic">DP</span>&#44; desvio padr&#227;o&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH&#8208;1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH nC1&#8208;INH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#250;mero de pacientes com &#8805; 1 crise de AEH tratados com icatibanto&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">18&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">10&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  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N&#250;mero de crises por paciente</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dia &#40;DP&#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">9&#44;2 &#40;9&#44;7&#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">6&#44;3 &#40;4&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;Q1&#44; Q3&#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">5&#44;5 &#40;1&#44;0&#44; 18&#44;0&#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">6&#44;0 &#40;5&#44;0&#44; 8&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Varia&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;17&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  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Porcentagem de crises necessitando de 1&#44; 2 ou 4 administra&#231;&#245;es de icatibanto &#40;&#37;&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Com base em um n&#250;mero total de 164 crises &#40;faltando uma&#41; em pacientes com AEH&#8208;1&#47;2 e um total de 60 crises &#40;faltando tr&#234;s&#41; em pacientes com AEH nC1&#8208;INH&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Frequ&#234;ncia de crises e administra&#231;&#245;es de icatibanto</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">C1&#8208;INH&#44; inibidor de C1&#59; AEH&#44; angioedema heredit&#225;rio&#59; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#59; SI&#44; sem informa&#231;&#245;es&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH&#8208;1&#47;2 &#40;n &#61; 164 &#91;SI &#61; 1&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH nC1&#8208;INH&#40;n &#61; 63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total&#40;n &#61; 227&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Analg&#233;sicos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;4&#44;3&#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">5 &#40;7&#44;9&#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">12 &#40;5&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiem&#233;ticos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;3&#44;0&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;2&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antifibrinol&#237;ticos&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">15 &#40;9&#44;1&#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">31 &#40;49&#44;2&#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">46 &#40;20&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;histam&#237;nicos&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">3 &#40;1&#44;8&#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">1 &#40;1&#44;6&#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">4 &#40;1&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Andr&#243;genos atenuados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;3&#44;0&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;2&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Concentrado de C1&#8208;INH&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">15 &#40;9&#44;1&#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&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">15 &#40;6&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fluidos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;6&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Plasma fresco congelado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;6&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Outros&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;3&#44;0&#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">1 &#40;1&#44;6&#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">6 &#40;2&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inibidores da bomba de pr&#243;tons&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;6&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiespasm&#243;dicos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;2&#44;4&#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">3 &#40;4&#44;8&#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">7 &#40;3&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Uso de medicamentos al&#233;m do icatibanto para crises de AEH tratadas durante o per&#237;odo de seguimento</p>"
        ]
      ]
      8 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Tabela 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">EA&#44; evento adverso&#59; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">EA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH&#8208;1&#47;2</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH nC1&#8208;INH</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pacientes&#40;n &#61; 26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eventos&#40;n &#61; 58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pacientes&#40;n &#61; 16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eventos&#40;n &#61; 25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Rea&#231;&#227;o no local da inje&#231;&#227;o</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Eritema<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;34&#44;6&#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">18 &#40;31&#44;0&#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">3 &#40;18&#44;8&#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">6 &#40;24&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dor no local de aplica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;7&#44;7&#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">3 &#40;5&#44;2&#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">1 &#40;6&#44;3&#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">1 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hematoma&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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;6&#44;3&#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">1 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hemorragia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;8&#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">1 &#40;1&#44;7&#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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hiperemia</span>&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">3 &#40;11&#44;5&#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">4 &#40;6&#44;9&#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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Edema localizado</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;8&#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">1 &#40;1&#44;7&#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">2 &#40;12&#44;5&#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">2 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dor</span>&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">3 &#40;11&#44;5&#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">3 &#40;5&#44;2&#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">1 &#40;6&#44;3&#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">1 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N&#225;usea</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;8&#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">1 &#40;1&#44;7&#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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Edema</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;8&#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">1 &#40;1&#44;7&#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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Angioedema</span><a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;8&#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">1 &#40;1&#44;7&#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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Excluindo relatos de uso <span class="elsevierStyleItalic">off&#8208;label</span>&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Inclui os termos preferenciais &#8220;Eritema no local da inje&#231;&#227;o&#8221; e &#8220;Eritema no local da aplica&#231;&#227;o&#8221;&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0040"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Esse evento foi classificado como EA grave&#46; O paciente recebeu duas doses de icatibanto antes de ser hospitalizado por 24 horas&#46; No hospital&#44; o paciente recebeu plasma fresco congelado e recebeu alta no dia seguinte sem sequelas&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Eventos adversos considerados como possivelmente ou provavelmente relacionados ao uso de icatibanto &#40;por termo preferencial&#41;<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a></p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:38 [
            0 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The clinical evaluation of angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46; Gill"
                            1 => "S&#46;D&#46; Betschel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.iac.2017.04.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunol Allergy Clin North Am&#46;"
                        "fecha" => "2017"
                        "volumen" => "37"
                        "paginaInicial" => "449"
                        "paginaFinal" => "466"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28687102"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fatal laryngeal attacks&#44; and mortality in hereditary angioedema due to C1&#8208;INH deficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46; Bork"
                            1 => "J&#46; Hardt"
                            2 => "G&#46; Witzke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2012.05.055"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol&#46;"
                        "fecha" => "2012"
                        "volumen" => "130"
                        "paginaInicial" => "692"
                        "paginaFinal" => "697"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22841766"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long&#8208;term prophylaxis therapy in patients with hereditary angioedema with C1 inhibitor deficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Craig"
                            1 => "P&#46; Busse"
                            2 => "R&#46;G&#46; Gower"
                            3 => "D&#46;T&#46; Johnston"
                            4 => "J&#46;M&#46; Kashkin"
                            5 => "H&#46;H&#46; Li"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.anai.2018.07.025"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol&#46;"
                        "fecha" => "2018"
                        "volumen" => "121"
                        "paginaInicial" => "673"
                        "paginaFinal" => "679"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30056152"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Diagnosis of Hereditary Angioedema&#58; Family Caregivers&#8217; Experiences"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Granero-Molina"
                            1 => "F&#46; S&#225;nchez-Hern&#225;ndez"
                            2 => "C&#46; Fern&#225;ndez-Sola"
                            3 => "M&#46;D&#46;M&#46; Jim&#233;nez-Lasserrotte"
                            4 => "L&#46;H&#46; Antequera-Raynal"
                            5 => "J&#46;M&#46; Hern&#225;ndez-Padilla"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/1054773818780102"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Nurs Res&#46;"
                        "fecha" => "2020"
                        "volumen" => "29"
                        "paginaInicial" => "117"
                        "paginaFinal" => "126"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29862835"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The burden of illness in patients with hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "A&#46; Banerji"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.anai.2013.08.019"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol&#46;"
                        "fecha" => "2013"
                        "volumen" => "111"
                        "paginaInicial" => "329"
                        "paginaFinal" => "336"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24125136"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Patient&#8208;reported burden of hereditary angioedema&#58; findings from a patient survey in the United States"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Banerji"
                            1 => "K&#46;H&#46; Davis"
                            2 => "T&#46;M&#46; Brown"
                            3 => "K&#46; Holis"
                            4 => "S&#46;M&#46; Hunter"
                            5 => "J&#46; Long"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.anai.2020.02.018"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol&#46;"
                        "fecha" => "2020"
                        "volumen" => "124"
                        "paginaInicial" => "600"
                        "paginaFinal" => "607"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32169514"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The international WAO&#47;EAACI guideline for the management of hereditary angioedema &#8208; the 2017 revision and update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Maurer"
                            1 => "M&#46; Magerl"
                            2 => "I&#46; Ansotegui"
                            3 => "E&#46; Ayg&#246;ren-P&#252;rs&#252;n"
                            4 => "S&#46; Betschel"
                            5 => "K&#46; Bork"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/all.13384"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2018"
                        "volumen" => "73"
                        "paginaInicial" => "1575"
                        "paginaFinal" => "1596"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29318628"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The International&#47;Canadian Hereditary Angioedema Guideline"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Betschel"
                            1 => "J&#46; Badiou"
                            2 => "K&#46; Binkley"
                            3 => "R&#46; Borici-Mazi"
                            4 => "J&#46; H&#233;bert"
                            5 => "A&#46; Kanani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13223-019-0376-8"
                      "Revista" => array:5 [
                        "tituloSerie" => "Allergy Asthma Clin Immunol&#46;"
                        "fecha" => "2019"
                        "volumen" => "15"
                        "paginaInicial" => "72"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31788005"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C1 inhibitor activity and angioedema attacks in patients with hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Kaplan"
                            1 => "D&#46; Pawaskar"
                            2 => "J&#46; Chiao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaip.2019.10.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol Pract&#46;"
                        "fecha" => "2020"
                        "volumen" => "8"
                        "paginaInicial" => "892"
                        "paginaFinal" => "900"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31655295"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of complement in hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Levi"
                            1 => "D&#46; Cohn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.tmrv.2019.08.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Transfus Med Rev&#46;"
                        "fecha" => "2019"
                        "volumen" => "33"
                        "paginaInicial" => "243"
                        "paginaFinal" => "247"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31676220"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Angioedema due to bradykinin dysregulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Cicardi"
                            1 => "B&#46;L&#46; Zuraw"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaip.2018.04.022"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol Pract&#46;"
                        "fecha" => "2018"
                        "volumen" => "6"
                        "paginaInicial" => "1132"
                        "paginaFinal" => "1141"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30033914"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46; Busse"
                            1 => "S&#46; Christiansen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra1808012"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med&#46;"
                        "fecha" => "2020"
                        "volumen" => "382"
                        "paginaInicial" => "1136"
                        "paginaFinal" => "1148"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32187470"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A myoferlin gain&#8208;of&#8208;function variant associates with a new type of hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Ariano"
                            1 => "M&#46; D&#8217;Apolito"
                            2 => "M&#46; Bova"
                            3 => "F&#46; Bellanti"
                            4 => "S&#46; Loffredo"
                            5 => "G&#46; D&#8217;Andrea"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2020"
                        "volumen" => "75"
                        "paginaInicial" => "2989"
                        "paginaFinal" => "2992"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An update on the genetics and pathogenesis of hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;Z&#46; Banday"
                            1 => "A&#46; Kaur"
                            2 => "A&#46;K&#46; Jindal"
                            3 => "A&#46; Rawat"
                            4 => "S&#46; Singh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.gendis.2019.07.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genes Dis&#46;"
                        "fecha" => "2019"
                        "volumen" => "7"
                        "paginaInicial" => "75"
                        "paginaFinal" => "83"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32181278"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema with a mutation in the plasminogen gene"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Bork"
                            1 => "K&#46; Wulff"
                            2 => "L&#46; Steinm&#252;ller-Magin"
                            3 => "I&#46; Braenne"
                            4 => "P&#46; Staubach-Renz"
                            5 => "G&#46; Witzke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/all.13270"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2018"
                        "volumen" => "73"
                        "paginaInicial" => "442"
                        "paginaFinal" => "450"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28795768"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary Angioedema with Normal C1 Inhibitor and F12 Mutations in 42 Brazilian Families"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;L&#46; Veronez"
                            1 => "A&#46;S&#46; Moreno"
                            2 => "R&#46;N&#46; Constantino-Silva"
                            3 => "L&#46;S&#46;M&#46; Maia"
                            4 => "M&#46;P&#46;L&#46; Ferriani"
                            5 => "F&#46;F&#46;M&#46; Castro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaip.2017.09.025"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol Pract&#46;"
                        "fecha" => "2018"
                        "volumen" => "6"
                        "paginaInicial" => "1209"
                        "paginaFinal" => "1216"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29128335"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Review of the Manitoba cohort of patients with hereditary angioedema with normal C1 inhibitor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L&#46; McKibbin"
                            1 => "C&#46; Barber"
                            2 => "C&#46; Kalicinsky"
                            3 => "R&#46; Warrington"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13223-019-0381-y"
                      "Revista" => array:5 [
                        "tituloSerie" => "Allergy Asthma Clin Immunol&#46;"
                        "fecha" => "2019"
                        "volumen" => "15"
                        "paginaInicial" => "66"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31749860"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema&#58; first report of the Brazilian registry and challenges"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;S&#46; Grumach"
                            1 => "S&#46;O&#46; Valle"
                            2 => "E&#46; Toledo"
                            3 => "D&#46;M&#46; Vasconselos"
                            4 => "M&#46;M&#46;S&#46; Villela"
                            5 => "E&#46; Mansour"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1468-3083.2012.04670.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Eur Acad Dermatol Venereol&#46;"
                        "fecha" => "2013"
                        "volumen" => "27"
                        "paginaInicial" => "e338"
                        "paginaFinal" => "e344"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22882421"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => """
                    ibge&#46;gov &#91;Internet&#93;&#46; Instituto Brasileiro de Geografia e Estat&#237;stica&#46; Proje&#231;&#227;o da popula&#231;&#227;o do Brasil e das Unidades da Federa&#231;&#227;o&#59; &#91;cited 2020 Nov 23&#93;&#46; Available from&#58; \n
                    <https: www.ibge.gov.br="" pps="" opulacao="" rojecao="" ndex.html="">\n
                     &#46;\n
                    </https:>
                    """
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema&#58; insights from a Brazilian family"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;F&#46; Ferraro"
                            1 => "A&#46;S&#46; Moreno"
                            2 => "E&#46;C&#46; Castelli"
                            3 => "E&#46;A&#46; Donadi"
                            4 => "M&#46;S&#46; Palma"
                            5 => "H&#46;A&#46; Arcuri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1398-9995.2011.02658.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2011"
                        "volumen" => "66"
                        "paginaInicial" => "1384"
                        "paginaFinal" => "1390"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21623829"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genotype&#8208;phenotype correlations in Brazilian patients with hereditary angioedema due to C1 inhibitor deficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;S&#46;M&#46; Maia"
                            1 => "A&#46;S&#46; Moreno"
                            2 => "M&#46;P&#46;L&#46; Ferriani"
                            3 => "F&#46;L&#46; Nunes"
                            4 => "M&#46;F&#46; Ferraro"
                            5 => "M&#46;M&#46; Dias"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/all.13699"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2019"
                        "volumen" => "74"
                        "paginaInicial" => "1013"
                        "paginaFinal" => "1016"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30556912"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema&#58; a prospective study of a Brazilian single&#8208;center cohort"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;L&#46;O&#46; Alonso"
                            1 => "S&#46;O&#46;R&#46; Valle"
                            2 => "R&#46;P&#46; T&#243;rtora"
                            3 => "A&#46;S&#46; Grumach"
                            4 => "A&#46;T&#46; Fran&#231;a"
                            5 => "M&#46;G&#46; Ribeiro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/ijd.14676"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Dermatol&#46;"
                        "fecha" => "2020"
                        "volumen" => "59"
                        "paginaInicial" => "341"
                        "paginaFinal" => "344"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31631315"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coagulation factor XII gene mutation in Brazilian families with hereditary angioedema with normal C1 inhibitor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;S&#46; Moreno"
                            1 => "S&#46;O&#46;R&#46; Valle"
                            2 => "S&#46; Levy"
                            3 => "A&#46;T&#46; Fran&#231;a"
                            4 => "F&#46;S&#46; Serpa"
                            5 => "H&#46;A&#46; Arcuri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000376547"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int Arch Allergy Immunol&#46;"
                        "fecha" => "2015"
                        "volumen" => "166"
                        "paginaInicial" => "114"
                        "paginaFinal" => "120"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25790805"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema type III &#40;estrogen&#8208;dependent&#41; report of three cases and literature review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46;R&#46; Miranda"
                            1 => "A&#46;P&#46;F&#46; de Ue"
                            2 => "D&#46;V&#46; Sabbag"
                            3 => "W&#46;J&#46; Furlani"
                            4 => "P&#46;K&#46; Souza"
                            5 => "O&#46; Rotta"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "An Bras Dermatol&#46;"
                        "fecha" => "2013"
                        "volumen" => "88"
                        "paginaInicial" => "578"
                        "paginaFinal" => "584"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "First report of a FXII gene mutation in a Brazilian family with hereditary angio&#8208;oedema with normal C1 inhibitor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Stieber"
                            1 => "A&#46;S&#46; Grumach"
                            2 => "E&#46; Cordeiro"
                            3 => "R&#46;N&#46; Constantino-Silva"
                            4 => "S&#46; Barth"
                            5 => "P&#46; Hoffmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/bjd.13791"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dermatol&#46;"
                        "fecha" => "2015"
                        "volumen" => "173"
                        "paginaInicial" => "1102"
                        "paginaFinal" => "1104"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25816745"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Assessment on hereditary angioedema burden of illness in Brazil&#58; a patient perspective"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;A&#46; Barbosa"
                            1 => "R&#46;O&#46; Martins"
                            2 => "R&#46; Martins"
                            3 => "A&#46;S&#46; Grumach"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Allergy Asthma Proc&#46;"
                        "fecha" => "2019"
                        "volumen" => "40"
                        "paginaInicial" => "193"
                        "paginaFinal" => "197"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema&#58; quality of life in Brazilian patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Gomide MACMS"
                            1 => "E&#46; Toledo"
                            2 => "S&#46;O&#46;R&#46; Valle"
                            3 => "R&#46;A&#46; Campos"
                            4 => "A&#46;T&#46; Fran&#231;a"
                            5 => "N&#46;P&#46; Gomez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clinics &#40;Sao Paulo&#41;&#46;"
                        "fecha" => "2013"
                        "volumen" => "68"
                        "paginaInicial" => "81"
                        "paginaFinal" => "83"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema attacks resolve faster and are shorter after early icatibant treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Maurer"
                            1 => "W&#46; Aberer"
                            2 => "L&#46; Bouillet"
                            3 => "T&#46; Caballero"
                            4 => "V&#46; Fabien"
                            5 => "G&#46; Kanny"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0053773"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One&#46;"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "e53773"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23390491"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema with normal C1 inhibitor in a French cohort&#58; clinical characteristics and response to treatment with icatibant"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Bouillet"
                            1 => "I&#46; Boccon-Gibod"
                            2 => "D&#46; Launay"
                            3 => "A&#46; Gompel"
                            4 => "A&#46; Kanny"
                            5 => "V&#46; Fabien"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Immun Inflamm Dis&#46;"
                        "fecha" => "2017"
                        "volumen" => "5"
                        "paginaInicial" => "29"
                        "paginaFinal" => "36"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plasminogen gene mutation with normal C1 inhibitor hereditary angioedema&#58; three additional French families"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Belb&#233;zier"
                            1 => "G&#46; Hardy"
                            2 => "R&#46; Marlu"
                            3 => "F&#46; Defendi"
                            4 => "C&#46;D&#46; Perard"
                            5 => "I&#46; Boccon-Gibod"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/all.13543"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2018"
                        "volumen" => "73"
                        "paginaInicial" => "2237"
                        "paginaFinal" => "2239"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29952006"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema with normal C1 inhibitor&#58; update on evaluation and treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Magerl"
                            1 => "A&#46;E&#46; Germenis"
                            2 => "C&#46; Maas"
                            3 => "M&#46; Maurer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.iac.2017.04.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunol Allergy Clin North Am&#46;"
                        "fecha" => "2017"
                        "volumen" => "37"
                        "paginaInicial" => "571"
                        "paginaFinal" => "584"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28687110"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema with normal C1 inhibitor function&#58; consensus of an international expert panel"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;L&#46; Zuraw"
                            1 => "K&#46; Bork"
                            2 => "K&#46;E&#46; Binkley"
                            3 => "A&#46; Banerji"
                            4 => "S&#46;C&#46; Christiansen"
                            5 => "A&#46; Castaldo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2500/aap.2012.33.3627"
                      "Revista" => array:7 [
                        "tituloSerie" => "Allergy Asthma Proc&#46;"
                        "fecha" => "2012"
                        "volumen" => "33"
                        "numero" => "Suppl 1"
                        "paginaInicial" => "S145"
                        "paginaFinal" => "S156"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23394603"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long&#8208;term effectiveness and safety of icatibant for the on&#8208;demand treatment of hereditary angioedema attacks&#58; 10 years of the Icatibant Outcome Survey"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Maurer"
                            1 => "H&#46;J&#46; Longhurst"
                            2 => "L&#46; Bouillet"
                            3 => "T&#46; Caballero"
                            4 => "A&#46;S&#46; Grumach"
                            5 => "J&#46; Botha"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Abstract 1118&#46; Allergy&#46;"
                        "fecha" => "2020"
                        "volumen" => "75"
                        "paginaInicial" => "59"
                        "paginaFinal" => "60"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bradykinin receptor 2 antagonist &#40;icatibant&#41; for hereditary angioedema type III attacks"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Bouillet"
                            1 => "I&#46; Boccon-Gibod"
                            2 => "D&#46; Ponard"
                            3 => "C&#46; Drouet"
                            4 => "J&#46;Y&#46; Cesbron"
                            5 => "C&#46; Dumestre-Perard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1081-1206(10)60369-9"
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol&#46;"
                        "fecha" => "2009"
                        "volumen" => "103"
                        "paginaInicial" => "448"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19927548"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema with normal C1 inhibitor and factor XII mutation&#58; a series of 57 patients from the French National Center of Reference for Angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Deroux"
                            1 => "I&#46; Boccon-Gibod"
                            2 => "O&#46; Fain"
                            3 => "P&#46; Pralong"
                            4 => "Y&#46; Ollivier"
                            5 => "A&#46; Pagneir"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/cei.12820"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Immunol&#46;"
                        "fecha" => "2016"
                        "volumen" => "185"
                        "paginaInicial" => "332"
                        "paginaFinal" => "337"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27271546"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Icatibant&#44; a new bradykinin&#8208;receptor antagonist&#44; in hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Cicardi"
                            1 => "A&#46; Banerji"
                            2 => "F&#46; Bracho"
                            3 => "A&#46; Malbr&#225;n"
                            4 => "B&#46; Rosenkranz"
                            5 => "M&#46; Riedl"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0906393"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med&#46;"
                        "fecha" => "2010"
                        "volumen" => "363"
                        "paginaInicial" => "532"
                        "paginaFinal" => "541"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20818888"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Randomized placebo&#8208;controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema&#58; the FAST&#8208;3 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;R&#46; Lumry"
                            1 => "H&#46;H&#46; Li"
                            2 => "R&#46;J&#46; Levy"
                            3 => "P&#46;C&#46; Potter"
                            4 => "H&#46; Farkas"
                            5 => "D&#46; Moldovan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.anai.2011.08.015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol&#46;"
                        "fecha" => "2011"
                        "volumen" => "107"
                        "paginaInicial" => "529"
                        "paginaFinal" => "537"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22123383"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety&#44; and efficacy of icatibant self&#8208;administration for acute hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "I&#46; Boccon-Gibod"
                            1 => "L&#46; Bouillet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2249.2012.04574.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Immunol&#46;"
                        "fecha" => "2012"
                        "volumen" => "168"
                        "paginaInicial" => "303"
                        "paginaFinal" => "307"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22519593"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack618630"
        "titulo" => "Agradecimentos"
        "texto" => "<p id="par0200" class="elsevierStylePara elsevierViewall">Sob a dire&#231;&#227;o dos autores&#44; Sophia Shumyatsky&#44; PharmD&#44; CMPP&#44; funcion&#225;ria da Excel Medical Affairs&#44; forneceu assist&#234;ncia na reda&#231;&#227;o deste manuscrito&#46; A assist&#234;ncia editorial na formata&#231;&#227;o&#44; revis&#227;o&#44; edi&#231;&#227;o e verifica&#231;&#227;o de fatos tamb&#233;m foi fornecida pela Excel Medical Affairs&#46; A Takeda Development Center Americas&#44; Inc&#46; financiou a Excel Medical Affairs para apoio na reda&#231;&#227;o e edi&#231;&#227;o deste manuscrito&#46; A interpreta&#231;&#227;o dos dados foi feita pelos autores de maneira independente&#46; O papel dos funcion&#225;rios da Takeda no projeto do estudo e coleta&#44; an&#225;lise e interpreta&#231;&#227;o dos dados e na reda&#231;&#227;o do manuscrito s&#227;o especificados na se&#231;&#227;o de contribui&#231;&#227;o dos autores&#46; Agradecemos a todos os investigadores do IOS por suas contribui&#231;&#245;es ao registro do IOS&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "pt"
  "url" => "/26662752/0000009700000004/v1_202207280537/S266627522200090X/v1_202207280537/pt/main.assets"
  "Apartado" => array:4 [
    "identificador" => "89618"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Artigo Original"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/26662752/0000009700000004/v1_202207280537/S266627522200090X/v1_202207280537/pt/main.pdf?idApp=UINPBA00008Z&text.app=https://clinics.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S266627522200090X?idApp=UINPBA00008Z"
]
Share
Journal Information

Statistics

Follow this link to access the full text of the article

Artigo original
Uso de icatibanto em pacientes brasileiros com angioedema hereditário (AEH) tipo 1 ou 2 e AEH com níveis normais de C1‐INH: achados do registro do estudo Icatibant Outcome Survey
Anete S. Grumacha,
Corresponding author
anete.grumach@fmabc.net

Autor para correspondência.
, Marina T. Henriquesa, Maine L.D. Bardoua, Daniele A. Pontarollia, Jaco Bothab, Mariangela Correac, for the IOS Brazil Study Group
a Imunologia Clínica, Faculdade de Medicina, Centro Universitario Saúde ABC, Santo André, SP, Brasil
b Takeda Pharmaceuticals International AG, Zurique, Suíça
c Takeda Distribuidora Ltda, São Paulo, SP, Brasil
Read
6963
Times
was read the article
2186
Total PDF
4777
Total HTML
Share statistics
 array:23 [
  "pii" => "S266627522200090X"
  "issn" => "26662752"
  "doi" => "10.1016/j.abdp.2022.06.001"
  "estado" => "S300"
  "fechaPublicacion" => "2022-07-01"
  "aid" => "546"
  "copyrightAnyo" => "2022"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by/4.0/"
  "subdocumento" => "fla"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "en" => array:18 [
      "pii" => "S0365059622000666"
      "issn" => "03650596"
      "doi" => "10.1016/j.abd.2021.09.009"
      "estado" => "S300"
      "fechaPublicacion" => "2022-07-01"
      "aid" => "546"
      "documento" => "article"
      "crossmark" => 1
      "licencia" => "http://creativecommons.org/licenses/by/4.0/"
      "subdocumento" => "fla"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:1 [
        "total" => 0
      ]
      "en" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
        "titulo" => "Icatibant use in Brazilian patients with hereditary angioedema &#40;HAE&#41; type 1 or 2 and HAE with normal C1-INH levels&#58; findings from the Icatibant Outcome Survey Registry Study"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "tieneResumen" => "en"
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "448"
            "paginaFinal" => "457"
          ]
        ]
        "contieneResumen" => array:1 [
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "en" => true
        ]
        "contienePdf" => array:1 [
          "en" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:8 [
            "identificador" => "fig0005"
            "etiqueta" => "Figure 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 463
                "Ancho" => 2508
                "Tamanyo" => 92579
              ]
            ]
            "detalles" => array:1 [
              0 => array:3 [
                "identificador" => "at0005"
                "detalle" => "Figure "
                "rol" => "short"
              ]
            ]
            "descripcion" => array:1 [
              "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Treatment-related time-to-event effectiveness outcomes&#46; Adapted from&#58; Maurer M&#44; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46; HAE&#44; Hereditary Angioedema&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Anete S&#46; Grumach, Marina T&#46; Henriques, Maine L&#46;D&#46; Bardou, Daniele A&#46; Pontarolli, Jaco Botha, Mariangela Correa"
            "autores" => array:7 [
              0 => array:2 [
                "nombre" => "Anete S&#46;"
                "apellidos" => "Grumach"
              ]
              1 => array:2 [
                "nombre" => "Marina T&#46;"
                "apellidos" => "Henriques"
              ]
              2 => array:2 [
                "nombre" => "Maine L&#46;D&#46;"
                "apellidos" => "Bardou"
              ]
              3 => array:2 [
                "nombre" => "Daniele A&#46;"
                "apellidos" => "Pontarolli"
              ]
              4 => array:2 [
                "nombre" => "Jaco"
                "apellidos" => "Botha"
              ]
              5 => array:2 [
                "nombre" => "Mariangela"
                "apellidos" => "Correa"
              ]
              6 => array:1 [
                "colaborador" => "for the IOS Brazil Study Group"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "pt" => array:9 [
          "pii" => "S266627522200090X"
          "doi" => "10.1016/j.abdp.2022.06.001"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "pt"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S266627522200090X?idApp=UINPBA00008Z"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622000666?idApp=UINPBA00008Z"
      "url" => "/03650596/0000009700000004/v1_202206290808/S0365059622000666/v1_202206290808/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2666275222000984"
    "issn" => "26662752"
    "doi" => "10.1016/j.abdp.2022.06.009"
    "estado" => "S300"
    "fechaPublicacion" => "2022-07-01"
    "aid" => "559"
    "copyright" => "Sociedade Brasileira de Dermatologia"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "fla"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "pt" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Artigo original</span>"
      "titulo" => "Diferencial de radia&#231;&#227;o UVB regula a express&#227;o de miRNAs no fotoenvelhecimento da pele"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "tieneResumen" => "pt"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "458"
          "paginaFinal" => "466"
        ]
      ]
      "contieneResumen" => array:1 [
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0030"
          "etiqueta" => "Figura 6"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr6.jpeg"
              "Alto" => 1971
              "Ancho" => 1675
              "Tamanyo" => 144201
            ]
          ]
          "descripcion" => array:1 [
            "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Valida&#231;&#227;o de miRNA&#8208;195a&#8208;5p utilizando RT&#8208;qPCR&#46; Os dados foram normalizados pela m&#233;dia &#177; erro padr&#227;o da m&#233;dia &#40;EPM&#41;&#46; &#42;&#42;&#42;p &#8804; 0&#44;001&#44; &#42;&#42;&#42;&#42;p &#8804; 0&#44;0001&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Yuan Fang, Lei Chen, Xin Wang, Xu Li, Wu Xiong, Xi Zhang, Yufang Zhang, Lu Han, Ke Cao, Xiang Chen, Haibo Li, Jianda Zhou"
          "autores" => array:12 [
            0 => array:2 [
              "nombre" => "Yuan"
              "apellidos" => "Fang"
            ]
            1 => array:2 [
              "nombre" => "Lei"
              "apellidos" => "Chen"
            ]
            2 => array:2 [
              "nombre" => "Xin"
              "apellidos" => "Wang"
            ]
            3 => array:2 [
              "nombre" => "Xu"
              "apellidos" => "Li"
            ]
            4 => array:2 [
              "nombre" => "Wu"
              "apellidos" => "Xiong"
            ]
            5 => array:2 [
              "nombre" => "Xi"
              "apellidos" => "Zhang"
            ]
            6 => array:2 [
              "nombre" => "Yufang"
              "apellidos" => "Zhang"
            ]
            7 => array:2 [
              "nombre" => "Lu"
              "apellidos" => "Han"
            ]
            8 => array:2 [
              "nombre" => "Ke"
              "apellidos" => "Cao"
            ]
            9 => array:2 [
              "nombre" => "Xiang"
              "apellidos" => "Chen"
            ]
            10 => array:2 [
              "nombre" => "Haibo"
              "apellidos" => "Li"
            ]
            11 => array:2 [
              "nombre" => "Jianda"
              "apellidos" => "Zhou"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0365059622000794"
        "doi" => "10.1016/j.abd.2022.01.003"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622000794?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222000984?idApp=UINPBA00008Z"
    "url" => "/26662752/0000009700000004/v1_202207280537/S2666275222000984/v1_202207280537/pt/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S2666275222000856"
    "issn" => "26662752"
    "doi" => "10.1016/j.abdp.2022.05.008"
    "estado" => "S300"
    "fechaPublicacion" => "2022-07-01"
    "aid" => "543"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "fla"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "pt" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Artigo original</span>"
      "titulo" => "Projeto ECHO na dermatite at&#243;pica na Argentina&#58; estrat&#233;gia inovadora para atingir &#225;reas carentes de conhecimento atualizado&#44; primeiro ano de experi&#234;ncia"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "tieneResumen" => "pt"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "443"
          "paginaFinal" => "447"
        ]
      ]
      "contieneResumen" => array:1 [
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => 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" => 880
              "Ancho" => 1734
              "Tamanyo" => 73466
            ]
          ]
          "descripcion" => array:1 [
            "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Distribui&#231;&#227;o dos participantes por especialidade&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Paula C&#46; Luna, Mar&#237;a Emilia Debernardi, Cristina Mariela Echeverr&#237;a, Mar&#237;a Valeria Angles, Luis D&#46; Mazzuoccolo"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "Paula C&#46;"
              "apellidos" => "Luna"
            ]
            1 => array:2 [
              "nombre" => "Mar&#237;a Emilia"
              "apellidos" => "Debernardi"
            ]
            2 => array:2 [
              "nombre" => "Cristina Mariela"
              "apellidos" => "Echeverr&#237;a"
            ]
            3 => array:2 [
              "nombre" => "Mar&#237;a Valeria"
              "apellidos" => "Angles"
            ]
            4 => array:2 [
              "nombre" => "Luis D&#46;"
              "apellidos" => "Mazzuoccolo"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0365059622000630"
        "doi" => "10.1016/j.abd.2021.09.006"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622000630?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222000856?idApp=UINPBA00008Z"
    "url" => "/26662752/0000009700000004/v1_202207280537/S2666275222000856/v1_202207280537/pt/main.assets"
  ]
  "pt" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Artigo original</span>"
    "titulo" => "Uso de icatibanto em pacientes brasileiros com angioedema heredit&#225;rio &#40;AEH&#41; tipo 1 ou 2 e AEH com n&#237;veis normais de C1&#8208;INH&#58; achados do registro do estudo <span class="elsevierStyleItalic">Icatibant Outcome Survey</span>"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "448"
        "paginaFinal" => "457"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Anete S&#46; Grumach, Marina T&#46; Henriques, Maine L&#46;D&#46; Bardou, Daniele A&#46; Pontarolli, Jaco Botha, Mariangela Correa"
        "autores" => array:7 [
          0 => array:4 [
            "nombre" => "Anete S&#46;"
            "apellidos" => "Grumach"
            "email" => array:1 [
              0 => "anete.grumach@fmabc.net"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Marina T&#46;"
            "apellidos" => "Henriques"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Maine L&#46;D&#46;"
            "apellidos" => "Bardou"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Daniele A&#46;"
            "apellidos" => "Pontarolli"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Jaco"
            "apellidos" => "Botha"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Mariangela"
            "apellidos" => "Correa"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          6 => array:1 [
            "colaborador" => "for the IOS Brazil Study Group"
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Imunologia Cl&#237;nica&#44; Faculdade de Medicina&#44; Centro Universitario Sa&#250;de ABC&#44; Santo Andr&#233;&#44; SP&#44; Brasil"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Takeda Pharmaceuticals International AG&#44; Zurique&#44; Su&#237;&#231;a"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Takeda Distribuidora Ltda&#44; S&#227;o Paulo&#44; SP&#44; Brasil"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Autor para correspond&#234;ncia&#46;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figura 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 1567
            "Ancho" => 3333
            "Tamanyo" => 317867
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Resultados de tempo para o evento&#46; As bordas inferior e superior das caixas representam os percentis 25 e 75&#44; respectivamente&#59; os <span class="elsevierStyleItalic">whiskers</span> das caixas denotam os valores m&#237;nimos e m&#225;ximos registrados&#46; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio tipo 1 ou 2&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#59; DP&#44; desvio padr&#227;o&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">O angioedema heredit&#225;rio &#40;AEH&#41; &#233; doen&#231;a gen&#233;tica rara associada a epis&#243;dios de edemas dolorosos que afetam os tecidos subcut&#226;neos e&#47;ou submucosos&#46; As crises geralmente afetam a regi&#227;o da cabe&#231;a e pesco&#231;o&#44; as extremidades e o abd&#244;men&#46; O edema lar&#237;ngeo pode ser potencialmente fatal em virtude do risco de asfixia&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">As crises de AEH recorrem com frequ&#234;ncia e gravidade imprevis&#237;veis&#44; afetando a vida pessoal e profissional dos pacientes e impondo uma pesada carga f&#237;sica e emocional aos pacientes&#44; familiares e cuidadores&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">3&#8211;5</span></a> Epis&#243;dios de edema dolorosos e potencialmente debilitantes podem afetar negativamente a produtividade do trabalho dos pacientes&#44; dificultar a realiza&#231;&#227;o de metas educacionais e levar &#224; ansiedade sobre crises futuras&#44; mesmo durante per&#237;odos sem crise&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">5&#44;6</span></a> De acordo com as diretrizes internacionais de manejo do AEH&#44; o tratamento oportuno de crises agudas e a preven&#231;&#227;o eficaz de crises futuras s&#227;o aspectos integrais do cuidado para pacientes com AEH&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">7&#44;8</span></a> O objetivo final &#233; reduzir a frequ&#234;ncia&#44; a dura&#231;&#227;o e a gravidade das crises&#44; minimizando assim a carga da doen&#231;a e ajudando a normalizar a vida di&#225;ria dos pacientes&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">3&#44;8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">O AEH tipo 1 &#40;em virtude dos baixos n&#237;veis e fun&#231;&#227;o do inibidor de C1 &#91;C1&#8208;INH&#93;&#41; ou tipo 2 &#40;em raz&#227;o da presen&#231;a de C1&#8208;INH disfuncional&#41; &#233; causado principalmente por muta&#231;&#245;es em <span class="elsevierStyleItalic">SERPING1</span>&#44; o gene que codifica o inibidor de C1 &#40;C1&#8208;INH&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">7&#44;9</span></a> C1&#8208;INH &#233; uma protease serina que desempenha papel fundamental na atividade de <span class="elsevierStyleItalic">down</span>&#8208;regula&#231;&#227;o em v&#225;rias cascatas de sinaliza&#231;&#227;o&#44; incluindo a via do complemento&#44; sistema de contato &#40;por meio da cascata calicre&#237;na&#8208;cinina&#41;&#44; via de coagula&#231;&#227;o e fibrin&#243;lise&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">10</span></a> Dentro da cascata de calicre&#237;na&#8208;cinina&#44; o C1&#8208;INH &#233; um inibidor essencial do fator XIIa e da calicre&#237;na plasm&#225;tica&#44; que s&#227;o proteases plasm&#225;ticas&#8208;chave envolvidas na produ&#231;&#227;o de bradicinina&#44; um potente vasodilatador&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">9&#44;10</span></a> A aus&#234;ncia de fun&#231;&#227;o suficiente de C1&#8208;INH leva &#224; ativa&#231;&#227;o descontrolada da via calicre&#237;na&#8208;cinina e &#224; superprodu&#231;&#227;o de bradicinina&#44; a causa subjacente de edema e incha&#231;o em pacientes com AEH tipo 1 ou 2 &#40;AEH&#8208;1&#47;2&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">9&#44;11&#44;12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A presen&#231;a de AEH em pacientes com n&#237;veis e fun&#231;&#227;o normais de C1&#8208;INH &#40;AEH NC1&#8208;INH&#41; tamb&#233;m est&#225; sendo cada vez mais identificada&#59; as vias patogen&#233;ticas ainda n&#227;o foram totalmente elucidadas&#46; V&#225;rias muta&#231;&#245;es em outros genes al&#233;m de <span class="elsevierStyleItalic">SERPING1</span> foram relatadas at&#233; o momento &#40;por exemplo&#44; <span class="elsevierStyleItalic">FXII</span>&#44; cadeia pesada de cininog&#234;nio&#8208;1&#44; plasminog&#234;nio&#44; angiopoietina&#8208;1&#41;&#44; e achados recentes sugerem que a presen&#231;a de uma variante de ganho de fun&#231;&#227;o de mioferlina pode <span class="elsevierStyleItalic">up</span>&#8208;regular a sinaliza&#231;&#227;o mediada pelo fator de crescimento endotelial vascular&#44; levando a permeabilidade vascular excessiva&#46; No entanto&#44; a muta&#231;&#227;o subjacente geralmente permanece desconhecida&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">12&#44;13</span></a> Como acredita&#8208;se que a bradicinina desempenhe papel importante na patog&#234;nese das manifesta&#231;&#245;es cl&#237;nicas do AEH NC1&#8208;INH&#44;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">11&#44;12&#44;14</span></a> terapias que interferem na produ&#231;&#227;o de bradicinina ou em atividades biol&#243;gicas mediadas pela bradicinina podem&#44; em princ&#237;pio&#44; tamb&#233;m ser eficazes em pacientes com essas formas de AEH&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">11</span></a> Nenhum ensaio cl&#237;nico controlado foi realizado at&#233; o momento nesse cen&#225;rio&#59; entretanto&#44; evid&#234;ncias de relatos de casos ou estudos observacionais mostram achados encorajadores em alguns pacientes&#44; incluindo aqueles tratados com icatibanto para crises agudas de AEH&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">15&#8211;17</span></a> Permanece uma necessidade urgente&#44; ainda n&#227;o atendida&#44; de avalia&#231;&#227;o adicional das op&#231;&#245;es de tratamento nessa popula&#231;&#227;o de pacientes&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">O <span class="elsevierStyleItalic">Icatibant Outcome Survey</span> &#40;IOS&#59; NCT01034969&#41; &#233; um estudo de registro p&#243;s&#8208;comercializa&#231;&#227;o&#44; observacional multic&#234;ntrico&#44; internacional e em andamento&#44; que monitora a seguran&#231;a e a efic&#225;cia do icatibanto&#44; um antagonista do receptor B<span class="elsevierStyleInf">2</span> da bradicinina&#44; usado no tratamento agudo de crises de angioedema&#46; O IOS foi iniciado &#40;pela Shire&#44; uma empresa Takeda&#41; em 2009&#44; e desde 30 de setembro de 2019 inscreveu 1&#46;491 pacientes de 13 pa&#237;ses&#44; incluindo 10 pa&#237;ses europeus&#44; al&#233;m de Austr&#225;lia&#44; Brasil e Israel&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">A caracteriza&#231;&#227;o formal do AEH no Brasil teve in&#237;cio em 2006&#44; com a cria&#231;&#227;o do registro brasileiro de AEH pela Rede Brasileira de Diagn&#243;stico&#44; Manejo e Tratamento de AEH&#59; o conhecimento sobre a popula&#231;&#227;o brasileira de pacientes com AEH continua a crescer&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">18</span></a> A preval&#234;ncia estimada de AEH no Brasil &#233; de 4&#46;220 pacientes &#40;com base em uma estimativa de 211 milh&#245;es de pessoas no Brasil em 2020 e uma preval&#234;ncia mundial presumida de AEH de &#8764;1&#58;50&#46;000&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">7&#44;19</span></a> As caracter&#237;sticas cl&#237;nicas e muta&#231;&#245;es gen&#233;ticas em pacientes brasileiros com AEH est&#227;o sendo cada vez mais relatados&#44; incluindo achados em pacientes com AEH&#8208;1&#47;2<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">20&#8211;22</span></a> e naqueles com AEH NC1&#8208;INH&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">16&#44;23&#8211;25</span></a> Estudos avaliando a qualidade de vida em pacientes brasileiros com AEH demonstram uma carga pesada da doen&#231;a nessa popula&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">26&#44;27</span></a> A maioria dos pacientes relatou medo cont&#237;nuo de crises potencialmente fatais e demonstrou comprometimento f&#237;sico e emocional&#59; o impacto negativo foi particularmente observado no que diz respeito &#224; vitalidade e fun&#231;&#227;o social&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A presente an&#225;lise relata achados de pacientes brasileiros &#40;recrutados no Brasil&#41; que foram inscritos no IOS at&#233; 30 de setembro de 2019&#44; incluindo dados demogr&#225;ficos&#44; caracter&#237;sticas cl&#237;nicas e resultados de tratamento em pacientes com AEH&#8208;1&#47;2 e aqueles com AEH NC1&#8208;INH&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Pacientes e resultados</span><p id="par0040" class="elsevierStylePara elsevierViewall">O IOS est&#225; em conformidade com os regulamentos e melhores pr&#225;ticas globais e locais relevantes e segue os princ&#237;pios da Declara&#231;&#227;o de Helsinque e as Diretrizes da <span class="elsevierStyleItalic">International Conference on Harmonisation &#8211; Good Clinical Practice</span>&#46; A aprova&#231;&#227;o foi concedida pelas autoridades de sa&#250;de e comit&#234;s de &#233;tica locais&#46; O consentimento informado por escrito foi fornecido por todos os pacientes &#40;ou seu representante legalmente autorizado&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">O registro IOS est&#225; aberto a todos os pacientes com AEH que receberam pelo menos uma dose de icatibanto&#46; &#201; digno de nota o fato de que&#44; diferentemente de outros pa&#237;ses do IOS&#44; os pacientes no Brasil precisavam ter idade &#8805; 18 para participar &#40;embora o icatibanto agora seja aprovado para uso em pacientes com idade &#60; 18 no Brasil&#41;&#46; De acordo com as descri&#231;&#245;es publicadas anteriormente do desenho de estudo do IOS&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">28</span></a> os dados demogr&#225;ficos dos pacientes&#44; suas caracter&#237;sticas cl&#237;nicas e hist&#243;rico de crises de AEH &#40;incluindo local&#44; frequ&#234;ncia&#44; gravidade&#44; dura&#231;&#227;o&#44; resultados do tratamento e tolerabilidade&#41; foram coletados na inscri&#231;&#227;o&#44; e as informa&#231;&#245;es relacionadas &#224;s crises de AEH foram registradas em visitas regulares de seguimento &#40;de prefer&#234;ncia a cada seis meses&#41;&#46; Os resultados tempo&#8208;at&#233;&#8208;o&#8208;evento relacionados ao tratamento avaliados foram o tempo at&#233; a primeira administra&#231;&#227;o de icatibanto &#40;dura&#231;&#227;o entre o in&#237;cio da crise e a primeira administra&#231;&#227;o de icatibanto&#41;&#59; tempo para resolu&#231;&#227;o completa &#40;dura&#231;&#227;o entre a primeira administra&#231;&#227;o de icatibanto e resolu&#231;&#227;o completa de todos os sintomas&#41; e dura&#231;&#227;o total da crise &#40;tempo entre o in&#237;cio da crise e a resolu&#231;&#227;o completa de todos os sintomas&#59; <a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Eventos adversos &#40;EAs&#41; foram categorizados de acordo com o <span class="elsevierStyleItalic">Dicion&#225;rio M&#233;dico para Classifica&#231;&#227;o de &#211;rg&#227;os do Sistema de Atividades Regulat&#243;rias e Termos Preferenciais</span>&#46; Os EAs ocorridos antes da inscri&#231;&#227;o foram registrados na entrada do paciente no IOS como parte do seu hist&#243;rico m&#233;dico&#44; enquanto os EAs ocorridos ap&#243;s a inscri&#231;&#227;o no IOS foram relatados durante as visitas de seguimento&#46; Embora o uso <span class="elsevierStyleItalic">off&#8208;label</span> tenha sido documentado no registro do IOS como parte das informa&#231;&#245;es de seguran&#231;a a serem relatadas de acordo com as normas regulat&#243;rias&#44; tais eventos n&#227;o foram considerados clinicamente significativos e&#44; como tal&#44; foram analisados separadamente da presente an&#225;lise de seguran&#231;a dos EAs&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">An&#225;lise estat&#237;stica</span><p id="par0055" class="elsevierStylePara elsevierViewall">Todas as an&#225;lises estat&#237;sticas foram realizadas com o software SAS&#174; vers&#227;o 9&#46;4 &#40;SAS Institute&#44; Cary&#44; NC&#44; Estados Unidos&#41;&#46; As medidas quantitativas dos resultados foram relatadas como n&#250;mero de observa&#231;&#245;es&#44; m&#233;dia &#40;desvio padr&#227;o &#91;DP&#93;&#41; ou mediana&#44; primeiro quartil &#40;25&#176; percentil&#41;&#44; terceiro quartil &#40;75&#176; percentil&#41;&#44; valores m&#237;nimos e m&#225;ximos&#46; As diferen&#231;as estat&#237;sticas nas caracter&#237;sticas basais entre pacientes com AEH&#8208;1&#47;2 e pacientes com AEH nC1&#8208;INH foram avaliadas usando o teste de Wilcoxon ou o teste Qui&#8208;Quadrado&#46; As avalia&#231;&#245;es dos resultados do tempo&#8208;at&#233;&#8208;o&#8208;tratamento foram realizadas usando um modelo misto para medidas repetidas com dados transformados em log<span class="elsevierStyleInf">10</span>&#46; As compara&#231;&#245;es de gravidade &#40;leve&#44; moderada <span class="elsevierStyleItalic">vs</span>&#46; grave&#44; muito grave&#41; foram realizadas utilizando um modelo misto linear generalizado de medidas repetidas&#46; Dada a natureza observacional deste registro&#44; todas as an&#225;lises foram consideradas explorat&#243;rias e os valores de p foram interpretados de maneira descritiva&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Resultados</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Caracter&#237;sticas basais</span><p id="par0060" class="elsevierStylePara elsevierViewall">Em 30 de setembro de 2019&#44; um total de 42 pacientes do Brasil estavam inscritos no registro IOS&#44; representando 2&#44;8&#37; do total de inscri&#231;&#245;es de pacientes &#40;AEH&#8208;1&#47;2&#44; n &#61; 26&#59; AEH nC1&#8208;INH&#44; n &#61; 16&#41;&#46; As caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas est&#227;o apresentadas na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a> e na <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>&#46; A maioria dos pacientes era do sexo feminino &#40;AEH&#8208;1&#47;2&#44; 84&#44;6&#37;&#59; AEH nC1&#8208;INH&#44; 100&#37;&#41;&#46; A maioria relatou hist&#243;ria familiar positiva &#40;AEH&#8208;1&#47;2&#44; 80&#44;8&#37;&#59; AEH nC1&#8208;INH&#44; 93&#44;8&#37;&#41;&#46; A mediana da idade no in&#237;cio dos sintomas foi significativamente menor em pacientes com AEH&#8208;1&#47;2 em rela&#231;&#227;o &#224;queles com AEH nC1&#8208;INH &#40;10&#44;0 <span class="elsevierStyleItalic">vs</span>&#46; 16&#44;5 anos&#59; p &#61; 0&#44;0105&#41;&#46; A mediana da idade ao diagn&#243;stico &#40;31&#44;1 <span class="elsevierStyleItalic">vs</span>&#46; 40&#44;9 anos&#59; p &#61; 0&#44;1276&#41; e a mediana do tempo entre o in&#237;cio dos sintomas e o diagn&#243;stico &#40;15&#44;0 <span class="elsevierStyleItalic">vs</span>&#46; 23&#44;8 anos&#59; p &#61; 0&#44;6680&#41; foram numericamente menores em pacientes com AEH&#8208;1&#47;2 do que naqueles com AEH nC1&#8208;INH&#44; respectivamente&#44; mas as diferen&#231;as n&#227;o foram estatisticamente significativas&#46; No momento do corte dos dados&#44; as informa&#231;&#245;es coletadas sobre a presen&#231;a ou aus&#234;ncia de muta&#231;&#245;es gen&#233;ticas espec&#237;ficas em pacientes com AEH nC1&#8208;INH estavam incompletas&#59; assim&#44; os resultados dessa an&#225;lise n&#227;o s&#227;o apresentados&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">N&#250;mero de crises e n&#250;mero de administra&#231;&#245;es de icatibanto</span><p id="par0065" class="elsevierStylePara elsevierViewall">Um total de 165 crises tratadas com icatibanto foi relatado em 18 pacientes com AEH&#8208;1&#47;2&#44; e 63 crises tratadas com icatibanto foram relatadas em 10 pacientes com AEH nC1&#8208;INH&#46; Uma administra&#231;&#227;o de icatibanto foi usada para a maioria das crises &#40;95&#44;7&#37; em pacientes com AEH&#8208;1&#47;2&#59; 96&#44;7&#37; naqueles com AEH nC1&#8208;INH&#41;&#44; conforme <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; &#201; digno de nota que a terapia de resgate concomitante com outros agentes al&#233;m do icatibanto para o tratamento de crises de AEH foi utilizada por alguns pacientes &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; Medicamentos de resgate concomitantes podem ter sido utilizados para ajudar a aliviar os sintomas da crise&#44; em vez de trat&#225;&#8208;la&#46; Por exemplo&#44; analg&#233;sicos e antiem&#233;ticos podem ter sido usados para tratar a dor&#44; n&#225;useas e v&#244;mitos que podem acompanhar crises abdominais&#44; e fluidos podem ter sido administrados como cuidados de suporte para a mesma crise&#46; Em alguns casos&#44; os pacientes utilizaram v&#225;rios medicamentos de resgate&#44; mas n&#227;o necessariamente para a mesma crise&#46; Os agentes utilizados para crises espec&#237;ficas n&#227;o foram registrados&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Ao longo de uma m&#233;dia &#40;DP&#41; de 4&#44;5 &#40;1&#44;66&#41; anos de seguimento &#40;desde a entrada no IOS at&#233; a data da extra&#231;&#227;o de dados ou descontinua&#231;&#227;o&#41; para pacientes com AEH&#8208;1&#47;2&#44; e uma m&#233;dia &#40;DP&#41; de 4&#44;3 &#40;1&#44;42&#41; anos de seguimento para pacientes com AEH nC1&#8208;INH&#44; o n&#250;mero m&#225;ximo de crises relatadas por paciente foi maior em pacientes com AEH&#8208;1&#47;2 &#40;29 crises&#41; do que naqueles com AEH nC1&#8208;INH &#40;17 crises&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Local e gravidade das crises</span><p id="par0075" class="elsevierStylePara elsevierViewall">Em pacientes com AEH&#8208;1&#47;2&#44; a maioria das crises &#40;72&#44;6&#37;&#41; afetou um &#250;nico local &#8211; mais comumente o abd&#244;men &#40;46&#44;3&#37;&#41;&#44; seguido pela pele &#40;22&#44;0&#37;&#59; <a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46; A combina&#231;&#227;o de locais mais comuns envolveu pele e abd&#244;men &#40;15&#44;2&#37;&#41;&#46; Em pacientes com AEH nC1&#8208;INH&#44; as crises tinham a mesma probabilidade de afetar um &#250;nico local ou v&#225;rios locais &#40;50&#37; cada&#41;&#46; A pele e o abd&#244;men foram os locais mais acometidos &#40;20&#37; cada&#41;&#46; A combina&#231;&#227;o de s&#237;tios mais comum envolveu pele e laringe &#40;25&#44;0&#37;&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Os pacientes com AEH nC1&#8208;INH eram mais propensos do que aqueles com AEH&#8208;1&#47;2 a apresentar crises graves ou muito graves antes do tratamento &#40;61&#44;7&#37; <span class="elsevierStyleItalic">vs</span>&#46; 48&#44;8&#37;&#44; respectivamente&#41;&#46; Entretanto&#44; essa diferen&#231;a &#40;grave <span class="elsevierStyleItalic">vs</span>&#46; muito grave&#41; n&#227;o foi significativa &#40;p &#61; 0&#44;8906&#41;&#44; assim como a diferen&#231;a na ocorr&#234;ncia de crises leves&#47;moderadas <span class="elsevierStyleItalic">vs</span>&#46; graves&#47;muito graves &#40;p &#61; 0&#44;1038&#59; <a class="elsevierStyleCrossRef" href="#fig0020">fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados de tempo&#8208;at&#233;&#8208;o&#8208;evento relacionados ao tratamento</span><p id="par0085" class="elsevierStylePara elsevierViewall">Os dados dos resultados do tratamento estavam dispon&#237;veis para at&#233; 142 crises em 17 pacientes com AEH&#8208;1&#47;2 e para at&#233; 52 crises em oito pacientes com AEH nC1&#8208;INH&#46; Todas as medianas &#40;varia&#231;&#227;o&#41; dos resultados de tempo&#8208;at&#233;&#8208;o&#8208;evento foram menores para pacientes com AEH nC1&#8208;INH &#40;<a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#44; incluindo o tempo desde o in&#237;cio da crise at&#233; a primeira administra&#231;&#227;o de icatibanto &#40;AEH nC1&#8208;INH&#44; n &#61; 47 crises&#44; 0&#44;5 &#91;0&#8208;96&#44;0&#93; horas&#59; AEH&#8208;1&#47;2&#44; n &#61; 135 crises&#44; 1&#44;0 &#91;0&#8208;94&#44;0&#93; horas&#41;&#59; tempo desde a primeira administra&#231;&#227;o de icatibanto at&#233; a resolu&#231;&#227;o completa dos sintomas &#40;AEH nC1&#8208;INH&#44; n &#61; 52 crises&#44; 1&#44;0 &#91;0&#8211;88&#44;0&#93; horas&#59; AEH&#8208;1&#47;2&#44; n &#61; 142 crises&#44; 5&#44;5 &#91;0&#8211;96&#44;0&#93; horas&#41;&#59; e dura&#231;&#227;o total da crise &#40;AEH nC1&#8208;INH&#44; n &#61; 45 crises&#44; 7&#44;0 &#91;0&#44;3&#8211;99&#44;0&#93; horas&#59; AEH&#8208;1&#47;2&#44; n &#61; 124 crises&#44; 18&#44;5 &#91;0&#44;1&#8211;100&#44;0&#93; horas&#41;&#46; &#201; importante notar que a m&#233;dia de tempo &#40;DP&#41; desde o in&#237;cio da crise at&#233; a resolu&#231;&#227;o foi significativamente menor para pacientes com AEH nC1&#8208;INH <span class="elsevierStyleItalic">vs</span>&#46; AEH&#8208;1&#47;2 &#40;9&#44;8 &#91;18&#44;7&#93; horas <span class="elsevierStyleItalic">vs</span>&#46; 19&#44;6 &#91;24&#44;0&#93; horas&#59; p &#61; 0&#44;0174&#59; <a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Seguran&#231;a</span><p id="par0090" class="elsevierStylePara elsevierViewall">Foram relatados 83 eventos em 42 pacientes&#44; a maioria classificado como leve &#40;66&#44;3&#37;&#41; ou moderado &#40;13&#44;3&#37;&#41; em gravidade e n&#227;o grave &#40;75&#44;9&#37;&#41;&#46; Nenhum dos eventos foi potencialmente fatal ou fatal&#46; Um total de 44 EAs foram relatados em 16 pacientes como possivelmente &#40;quatro eventos&#41; ou provavelmente &#40;40 eventos&#41; relacionados ao uso de icatibanto&#46; O EA mais comum relacionado ao icatibanto foi o eritema no local da inje&#231;&#227;o&#44; afetando 34&#44;6&#37; dos pacientes com AEH&#8208;1&#47;2 e 18&#44;8&#37; daqueles com AEH nC1&#8208;INH &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46; Nenhum evento inesperado ou novos sinais relacionados &#224; seguran&#231;a foram detectados&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discuss&#227;o</span><p id="par0095" class="elsevierStylePara elsevierViewall">Os achados da an&#225;lise atual fornecem uma representa&#231;&#227;o valiosa no mundo real em rela&#231;&#227;o ao uso de icatibanto no tratamento de pacientes com AEH&#8208;1&#47;2 e AEH nC1&#8208;INH no Brasil&#46; Embora apenas um local no Brasil tenha participado&#44; um n&#250;mero substancial de pacientes foi inclu&#237;do&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">As caracter&#237;sticas basais e as caracter&#237;sticas cl&#237;nicas de pacientes com AEH nC1&#8208;INH foram geralmente consistentes com achados publicados anteriormente de coortes de pacientes franceses e brasileiros com AEH nC1&#8208;INH&#44;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">16&#44;23&#44;29&#44;30</span></a> e os achados em pacientes com AEH&#8208;1&#47;2 foram consistentes com caracter&#237;sticas publicadas anteriormente em coortes brasileiras de pacientes com AEH&#8208;1&#47;2&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">18&#44;21&#44;22</span></a> Em compara&#231;&#227;o com pacientes com AEH&#8208;1&#47;2&#44; os pacientes com AEH nC1&#8208;INH tinham uma mediana de idade maior no in&#237;cio dos sintomas&#44; uma idade avan&#231;ada ao diagn&#243;stico e tempo prolongado entre o in&#237;cio dos sintomas e o diagn&#243;stico&#46; Ao longo de um per&#237;odo de seguimento semelhante para os dois grupos de pacientes&#44; os pacientes com AEH nC1&#8208;INH tiveram menos crises de AEH do que aqueles com AEH&#8208;1&#47;2&#46; Esse achado &#233; consistente com uma probabilidade maior de intervalos livres de doen&#231;a descritos anteriormente em pacientes com AEH nC1&#8208;INH&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">31</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Na presente an&#225;lise&#44; a localiza&#231;&#227;o das crises em pacientes com AEH&#8208;1&#47;2 &#40;mais comumente afetando o abd&#244;men ou a pele&#41; foi compar&#225;vel &#224;quelas relatadas anteriormente em outras coortes brasileiras de pacientes com AEH&#8208;1&#47;2&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">18&#44;22</span></a> Pacientes com AEH nC1&#8208;INH eram mais propensos a sofrer crises lar&#237;ngeas e menos propensos a sofrer crises abdominais do que os com AEH&#8208;1&#47;2&#44; consistente com relatos anteriores&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">31&#44;32</span></a> Deve&#8208;se notar&#44; no entanto&#44; que v&#225;rios achados relatados recentemente demonstram a ocorr&#234;ncia de crises abdominais em &#62; 50&#37; dos pacientes com AEH nC1&#8208;INH&#44; especialmente na presen&#231;a de muta&#231;&#245;es FXII&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">16&#44;23&#44;29</span></a> Os achados do presente estudo mostraram ainda que&#44; independentemente do tipo de AEH&#44; a maioria das crises foi efetivamente tratada com uma administra&#231;&#227;o de icatibanto&#44; como relatado anteriormente em pacientes franceses com AEH&#8208;1&#47;2&#44; bem como naqueles com AEH nC1&#8208;INH inclu&#237;dos no IOS&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">29</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Os achados positivos desta an&#225;lise de pacientes brasileiros do IOS baseiam&#8208;se na efic&#225;cia e seguran&#231;a a longo prazo do icatibanto&#44; demonstrada em mais de 10 anos de experi&#234;ncia com 1&#46;052 pacientes com AEH&#8208;1&#47;2 no registro do IOS em mar&#231;o de 2019&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">33</span></a> Naquela an&#225;lise&#44; com base em dados de 5&#46;253 crises tratadas&#44; a resolu&#231;&#227;o completa dos sintomas relacionados &#224; crise ocorreu em uma m&#233;dia de 6 horas ap&#243;s a administra&#231;&#227;o da primeira dose de icatibanto&#46; A dura&#231;&#227;o m&#233;dia total da crise foi de 9 horas&#46; De 618 pacientes com AEH&#8208;1&#47;2 expostos ao icatibanto durante o per&#237;odo de seguimento&#44; 24 relataram um total de 75 EAs que foram considerados possivelmente ou provavelmente relacionados ao uso de icatibanto&#46; Os EAs mais frequentes relacionados ao icatibanto foram eritema no local da inje&#231;&#227;o &#40;29&#44;3&#37;&#41; e astenia &#40;9&#44;3&#37;&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Estudos n&#227;o controlados mostraram resultados encorajadores do tratamento com icatibanto em pacientes com AEH nC1&#8208;INH&#44; incluindo relatos de casos e an&#225;lises retrospectivas&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">15&#44;17&#44;30&#44;34&#44;35</span></a> De fato&#44; o icatibanto est&#225; entre as op&#231;&#245;es de tratamento recomendadas pelas atuais diretrizes internacionais&#47;canadenses para o manejo de AEH no tratamento de crises agudas de AEH em pacientes com AEH nC1&#8208;INH &#40;com base no n&#237;vel de evid&#234;ncia de consenso&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">8</span></a> Os resultados da an&#225;lise atual de pacientes brasileiros do IOS enfatizam ainda mais os benef&#237;cios do icatibanto em pacientes com AEH nC1&#8208;INH&#46; Os achados mostraram uma tend&#234;ncia favor&#225;vel para efeitos mais r&#225;pidos do que em pacientes com AEH&#8208;1&#47;2&#44; incluindo mediana de tempo mais curta para atingir a resolu&#231;&#227;o e dura&#231;&#227;o mediana total de crise mais curta&#44; embora a &#250;nica diferen&#231;a estatisticamente significativa entre os dois grupos de pacientes nessa coorte tenha sido a m&#233;dia de tempo desde a primeira administra&#231;&#227;o de icatibanto at&#233; a resolu&#231;&#227;o completa dos sintomas&#46; &#201; importante notar que o menor tempo m&#233;dio desde o in&#237;cio da crise at&#233; a primeira administra&#231;&#227;o de icatibanto para pacientes com AEH nC1&#8208;INH pode ter contribu&#237;do para os melhores resultados de tempo&#8208;at&#233;&#8208;o&#8208;evento em compara&#231;&#227;o com pacientes com AEH&#8208;1&#47;2&#44; de acordo com os dados do IOS publicados anteriormente&#44; mostrando que a administra&#231;&#227;o precoce de icatibanto resulta em resolu&#231;&#227;o mais r&#225;pida das crises de AEH&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">28</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">O perfil de seguran&#231;a do icatibanto na an&#225;lise atual foi compar&#225;vel entre pacientes com AEH&#8208;1&#47;2 e aqueles com AEH nC1&#8208;INH&#59; as rea&#231;&#245;es relacionadas ao local da inje&#231;&#227;o foram os EAs mais frequentemente relatados&#46; Os achados s&#227;o consistentes com o perfil de seguran&#231;a do icatibanto relatado em estudos controlados&#8208;chave em pacientes com AEH&#8208;1&#47;2&#44;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">36&#44;37</span></a> bem como em outras an&#225;lises p&#243;s&#8208;comercializa&#231;&#227;o em pacientes do IOS e pacientes tratados com icatibanto com AEH nC1&#8208;INH em estudos n&#227;o controlados&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">29&#44;34&#44;38</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">V&#225;rias limita&#231;&#245;es s&#227;o inerentes a um desenho de estudo observacional&#44; incluindo a falta de comparador de tratamento e depend&#234;ncia da mem&#243;ria do paciente&#44; potencialmente levando a subnotifica&#231;&#227;o de crises mais leves ou relato incompleto de sintomas&#46; Al&#233;m disso&#44; todas as an&#225;lises foram <span class="elsevierStyleItalic">post hoc</span>&#44; e a amostra n&#227;o tinha poder para mostrar as diferen&#231;as&#59; dessa maneira&#44; os resultados das compara&#231;&#245;es entre os dois grupos de pacientes devem ser interpretados com cautela&#46; Entretanto&#44; apesar dessas limita&#231;&#245;es inerentes&#44; registros como o IOS s&#227;o ferramentas &#250;teis para obter informa&#231;&#245;es sobre o AEH al&#233;m das configura&#231;&#245;es de ensaios cl&#237;nicos controlados e para avaliar a efic&#225;cia e a seguran&#231;a do icatibanto por longos per&#237;odos de tempo&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Vale ressaltar que o icatibanto foi lan&#231;ado no Brasil em 2009 e &#233; aprovado pela Ag&#234;ncia Nacional de Vigil&#226;ncia Sanit&#225;ria &#40;Anvisa&#41;&#44; por&#233;m n&#227;o foi introduzido no protocolo oficial do Minist&#233;rio da Sa&#250;de do Brasil&#46; Desse modo&#44; n&#227;o h&#225; financiamento do governo atualmente para o seu uso&#59; portanto&#44; o acesso do paciente a essa terapia continua sendo um desafio&#46; Espera&#8208;se que o relato cont&#237;nuo dos achados de efic&#225;cia e seguran&#231;a do icatibanto&#44; como os feitos aqui&#44; ajude a melhorar a acessibilidade a essa medica&#231;&#227;o para o tratamento de AEH no Brasil&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclus&#245;es</span><p id="par0135" class="elsevierStylePara elsevierViewall">A caracteriza&#231;&#227;o de v&#225;rias formas de AEH em todo o mundo continua a crescer&#44; abrindo caminho para uma melhor compreens&#227;o das muta&#231;&#245;es gen&#233;ticas subjacentes&#44; dados demogr&#225;ficos dos pacientes e resultados do tratamento em v&#225;rias popula&#231;&#245;es de pacientes com AEH&#46; A presente an&#225;lise fornece suporte para a efic&#225;cia&#44; seguran&#231;a e tolerabilidade do icatibanto em pacientes brasileiros com AEH&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Suporte financeiro</span><p id="par0160" class="elsevierStylePara elsevierViewall">Anete S&#46; Grumach &#233; bolsista de produtividade CNPq&#46; &#40;309824&#47;2021&#8208;4&#41;&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Esta pesquisa foi patrocinada pela <span class="elsevierStyleItalic">Shire Human Genetic Therapies</span>&#44; Inc&#46;&#44; uma empresa Takeda&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Contribui&#231;&#227;o dos autores</span><p id="par0165" class="elsevierStylePara elsevierViewall">Anete S&#46; Grumach&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Marina T&#46; Henriques&#58; Obten&#231;&#227;o&#44; an&#225;lise e&#47;ou interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Maine L&#46; D&#46; Bardou&#58; Obten&#231;&#227;o&#44; an&#225;lise e&#47;ou interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Daniele A&#46; Pontarolli&#58; Obten&#231;&#227;o&#44; an&#225;lise e&#47;ou interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Jaco Botha&#58; Obten&#231;&#227;o&#44; an&#225;lise e&#47;ou interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Mariangela Correa&#58; Obten&#231;&#227;o&#44; an&#225;lise e&#47;ou interpreta&#231;&#227;o dos dados&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito e revis&#227;o cr&#237;tica do manuscrito&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflito de interesses</span><p id="par0195" class="elsevierStylePara elsevierViewall">Anete S&#46; Grumach foi palestrante ou consultora da BioCryst&#44; Biotest&#44; CSL Behring e Takeda&#46; Marina T&#46; Henriques&#44; Maine L&#46; D&#46; Bardou e Daniele A&#46; Pontarolli n&#227;o t&#234;m conflito de interesses a declarar&#46; J&#46; Botha &#233; funcion&#225;rio e possui op&#231;&#245;es de compra de a&#231;&#245;es&#47;a&#231;&#245;es da Takeda&#46; M&#46; Correa era funcion&#225;ria e possu&#237;a op&#231;&#245;es de compra de a&#231;&#245;es&#47;a&#231;&#245;es da Takeda no momento desta an&#225;lise&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:12 [
        0 => array:3 [
          "identificador" => "xres1751126"
          "titulo" => "Resumo"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Fundamento"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "M&#233;todos"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Objetivo"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Resultados"
            ]
            4 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Limita&#231;&#245;es do estudo"
            ]
            5 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Conclus&#245;es"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1542398"
          "titulo" => "Palavras&#8208;chave"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introdu&#231;&#227;o"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "M&#233;todos"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Pacientes e resultados"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "An&#225;lise estat&#237;stica"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "sec0025"
          "titulo" => "Resultados"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Caracter&#237;sticas basais"
            ]
            1 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "N&#250;mero de crises e n&#250;mero de administra&#231;&#245;es de icatibanto"
            ]
            2 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Local e gravidade das crises"
            ]
            3 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Resultados de tempo&#8208;at&#233;&#8208;o&#8208;evento relacionados ao tratamento"
            ]
            4 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Seguran&#231;a"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Discuss&#227;o"
        ]
        6 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conclus&#245;es"
        ]
        7 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Suporte financeiro"
        ]
        8 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Contribui&#231;&#227;o dos autores"
        ]
        9 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Conflito de interesses"
        ]
        10 => array:2 [
          "identificador" => "xack618630"
          "titulo" => "Agradecimentos"
        ]
        11 => array:1 [
          "titulo" => "Refer&#234;ncias"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2021-05-21"
    "fechaAceptado" => "2021-09-15"
    "PalabrasClave" => array:1 [
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras&#8208;chave"
          "identificador" => "xpalclavsec1542398"
          "palabras" => array:4 [
            0 => "Angioedema heredit&#225;rio"
            1 => "Bradicinina"
            2 => "Brasil"
            3 => "Receptor de bradicinina"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamento</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">O angioedema heredit&#225;rio pode ser causado por defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1 &#40;C1&#8208;INH&#59; AEH&#8208;1&#47;2&#41; ou pode ocorrer em pacientes com C1&#8208;INH normal &#40;AEH nC1&#8208;INH&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">O registro <span class="elsevierStyleItalic">Icatibant Outcome Survey</span> &#40;IOS&#59; NCT01034969&#41; monitora a seguran&#231;a e a efic&#225;cia do icatibanto no tratamento do angioedema agudo&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Objetivo</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Apresentar achados de pacientes brasileiros com AEH&#8208;1&#47;2 e AEH nC1&#8208;INH participantes do IOS&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos 42 pacientes &#40;AEH&#8208;1&#47;2&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#59; AEH nC1&#8208;INH&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&#46; A idade mediana no in&#237;cio dos sintomas foi significativamente menor com AEH&#8208;1&#47;2 <span class="elsevierStyleItalic">vs</span>&#46; AEH nC1&#8208;INH &#40;10&#44;0 <span class="elsevierStyleItalic">vs</span>&#46; 16&#44;5 anos&#44; respectivamente&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0105&#41;&#44; enquanto a mediana da idade no diagn&#243;stico &#40;31&#44;1 <span class="elsevierStyleItalic">vs</span>&#46; 40&#44;9 anos&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;1276&#41; e a mediana do tempo entre o in&#237;cio dos sintomas e o diagn&#243;stico &#40;15&#44;0 <span class="elsevierStyleItalic">vs</span>&#46; 23&#44;8 anos&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;6680&#41; foram numericamente menores <span class="elsevierStyleItalic">vs</span>&#46; AEH nC1&#8208;INH&#44; respectivamente&#46; Uma dose de icatibanto foi utilizada para &#62; 95&#37; das crises de AEH&#46; A mediana dos desfechos &#40;intervalo&#41; de tempo&#8208;at&#233;&#8208;o&#8208;evento foram menores para pacientes com AEH nC1&#8208;INH vs&#46; AEH&#8208;1&#47;2&#44; incluindo o tempo at&#233; a primeira administra&#231;&#227;o &#40;0&#44;5 &#91;0&#8211;96&#44;0&#93; vs&#46; 1&#44;0 &#91;0&#8211;94&#44;0&#93; hora&#44; respectivamente&#41;&#44; tempo desde a primeira administra&#231;&#227;o at&#233; a resolu&#231;&#227;o completa &#40;1&#44;0 &#91;0&#8211;88&#44;0&#93; <span class="elsevierStyleItalic">vs</span>&#46; 5&#44;5 &#91;0&#8211;96&#44;0&#93; horas&#44; respectivamente&#41; e dura&#231;&#227;o total da crise &#40;7&#44;0 &#91;0&#44;3&#8211;99&#44;0&#93; <span class="elsevierStyleItalic">vs</span>&#46; 18&#44;5 &#91;0&#44;1&#8211;100&#44;0&#93; horas&#44; respectivamente&#41;&#46; O tempo m&#233;dio &#40;DP&#41; desde o in&#237;cio da crise at&#233; a resolu&#231;&#227;o foi significativamente menor em pacientes com AEH nC1&#8208;INH <span class="elsevierStyleItalic">vs</span>&#46; AEH&#8208;1&#47;2 &#40;9&#44;8 &#91;18&#44;7&#93; <span class="elsevierStyleItalic">vs</span>&#46; 19&#44;6 &#91;24&#44;0&#93; horas&#44; respectivamente&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0174&#41;&#46; Foram relatados 83 eventos adversos &#40;EAs&#41; em 42 pacientes&#59; a maioria foi leve &#40;66&#44;3&#37;&#41; ou moderada &#40;13&#44;3&#37;&#41; e n&#227;o grave &#40;75&#44;9&#37;&#41;&#46; O EA mais comum relacionado ao icatibanto foi eritema no local da inje&#231;&#227;o &#40;AEH&#8208;1&#47;2&#44; 34&#44;6&#37;&#59; AEH nC1&#8208;INH&#44; 18&#44;8&#37;&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Este foi um estudo observacional que n&#227;o tinha um comparador de tratamento e baseou&#8208;se nas recorda&#231;&#245;es dos pacientes&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Os achados demonstram efic&#225;cia e tolerabilidade do icatibanto em pacientes brasileiros com AEH&#46;</p></span>"
        "secciones" => array:6 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Fundamento"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Objetivo"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Limita&#231;&#245;es do estudo"
          ]
          5 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Conclus&#245;es"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0045">Como citar este artigo&#58; Grumach AS&#44; Henriques MT&#44; Bardou MLD&#44; Pontarolli DA&#44; Botha J&#44; Correa M&#46; Icatibant use in Brazilian patients with hereditary angioedema &#40;HAE&#41; type&#160;1&#160;or&#160;2 and HAE with normal C1&#8208;INH levels&#58; findings from the Icatibant Outcome Survey Registry Study&#46; An Bras Dermatol&#46; 2022&#59;97&#58;448&#8211;57&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0050">Trabalho realizado na Imunologia Cl&#237;nica&#44; Faculdade de Medicina&#44; Centro Universit&#225;rio Sa&#250;de ABC&#44; Santo Andr&#233;&#44; SP&#44; Brasil&#46;</p>"
      ]
    ]
    "multimedia" => array:9 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 629
            "Ancho" => 3333
            "Tamanyo" => 145061
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Resultados da efic&#225;cia do tempo&#8208;at&#233;&#8208;o&#8208;evento relacionados ao tratamento&#46; Adaptada de&#58; Maurer M et al&#46;&#44; <a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">28</span></a>&#46; AEH&#44; angioedema heredit&#225;rio&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2790
            "Ancho" => 1675
            "Tamanyo" => 187136
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Dados demogr&#225;ficos basais&#46; &#40;a&#41; Mediana da idade no in&#237;cio dos sintomas de angioedema heredit&#225;rio &#40;p &#61; 0&#44;0105&#41;&#46; &#40;b&#41; Mediana da idade no diagn&#243;stico &#40;p &#61; 0&#44;1276&#41;&#46; &#40;c&#41; Mediana do tempo desde o in&#237;cio dos sintomas at&#233; o diagn&#243;stico &#40;diferen&#231;a entre a idade dos primeiros sintomas e a idade de diagn&#243;stico&#59; p &#61; 0&#44;6680&#41;&#46; As bordas esquerda e direita das caixas representam os percentis 25 e 75&#44; respectivamente&#59; os <span class="elsevierStyleItalic">whiskers</span> da caixa denotam os valores m&#237;nimos e m&#225;ximos registrados&#46; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1542
            "Ancho" => 2175
            "Tamanyo" => 140219
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Local mais comum de crises de angioedema heredit&#225;rio&#46; AEH&#8208;1&#47;2&#44; n &#61; 164 crises &#40;um faltando&#41;&#59; AEH nC1&#8208;INH&#44; n &#61; 60 crises &#40;tr&#234;s faltando&#41;&#46; Apenas os locais &#250;nicos e combina&#231;&#245;es de locais mais comuns s&#227;o mostrados&#59; assim&#44; os percentuais n&#227;o totalizam 100&#37;&#46; As crises que afetam a pele referem&#8208;se aos seguintes locais&#58; bra&#231;os&#44; pavilh&#245;es auriculares&#44; p&#225;lpebras&#44; face&#44; p&#233;s&#44; genitais&#44; m&#227;os&#44; pernas&#44; l&#225;bios&#44; nariz&#44; tronco&#44; outros&#44; desconhecidos&#46; Crises abdominais referem&#8208;se especificamente a crises que afetam a mucosa gastrintestinal&#46; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figura 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 992
            "Ancho" => 2175
            "Tamanyo" => 135903
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Gravidade das crises de angioedema heredit&#225;rio antes do tratamento&#46; AEH&#8208;1&#47;2&#44; n &#61; 164 crises &#40;falta uma&#41;&#59; AEH nC1&#8208;INH&#44; n &#61; 60 crises &#40;faltam tr&#234;s&#41;&#46; A gravidade da crise foi avaliada com base nas seguintes descri&#231;&#245;es&#58; Leve&#58; interfer&#234;ncia leve nas atividades di&#225;rias&#59; Moderada&#58; interfer&#234;ncia moderada nas atividades di&#225;rias e sem necessidade de outras contramedidas&#59; Grave&#58; interfer&#234;ncia grave nas atividades di&#225;rias e com ou sem outras contramedidas&#59; Muito grave&#58; interfer&#234;ncia muito grave nas atividades di&#225;rias e outras contramedidas necess&#225;rias&#46; A diferen&#231;a entre os dois grupos de pacientes na ocorr&#234;ncia de crises leves&#47;moderadas versus graves&#47;muito graves n&#227;o foi significativa &#40;p &#61; 0&#44;1038&#41;&#46; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figura 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 1567
            "Ancho" => 3333
            "Tamanyo" => 317867
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Resultados de tempo para o evento&#46; As bordas inferior e superior das caixas representam os percentis 25 e 75&#44; respectivamente&#59; os <span class="elsevierStyleItalic">whiskers</span> das caixas denotam os valores m&#237;nimos e m&#225;ximos registrados&#46; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio tipo 1 ou 2&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#59; DP&#44; desvio padr&#227;o&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabela 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">AEH</span>&#44; angioedema heredit&#225;rio&#59; <span class="elsevierStyleItalic">AEH&#8208;1&#47;2</span>&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; <span class="elsevierStyleItalic">AEH nC1&#8208;INH</span>&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#59; <span class="elsevierStyleItalic">IOS</span>&#44; <span class="elsevierStyleItalic">Icatibant Outcome Survey</span>&#59; <span class="elsevierStyleItalic">DP</span>&#44; desvio padr&#227;o&#59; SI&#44; sem informa&#231;&#245;es&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Caracter&#237;stica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH&#8208;1&#47;2&#40;n &#61; 26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH nC1&#8208;INH &#40;n &#61; 16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Geral&#40;n &#61; 42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">26 &#40;0&#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">16 &#40;0&#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">42 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Feminino&#44; n &#40;&#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">22 &#40;84&#44;6&#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">16 &#40;100&#44;0&#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">38 &#40;90&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Masculino&#44; n &#40;&#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">4 &#40;15&#44;4&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;9&#44;5&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade no in&#237;cio dos sintomas de AEH &#40;anos&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">23 &#40;3&#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">16 &#40;0&#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">39 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dia &#40;DP&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;5 &#40;9&#44;4&#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">18&#44;9 &#40;10&#44;1&#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">14&#44;0 &#40;10&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;varia&#231;&#227;o&#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">10&#44;0 &#40;0&#44;3&#8211;35&#44;0&#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">16&#44;5 &#40;3&#44;0&#8211;35&#44;0&#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">14&#44;0 &#40;0&#44;3&#8211;35&#44;0&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade no diagn&#243;stico de AEH &#40;anos&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">25 &#40;1&#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">16 &#40;0&#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">41 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dia &#40;DP&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;6 &#40;16&#44;2&#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">37&#44;6 &#40;15&#44;8&#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">33&#44;9 &#40;16&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;varia&#231;&#227;o&#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">31&#44;1 &#40;5&#44;1&#8211;68&#44;0&#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">40&#44;9 &#40;7&#44;8&#8211;62&#44;3&#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">33&#44;8 &#40;5&#44;1&#8211;68&#44;0&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tempo entre o in&#237;cio dos sintomas de AEH e o diagn&#243;stico &#40;anos&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">22 &#40;4&#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">16 &#40;0&#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">38 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dia &#40;DP&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;8 &#40;17&#44;8&#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">18&#44;8 &#40;15&#44;9&#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">18&#44;8 &#40;16&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;varia&#231;&#227;o&#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">15&#44;0 &#40;0&#8211;66&#44;9&#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">23&#44;8 &#40;0&#8211;48&#44;3&#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">16&#44;1 &#40;0&#8211;66&#44;9&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hist&#243;ria familiar de AEH</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">24 &#40;2&#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">16 &#40;0&#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">40 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; n &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;87&#44;5&#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">15 &#40;93&#44;8&#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">36 &#40;90&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&#44; n &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;12&#44;5&#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">1 &#40;6&#44;3&#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">4 &#40;10&#44;0&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade na inclus&#227;o do IOS &#40;anos&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>n &#40;SI&#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">26 &#40;0&#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">16 &#40;0&#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">42 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dia &#40;DP&#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">41&#44;9 &#40;13&#44;0&#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">42&#44;1 &#40;13&#44;8&#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">42&#44;0 &#40;13&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;varia&#231;&#227;o&#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">39&#44;8 &#40;19&#44;0&#8211;0&#44;7&#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">42&#44;9 &#40;18&#44;3&#8211;64&#44;3&#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">41&#44;9 &#40;18&#44;3&#8211;70&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:4 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">p &#61; 0&#44;0105&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">p &#61; 0&#44;1276&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">p &#61; 0&#44;6880&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Porcentagens excluem valores faltantes&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas basais</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">AEH</span>&#44; angioedema heredit&#225;rio&#59; <span class="elsevierStyleItalic">AEH&#8208;1&#47;2</span>&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; <span class="elsevierStyleItalic">AEH nC1&#8208;INH</span>&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#59; <span class="elsevierStyleItalic">Q</span>&#44; quartil&#59; <span class="elsevierStyleItalic">DP</span>&#44; desvio padr&#227;o&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH&#8208;1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH nC1&#8208;INH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#250;mero de pacientes com &#8805; 1 crise de AEH tratados com icatibanto&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">18&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">10&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  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N&#250;mero de crises por paciente</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>M&#233;dia &#40;DP&#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">9&#44;2 &#40;9&#44;7&#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">6&#44;3 &#40;4&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;Q1&#44; Q3&#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">5&#44;5 &#40;1&#44;0&#44; 18&#44;0&#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">6&#44;0 &#40;5&#44;0&#44; 8&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Varia&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;17&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  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Porcentagem de crises necessitando de 1&#44; 2 ou 4 administra&#231;&#245;es de icatibanto &#40;&#37;&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Com base em um n&#250;mero total de 164 crises &#40;faltando uma&#41; em pacientes com AEH&#8208;1&#47;2 e um total de 60 crises &#40;faltando tr&#234;s&#41; em pacientes com AEH nC1&#8208;INH&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Frequ&#234;ncia de crises e administra&#231;&#245;es de icatibanto</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">C1&#8208;INH&#44; inibidor de C1&#59; AEH&#44; angioedema heredit&#225;rio&#59; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#59; SI&#44; sem informa&#231;&#245;es&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH&#8208;1&#47;2 &#40;n &#61; 164 &#91;SI &#61; 1&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH nC1&#8208;INH&#40;n &#61; 63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total&#40;n &#61; 227&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Analg&#233;sicos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;4&#44;3&#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">5 &#40;7&#44;9&#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">12 &#40;5&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiem&#233;ticos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;3&#44;0&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;2&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antifibrinol&#237;ticos&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">15 &#40;9&#44;1&#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">31 &#40;49&#44;2&#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">46 &#40;20&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;histam&#237;nicos&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">3 &#40;1&#44;8&#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">1 &#40;1&#44;6&#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">4 &#40;1&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Andr&#243;genos atenuados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;3&#44;0&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;2&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Concentrado de C1&#8208;INH&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">15 &#40;9&#44;1&#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&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">15 &#40;6&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fluidos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;6&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Plasma fresco congelado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;6&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Outros&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;3&#44;0&#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">1 &#40;1&#44;6&#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">6 &#40;2&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inibidores da bomba de pr&#243;tons&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;6&#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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiespasm&#243;dicos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;2&#44;4&#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">3 &#40;4&#44;8&#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">7 &#40;3&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Uso de medicamentos al&#233;m do icatibanto para crises de AEH tratadas durante o per&#237;odo de seguimento</p>"
        ]
      ]
      8 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Tabela 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">EA&#44; evento adverso&#59; AEH&#8208;1&#47;2&#44; angioedema heredit&#225;rio com defici&#234;ncia e&#47;ou disfun&#231;&#227;o do inibidor de C1&#59; AEH nC1&#8208;INH&#44; angioedema heredit&#225;rio com n&#237;veis e fun&#231;&#227;o normais do inibidor de C1&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">EA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH&#8208;1&#47;2</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AEH nC1&#8208;INH</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pacientes&#40;n &#61; 26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eventos&#40;n &#61; 58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pacientes&#40;n &#61; 16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eventos&#40;n &#61; 25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Rea&#231;&#227;o no local da inje&#231;&#227;o</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Eritema<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;34&#44;6&#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">18 &#40;31&#44;0&#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">3 &#40;18&#44;8&#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">6 &#40;24&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dor no local de aplica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;7&#44;7&#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">3 &#40;5&#44;2&#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">1 &#40;6&#44;3&#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">1 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hematoma&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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;6&#44;3&#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">1 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hemorragia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;8&#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">1 &#40;1&#44;7&#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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hiperemia</span>&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">3 &#40;11&#44;5&#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">4 &#40;6&#44;9&#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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Edema localizado</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;8&#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">1 &#40;1&#44;7&#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">2 &#40;12&#44;5&#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">2 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dor</span>&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">3 &#40;11&#44;5&#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">3 &#40;5&#44;2&#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">1 &#40;6&#44;3&#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">1 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N&#225;usea</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;8&#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">1 &#40;1&#44;7&#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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Edema</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;8&#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">1 &#40;1&#44;7&#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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Angioedema</span><a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#44;8&#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">1 &#40;1&#44;7&#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">&#8211;&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">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Excluindo relatos de uso <span class="elsevierStyleItalic">off&#8208;label</span>&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Inclui os termos preferenciais &#8220;Eritema no local da inje&#231;&#227;o&#8221; e &#8220;Eritema no local da aplica&#231;&#227;o&#8221;&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0040"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Esse evento foi classificado como EA grave&#46; O paciente recebeu duas doses de icatibanto antes de ser hospitalizado por 24 horas&#46; No hospital&#44; o paciente recebeu plasma fresco congelado e recebeu alta no dia seguinte sem sequelas&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Eventos adversos considerados como possivelmente ou provavelmente relacionados ao uso de icatibanto &#40;por termo preferencial&#41;<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a></p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:38 [
            0 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The clinical evaluation of angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46; Gill"
                            1 => "S&#46;D&#46; Betschel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.iac.2017.04.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunol Allergy Clin North Am&#46;"
                        "fecha" => "2017"
                        "volumen" => "37"
                        "paginaInicial" => "449"
                        "paginaFinal" => "466"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28687102"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fatal laryngeal attacks&#44; and mortality in hereditary angioedema due to C1&#8208;INH deficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46; Bork"
                            1 => "J&#46; Hardt"
                            2 => "G&#46; Witzke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2012.05.055"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol&#46;"
                        "fecha" => "2012"
                        "volumen" => "130"
                        "paginaInicial" => "692"
                        "paginaFinal" => "697"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22841766"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long&#8208;term prophylaxis therapy in patients with hereditary angioedema with C1 inhibitor deficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Craig"
                            1 => "P&#46; Busse"
                            2 => "R&#46;G&#46; Gower"
                            3 => "D&#46;T&#46; Johnston"
                            4 => "J&#46;M&#46; Kashkin"
                            5 => "H&#46;H&#46; Li"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.anai.2018.07.025"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol&#46;"
                        "fecha" => "2018"
                        "volumen" => "121"
                        "paginaInicial" => "673"
                        "paginaFinal" => "679"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30056152"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Diagnosis of Hereditary Angioedema&#58; Family Caregivers&#8217; Experiences"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Granero-Molina"
                            1 => "F&#46; S&#225;nchez-Hern&#225;ndez"
                            2 => "C&#46; Fern&#225;ndez-Sola"
                            3 => "M&#46;D&#46;M&#46; Jim&#233;nez-Lasserrotte"
                            4 => "L&#46;H&#46; Antequera-Raynal"
                            5 => "J&#46;M&#46; Hern&#225;ndez-Padilla"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/1054773818780102"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Nurs Res&#46;"
                        "fecha" => "2020"
                        "volumen" => "29"
                        "paginaInicial" => "117"
                        "paginaFinal" => "126"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29862835"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The burden of illness in patients with hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "A&#46; Banerji"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.anai.2013.08.019"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol&#46;"
                        "fecha" => "2013"
                        "volumen" => "111"
                        "paginaInicial" => "329"
                        "paginaFinal" => "336"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24125136"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Patient&#8208;reported burden of hereditary angioedema&#58; findings from a patient survey in the United States"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Banerji"
                            1 => "K&#46;H&#46; Davis"
                            2 => "T&#46;M&#46; Brown"
                            3 => "K&#46; Holis"
                            4 => "S&#46;M&#46; Hunter"
                            5 => "J&#46; Long"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.anai.2020.02.018"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol&#46;"
                        "fecha" => "2020"
                        "volumen" => "124"
                        "paginaInicial" => "600"
                        "paginaFinal" => "607"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32169514"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The international WAO&#47;EAACI guideline for the management of hereditary angioedema &#8208; the 2017 revision and update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Maurer"
                            1 => "M&#46; Magerl"
                            2 => "I&#46; Ansotegui"
                            3 => "E&#46; Ayg&#246;ren-P&#252;rs&#252;n"
                            4 => "S&#46; Betschel"
                            5 => "K&#46; Bork"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/all.13384"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2018"
                        "volumen" => "73"
                        "paginaInicial" => "1575"
                        "paginaFinal" => "1596"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29318628"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The International&#47;Canadian Hereditary Angioedema Guideline"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Betschel"
                            1 => "J&#46; Badiou"
                            2 => "K&#46; Binkley"
                            3 => "R&#46; Borici-Mazi"
                            4 => "J&#46; H&#233;bert"
                            5 => "A&#46; Kanani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13223-019-0376-8"
                      "Revista" => array:5 [
                        "tituloSerie" => "Allergy Asthma Clin Immunol&#46;"
                        "fecha" => "2019"
                        "volumen" => "15"
                        "paginaInicial" => "72"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31788005"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C1 inhibitor activity and angioedema attacks in patients with hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Kaplan"
                            1 => "D&#46; Pawaskar"
                            2 => "J&#46; Chiao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaip.2019.10.003"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol Pract&#46;"
                        "fecha" => "2020"
                        "volumen" => "8"
                        "paginaInicial" => "892"
                        "paginaFinal" => "900"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31655295"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of complement in hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Levi"
                            1 => "D&#46; Cohn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.tmrv.2019.08.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Transfus Med Rev&#46;"
                        "fecha" => "2019"
                        "volumen" => "33"
                        "paginaInicial" => "243"
                        "paginaFinal" => "247"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31676220"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Angioedema due to bradykinin dysregulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Cicardi"
                            1 => "B&#46;L&#46; Zuraw"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaip.2018.04.022"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol Pract&#46;"
                        "fecha" => "2018"
                        "volumen" => "6"
                        "paginaInicial" => "1132"
                        "paginaFinal" => "1141"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30033914"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46; Busse"
                            1 => "S&#46; Christiansen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra1808012"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med&#46;"
                        "fecha" => "2020"
                        "volumen" => "382"
                        "paginaInicial" => "1136"
                        "paginaFinal" => "1148"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32187470"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A myoferlin gain&#8208;of&#8208;function variant associates with a new type of hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Ariano"
                            1 => "M&#46; D&#8217;Apolito"
                            2 => "M&#46; Bova"
                            3 => "F&#46; Bellanti"
                            4 => "S&#46; Loffredo"
                            5 => "G&#46; D&#8217;Andrea"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2020"
                        "volumen" => "75"
                        "paginaInicial" => "2989"
                        "paginaFinal" => "2992"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An update on the genetics and pathogenesis of hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;Z&#46; Banday"
                            1 => "A&#46; Kaur"
                            2 => "A&#46;K&#46; Jindal"
                            3 => "A&#46; Rawat"
                            4 => "S&#46; Singh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.gendis.2019.07.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genes Dis&#46;"
                        "fecha" => "2019"
                        "volumen" => "7"
                        "paginaInicial" => "75"
                        "paginaFinal" => "83"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32181278"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema with a mutation in the plasminogen gene"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Bork"
                            1 => "K&#46; Wulff"
                            2 => "L&#46; Steinm&#252;ller-Magin"
                            3 => "I&#46; Braenne"
                            4 => "P&#46; Staubach-Renz"
                            5 => "G&#46; Witzke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/all.13270"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2018"
                        "volumen" => "73"
                        "paginaInicial" => "442"
                        "paginaFinal" => "450"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28795768"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary Angioedema with Normal C1 Inhibitor and F12 Mutations in 42 Brazilian Families"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;L&#46; Veronez"
                            1 => "A&#46;S&#46; Moreno"
                            2 => "R&#46;N&#46; Constantino-Silva"
                            3 => "L&#46;S&#46;M&#46; Maia"
                            4 => "M&#46;P&#46;L&#46; Ferriani"
                            5 => "F&#46;F&#46;M&#46; Castro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaip.2017.09.025"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol Pract&#46;"
                        "fecha" => "2018"
                        "volumen" => "6"
                        "paginaInicial" => "1209"
                        "paginaFinal" => "1216"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29128335"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Review of the Manitoba cohort of patients with hereditary angioedema with normal C1 inhibitor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L&#46; McKibbin"
                            1 => "C&#46; Barber"
                            2 => "C&#46; Kalicinsky"
                            3 => "R&#46; Warrington"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13223-019-0381-y"
                      "Revista" => array:5 [
                        "tituloSerie" => "Allergy Asthma Clin Immunol&#46;"
                        "fecha" => "2019"
                        "volumen" => "15"
                        "paginaInicial" => "66"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31749860"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema&#58; first report of the Brazilian registry and challenges"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;S&#46; Grumach"
                            1 => "S&#46;O&#46; Valle"
                            2 => "E&#46; Toledo"
                            3 => "D&#46;M&#46; Vasconselos"
                            4 => "M&#46;M&#46;S&#46; Villela"
                            5 => "E&#46; Mansour"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1468-3083.2012.04670.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Eur Acad Dermatol Venereol&#46;"
                        "fecha" => "2013"
                        "volumen" => "27"
                        "paginaInicial" => "e338"
                        "paginaFinal" => "e344"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22882421"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => """
                    ibge&#46;gov &#91;Internet&#93;&#46; Instituto Brasileiro de Geografia e Estat&#237;stica&#46; Proje&#231;&#227;o da popula&#231;&#227;o do Brasil e das Unidades da Federa&#231;&#227;o&#59; &#91;cited 2020 Nov 23&#93;&#46; Available from&#58; \n
                    <https: www.ibge.gov.br="" pps="" opulacao="" rojecao="" ndex.html="">\n
                     &#46;\n
                    </https:>
                    """
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema&#58; insights from a Brazilian family"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;F&#46; Ferraro"
                            1 => "A&#46;S&#46; Moreno"
                            2 => "E&#46;C&#46; Castelli"
                            3 => "E&#46;A&#46; Donadi"
                            4 => "M&#46;S&#46; Palma"
                            5 => "H&#46;A&#46; Arcuri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1398-9995.2011.02658.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2011"
                        "volumen" => "66"
                        "paginaInicial" => "1384"
                        "paginaFinal" => "1390"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21623829"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genotype&#8208;phenotype correlations in Brazilian patients with hereditary angioedema due to C1 inhibitor deficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;S&#46;M&#46; Maia"
                            1 => "A&#46;S&#46; Moreno"
                            2 => "M&#46;P&#46;L&#46; Ferriani"
                            3 => "F&#46;L&#46; Nunes"
                            4 => "M&#46;F&#46; Ferraro"
                            5 => "M&#46;M&#46; Dias"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/all.13699"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2019"
                        "volumen" => "74"
                        "paginaInicial" => "1013"
                        "paginaFinal" => "1016"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30556912"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema&#58; a prospective study of a Brazilian single&#8208;center cohort"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;L&#46;O&#46; Alonso"
                            1 => "S&#46;O&#46;R&#46; Valle"
                            2 => "R&#46;P&#46; T&#243;rtora"
                            3 => "A&#46;S&#46; Grumach"
                            4 => "A&#46;T&#46; Fran&#231;a"
                            5 => "M&#46;G&#46; Ribeiro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/ijd.14676"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Dermatol&#46;"
                        "fecha" => "2020"
                        "volumen" => "59"
                        "paginaInicial" => "341"
                        "paginaFinal" => "344"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31631315"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coagulation factor XII gene mutation in Brazilian families with hereditary angioedema with normal C1 inhibitor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;S&#46; Moreno"
                            1 => "S&#46;O&#46;R&#46; Valle"
                            2 => "S&#46; Levy"
                            3 => "A&#46;T&#46; Fran&#231;a"
                            4 => "F&#46;S&#46; Serpa"
                            5 => "H&#46;A&#46; Arcuri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000376547"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int Arch Allergy Immunol&#46;"
                        "fecha" => "2015"
                        "volumen" => "166"
                        "paginaInicial" => "114"
                        "paginaFinal" => "120"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25790805"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema type III &#40;estrogen&#8208;dependent&#41; report of three cases and literature review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46;R&#46; Miranda"
                            1 => "A&#46;P&#46;F&#46; de Ue"
                            2 => "D&#46;V&#46; Sabbag"
                            3 => "W&#46;J&#46; Furlani"
                            4 => "P&#46;K&#46; Souza"
                            5 => "O&#46; Rotta"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "An Bras Dermatol&#46;"
                        "fecha" => "2013"
                        "volumen" => "88"
                        "paginaInicial" => "578"
                        "paginaFinal" => "584"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "First report of a FXII gene mutation in a Brazilian family with hereditary angio&#8208;oedema with normal C1 inhibitor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Stieber"
                            1 => "A&#46;S&#46; Grumach"
                            2 => "E&#46; Cordeiro"
                            3 => "R&#46;N&#46; Constantino-Silva"
                            4 => "S&#46; Barth"
                            5 => "P&#46; Hoffmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/bjd.13791"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dermatol&#46;"
                        "fecha" => "2015"
                        "volumen" => "173"
                        "paginaInicial" => "1102"
                        "paginaFinal" => "1104"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25816745"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Assessment on hereditary angioedema burden of illness in Brazil&#58; a patient perspective"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;A&#46; Barbosa"
                            1 => "R&#46;O&#46; Martins"
                            2 => "R&#46; Martins"
                            3 => "A&#46;S&#46; Grumach"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Allergy Asthma Proc&#46;"
                        "fecha" => "2019"
                        "volumen" => "40"
                        "paginaInicial" => "193"
                        "paginaFinal" => "197"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema&#58; quality of life in Brazilian patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Gomide MACMS"
                            1 => "E&#46; Toledo"
                            2 => "S&#46;O&#46;R&#46; Valle"
                            3 => "R&#46;A&#46; Campos"
                            4 => "A&#46;T&#46; Fran&#231;a"
                            5 => "N&#46;P&#46; Gomez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clinics &#40;Sao Paulo&#41;&#46;"
                        "fecha" => "2013"
                        "volumen" => "68"
                        "paginaInicial" => "81"
                        "paginaFinal" => "83"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema attacks resolve faster and are shorter after early icatibant treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Maurer"
                            1 => "W&#46; Aberer"
                            2 => "L&#46; Bouillet"
                            3 => "T&#46; Caballero"
                            4 => "V&#46; Fabien"
                            5 => "G&#46; Kanny"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0053773"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One&#46;"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "e53773"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23390491"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema with normal C1 inhibitor in a French cohort&#58; clinical characteristics and response to treatment with icatibant"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Bouillet"
                            1 => "I&#46; Boccon-Gibod"
                            2 => "D&#46; Launay"
                            3 => "A&#46; Gompel"
                            4 => "A&#46; Kanny"
                            5 => "V&#46; Fabien"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Immun Inflamm Dis&#46;"
                        "fecha" => "2017"
                        "volumen" => "5"
                        "paginaInicial" => "29"
                        "paginaFinal" => "36"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plasminogen gene mutation with normal C1 inhibitor hereditary angioedema&#58; three additional French families"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Belb&#233;zier"
                            1 => "G&#46; Hardy"
                            2 => "R&#46; Marlu"
                            3 => "F&#46; Defendi"
                            4 => "C&#46;D&#46; Perard"
                            5 => "I&#46; Boccon-Gibod"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/all.13543"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy&#46;"
                        "fecha" => "2018"
                        "volumen" => "73"
                        "paginaInicial" => "2237"
                        "paginaFinal" => "2239"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29952006"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema with normal C1 inhibitor&#58; update on evaluation and treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Magerl"
                            1 => "A&#46;E&#46; Germenis"
                            2 => "C&#46; Maas"
                            3 => "M&#46; Maurer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.iac.2017.04.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunol Allergy Clin North Am&#46;"
                        "fecha" => "2017"
                        "volumen" => "37"
                        "paginaInicial" => "571"
                        "paginaFinal" => "584"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28687110"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema with normal C1 inhibitor function&#58; consensus of an international expert panel"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;L&#46; Zuraw"
                            1 => "K&#46; Bork"
                            2 => "K&#46;E&#46; Binkley"
                            3 => "A&#46; Banerji"
                            4 => "S&#46;C&#46; Christiansen"
                            5 => "A&#46; Castaldo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2500/aap.2012.33.3627"
                      "Revista" => array:7 [
                        "tituloSerie" => "Allergy Asthma Proc&#46;"
                        "fecha" => "2012"
                        "volumen" => "33"
                        "numero" => "Suppl 1"
                        "paginaInicial" => "S145"
                        "paginaFinal" => "S156"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23394603"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long&#8208;term effectiveness and safety of icatibant for the on&#8208;demand treatment of hereditary angioedema attacks&#58; 10 years of the Icatibant Outcome Survey"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Maurer"
                            1 => "H&#46;J&#46; Longhurst"
                            2 => "L&#46; Bouillet"
                            3 => "T&#46; Caballero"
                            4 => "A&#46;S&#46; Grumach"
                            5 => "J&#46; Botha"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Abstract 1118&#46; Allergy&#46;"
                        "fecha" => "2020"
                        "volumen" => "75"
                        "paginaInicial" => "59"
                        "paginaFinal" => "60"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bradykinin receptor 2 antagonist &#40;icatibant&#41; for hereditary angioedema type III attacks"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Bouillet"
                            1 => "I&#46; Boccon-Gibod"
                            2 => "D&#46; Ponard"
                            3 => "C&#46; Drouet"
                            4 => "J&#46;Y&#46; Cesbron"
                            5 => "C&#46; Dumestre-Perard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1081-1206(10)60369-9"
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol&#46;"
                        "fecha" => "2009"
                        "volumen" => "103"
                        "paginaInicial" => "448"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19927548"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary angioedema with normal C1 inhibitor and factor XII mutation&#58; a series of 57 patients from the French National Center of Reference for Angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Deroux"
                            1 => "I&#46; Boccon-Gibod"
                            2 => "O&#46; Fain"
                            3 => "P&#46; Pralong"
                            4 => "Y&#46; Ollivier"
                            5 => "A&#46; Pagneir"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/cei.12820"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Immunol&#46;"
                        "fecha" => "2016"
                        "volumen" => "185"
                        "paginaInicial" => "332"
                        "paginaFinal" => "337"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27271546"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Icatibant&#44; a new bradykinin&#8208;receptor antagonist&#44; in hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Cicardi"
                            1 => "A&#46; Banerji"
                            2 => "F&#46; Bracho"
                            3 => "A&#46; Malbr&#225;n"
                            4 => "B&#46; Rosenkranz"
                            5 => "M&#46; Riedl"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0906393"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med&#46;"
                        "fecha" => "2010"
                        "volumen" => "363"
                        "paginaInicial" => "532"
                        "paginaFinal" => "541"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20818888"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Randomized placebo&#8208;controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema&#58; the FAST&#8208;3 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;R&#46; Lumry"
                            1 => "H&#46;H&#46; Li"
                            2 => "R&#46;J&#46; Levy"
                            3 => "P&#46;C&#46; Potter"
                            4 => "H&#46; Farkas"
                            5 => "D&#46; Moldovan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.anai.2011.08.015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol&#46;"
                        "fecha" => "2011"
                        "volumen" => "107"
                        "paginaInicial" => "529"
                        "paginaFinal" => "537"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22123383"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety&#44; and efficacy of icatibant self&#8208;administration for acute hereditary angioedema"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "I&#46; Boccon-Gibod"
                            1 => "L&#46; Bouillet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2249.2012.04574.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Immunol&#46;"
                        "fecha" => "2012"
                        "volumen" => "168"
                        "paginaInicial" => "303"
                        "paginaFinal" => "307"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22519593"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack618630"
        "titulo" => "Agradecimentos"
        "texto" => "<p id="par0200" class="elsevierStylePara elsevierViewall">Sob a dire&#231;&#227;o dos autores&#44; Sophia Shumyatsky&#44; PharmD&#44; CMPP&#44; funcion&#225;ria da Excel Medical Affairs&#44; forneceu assist&#234;ncia na reda&#231;&#227;o deste manuscrito&#46; A assist&#234;ncia editorial na formata&#231;&#227;o&#44; revis&#227;o&#44; edi&#231;&#227;o e verifica&#231;&#227;o de fatos tamb&#233;m foi fornecida pela Excel Medical Affairs&#46; A Takeda Development Center Americas&#44; Inc&#46; financiou a Excel Medical Affairs para apoio na reda&#231;&#227;o e edi&#231;&#227;o deste manuscrito&#46; A interpreta&#231;&#227;o dos dados foi feita pelos autores de maneira independente&#46; O papel dos funcion&#225;rios da Takeda no projeto do estudo e coleta&#44; an&#225;lise e interpreta&#231;&#227;o dos dados e na reda&#231;&#227;o do manuscrito s&#227;o especificados na se&#231;&#227;o de contribui&#231;&#227;o dos autores&#46; Agradecemos a todos os investigadores do IOS por suas contribui&#231;&#245;es ao registro do IOS&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "pt"
  "url" => "/26662752/0000009700000004/v1_202207280537/S266627522200090X/v1_202207280537/pt/main.assets"
  "Apartado" => array:4 [
    "identificador" => "89618"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Artigo Original"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/26662752/0000009700000004/v1_202207280537/S266627522200090X/v1_202207280537/pt/main.pdf?idApp=UINPBA00008Z&text.app=https://clinics.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S266627522200090X?idApp=UINPBA00008Z"
]
Article information
ISSN: 26662752
Original language: Portuguese
The statistics are updated each day
Year/Month Html Pdf Total
2024 November 29 9 38
2024 October 230 84 314
2024 September 285 90 375
2024 August 322 126 448
2024 July 210 116 326
2024 June 179 124 303
2024 May 167 78 245
2024 April 204 97 301
2024 March 199 95 294
2024 February 253 94 347
2024 January 224 66 290
2023 December 130 66 196
2023 November 186 95 281
2023 October 155 84 239
2023 September 184 115 299
2023 August 163 57 220
2023 July 127 43 170
2023 June 189 54 243
2023 May 151 38 189
2023 April 110 39 149
2023 March 176 68 244
2023 February 83 36 119
2023 January 70 61 131
2022 December 136 35 171
2022 November 127 65 192
2022 October 242 94 336
2022 September 88 90 178
2022 August 79 77 156
2022 July 69 72 141
2022 June 10 18 28
Show all

Follow this link to access the full text of the article

Idiomas
Anais Brasileiros de Dermatologia
en pt
Cookies policy Política de cookies
To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.