Estadísticas

 array:23 [
  "pii" => "S0001731014004128"
  "issn" => "00017310"
  "doi" => "10.1016/j.ad.2014.09.001"
  "estado" => "S300"
  "fechaPublicacion" => "2015-03-01"
  "aid" => "1053"
  "copyright" => "Elsevier España, S.L.U. and AEDV"
  "copyrightAnyo" => "2014"
  "documento" => "article"
  "subdocumento" => "fla"
  "cita" => "Actas Dermosifiliogr. 2015;106:126-32"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 1129
    "formatos" => array:3 [
      "EPUB" => 44
      "HTML" => 695
      "PDF" => 390
    ]
  ]
  "Traduccion" => array:1 [
    "en" => array:18 [
      "pii" => "S1578219015000323"
      "issn" => "15782190"
      "doi" => "10.1016/j.adengl.2014.09.018"
      "estado" => "S300"
      "fechaPublicacion" => "2015-03-01"
      "aid" => "1053"
      "copyright" => "Elsevier España, S.L.U. and AEDV"
      "documento" => "article"
      "subdocumento" => "fla"
      "cita" => "Actas Dermosifiliogr. 2015;106:126-32"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:2 [
        "total" => 1299
        "formatos" => array:3 [
          "EPUB" => 41
          "HTML" => 535
          "PDF" => 723
        ]
      ]
      "en" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
        "titulo" => "Assessment of the Efficacy and Safety of a Combination of 2 Topical Retinoids &#40;RetinSphere&#41; in Maintaining Post-Treatment Response of Acne to Oral Isotretinoin"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "tieneResumen" => array:2 [
          0 => "en"
          1 => "es"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "126"
            "paginaFinal" => "132"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "es" => array:1 [
            "titulo" => "Eficacia y seguridad del uso combinado de 2 retinoides t&#243;picos &#40;Retinsphere<span class="elsevierStyleSup">&#174;</span>&#41; para el mantenimiento de la respuesta obtenida tras el tratamiento con isotretino&#237;na oral"
          ]
        ]
        "contieneResumen" => array:2 [
          "en" => true
          "es" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "en" => true
        ]
        "contienePdf" => array:1 [
          "en" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "M&#46;T&#46; Truchuelo, N&#46; Jim&#233;nez, D&#46; Mavura, P&#46; Ja&#233;n"
            "autores" => array:4 [
              0 => array:2 [
                "nombre" => "M&#46;T&#46;"
                "apellidos" => "Truchuelo"
              ]
              1 => array:2 [
                "nombre" => "N&#46;"
                "apellidos" => "Jim&#233;nez"
              ]
              2 => array:2 [
                "nombre" => "D&#46;"
                "apellidos" => "Mavura"
              ]
              3 => array:2 [
                "nombre" => "P&#46;"
                "apellidos" => "Ja&#233;n"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S0001731014004128"
          "doi" => "10.1016/j.ad.2014.09.001"
          "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/S0001731014004128?idApp=UINPBA000044"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219015000323?idApp=UINPBA000044"
      "url" => "/15782190/0000010600000002/v2_201502240233/S1578219015000323/v2_201502240233/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S0001731014003160"
    "issn" => "00017310"
    "doi" => "10.1016/j.ad.2014.05.003"
    "estado" => "S300"
    "fechaPublicacion" => "2015-03-01"
    "aid" => "1022"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; y AEDV"
    "documento" => "simple-article"
    "subdocumento" => "crp"
    "cita" => "Actas Dermosifiliogr. 2015;106:e7-e12"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 1506
      "formatos" => array:3 [
        "EPUB" => 2
        "HTML" => 802
        "PDF" => 702
      ]
    ]
    "es" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">e-Casos cl&#237;nicos</span>"
      "titulo" => "Respuesta parad&#243;jica al tratamiento antituberculoso en un caso de lupus vulgar"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "e7"
          "paginaFinal" => "e12"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Paradoxical Reaction to Antituberculosis Therapy in a Patient With Lupus Vulgaris"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0020"
          "etiqueta" => "Figura 4"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr4.jpeg"
              "Alto" => 689
              "Ancho" => 1550
              "Tamanyo" => 225723
            ]
          ]
          "descripcion" => array:1 [
            "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A y B&#46; Resultado cl&#237;nico tras 12 meses de tratamiento antituberculoso&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "R&#46; Santesteban, B&#46; Bonaut, A&#46; C&#243;rdoba, I&#46; Yanguas"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "Santesteban"
            ]
            1 => array:2 [
              "nombre" => "B&#46;"
              "apellidos" => "Bonaut"
            ]
            2 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "C&#243;rdoba"
            ]
            3 => array:2 [
              "nombre" => "I&#46;"
              "apellidos" => "Yanguas"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S1578219014003382"
        "doi" => "10.1016/j.adengl.2014.12.012"
        "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/S1578219014003382?idApp=UINPBA000044"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731014003160?idApp=UINPBA000044"
    "url" => "/00017310/0000010600000002/v2_201502240236/S0001731014003160/v2_201502240236/es/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S0001731014004086"
    "issn" => "00017310"
    "doi" => "10.1016/j.ad.2014.08.005"
    "estado" => "S300"
    "fechaPublicacion" => "2015-03-01"
    "aid" => "1049"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and AEDV"
    "documento" => "article"
    "subdocumento" => "fla"
    "cita" => "Actas Dermosifiliogr. 2015;106:117-25"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 2951
      "formatos" => array:3 [
        "EPUB" => 2
        "HTML" => 1420
        "PDF" => 1529
      ]
    ]
    "es" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original</span>"
      "titulo" => "Leiomiomatosis cut&#225;nea y uterina m&#250;ltiple o s&#237;ndrome de Reed&#58; estudio retrospectivo de 13 casos"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "117"
          "paginaFinal" => "125"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Multiple Cutaneous and Uterine Leiomyomatosis or Reed Syndrome&#58; A Retrospective Study of 13 Cases"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figura 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1403
              "Ancho" => 1400
              "Tamanyo" => 276257
            ]
          ]
          "descripcion" => array:1 [
            "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Caso 2&#46; A&#46; Leiomiomas agrupados en forma de placa a nivel dorsal&#46; B&#46; Agrupados en la extremidad superior&#46; C&#46; Dispersos en la extremidad superior&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "H&#46; Collgros, M&#46; Iglesias-Sancho, M&#46;J&#46; Trib&#243;-Boixareu, L&#46; Creus-Vila, P&#46; Umbert-Millet, M&#46; Salleras-Redonnet"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "H&#46;"
              "apellidos" => "Collgros"
            ]
            1 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Iglesias-Sancho"
            ]
            2 => array:2 [
              "nombre" => "M&#46;J&#46;"
              "apellidos" => "Trib&#243;-Boixareu"
            ]
            3 => array:2 [
              "nombre" => "L&#46;"
              "apellidos" => "Creus-Vila"
            ]
            4 => array:2 [
              "nombre" => "P&#46;"
              "apellidos" => "Umbert-Millet"
            ]
            5 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Salleras-Redonnet"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S1578219014003394"
        "doi" => "10.1016/j.adengl.2014.12.013"
        "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/S1578219014003394?idApp=UINPBA000044"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731014004086?idApp=UINPBA000044"
    "url" => "/00017310/0000010600000002/v2_201502240236/S0001731014004086/v2_201502240236/es/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
    "titulo" => "Assessment of the Efficacy and Safety of a Combination of 2 Topical Retinoids &#40;RetinSphere&#41; in Maintaining Post-Treatment Response of Acne to Oral Isotretinoin"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "126"
        "paginaFinal" => "132"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "M&#46;T&#46; Truchuelo, N&#46; Jim&#233;nez, D&#46; Mavura, P&#46; Ja&#233;n"
        "autores" => array:4 [
          0 => array:4 [
            "nombre" => "M&#46;T&#46;"
            "apellidos" => "Truchuelo"
            "email" => array:1 [
              0 => "maytetd&#64;yahoo&#46;es"
            ]
            "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" => "N&#46;"
            "apellidos" => "Jim&#233;nez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "D&#46;"
            "apellidos" => "Mavura"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "P&#46;"
            "apellidos" => "Ja&#233;n"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "University Ram&#243;n y Cajal Hospital&#44; Madrid&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Regional Dermatology Training Centre Kilimanjaro Christion Medical Center&#44; Moshi&#44; Tanzania"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Eficacia y seguridad del uso combinado de 2 retinoides t&#243;picos &#40;Retinsphere<span class="elsevierStyleSup">&#174;</span>&#41; para el mantenimiento de la respuesta obtenida tras el tratamiento con isotretino&#237;na oral"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acne is a common complaint among adolescents&#44; although onset can occur at other stages of life&#46; In fact&#44; acne affects to a greater or lesser extent between 80 and 85&#37; of individuals aged between 12 and 25 years<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and in addition to the potential physical discomfort &#40;for example&#44; pain&#44; itching&#44; superinfection&#44; and scarring&#41;&#44; serious psychological repercussions may occur as the face is often targeted by this disease&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">We can classify acne into different types according to the predominant lesion&#44; with classic forms including papulopustular&#44; comedonal&#44; and nodulocystic acne&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> There are several classes of therapeutic drugs used to tackle different types of acne&#46; One of the most widely used medications is oral isotretinoin as it targets all levels of acne pathogenesis&#46; According to expert consensus&#44; the recommended dose is 0&#46;3&#8211;0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d for moderate papulopustular or nodular acne and more than 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d for at least 6 months &#40;with a mean total cumulative dose of 120&#8211;150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; for acne conglobata&#46; Other authors&#44; however&#44; recommend lower or pulsed doses for longer periods in cases of moderate acne&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Regardless of the dosage regimen used&#44; at the end of treatment most patients show substantial improvement in acne lesions&#44; although this is coupled with erythema and deterioration in the quality of skin due to the extreme cutaneous dryness induced by the treatment&#46; Moreover&#44; recurrence of acne lesions following isotretinoin treatment remains an unsolved problem&#46; According to recent studies&#44; the percentage of patients with relapses is very variable and ranges between 10 and 61&#37; depending on the cumulative dose&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> population characteristics&#44; and duration of follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> There is some debate as to whether failure to reach the target dose leads to the early onset of acne relapse&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> To establish a basis for comparison of the mean relapse rate&#44; the study with the greatest number of patients &#40;17<span class="elsevierStyleHsp" style=""></span>351&#41;&#44; which described a mean relapse rate of 41&#37;&#44; can be taken as a reference&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However&#44; there are no specific data on relapse percentages over short periods of time after discontinuing isotretinoin administered at the standard dose of 120&#8211;150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">To avoid relapses after isotretinoin administration&#44; topical retinoids have been used for many years in patients with acne due to their capacity to reduce hyperseborrhea &#40;by inhibiting the proliferation and differentiation of sebocytes&#41; and normalize keratinization&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Some authors have suggested that their use at the end of treatment with oral isotretinoin may help prevent future relapses&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;9&#8211;12</span></a> Consequently&#44; the main objective of the present study is to demonstrate that a new product&#44; whose main component is Retinsphere technology&#44; is effective for reducing acne relapses or maintaining the results obtained by acne patients after treatment with oral isotretinoin&#46; Furthermore&#44; we will determine tolerance to the new product in these patients&#44; without the usual adverse events seen with other retinoids&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Materials and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A prospective&#44; randomized&#44; double-blind&#44; placebo-controlled &#40;vehicle&#41; study was carried out on both sides of the face&#46; Thirty-two patients were recruited&#46; Treatment with the retinoid combination was applied on a split-face model&#44; applying the active product to one side of the face and the vehicle to the other&#44; once daily for 3 months&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Inclusion criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">Patients greater than 14 years of age who had finished treatment with oral isotretinoin &#40;including patients who had or had not reached the conventional target dose of 120&#8211;150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; in the previous 6 months were included&#46; Family and individual medical histories&#44; previous treatments&#44; weight&#44; ingestion time of oral isotretinoin&#44; time since discontinuation of oral isotretinoin&#44; daily dose&#44; total cumulative dose&#44; and informed consent were recorded&#46; The protocol was approved by the ethics committee of our hospital&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Exclusion criteria</span><p id="par0035" class="elsevierStylePara elsevierViewall">Patients less than 14 years of age and those with other concomitant dermatoses or sensitization to any of the components of the product were excluded from this study&#46; Women not using a contraceptive method were also excluded from the study&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Treatment</span><p id="par0040" class="elsevierStylePara elsevierViewall">The test product was a combination of 2 retinoids&#44; retinol encapsulated in glycospheres and hydroxypinacolone retinoate&#44; marketed under the name Retinsphere Technology&#44; in a base enriched with natural humectant factors&#46; The treatment protocol included the application of a fingertip of this retinoid combination &#40;Biretix gel &#91;Industrial Farmac&#233;utica Cantabria SA&#44; Madrid&#44; Spain&#93;&#41; to one side of the face and vehicle alone to the other side of the face at night&#44; for 3 months&#46; Thus&#44; each patient acted as his or her own control&#46; All patients and&#44; if required&#44; their legal guardian&#44; signed the informed consent&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Randomization was performed by an independent statistician using the Random Function of standard computer software&#46; The code&#44; which established which side of the face to apply product or vehicle&#44; was kept in a sealed envelope until the end of the study&#46; Neither the patient nor the investigator was informed about the composition of the 2 creams&#44; which had the same texture and odor and were only distinguishable by the color of the tube&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinical assessment</span><p id="par0050" class="elsevierStylePara elsevierViewall">The assessments were carried out at baseline &#40;T0&#41; then after 1&#46;5 months &#40;T1&#41; and 3 months &#40;T2&#41; by the same&#44; blinded investigator&#46; A physical examination was carried out together with a standard photographic record with RBX technology &#40;Reveal&#44; Canfield Inc&#46;&#44; Fairfield&#44; NJ&#44; USA&#41; on each visit&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Primary endpoint</span><p id="par0055" class="elsevierStylePara elsevierViewall">The primary endpoint was relapse incidence after 3 months from treatment with oral isotretinoin&#44; compared to the standard relapse incidence without post-isotretinoin treatment &#40;vehicle&#41;&#46; Given the lack of consensus on the definition of relapse and that hardly any patients had acne lesions at the start of the study &#40;as they had recently finished treatment with isotretinoin&#41;&#44; we defined relapse as an increase in the number of lesions &#40;comedones&#44; papules or pustules&#41;&#44; that is&#44; when one or more new lesions compared to T0 appeared on either side of the face &#40;T2<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>relapse&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Secondary endpoints</span><p id="par0060" class="elsevierStylePara elsevierViewall">The following were secondary endpoints<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Lesion count</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Investigator&#39;s Global Assessment &#40;IGA&#41;&#58; Validated scale&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Scores ranged from 0 to 5&#44; where 0 indicated absence of inflammatory and non-inflammatory lesions&#59; 1&#44; almost clear&#59; 2&#44; mild severity&#59; 3&#44; moderate severity&#59; 4&#44; severe&#59; and 5&#44; very severe&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Quality-of-life&#58; Improved quality-of-life of the patient measured by the Social Quality-of-Life &#40;SOQOL&#41; scale<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> &#40;0&#44; no involvement to 27&#44; intense involvement&#41;&#46; There are 9 items &#40;body perception&#44; social aspects&#44; emotional aspects&#44; and symptoms of acne&#41;&#46; Each item is graded from 0 to 3 where 0 indicates no involvement&#59; 1&#44; mild involvement&#44; 2&#44; moderate involvement&#59; and 3&#44; intense involvement&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Improvement perceived by the patient with the Patient Global Assessment scale&#44; &#40;PGA&#41;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#58; scores ranged from 0 to 4 where 0 indicated deterioration or no change&#59; 1&#44; mild improvement&#59; 2&#44; moderate improvement&#59; 3&#44; great improvement&#59; and 4&#44; excellent improvement&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Patient satisfaction with previous treatments and after the retinoid combination &#40;0&#8211;10&#44; where 0 indicated no satisfaction and 10&#44; maximum satisfaction&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Shine subjectively perceived by the investigator &#40;0&#44; nonexistent when no shine at all was perceived&#59; 1&#44; mild when slight degree of shine in some areas of the face was perceived but it was not intense&#59; and 2&#44; intense when a high degree of shine all over the face was perceived&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Erythema subjectively perceived by the investigator &#40;0&#44; nonexistent when no erythema at all was perceived&#59; 1&#44; mild when some areas of the face showed redness&#59; 2&#44; intense when almost all the face was red&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Scaling subjectively perceived by the investigator &#40;0&#44; nonexistent when no desquamation was perceived&#59; 1&#44; mild when some grade of desquamation was perceived in some areas of the face&#59; or 2&#44; intense when rough desquamation was perceived in all the face&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Hydration subjectively perceived by the investigator &#40;0&#44; nonexistent when all the face was dry&#59; 1&#44; mild when hydrated areas are mixed with dry ones&#59; or 2&#44; intense when no dry areas were perceived&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Degree of improvement in scars &#40;SCAR-S&#41;&#44; according to the Goodman scale<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> based on the morphology graded from 0 to 4&#44; where 0 indicates absence of scars&#59; 1&#44; macular scars&#59; 2&#44; mild scars &#40;depressions or millimetric papules&#41;&#59; 3&#44; moderate &#40;boxcar&#44; deeper depressions or papular or hypertrophic scars&#41;&#59; and 4&#44; severe &#40;ice pick&#44; deep&#44; dystrophic scars&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Subjective adverse effects reported by the patient&#58; scaling&#44; itching&#44; burning&#44; erythema or dryness &#40;0&#44; non-existent&#59; 1&#44; mild&#59; or 2&#44; intense&#41;&#46;</p></li></ul></p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Statistical analysis</span><p id="par0120" class="elsevierStylePara elsevierViewall">Statistical analysis was performed with SPSS v18&#46;0 software &#40;Chicago&#44; IL&#44; USA&#41;&#46; Results are presented as mean &#40;SD&#41; values&#46; The Wilcoxon nonparametric test for paired data&#44; as the comparisons were paired both in time and between treatments&#46; In the subsection where the isotretinoin dose was analyzed for influence on the response to the product compared to vehicle&#44; the Mann&#8211;Whitney non-parametric test was used&#44; as they are two independent groups&#46; The percentages of patients with deterioration and improvement were calculated for each group&#44; and the McNemar test was used to determine the statistical significance of the difference between 2 percentages&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Before initiating the study and based on previous studies&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> in which the number of lesions decreased 90&#37; after 3 months&#44; assuming 10&#37; rate of recurrent or persistent lesions&#44; the statistical software estimated a sample size of 30 patients&#44; assuming an SD of 3&#46; Statistical significance was set to <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Results</span><p id="par0130" class="elsevierStylePara elsevierViewall">Thirty-two patients who completed treatment with isotretinoin in the last year were included&#46; Of these&#44; 40&#46;6&#37; were male &#40;mean age&#44; 18&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;2 years&#41; and 59&#46;4&#37; female &#40;mean age&#44; 23&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;6 years&#41;&#46; Two patients did not complete the study due to work commitments&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The mean period from discontinuation of treatment with isotretinoin until initiation of the study was 2 months &#40;range&#44; 2 weeks to 6 months&#41;&#46; Of the 30 patients who completed the study&#44; 7 &#40;23&#37;&#41; had reached the standard cumulative target dose of isotretinoin &#40;mean dose for these patients&#44; 147&#46;71<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#46; Twenty-three of the 30 patients &#40;77&#37;&#41; had not reached the target dose but had reached a mean of 68&#46;34<span class="elsevierStyleHsp" style=""></span>mg&#47;kg by the time they suspended oral isotretinoin due to the arrival of summer&#44; intolerance or clearance of lesions&#46; Thus&#44; the majority of our patients had not reached the total cumulative target dose of 120&#8211;150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Relapses</span><p id="par0140" class="elsevierStylePara elsevierViewall">The percentage of relapses on the side treated with the retinoid combination was almost 17&#37; compared to 43&#37; on the vehicle side&#59; this difference was statistically significant &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;021&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">There were no statistically significant differences in the number of relapses &#40;regardless of whether they were inflammatory or non-inflammatory lesions&#41; between those who stopped treatment with isotretinoin after reaching the target dose and those who stopped due to the arrival of summer&#44; and therefore did not reach the total cumulative dose &#40;<span class="elsevierStyleItalic">data not shown</span>&#41;&#46;</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Lesion count</span><p id="par0150" class="elsevierStylePara elsevierViewall">The reduction in the overall number of lesions at visits T1 and T2 on the treated side was statistically significant compared to the baseline count &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001 and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#44; respectively&#41;&#44; whilst on the vehicle side it was only significant at T1 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; but not at T2 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;08&#41;&#46; In the case of comedones&#44; the final reduction &#40;T2&#41; in the mean number of comedones on the treated side was statistically significant when compared to baseline &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41; and so was the final reduction &#40;T2&#41; in the mean number of papules &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#46; An increase &#40;not significant&#41; in the final number of pustules was observed on the treated side compared to the baseline count&#44; whilst on the vehicle side a 5-fold increase at visit T2 compared to the number of baseline pustules was observed &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">When comparing the results of both sides&#44; the average number of comedones on the treated side showed an almost 20&#37; larger reduction at visit T2 compared with the vehicle side&#44; although the difference was not statistically significant &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;21&#41;&#46; For papules on the treated compared to vehicle side&#44; although the mean reduction on the treated side on visit T2 was almost 50&#37; higher than that obtained with vehicle&#44; the difference as not statistically significant &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; The average total number of lesions was significantly lower on the side treated with the active product &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; compared to vehicle-treated side &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Clinical improvement</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Degree of investigator-reported improvement&#44; according to IGA</span><p id="par0160" class="elsevierStylePara elsevierViewall">The mean IGA obtained at baseline was 2&#46;2 &#40;mild severity&#41; on both sides of the face with no significant differences between them&#44; while the IGA on finishing treatment at T2 on the side treated with retinoids was on average 1&#46;4 &#40;almost clear&#41;&#44; significantly better than baseline &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; unlike the vehicle side where significant post-baseline changes were not observed &#40;the mean severity at T2 was 2 &#91;mild&#93;&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;106&#41;&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The IGA improvement perceived by the investigator was demonstrated in 60&#37; of the sides of the face treated with the product versus 30&#37; of the sides of the face treated with vehicle&#46;</p></span></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Patient-reported improvement</span><p id="par0170" class="elsevierStylePara elsevierViewall">The mean quality-of-life score&#44; as measured by the SOQOL scale at baseline &#40;T0&#41; after discontinuation of isotretinoin treatment&#44; was 3&#46;8 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&#41; while the impact after topical treatment with the study product further improved this quality-of-life data by reducing the SOQOL score to 1&#46;8 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&#41; at T2&#44; after 3 months&#46; The increase in overall satisfaction indicated an improvement in the perception of skin appearance described by the patient&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Overall&#44; 90&#37; of patients who received treatment experienced some degree of improvement during the treatment and almost 50&#37; showed good or excellent improvement&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Investigator-reported skin quality and cutaneous tolerance</span><p id="par0180" class="elsevierStylePara elsevierViewall">There were no differences between either side of the face in the scoring of shineness or scaling&#44; either at the beginning or the end of the treatment&#46; The mean baseline hydration was 0&#46;53 &#40;between non-existent and mild&#41; with no differences between treated and untreated sides of the face&#46; At T2&#44; significant differences were observed &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; with a score of 1&#46;3 &#40;mild&#41; on the side treated with the combination of retinoids versus 0&#46;2 &#40;non-existent&#41; on the side treated with vehicle&#46; In the case of erythema&#44; on T2 the mean erythema showed no significant differences between either treatments indicating an excellent tolerance to retinoids&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Patient perception</span><p id="par0185" class="elsevierStylePara elsevierViewall">No significant differences were registered at any time regarding subjective discomfort perceived by the patient &#40;scaling&#44; dryness&#44; itching&#44; burning and erythema&#41;&#46; Only one case of pruritus was described on visit T1&#44; which disappeared by visit T2&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Other variables</span><p id="par0190" class="elsevierStylePara elsevierViewall">At the end of the study &#40;T2&#41;&#44; a significant improvement in extent of scarring was observed on the treated side compared with the vehicle side &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">No statistical differences in the PGA were found after the treatment compared with baseline&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Discussion</span><p id="par0200" class="elsevierStylePara elsevierViewall">In this study we have demonstrated the efficacy of a new product in decreasing the number of relapses following isotretinoin treatment compared to vehicle&#44; while showing excellent tolerance and no adverse events&#46; Although a significant reduction in the total number of lesions was found on the treated side compared to the vehicle side&#44; when individual lesions were studied this difference was not statistically significant&#46; This effect may be due to the small sample size and low number of total lesions at the beginning of the study &#40;T0&#41;&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">At the end of the treatment&#44; the vehicle side showed a trend toward relapse of 43&#37;&#44; similar to that observed in literature in the follow-up of groups without post-isotretinoin treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Interestingly&#44; the side treated with Retinsphere technology showed a significantly lower relapse rate &#40;17&#37;&#41;&#44; demonstrating the efficacy of maintenance treatment with these topical retinoids&#46; Although we did not find any significant differences between the target dose and onset of relapse&#44; among patients with relapse &#40;16 subjects&#41;&#44; just 25&#37; &#40;4&#47;16&#41; had reached the target dose of 120<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">These results are consistent with those reported in some other published studies <a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> but could also be due to the small sample size&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The mean follow-up time from suspension of oral isotretinoin to the end of the study was 6 months&#44; which may appear short but given that the majority of patients &#40;77&#37;&#41; in our study had not reached the target dose at the time of discontinuation &#40;due to the arrival of summer&#44; intolerance or clearance of lesions&#41;&#44; in theory we expected an early relapse&#44; although this latter point is controversial&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Quereux et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> defined a maintenance treatment with topical retinoids as the most important protective factor for the prevention of relapse&#46; Borghi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> described the use of maintenance therapy with topical retinoids for 1 year after discontinuation of oral isotretinoin&#44; with a very low relapse rate &#40;9&#37;&#41; in spite of having used low doses of oral isotretinoin&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">In our study&#44; investigator-reported improvement was observed in 60&#37; of patients treated with topical retinoids compared with an improvement of 30&#37; on the vehicle side&#44; demonstrating that Retinsphere technology is effective in improving acne lesions that persist after treatment with isotretinoin&#46; Improvement on the vehicle side in our study can be attributed to long-term improvements induced by cumulative isotretinoin dose and the effect of the vehicle in improving skin quality after treatment with oral isotretinoin&#46; According to our results&#44; topical retinoids are useful in improving persistent non-inflammatory and inflammatory lesions&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">The excellent tolerance and cutaneous compatibility of the product is supported by the immunomodulatory role of retinoids&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> their theoretical capacity for accelerated cutaneous regeneration<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> attributed to the stimulation of neocollagenesis&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> as well as to the possible role&#44; yet to be confirmed&#44; of transforming growth factor <span class="elsevierStyleItalic">&#946;</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Topical retinoids can be associated with skin irritation but this innovative retinoid combination maintained the efficacy of topical retinoids without observing associated dermatitis&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">The new product is based on Retinsphere technology&#44; which combines 2 topical retinoids&#44; retinol encapsulated in glycospheres and hydroxypinacolone retinoate&#46; This combination has been used previously in patients with active acne&#44; with an improvement in the lesion count &#40;macrocomedones and microcomedones&#41;&#44; follicular keratinization&#44; and measures of seborrhoea and acne severity according to the Global Acne Grading System with few side effects&#44; all mild&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The ester of retinoic acid&#44; hydroxypinacolone retinoate&#44; acts in a similar way to tretinoin but does not cause the irritation observed with this retinoid&#46; Recently&#44; Veraldi<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> showed that the use of this new combination for 2 weeks in patients improved skin roughness by 50&#37; and scaling by 40&#37;&#46; Unlike retinol and other derivatives that need to be converted to the biologically active form of retinoic acid&#44; hydroxypinacolone retinoate binds directly to retinoic acid receptors&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;23</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">Some limitations of the study were that the time lapse between finishing oral isotretinoin and starting with topical treatment was very variable&#44; ranging from 2 weeks to 6 months&#44; possibly leading to increased variability of the results&#46; In addition&#44; the patients had received different total doses of oral isotretinoin&#46; These limitations hinder assessment of whether the emergence of relapses is related to the total cumulative dose and&#47;or to the small sample size&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">The importance of maintenance treatment with retinoids is noteworthy from a psychological standpoint&#44; as it helps to sustain an improved quality-of-life after use of oral isotretinoin&#44; as well as the perception of improvement and satisfaction described by the patient&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Conclusions</span><p id="par0250" class="elsevierStylePara elsevierViewall">Avoidance of a relapse after treatment with isotretinoin&#44; especially if the target dose is not reached&#44; has not been studied in depth&#46; To prevent such relapses&#44; this new retinoid combination has proven effective and is able to significantly improve acne lesions compared with baseline and with treatment with vehicle&#46; In conclusion&#44; the use of topical retinoids&#44; after suspending isotretinoin either in the initial months or during the post-treatment year&#44; when relapse rates are higher&#44; could be a protective factor to prevent relapse&#44; with efficacy and tolerance statistically demonstrated in this and previous studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;11&#44;12</span></a> Likewise&#44; this study confirms that maintenance therapy with retinoids after discontinuation of oral isotretinoin with residual acne lesions can reduce both non-inflammatory and inflammatory lesions&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Retinsphere technology has proven effective and safe in the maintenance treatment after oral isotretinoin in patients with acne&#44; although future studies with a longer follow-up period may confirm the results observed&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Ethical disclosures</span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Protection of human and animal subjects</span><p id="par0260" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Confidentiality of data</span><p id="par0265" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Right to privacy and informed consent</span><p id="par0270" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Funding</span><p id="par0290" class="elsevierStylePara elsevierViewall">The conduct of the present study was funded by Industrial Farmaceutica Cantabria S&#46;A&#46; &#40;IFC S&#46;A&#46;&#44; Madrid&#44; Spain&#41;&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Conflicts of interest</span><p id="par0295" class="elsevierStylePara elsevierViewall">M&#46;T&#46; Truchuelo receive economic compensation of IFC laboratories for external advice&#46; The remaining authors declare that they have no conflict of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:21 [
        0 => array:3 [
          "identificador" => "xres437283"
          "titulo" => "Abstract"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Introduction"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Aims"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Patients and methods"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Results"
            ]
            4 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Conclusions"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec460469"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres437284"
          "titulo" => "Resumen"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Introducci&#243;n"
            ]
            1 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Objetivos"
            ]
            2 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Pacientes y M&#233;todos"
            ]
            3 => array:2 [
              "identificador" => "abst0045"
              "titulo" => "Resultados"
            ]
            4 => array:2 [
              "identificador" => "abst0050"
              "titulo" => "Conclusiones"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec460468"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Inclusion criteria"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Exclusion criteria"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Treatment"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0030"
          "titulo" => "Clinical assessment"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Primary endpoint"
            ]
            1 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Secondary endpoints"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Statistical analysis"
        ]
        8 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Results"
        ]
        9 => array:3 [
          "identificador" => "sec0055"
          "titulo" => "Relapses"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Lesion count"
            ]
            1 => array:3 [
              "identificador" => "sec0065"
              "titulo" => "Clinical improvement"
              "secciones" => array:1 [
                0 => array:2 [
                  "identificador" => "sec0070"
                  "titulo" => "Degree of investigator-reported improvement&#44; according to IGA"
                ]
              ]
            ]
          ]
        ]
        10 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Patient-reported improvement"
        ]
        11 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Investigator-reported skin quality and cutaneous tolerance"
        ]
        12 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Patient perception"
        ]
        13 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Other variables"
        ]
        14 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Discussion"
        ]
        15 => array:2 [
          "identificador" => "sec0100"
          "titulo" => "Conclusions"
        ]
        16 => array:3 [
          "identificador" => "sec0105"
          "titulo" => "Ethical disclosures"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0110"
              "titulo" => "Protection of human and animal subjects"
            ]
            1 => array:2 [
              "identificador" => "sec0115"
              "titulo" => "Confidentiality of data"
            ]
            2 => array:2 [
              "identificador" => "sec0120"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
        17 => array:2 [
          "identificador" => "sec0135"
          "titulo" => "Funding"
        ]
        18 => array:2 [
          "identificador" => "sec0130"
          "titulo" => "Conflicts of interest"
        ]
        19 => array:2 [
          "identificador" => "xack131326"
          "titulo" => "Acknowledgements"
        ]
        20 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2014-03-22"
    "fechaAceptado" => "2014-09-01"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec460469"
          "palabras" => array:6 [
            0 => "Acne"
            1 => "Recurrences"
            2 => "Relapses"
            3 => "Maintenance therapy"
            4 => "Topical retinoids"
            5 => "Oral isotretinoin"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec460468"
          "palabras" => array:6 [
            0 => "Acn&#233;"
            1 => "Recurrencias"
            2 => "Reca&#237;das"
            3 => "Terapia de mantenimiento"
            4 => "Retinoides t&#243;picos"
            5 => "Isotretino&#237;na oral"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved&#46; To avoid or minimize relapses&#44; topical retinoids have been used for many years as maintenance treatment&#46; However&#44; adverse effects frequently occur&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Aims</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine the efficacy and safety of a new retinoid combination &#40;Retinsphere technology&#41; in maintaining post-treatment response to oral isotretinoin&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Patients and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Prospective&#44; randomized&#44; double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin&#46; Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other&#44; once daily&#44; for 3 months&#46; Standardized photographs were taken using RBX technology at baseline&#44; 1&#46;5 months and 3 months&#46; The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side&#46; Other endpoints included lesion count&#44; investigator-reported improvement&#44; patient-reported improvement&#44; impact on quality-of-life&#44; and side effects&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Although the majority of patients did not reach the total target dose of oral isotretinoin&#44; the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side&#46; Likewise&#44; improved lesion count and excellent tolerance were observed&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">This new retinoid combination &#40;Retinsphere technology&#41; were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Aims"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Patients and methods"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Existe un alto porcentaje de pacientes que presentan reidivas de acn&#233; tras el uso de isotretino&#237;na oral&#46; Para evitar o minimizar dichas recidivas el uso de retinoides t&#243;picos se ha utilizado en ocasiones&#44; aunque con mala tolerancia dada la sensibilidad de la piel tras los tratamientos con isotretino&#237;na oral&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Determinar la eficacia y seguridad de una nueva combinaci&#243;n de retinoides &#40;tecnolog&#237;a Retinsphere<span class="elsevierStyleSup">&#174;</span>&#41; en el mantenimiento de la respuesta postratamiento con isotretino&#237;na oral&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Pacientes y M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo&#44; aleatorizado&#44; doble ciego controlado con veh&#237;culo en 30 pacientes con acn&#233; tratado previamente con isotretino&#237;na oral&#46; El tratamiento con la combinaci&#243;n de retinoides se aplic&#243; en una hemicara&#44; mientras que en la otra hemicara se aplic&#243; veh&#237;culo&#44; durante 3 meses&#46; Se tomaron fotograf&#237;as estandarizadas con tecnolog&#237;a RBX en el momento basal&#44; al mes y medio y a los 3 meses&#46; La variable principal para determinar la eficacia fue la aparici&#243;n de recidivas en el &#225;rea tratada con retinoides vs lado tratado con veh&#237;culo&#46; Otras variables estudiadas fueron recuento de lesiones&#44; mejor&#237;a percibida por el investigador y el paciente&#44; impacto en la calidad de vida y efectos adversos&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La mayor&#237;a de los pacientes no hab&#237;an alcanzado la dosis diana de isotretino&#237;na oral&#44; y sin embargo el porcentaje de recidivas fue significativamente menor en el lado tratado con retinoides frente al lado tratado con veh&#237;culo&#46; Adem&#225;s se objetiv&#243; una disminuci&#243;n en el recuento de lesiones y una excelente tolerancia&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Esta nueva combinaci&#243;n de retinoides &#40;tecnolog&#237;a Retinsphere<span class="elsevierStyleSup">&#174;</span>&#41; demostr&#243; eficacia y seguridad en el mantenimiento de respuesta postratamiento con isotreino&#237;na oral en pacientes con acn&#233;&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Objetivos"
          ]
          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Pacientes y M&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Comedones</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Papules</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Pustules</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Global count</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="9" align="left" valign="top"><span class="elsevierStyleItalic">Treated side</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Relapse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">13&#46;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No changes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">73&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="9" align="left" valign="top"><span class="elsevierStyleItalic">Vehicle side</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Relapse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">36&#46;7</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>No changes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">73&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab682511.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Evolution of lesions after 3 months of maintenance treatment with the retinoid combination&#46; The percentage of relapses on the treated and vehicle side are shaded in a darker color and are significantly greater on the vehicle side&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Vehicle side</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Treated side</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Comedones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;027&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Papules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Pustules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab682510.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Mean number of global lesions and individual lesions &#40;comedones&#44; papules and pustules&#41; in each visit &#40;T0&#44; T1 and T2&#41; on treated side and vehicle side&#46; SD &#40;standard deviation&#41;&#46; Statistical significance &#40;<span class="elsevierStyleItalic">P</span>&#41; refers to the mean number of lesions during visits T1 and T2 compared to the basal visit &#40;T0&#41;&#44; showing the vehicle side and the treated side&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Mean</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Standard deviation</th><th class="td" title="table-head  " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Vehicle side&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treated side&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Vehicle side&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treated side&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Global&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Comedones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Papules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Pustules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab682509.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Comparison at the end of the study &#40;T2&#41; between the vehicle side and the side treated with product&#44; showing significant differences in the mean number of global lesions&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:23 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gu&#237;as colombianas para el manejo del acne&#58; una revisi&#243;n basada en la evidencia por el Grupo Colombiano de Estudio en Acne"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Orozco"
                            1 => "M&#46;E&#46; Campo"
                            2 => "L&#46;E&#46; Anaya"
                            3 => "J&#46; Atuesta"
                            4 => "M&#46;J&#46; &#193;vila"
                            5 => "L&#46;F&#46; Balc&#225;zar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Asoc Colomb Dermatol"
                        "fecha" => "2011"
                        "volumen" => "19"
                        "paginaInicial" => "129"
                        "paginaFinal" => "158"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oral isotretinoin in different dose regimens for acne vulgaris&#58; a randomized comparative trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "U&#46;S&#46; Agarwal"
                            1 => "R&#46;K&#46; Besarwal"
                            2 => "K&#46; Bhola"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4103/0378-6323.86482"
                      "Revista" => array:6 [
                        "tituloSerie" => "Indian J Dermatol Venereol Leprol"
                        "fecha" => "2011"
                        "volumen" => "77"
                        "paginaInicial" => "688"
                        "paginaFinal" => "694"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22016276"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low-cumulative dose isotretinoin treatment in mild-to-moderate acne&#58; efficacy in achieving stable remission"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Borghi"
                            1 => "L&#46; Mantovani"
                            2 => "S&#46; Minghetti"
                            3 => "S&#46; Giari"
                            4 => "A&#46; Virgili"
                            5 => "V&#46; Bettoli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1468-3083.2010.03933.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Eur Acad Dermatol Venereol"
                        "fecha" => "2011"
                        "volumen" => "25"
                        "paginaInicial" => "1094"
                        "paginaFinal" => "1098"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21198947"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Isotretinoin therapy for acne&#58; results of a multicenter dose-response study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;S&#46; Straus"
                            1 => "R&#46;P&#46; Rapini"
                            2 => "A&#46;R&#46; Shalita"
                            3 => "E&#46; Konecky"
                            4 => "P&#46;E&#46; Pochi"
                            5 => "H&#46; Comite"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1984"
                        "volumen" => "10"
                        "paginaInicial" => "490"
                        "paginaFinal" => "496"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6233335"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High-dose isotretinoin treatment and the rate of retrial&#44; relapse&#44; and adverse effects in patients with acne vulgaris"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46;C&#46; Blasiak"
                            1 => "C&#46;R&#46; Stamey"
                            2 => "C&#46;N&#46; Burkhart"
                            3 => "A&#46; Lugo-Somolinos"
                            4 => "D&#46;S&#46; Morrell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamadermatol.2013.6746"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA Dermatol"
                        "fecha" => "2013"
                        "volumen" => "149"
                        "paginaInicial" => "1392"
                        "paginaFinal" => "1398"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24173086"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Could higher doses of isotretinoin reduce the frequency of treatment failure in patients with acne&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Coloe"
                            1 => "H&#46; Du"
                            2 => "D&#46;S&#46; Morrell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2010.06.025"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2011"
                        "volumen" => "65"
                        "paginaInicial" => "422"
                        "paginaFinal" => "423"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21763566"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acne relapse rate and predictors of relapse following treatment with oral isotretinoin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46;A&#46; Morales-Cardona"
                            1 => "G&#46; S&#225;nchez-Vanegas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ad.2012.05.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Actas Dermosifiliogr"
                        "fecha" => "2013"
                        "volumen" => "104"
                        "paginaInicial" => "61"
                        "paginaFinal" => "66"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22795452"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Isotretinoin therapy and the incidence of acne relapse&#58; a nested case-control study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46; Azoulay"
                            1 => "D&#46; Orachi"
                            2 => "A&#46; Berard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2133.2007.08250.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Dermatol"
                        "fecha" => "2007"
                        "volumen" => "157"
                        "paginaInicial" => "1240"
                        "paginaFinal" => "1248"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17970803"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New insights into the management of acne&#58; an update from the Global Alliance to Improve Outcomes in Acne group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Thiboutot"
                            1 => "H&#46; Gollnick"
                            2 => "V&#46; Bettoli"
                            3 => "B&#46; Dr&#233;no"
                            4 => "S&#46; Kang"
                            5 => "J&#46;J&#46; Leyden"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2009.01.019"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2009"
                        "volumen" => "60"
                        "numero" => "5 Suppl&#46;"
                        "paginaInicial" => "S1"
                        "paginaFinal" => "S50"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19376456"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acne maintenance therapy&#58; expanding the role of topical retinoids&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "L&#46; Zane"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archderm.142.5.638"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dermatol"
                        "fecha" => "2006"
                        "volumen" => "142"
                        "paginaInicial" => "638"
                        "paginaFinal" => "640"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16702503"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maintenance therapy for acne vulgaris&#58; efficacy of a 12-month treatment with adapalene-benzoyl peroxide after oral isotretinoin and a review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46; Bettoli"
                            1 => "A&#46; Borghi"
                            2 => "S&#46; Zauli"
                            3 => "G&#46; Toni"
                            4 => "M&#46; Ricci"
                            5 => "S&#46; Giari"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000350820"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatology"
                        "fecha" => "2013"
                        "volumen" => "227"
                        "paginaInicial" => "97"
                        "paginaFinal" => "102"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24029411"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Double-blinded&#44; vehicle-controlled proof of concept study to investigate the recurrence of inflammatory and noninflammatory acne lesions using tretinoin gel &#40;microsphere&#41; 0&#46;04&#37; in male patients after oral isotretinoin use"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46; Vender"
                            1 => "R&#46; Vender"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2012/736532"
                      "Revista" => array:5 [
                        "tituloSerie" => "Dermatol Res Pract"
                        "fecha" => "2012"
                        "volumen" => "2012"
                        "paginaInicial" => "736532"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22577372"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Guidance for Industry Acne Vulgaris&#58; Developing Drugs for Treatment&#46; 2005J&#58;&#92;GUIDANC&#92;6499dftcln3&#46;doc&#46; U&#46;S&#46; Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research &#40;CDER&#41;&#46; September 2005&#46; Clinical&#47;Medical&#46;"
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Social sensitivity and acne&#58; the role of personality in negative social consequences and quality of life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46; Krejci-Manwaring"
                            1 => "K&#46; Kerchner"
                            2 => "S&#46;R&#46; Feldman"
                            3 => "D&#46;A&#46; Rapp"
                            4 => "S&#46;R&#46; Rapp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Psychiatry Med"
                        "fecha" => "2006"
                        "volumen" => "36"
                        "paginaInicial" => "121"
                        "paginaFinal" => "130"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16927583"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High-dose isotretinoin in acne vulgaris&#58; improved treatment outcomes and quality of life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;A&#46; Cyrulnik"
                            1 => "K&#46;V&#46; Viola"
                            2 => "A&#46;J&#46; Gewirtzman"
                            3 => "S&#46;R&#46; Cohen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-4632.2011.05409.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Dermatol"
                        "fecha" => "2012"
                        "volumen" => "51"
                        "paginaInicial" => "1123"
                        "paginaFinal" => "1130"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22909370"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An open study to evaluate the efficacy and safety of tazarotene gel &#40;0&#46;1&#37;&#41; in acn&#233; vulgaris"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;G&#46; Saple"
                            1 => "R&#46;G&#46; Torsekar"
                            2 => "V&#46; Pawanarkar"
                            3 => "U&#46;R&#46; Dhanalakshmi"
                            4 => "G&#46; Ravichandran"
                            5 => "D&#46; Kaur"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Indian J Dermatol Venereol Leprol"
                        "fecha" => "2004"
                        "volumen" => "70"
                        "paginaInicial" => "92"
                        "paginaFinal" => "95"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17642573"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prospective study of risk factors of relapse after treatment of acne with oral isotretinoin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G&#46; Quereux"
                            1 => "C&#46; Volteau"
                            2 => "J&#46;M&#46; N&#8217;Guyen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000090658"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatology"
                        "fecha" => "2006"
                        "volumen" => "212"
                        "paginaInicial" => "168"
                        "paginaFinal" => "176"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16484824"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Retinoides en dermatolog&#237;a"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;M&#46; Fernandez-Vozmedian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Med Cutan Iber Lat Am"
                        "fecha" => "2003"
                        "volumen" => "31"
                        "paginaInicial" => "271"
                        "paginaFinal" => "294"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of retinoids in wound healing"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;L&#46; Elson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "1998"
                        "volumen" => "39"
                        "paginaInicial" => "S79"
                        "paginaFinal" => "S81"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9703129"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The potential immunomodulatory effects of topical retinoids &#40;review&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46;A&#46; Jones"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Dermatol Online J"
                        "fecha" => "2005"
                        "volumen" => "11"
                        "paginaInicial" => "3"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16409899"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Valutazione dell&#8217;eficacia dell&#8217;associazione di due retinoidi nel trattamento dell&#8217;acne lieve-moderata"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46; Fabbrocini"
                            1 => "S&#46; Cacciapuoti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Esper Dermatol"
                        "fecha" => "2012"
                        "volumen" => "14"
                        "paginaInicial" => "1"
                        "paginaFinal" => "4"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of comedonal-papular mild acne with a fixed combination of hydroxypinacolone retinoate&#44; retinol glycospheres and papain glycospheres&#46; Preliminary results of a sponsor-free&#44; pilot&#44; open multicentre study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46; Veraldi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Acne Relat Dis"
                        "fecha" => "2012"
                        "volumen" => "3"
                        "paginaInicial" => "13"
                        "paginaFinal" => "15"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "DATA ON FILE 2008&#58; TOPICAL HYDROXYPINACOLONE RETINOATE Skin Diffusion&#44; Receptor Activity&#44; Metabolism and Mildness&#46; John Gormley&#46; Grant Industries Inc&#46; 2008&#46;"
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack131326"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0275" class="elsevierStylePara elsevierViewall">The authors thank Mar&#237;a Vitale&#44; M&#46;D&#46;&#44; Medical Manager working at IFC laboratories for her contribution to this study and support while preparing the present manuscript&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/00017310/0000010600000002/v2_201502240236/S0001731014004128/v2_201502240236/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "14153"
    "tipo" => "SECCION"
    "es" => array:2 [
      "titulo" => "Originales"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "es"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/00017310/0000010600000002/v2_201502240236/S0001731014004128/v2_201502240236/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731014004128?idApp=UINPBA000044"
]