metricas
covid
Buscar en
Medicina Clínica (English Edition)
Toda la web
Inicio Medicina Clínica (English Edition) Metformin improves survival in lung cancer patients with type 2 diabetes mellitu...
Journal Information

Statistics

Follow this link to access the full text of the article

Original
Metformin improves survival in lung cancer patients with type 2 diabetes mellitus: A meta-analysis
La metformina mejora la supervivencia en pacientes con cáncer de pulmón y diabetes mellitus tipo 2: metaanálisis
Sha Zeng, Hua-Xia Gan, Ji-Xiong Xu, Jian-Ying Liu
Corresponding author
JYT-88@medmail.com.cn

Corresponding author.
Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
Read
70
Times
was read the article
2
Total PDF
68
Total HTML
Share statistics
 array:21 [
  "pii" => "S2387020619301093"
  "issn" => "23870206"
  "doi" => "10.1016/j.medcle.2018.06.018"
  "estado" => "S300"
  "fechaPublicacion" => "2019-04-18"
  "aid" => "4597"
  "copyrightAnyo" => "2019"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "cita" => "Med Clin. 2019;152:291-7"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2387020619300889"
    "issn" => "23870206"
    "doi" => "10.1016/j.medcle.2018.06.017"
    "estado" => "S300"
    "fechaPublicacion" => "2019-04-18"
    "aid" => "4596"
    "copyright" => "Elsevier España, S.L.U."
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Med Clin. 2019;152:298-302"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Approach to the risk of delirium in an orthogeriatric unit"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "298"
          "paginaFinal" => "302"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Abordaje del riesgo de delirium en una unidad de ortogeriatr&#237;a"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Eugenia Sopena Bert, Rami Qanneta, Vicente Valent&#237; Moreno, Antonio San Jos&#233; Laporte"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Eugenia"
              "apellidos" => "Sopena Bert"
            ]
            1 => array:2 [
              "nombre" => "Rami"
              "apellidos" => "Qanneta"
            ]
            2 => array:2 [
              "nombre" => "Vicente"
              "apellidos" => "Valent&#237; Moreno"
            ]
            3 => array:2 [
              "nombre" => "Antonio"
              "apellidos" => "San Jos&#233; Laporte"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0025775318304482"
        "doi" => "10.1016/j.medcli.2018.06.025"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775318304482?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619300889?idApp=UINPBA00004N"
    "url" => "/23870206/0000015200000008/v1_201904100623/S2387020619300889/v1_201904100623/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original</span>"
    "titulo" => "Metformin improves survival in lung cancer patients with type 2 diabetes mellitus&#58; A meta-analysis"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "291"
        "paginaFinal" => "297"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Sha Zeng, Hua-Xia Gan, Ji-Xiong Xu, Jian-Ying Liu"
        "autores" => array:4 [
          0 => array:2 [
            "nombre" => "Sha"
            "apellidos" => "Zeng"
          ]
          1 => array:2 [
            "nombre" => "Hua-Xia"
            "apellidos" => "Gan"
          ]
          2 => array:2 [
            "nombre" => "Ji-Xiong"
            "apellidos" => "Xu"
          ]
          3 => array:4 [
            "nombre" => "Jian-Ying"
            "apellidos" => "Liu"
            "email" => array:1 [
              0 => "JYT-88&#64;medmail&#46;com&#46;cn"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:2 [
            "entidad" => "Department of Endocrinology and Metabolism&#44; First Affiliated Hospital of Nanchang University&#44; Nanchang&#44; Jiangxi 330006&#44; China"
            "identificador" => "aff0005"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "La metformina mejora la supervivencia en pacientes con c&#225;ncer de pulm&#243;n y diabetes mellitus tipo 2&#58; metaan&#225;lisis"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 3325
            "Ancho" => 1549
            "Tamanyo" => 524000
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Subgroup analysis result of OS&#58; &#40;i&#41; geographic region &#40;West or Asian&#41;&#59; &#40;ii&#41; lung cancer subtype &#40;NSCLC&#44; non-divided&#44; or SCLC&#41;&#59; &#40;iii&#41; study design &#40;cohort or case&#8211;control study&#41;&#46; Data from&#58; &#40;a&#41; Vanderbilt University Medical Center&#59; &#40;b&#41; metformin vs&#46; other drug&#59; &#40;c&#41; metformin vs&#46; insulin&#59; &#40;d&#41; metformin vs&#46; none&#59; &#40;e&#41; Mayo Clinic medical data&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Lung cancer is the number one cause of cancer deaths worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a> Many clinical epidemiologic factors&#44; such as cigarette smoking&#44; air pollution&#44; pulmonary tuberculosis&#44; exposure to carcinogens&#44; and familial history of lung cancer&#44; have been identified<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">2&#8211;3</span></a> Despite the rapid development of diagnosis and treatment modalities&#44; the prognosis of lung cancer remains poor&#44; with a 5-year survival of only about 15&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a> Therefore&#44; there is an urgent need to find treatments that have a therapeutic effect on lung cancer&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Diabetes is a common and devastating chronic disease&#44; with a projected global population of 366 million having this disease by 2030&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">5</span></a> With an aging population&#44; the number of cancer patients with diabetes is on the rise&#46; Increasing epidemiological evidence suggests that there is an association between diabetes mellitus &#40;DM&#41; and various cancers&#46; Early epidemiological studies suggest that diabetes is not associated with the development of lung cancer&#59; however&#44; several recent studies suggest that diabetes is significantly associated with the development of lung cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Metformin&#44; an oral anti-diabetic drug that is less expensive than any anti-cancer agent that is currently in routine use&#44; first attracted attention in 2005 for its potential to suppress not only serum glucose levels&#44; but also the incidence of various cancers in an observational study&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">8</span></a> Metformin has subsequently been investigated as an anti-cancer medicine for malignancies&#44; including lung cancer&#44; in diabetic and non-diabetic subjects&#46; In recent years&#44; an increasing number of studies have investigated metformin and lung cancer&#44; with the results showing that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">9&#44;10</span></a> However&#44; Medairos et al&#46; reported that Metformin exposure in diabetic patients with early-stage non-small cell lung cancer may be associated with improved progression-free survival&#44; but no effect was seen on overall survival&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">11</span></a> Based on these studies&#44; the relationship between metformin and lung cancer is complicated&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In order to elucidate the relationship between metformin and lung cancer&#44; we conducted a meta-analysis of the existing relevant observational studies in the literature and systematically re-evaluated the impact of metformin on the survival outcomes of diabetic patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Literature search</span><p id="par0025" class="elsevierStylePara elsevierViewall">An electronic search of the Medical literature was conducted for articles with dates of publication up to 27 July 2017&#44; in the following databases&#58; PubMed&#44; Embase&#44; and Cochrane library&#46; The search was without language restrictions and independently checked by two of the authors&#46; We developed a search strategy using the following terms&#58; &#8220;Metformin&#8221; or &#8220;Dimethylbiguanidine&#8221; or &#8220;Dimethylguanylguanidine&#8221; or &#8220;Glucophage&#8221; or &#8220;Metformin Hydrochloride&#8221; or &#8220;Hydrochloride&#44; Metformin&#8221; or &#8220;Metformin HCl&#8221; or &#8220;HCl&#44; Metformin&#8221; and &#8220;lung neoplasms&#8221; or &#8220;Pulmonary Neoplasms&#8221; or &#8220;Neoplasms&#44; Lung&#8221; or &#8220;Lung Neoplasm&#8221; or &#8220;Neoplasm&#44; Lung&#8221; or &#8220;Neoplasms&#44; Pulmonary&#8221; or &#8220;Neoplasm&#44; Pulmonary&#8221; or &#8220;Pulmonary Neoplasm&#8221; or &#8220;Lung Cancer&#8221; or &#8220;Cancer&#44; Lung&#8221; or &#8220;Cancers&#44; Lung&#8221; or &#8220;Lung Cancers&#8221; or &#8220;Pulmonary Cancer&#8221; or &#8220;Cancer&#44; Pulmonary&#8221; or &#8220;Cancers&#44; Pulmonary&#8221; or &#8220;Pulmonary Cancers&#8221; or &#8220;Cancer of the Lung&#8221; or &#8220;Cancer of Lung&#8221;&#46; In addition&#44; we screened the bibliographies of selected original studies and review articles to identify any other relevant studies that were not retrieved through the initial database search&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Selection criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">Studies&#44; or subsets of studies&#44; were included if they satisfied all the following criteria&#58; &#40;a&#41; randomized controlled clinical trials&#44; data-based&#44; or cohort studies&#59; &#40;b&#41; studies evaluating the effect of metformin on survival of lung cancer in patients with diabetes&#59; and&#44; &#40;c&#41; studies reporting the hazard ratios &#40;HRs&#41; with corresponding 95&#37; confidence intervals &#40;CIs&#41;&#44; or providing sufficient data to calculate these values&#46; If more than one paper was based on the same study&#44; we included the one which provided the most abundant information or the one containing the largest number of cases&#46; Studies were excluded if they were published as letters&#44; editorials&#44; reviews&#44; cell-line studies&#44; animal studies&#44; and studies without controls&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Exclusion criteria</span><p id="par0035" class="elsevierStylePara elsevierViewall">Two authors performed the data extraction independently&#46; For the eligible studies&#44; collected data included the following&#58; &#40;1&#41; basic information of each study&#44; such as author names&#44; year of publication&#44; country or area of origin&#44; and study design&#59; &#40;2&#41; characteristics of patients&#44; such as median or mean age&#44; gender composition&#44; and tumor type&#59; &#40;3&#41; information of study designation&#44; such as the number of enrolled subjects&#44; group sample size&#44; and follow-up time&#59; and&#44; &#40;4&#41; results of treatment&#44; such as overall survival &#40;OS&#41;&#44; median disease-free survival &#40;DFS&#41;&#44; or progression-free survival &#40;PFS&#41; and adjusted HRs with the associated 95&#37; CIs&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data extraction quality assessment</span><p id="par0040" class="elsevierStylePara elsevierViewall">To assess the quality of the included studies&#44; the Newcastle-Ottawa Scale &#40;NOS&#41; was applied to this meta-analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a> We evaluated the included studies based on selection of participants&#44; comparability of participants&#44; and ascertainment of outcomes&#44; with the methodological quality then being scored&#46; Quality assessment was independently conducted by two authors&#44; with third party assessment &#40;Liu&#41; being performed when necessary&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analyses</span><p id="par0045" class="elsevierStylePara elsevierViewall">To assess the association between metformin treatment and the survival of patients with lung neoplasms&#44; summary HRs with their corresponding 95&#37; CIs were calculated through meta-analysis&#46; Heterogeneity analysis was performed using the Cochran Q statistic and the <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> statistic&#46; Statistical significance for heterogeneity was considered if <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 or <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>50&#37;&#46; A fixed-effects model was applied when <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05 and <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50&#37;&#44; while a random-effects model was chosen when <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 or <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>50&#37;&#46; To identify the sources of heterogeneity&#44; we performed subgroup analyses&#46; In addition&#44; we conducted a sensitivity analysis by removing one study at a time and re-calculating the pooled effects&#46; Potential publications bias &#40;considered present if <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41; was assessed by conducting statistical tests for funnel plot asymmetry&#44; as well as Egger&#39;s test and Begg&#39;s test&#46; All statistical analyses were conducted using Stata version 12&#46;0 software &#40;Stata Corp&#46;&#44; College Station&#44; TX&#44; USA&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Literature search</span><p id="par0050" class="elsevierStylePara elsevierViewall">Our detailed study selection process is described in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; The literature search identified 426 potentially relevant articles&#44; with 141 papers being excluded because of duplicates&#46; After screening titles and abstracts&#44; 233 articles were excluded because they were animal or in vitro studies&#44; involved other cancers or treatment agents&#44; or were letters&#44; commentaries&#44; case reports&#44; review articles&#44; or Abstracts&#46; After reading the full text of the remaining 52 articles&#44; 42 were excluded due insufficient data&#46; Finally&#44; 10 studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">13&#8211;22</span></a> including a total of 4397 patients&#44; were included in the current meta-analysis&#46; The current meta-analysis was conducted in accordance with PRISMA guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">23</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Characteristics of the included studies</span><p id="par0055" class="elsevierStylePara elsevierViewall">The baseline characteristics of each study are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; These 10 studies were all retrospective&#44; including 8 cohort studies and 2 case&#8211;controlled studies&#46; Most of these were published very recently between 2015 and 2017&#44; and originated from China&#44; the USA&#44; Netherlands&#44; Mexico&#44; and the United Kingdom&#46; All subtypes of lung cancer&#44; including small cell lung cancer &#40;SCLC&#41; and non-small cell lung cancer &#40;NSCLC&#41;&#44; with stage I&#8211;IV disease were involved&#46; The median age of the enrolled patients ranged from 56&#46;2 to 72&#46;5 years&#46; The NOS score of the selected studies ranged from 6&#8211;8 stars on the scale&#44; which suggested moderate to high quality studies &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Quantitative synthesis</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Publication bias and heterogeneity</span><p id="par0060" class="elsevierStylePara elsevierViewall">To assess the possibility of publication bias among the studies&#44; funnel plots were generated&#46; No evidence of asymmetry in the funnel plot was detected&#44; indicating that there was no obvious publication bias in our study&#44; which was also supported by the Egger&#39;s test and Begg&#39;s test &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Metformin use and survival of lung cancer</span><p id="par0065" class="elsevierStylePara elsevierViewall">A total of 10 studies reporting OS were incorporated into this meta-analysis&#46; The heterogeneity test indicated that a fixed-effect model could be selected &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&#46;5&#37;&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#46; The pooled results showed that there was a significant difference in OS between lung cancer patients who did and did not receive metformin &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;75&#44; 95&#37; CI&#58; 0&#46;70&#8211;0&#46;80&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Subgroup analysis</span><p id="par0070" class="elsevierStylePara elsevierViewall">Subgroup analysis was adopted to explore the causes of heterogeneity for the analysis of OS &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; The analyzed studies were stratified to evaluate OS according to geographic region&#44; study design&#44; and lung cancer subtype&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">In this analysis&#44; the studies from Western countries showed that metformin was associated with reduced mortality risk&#44; as well as in Asian countries&#46; For lung cancer subtype&#44; the relative survival benefit associated with metformin remained for all subtypes&#46; When analyzing study design&#44; both cohort-based and case&#8211;controlled studies were significant in terms of OS and metformin use&#41;&#46; However&#44; the heterogeneity of Western countries&#44; non-divide group and case&#8211;control studies were significant &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>57&#46;7&#37;&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70&#46;0&#37;&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>72&#46;3&#37;&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#59; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Sensitivity analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">Considering the large variations across studies&#44; we performed sensitivity analysis by the sequential omission of individual studies to recalculate the pooled HR&#44; and none of the exclusions of a specific study would substantially alter the trend of our primary pooled results&#59; this showed a significant association of metformin administration and improved OS&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">In this study&#44; we analyzed the association of metformin use with the survival of lung cancer using a meta-analysis&#46; To our knowledge&#44; this is the first meta-analysis providing comprehensive insights into the effects of metformin treatment and the survival of lung cancer&#46; This meta-analysis included a pooled analysis of 8 cohort studies and 2 case&#8211;control studies&#44; which investigated the effect of metformin use on the survival of lung cancer patients&#46; We found that&#44; metformin treatment significantly improved the survival of lung cancer patients &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;75&#44; 95&#37; CI&#58; 0&#46;70&#8211;0&#46;80&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In the sub-group analysis&#44; metformin use was significantly associated with good prognosis in patients with lung cancer&#44; independent of tumor type and region&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Diabetes and malignant tumors are common diseases&#44; where the development of urbanization and industrialization has led to a yearly increase in incidence&#44; which seriously affects the health of large populations&#46; There are many common risk factors for diabetes and lung cancer&#46; First&#44; smoking is an important risk factor for lung cancer&#46; Studies have shown that smoking can also increase the risk of diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a> Second&#44; lung cancer and diabetes are age-related diseases&#46; Third&#44; epidemiological studies have shown that vitamin D levels are negatively correlated with the occurrence of lung cancer<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> Lucato et al&#46; published a meta-analysis that demonstrated vitamin D supplementation can improve insulin sensitivity and reduce the risk of diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">26</span></a> The classical pathways shared by diabetes mellitus and cancer are the insulin&#47;IGF-axis&#46; Hyperglycemia is a feature of diabetes mellitus&#44; and Warburg first hypothesized that hyperglycemia itself might have carcinogenic potential&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">27</span></a> Direct carcinogenic effects of hyperglycemia&#44; combined with the Wnt signaling pathway&#44; were recently proposed as promoting carcinogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">28</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Metformin has been administered in routine clinical use for more than 50 years&#46; It is one of the most widely used oral hypoglycemic agents in the world&#46; In recent years&#44; although a number of new hypoglycemic drugs have been implemented&#44; metformin is still the world&#39;s most used classic oral hypoglycemic agent&#46; Evans et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a> found that metformin was associated with a reduced cancer risk and observed that with increasing use&#44; the protective effect of metformin gradually increased&#46; However&#44; the specific mechanism underlying the anti-tumor effect of metformin remains unknown&#44; with most studies focusing on the AMP activated protein kinase &#40;AMPK&#41; signaling pathway&#46; Many studies have shown that metformin can activate the AMPK pathway&#44; which may not only affect metabolism&#44; but also inhibit the occurrence and development of tumors&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">29&#8211;32</span></a> In addition&#44; Metformin reduces insulin levels in the circulatory system&#44; reduces insulin-like growth factor binding protein levels&#44; and reduces the synthesis and secretion of the IGF-1&#44; which plays a role in the metabolic regulation and proliferative inhibition of lung cancer cells&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The current meta-analysis has several strengths&#46; First&#44; the major strength of this study is that we comprehensively assessed the effects of metformin use on lung cancer&#44; using survival as the primary outcome&#46; Second&#44; the sensitivity analysis did not show that a single study influenced the pooled results and no publication bias was detected&#46; Given these characteristics&#44; this meta-analysis is a comprehensive study of the effect of metformin on lung cancer&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">However&#44; several limitations in our study should be acknowledged&#46; First&#44; 2 of the studies included in this meta-analysis did not report adjustments&#44; while the adjustments of the other 8 studies were either inconsistent or incomplete&#46; Many other confounders&#44; such as gender ratio of the subjects&#44; cumulative dose&#44; use of concomitant medications&#44; and time-related bias&#44; were not controlled&#46; These aspects are important in understanding the role of metformin&#46; Second&#44; patients with small-cell lung cancer were all from Asian populations&#46; Therefore&#44; we do not know whether metformin&#39;s role in these populations is related to ethnicity&#46; The average age of the subjects in this study was between 56&#46;2 and 74&#46;5&#46; Therefore&#44; we do not know whether metformin is consistent with this study in those who are younger than 54&#46;2 years old or older than 74&#46;5 years old&#46; In other words&#44; we do not know whether age affects the effect of metformin on lung cancer&#46; Finally&#44; there is some heterogeneity between lung cancer survival rates &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&#46;5&#37;&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#46; With this in mind&#44; we conducted a subgroup analysis according to region&#44; study design&#44; and cancer subtype&#46; From these results&#44; we observed that heterogeneity may be derived from non-divided lung cancer types and case&#8211;control studies&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Compliance with ethical standards</span><p id="par0110" class="elsevierStylePara elsevierViewall">The manuscript does not contain clinical studies or patient data&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Authors&#8217; contributions</span><p id="par0115" class="elsevierStylePara elsevierViewall">Sha Zeng and Hua-Xia Gan contributed equally to this work&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicts of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that no conflicts of interest exist&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:14 [
        0 => array:3 [
          "identificador" => "xres1178782"
          "titulo" => "Abstract"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Background and objective"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Material and methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1100236"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xpalclavsec1100237"
          "titulo" => "Abbreviations"
        ]
        3 => array:3 [
          "identificador" => "xres1178781"
          "titulo" => "Resumen"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Antecedentes y objetivo"
            ]
            1 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Materiales y m&#233;todos"
            ]
            2 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Resultados"
            ]
          ]
        ]
        4 => array:2 [
          "identificador" => "xpalclavsec1100235"
          "titulo" => "Palabras clave"
        ]
        5 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        6 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Literature search"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Selection criteria"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Exclusion criteria"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Data extraction quality assessment"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Statistical analyses"
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Results"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Literature search"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Characteristics of the included studies"
            ]
            2 => array:3 [
              "identificador" => "sec0055"
              "titulo" => "Quantitative synthesis"
              "secciones" => array:1 [
                0 => array:2 [
                  "identificador" => "sec0060"
                  "titulo" => "Publication bias and heterogeneity"
                ]
              ]
            ]
            3 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Metformin use and survival of lung cancer"
            ]
            4 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Subgroup analysis"
            ]
            5 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Sensitivity analysis"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Discussion"
        ]
        9 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Compliance with ethical standards"
        ]
        10 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Authors&#8217; contributions"
        ]
        11 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Conflicts of interest"
        ]
        12 => array:2 [
          "identificador" => "xack402464"
          "titulo" => "Acknowledgments"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-03-01"
    "fechaAceptado" => "2018-06-21"
    "PalabrasClave" => array:2 [
      "en" => array:2 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1100236"
          "palabras" => array:5 [
            0 => "Metformin"
            1 => "Survival"
            2 => "Lung cancer"
            3 => "Type 2 diabetes mellitus"
            4 => "Meta-analysis"
          ]
        ]
        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1100237"
          "palabras" => array:9 [
            0 => "HR&#40;s&#41;"
            1 => "CI&#40;s&#41;"
            2 => "OS"
            3 => "DM"
            4 => "DFS"
            5 => "PFS"
            6 => "NOS"
            7 => "SCLC"
            8 => "NSCLC"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1100235"
          "palabras" => array:5 [
            0 => "Metformina"
            1 => "Supervivencia"
            2 => "C&#225;ncer de pulm&#243;n"
            3 => "Diabetes mellitus tipo 2"
            4 => "Metaan&#225;lisis"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In recent years&#44; many studies have investigated metformin and its effects on lung cancer&#46; However&#44; since previous studies have shown that the relationship between metformin and lung cancer is complicated&#44; we performed a meta-analysis to analyze this relationship&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">An electronic database search was conducted using PubMed&#44; Embase&#44; and Cochrane library&#46; Outcomes were quantified with hazard ratios and 95&#37; confidence intervals to compare lung cancer survival in patients treated with or without metformin&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Ten studies&#44; involving 4397 participants&#44; were included&#46; In the pooled analysis&#44; we found that metformin treatment significantly improved the survival of lung cancer patients &#40;hazard ratio<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;75&#44; 95&#37; confidence interval&#58; 0&#46;70&#8211;0&#46;80&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Subgroup analysis showed that when stratified by geographic region&#44; the hazard ratios for overall survival were 0&#46;76 &#40;95&#37; confidence interval&#58; 0&#46;71&#8211;0&#46;81&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and 0&#46;51 &#40;95&#37; confidence interval&#58; 0&#46;25&#8211;0&#46;78&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; for Western and Asian countries&#44; respectively&#46; When stratified by lung cancer subtype&#44; the hazard ratios for overall survival were 0&#46;78 &#40;95&#37; confidence interval&#58; 0&#46;71&#8211;0&#46;84&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; 0&#46;73 &#40;95&#37; confidence interval&#58; 0&#46;66&#8211;0&#46;81&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and 0&#46;51 &#40;95&#37; confidence interval&#58; 0&#46;25&#8211;0&#46;78&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; for non-divided&#44; non-small cell&#44; and small-cell lung cancer subtypes&#44; respectively&#46; When stratified by study design&#44; the hazard ratios for overall survival were 0&#46;77 &#40;95&#37; confidence interval&#58; 0&#46;71&#8211;0&#46;83&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and 0&#46;71 &#40;95&#37; confidence interval&#58; 0&#46;63&#8211;0&#46;80&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; for cohort-based and case&#8211;controlled studies&#44; respectively&#46;</p></span>"
        "secciones" => array:3 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Antecedentes y objetivo</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">En los &#250;ltimos a&#241;os&#44; muchos estudios han investigado los efectos de la metformina sobre el c&#225;ncer de pulm&#243;n&#46; Sin embargo&#44; dado que estudios previos hab&#237;an demostrado que la relaci&#243;n entre la metformina y el c&#225;ncer de pulm&#243;n era complicada&#44; realizamos un metaan&#225;lisis para estudiar esta relaci&#243;n&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Materiales y m&#233;todos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; una b&#250;squeda en las bases de datos electr&#243;nicas PubMed&#44; Embase y Cochrane Library&#46; Los resultados se cuantificaron con cociente de riesgos instant&#225;neos e intervalos de confianza del 95&#37; para comparar la supervivencia del c&#225;ncer de pulm&#243;n en pacientes tratados con o sin metformina&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Resultados</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 10 estudios con un total de 4&#46;397 participantes&#46; En el an&#225;lisis combinado&#44; el tratamiento con metformina mejor&#243; significativamente la supervivencia de los pacientes con c&#225;ncer de pulm&#243;n &#40;cociente de riesgos instant&#225;neos<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;75&#59; intervalo de confianza del 95&#37;&#58; 0&#44;70-0&#44;80&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; El an&#225;lisis de subgrupos mostr&#243; que cuando se estratific&#243; por regi&#243;n geogr&#225;fica&#44; los cocientes de riesgos para la supervivencia global fueron de 0&#44;76 &#40;intervalo de confianza del 95&#37;&#58; 0&#44;71-0&#44;81&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y 0&#44;51 &#40;intervalo de confianza del 95&#37;&#58; 0&#44;25-0&#44;78&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; para los pa&#237;ses occidentales y asi&#225;ticos&#44; respectivamente&#46; Cuando se estratific&#243; por subtipo de c&#225;ncer de pulm&#243;n&#44; los cocientes de riesgo para la supervivencia global fueron de 0&#44;78 &#40;intervalo de confianza del 95&#37;&#58; 0&#44;71-0&#44;84&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; de 0&#44;73 &#40;intervalo de confianza del 95&#37;&#58; 0&#44;66-0&#44;81&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y de 0&#44;51 &#40;intervalo de confianza del 95&#37;&#58; 0&#44;25-0&#44;78&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; para subtipos de c&#225;ncer de pulm&#243;n no microc&#237;tico&#44; de c&#233;lulas no peque&#241;as y de c&#233;lulas peque&#241;as&#44; respectivamente&#46; Cuando se estratific&#243; seg&#250;n el dise&#241;o del estudio&#44; los cocientes de riesgo para la supervivencia global fueron de 0&#44;77 &#40;intervalo de confianza del 95&#37;&#58; 0&#44;71-0&#44;83&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y de 0&#44;71 &#40;intervalo de confianza del 95&#37;&#58; 0&#44;63-0&#44;80&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; para estudios de cohortes y de casos-controles&#44; respectivamente&#46;</p></span>"
        "secciones" => array:3 [
          0 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Antecedentes y objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Materiales y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Resultados"
          ]
        ]
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2136
            "Ancho" => 2500
            "Tamanyo" => 282649
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Flow chart showing the process of study selection&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1866
            "Ancho" => 2500
            "Tamanyo" => 205076
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Egger&#39;s funnel plots &#40;A&#41; and Begg&#39;s funnel plots &#40;B&#41; for the publication bias test &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;963&#44; Egger&#39;s test&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;000&#44; Begg&#39;s test&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1516
            "Ancho" => 2500
            "Tamanyo" => 238759
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Meta-analysis result of OS&#58; &#40;a&#41; Vanderbilt University Medical Center medical data&#59; &#40;b&#41; metformin vs&#46; other drug&#59; &#40;c&#41; metformin vs&#46; Insulin&#59; &#40;d&#41; metformin vs&#46; none&#59; &#40;e&#41; Mayo Clinic medical data&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 3325
            "Ancho" => 1549
            "Tamanyo" => 524000
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Subgroup analysis result of OS&#58; &#40;i&#41; geographic region &#40;West or Asian&#41;&#59; &#40;ii&#41; lung cancer subtype &#40;NSCLC&#44; non-divided&#44; or SCLC&#41;&#59; &#40;iii&#41; study design &#40;cohort or case&#8211;control study&#41;&#46; Data from&#58; &#40;a&#41; Vanderbilt University Medical Center&#59; &#40;b&#41; metformin vs&#46; other drug&#59; &#40;c&#41; metformin vs&#46; insulin&#59; &#40;d&#41; metformin vs&#46; none&#59; &#40;e&#41; Mayo Clinic medical data&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">M&#44; metformin use group&#59; N-M&#44; non-metformin use group&#59; OS&#44; overall survival&#59; HR&#44; hazard ratio&#59; DFS&#44; disease-free survival&#59; y&#44; year&#59; mo&#44; month&#59; LL&#44; lower limit&#59; UL&#44; upper limit&#59; SCLC&#44; small cell lung cancer&#59; NSCLC&#44; non-small cell lung cancer&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Year</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Country</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rage</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Design</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Stage</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Sample size</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Median<br>age</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">OS&#47;mo</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HR-OS<br>&#40;LL-UL&#41;</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">DFS&#47;mo</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HR-DFS<br>&#40;LL-UL&#41;</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">M&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">NM&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">M&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">NM&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">M&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">NM&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lin et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2002&#8211;2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NSCLC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&#8211;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">259&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">377&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&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;76 &#40;0&#46;65&#8211;0&#46;88&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Wink et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Netherlands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2008&#8211;2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NSCLC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">623&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&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;86 &#40;0&#46;57&#8211;1&#46;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Arrieta et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mexico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2008&#8211;2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NSCLC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">II&#8211;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">111&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#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">13&#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;57 &#40;0&#46;36&#8211;0&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Menamin et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">United Kingdom&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1998&#8211;2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Non-<br>divided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">251&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">282&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&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;86 &#40;0&#46;68&#8211;1&#46;09&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ahmed et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1999&#8211;2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NSCLC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">I&#8211;IV&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">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#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">19&#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">1&#46;73 &#40;0&#46;78&#8211;3&#46;85&#41;&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;7<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;1<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;4 &#40;0&#46;65&#8211;3&#46;04&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kong et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2001&#8211;2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SCLC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">139&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#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;485 &#40;0&#46;178&#8211;0&#46;887&#41;&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;5&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">0&#46;504 &#40;0&#46;255&#8211;0&#46;954&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="6" align="left" valign="top">Xu et al&#46;</td><td class="td" title="table-entry  " rowspan="6" align="left" valign="top">2015</td><td class="td" title="table-entry  " rowspan="6" align="left" valign="top">USA</td><td class="td" title="table-entry  " rowspan="6" align="left" valign="top">1995&#8211;2010</td><td class="td" title="table-entry  " rowspan="6" align="left" valign="top">Case&#8211;<br>control</td><td class="td" title="table-entry  " rowspan="6" align="left" valign="top">Non-<br>divided</td><td class="td" title="table-entry  " rowspan="6" align="left" valign="top">&#8212;</td><td class="td" title="table-entry  " rowspan="6" align="char" valign="top">367</td><td class="td" title="table-entry  " rowspan="6" align="char" valign="top">358</td><td class="td" title="table-entry  " rowspan="6" align="char" valign="top">63</td><td class="td" title="table-entry  " rowspan="6" align="char" valign="top">&#8212;</td><td class="td" title="table-entry  " rowspan="6" align="char" valign="top">&#8212;</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9 &#40;0&#46;64&#8211;1&#46;28&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="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="" valign="top">&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">0&#46;93 &#40;0&#46;48&#8211;1&#46;8&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="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="" valign="top">&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">0&#46;8 &#40;0&#46;63&#8211;1&#46;01&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a>&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="" valign="top">&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">0&#46;76 &#40;0&#46;58&#8211;0&#46;99&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">f</span></a>&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="" valign="top">&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">0&#46;59 &#40;0&#46;4&#8211;0&#46;85&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">f</span></a>&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="" valign="top">&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">0&#46;58 &#40;0&#46;47&#8211;0&#46;73&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">f</span></a>&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="" valign="top">&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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lin et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2007&#8211;2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NSCLC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">458&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">292&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&#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">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&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 &#40;0&#46;71&#8211;0&#46;89&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Xu et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2000&#8211;2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SCLC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&#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">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#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;549 &#40;0&#46;198&#8211;0&#46;978&#41;&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;8&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;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;568 &#40;0&#46;262&#8211;0&#46;897&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mazzone<br>et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2001&#8211;2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Case&#8211;<br>control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Non-<br>divided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">507&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&#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">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&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;47 &#40;1&#46;12&#8211;1&#46;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2008643.png"
              ]
            ]
          ]
          "notaPie" => array:6 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Progress-free survival reported instead of DFS&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">From Vanderbilt University Medical Center medical data&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Metformin vs&#46; other drug&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Metformin vs&#46; insulin&#46;</p>"
            ]
            4 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "e"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Metformin vs&#46; none&#46;</p>"
            ]
            5 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "f"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">From Mayo Clinic medical data&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The baseline characteristics of each study&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author&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">Year&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">Country&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">Design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Selection &#40;4&#41;</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Comparability &#40;2&#41;</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Outcome &#40;3&#41;</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lin et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Wink et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Netherlands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Arrieta et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mexico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Menamin et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">United Kingdom&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ahmed et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kong et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Xu et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Case&#8211;control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lin et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Xu et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mazzone et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Case&#8211;control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8902;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2008644.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">The quality of the 10 included studies appraised in reference to the Newcastle-Ottawa statement&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:33 [
            0 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global cancer incidence and mortality rates and trends &#8211; an update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L&#46;A&#46; Torre"
                            1 => "R&#46;L&#46; Siegel"
                            2 => "E&#46;M&#46; Ward"
                            3 => "A&#46; Jemal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Cancer Epidemiol Biomark Prev"
                        "fecha" => "2016"
                        "volumen" => "25"
                        "paginaInicial" => "16"
                        "paginaFinal" => "27"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer and related risk factors&#58; an update of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Ruano-Ravina"
                            1 => "A&#46; Figueiras"
                            2 => "J&#46;M&#46; Barros-Dios"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0033-3506(02)00023-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Public Health"
                        "fecha" => "2003"
                        "volumen" => "117"
                        "paginaInicial" => "149"
                        "paginaFinal" => "156"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12825464"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung cancer susceptibility model based on age&#44; family history and genetic variants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;P&#46; Young"
                            1 => "R&#46;J&#46; Hopkins"
                            2 => "B&#46;A&#46; Hay"
                            3 => "M&#46;J&#46; Epton"
                            4 => "G&#46;D&#46; Mills"
                            5 => "P&#46;N&#46; Black"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0005302"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2009"
                        "volumen" => "4"
                        "paginaInicial" => "e5302"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19390575"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical practice&#44; lung cancer screening"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;L&#46; Mulshine"
                            1 => "D&#46;C&#46; Sullivan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMcp042630"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2005"
                        "volumen" => "352"
                        "paginaInicial" => "2714"
                        "paginaFinal" => "2720"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15987920"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global prevalence of diabetes&#58; estimates for the year 2000 and projections for 2030"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Wild"
                            1 => "G&#46; Roglic"
                            2 => "A&#46; Green"
                            3 => "R&#46; Sicree"
                            4 => "H&#46; King"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2004"
                        "volumen" => "27"
                        "paginaInicial" => "1047"
                        "paginaFinal" => "1053"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15111519"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diabetes and cancer risk for all and specific sites among Japanese men and women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46; Kuriki"
                            1 => "K&#46; Hirose"
                            2 => "K&#46; Tajima"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Cancer"
                        "fecha" => "2007"
                        "volumen" => "16"
                        "paginaInicial" => "83"
                        "paginaFinal" => "89"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diabetes mellitus as an independent risk factor for lung cancer&#58; a meta-analysis of observational studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46; Lee"
                            1 => "I&#46; Jeon"
                            2 => "J&#46;M&#46; Lee"
                            3 => "J&#46;M&#46; Yoon"
                            4 => "S&#46;M&#46; Park"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ejca.2013.02.025"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Cancer"
                        "fecha" => "2013"
                        "volumen" => "49"
                        "paginaInicial" => "2411"
                        "paginaFinal" => "2423"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23562551"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metformin and reduced risk of cancer in diabetic patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;M&#46; Evans"
                            1 => "L&#46;A&#46; Donnelly"
                            2 => "A&#46;M&#46; Emslie-Smith"
                            3 => "D&#46;R&#46; Alessi"
                            4 => "A&#46;D&#46; Morris"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmj.38415.708634.F7"
                      "Revista" => array:6 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "2005"
                        "volumen" => "330"
                        "paginaInicial" => "1304"
                        "paginaFinal" => "1305"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15849206"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;X&#46; Tan"
                            1 => "W&#46;X&#46; Yao"
                            2 => "J&#46; Ge"
                            3 => "X&#46;C&#46; Peng"
                            4 => "X&#46;B&#46; Du"
                            5 => "R&#46; Zhang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cncr.26151"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "2011"
                        "volumen" => "117"
                        "paginaInicial" => "5103"
                        "paginaFinal" => "5111"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21523768"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;M&#46; Della Corte"
                            1 => "V&#46; Ciaramella"
                            2 => "C&#46; Di Mauro"
                            3 => "M&#46;D&#46; Castellone"
                            4 => "F&#46; Papaccio"
                            5 => "M&#46; Fasano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.18632/oncotarget.6559"
                      "Revista" => array:6 [
                        "tituloSerie" => "Oncotarget"
                        "fecha" => "2016"
                        "volumen" => "7"
                        "paginaInicial" => "4265"
                        "paginaFinal" => "4278"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26673006"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "55-61&#46;e1"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metformin exposure is associated with improved progression-free survival in diabetic patients after resection for early-stage non-small cell lung cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;A&#46; Medairos"
                            1 => "J&#46; Clark"
                            2 => "S&#46; Holoubek"
                            3 => "J&#46;C&#46; Kubasiak"
                            4 => "R&#46; Pithadia"
                            5 => "F&#46; Hamid"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "J Thorac Cardiovasc Surg"
                        "fecha" => "2016"
                        "volumen" => "152"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "A&#46; Stang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10654-010-9491-z"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Epidemiol"
                        "fecha" => "2010"
                        "volumen" => "25"
                        "paginaInicial" => "603"
                        "paginaFinal" => "605"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20652370"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metformin use and survival after non-small cell lung cancer&#58; a cohort study in the US Military health system"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Lin"
                            1 => "A&#46; Gill"
                            2 => "S&#46;H&#46; Zahm"
                            3 => "C&#46;A&#46; Carter"
                            4 => "C&#46;D&#46; Shriver"
                            5 => "J&#46;A&#46; Nations"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ijc.30724"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Cancer"
                        "fecha" => "2017"
                        "volumen" => "141"
                        "paginaInicial" => "254"
                        "paginaFinal" => "263"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28380674"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer &#40;NSCLC&#41; using metformin during concurrent chemoradiotherapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;C&#46; Wink"
                            1 => "J&#46;S&#46; Belderbos"
                            2 => "E&#46;M&#46; Dieleman"
                            3 => "M&#46; Rossi"
                            4 => "C&#46;R&#46; Rasch"
                            5 => "R&#46;A&#46; Damhuis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.radonc.2016.01.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Radiother Oncol"
                        "fecha" => "2016"
                        "volumen" => "118"
                        "paginaInicial" => "453"
                        "paginaFinal" => "459"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26861738"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metformin use and its effect on survival in diabetic patients with advanced non-small cell lung cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "O&#46; Arrieta"
                            1 => "E&#46; Varela-Santoyo"
                            2 => "E&#46; Soto-Perez-De-Celis"
                            3 => "R&#46; S&#225;nchez-Reyes"
                            4 => "M&#46; De la Torre-Vallejo"
                            5 => "S&#46; Mu&#241;iz-Hern&#225;ndez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12885-016-2658-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "BMC Cancer"
                        "fecha" => "2016"
                        "volumen" => "16"
                        "paginaInicial" => "633"
                        "paginaFinal" => "641"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27519177"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metformin use and survival from lung cancer&#58; a population-based cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Menamin &#218;&#46;C&#46;"
                            1 => "C&#46;R&#46; Cardwell"
                            2 => "C&#46;M&#46; Hughes"
                            3 => "L&#46;M&#46; Murray"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.lungcan.2016.01.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lung Cancer"
                        "fecha" => "2016"
                        "volumen" => "94"
                        "paginaInicial" => "35"
                        "paginaFinal" => "39"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26973204"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of metformin use on survival in locally-advanced&#44; inoperable non-small cell lung cancer treated with definitive chemoradiation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Ahmed"
                            1 => "A&#46; Ferro"
                            2 => "A&#46; Cohler"
                            3 => "J&#46; Langenfeld"
                            4 => "S&#46;G&#46; Surakanti"
                            5 => "J&#46; Aisner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3978/j.issn.2072-1439.2014.12.32"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Thorac Dis"
                        "fecha" => "2015"
                        "volumen" => "7"
                        "paginaInicial" => "346"
                        "paginaFinal" => "355"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25922712"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metformin use improves the survival of diabetic combined small-cell lung cancer patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Kong"
                            1 => "F&#46; Gao"
                            2 => "H&#46; Liu"
                            3 => "L&#46; Chen"
                            4 => "R&#46; Zheng"
                            5 => "J&#46; Yu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Tumor Biol"
                        "fecha" => "2015"
                        "volumen" => "36"
                        "paginaInicial" => "8101"
                        "paginaFinal" => "8106"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognosis of small cell lung cancer patients with diabetes treated with metformin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "T&#46; Xu"
                            1 => "G&#46; Liang"
                            2 => "L&#46; Yang"
                            3 => "F&#46; Zhang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12094-015-1311-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Transl Oncol"
                        "fecha" => "2015"
                        "volumen" => "17"
                        "paginaInicial" => "819"
                        "paginaFinal" => "824"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26063645"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Survival of patients with stage IV lung cancer with diabetes treated with metformin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;J&#46; Lin"
                            1 => "E&#46;J&#46; Gallagher"
                            2 => "K&#46; Sigel"
                            3 => "G&#46; Mhango"
                            4 => "M&#46;D&#46; Galsky"
                            5 => "C&#46;B&#46; Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201407-1395OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2015"
                        "volumen" => "191"
                        "paginaInicial" => "448"
                        "paginaFinal" => "454"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25522257"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Validating drug repurposing signals using electronic health records&#58; a case study of metformin associated with reduced cancer mortality"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Xu"
                            1 => "M&#46;C&#46; Aldrich"
                            2 => "Q&#46; Chen"
                            3 => "H&#46; Liu"
                            4 => "N&#46;B&#46; Peterson"
                            5 => "Q&#46; Dai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/amiajnl-2014-002649"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Med Inform Assoc"
                        "fecha" => "2015"
                        "volumen" => "22"
                        "paginaInicial" => "179"
                        "paginaFinal" => "191"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25053577"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of metformin and thiazolidinedione use on lung cancer in diabetics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P&#46;J&#46; Mazzone"
                            1 => "H&#46; Rai"
                            2 => "M&#46; Beukemann"
                            3 => "M&#46; Xu"
                            4 => "A&#46; Jain"
                            5 => "M&#46; Sasidhar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2407-12-410"
                      "Revista" => array:6 [
                        "tituloSerie" => "BMC Cancer"
                        "fecha" => "2012"
                        "volumen" => "12"
                        "paginaInicial" => "410"
                        "paginaFinal" => "416"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22978440"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PRISMA Group&#46; Preferred reporting items for systematic reviews and meta-analyses&#58; The PRISMA statement"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46; Moher"
                            1 => "A&#46; Liberati"
                            2 => "J&#46; Tetzlaff"
                            3 => "D&#46;G&#46; Altman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Surg"
                        "fecha" => "2010"
                        "volumen" => "6"
                        "paginaInicial" => "336"
                        "paginaFinal" => "341"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Smoking and risk for diabetes incidence and mortality in Korean men and women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46;H&#46; Jee"
                            1 => "A&#46;W&#46; Foong"
                            2 => "N&#46;W&#46; Hur"
                            3 => "J&#46;M&#46; Samet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2337/dc10-0261"
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes Care"
                        "fecha" => "2010"
                        "volumen" => "33"
                        "paginaInicial" => "2567"
                        "paginaFinal" => "2572"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20823342"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D status and the risk of lung cancer&#58; a cohort study in Finland"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Kilkkinen"
                            1 => "P&#46; Knekt"
                            2 => "M&#46; Heliovaara"
                            3 => "H&#46; Rissanen"
                            4 => "J&#46; Marniemi"
                            5 => "T&#46; Hakulinen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Cancer Epidemiol Biomark Prev"
                        "fecha" => "2008"
                        "volumen" => "17"
                        "paginaInicial" => "3274"
                        "paginaFinal" => "3278"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low vitamin D levels increase the risk of type 2 diabetes in older adults&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Lucato"
                            1 => "M&#46; Solmi"
                            2 => "S&#46; Maggi"
                            3 => "A&#46; Bertocco"
                            4 => "G&#46; Bano"
                            5 => "C&#46; Trevisan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.maturitas.2017.02.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Maturitas"
                        "fecha" => "2017"
                        "volumen" => "100"
                        "paginaInicial" => "8"
                        "paginaFinal" => "15"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28539181"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "On the origin of cancer cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "O&#46; Warburg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "1956"
                        "volumen" => "123"
                        "paginaInicial" => "309"
                        "paginaFinal" => "314"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13298683"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glucose-induced beta-catenin acetylation enhances Wnt signaling in cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46; Chocarro-Calvo"
                            1 => "J&#46;M&#46; Garcia-Martinez"
                            2 => "S&#46; Ardila-Gonzalez"
                            3 => "A&#46; De la Vieja"
                            4 => "C&#46; Garc&#237;a-Jim&#233;nez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.molcel.2012.11.022"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Cell"
                        "fecha" => "2013"
                        "volumen" => "49"
                        "paginaInicial" => "474"
                        "paginaFinal" => "486"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23273980"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "AMPK&#44; the metabolic syndrome and cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Z&#46; Luo"
                            1 => "A&#46;K&#46; Saha"
                            2 => "X&#46; Xiang"
                            3 => "N&#46;B&#46; Ruderman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.tips.2004.12.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Trends Pharmacol Sci"
                        "fecha" => "2005"
                        "volumen" => "26"
                        "paginaInicial" => "69"
                        "paginaFinal" => "76"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15681023"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Musi"
                            1 => "M&#46;F&#46; Hirshman"
                            2 => "J&#46; Nygren"
                            3 => "M&#46; Svanfeldt"
                            4 => "P&#46; Bavenholm"
                            5 => "O&#46; Rooyackers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes"
                        "fecha" => "2002"
                        "volumen" => "51"
                        "paginaInicial" => "2074"
                        "paginaFinal" => "2081"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12086935"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46;A&#46; Hawley"
                            1 => "A&#46;E&#46; Gadalla"
                            2 => "G&#46;S&#46; Olsen"
                            3 => "D&#46;G&#46; Hardie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes"
                        "fecha" => "2002"
                        "volumen" => "51"
                        "paginaInicial" => "2420"
                        "paginaFinal" => "2425"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12145153"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46;G&#46; Fryer"
                            1 => "A&#46; Parbu-Patel"
                            2 => "D&#46; Carling"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.M202489200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2002"
                        "volumen" => "277"
                        "paginaInicial" => "25226"
                        "paginaFinal" => "25232"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11994296"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metformin prevents tobacco carcinogen-induced lung tumorigenesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46;M&#46; Memmott"
                            1 => "J&#46;R&#46; Mercado"
                            2 => "C&#46;R&#46; Maier"
                            3 => "S&#46; Kawabata"
                            4 => "S&#46;D&#46; Fox"
                            5 => "P&#46;A&#46; Dennis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Cancer Prev Res"
                        "fecha" => "2010"
                        "volumen" => "3"
                        "paginaInicial" => "1066"
                        "paginaFinal" => "1076"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack402464"
        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0125" class="elsevierStylePara elsevierViewall">The study was supported by grants from the <span class="elsevierStyleGrantSponsor" id="gs1">National Natural Science Funds of China</span> &#40;No&#46; <span class="elsevierStyleGrantNumber" refid="gs1">81260336</span>&#41;&#44; <span class="elsevierStyleGrantSponsor" id="gs2">Jiangxi Provincial Natural Science Foundation of China Science</span> &#40;No&#46; <span class="elsevierStyleGrantNumber" refid="gs2">20132BAB205017</span>&#41;&#44; and <span class="elsevierStyleGrantSponsor" id="gs3">Jiangxi Provincial Science and Technology Project of China</span> &#40;No&#46; <span class="elsevierStyleGrantNumber" refid="gs3">20121BBG70045</span>&#41;&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/23870206/0000015200000008/v1_201904100623/S2387020619301093/v1_201904100623/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "43310"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015200000008/v1_201904100623/S2387020619301093/v1_201904100623/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619301093?idApp=UINPBA00004N"
]
Article information
ISSN: 23870206
Original language: English
The statistics are updated each day
Year/Month Html Pdf Total
2024 September 2 0 2
2024 July 2 0 2
2024 June 4 0 4
2024 May 1 0 1
2024 April 1 0 1
2024 March 1 0 1
2024 January 2 0 2
2023 December 5 0 5
2023 November 4 0 4
2023 October 3 0 3
2023 September 3 0 3
2023 August 2 0 2
2023 July 2 0 2
2023 June 2 0 2
2023 May 3 0 3
2023 March 2 0 2
2023 January 3 0 3
2022 December 1 0 1
2022 November 3 0 3
2022 October 3 0 3
2022 September 6 2 8
2022 August 3 0 3
2022 July 2 0 2
2022 June 1 0 1
2022 May 2 0 2
2022 April 3 0 3
2022 March 2 0 2
Show all

Follow this link to access the full text of the article

es en pt

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

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

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos