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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A vitamina D &#40;Vit&#8208;D&#41; tem uma import&#226;ncia fundamental no organismo&#44; desde a estrutura &#243;ssea at&#233; a fun&#231;&#227;o cerebral&#44; e tamb&#233;m &#233; vital para a pele saud&#225;vel&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">1</span></a> Al&#233;m disso&#44; desempenha um papel de destaque no sistema imunol&#243;gico&#46; Sabe&#8208;se que a hipovitaminose D est&#225; associada a dist&#250;rbios do metabolismo do c&#225;lcio e dos carboidratos&#44; c&#226;ncer&#44; doen&#231;as cardiovasculares e v&#225;rias doen&#231;as autoimunes&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">2</span></a> O vitiligo &#233; uma doen&#231;a cut&#226;nea conhecida por ter etiologia metab&#243;lica&#44; citot&#243;xica&#44; inflamat&#243;ria e autoimune&#44; entre v&#225;rios outros fatores&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">3&#44;4</span></a> Foi relatado que a forma ativa da Vit&#8208;D&#44; 1&#44;25&#8208;di&#8208;hidroxivitamina D3 &#40;1&#44;25&#91;OH&#93;D&#41; est&#225; associada &#224; patog&#234;nese do vitiligo&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">1&#8211;3</span></a> Quando a epiderme &#233; afetada no vitiligo&#44; podem ser evidenciadas altera&#231;&#245;es nos n&#237;veis circulat&#243;rios de Vit&#8208;D&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Os estudos dispon&#237;veis na literatura s&#227;o inconsistentes quanto aos n&#237;veis de Vit&#8208;D&#44; e a hipovitaminose D ainda &#233; controversa no vitiligo&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">5&#8211;34</span></a> Nesta revis&#227;o sistem&#225;tica atualizada e metan&#225;lise sobre vitiligo e os n&#237;veis de Vit&#8208;D &#40;Estudo ViViD&#41;&#44; os n&#237;veis circulat&#243;rios de Vit&#8208;D e sua associa&#231;&#227;o com vari&#225;veis como idade&#44; dura&#231;&#227;o da doen&#231;a&#44; &#225;rea de superf&#237;cie corporal &#40;ASC&#41; afetada e o Vitiligo Activity and Severity Index &#40;VASI&#41; foram estudados em pacientes com vitiligo em compara&#231;&#227;o com controles&#46; Uma metan&#225;lise de subgrupo foi conduzida para estudar os n&#237;veis de Vit&#8208;D em rela&#231;&#227;o a sexo&#44; fototipo&#44; tipo de vitiligo&#44; atividade da doen&#231;a&#44; hist&#243;ria do vitiligo&#44; comorbidades autoimunes e tipo de trabalho interno&#8208;externo de pacientes com a doen&#231;a&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Material e m&#233;todos</span><p id="par0015" class="elsevierStylePara elsevierViewall">Os crit&#233;rios da lista de verifica&#231;&#227;o PRISMA &#40;Preferred Reporting Items for Systematic reviews and Meta&#8208;Analysis&#41; foram seguidos na condu&#231;&#227;o e no relato deste estudo&#46; O protocolo do estudo foi registrado na base PROSPERO sob o n&#250;mero de registro CRD42019142156 &#40;<a href="https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=142156">https&#58;&#47;&#47;www&#46;crd&#46;york&#46;ac&#46;uk&#47;PROSPERO&#47;display&#95;record&#46;php&#63;RecordID&#61;142156</a>&#41;&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Estrat&#233;gia de busca de literatura</span><p id="par0020" class="elsevierStylePara elsevierViewall">A pesquisa bibliogr&#225;fica foi realizada principalmente no banco de dados PubMed&#47;MEDLINE do NCBI&#44; usando as estrat&#233;gias de pesquisa de palavras&#8208;chave e MESH&#46; A seguinte linha de pesquisa foi desenvolvida&#58; &#40;&#8220;vitamin&#160;D&#8221; &#40;MeSH Terms&#41; OR &#8220;vitamin&#160;D&#8221; &#40;All Fields&#41; OR &#8220;ergocalciferols&#8221; &#40;MeSH Terms&#41; OR &#8220;ergocalciferols&#8221; &#40;All Fields&#41;&#41; AND &#40;&#8220;vitiligo&#8221; &#40;MeSH Terms&#41; OR &#8220;vitiligo&#8221; &#40;All Fields&#41;&#41;&#46; Os outros termos utilizados para Vit&#8208;D foram 25&#8208;Hydroxyvitamin D&#44; 25&#8208;Hydroxycholecalciferol&#44; calcidiol&#44; 1&#46;25&#8208;dihydroxyvitamin D3 e calcitriol&#46; Os bancos de dados do Google Scholar&#44; da Cochrane Library&#44; do Springer&#39;s author mapper&#44; o Science Direct&#44; os registros de ensaios cl&#237;nicos e CINHAL tamb&#233;m foram pesquisados em busca de artigos que relatassem n&#237;veis circulat&#243;rios de Vit&#8208;D em pacientes com vitiligo&#46; Al&#233;m disso&#44; as refer&#234;ncias dos artigos publicados foram pesquisadas manualmente para identificar estudos adicionais&#46; Dois autores realizaram a pesquisa bibliogr&#225;fica de maneira independente&#44; e quaisquer desacordos foram resolvidos ap&#243;s discuss&#227;o&#46; Foram feitos esfor&#231;os para obter dados&#44; se houvesse&#44; de fontes n&#227;o publicadas&#46; Quando necess&#225;rio&#44; os autores correspondentes dos respectivos artigos foram contatados por e&#8208;mail para obten&#231;&#227;o de dados&#47;esclarecimentos&#46; Todas as pesquisas bibliogr&#225;ficas foram realizadas antes de 5 de setembro de 2019&#44; sem intervalo de tempo especificado&#44; com e sem estudos com seres humanos definidos como limite&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Crit&#233;rios de sele&#231;&#227;o dos estudos</span><p id="par0025" class="elsevierStylePara elsevierViewall">Os seguintes crit&#233;rios foram preenchidos para estudos individuais a serem inclu&#237;dos nesta metan&#225;lise&#58; &#40;1&#41; artigos publicados em revistas revisadas por pares&#59; &#40;2&#41; que forneceram dados originais&#59; &#40;3&#41; os sujeitos do estudo eram seres humanos com descri&#231;&#227;o de vitiligo e controles&#59; &#40;4&#41; estudos em que os n&#237;veis circulat&#243;rios de Vit&#8208;D em pacientes com vitiligo foram comparados com os controles&#59; &#40;5&#41; que forneceram descri&#231;&#227;o do m&#233;todo para estimativa dos n&#237;veis de Vit&#8208;D&#59; &#40;6&#41; artigos escritos em ingl&#234;s&#47;chin&#234;s com dados claros&#59; &#40;7&#41; estudos com diagn&#243;stico cl&#237;nico de vitiligo feito por dermatologista&#46; Os crit&#233;rios de exclus&#227;o foram os seguintes&#58; &#40;1&#41; estudos sem grupo controle&#59; &#40;2&#41; relato de outras doen&#231;as de pele&#59; &#40;3&#41; os n&#237;veis de Vit&#8208;D foram mostrados apenas por pictogramas sem dados&#59; &#40;4&#41; artigos de revis&#227;o&#44; coment&#225;rios e cartas ao editor&#46; Quando algum artigo duplicado era encontrado&#44; apenas um relato recente ou todas as informa&#231;&#245;es relevantes de qualquer um dos estudos eram inclu&#237;dos&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Extra&#231;&#227;o de dados e avalia&#231;&#227;o de qualidade</span><p id="par0030" class="elsevierStylePara elsevierViewall">As informa&#231;&#245;es a seguir foram extra&#237;das de cada um dos estudos inclu&#237;dos&#58; nomes dos primeiros autores&#44; pa&#237;s&#44; tipo de estudo e ano de publica&#231;&#227;o&#44; n&#250;mero de indiv&#237;duos com vitiligo e controles&#44; indiv&#237;duos do sexo masculino e feminino em cada grupo&#44; valores m&#233;dios&#47;medianas de idade&#44; dura&#231;&#227;o da doen&#231;a&#44; m&#233;dias e DP dos n&#237;veis de Vit&#8208;D&#44; meio usado para sua medida&#44; m&#233;todo e unidades&#44; tipo e hist&#243;ria de vitiligo&#44; atividade da doen&#231;a&#44; fototipo&#44; comorbidades autoimunes e outras caracter&#237;sticas do estudo&#46; Uma avalia&#231;&#227;o do escore de qualidade dos estudos inclu&#237;dos foi realizada de acordo com a Escala Newcastle&#8208;Ottawa &#40;NOS&#44; do ingl&#234;s Newcastle&#8208;Ottawa Scale&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">35</span></a> A avalia&#231;&#227;o da qualidade dos estudos variou de 0 a 9 pontos&#44; incluindo tr&#234;s componentes&#58; sele&#231;&#227;o&#44; comparabilidade e exposi&#231;&#227;o&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">An&#225;lise estat&#237;stica</span><p id="par0035" class="elsevierStylePara elsevierViewall">Metan&#225;lises e an&#225;lises de subgrupos foram conduzidas se houvesse tr&#234;s ou mais estudos relatando os n&#237;veis circulat&#243;rios de Vit&#8208;D em vitiligo e grupos de controle&#46; Calculamos a diferen&#231;a m&#233;dia padronizada &#40;DMP&#41; e seu intervalo de confian&#231;a &#40;IC&#41; de 95&#37; como uma estat&#237;stica resumida para a diferen&#231;a dos n&#237;veis de Vit&#8208;D entre pacientes com vitiligo e controles&#46; Al&#233;m disso&#44; tamb&#233;m realizamos uma metan&#225;lise das correla&#231;&#245;es entre Vit&#8208;D e outros par&#226;metros no vitiligo&#46; O tamanho do efeito para DMP e os valores do coeficiente de correla&#231;&#227;o agrupados foram apresentados como um escore&#8208;Z&#46; O escore Z com valor de p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 foi considerado estatisticamente significativo&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A heterogeneidade entre os estudos foi examinada pela estat&#237;stica Q de Cochrane e expressa como as porcentagens de I<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">2</span></a>&#46; Um valor de p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 ou estat&#237;stica I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#62; 50&#37; indicou uma heterogeneidade significativa&#46; Um modelo de efeitos aleat&#243;rios foi utilizado para calcular a DMP&#46; A an&#225;lise de metarregress&#227;o foi realizada para identificar a fonte potencial de heterogeneidade usando v&#225;rias covari&#225;veis&#44; como idade&#44; tamanho da amostra&#44; n&#250;mero de homens&#47;mulheres&#44; dura&#231;&#227;o da doen&#231;a&#44; m&#233;todo de mensura&#231;&#227;o da Vit&#8208;D&#44; pa&#237;s e ano de publica&#231;&#227;o&#46; O risco de vi&#233;s de publica&#231;&#227;o foi estudado pela assimetria do gr&#225;fico de funil com os testes de Begg e Egger&#46; No entanto&#44; para evitar o risco de vi&#233;s&#44; os termos de pesquisa gerais foram escolhidos para uma recupera&#231;&#227;o garantida para a inclus&#227;o de artigos relatando os n&#237;veis de Vit&#8208;D como um desfecho secund&#225;rio&#46; No caso de um p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 sugerindo signific&#226;ncia estat&#237;stica&#44; o m&#233;todo <span class="elsevierStyleItalic">trim and fill</span> foi utilizado para corrigir esse vi&#233;s&#46; Para testar a robustez desta metan&#225;lise foi realizada uma an&#225;lise de sensibilidade com exclus&#227;o de um estudo a cada vez &#40;<span class="elsevierStyleItalic">one&#8208;study leave&#8208;out</span>&#41;&#46; Todas as compara&#231;&#245;es foram bicaudais e todas as an&#225;lises foram conduzidas utilizando&#8208;se o software Review Manager vers&#227;o 5&#46;3&#44; que apresenta DMP como g de Hedges&#59; a diferen&#231;a entre as duas m&#233;dias dividida pelo desvio&#8208;padr&#227;o agrupado&#44; com uma corre&#231;&#227;o para o vi&#233;s da amostra&#46; O MedCalc vers&#227;o 16&#46;2&#46;0 foi usado para a metan&#225;lise de correla&#231;&#245;es&#46; A metarregress&#227;o e o vi&#233;s de publica&#231;&#227;o foram realizados&#44; respectivamente&#44; utilizando os softwares OpenMeta e Comprehensive meta&#8208;analysis&#44; vers&#227;o 3&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Resultados</span><p id="par0045" class="elsevierStylePara elsevierViewall">Foram identificados 167 artigos para os n&#237;veis de Vit&#8208;D no vitiligo&#44; dos quais 63 foram recuperados para revis&#227;o de resumo e texto completo&#46; Desses&#44; 31 artigos n&#227;o tratavam dos n&#237;veis s&#233;ricos de Vit&#8208;D no vitiligo e&#44; portanto&#44; foram exclu&#237;dos&#46; Em outro artigo&#44; nenhum dado foi relatado e&#44; portanto&#44; ele n&#227;o foi inclu&#237;do&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">36</span></a> Um estudo&#44; embora n&#227;o tivesse grupo controle&#44; foi inclu&#237;do para a an&#225;lise de subgrupo das diferen&#231;as entre homens e mulheres com rela&#231;&#227;o aos n&#237;veis de Vit&#8208;D no vitiligo&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">37</span></a> Um estudo de Xu et al&#46; foi considerado duas vezes&#44; pois os n&#237;veis de Vit&#8208;D foram relatados em dois grupos separados de vitiligo e controles estudados em diferentes per&#237;odos de tempo&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">33</span></a> Ao final&#44; 31 artigos foram inclu&#237;dos nesta metan&#225;lise&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">5&#8211;34</span></a> O diagrama de fluxo PRISMA para esta metan&#225;lise &#233; mostrado na <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#46; As caracter&#237;sticas detalhadas dos estudos inclu&#237;dos e os escores de qualidade da NOS s&#227;o apresentados na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; Com o escore obtido variando de 4 a 8&#44; a qualidade geral dos estudos foi de m&#233;dia a alta&#46; Dos estudos inclu&#237;dos&#44; 15 mediram Vit&#8208;D por ELISA&#44; seis por quimioluminesc&#234;ncia&#44; dois por RIA&#44; um por LCMS&#44; e esse dado n&#227;o est&#225; claro em sete estudos&#46; Enquanto todos os estudos relataram n&#237;veis de calcidiol&#44; um relatou n&#237;veis de calcitriol&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">5</span></a> Exceto por dois estudos que utilizaram plasma&#44; todos os demais utilizaram soro para medir os n&#237;veis de Vit&#8208;D&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">13&#44;30</span></a> A maioria dos estudos excluiu tratamento anterior para vitiligo&#44; suplementa&#231;&#227;o oral de Vit&#8208;D e qualquer tratamento t&#243;pico ou sist&#234;mico que possa afetar os n&#237;veis de vitamina D&#59; no entanto&#44; isso n&#227;o est&#225; claro em alguns estudos&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">8&#44;12&#44;18&#44;28</span></a> Em trabalhos em que o tratamento com ultravioleta B de banda estreita &#40;NB&#8208;UVB&#41; e&#47;ou interven&#231;&#227;o com Vit&#8208;D foi estudado&#44; apenas os n&#237;veis basais de Vit&#8208;D em pacientes com vitiligo em compara&#231;&#227;o com os controles foram considerados para a metan&#225;lise&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">14&#44;16&#44;20&#44;27&#44;32</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">N&#237;vel s&#233;rico de Vit&#8208;D no vitiligo em compara&#231;&#227;o com os controles</span><p id="par0050" class="elsevierStylePara elsevierViewall">Como mostrado na <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>&#44; os pacientes com vitiligo apresentavam n&#237;veis diminu&#237;dos de Vit&#8208;D em compara&#231;&#227;o com os controles&#46; Com uma heterogeneidade significativa entre os estudos &#40;I<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>95&#37;&#59; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;00001&#41;&#44; a DMP agrupada &#40;IC 95&#37;&#41; obtida com o modelo de efeitos aleat&#243;rios foi de &#8722;1&#44;03 &#40;&#8722;1&#44;35 a &#8722;0&#44;71&#41;&#46; Esse resultado sugere uma diferen&#231;a significativa nos n&#237;veis m&#233;dios de Vit&#8208;D entre pacientes com vitiligo e os controles&#44; e o tamanho do efeito geral para a diferen&#231;a m&#233;dia obtida corrigida para desvios&#8208;padr&#227;o e vi&#233;s de amostra foi estatisticamente significativo &#40;Z<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#44;22&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;00001&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lises de subgrupo e metarregress&#227;o</span><p id="par0055" class="elsevierStylePara elsevierViewall">Os resultados da metan&#225;lise de subgrupo com base no pa&#237;s&#44; m&#233;todo de mensura&#231;&#227;o de Vit&#8208;D&#44; tipo de vitiligo&#44; sexo&#44; fototipo&#44; hist&#243;ria de vitiligo&#44; hist&#243;ria de comorbidades&#47;autoimune&#44; atividade da doen&#231;a &#40;progressiva&#47;ativa ou est&#225;vel&#41;&#44; tipo de trabalho &#40;interno ou externo&#41; e a indexa&#231;&#227;o das revistas &#40;PubMed&#47; N&#227;o PubMed&#41; s&#227;o apresentados na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; A DMP agrupada foi estatisticamente significativa nos subgrupos &#8220;Egito&#8221;&#44; &#8220;n&#227;o Egito&#8221;&#44; &#8220;ELISA&#8221;&#44; &#8220;interno <span class="elsevierStyleItalic">vs</span>&#46; externo&#8221;&#44; &#8220;PubMed&#8221; e &#8220;N&#227;o PubMed&#8221;&#46; A signific&#226;ncia estat&#237;stica n&#227;o foi alcan&#231;ada em todos os outros subgrupos&#44; incluindo diferentes tipos de vitiligo&#44; tipo de pele&#44; atividade da doen&#231;a&#44; hist&#243;ria de vitiligo&#44; AIC e entre os sexos masculino e feminino em pacientes com vitiligo&#44; o que &#233; sugestivo de poss&#237;vel fonte de heterogeneidade&#46; Entre as v&#225;rias covari&#225;veis utilizadas na metarregress&#227;o &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#44; a vari&#225;vel &#8220;pa&#237;s&#8221; produziu um resultado estatisticamente significativo &#40;coeficiente<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;19&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41; indicativo de fonte significativa de heterogeneidade entre os estudos inclu&#237;dos&#46; Os resultados da metan&#225;lise de correla&#231;&#227;o apresentados na <a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a> n&#227;o mostraram associa&#231;&#245;es significativas da Vit&#8208;D com idade&#44; dura&#231;&#227;o da doen&#231;a&#44; ASC e VASI&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Vi&#233;s de publica&#231;&#227;o e an&#225;lise de sensibilidade</span><p id="par0060" class="elsevierStylePara elsevierViewall">A an&#225;lise do gr&#225;fico de funil com correla&#231;&#227;o de Begg &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; e os testes de regress&#227;o de Egger &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; indicam que pode haver um vi&#233;s de publica&#231;&#227;o entre os estudos inclu&#237;dos &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46; No entanto&#44; &#233; improv&#225;vel que o vi&#233;s de publica&#231;&#227;o representasse um efeito significativo sobre esta metan&#225;lise&#44; pois a corre&#231;&#227;o desse vi&#233;s com o m&#233;todo <span class="elsevierStyleItalic">trim and fill</span> validou nossos resultados originais&#46; Com sete estudos a serem cortados&#44; os valores corrigidos &#40;DMP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;1&#44;41&#44; IC 95&#37;&#58; &#8722;1&#44;81 a &#8722;1&#44;00&#41; ainda indicavam n&#237;veis significativamente mais baixos de Vit&#8208;D no vitiligo em compara&#231;&#227;o com os controles&#46; Al&#233;m disso&#44; uma an&#225;lise de sensibilidade com exclus&#227;o de um estudo a cada vez &#40;<span class="elsevierStyleItalic">one&#8208;study leave&#8208;out</span>&#41; mostrou que nenhum estudo individual influenciou significativamente o tamanho do efeito combinado&#46; A DMP combinada obtida era est&#225;vel e permaneceu estatisticamente significativa ap&#243;s a elimina&#231;&#227;o de qualquer estudo em particular na an&#225;lise de sensibilidade &#40;<a class="elsevierStyleCrossRef" href="#fig0020">fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discuss&#227;o</span><p id="par0065" class="elsevierStylePara elsevierViewall">A literatura dispon&#237;vel mostra resultados contrastantes em rela&#231;&#227;o aos n&#237;veis de Vit&#8208;D no vitiligo&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">5&#8211;34</span></a> Que seja de nosso conhecimento&#44; as duas revis&#245;es sistem&#225;ticas dispon&#237;veis sobre o t&#243;pico n&#227;o s&#227;o atualizadas e s&#227;o limitadas em rela&#231;&#227;o ao n&#250;mero de estudos inclu&#237;dos&#44; subgrupo e an&#225;lises de metarregress&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#44;3</span></a> Al&#233;m disso&#44; em um desses dois estudos&#44; a extra&#231;&#227;o de dados em rela&#231;&#227;o a um estudo inclu&#237;do estava errada&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#44;33</span></a> E&#44; no outro&#44; tanto o vitiligo adulto quanto o infantil foram inclu&#237;dos na metan&#225;lise&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">3</span></a> Neste estudo atualizado&#44; realizamos uma metan&#225;lise incluindo 1&#46;840 pacientes com vitiligo e 1&#46;539 controles de 31 relatos&#46; O resultado de nossa metan&#225;lise mostra que a concentra&#231;&#227;o de Vit&#8208;D na circula&#231;&#227;o &#233; significativamente menor em pacientes com vitiligo em compara&#231;&#227;o com os controles &#40;DMP<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;1&#44;03&#44; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;00001&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">A forma ativa da Vit&#8208;D e do receptor da vitamina D &#40;RVD&#41; &#233; mediadora de v&#225;rias fun&#231;&#245;es biol&#243;gicas importantes&#44; como o metabolismo do c&#225;lcio e do fosfato&#44; a forma&#231;&#227;o&#44; o crescimento e a diferencia&#231;&#227;o &#243;ssea&#46; Estudos indicaram que polimorfismos do RVD est&#227;o associados aos n&#237;veis de Vit&#8208;D e exibem uma predisposi&#231;&#227;o gen&#233;tica para o vitiligo&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">3&#44;36</span></a> Embora a etiopatog&#234;nese do vitiligo n&#227;o esteja completamente esclarecida&#44; a Vit&#8208;D &#233; conhecida por mediar a regula&#231;&#227;o imunol&#243;gica e doen&#231;as imunes&#44; al&#233;m de diabetes e doen&#231;as cardiovasculares&#44; entre outras&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">1&#8211;3</span></a> Tamb&#233;m se sabe que o vitiligo est&#225; associado a comorbidades autoimunes e&#44; portanto&#44; n&#237;veis circulat&#243;rios alterados de Vit&#8208;D podem estar associados a pacientes com vitiligo&#46; Os v&#225;rios fatores que podem influenciar o n&#237;vel circulat&#243;rio de Vit&#8208;D incluem tipo de vitiligo&#44; tipo de pele&#44; atividade da doen&#231;a&#44; hist&#243;ria de vitiligo&#44; comorbidades autoimunes&#44; idade&#44; tipo de trabalho em ambientes fechados e ao ar livre&#44; exposi&#231;&#227;o ao sol&#44; varia&#231;&#245;es sazonais e m&#233;todos de mensura&#231;&#227;o de Vit&#8208;D&#46; Em um estudo de coorte&#44; foi relatado que n&#237;veis baixos de Vit&#8208;D est&#227;o associados a comorbidades autoimunes &#40;<span class="elsevierStyleItalic">odds ratio</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#44;00&#41;&#44; mas n&#227;o com idade&#44; sexo&#44; ra&#231;a&#47;etnia&#44; hist&#243;ria familiar de vitiligo ou doen&#231;a autoimune&#44; doen&#231;a de in&#237;cio recente ou ASC afetada&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">38</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Nossa an&#225;lise de subgrupo produziu resultados interessantes&#46; Como havia dez estudos do Egito&#44; o m&#225;ximo para qualquer outro pa&#237;s&#44; realizamos uma metan&#225;lise de subgrupo com base em estudos eg&#237;pcios e n&#227;o eg&#237;pcios &#40;21 estudos&#41;&#46; Em ambos os casos&#44; a signific&#226;ncia estat&#237;stica foi mantida para um n&#237;vel diminu&#237;do de Vit&#8208;D no vitiligo&#46; Entretanto&#44; quando os pa&#237;ses n&#227;o eg&#237;pcios foram estratificados adicionalmente&#44; o subgrupo &#205;ndia &#40;sete estudos&#41; mostrou uma signific&#226;ncia estat&#237;stica&#44; enquanto os subgrupos de estudos da China &#40;tr&#234;s estudos&#41; e da Turquia &#40;quatro estudos&#41; n&#227;o produziram uma diferen&#231;a estatisticamente significativa em n&#237;veis de Vit&#8208;D entre seus respectivos grupos de vitiligo e controle &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; Isso &#233; sugestivo de uma heterogeneidade entre os estudos em decorr&#234;ncia do &#8220;pa&#237;s&#8221; dos estudos inclu&#237;dos&#59; os n&#237;veis circulat&#243;rios de Vit&#8208;D podem variar entre os pa&#237;ses por causa de diferentes latitudes&#44; fatores gen&#233;ticos e alimentares&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#44;3</span></a> Tal fato &#233; comprovado por nossa metan&#225;lise de regress&#227;o indicando o &#8220;pa&#237;s&#8221; como uma fonte significativa de heterogeneidade &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; Nenhuma diferen&#231;a significativa foi observada quando os n&#237;veis de Vit&#8208;D foram comparados entre diferentes tipos de vitiligo n&#227;o segmentar&#44; presen&#231;a ou aus&#234;ncia de hist&#243;ria de vitiligo e comorbidades autoimunes&#46; Embora os pacientes com vitiligo do sexo feminino e com o fototipo IV tenham apresentado n&#237;veis mais baixos de Vit&#8208;D&#44; n&#227;o houve signific&#226;ncia estat&#237;stica quando comparados aos do sexo masculino e com o fototipo III&#44; respectivamente&#46; A atividade da doen&#231;a parece ter algum efeito&#44; com o vitiligo est&#225;vel mostrando n&#237;veis mais baixos de Vit&#8208;D em compara&#231;&#227;o ao vitiligo ativo&#59; nenhum valor de p significativo foi encontrado &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; Al&#233;m disso&#44; nenhuma influ&#234;ncia significativa de idade&#44; sexo&#44; tamanho da amostra&#44; ano de publica&#231;&#227;o e dura&#231;&#227;o da doen&#231;a foi observada na an&#225;lise de metarregress&#227;o&#46; Assim&#44; a metan&#225;lise dos coeficientes de correla&#231;&#227;o tamb&#233;m n&#227;o resultou em associa&#231;&#245;es estatisticamente significativas de Vit&#8208;D com idade&#44; dura&#231;&#227;o da doen&#231;a&#44; ASC e escore VASI &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">&#201; digno de nota que os n&#237;veis de Vit&#8208;D foram significativamente mais baixos em pacientes com vitiligo que tinham trabalho interno&#47;urbano quando comparados aos seus equivalentes que exerciam trabalho externo&#47;rural &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; Esse dado claramente sugere que menos atividade ao ar livre est&#225; associada &#224; diminui&#231;&#227;o dos n&#237;veis de Vit&#8208;D no vitiligo&#44; o que indica que o ambiente e&#44; portanto&#44; a intensidade da exposi&#231;&#227;o ao sol&#44; podem influenciar os n&#237;veis de Vit&#8208;D&#46; Embora tenha sido poss&#237;vel extrair e resumir os dados na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#44; al&#233;m das diferentes esta&#231;&#245;es&#47;per&#237;odos de tempo durante os quais os estudos inclu&#237;dos foram realizados e as mensura&#231;&#245;es de Vit&#8208;D foram feitas&#44; esses dados foram insuficientes para conduzir uma metan&#225;lise sobre a influ&#234;ncia sazonal e varia&#231;&#245;es da Vit&#8208;D associadas no vitiligo&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Quando uma metan&#225;lise separada foi realizada com base em estudos com ELISA &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#41; e estudos n&#227;o ELISA &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41;&#44; a signific&#226;ncia estat&#237;stica foi mantida apenas em um grupo utilizando ELISA&#44; enquanto a metodologia n&#227;o ELISA &#40;particularmente&#44; quimioluminesc&#234;ncia&#41; &#233; um fator importante que contribui para a heterogeneidade entre os estudos&#46; Entretanto&#44; na metarregress&#227;o &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41;&#44; o &#8220;m&#233;todo&#8221; usado como covari&#225;vel n&#227;o mostrou um valor estatisticamente significativo&#46; Considerando que os artigos indexados na base de dados PubMed&#47;MEDLINE s&#227;o de boa qualidade&#44; com informa&#231;&#245;es confi&#225;veis&#44; repetimos uma metan&#225;lise separada no PubMed &#40;18 artigos&#41; e estudos n&#227;o PubMed &#40;13 artigos&#41;&#44; e os resultados mantiveram signific&#226;ncia estat&#237;stica em ambos os casos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Considerando o risco aumentado de vitiligo e o risco de comorbidades autoimunes associadas &#224; diminui&#231;&#227;o dos n&#237;veis de Vit&#8208;D&#44; nossa metan&#225;lise e estudos anteriores apontam para a necessidade de manter n&#237;veis suficientes de Vit&#8208;D por fototerapia com NB&#8208;UVB e&#47;ou suplementa&#231;&#227;o de Vit&#8208;D&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">39&#8211;41</span></a> Al&#233;m disso&#44; a suplementa&#231;&#227;o com antioxidantes em combina&#231;&#227;o com fototerapia tamb&#233;m foi estudada no vitiligo&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">42&#44;43</span></a> Um estudo recente fornece uma nova evid&#234;ncia sobre uma associa&#231;&#227;o positiva significativa de n&#237;veis suficientes de Vit&#8208;D com a estabilidade da doen&#231;a e um processo de repigmenta&#231;&#227;o satisfat&#243;rio em pacientes adultos com vitiligo&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">41</span></a> Essa evid&#234;ncia anterior e essa metan&#225;lise tamb&#233;m refor&#231;am a necessidade de avaliar o n&#237;vel da Vit&#8208;D no vitiligo&#46; Considerando que a efic&#225;cia terap&#234;utica da suplementa&#231;&#227;o de Vit&#8208;D e uma correla&#231;&#227;o relatada entre n&#237;veis suficientes de Vit&#8208;D e o curso do vitiligo s&#227;o promissoras&#44; mais ensaios cl&#237;nicos randomizados s&#227;o necess&#225;rios sobre o papel da suplementa&#231;&#227;o da Vit&#8208;D&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">40&#44;41</span></a> Isso tamb&#233;m abre o escopo para uma futura metan&#225;lise de ECR sobre a efic&#225;cia da suplementa&#231;&#227;o de Vit&#8208;D no vitiligo&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">As limita&#231;&#245;es do nosso estudo incluem a heterogeneidade entre os estudos&#44; que pode ser atribu&#237;da a popula&#231;&#245;es de estudo heterog&#234;neas de diferentes pa&#237;ses&#44; diferentes tamanhos de amostra e diferen&#231;as em metodologias&#44; diversos fatores ambientais&#44; gen&#233;ticos&#44; diet&#233;ticos e h&#225;bitos de estilo de vida e outras limita&#231;&#245;es inerentes a desenhos de estudos de caso&#8208;controle&#47;observacionais&#46; Entretanto&#44; como a heterogeneidade n&#227;o pode ser completamente eliminada em uma metan&#225;lise&#44; isso foi abordado aplicando o modelo de efeitos aleat&#243;rios para estimar o tamanho do efeito geral e por meio de uma an&#225;lise de sensibilidade cumulativa e com exclus&#227;o de um estudo a cada vez &#40;<span class="elsevierStyleItalic">one&#8208;study leave&#8208;out</span>&#41; para avaliar se algum estudo individual afetaria significativamente o tamanho de efeito geral obtido&#46; A an&#225;lise de sensibilidade com exclus&#227;o de um estudo a cada vez &#40;<span class="elsevierStyleItalic">one&#8208;study leave&#8208;out</span>&#41; revelou que nenhum estudo&#47;observa&#231;&#227;o individual tinha influenciado significativamente o tamanho de efeito geral agrupado&#46; Portanto&#44; nossos resultados foram considerados robustos&#46; Al&#233;m disso&#44; todos os estudos inclu&#237;dos foram pareados para fatores de confus&#227;o como idade e sexo&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Em conclus&#227;o&#44; nossa metan&#225;lise indica diminui&#231;&#227;o do n&#237;vel de Vit&#8208;D em pacientes com vitiligo em compara&#231;&#227;o com os controles&#46; Esses resultados de nossa metan&#225;lise destacam a necessidade de avaliar a Vit&#8208;D para melhorar seu n&#237;vel no vitiligo&#46; Mais estudos sobre o papel da Vit&#8208;D em rela&#231;&#227;o &#224; patog&#234;nese e gravidade do vitiligo s&#227;o necess&#225;rios no futuro&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Suporte financeiro</span><p id="par0105" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Contribui&#231;&#245;es dos autores</span><p id="par0110" class="elsevierStylePara elsevierViewall">Seshadri Reddy Varikasuvu&#58; Concep&#231;&#227;o do estudo&#59; realiza&#231;&#227;o da pesquisa bibliogr&#225;fica&#59; an&#225;lise dos dados&#59; elabora&#231;&#227;o do manuscrito&#59; leitura e aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Sowjanya Aloori&#58; Realiza&#231;&#227;o da pesquisa bibliogr&#225;fica&#59; crit&#233;rios de sele&#231;&#227;o&#59; coleta de dados e revis&#245;es&#59; leitura e aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Saurabh Varshney&#58; Realiza&#231;&#227;o da pesquisa bibliogr&#225;fica&#59; crit&#233;rios de sele&#231;&#227;o&#59; coleta de dados e revis&#245;es&#59; leitura e aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Aparna Varma Bhongir&#58; Auxiliou na realiza&#231;&#227;o da pesquisa bibliogr&#225;fica&#59; revis&#227;o do manuscrito&#59; leitura e aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflito de interesses</span><p id="par0130" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Dados sobre n&#237;vel s&#233;rico de vitamina D em pacientes com vitiligo s&#227;o amb&#237;guos quando comparado aos controles&#46; Foram conduzidas uma revis&#227;o sistem&#225;tica e uma metan&#225;lise atualizada para avaliar a associa&#231;&#227;o entre vitamina D e vitiligo&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudos relevantes foram identificados por meio de pesquisa na PubMed e outras bases de dados&#46; O modelo de efeitos aleat&#243;rios foi usado para obter as diferen&#231;as m&#233;dias padronizadas e coeficientes de correla&#231;&#227;o agrupados&#46; Metarregress&#227;o e an&#225;lises de subgrupos foram realizadas para explorar a heterogeneidade&#46; A presen&#231;a de vi&#233;s de publica&#231;&#227;o e a robustez do estudo foram testados utilizando o gr&#225;fico de funil e an&#225;lises de sensibilidade&#44; respectivamente&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Ao final&#44; esta metan&#225;lise incluiu 31 estudos&#46; Em compara&#231;&#227;o com os controles&#44; os pacientes com vitiligo apresentaram n&#237;veis circulat&#243;rios de vitamina D significativamente diminu&#237;dos &#40;diferen&#231;a m&#233;dia padronizada<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;1&#44;03&#59; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;&#46; A an&#225;lise de subgrupo mostrou que pacientes com vitiligo com trabalho interno&#47;urbano apresentaram um n&#237;vel de vitamina D significativamente mais baixo quando comparados a seu hom&#243;logo trabalho externo&#47;rural &#40;diferen&#231;a m&#233;dia padronizada<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#44;45&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#41;&#46; A an&#225;lise de sensibilidade indicou que nenhum estudo individual teve influ&#234;ncia significativa no resultado geral&#44; sugerindo a robustez desta metan&#225;lise&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Tamanhos variados de amostras e popula&#231;&#245;es de estudo heterog&#234;neas de diferentes pa&#237;ses s&#227;o as limita&#231;&#245;es deste estudo&#46; Entretanto&#44; a heterogeneidade entre os estudos foi abordada pelo modelo de efeitos aleat&#243;rios com metarregress&#227;o e an&#225;lises de sensibilidade&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclus&#245;es</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Esta metan&#225;lise mostrou diminui&#231;&#227;o significativa do n&#237;vel de vitamina D no vitiligo e sua associa&#231;&#227;o com o tipo de trabalho interno&#47;externo de pacientes com vitiligo&#46; Este estudo enfatiza a necessidade de avaliar o n&#237;vel da vitamina D para melhor&#225;&#8208;lo no vitiligo&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Trabalho realizado no All India Institute of Medical Sciences&#44; Deoghar&#44; Jharkhand&#44; &#205;ndia&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">NC&#44; n&#227;o claro&#59; ND&#44; n&#227;o dispon&#237;vel&#59; SD&#44; sem diferen&#231;a&#59; NOS&#44; Escala Newcastle&#8208;Ottawa&#59; SI&#44; significativamente inferior&#59; DD&#44; dura&#231;&#227;o da doen&#231;a&#59; SKT&#44; Tipos de pele de Fitzpatrick&#59; a&#44; anos&#59; M&#44; masculino&#59; F&#44; feminino&#59; n&#44; tamanho da amostra&#59; Def&#44; Defici&#234;ncia&#59; Insuf&#44; Insufici&#234;ncia&#59; Suf&#44; Sufici&#234;ncia&#46;</p>"
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                0 => """
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Estudo&#47;pa&#237;s &#40;per&#237;odo do estudo&#41; &#40;REF&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Tipo do estudo&#47;SKT&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vitiligo</th><th class="td" title="\n
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                  \t\t\t\t" scope="col">Pareados&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">NOS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">N &#40;M&#47;F&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Idade&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Tipo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">DD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">N &#40;M&#47;F&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col">Idade &#40;a&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">Amostra&#47; M&#233;todo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">Unidades &#40;altera&#231;&#227;o&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Vit&#46; D&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aly et al&#46;&#44; 2017&#47; Egito&#40;Nov&#8208;Dez 2015&#41; <a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Transversal&#47;III&#44; IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;9&#47;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#44;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o segmentar&#59; vulgaracrofacialfocal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;83a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;19&#47;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#44;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 10&#44; 10&#8208;30&#44; &#8805; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amon et al&#46;&#44; 2018&#47;EUA&#40;Jul 2015&#8208;Jun 2016&#41; <a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">6</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospectivo&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">113 &#40;57&#47;56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71 &#40;17&#47;54&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#8804; 20 ng&#47;mL&#44; ND&#44; ND&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Beheshti et al&#46;&#44; 2014&#47;Ir&#227; &#40;Mar&#8208;Jun 2012&#41; <a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Transversal&#47;III&#44; IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 &#40;42&#47;58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vulgar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sem Grupo controle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;EIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">nmoL&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 25&#44; 25&#8208;47&#44; 47&#44;7&#8208;144 nmoL&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cerman et al&#46;&#44; 2014&#47;Turquia&#40;Nov 2012&#8208;Mar 2013&#41; <a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Transversal&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44 &#40;27&#47;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#44;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#44;55m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 &#40;34&#47;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#44;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&#44; IMC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;LCMS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#8804; 20 ng&#47;mL&#44; ND&#44; ND&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deepthi &#38; Geetharani 2018 &#47;&#205;ndia&#40;Dez16&#8208;Maio17&#41; <a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">8</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Disserta&#231;&#227;o&#47;III&#44; IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120 &#40;59&#47;61&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Segmental&#44; vulgar&#44; universal&#44; focal&#44; acrofacial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8804;5a &#8805;21a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;29&#47;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#8804; 20&#44; 20&#8208;30&#44;<span class="elsevierStyleHsp" style=""></span>&#62; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doss et al&#46;&#44; 2015&#47; Egito&#40;Jun&#8208;Set 2013&#41; <a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">9</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;20&#47;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UniversalGeneralizadoLocalizado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#44;4m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">30 &#40;16&#47;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#8804; 20&#44; 20&#8208;30&#44; &#8805; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">El&#8208;Hanbuli et al&#46;&#44; 2018&#47; Egito&#40;Jun&#8208;Set 2016&#41; <a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">10</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;16&#47;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#44;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;87m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;16&#47;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#44;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&#44; tipo de pele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 12&#44; 12&#8208;20&#44;<span class="elsevierStyleHsp" style=""></span>&#62; 20 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Farag et al&#46;&#44; 2018&#47; Egito&#40;Mar&#8208;Jun 2016&#41; <a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">11</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;III&#44; IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;18&#47;32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AcrofacialGeneralizado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;5a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;10&#47;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&#44; tipo de pele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">nmoL&#47;L &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 25&#44; 25&#8208;74&#44; &#8805; 75 nmoL&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Firjani 2019&#47; Egito <a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">12</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hassan et al&#46;&#44; 2019&#47;&#205;ndia <a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 &#40;39&#47;61&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;81a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 &#40;40&#47;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Plasma&#47;CLIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 20&#44; 20&#8208;30&#44; &#8805; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ibrahim et al&#46;&#44; 2018&#47;Egito&#40;Dez 2015&#8208;Dez 2016&#41; <a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;III&#44; IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80 &#40;40&#47;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#44;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;10&#47;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#44;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">nmoL&#47;L &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 10&#44; 10&#8208;29&#44;<span class="elsevierStyleHsp" style=""></span>&#62; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Karag&#252;n et al&#46;&#44; 2016&#47; Turquia&#40;Dez 2013&#8208;Mar 2014&#41; <a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;28&#47;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#44;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Generalizado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;25a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47 &#40;30&#47;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&#44; tipo de pele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL&#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Khodair et al&#46;&#44; 2019&#47; Egito &#40;Mar&#8208;Jun 2018&#41; <a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Transversal&#47;II&#8208;V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;6&#47;24&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LocalizadoGeneralizado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#44;5a&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">30 &#40;10&#47;20&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Khurrum et al&#46;&#44; 2016&#47; Ar&#225;bia Saudita &#40;Jan 2011&#8208;Dez 2012&#41; <a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">150 &#40;90&#47;60&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">30&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">GeneralizadoAcralFocal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">150 &#40;76&#47;74&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">30&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;CLIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 10&#44; 10&#8208;30&#44; &#8805; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">137&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">136&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liu et al&#46;&#44; 2014&#47;China <a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">19&#8211;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19&#8211;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">nmoL&#47;L &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 25&#44; 25&#8208;47&#44;6&#44; 47&#44;4&#8208;250 nmoL&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ochoa&#8208;Ram&#237;rez et al&#46;&#44; 2019&#47; M&#233;xico <a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">173 &#40;81&#47;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#8211;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Disseminado &#40;generalizado&#44; universal&#41;&#44; localizado &#40;focal&#44; acrofacial&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">184&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Omidian &#38; Asadian 2018&#47;Ir&#227; &#40;Apr 2015&#8208;Mar 2016&#41; <a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ensaio cl&#237;nico&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;12&#47;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#44;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Generalizado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;11&#47;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ECL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">nmoL&#47;L &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#8804; 10&#44; 10&#8208;29&#44; 30&#8208;100 nmoL&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pillai &#38; Dinachandran 2019&#47;&#205;ndia &#40;Jan&#8208;Abr 2018&#41; <a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;27&#47;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#44;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Generalizado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;25a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;30&#47;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&#44; tipo de pele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prakash &#38; Karthikeyan 2017&#47;&#205;ndia &#40;Out 2014&#8208;Maio 2016&#41; <a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45 &#40;26&#47;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#44;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VulgarAcrofacialFocal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#44;04m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 20&#44; 20&#8208;30&#44;<span class="elsevierStyleHsp" style=""></span>&#62; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ramalingam &#38; Tang 2018&#47; Mal&#225;sia &#40;Jul&#8208;Dez 2014&#41; <a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Transversal&#47;I&#8208;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">93 &#40;46&#47;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">40&#44;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o segmentarsegmentar&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3a&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">87 &#40;43&#47;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#44;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&#44; etnia&#44; IMC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#8804; 20&#44; 20&#8208;30&#44;<span class="elsevierStyleHsp" style=""></span>&#62; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Saleh et al&#46;&#44; 2013&#47;Egito &#40;Abr&#8208;Jun 2011&#41; <a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;III&#8208;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">40 &#40;18&#47;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">34&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o segmentar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#44;5a&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">40 &#40;18&#47;22&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">34&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&#44; tipo de pele&#44; ingest&#227;o de Vit&#46; D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;RIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#8804; 20&#44; 20&#8208;30&#44; &#8805; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Saniee et al&#46;&#44; 2019&#47;Ir&#227; &#40;primavera e ver&#227;o 2017&#41; <a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;III&#8208;IV&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">98 &#40;50&#47;48&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">30&#44;06&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">34&#44;65m&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">98 &#40;53&#47;45&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">29&#44;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#40;&#60; 10&#44; 10&#8208;30&#44;<span class="elsevierStyleHsp" style=""></span>&#62; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sanjay &#38; Raval 2019&#47; &#205;ndia &#40;per&#237;odo de 1 ano&#41; <a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Transversal&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">25 &#40;15&#47;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">23&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FocalGeneralizadoAcrofacialMucoso&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">25 &#40;16&#47;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">24&#44;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ECL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sehrawat et al&#46;&#44; 2014&#47;&#205;ndia <a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudo cl&#237;nico&#47;IV&#8208;V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;10&#47;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Generalizado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;47a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;10&#47;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">nmoL&#47;L &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 25&#44; 25&#8208;74&#44; 75&#8208;250 nmoL&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shalaby et al&#46;&#44; 2017&#47;Egito&#40;Dez 2014&#8208;Jun 2016&#41; <a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;30&#47;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o segmentar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;7a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;25&#47;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#44;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">nmoL&#47;L &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 10&#44; 10&#8208;30&#44;<span class="elsevierStyleHsp" style=""></span>&#62; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sobeih et al&#46;&#44; 2016&#47;Egito &#40;Jul&#8208;Dez 2013&#41; <a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;III&#8208;V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VulgarAcrofacialSegmentar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;5a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Srirama 2016&#47;&#205;ndia &#40;per&#237;odo de 4m&#41; <a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">29</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;11&#47;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cl&#237;nico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;5a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;11&#47;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;CLIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 20&#44; 20&#8208;30&#44;<span class="elsevierStyleHsp" style=""></span>&#62; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Takci et al&#46;&#44; 2015&#47;Turquia &#40;Inverno&#58; Nov 2011&#8208;Fev 2012&#41; <a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">30</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;I&#44; III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44 &#40;24&#47;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VulgarGeneralizadoLocalizado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#44;8m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43 &#40;10&#47;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&#44; tipo de pele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Plasma&#47;RIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 20&#44; 20&#8208;30&#44;<span class="elsevierStyleHsp" style=""></span>&#62; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustun et al&#46;&#44; 2014&#47;Turquia &#40;b&#47;w 2010&#8208;2011&#41; <a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Transversal&#47;II&#44; III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;13&#47;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vulgar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;36a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;20&#47;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&#44; sexo&#44; tipo de pele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;CLIA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 20&#44; 21&#8208;29&#44; 30&#8208;100 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Watabe et al&#46;&#44; 2018&#47;Jap&#227;o &#40;Set 2015&#8208;Jan 2016&#41; <a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ECR&#47;III&#44; IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#44;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vulgar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pareado por idade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Idade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soro&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ng&#47;mL &#40;SI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;&#60; 20&#44; 20&#8208;30&#44;<span class="elsevierStyleHsp" style=""></span>&#62; 30 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Xu et al&#46;&#44; 2012&#47;China&#40;Mar&#8208;Mai 2011&#41; <a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">171 &#40;80&#47;91&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">34&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Segmentar&#44;n&#227;o segmentar&#59; generalizado&#44; universal&#44; focal&#44; halo de nevos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">nmol&#47;L &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Xu et al&#46;&#44; 2012&#47;China &#40;Set&#8208;Out 2010&#41; <a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caso controle&#47;NC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Segmentar&#44;n&#227;o segmentar&#59; generalizado&#44; universal&#44; focal&#44; halo de nevos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">&#8722;0&#44;53&#59; 0&#44;96&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Masculino <span class="elsevierStyleItalic">vs</span>&#46; Feminino&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8722;0&#44;09&#59; 0&#44;56&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">Ativa <span class="elsevierStyleItalic">vs</span>&#46; Est&#225;vel&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">SKT&#8208;III <span class="elsevierStyleItalic">vs</span>&#46; IV&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Interno <span class="elsevierStyleItalic">vs</span>&#46; Externo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Interno <span class="elsevierStyleItalic">vs</span>&#46; Externo &#38; U&#47;R&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Artigo de Revista indexada&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">PubMed&#47;MEDLINE&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">N&#227;o PubMed&#47;MEDLINE&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;96&#59; &#8722;0&#44;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2604407.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">An&#225;lise de subgrupos</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vari&#225;veis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Coeficientes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IC95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">EP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&#8208;valor&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;003&#59; 0&#44;012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;253&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vitiligo n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;009&#59; 0&#44;016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;612&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Controles n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;001&#59; 0&#44;031&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;059&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vitiligo&#8208;Masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;015&#59; 0&#44;034&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;468&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vitiligo&#8208;Feminino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;018&#59; 0&#44;032&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;593&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vitiligo&#8208; Raz&#227;o M&#47;F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;030&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;073&#59; 0&#44;134&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;053&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;566&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Controles &#8208; Masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;038&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;001&#59; 0&#44;075&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;044&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Controles &#8208; Feminino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;031&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;007&#59; 0&#44;068&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;107&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Controles &#8208; Raz&#227;o M&#47;F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;030&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;073&#59; 0&#44;134&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;053&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;566&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vitiligo &#8208; Idade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;042&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;056&#59; 0&#44;140&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;050&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;405&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Controles &#8208; Idade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;105&#59; 0&#44;130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;060&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;837&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dura&#231;&#227;o da doen&#231;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;0&#44;261&#59; 0&#44;219&nbsp;\t\t\t\t\t\t\n
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Journal Information
Vol. 96. Issue 3.
Pages 284-294 (1 May 2021)
Visits
10126
Vol. 96. Issue 3.
Pages 284-294 (1 May 2021)
Artigo original
Open Access
Diminuição dos níveis circulatórios de vitamina D no vitiligo: uma metanálise
Visits
10126
Seshadri Reddy Varikasuvua,
Corresponding author
lifeschemistry@live.com

Autor para correspondência.
, Sowjanya Aloorib, Saurabh Varshneyc, Aparna Varma Bhongird
a Department of Biochemistry, All India Institute of Medical Sciences, Deoghar, Índia
b Department of Health Education, Telangana State Residential School & College, Choutuppal, Índia
c All India Institute of Medical Sciences, Deoghar, Índia
d Department of Biochemistry, All India Institute of Medical Sciences, Bibinagar, Índia
Related content
Seshadri Reddy Varikasuvu, Sowjanya Aloori, Saurabh Varshney, Aparna Varma Bhongir
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Abstract
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Bibliography
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Figures (4)
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Tables (4)
Tabela 1. Características do estudo
Tabela 2. Análise de subgrupos
Tabela 3. Análise de metarregressão
Tabela 4. Metanálise de correlações
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Resumo
Fundamentos

Dados sobre nível sérico de vitamina D em pacientes com vitiligo são ambíguos quando comparado aos controles. Foram conduzidas uma revisão sistemática e uma metanálise atualizada para avaliar a associação entre vitamina D e vitiligo.

Métodos

Estudos relevantes foram identificados por meio de pesquisa na PubMed e outras bases de dados. O modelo de efeitos aleatórios foi usado para obter as diferenças médias padronizadas e coeficientes de correlação agrupados. Metarregressão e análises de subgrupos foram realizadas para explorar a heterogeneidade. A presença de viés de publicação e a robustez do estudo foram testados utilizando o gráfico de funil e análises de sensibilidade, respectivamente.

Resultados

Ao final, esta metanálise incluiu 31 estudos. Em comparação com os controles, os pacientes com vitiligo apresentaram níveis circulatórios de vitamina D significativamente diminuídos (diferença média padronizada=−1,03; p <0,0001). A análise de subgrupo mostrou que pacientes com vitiligo com trabalho interno/urbano apresentaram um nível de vitamina D significativamente mais baixo quando comparados a seu homólogo trabalho externo/rural (diferença média padronizada=−0,45; p=0,03). A análise de sensibilidade indicou que nenhum estudo individual teve influência significativa no resultado geral, sugerindo a robustez desta metanálise.

Limitações do estudo

Tamanhos variados de amostras e populações de estudo heterogêneas de diferentes países são as limitações deste estudo. Entretanto, a heterogeneidade entre os estudos foi abordada pelo modelo de efeitos aleatórios com metarregressão e análises de sensibilidade.

Conclusões

Esta metanálise mostrou diminuição significativa do nível de vitamina D no vitiligo e sua associação com o tipo de trabalho interno/externo de pacientes com vitiligo. Este estudo enfatiza a necessidade de avaliar o nível da vitamina D para melhorá‐lo no vitiligo.

Palavras‐chave:
Metanálise
Vitamina D
Vitiligo
25‐hidroxivitamina D2
Full Text
Introdução

A vitamina D (Vit‐D) tem uma importância fundamental no organismo, desde a estrutura óssea até a função cerebral, e também é vital para a pele saudável.1 Além disso, desempenha um papel de destaque no sistema imunológico. Sabe‐se que a hipovitaminose D está associada a distúrbios do metabolismo do cálcio e dos carboidratos, câncer, doenças cardiovasculares e várias doenças autoimunes.2 O vitiligo é uma doença cutânea conhecida por ter etiologia metabólica, citotóxica, inflamatória e autoimune, entre vários outros fatores.3,4 Foi relatado que a forma ativa da Vit‐D, 1,25‐di‐hidroxivitamina D3 (1,25[OH]D) está associada à patogênese do vitiligo.1–3 Quando a epiderme é afetada no vitiligo, podem ser evidenciadas alterações nos níveis circulatórios de Vit‐D.2–4

Os estudos disponíveis na literatura são inconsistentes quanto aos níveis de Vit‐D, e a hipovitaminose D ainda é controversa no vitiligo.5–34 Nesta revisão sistemática atualizada e metanálise sobre vitiligo e os níveis de Vit‐D (Estudo ViViD), os níveis circulatórios de Vit‐D e sua associação com variáveis como idade, duração da doença, área de superfície corporal (ASC) afetada e o Vitiligo Activity and Severity Index (VASI) foram estudados em pacientes com vitiligo em comparação com controles. Uma metanálise de subgrupo foi conduzida para estudar os níveis de Vit‐D em relação a sexo, fototipo, tipo de vitiligo, atividade da doença, história do vitiligo, comorbidades autoimunes e tipo de trabalho interno‐externo de pacientes com a doença.

Material e métodos

Os critérios da lista de verificação PRISMA (Preferred Reporting Items for Systematic reviews and Meta‐Analysis) foram seguidos na condução e no relato deste estudo. O protocolo do estudo foi registrado na base PROSPERO sob o número de registro CRD42019142156 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=142156).

Estratégia de busca de literatura

A pesquisa bibliográfica foi realizada principalmente no banco de dados PubMed/MEDLINE do NCBI, usando as estratégias de pesquisa de palavras‐chave e MESH. A seguinte linha de pesquisa foi desenvolvida: (“vitamin D” (MeSH Terms) OR “vitamin D” (All Fields) OR “ergocalciferols” (MeSH Terms) OR “ergocalciferols” (All Fields)) AND (“vitiligo” (MeSH Terms) OR “vitiligo” (All Fields)). Os outros termos utilizados para Vit‐D foram 25‐Hydroxyvitamin D, 25‐Hydroxycholecalciferol, calcidiol, 1.25‐dihydroxyvitamin D3 e calcitriol. Os bancos de dados do Google Scholar, da Cochrane Library, do Springer's author mapper, o Science Direct, os registros de ensaios clínicos e CINHAL também foram pesquisados em busca de artigos que relatassem níveis circulatórios de Vit‐D em pacientes com vitiligo. Além disso, as referências dos artigos publicados foram pesquisadas manualmente para identificar estudos adicionais. Dois autores realizaram a pesquisa bibliográfica de maneira independente, e quaisquer desacordos foram resolvidos após discussão. Foram feitos esforços para obter dados, se houvesse, de fontes não publicadas. Quando necessário, os autores correspondentes dos respectivos artigos foram contatados por e‐mail para obtenção de dados/esclarecimentos. Todas as pesquisas bibliográficas foram realizadas antes de 5 de setembro de 2019, sem intervalo de tempo especificado, com e sem estudos com seres humanos definidos como limite.

Critérios de seleção dos estudos

Os seguintes critérios foram preenchidos para estudos individuais a serem incluídos nesta metanálise: (1) artigos publicados em revistas revisadas por pares; (2) que forneceram dados originais; (3) os sujeitos do estudo eram seres humanos com descrição de vitiligo e controles; (4) estudos em que os níveis circulatórios de Vit‐D em pacientes com vitiligo foram comparados com os controles; (5) que forneceram descrição do método para estimativa dos níveis de Vit‐D; (6) artigos escritos em inglês/chinês com dados claros; (7) estudos com diagnóstico clínico de vitiligo feito por dermatologista. Os critérios de exclusão foram os seguintes: (1) estudos sem grupo controle; (2) relato de outras doenças de pele; (3) os níveis de Vit‐D foram mostrados apenas por pictogramas sem dados; (4) artigos de revisão, comentários e cartas ao editor. Quando algum artigo duplicado era encontrado, apenas um relato recente ou todas as informações relevantes de qualquer um dos estudos eram incluídos.

Extração de dados e avaliação de qualidade

As informações a seguir foram extraídas de cada um dos estudos incluídos: nomes dos primeiros autores, país, tipo de estudo e ano de publicação, número de indivíduos com vitiligo e controles, indivíduos do sexo masculino e feminino em cada grupo, valores médios/medianas de idade, duração da doença, médias e DP dos níveis de Vit‐D, meio usado para sua medida, método e unidades, tipo e história de vitiligo, atividade da doença, fototipo, comorbidades autoimunes e outras características do estudo. Uma avaliação do escore de qualidade dos estudos incluídos foi realizada de acordo com a Escala Newcastle‐Ottawa (NOS, do inglês Newcastle‐Ottawa Scale).35 A avaliação da qualidade dos estudos variou de 0 a 9 pontos, incluindo três componentes: seleção, comparabilidade e exposição.

Análise estatística

Metanálises e análises de subgrupos foram conduzidas se houvesse três ou mais estudos relatando os níveis circulatórios de Vit‐D em vitiligo e grupos de controle. Calculamos a diferença média padronizada (DMP) e seu intervalo de confiança (IC) de 95% como uma estatística resumida para a diferença dos níveis de Vit‐D entre pacientes com vitiligo e controles. Além disso, também realizamos uma metanálise das correlações entre Vit‐D e outros parâmetros no vitiligo. O tamanho do efeito para DMP e os valores do coeficiente de correlação agrupados foram apresentados como um escore‐Z. O escore Z com valor de p <0,05 foi considerado estatisticamente significativo.

A heterogeneidade entre os estudos foi examinada pela estatística Q de Cochrane e expressa como as porcentagens de I2. Um valor de p <0,05 ou estatística I2> 50% indicou uma heterogeneidade significativa. Um modelo de efeitos aleatórios foi utilizado para calcular a DMP. A análise de metarregressão foi realizada para identificar a fonte potencial de heterogeneidade usando várias covariáveis, como idade, tamanho da amostra, número de homens/mulheres, duração da doença, método de mensuração da Vit‐D, país e ano de publicação. O risco de viés de publicação foi estudado pela assimetria do gráfico de funil com os testes de Begg e Egger. No entanto, para evitar o risco de viés, os termos de pesquisa gerais foram escolhidos para uma recuperação garantida para a inclusão de artigos relatando os níveis de Vit‐D como um desfecho secundário. No caso de um p <0,05 sugerindo significância estatística, o método trim and fill foi utilizado para corrigir esse viés. Para testar a robustez desta metanálise foi realizada uma análise de sensibilidade com exclusão de um estudo a cada vez (one‐study leave‐out). Todas as comparações foram bicaudais e todas as análises foram conduzidas utilizando‐se o software Review Manager versão 5.3, que apresenta DMP como g de Hedges; a diferença entre as duas médias dividida pelo desvio‐padrão agrupado, com uma correção para o viés da amostra. O MedCalc versão 16.2.0 foi usado para a metanálise de correlações. A metarregressão e o viés de publicação foram realizados, respectivamente, utilizando os softwares OpenMeta e Comprehensive meta‐analysis, versão 3.

Resultados

Foram identificados 167 artigos para os níveis de Vit‐D no vitiligo, dos quais 63 foram recuperados para revisão de resumo e texto completo. Desses, 31 artigos não tratavam dos níveis séricos de Vit‐D no vitiligo e, portanto, foram excluídos. Em outro artigo, nenhum dado foi relatado e, portanto, ele não foi incluído.36 Um estudo, embora não tivesse grupo controle, foi incluído para a análise de subgrupo das diferenças entre homens e mulheres com relação aos níveis de Vit‐D no vitiligo.37 Um estudo de Xu et al. foi considerado duas vezes, pois os níveis de Vit‐D foram relatados em dois grupos separados de vitiligo e controles estudados em diferentes períodos de tempo.33 Ao final, 31 artigos foram incluídos nesta metanálise.5–34 O diagrama de fluxo PRISMA para esta metanálise é mostrado na figura 1. As características detalhadas dos estudos incluídos e os escores de qualidade da NOS são apresentados na tabela 1. Com o escore obtido variando de 4 a 8, a qualidade geral dos estudos foi de média a alta. Dos estudos incluídos, 15 mediram Vit‐D por ELISA, seis por quimioluminescência, dois por RIA, um por LCMS, e esse dado não está claro em sete estudos. Enquanto todos os estudos relataram níveis de calcidiol, um relatou níveis de calcitriol.5 Exceto por dois estudos que utilizaram plasma, todos os demais utilizaram soro para medir os níveis de Vit‐D.13,30 A maioria dos estudos excluiu tratamento anterior para vitiligo, suplementação oral de Vit‐D e qualquer tratamento tópico ou sistêmico que possa afetar os níveis de vitamina D; no entanto, isso não está claro em alguns estudos.8,12,18,28 Em trabalhos em que o tratamento com ultravioleta B de banda estreita (NB‐UVB) e/ou intervenção com Vit‐D foi estudado, apenas os níveis basais de Vit‐D em pacientes com vitiligo em comparação com os controles foram considerados para a metanálise.14,16,20,27,32

Figura 1.

Diagrama de fluxo PRISMA desta metanálise.

(0.3MB).
Tabela 1.

Características do estudo

Estudo/país (período do estudo) (REF)  Tipo do estudo/SKT  VitiligoControlesPareados  Vitamina DNOS 
    N (M/F)  Idade  Tipo  DD  N (M/F)  Idade (a)    Amostra/ Método  Unidades (alteração)  Vit. D  Vitiligo (n)Controles (n) 
                        Def.  Insuf.  Suf.  Def.  Insuf.  Suf.   
Aly et al., 2017/ Egito(Nov‐Dez 2015) 5  Transversal/III, IV  30 (9/21)  30,23  Não segmentar; vulgaracrofacialfocal  5,83a  40 (19/21)  35,38  Idade, sexo  Soro/ELISA  ng/mL (SI)  (< 10, 10‐30, ≥ 30 ng/mL)  25  34 
Amon et al., 2018/EUA(Jul 2015‐Jun 2016) 6  Retrospectivo/NC  113 (57/56)  38,2  NC  ND  71 (17/54)  49,2  NC  Soro/ELISA  ng/mL (SI)  (≤ 20 ng/mL, ND, ND)  46  ND  ND  ND  ND 
Beheshti et al., 2014/Irã (Mar‐Jun 2012) 37  Transversal/III, IV  100 (42/58)  28,7  Vulgar  5a  Sem Grupo controle    Soro/EIA  nmoL/L  (< 25, 25‐47, 47,7‐144 nmoL/L)  ND  ND  ND  ND  ND  ND   
Cerman et al., 2014/Turquia(Nov 2012‐Mar 2013) 7  Transversal/NC  44 (27/17)  33,64  ND  60,55m  58 (34/24)  32,55  Idade, sexo, IMC  Soro/LCMS  ng/mL (SI)  (≤ 20 ng/mL, ND, ND)  31  ND  ND  19  ND  ND 
Deepthi & Geetharani 2018 /Índia(Dez16‐Maio17) 8  Dissertação/III, IV  120 (59/61)  37,6  Segmental, vulgar, universal, focal, acrofacial  ≤5a ≥21a  60 (29/31)  36,2  Idade, sexo  Soro/ELISA  ng/mL (SI)  (≤ 20, 20‐30,> 30 ng/mL)  70  28  22  22  12  26 
Doss et al., 2015/ Egito(Jun‐Set 2013) 9  Caso controle/IV  30 (20/10)  32,5  UniversalGeneralizadoLocalizado  58,4m  30 (16/14)  28,0  Idade, sexo  Soro/ELISA  ng/mL (SI)  (≤ 20, 20‐30, ≥ 30 ng/mL)  12  10  29 
El‐Hanbuli et al., 2018/ Egito(Jun‐Set 2016) 10  Caso controle/IV  30 (16/14)  29,53  ND  14,87m  30 (16/14)  29,53  Idade, sexo, tipo de pele  Soro/ELISA  ng/mL (SI)  (< 12, 12‐20,> 20 ng/mL)  20  30 
Farag et al., 2018/ Egito(Mar‐Jun 2016) 11  Caso controle/III, IV  50 (18/32)  28,76  AcrofacialGeneralizado  3,5a  25 (10/15)  28,16  Idade, sexo, tipo de pele  Soro/ELISA  nmoL/L (SI)  (< 25, 25‐74, ≥ 75 nmoL/L)  40  10  23 
Firjani 2019/ Egito 12  Caso controle/NC  21  ND  ND  ND  21  ND  Idade, sexo  Soro/NC  ng/mL (SI)  ND  ND  ND  ND  ND  ND  ND 
Hassan et al., 2019/Índia 13  Caso controle/NC  100 (39/61)  28,66  NC  3,81a  100 (40/60)  ND  Idade, sexo  Plasma/CLIA  ng/mL (SI)  (< 20, 20‐30, ≥ 30 ng/mL)  75  15  10  19  35  46 
Ibrahim et al., 2018/Egito(Dez 2015‐Dez 2016) 14  Caso controle/III, IV  80 (40/40)  34,27  NC  ND  20 (10/10)  35,20  Idade, sexo  Soro/ELISA  nmoL/L (SI)  (< 10, 10‐29,> 30 ng/mL)  ND  ND  ND  ND  ND  ND 
Karagün et al., 2016/ Turquia(Dez 2013‐Mar 2014) 15  Caso controle/NC  50 (28/22)  30,96  Generalizado  2–25a  47 (30/17)  31,45  Idade, sexo, tipo de pele  Soro/NC  ng/mL(SD)  ND  ND  ND  ND  ND  ND  ND 
Khodair et al., 2019/ Egito (Mar‐Jun 2018) 16  Transversal/II‐V  30 (6/24)  30,7  LocalizadoGeneralizado  4,5a  30 (10/20)  30,3  Idade, sexo  Soro/ELISA  ng/mL (SI)  ND  22  11  19 
Khurrum et al., 2016/ Arábia Saudita (Jan 2011‐Dez 2012) 17  Caso controle/NC  150 (90/60)  30,6  GeneralizadoAcralFocal  8m  150 (76/74)  30,7  Idade, sexo  Soro/CLIA  ng/mL (SD)  (< 10, 10‐30, ≥ 30 ng/mL)  137  13  136  14 
Liu et al., 2014/China 18  Caso controle/NC  86  19–56  ND  NC  30  19–56  Idade, sexo  Soro/ELISA  nmoL/L (SD)  (< 25, 25‐47,6, 47,4‐250 nmoL/L)  32  44  10  19 
Ochoa‐Ramírez et al., 2019/ México 19  Caso controle/NC  173 (81/92)  18–45  Disseminado (generalizado, universal), localizado (focal, acrofacial)  ND  184  ND  Idade, sexo  Soro/ELISA  ng/mL (SI)  ND  ND  ND  ND  ND  ND  ND 
Omidian & Asadian 2018/Irã (Apr 2015‐Mar 2016) 20  Ensaio clínico/NC  30 (12/18)  36,93  Generalizado  ND  30 (11/19)  32,03  Idade, sexo  Soro/ECL  nmoL/L (SI)  (≤ 10, 10‐29, 30‐100 nmoL/L)  14  13  18  10 
Pillai & Dinachandran 2019/Índia (Jan‐Abr 2018) 21  Caso controle/NC  50 (27/23)  30,96  Generalizado  2–25a  50 (30/20)  31,45  Idade, sexo, tipo de pele  Soro/NC  ng/mL (SD)  NA  NA  NA  NA  NA  NA  NA 
Prakash & Karthikeyan 2017/Índia (Out 2014‐Maio 2016) 22  Caso controle/V  45 (26/19)  43,78  VulgarAcrofacialFocal  51,04m  45  ND  Idade, sexo  Soro/ELISA  ng/mL (SD)  (< 20, 20‐30,> 30 ng/mL)  23  22  21  21 
Ramalingam & Tang 2018/ Malásia (Jul‐Dez 2014) 23  Transversal/I‐IV  93 (46/47)  40,43  Não segmentarsegmentar  3a  87 (43/44)  39,95  Idade, sexo, etnia, IMC  Soro/NC  ng/mL (SD)  (≤ 20, 20‐30,> 30 ng/mL)  37  29  27  42  23  22 
Saleh et al., 2013/Egito (Abr‐Jun 2011) 24  Caso controle/III‐IV  40 (18/22)  34,1  Não segmentar  3,5a  40 (18/22)  34,2  Idade, sexo, tipo de pele, ingestão de Vit. D  Soro/RIA  ng/mL (SI)  (≤ 20, 20‐30, ≥ 30 ng/mL)  39  33 
Saniee et al., 2019/Irã (primavera e verão 2017) 25  Caso controle/III‐IV  98 (50/48)  30,06  NC  34,65m  98 (53/45)  29,45  Idade, sexo  Soro/ELISA  ng/mL (SD)  (< 10, 10‐30,> 30 ng/mL)  17  53  28  17  46  35 
Sanjay & Raval 2019/ Índia (período de 1 ano) 26  Transversal/NC  25 (15/10)  23,0  FocalGeneralizadoAcrofacialMucoso  NA  25 (16/9)  24,12  Idade, sexo  Soro/ECL  ng/mL (SD)  NA  NA  NA  NA  NA  NA  NA 
Sehrawat et al., 2014/Índia 27  Estudo clínico/IV‐V  30 (10/20)  31,33  Generalizado  10,47a  30 (10/20)  NA  Idade, sexo  Soro/ELISA  nmoL/L (SI)  (< 25, 25‐74, 75‐250 nmoL/L)  24  27 
Shalaby et al., 2017/Egito(Dez 2014‐Jun 2016) 34  Caso controle/NC  40 (30/10)  28,70  Não segmentar  4,7a  40 (25/15)  32,95  Idade, sexo  Soro/ELISA  nmoL/L (SI)  (< 10, 10‐30,> 30 ng/mL)  22  10  36 
Sobeih et al., 2016/Egito (Jul‐Dez 2013) 28  Caso controle/III‐V  75  31,5  VulgarAcrofacialSegmentar  5,5a  75  NA  Idade, sexo  Soro/ELISA  ng/mL (SL)  NA  NA  NA  NA  NA  NA  NA 
Srirama 2016/Índia (período de 4m) 29  Caso controle/NC  30 (11/19)  43,9  Clínico  2–5a  30 (11/19)  49,8  Idade, sexo  Soro/CLIA  ng/mL (SL)  (< 20, 20‐30,> 30 ng/mL)  NA  NA  NA  NA  NA  NA 
Takci et al., 2015/Turquia (Inverno: Nov 2011‐Fev 2012) 30  Caso controle/I, III  44 (24/20)  34,5  VulgarGeneralizadoLocalizado  38,8m  43 (10/33)  33,0  Idade, sexo, tipo de pele  Plasma/RIA  ng/mL (SL)  (< 20, 20‐30,> 30 ng/mL)  32  NA  NA  13  NA  NA 
Ustun et al., 2014/Turquia (b/w 2010‐2011) 31  Transversal/II, III  25 (13/12)  33,9  Vulgar  5,36a  41 (20/21)  34,7  Idade, sexo, tipo de pele  Soro/CLIA  ng/mL (SD)  (< 20, 21‐29, 30‐100 ng/mL)  20  34 
Watabe et al., 2018/Japão (Set 2015‐Jan 2016) 32  ECR/III, IV  45  50,89  Vulgar  NC  45  Pareado por idade  Idade  Soro/NC  ng/mL (SI)  (< 20, 20‐30,> 30 ng/mL)  30  12  17  20 
Xu et al., 2012/China(Mar‐Mai 2011) 33  Caso controle/NC  171 (80/91)  34,1  Segmentar,não segmentar; generalizado, universal, focal, halo de nevos  NC  93  34,6  Idade, sexo  Soro/NC  nmol/L (SD)  (< 25, 25‐75,> 75 nmoL/L)  57  114  57  36 
Xu et al., 2012/China (Set‐Out 2010) 33  Caso controle/NC  30  ND  Segmentar,não segmentar; generalizado, universal, focal, halo de nevos  NC  20  NA  Idade, sexo  Soro/NC  nmol/L (SD)  (< 25, 25‐75,> 75 nmoL/L)  27  18 

NC, não claro; ND, não disponível; SD, sem diferença; NOS, Escala Newcastle‐Ottawa; SI, significativamente inferior; DD, duração da doença; SKT, Tipos de pele de Fitzpatrick; a, anos; M, masculino; F, feminino; n, tamanho da amostra; Def, Deficiência; Insuf, Insuficiência; Suf, Suficiência.

Nível sérico de Vit‐D no vitiligo em comparação com os controles

Como mostrado na figura 2, os pacientes com vitiligo apresentavam níveis diminuídos de Vit‐D em comparação com os controles. Com uma heterogeneidade significativa entre os estudos (I2=95%; p <0,00001), a DMP agrupada (IC 95%) obtida com o modelo de efeitos aleatórios foi de −1,03 (−1,35 a −0,71). Esse resultado sugere uma diferença significativa nos níveis médios de Vit‐D entre pacientes com vitiligo e os controles, e o tamanho do efeito geral para a diferença média obtida corrigida para desvios‐padrão e viés de amostra foi estatisticamente significativo (Z=6,22, p=0,00001).

Figura 2.

Gráfico em floresta e metanálise cumulativa dos estudos incluídos.

(0.44MB).
Análises de subgrupo e metarregressão

Os resultados da metanálise de subgrupo com base no país, método de mensuração de Vit‐D, tipo de vitiligo, sexo, fototipo, história de vitiligo, história de comorbidades/autoimune, atividade da doença (progressiva/ativa ou estável), tipo de trabalho (interno ou externo) e a indexação das revistas (PubMed/ Não PubMed) são apresentados na tabela 2. A DMP agrupada foi estatisticamente significativa nos subgrupos “Egito”, “não Egito”, “ELISA”, “interno vs. externo”, “PubMed” e “Não PubMed”. A significância estatística não foi alcançada em todos os outros subgrupos, incluindo diferentes tipos de vitiligo, tipo de pele, atividade da doença, história de vitiligo, AIC e entre os sexos masculino e feminino em pacientes com vitiligo, o que é sugestivo de possível fonte de heterogeneidade. Entre as várias covariáveis utilizadas na metarregressão (tabela 3), a variável “país” produziu um resultado estatisticamente significativo (coeficiente=0,19; p=0,01) indicativo de fonte significativa de heterogeneidade entre os estudos incluídos. Os resultados da metanálise de correlação apresentados na tabela 4 não mostraram associações significativas da Vit‐D com idade, duração da doença, ASC e VASI.

Tabela 2.

Análise de subgrupos

Subgrupo  No de estudos  I2 (%)  DMP  IC95%  Efeito geral (Z)  p‐valor 
Geral  31  95  −1,03  −1,35; −0,71  6,22  <0,00001 
País             
Egito  10  94  −2,46  −3,21; −1,70  6,39  <0,00001 
Não Egito  21  90  −0,43  −0,69; −0,17  3,22  0,001 
Alemanha  NA  −1,80  −2,15; −1,45  10,09  <0,00001 
China  −0,14  −0,34; 0,06  1,34  0,18 
Índia  88  −0,63  −1,08; −0,17  2,70  0,007 
Irã  56  0,12  −0,30; 0,55  0,56  0,57 
Japão  NA  −0,63  −1,05; −0,20  2,91  0,004 
Malásia  NA  0,07  −0,23; 0,36  0,45  0,65 
México  NA  0,65  −1,13; −0,17  2,64  0,008 
Arábia Saudita  NA  0,17  −0,06; 0,40  1,47  0,14 
Turquia  77  −0,39  −0,84; 0,06  1,71  0,09 
Método             
ELISA  15  95  −1,72  −2,27; −1,16  6,04  <0,00001 
Não ELISA  94  −0,54  −1,09; 0,02  1,91  0,06 
QL  94  −0,20  −0,86; 0,46  0,59  0,56 
RIA  94  −1,42  −2,86; 0,02  1,93  0,05 
LCMS  NA  −0,86  −1,27; −0,45  4,11  <0,0001 
ND/NC  66  −0,26  −0,52; −0,00  1,98  0,05 
Vitiligo             
Tipo A vs. B  10  −0,08  −0,41; 0,25  0,48  0,63 
Tipo A vs. C  37  0,37  −0,11; 0,86  1,51  0,13 
Tipo B vs. C  22  0,22  −0,53; 0,96  0,57  0,57 
Masculino vs. Feminino  11  80  0,24  −0,09; 0,56  1,43  0,15 
Ativa vs. Estável  41  0,18  −0,21; 0,57  0,92  0,36 
SKT‐III vs. IV  48  −0,20  −0,64; 0,24  0,91  0,36 
VFH‐Positivo vs. Negativo  26  0,15  −0,16; 0,46  0,93  0,35 
AIC‐Positivo vs. Negativo  64  0,04  −0,48; 0,56  0,15  0,88 
Interno vs. Externo  68  −0,57  −1,15; 0,01  1,94  0,05 
Interno vs. Externo & U/R  60  −0,45  −0,86; −0,04  2,17  0,03 
Artigo de Revista indexada             
PubMed/MEDLINE  18  96  −1,37  −1,86; −0,88  5,47  <0,00001 
Não PubMed/MEDLINE  13  90  −0,59  −0,96; −0,23  3,16  0,002 

DMP, diferença média padronizada; IC, intervalo de confiança; U/R, Urbano ou Rural; SKT, tipo de pele de Fitzpatrick; ND/NC, não disponível/não claro; ELISA, Enzyme Linked Immunsorbant Assay; RIA, Radioimunoensaio; QL, quimiluminescência; LCMS, Espectrometria de Massa por Cromatografia Líquida; I2, Heterogeneidade; Tipo A, Vulgar/generalizado/disseminado; Tipo B, Acrofacial; Tipo C, Focal/localizado.

Tabela 3.

Análise de metarregressão

Variáveis  Coeficientes  IC95%  EP  p‐valor 
Total n  0,004  −0,003; 0,012  0,004  0,253 
Vitiligo n  0,003  −0,009; 0,016  0,006  0,612 
Controles n  0,015  −0,001; 0,031  0,008  0,059 
Vitiligo‐Masculino  0,009  −0,015; 0,034  0,013  0,468 
Vitiligo‐Feminino  0,007  −0,018; 0,032  0,013  0,593 
Vitiligo‐ Razão M/F  0,030  −0,073; 0,134  0,053  0,566 
Controles ‐ Masculino  0,038  0,001; 0,075  0,019  0,044 
Controles ‐ Feminino  0,031  −0,007; 0,068  0,019  0,107 
Controles ‐ Razão M/F  0,030  −0,073; 0,134  0,053  0,566 
Vitiligo ‐ Idade  0,042  −0,056; 0,140  0,050  0,405 
Controles ‐ Idade  0,012  −0,105; 0,130  0,060  0,837 
Duração da doença  −0,021  −0,261; 0,219  0,122  0,863 
Ano  −0,086  −0,313; 0,140  0,116  0,455 
País  0,194  0,041; 0,347  0,078  0,013 
Método  −0,450  −1,206; 0,306  0,386  0,243 
NOS  −0,166  −0,756; 0,425  0,301  0,583 
Tabela 4.

Metanálise de correlações

Correlação da Vit. D com  Estudos  I2 (%)  IC95% 
Idade  317  86,92  −0,144  −0,438‐0,178  −0,874  0,38 
DD  342  4,97  0,061  −0,052‐0,173  1,057  0,29 
ASC  202  0,00  0,135  −0,006‐0,271  1,876  0,06 
VASI  220  82,68  −0,197  −0,494‐0,142  −1,143  0,25 

Idade, Idade dos pacientes com Vitiligo em anos; DD, duração da doença de Vitiligo; ASC, área da superfície corporal afetada; VASI, Vitiligo Area and Severity Index; I2, Inconsistência; r, coeficiente de correlação agrupado; IC, Intervalo de Confiança.

Viés de publicação e análise de sensibilidade

A análise do gráfico de funil com correlação de Begg (p <0,001) e os testes de regressão de Egger (p <0,001) indicam que pode haver um viés de publicação entre os estudos incluídos (fig. 3). No entanto, é improvável que o viés de publicação representasse um efeito significativo sobre esta metanálise, pois a correção desse viés com o método trim and fill validou nossos resultados originais. Com sete estudos a serem cortados, os valores corrigidos (DMP=−1,41, IC 95%: −1,81 a −1,00) ainda indicavam níveis significativamente mais baixos de Vit‐D no vitiligo em comparação com os controles. Além disso, uma análise de sensibilidade com exclusão de um estudo a cada vez (one‐study leave‐out) mostrou que nenhum estudo individual influenciou significativamente o tamanho do efeito combinado. A DMP combinada obtida era estável e permaneceu estatisticamente significativa após a eliminação de qualquer estudo em particular na análise de sensibilidade (fig. 4).

Figura 3.

Gráfico em funil do viés de publicação.

(0.11MB).
Figura 4.

Análise de sensibilidade com exclusão de um estudo a cada vez (one‐study leave‐out).

(0.6MB).
Discussão

A literatura disponível mostra resultados contrastantes em relação aos níveis de Vit‐D no vitiligo.5–34 Que seja de nosso conhecimento, as duas revisões sistemáticas disponíveis sobre o tópico não são atualizadas e são limitadas em relação ao número de estudos incluídos, subgrupo e análises de metarregressão.2,3 Além disso, em um desses dois estudos, a extração de dados em relação a um estudo incluído estava errada.2,33 E, no outro, tanto o vitiligo adulto quanto o infantil foram incluídos na metanálise.3 Neste estudo atualizado, realizamos uma metanálise incluindo 1.840 pacientes com vitiligo e 1.539 controles de 31 relatos. O resultado de nossa metanálise mostra que a concentração de Vit‐D na circulação é significativamente menor em pacientes com vitiligo em comparação com os controles (DMP=−1,03, p <0,00001).

A forma ativa da Vit‐D e do receptor da vitamina D (RVD) é mediadora de várias funções biológicas importantes, como o metabolismo do cálcio e do fosfato, a formação, o crescimento e a diferenciação óssea. Estudos indicaram que polimorfismos do RVD estão associados aos níveis de Vit‐D e exibem uma predisposição genética para o vitiligo.3,36 Embora a etiopatogênese do vitiligo não esteja completamente esclarecida, a Vit‐D é conhecida por mediar a regulação imunológica e doenças imunes, além de diabetes e doenças cardiovasculares, entre outras.1–3 Também se sabe que o vitiligo está associado a comorbidades autoimunes e, portanto, níveis circulatórios alterados de Vit‐D podem estar associados a pacientes com vitiligo. Os vários fatores que podem influenciar o nível circulatório de Vit‐D incluem tipo de vitiligo, tipo de pele, atividade da doença, história de vitiligo, comorbidades autoimunes, idade, tipo de trabalho em ambientes fechados e ao ar livre, exposição ao sol, variações sazonais e métodos de mensuração de Vit‐D. Em um estudo de coorte, foi relatado que níveis baixos de Vit‐D estão associados a comorbidades autoimunes (odds ratio=10,00), mas não com idade, sexo, raça/etnia, história familiar de vitiligo ou doença autoimune, doença de início recente ou ASC afetada.38

Nossa análise de subgrupo produziu resultados interessantes. Como havia dez estudos do Egito, o máximo para qualquer outro país, realizamos uma metanálise de subgrupo com base em estudos egípcios e não egípcios (21 estudos). Em ambos os casos, a significância estatística foi mantida para um nível diminuído de Vit‐D no vitiligo. Entretanto, quando os países não egípcios foram estratificados adicionalmente, o subgrupo Índia (sete estudos) mostrou uma significância estatística, enquanto os subgrupos de estudos da China (três estudos) e da Turquia (quatro estudos) não produziram uma diferença estatisticamente significativa em níveis de Vit‐D entre seus respectivos grupos de vitiligo e controle (tabela 2). Isso é sugestivo de uma heterogeneidade entre os estudos em decorrência do “país” dos estudos incluídos; os níveis circulatórios de Vit‐D podem variar entre os países por causa de diferentes latitudes, fatores genéticos e alimentares.2,3 Tal fato é comprovado por nossa metanálise de regressão indicando o “país” como uma fonte significativa de heterogeneidade (tabela 3). Nenhuma diferença significativa foi observada quando os níveis de Vit‐D foram comparados entre diferentes tipos de vitiligo não segmentar, presença ou ausência de história de vitiligo e comorbidades autoimunes. Embora os pacientes com vitiligo do sexo feminino e com o fototipo IV tenham apresentado níveis mais baixos de Vit‐D, não houve significância estatística quando comparados aos do sexo masculino e com o fototipo III, respectivamente. A atividade da doença parece ter algum efeito, com o vitiligo estável mostrando níveis mais baixos de Vit‐D em comparação ao vitiligo ativo; nenhum valor de p significativo foi encontrado (tabela 2). Além disso, nenhuma influência significativa de idade, sexo, tamanho da amostra, ano de publicação e duração da doença foi observada na análise de metarregressão. Assim, a metanálise dos coeficientes de correlação também não resultou em associações estatisticamente significativas de Vit‐D com idade, duração da doença, ASC e escore VASI (tabela 4).

É digno de nota que os níveis de Vit‐D foram significativamente mais baixos em pacientes com vitiligo que tinham trabalho interno/urbano quando comparados aos seus equivalentes que exerciam trabalho externo/rural (tabela 2). Esse dado claramente sugere que menos atividade ao ar livre está associada à diminuição dos níveis de Vit‐D no vitiligo, o que indica que o ambiente e, portanto, a intensidade da exposição ao sol, podem influenciar os níveis de Vit‐D. Embora tenha sido possível extrair e resumir os dados na tabela 1, além das diferentes estações/períodos de tempo durante os quais os estudos incluídos foram realizados e as mensurações de Vit‐D foram feitas, esses dados foram insuficientes para conduzir uma metanálise sobre a influência sazonal e variações da Vit‐D associadas no vitiligo.

Quando uma metanálise separada foi realizada com base em estudos com ELISA (n=15) e estudos não ELISA (n=9), a significância estatística foi mantida apenas em um grupo utilizando ELISA, enquanto a metodologia não ELISA (particularmente, quimioluminescência) é um fator importante que contribui para a heterogeneidade entre os estudos. Entretanto, na metarregressão (n=24), o “método” usado como covariável não mostrou um valor estatisticamente significativo. Considerando que os artigos indexados na base de dados PubMed/MEDLINE são de boa qualidade, com informações confiáveis, repetimos uma metanálise separada no PubMed (18 artigos) e estudos não PubMed (13 artigos), e os resultados mantiveram significância estatística em ambos os casos (tabela 2).

Considerando o risco aumentado de vitiligo e o risco de comorbidades autoimunes associadas à diminuição dos níveis de Vit‐D, nossa metanálise e estudos anteriores apontam para a necessidade de manter níveis suficientes de Vit‐D por fototerapia com NB‐UVB e/ou suplementação de Vit‐D.39–41 Além disso, a suplementação com antioxidantes em combinação com fototerapia também foi estudada no vitiligo.42,43 Um estudo recente fornece uma nova evidência sobre uma associação positiva significativa de níveis suficientes de Vit‐D com a estabilidade da doença e um processo de repigmentação satisfatório em pacientes adultos com vitiligo.41 Essa evidência anterior e essa metanálise também reforçam a necessidade de avaliar o nível da Vit‐D no vitiligo. Considerando que a eficácia terapêutica da suplementação de Vit‐D e uma correlação relatada entre níveis suficientes de Vit‐D e o curso do vitiligo são promissoras, mais ensaios clínicos randomizados são necessários sobre o papel da suplementação da Vit‐D.40,41 Isso também abre o escopo para uma futura metanálise de ECR sobre a eficácia da suplementação de Vit‐D no vitiligo.

As limitações do nosso estudo incluem a heterogeneidade entre os estudos, que pode ser atribuída a populações de estudo heterogêneas de diferentes países, diferentes tamanhos de amostra e diferenças em metodologias, diversos fatores ambientais, genéticos, dietéticos e hábitos de estilo de vida e outras limitações inerentes a desenhos de estudos de caso‐controle/observacionais. Entretanto, como a heterogeneidade não pode ser completamente eliminada em uma metanálise, isso foi abordado aplicando o modelo de efeitos aleatórios para estimar o tamanho do efeito geral e por meio de uma análise de sensibilidade cumulativa e com exclusão de um estudo a cada vez (one‐study leave‐out) para avaliar se algum estudo individual afetaria significativamente o tamanho de efeito geral obtido. A análise de sensibilidade com exclusão de um estudo a cada vez (one‐study leave‐out) revelou que nenhum estudo/observação individual tinha influenciado significativamente o tamanho de efeito geral agrupado. Portanto, nossos resultados foram considerados robustos. Além disso, todos os estudos incluídos foram pareados para fatores de confusão como idade e sexo.

Em conclusão, nossa metanálise indica diminuição do nível de Vit‐D em pacientes com vitiligo em comparação com os controles. Esses resultados de nossa metanálise destacam a necessidade de avaliar a Vit‐D para melhorar seu nível no vitiligo. Mais estudos sobre o papel da Vit‐D em relação à patogênese e gravidade do vitiligo são necessários no futuro.

Suporte financeiro

Nenhum.

Contribuições dos autores

Seshadri Reddy Varikasuvu: Concepção do estudo; realização da pesquisa bibliográfica; análise dos dados; elaboração do manuscrito; leitura e aprovação da versão final do manuscrito.

Sowjanya Aloori: Realização da pesquisa bibliográfica; critérios de seleção; coleta de dados e revisões; leitura e aprovação da versão final do manuscrito.

Saurabh Varshney: Realização da pesquisa bibliográfica; critérios de seleção; coleta de dados e revisões; leitura e aprovação da versão final do manuscrito.

Aparna Varma Bhongir: Auxiliou na realização da pesquisa bibliográfica; revisão do manuscrito; leitura e aprovação da versão final do manuscrito.

Conflito de interesses

Nenhum.

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Como citar este artigo: Varikasuvu SR, Aloori S, Varshney S, Bhongir AV. Decreased circulatory levels of Vitamin D in Vitiligo: a meta‐analysis. An Bras Dermatol. 2021;96:284–94.

Trabalho realizado no All India Institute of Medical Sciences, Deoghar, Jharkhand, Índia.

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