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Association of Psoriasis and Metabolic Syndrome in Latin America: A Systematic Review and Meta-Analysis
Relación entre psoriasis y síndrome metabólico en Latinoamérica. Revisión sistemática y metaanálisis
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Rodríguez-Zúñiga, F. Cortez-Franco, E. Quijano-Gomero" "autores" => array:3 [ 0 => array:4 [ "nombre" => "M.J.M." "apellidos" => "Rodríguez-Zúñiga" "email" => array:2 [ 0 => "milton_rz@hotmail.com" 1 => "mijomax@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "F." "apellidos" => "Cortez-Franco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "E." "apellidos" => "Quijano-Gomero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Nacional Daniel Alcides Carrión, Callao, Peru" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universidad Nacional Mayor de San Marcos, Lima, Peru" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Relación entre psoriasis y síndrome metabólico en Latinoamérica. Revisión sistemática y metaanálisis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1488 "Ancho" => 2734 "Tamanyo" => 314465 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Forest plots of the prevalence of metabolic syndrome in subgroups of patients with psoriasis formed according to patient characteristics. A Mantel-Haenszel (M-H) fixed-effect method was used to calculate the ORs and 95%<span class="elsevierStyleHsp" style=""></span>CIs. Pso refers to psoriasis at any level of severity or point in diagnosis; OR, odds ratio.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The chronic inflammatory skin disease psoriasis has a prevalence around 2% in Western countries<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">1</span></a> and is recognized to be the most common immunologic disorder. The prevalence is 2.5% in Peru.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">2</span></a> Severity ranges from mild forms affecting small areas of the body to serious disease causing lesions extending over large areas and greatly affecting patients’ quality of life.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Various cardiovascular risk factors have been associated with psoriasis in recent years, attributable to chronic systemic inflammation that leads to atherosclerosis and finally cardiovascular disease.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">4</span></a> Metabolic syndrome, which doubles the risk of coronary disease, offers a way to assess a patient for cardiovascular disease.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">5</span></a> This syndrome involves a constellation of conditions (obesity, dyslipidemia, diabetes mellitus, and hypertension) that have a greater effect on cardiovascular disease when they occur together than when they develop in isolation. About 25% of Latin Americans (17% in Peru) have metabolic syndrome 17%.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">6</span></a> Insulin resistance and abnormal functioning of adipose tissue are thought to be the underlying mechanism.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Recent meta-analyses have found that patients with psoriasis are at risk for metabolic syndrome, with odds ratios (ORs) between 1.84 and 2.26<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">8</span></a>) and that severe psoriasis puts patients at greater risk (OR, 1.98; 95%<span class="elsevierStyleHsp" style=""></span>CI, 1.62–2.43) than mild forms of the disease (OR, 1.22; 95%<span class="elsevierStyleHsp" style=""></span>CI, 1.11–1.35).<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">9</span></a> The analyzed studies have not included Latin American populations, however.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The prevalence of metabolic syndrome in patients with psoriasis in Latin America ranges from 40% in Mexico<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">10</span></a> to 70% in Honduras.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">11</span></a> In Peru the prevalence is 46%.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">12</span></a> Few original studies have addressed this question in this part of the world, however.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Consequently, although current recommendations suggest we screen for metabolic syndrome in patients with psoriasis, the strength of association between the 2 conditions has not been studied systematically in Latin America.</p><p id="par0030" class="elsevierStylePara elsevierViewall">We undertook a meta-analysis with the main objective of assessing our current understanding the association between metabolic syndrome and psoriasis in Latin American patients.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">We followed the MOOSE reporting guidelines (for Meta-analysis of Observational Studies in Epidemiology)<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">13</span></a> to design a systematic review of the literature. Included in the search were observational studies of various types: retrospective and prospective, cross-sectional, and case–control or cohort designs. We sought studies published between January 1980 and January 2016. Included studies had to assess the association between psoriasis and metabolic syndrome diagnosed by physical examination following predefined criteria or by a review of medical records. Studies also had to have 2 arms (psoriasis patients and controls) and report the incidence or prevalence of metabolic syndrome in each arm. Articles could be published in either English or Spanish.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Population characteristics were men or women aged 18 years or older who were native to any Latin American country and who had been diagnosed with psoriasis based on specific criteria. We excluded studies for which full datasets were unavailable even if we made the effort to contact authors.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The literature search was carried out in MEDLINE, Scopus, SciELO, Google Scholar, Science Direct, LILACS and the virtual libraries of universities. The following search terms were used: ([psoriasis] or [vulgar psoriasis]) and ([metabolic syndrome] or [metabolic syndrome <span class="elsevierStyleSmallCaps">X</span>]) and ([insulin resistance syndrome <span class="elsevierStyleSmallCaps">X</span>] <span class="elsevierStyleSmallCaps">or</span> [<span class="elsevierStyleSmallCaps">syndrome</span><span class="elsevierStyleSmallCaps">X</span>, metabolic] or [metabolic <span class="elsevierStyleSmallCaps">X</span> syndrome]). The search string was adapted to the syntax of each database. The initial search yielded 1493 titles. After eliminating studies not done in Latin American populations, we were left with 75 articles. Eight additional studies were identified by checking the references lists of the 75 indexed studies and from other sources of information. Two authors (M.R. and F.C.) screened the titles and abstracts of the 83 candidate studies to determine whether they seemed to meet the inclusion criteria. Ten were initially chosen but after careful review, 5 of them were excluded because 2 had no control group, 2 studied individual components of metabolic syndrome, and 1 used a population already included in another study. Thus, 5 articles met the inclusion criteria for systematic review and meta-analysis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). If the screening authors did not agree on whether to include or exclude an article, the third author (E.Q.) was consulted to resolve the disagreement.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The following data were gathered into a model spreadsheet in MS Excel for analysis: year of publication, country where the patients lived, design, number of participants in each group, mean age, prevalence of metabolic syndrome in each group, and adjustment for covariates. Authors M.R. and F.C. checked data twice for accuracy; discrepancies were resolved in consultation with E.Q.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Metabolic syndrome was defined in accordance with specific criteria. According to the Third Report of the National Cholesterol Education Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (the Adult Treatment Panel III [ATP-III]),<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">14</span></a> metabolic syndrome is defined by the presence of 3 out of 5 of the following factors: 1) high blood pressure of at least 130/85<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>Hg (or on antihypertensive medication), 2) high fasting blood sugar level of 100<span class="elsevierStyleHsp" style=""></span>mg/dL or higher (or on medication to lower sugar levels), 3) triglyceride level of 150<span class="elsevierStyleHsp" style=""></span>mg/dL or higher (or on medication to lower the level), 4) a high-density lipoprotein level of 40<span class="elsevierStyleHsp" style=""></span>mg/dL or less in men or 50<span class="elsevierStyleHsp" style=""></span>mg/dL or less in women (or on therapy to raise that level), and 5) waist circumference of 102<span class="elsevierStyleHsp" style=""></span>cm or more in men or 88<span class="elsevierStyleHsp" style=""></span>cm or more in women.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Similar criteria were proposed by the International Diabetes Federation (IDF),<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">15</span></a> but they named obesity as a necessary condition, defined by a body mass index greater than 30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> and specifying waist measurements for different ethnic groups. Although measurements for a Latin American population were not given, the IDF advised using those for a South Asian population (waist circumference of 90<span class="elsevierStyleHsp" style=""></span>cm in men and 80<span class="elsevierStyleHsp" style=""></span>cm in women.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The main outcome measure was the association between psoriasis and metabolic syndrome, reflected by an OR and 95% CI. We also calculated pooled ORs and 95% CIs by means of a random effects model. Significance was set at <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.05. Results for subgroups formed according to patient characteristics and criteria used to define metabolic syndrome were also analyzed. Heterogeneity between studies was measured with the <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> statistic. A value for <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> greater than 50% indicated heterogeneity.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">16</span></a> Descriptive statistics (percentages and means) were tabulated for the included studies; they were analyzed and figures created with the Stata13 program and Review Manager Version 5.1</p><p id="par0070" class="elsevierStylePara elsevierViewall">The quality of studies was evaluated with a modified version of the Cochrane risk of bias tool for observational studies. The tool lists 6 traits to score as 0 (absent) or 1 (present). A total score of 3 or less indicated low quality and a score of 4 or 5 indicated high quality, as described elsewhere.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">17</span></a> These scores were used in the subgroup analysis.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Publication bias was measured by constructing funnel plots. A symmetric, inverted funnel indicated a high probability that no publication bias was present.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Finally, sensitivity was assessed by removing a study to test its effect on the pooled OR. Similarity between pooled ORs with and without the article removed would indicate a high degree of certainty of results.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0085" class="elsevierStylePara elsevierViewall">We included 5 trials from 3 Latin American countries (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The trials analyzed 545 patients (241 with psoriasis and 304 controls). The meta-analyzed sample included 159 patients who had a recent diagnosis of psoriasis or who had not received systemic treatment (vs 218 controls); 82 patients with chronic psoriasis or who were on a systemic treatment were also included (vs 86 controls). All the trials were prospective case–control studies The ATP-III criteria for metabolic syndrome were applied in 2 of the studies,<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">10,12</span></a> and the IDF diagnostic criteria were applied in the others<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">18–20</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Metabolic syndrome was diagnosed in 46.5% in the psoriasis arm and in 24.7% of the controls (pooled OR, 2.63; 95%<span class="elsevierStyleHsp" style=""></span>CI, 1.11–6.23; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.03; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>78%) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">The funnel plots revealed asymmetry along the mean, suggesting high likelihood of publication bias (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">The subgroup analysis showed that the association between metabolic syndrome and psoriasis was stronger in the studies that used the ATP-III criteria (pooled OR, 3.97; 95%<span class="elsevierStyleHsp" style=""></span>CI, 1.27–12.42) than in those that used the IDF criteria (pooled OR, 2.75; 95%<span class="elsevierStyleHsp" style=""></span>CI, 0.50–15.27). Likewise, studies that included patients recently diagnosed with psoriasis, or not yet prescribed systemic treatment (psoriasis de novo subgroup), detected a significantly lower risk of metabolic syndrome (pooled OR, 1.50; 95%<span class="elsevierStyleHsp" style=""></span>CI, 0.52–4.30) than those with only patients with chronic disease or treated with systemic drugs (psoriasis-in-treatment subgroup) (pooled OR, 6.65; 95%<span class="elsevierStyleHsp" style=""></span>CI: 3.32–13.31) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Finally, analysis by quality of research design showed that risk of metabolic syndrome in psoriasis patients was higher in high-quality studies (pooled OR, 3.48; 95%<span class="elsevierStyleHsp" style=""></span>CI, 2.22–5.45) than in low-quality studies (pooled OR, 1.44; 95%<span class="elsevierStyleHsp" style=""></span>CI, 0.75–2.77). <a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a> shows the results of an analysis of risk of bias in these studies.</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Analysis of sensitivity (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>) showed that the results for effect direction and size were not significantly affected by removing any study's data from the meta-analysis, suggesting the overall findings are robust.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Association Between Metabolic Syndrome and Psoriasis</span><p id="par0115" class="elsevierStylePara elsevierViewall">This meta-analysis is the first to include data for 241 Latin American patients with psoriasis, who were compared to 304 control patients to explore the relationship between metabolic syndrome and psoriasis in this region. We found that patients with psoriasis have a 3-fold higher risk for metabolic syndrome, which was present in 47% of these patients versus 25% of the controls (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). This level of risk is greater than that reported by Armstrong et al.,<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">9</span></a> who found a pooled OR of 2.26 (95%<span class="elsevierStyleHsp" style=""></span>CI, 1.70–3.01; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>86%), or by Miller et al.,<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">8</span></a> who calculated a pooled OR of 1.84 (95%<span class="elsevierStyleHsp" style=""></span>CI, 1.2–2.8; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">75</span>%).</p><p id="par0120" class="elsevierStylePara elsevierViewall">It is important to bear in mind that the rate of metabolic syndrome in Latin America is high (around 25%; range, 18.8% to 43.3%<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">23</span></a>) because of the rising prevalence of obesity and diabetes mellitus in a region whose nutritional situation is in transition.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">24</span></a> The control population in our analysis, which consisted mainly of patients hospitalized in large cities, had a metabolic syndrome prevalence of 24.7%. That figure is consistent with other Latin American statistics, supporting the validity of our data.</p><p id="par0125" class="elsevierStylePara elsevierViewall">These results show that metabolic syndrome is even more common among Latin Americans with psoriasis than in European cohorts, where the pooled OR in a meta-analysis of 5 observational studies was 2.36 (95%<span class="elsevierStyleHsp" style=""></span>CI, 1.53–3.67).<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">9</span></a> Early screening for this syndrome is therefore key to preventing cardiovascular complications, particularly in Latin America.</p><p id="par0130" class="elsevierStylePara elsevierViewall">The heterogeneity analysis showed a high degree of variability between studies (<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>78%) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Differences in age ranges and gender distributions in the studies and the failure to calculate adjusted ORs controlling for those variables account for the variability. In addition, the studies enrolled patients with different levels of psoriasis severity and used different diagnostic criteria for metabolic syndrome. One study reported findings that countered the trend. The results of our meta-analysis, therefore, should be interpreted cautiously. In fact, however, previous meta-analyses on this topic have met with similar limitations.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Nonetheless, our sensitivity analysis supports the robustness of our results, given that none of the exclusions we explored changed the original findings significantly (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). One study, however, found evidence that contradicted the general trend.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">20</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Finally, we detected a high risk of publication bias, demonstrated by asymmetry in the funnel plots (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Biological Basis for the Association Between Metabolic Syndrome and Psoriasis</span><p id="par0145" class="elsevierStylePara elsevierViewall">Various biological mechanisms account for the association between metabolic syndrome and psoriasis.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">25</span></a> The activation of T cells in psoriasis leads to the release of proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin 2, and interferon gamma.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">26</span></a> These in turn induce the release of more cytokines and the expression of adhesion molecules, nitric oxide synthase, interleukin 6, and angiotensin II.<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">27,28</span></a> TNF also mediates insulin resistance by favoring the release of free fatty acids, inhibiting the tyrosine kinase activity of the insulin receptor, and also modulating adipogenesis by suppressing adiponectin secretion from adipocytes<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">29</span></a> while increasing leptin secretion.<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">30,31</span></a> In this process, insulin-like growth factor II levels increase, promoting atherosclerosis, epidermal proliferation, hyperlipidemia, and diabetes mellitus.<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">32</span></a> In addition, TNF leads to endothelial damage by promoting increased expression of adhesion molecules and atheromatous plaque formation. Plasminogen activator inhibitor 1 levels also rise, favoring thrombosis.<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">33</span></a> Adipose tissue, a key participant in obesity disorders and metabolic syndrome, liberates multiple proinflammatory cytokines<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">24</span></a> that are responsible for insulin resistance and endothelial dysfunction, similar to the process in psoriasis. Thus, the components of chronic inflammation, angiogenesis, and epidermal proliferation associated with psoriasis favor diabetes mellitus, thrombosis, and atherosclerosis alike.<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">34</span></a> The proinflammatory state that develops in obesity, diabetes mellitus, and atherosclerosis increases susceptibility to psoriasis or exacerbates its severity.<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">35,36</span></a> In addition, the elevated plasma renin and angiotensin converting enzyme activity<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">37</span></a> of patients with psoriasis is implicated in the pathogenesis of hypertension in metabolic syndrome along with the presence of angiotensinogen, resistin, and leptin secretion by adipose tissue.<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">38</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Part of the hereditary aspect of the association between metabolic syndrome and psoriasis would derive from the fact that both psoriasis and diabetes mellitus share the cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like gene locus<span class="elsevierStyleItalic">.</span><a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">39</span></a> Psoriasis susceptibility genes (<span class="elsevierStyleItalic">PSORS 2, PSORS 3</span>, and <span class="elsevierStyleItalic">PSORS 4</span>) are also associated with greater susceptibility to metabolic syndrome, diabetes mellitus, dyslipidemia, and cardiovascular disease.<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">40</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Analysis According to Diagnostic Criteria for Metabolic Syndrome</span><p id="par0155" class="elsevierStylePara elsevierViewall">We found that the studies that used the ATP-III criteria reported stronger associations between metabolic syndrome and psoriasis than studies using the IDF criteria. However, the study by Vásquez-Bayas 2014<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">20</span></a> clearly had a strong influence on those results, as their data went counter to the general trend and could potentially confound interpretation. After removing that study from the meta-analysis, the pooled OR for the other studies that used the IDF diagnostic criteria was much higher (6.65; 95%<span class="elsevierStyleHsp" style=""></span>CI, 3.32–13.31) than the studies using the ATP-III criteria (pooled OR, 3.97; 95%<span class="elsevierStyleHsp" style=""></span>CI, 1.27–21.42). Both ORs were statistically significant (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>).</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0160" class="elsevierStylePara elsevierViewall">For a diagnosis of metabolic syndrome, the IDF criteria require the presence of obesity (defined by a waist circumference of at least 90<span class="elsevierStyleHsp" style=""></span>cm in men and 80<span class="elsevierStyleHsp" style=""></span>cm in women). The obesity criterion is optional in the ATP-III criteria, on the other hand, and is defined by a waist circumference of at least 102<span class="elsevierStyleHsp" style=""></span>cm in men and 88<span class="elsevierStyleHsp" style=""></span>cm in women.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Thus, the IDF criteria<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">21</span></a> stipulate lower obesity thresholds than the ATP-III criteria and, although obesity is a required factor, the IDF criteria can be expected to classify more patients as having metabolic syndrome.<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">41</span></a> We therefore suggest that future studies on the association between metabolic syndrome and psoriasis should apply the ATP-III criteria, given consensus among some authors that these offer the most useful tool for assessing vascular damage and cardiovascular events in nondiabetic persons.<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">42</span></a> Moreover, they define specific criteria for Latin American populations.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Psoriasis Severity and Metabolic Syndrome</span><p id="par0170" class="elsevierStylePara elsevierViewall">Patients with psoriasis who were not on systemic treatments or recently diagnosed were at lower risk for metabolic syndrome than patients with chronic psoriasis who were on systemic drugs (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>). It is therefore reasonable to conclude that studies in chronic patients with severe disease found they were at greater risk for metabolic syndrome compared to recently diagnosed patients whose disease was mild.</p><p id="par0175" class="elsevierStylePara elsevierViewall">Several studies have found that psoriasis severity bears a directly proportional association with metabolic syndrome.<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">43–45</span></a> Armstrong et al.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">9</span></a> found a dose–response relationship in a meta-analysis that calculated pooled ORs of 1.22, 1.56, and 1.98 for mild, moderate, and severe psoriasis, respectively.</p><p id="par0180" class="elsevierStylePara elsevierViewall">The basis for this observation can be found in a recent report that patients with severe psoriasis have higher expression of inflammatory markers such as p-selectin and platelet-derived microparticles.<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">46</span></a> Microparticles have been said to contribute to accelerated atherogenesis in psoriasis.<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">47</span></a> Cell membrane vesicles contain nucleic acids and inflammatory mediators such as interleukin 1, CD40, and intercellular adhesion molecule 1 that are released after cell activation or apoptosis and contribute to vascular inflammation, thrombosis, and angiogenesis.<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">48</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Limitations</span><p id="par0185" class="elsevierStylePara elsevierViewall">The limitations of this meta-analysis derive from the scarcity of published studies and the inconsistency of design and reporting in those that are available. A large proportion of publications on the association between metabolic syndrome and psoriasis in Latin America are descriptive, making meta-analysis of data impossible. This problem of few qualitative studies reporting only descriptive statistics has been encountered in previous meta-analyses. We were able to include 5 studies from 3 Latin American countries. Although they are not representative of the entire geographic area of interest, the sample does allow us to extrapolate to obtain important information that warns of high rates of metabolic syndrome in our psoriasis patients.</p><p id="par0190" class="elsevierStylePara elsevierViewall">The studies we included also differed in the diagnostic and inclusion criteria they applied, and they generally failed to report ORs adjusted for demographic variables such as age and sex. It is necessary to improve future studies by unifying design and analysis.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusions</span><p id="par0195" class="elsevierStylePara elsevierViewall">This systematic review and meta-analysis shows that risk for metabolic syndrome is nearly 3-fold higher in Latin American patients with psoriasis than in the general population. Furthermore, the risk is higher for patients with severe or chronic psoriatic disease. Finally, we advise using the ATP-III criteria in future studies on this subject.</p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Clinical Application</span><p id="par0200" class="elsevierStylePara elsevierViewall">Our findings stress the importance of screening psoriasis patients for metabolic syndrome and forming multidisciplinary treatment teams, particularly in Latin America. Patients should be enrolled in programs to detect cardiovascular risk factors; control weight, diet, and lifestyle; and treat obesity, diabetes mellitus, hypertension and dyslipidemia early. Clear clinical improvement of psoriasis after weight reduction through dieting and other means and specific adjuvant treatments has been demonstrated.<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">49</span></a> Patients should be encouraged to adopt a healthy diet and engage in regular physical exercise.</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Implications for Research</span><p id="par0205" class="elsevierStylePara elsevierViewall">New studies are still needed to help us understand the strength of the association between psoriasis and metabolic syndrome in Latin America as well as to clarify the relation to cardiovascular events. Future studies applying better prospective designs and unified criteria are therefore planned. Furthermore, we propose wider use of the ATP-III diagnostic criteria for metabolic syndrome in the interest of greater consistency of results and because those criteria, which are specifically applicable to Latin American ethnic groups, are better able to predict cardiovascular risk.</p></span></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ethical Disclosures</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Protection of human and animal subjects</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Data confidentiality</span><p id="par0215" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data are disclosed in this article.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Right to privacy and informed consent</span><p id="par0220" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data are disclosed in this article.</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of Interest</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres834147" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methodology" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec830179" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres834148" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Metodología" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec830180" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Discussion" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Association Between Metabolic Syndrome and Psoriasis" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Biological Basis for the Association Between Metabolic Syndrome and Psoriasis" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Analysis According to Diagnostic Criteria for Metabolic Syndrome" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Psoriasis Severity and Metabolic Syndrome" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Limitations" ] ] ] 8 => array:3 [ "identificador" => "sec0050" "titulo" => "Conclusions" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0055" "titulo" => "Clinical Application" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Implications for Research" ] ] ] ] ] 9 => array:3 [ "identificador" => "sec0065" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflicts of Interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-07-16" "fechaAceptado" => "2016-11-06" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec830179" "palabras" => array:4 [ 0 => "Psoriasis" 1 => "Metabolic syndrome" 2 => "Meta-analysis" 3 => "Latin America" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec830180" "palabras" => array:4 [ 0 => "Psoriasis" 1 => "Síndrome metabólico" 2 => "Metaanálisis" 3 => "Latinoamérica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Meta-analyses have found evidence of a relationship between psoriasis and metabolic syndrome, but Latin American populations have not been included.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methodology</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We performed a systematic review and meta-analysis of observational studies including adults with psoriasis and metabolic syndrome indexed in Medline, Scopus, SciELO, Google Scholar, Science Direct, and LILACS between 1980 and 2016. We computed pooled odds ratios (OR) with a random effects model and analyzed subgroups according to patient variables used in the studies.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Five studies with a total of 241 patients with psoriasis were found; 46.5% of the patients also had metabolic syndrome (pooled OR, 2.63; 95% CI: 1.11-6.23; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.03). In studies using the Adult Treatment Panel <span class="elsevierStyleSmallCaps">III</span> (ATP-<span class="elsevierStyleSmallCaps">III</span>) criteria for metabolic syndrome, the pooled OR was similar at 3.97 (95% CI: 1.27-21.42). Studies that included patients with chronic and severe disease detected higher risk for metabolic syndrome (pooled OR, 6.65; 95% CI: 3.32-13.31). Limitations are that few studies have been done in Latin America, heterogeneity was high, and inconsistency was found across studies.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The association between psoriasis and metabolic syndrome is high in Latin America. The association is stronger when psoriasis is chronic and severe and when the ATP-<span class="elsevierStyleSmallCaps">III</span> criteria are used for diagnosis.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methodology" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Diversos estudios de metaanálisis han demostrado la relación entre psoriasis y síndrome metabólico (SM), sin embargo, no incluyen población latina.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Metodología</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realizó una revisión sistemática y metaanálisis con trabajos observacionales incluidos en Medline, Scopus, SciELO, Google Scholar, Science Direct, LILACS, desde 1980 hasta 2016, sobre psoriasis y SM en adultos. Se halló el odds ratio combinado (ORC) con modelo de efectos aleatorios y se realizó un análisis por subgrupos según las variables de los estudios.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 5 trabajos, con 241 pacientes con psoriasis, y se encontró que el SM se presentó en el 46,5% del grupo de psoriasis, con un ORC de 2,63 (IC 95%: 1,11-6,23; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,03). Los estudios que utilizaron los criterios <span class="elsevierStyleItalic">Adult Treatment Panel III</span> (ATP-<span class="elsevierStyleSmallCaps">III</span>) tuvieron una relación similar (ORC 3,97; IC 95%: 1,27-21,42), mientras que los que incluyeron pacientes crónicos y con enfermedad grave tuvieron un mayor riesgo de SM (ORC 6,65; IC 95%: 3,32-13,31). Entre las limitaciones del estudio tenemos la escasez de trabajos analíticos, la alta heterogeneidad, y la inconsistencia entre las publicaciones.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Existe una alta asociación entre psoriasis y SM en pacientes latinos, con mayor relación con cronicidad y gravedad de la enfermedad, y mejor desempeño de los criterios ATP-<span class="elsevierStyleSmallCaps">III</span> para el diagnóstico de SM.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Metodología" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as: Rodríguez-Zúñiga MJM, Cortez-Franco F, Quijano-Gomero E. Relación entre psoriasis y síndrome metabólico en Latinoamérica. Revisión sistemática y metaanálisis. Actas Dermosifiliogr. 2017;108:326–334.</p>" ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2392 "Ancho" => 1630 "Tamanyo" => 158527 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow chart of the process of screening observational studies on the association between psoriasis and metabolic syndrome.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1164 "Ancho" => 2672 "Tamanyo" => 216089 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Forest plot of the prevalence of metabolic syndrome in psoriasis patients in the meta-analyzed observational studies. A Mantel-Haenszel (M-H) fixed-effect method was used to calculate the ORs and 95%<span class="elsevierStyleHsp" style=""></span>CIs. Pso refers to psoriasis at any level of severity or point in diagnosis; OR, odds ratio.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1208 "Ancho" => 1590 "Tamanyo" => 73520 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Funnel plot of the prevalence of metabolic syndrome in patients with psoriasis according to quality of study design used in the meta-analyzed studies. OR refers to odds ratio; SE, standard error.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1488 "Ancho" => 2734 "Tamanyo" => 314465 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Forest plots of the prevalence of metabolic syndrome in subgroups of patients with psoriasis formed according to patient characteristics. A Mantel-Haenszel (M-H) fixed-effect method was used to calculate the ORs and 95%<span class="elsevierStyleHsp" style=""></span>CIs. Pso refers to psoriasis at any level of severity or point in diagnosis; OR, odds ratio.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1719 "Ancho" => 1645 "Tamanyo" => 226434 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Assessment of risk of bias. A, Within studies. B, Between studies.</p>" ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1561 "Ancho" => 2742 "Tamanyo" => 325756 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Forest plot of the prevalences of metabolic syndrome in subgroups based on the diagnostic criteria (ATP-III or IDF) applied. The 2014 study by Vásquez-Bayas<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">20</span></a> was excluded from this analysis because its results ran counter to the trend. Pso refers to psoriasis at any level of severity or point in diagnosis; OR, odds ratio; NCEP-ATP III, Third Report of the National Cholesterol Education Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (the Adult Treatment Panel III)<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">22</span></a>; IDF, International Diabetes Federation.</p>" ] ] 6 => 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="spar0080" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: ATP-III, Third Report of the National Cholesterol Education Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (the Adult Treatment Panel III)<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">22</span></a>; C, controls; C–C, case–control; Dec, December; Feb, February; IDF, International Diabetes Federation; Jan, January; NR, not reported; Oct, October; OR, odds ratio; PASI, Psoriasis Area and Severity Index; Pso, psoriasis; Sept, September; ST, systemic treatment.</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-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Country \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Period \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Study Design \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Patient Type (Severity, Treatment) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Metabolic Syndrome Diagnostic Criteria \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Quality of Design \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Patients Studied</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Mean Age, y</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Metabolic Syndrome</th><th class="td" title="table-head " align="left" valign="top" scope="col">Pooled OR (95% CI)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">N \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">Pso, n (%) \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">C, n (%) \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">Pso \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">C \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">n (%) \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">Pso, n (%) \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">C, n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Berrú-Chamba,<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">19</span></a> 2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ecuador \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">July–Sept 2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C–C, prospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PASI ><span class="elsevierStyleHsp" style=""></span>0, all Pso patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IDF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Low \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 (47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 (53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 (58) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.5 (1.65–19.39) \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">Espinoza et al.,<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">10</span></a> 2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mexico \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Feb 2010–Feb 2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C–C, prospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PASI ><span class="elsevierStyleHsp" style=""></span>0, Pso de novo or no ST \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ATP-III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">209 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">103 (49) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">106 (51) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 (31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43 (42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.9 (1.50–5.67) \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">Mussallam et al.,<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">18</span></a> 2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Peru \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Jan–Dec 2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C–C, prospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PAS<span class="elsevierStyleSmallCaps">I</span> ><span class="elsevierStyleHsp" style=""></span>0, all Pso \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IDF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">102 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43 (42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 (65) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.5 (2.82–20.60) \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">Vásquez-Bayas,<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">20</span></a> 2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ecuador \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Oct–Dec 2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C–C, prospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PASI ><span class="elsevierStyleHsp" style=""></span>0, Pso de novo or no ST \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IDF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Low \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 (67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 (31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.49 (0.15–1.43) \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">Bartolo et al.,<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">12</span></a> 2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Peru \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Feb 2010–Jan 2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C–C, prospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PASI ><span class="elsevierStyleHsp" style=""></span>0, Pso de novo or no ST \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ATP-III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 (67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 (46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.05 (0.65–6.36) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1406691.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Only pooled ORs are listed in the column because only 1 study (Mussallam et al.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">18</span></a>) calculated an OR (7.5; 95%<span class="elsevierStyleHsp" style=""></span>CI, 3.1–18.5) adjusted for obesity, hypertension, diabetes mellitus, and dyslipidemia.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the Studies Included in the Meta-analysis and the Patients Enrolled.</p>" ] ] 7 => 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">Study Removed \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">Pooled OR (95%<span class="elsevierStyleHsp" style=""></span>CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span>, % \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \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">No removal (all studies) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.63 (1.11–6.23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.030 \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">Mussallam et al.,<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">18</span></a> 2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.02 (0.81–5.06) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.130 \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">Vásquez-Bayas,<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">20</span></a> 2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.84 (2.20–6.69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.000 \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">Berrú-Chamba,<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">19</span></a> 2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.22 (0.81–6.10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.120 \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">Espinoza et al., 2014<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">10</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.56 (0.75–8.73) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.130 \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">Bartolo et al.,<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">12</span></a> 2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.79 (0.95–8.17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.060 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1406690.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Analysis of Sensitivity of the Meta-analysis to Study Removals.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:49 [ 0 => array:3 [ "identificador" => "bib0250" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Psoriasis and the risk of major cardiovascular events: Cohort study using the clinical practice research datalink" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 20 | 15 | 35 |
| 2024 October | 105 | 45 | 150 |
| 2024 September | 87 | 39 | 126 |
| 2024 August | 101 | 83 | 184 |
| 2024 July | 99 | 37 | 136 |
| 2024 June | 92 | 37 | 129 |
| 2024 May | 74 | 42 | 116 |
| 2024 April | 120 | 44 | 164 |
| 2024 March | 95 | 37 | 132 |
| 2024 February | 76 | 35 | 111 |
| 2024 January | 51 | 31 | 82 |
| 2023 December | 50 | 20 | 70 |
| 2023 November | 140 | 33 | 173 |
| 2023 October | 71 | 16 | 87 |
| 2023 September | 55 | 26 | 81 |
| 2023 August | 47 | 28 | 75 |
| 2023 July | 72 | 32 | 104 |
| 2023 June | 55 | 32 | 87 |
| 2023 May | 68 | 35 | 103 |
| 2023 April | 57 | 33 | 90 |
| 2023 March | 94 | 34 | 128 |
| 2023 February | 73 | 19 | 92 |
| 2023 January | 54 | 35 | 89 |
| 2022 December | 67 | 31 | 98 |
| 2022 November | 55 | 28 | 83 |
| 2022 October | 50 | 26 | 76 |
| 2022 September | 36 | 46 | 82 |
| 2022 August | 34 | 40 | 74 |
| 2022 July | 28 | 53 | 81 |
| 2022 June | 21 | 33 | 54 |
| 2022 May | 42 | 27 | 69 |
| 2022 April | 62 | 63 | 125 |
| 2022 March | 61 | 59 | 120 |
| 2022 February | 37 | 34 | 71 |
| 2022 January | 78 | 50 | 128 |
| 2021 December | 69 | 38 | 107 |
| 2021 November | 77 | 33 | 110 |
| 2021 October | 67 | 80 | 147 |
| 2021 September | 48 | 48 | 96 |
| 2021 August | 49 | 43 | 92 |
| 2021 July | 38 | 25 | 63 |
| 2021 June | 39 | 31 | 70 |
| 2021 May | 43 | 41 | 84 |
| 2021 April | 88 | 83 | 171 |
| 2021 March | 58 | 29 | 87 |
| 2021 February | 38 | 11 | 49 |
| 2021 January | 35 | 20 | 55 |
| 2020 December | 45 | 18 | 63 |
| 2020 November | 37 | 22 | 59 |
| 2020 October | 41 | 12 | 53 |
| 2020 September | 45 | 9 | 54 |
| 2020 August | 26 | 11 | 37 |
| 2020 July | 29 | 13 | 42 |
| 2020 June | 39 | 27 | 66 |
| 2020 May | 23 | 9 | 32 |
| 2020 April | 21 | 21 | 42 |
| 2020 March | 26 | 13 | 39 |
| 2020 February | 3 | 0 | 3 |
| 2020 January | 1 | 0 | 1 |
| 2019 September | 1 | 0 | 1 |
| 2019 August | 3 | 0 | 3 |
| 2019 May | 0 | 1 | 1 |
| 2019 April | 4 | 3 | 7 |
| 2019 February | 3 | 0 | 3 |
| 2019 January | 2 | 0 | 2 |
| 2018 December | 2 | 0 | 2 |
| 2018 November | 11 | 0 | 11 |
| 2018 October | 14 | 0 | 14 |
| 2018 September | 6 | 0 | 6 |
| 2018 February | 27 | 6 | 33 |
| 2018 January | 40 | 7 | 47 |
| 2017 December | 45 | 10 | 55 |
| 2017 November | 46 | 12 | 58 |
| 2017 October | 28 | 11 | 39 |
| 2017 September | 33 | 16 | 49 |
| 2017 August | 41 | 18 | 59 |
| 2017 July | 23 | 15 | 38 |
| 2017 June | 57 | 15 | 72 |
| 2017 May | 77 | 47 | 124 |
| 2017 April | 15 | 33 | 48 |
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