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e pirimidina&#8208;pirimidona &#40;6&#8208;4PP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">O diagn&#243;stico e o tratamento de QAs s&#227;o importantes porque apresentam risco de progress&#227;o para carcinoma espinocelular &#40;CEC&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#44;6</span></a> Geralmente&#44; m&#250;ltiplas QAs ocorrem na mesma &#225;rea da pele com fotodano&#44; o que acumula altera&#231;&#245;es no material gen&#233;tico dos ceratin&#243;citos e define o campo de canceriza&#231;&#227;o cut&#226;neo &#40;CCC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Recentemente&#44; a fotoliase&#44; uma enzima monom&#233;rica n&#227;o encontrada nas c&#233;lulas de mam&#237;feros placent&#225;rios&#44; surgiu como alternativa para o tratamento de QA e CCC&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">8&#8211;10</span></a> A enzima tem a capacidade de quebrar os d&#237;meros DPC e 6&#8208;4PP atrav&#233;s da luz vis&#237;vel&#44; um processo denominado fotorreativa&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a> Puig et al&#46; publicaram um artigo de revis&#227;o que concluiu que h&#225; evid&#234;ncias para apoiar os efeitos ben&#233;ficos do tratamento com fotoliase t&#243;pica em QA e CCC&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Considerando os danos indiretos causados pela RUV&#44; por meio da forma&#231;&#227;o de EROs&#44; foram iniciados estudos com agentes antioxidantes &#40;AOx&#41;&#46; A vitamina C &#40;&#225;cido asc&#243;rbico&#41; &#233; o AOx sol&#250;vel em &#225;gua mais prevalente na epiderme&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> Ele neutraliza os radicais livres e EROs nos compartimentos aquosos da pele e desempenha papel importante na regenera&#231;&#227;o da vitamina E &#40;tocoferol&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">13</span></a> A vitamina E &#233; um AOx sol&#250;vel em gordura presente na camada c&#243;rnea&#44; produzida nas gl&#226;ndulas seb&#225;ceas&#44; com capacidade de proteger a membrana celular do estresse oxidativo&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> Murray et al&#46; demonstraram que a combina&#231;&#227;o de tr&#234;s AOx &#40;&#225;cido L&#8208;asc&#243;rbico 15&#37;&#44; alfa&#8208;tocoferol 1&#37; e &#225;cido fer&#250;lico 0&#44;5&#37;&#41;&#44; quando comparada ao placebo &#40;ve&#237;culo&#41;&#44; apresentou efeito fotoprotetor ao reduzir o eritema induzido pela RUV&#44; reduzindo significantemente a forma&#231;&#227;o de &#8220;<span class="elsevierStyleItalic">sunburns cells</span>&#8221;&#44; al&#233;m de reduzir a express&#227;o de p53 e a forma&#231;&#227;o de d&#237;meros de timina&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A maioria dos estudos com f&#243;rmulas antioxidantes se concentra em suas propriedades fotoprotetoras&#46; Por&#233;m&#44; nenhum estudo avaliou sua efic&#225;cia no tratamento das QAs&#46; Al&#233;m disso&#44; a combina&#231;&#227;o de antioxidantes e fotoliase n&#227;o foi descrita na literatura at&#233; agora&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">O objetivo deste estudo foi avaliar a efic&#225;cia do uso de protetor solar com fotoliase em compara&#231;&#227;o ao protetor solar comum&#44; bem como comparar a combina&#231;&#227;o da formula&#231;&#227;o t&#243;pica de antioxidantes <span class="elsevierStyleItalic">versus</span> placebo no tratamento de fotodano avan&#231;ado&#44; caracterizado pela presen&#231;a de QAs e CCC nos antebra&#231;os&#44; ap&#243;s intervalo de oito semanas&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Tipo de estudo</span><p id="par0035" class="elsevierStylePara elsevierViewall">Este foi um ensaio cl&#237;nico randomizado &#40;ECR&#41; controlado&#44; com desenho fatorial aberto para protetor solar comum e protetor solar contendo fotoliase e duplo&#8208;cego para antioxidante t&#243;pico e creme placebo&#46; O estudo foi aprovado pelo Comit&#234; de &#201;tica da institui&#231;&#227;o &#40;n&#176; 2&#46;529&#46;697&#41; e foi registrado no Registro Brasileiro de Ensaios Cl&#237;nicos &#40;n&#176; RBR&#8208;957zf2&#41;&#46; A aloca&#231;&#227;o foi feita na propor&#231;&#227;o de 1&#58;1&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Participantes</span><p id="par0040" class="elsevierStylePara elsevierViewall">Participantes de ambos os sexos&#44; com idade entre 60 e 90 anos&#44; com diagn&#243;stico cl&#237;nico de QA em antebra&#231;o &#40;tr&#234;s a dez les&#245;es em cada antebra&#231;o&#41; e que n&#227;o tinham sido submetidos a tratamento para QAs &#40;exceto com protetor solar&#41; nos &#250;ltimos seis meses foram inclu&#237;dos ap&#243;s assinatura do termo de consentimento livre e esclarecido&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Os crit&#233;rios de exclus&#227;o foram os seguintes&#58; outras dermatoses extensas afetando os antebra&#231;os&#59; hipersensibilidade ou alergia a qualquer uma das subst&#226;ncias em estudo&#59; uso de qualquer subst&#226;ncia imunossupressora sist&#234;mica ou t&#243;pica&#44; retinoides orais ou outros tratamentos locais &#40;corticosteroides&#44; anti&#8208;inflamat&#243;rios&#44; retinoides&#41;&#59; imunocomprometimento&#59; e dist&#250;rbios de coagula&#231;&#227;o&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Interven&#231;&#245;es</span><p id="par0050" class="elsevierStylePara elsevierViewall">Os participantes foram randomizados para receber tratamento com protetor solar com fator de prote&#231;&#227;o solar 99 &#40;FPS 99&#41; contendo fotoliase &#40;PS &#43; F&#41; em lipossomas multilamelares e usando octocrileno&#44; di&#243;xido de tit&#226;nio&#44; avobenzona e Tinosorb&#8208;S&#44; para ser utilizado duas vezes ao dia com aplica&#231;&#227;o em ambos os antebra&#231;os&#44; ou protetor solar comum com FPS 99 &#40;PS&#41; utilizando como protetores qu&#237;micos Tinosorb&#8208;M&#44; Tinosorb&#8208;S&#44; avobenzona&#44; octil&#8208;triazona e 4&#8208;metilbenzilideno c&#226;nfora&#44; com o mesmo FPS do produto contendo fotoliase&#44; tamb&#233;m para uso duas vezes ao dia em ambos os antebra&#231;os&#46; Essas interven&#231;&#245;es n&#227;o foram realizadas &#224;s cegas para os participantes e pesquisadores&#44; pois n&#227;o havia possibilidade de ocultar as apresenta&#231;&#245;es dos produtos utilizados&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Os antebra&#231;os dos participantes de cada um dos grupos foram randomizados para aplicar creme hidratante &#40;placebo&#41; em um antebra&#231;o e creme composto por agentes antioxidantes formulados com 15&#37; de &#225;cido L&#8208;asc&#243;rbico&#44; 1&#37; de alfa&#8208;tocoferol e 0&#44;5&#37; de &#225;cido fer&#250;lico no outro antebra&#231;o &#40;AOx&#41;&#44; ambos aplicados uma vez ao dia&#46; Para essas interven&#231;&#245;es noturnas&#44; houve cegamento tanto para os participantes quanto para os pesquisadores&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Assim&#44; houve a forma&#231;&#227;o de quatro grupos compostos por antebra&#231;os&#58; protetor solar comum e antioxidante t&#243;pico &#40;PS&#47;AOx&#41;&#44; protetor solar comum e placebo &#40;PS&#47;placebo&#41;&#44; protetor solar contendo fotoliase e antioxidante t&#243;pico &#40;PS &#43; F&#47;AOx&#41;&#44; e protetor solar contendo fotoliase e placebo &#40;PS &#43; F&#47;placebo&#41; &#8211; <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#46; O placebo e o AOx foram manipulados em uma emuls&#227;o trif&#225;sica&#44; de cor branca e inodora&#46; Ambos os produtos foram acondicionados em embalagens a v&#225;cuo id&#234;nticas&#44; o que evitou a oxida&#231;&#227;o do &#225;cido asc&#243;rbico contido em uma das formula&#231;&#245;es&#46; As embalagens foram rotuladas apenas com os t&#243;picos de identifica&#231;&#227;o 1 e 2&#46; Ap&#243;s essa randomiza&#231;&#227;o final&#44; as embalagens foram identificadas com as letras &#8220;D&#8221; para aplica&#231;&#227;o do produto no antebra&#231;o direito e &#8220;E&#8221; para aplica&#231;&#227;o no antebra&#231;o esquerdo&#44; para que o paciente pudesse identificar em qual lado aplicar cada produto&#46; Para cada paciente&#44; os tratamentos propostos duraram oito semanas&#46; Houve padroniza&#231;&#227;o das &#225;reas para contagem e avalia&#231;&#227;o de les&#245;es de QA e CCC&#44; e isso se limitou a uma linha que cruza as articula&#231;&#245;es metacarpofalangianas como limite distal&#44; e uma linha que se estendia da fossa antecubital ao epic&#244;ndilo lateral dos antebra&#231;os como limite proximal&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Desfechos</span><p id="par0065" class="elsevierStylePara elsevierViewall">Os desfechos prim&#225;rios foram a elimina&#231;&#227;o total das QAs&#44; redu&#231;&#227;o na atividade de CCC avaliada pela melhora na escala de fotoenvelhecimento do antebra&#231;o &#40;FPS&#44; do ingl&#234;s <span class="elsevierStyleItalic">forearm photoaging scale</span>&#41;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">1</span></a> e a redu&#231;&#227;o no escore de gravidade de QA &#40;AKSS&#44; do ingl&#234;s <span class="elsevierStyleItalic">actinic queratosis severity score</span>&#41;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a> ap&#243;s oito semanas de tratamento&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Os desfechos secund&#225;rios foram redu&#231;&#227;o na contagem de QAs&#44; taxa de elimina&#231;&#227;o parcial &#40;redu&#231;&#227;o de 50&#37; ou mais&#41;&#44; efeitos adversos relacionados ao tratamento&#44; tolerabilidade e aparecimento de tumores cut&#226;neos n&#227;o melanomas&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">C&#225;lculo da amostra</span><p id="par0075" class="elsevierStylePara elsevierViewall">O tamanho da amostra foi calculado para detectar redu&#231;&#227;o na diferen&#231;a de mais de 10&#37; entre os grupos e desvio padr&#227;o equivalente das diferen&#231;as&#46; Adotou&#8208;se poder de 0&#44;9&#44; alfa de 0&#44;05 e estimativa de abandono de 10&#37;&#44; resultando em 40 pacientes &#40;80 antebra&#231;os&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Randomiza&#231;&#227;o e avalia&#231;&#245;es</span><p id="par0080" class="elsevierStylePara elsevierViewall">Os participantes e antebra&#231;os foram randomizados em blocos utilizando uma simula&#231;&#227;o de computador&#46; Ap&#243;s a randomiza&#231;&#227;o computacional&#44; as combina&#231;&#245;es de tratamentos geradas foram separadas individualmente em envelopes lacrados&#46; Os envelopes foram mantidos com o pesquisador e&#44; no momento da inclus&#227;o&#44; foi selecionado aleatoriamente um envelope para orientar o tratamento do paciente&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Os participantes foram avaliados em dois momentos&#58; T0&#44; inclus&#227;o&#44; randomiza&#231;&#227;o&#44; avalia&#231;&#227;o cl&#237;nica e in&#237;cio dos tratamentos&#59; T60&#44; avalia&#231;&#227;o cl&#237;nica&#44; avalia&#231;&#227;o de efeitos adversos e tolerabilidade&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">No momento da inclus&#227;o&#44; as QAs foram contadas e marcadas com uma caneta para cada antebra&#231;o&#44; respeitando os limites anat&#244;micos considerados acima&#59; a ficha de avalia&#231;&#227;o foi preenchida e a escala de fotoenvelhecimento do antebra&#231;o e o escore de gravidade da QAs do antebra&#231;o foram aplicados&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">A escala FPS considera o n&#250;mero de QAs superficiais e hipertr&#243;ficas&#44; quantidade e gravidade das rugas&#44; lentiginose solar&#44; p&#250;rpura vis&#237;vel&#44; cicatrizes atr&#243;ficas em formato estrelado&#44; elastose e perda de elasticidade&#46; Todos os par&#226;metros somados formam uma escala que varia de 0 a 192&#44; e valores totais mais altos indicam maior fotodano&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">1</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">O escore AKSS considera o n&#250;mero de les&#245;es e as seguintes caracter&#237;sticas&#58; grau de eritema&#44; hiperceratose&#44; infiltra&#231;&#227;o e di&#226;metro &#40;medido em mil&#237;metros&#41; das QAs&#46; Cada um dos crit&#233;rios &#233; graduado de 0 a 3&#46; As les&#245;es foram caracterizadas individualmente&#44; e os valores foram somados para obter o total na &#225;rea estudada&#46; Quanto maior o valor total&#44; maior a gravidade das QAs e CCC&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a> Esse escore de gravidade foi publicado e validado para QAs e CCC da cabe&#231;a&#46; Recentemente&#44; esse escore foi aplicado &#224; avalia&#231;&#227;o das QAs dos antebra&#231;os&#44; e sua valida&#231;&#227;o est&#225; em andamento&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">As avalia&#231;&#245;es dos pacientes em ambos os momentos foram realizadas pelo mesmo pesquisador&#44; que desconhecia se o tratamento tinha utilizado antioxidantes t&#243;picos ou placebo&#46; Os pacientes tamb&#233;m n&#227;o sabiam qual f&#243;rmula era o placebo e qual era o antioxidante t&#243;pico&#46; Ao final do estudo&#44; a aloca&#231;&#227;o do grupo foi revelada&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">An&#225;lise estat&#237;stica</span><p id="par0110" class="elsevierStylePara elsevierViewall">Todos os participantes inclu&#237;dos no estudo e randomizados faziam parte da popula&#231;&#227;o com inten&#231;&#227;o de tratar &#40;ITT&#44; do ingl&#234;s <span class="elsevierStyleItalic">intention to treat</span>&#41;&#46; A an&#225;lise de dados foi realizada para a popula&#231;&#227;o ITT utilizando um modelo linear generalizado de efeitos mistos que lida com os dados ausentes em sua estrutura anal&#237;tica&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">As vari&#225;veis categ&#243;ricas foram apresentadas como n&#250;meros absolutos e porcentagens&#46; As vari&#225;veis cont&#237;nuas foram avaliadas quanto &#224; normalidade pelo teste de Shapiro&#8208;Wilk e representadas por m&#233;dias e desvios&#8208;padr&#227;o&#44; ou medianas e quartis &#40;p25&#8208;p75&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">O n&#250;mero de QAs&#44; a escala de FPS e o escore de gravidade de QAs do antebra&#231;o foram comparados por tempo e grupos &#40;ao longo do tempo&#41; utilizando o modelo linear generalizado de efeitos mistos&#44; estrutura de covari&#226;ncia robusta&#44; matriz de covari&#226;ncia autorregressiva tipo 1&#44; compara&#231;&#227;o <span class="elsevierStyleItalic">post&#8208;hoc</span> com a Compara&#231;&#227;o de Sidak e ajuste de probabilidade binomial ou gama negativo&#44; quando indicado&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">O tamanho do efeito foi calculado como a diferen&#231;a nas m&#233;dias de cada vari&#225;vel em T60 e T0 e o intervalo de confian&#231;a pela t&#233;cnica de <span class="elsevierStyleItalic">bootstrap</span> com 1&#46;000 reamostragens&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Os dados foram analisados em IBM SPSS 25<span class="elsevierStyleHsp" style=""></span>v&#46; A signific&#226;ncia foi fixada em p &#60; 0&#44;05&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Resultados</span><p id="par0135" class="elsevierStylePara elsevierViewall">Entre janeiro de 2019 e janeiro de 2020&#44; 40 participantes foram considerados eleg&#237;veis e randomizados para o estudo&#46; Vinte antebra&#231;os constitu&#237;ram parte do grupo PS &#43; F&#47;AOx e do grupo PS &#43; F&#47;placebo&#46; Vinte antebra&#231;os constitu&#237;ram parte dos grupos PS&#47;AOx e PS&#47;placebo&#46; Houve duas desist&#234;ncias no grupo PS &#43; F&#44; n&#227;o associadas &#224;s interven&#231;&#245;es&#44; pois os pacientes n&#227;o retornaram para reavalia&#231;&#227;o na data agendada &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Os principais dados cl&#237;nicos e demogr&#225;ficos dos 40 participantes no in&#237;cio do estudo &#40;T0&#41; s&#227;o apresentados na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; N&#227;o houve diferen&#231;a significativa entre os grupos para nenhuma das vari&#225;veis&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">N&#227;o houve diferen&#231;a significativa nos desfechos prim&#225;rios e secund&#225;rios entre os grupos de protetor solar comum e protetor solar contendo fotoliase &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; A elimina&#231;&#227;o total de QAs foi alcan&#231;ada em tr&#234;s antebra&#231;os tratados com antioxidante t&#243;pico &#40;7&#44;9&#37;&#59; IC 95&#37; 2&#44;6&#8208;13&#44;2&#37;&#41; e um antebra&#231;o tratado com placebo &#40;2&#44;6&#37;&#59; IC 95&#37; 0&#8208;7&#44;9&#37;&#41;&#44; sem diferen&#231;a estat&#237;stica &#40;p &#61; 0&#44;997&#41;&#46; Elimina&#231;&#227;o parcial foi alcan&#231;ada em 18 antebra&#231;os tratados com antioxidante t&#243;pico &#40;47&#44;4&#37;&#59; IC 95&#37; 34&#44;2&#8208;60&#44;5&#37;&#41; e nove antebra&#231;os tratados com placebo &#40;23&#44;7&#37;&#59; IC 95&#37; 13&#44;2&#8208;34&#44;2&#37;&#59; p &#61; 0&#44;018&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Houve redu&#231;&#227;o na contagem de QAs em todos os grupos ao longo do tempo &#40;p &#60; 0&#44;05&#41;&#46; Al&#233;m disso&#44; houve redu&#231;&#227;o na contagem de QAs nos grupos que utilizaram antioxidante t&#243;pico &#40;PS&#47;AOx e PS &#43; F&#47;AOx&#41; em rela&#231;&#227;o aos que utilizaram placebo &#40;p &#60; 0&#44;05&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a> e <a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">O escore na escala FPS diminuiu para todos os grupos ao longo do tempo &#40;p &#60; 0&#44;05&#41;&#44; independentemente do grupo de tratamento &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; N&#227;o houve diferen&#231;a estatisticamente significativa entre as outras interven&#231;&#245;es para esse desfecho&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Da mesma maneira&#44; houve redu&#231;&#227;o do escore AKSS para todos os grupos ao longo do tempo &#40;p &#60; 0&#44;05&#41;&#44; sem superioridade para nenhum tratamento &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Os tamanhos de efeito para os desfechos s&#227;o mostrados na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46; A diferen&#231;a nas m&#233;dias de AKSS e elimina&#231;&#227;o parcial foi maior nos grupos que usaram protetor solar com fotoliase e antioxidante t&#243;pico &#40;PS &#43; F&#47;AOx&#41; em compara&#231;&#227;o com os grupos que utilizaram placebo&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Seguran&#231;a e tolerabilidade</span><p id="par0170" class="elsevierStylePara elsevierViewall">Prurido foi descrito com o uso de antioxidante t&#243;pico e placebo por um participante&#59; outro indiv&#237;duo descreveu prurido com o uso de protetor solar contendo fotoliase&#46; N&#227;o houve relatos de eritema&#44; edema&#44; ulcera&#231;&#227;o ou bolhas&#44; e os tratamentos propostos foram bem tolerados&#46; Houve caso de carcinoma basocelular &#40;CBC&#41; no antebra&#231;o esquerdo de um dos participantes&#44; onde ele estava aplicando protetor solar contendo fotoliase e antioxidante t&#243;pico&#46; Outro participante desenvolveu carcinoma espinocelular &#40;CEC&#41; no antebra&#231;o esquerdo&#44; onde estava aplicando protetor solar comum e antioxidante t&#243;pico&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discuss&#227;o</span><p id="par0175" class="elsevierStylePara elsevierViewall">N&#227;o foram encontradas diferen&#231;as no tratamento de fotodano avan&#231;ado e CCC na compara&#231;&#227;o entre o uso de protetor solar com fotoliase e protetor solar comum sem fotoliase&#46; No entanto&#44; o uso de f&#243;rmula antioxidante proporcionou redu&#231;&#227;o na contagem de QAs&#44; o que reflete redu&#231;&#227;o na atividade do CCC&#46; Embora o antioxidante t&#243;pico seja frequentemente utilizado como um produto antienvelhecimento&#44; o presente estudo mostrou melhora na contagem de QAs&#44; sem mudan&#231;a significativa em outros aspectos da escala de fotoenvelhecimento do antebra&#231;o&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Quando as interven&#231;&#245;es foram analisadas ao longo do tempo&#44; todos os par&#226;metros mostraram melhoras estatisticamente significantes&#46; A redu&#231;&#227;o ou resolu&#231;&#227;o das QAs pode ocorrer em at&#233; 21&#37; dos pacientes em um ano&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a> No presente ensaio cl&#237;nico&#44; todos os participantes utilizaram pelo menos protetor solar comum&#44; com redu&#231;&#227;o ou resolu&#231;&#227;o de 38&#44;7&#37; nas QAs nos antebra&#231;os&#46; Al&#233;m disso&#44; em duas publica&#231;&#245;es foram relatadas que o uso regular de protetor solar reduziu a contagem de QAs em at&#233; 25&#37; em pacientes imunocompetentes e 50&#37; em pacientes transplantados com &#243;rg&#227;os s&#243;lidos&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">19&#44;20</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Puig et al&#46; analisaram as evid&#234;ncias dispon&#237;veis nos &#250;ltimos dez anos sobre o uso de protetor solar contendo fotoliase&#46; Os autores analisaram 11 estudos&#44; totalizando 228 participantes&#44; dos quais apenas tr&#234;s eram ECRs&#44; e conclu&#237;ram que havia evid&#234;ncias para apoiar o uso de fotoliase para o tratamento de QAs e CCC&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Um dos ensaios cl&#237;nicos foi o de Moscarela et al&#46;&#44; que comparou o uso de protetor solar com fotoliase e protetor solar comum com FPS 50 em pacientes com quatro ou mais QAs na face e no couro cabeludo&#46; O estudo incluiu 50 participantes&#44; mas teve 14 desist&#234;ncias&#44; resultando em 17 participantes que utilizaram protetor solar com fotoliase e 19 que usaram protetor solar comum com FPS 50&#46; Ap&#243;s seis meses de seguimento&#44; houve redu&#231;&#227;o na contagem de QAs em ambos os grupos&#44; o que n&#227;o obteve signific&#226;ncia estat&#237;stica&#46; Ao avaliar o subgrupo de participantes com at&#233; 10 QAs &#40;n &#61; 20&#41;&#44; o grupo de protetor solar com fotoliase mostrou&#8208;se superior na redu&#231;&#227;o da contagem de QAs&#46; Nesse subgrupo&#44; 14&#37; dos participantes que utilizaram protetor solar com fotoliase apresentaram novas les&#245;es em compara&#231;&#227;o com 54&#37; daqueles que usaram protetor solar comum com FPS 50&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a> No presente estudo&#44; apenas um paciente no grupo de protetor solar com fotoliase apresentou novas QAs&#44; contra nenhum no grupo de protetor solar comum&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Eibenschutz et al&#46; conduziram um ensaio cl&#237;nico com 30 participantes para avaliar a efic&#225;cia do protetor solar com fotoliase <span class="elsevierStyleItalic">versus</span> protetor solar comum no tratamento de QAs e CCC da face e do couro cabeludo ap&#243;s sess&#227;o de terapia fotodin&#226;mica com metil&#8208;aminolevulinato &#40;MAL&#8208;PDT&#41;&#46; Aumento no n&#250;mero de QAs foi observado ap&#243;s nove meses de tratamento nos participantes que utilizaram protetor solar comum&#44; enquanto houve redu&#231;&#227;o nas QAs nos participantes que utilizaram protetor solar com fotoliase &#40;p &#61; 0&#44;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">22</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Puig et al&#46; desenvolveram um estudo prospectivo&#44; controlado e n&#227;o randomizado com 13 participantes com QAs em &#225;reas expostas para avaliar a efic&#225;cia do protetor solar com fotoliase <span class="elsevierStyleItalic">versus</span> protetor solar comum por quatro semanas no tratamento de QAs e CCC&#46; Os grupos eram formados por nove participantes utilizando protetor solar com fotoliase e tr&#234;s utilizando protetor solar comum&#46; O estudo analisou os seguintes desfechos&#58; melhora cl&#237;nica&#44; dermatoscopia&#44; imuno&#8208;histoqu&#237;mica e aspecto &#224; microscopia confocal&#46; Houve melhora estatisticamente significante em todos os desfechos estudados no grupo que usou protetor solar com fotoliase&#44; mas n&#227;o houve melhora no grupo que usou protetor solar comum&#46; Entretanto&#44; esse foi um estudo n&#227;o randomizado&#44; com baixo n&#250;mero de participantes&#44; e a contagem de QAs n&#227;o foi analisada como desfecho&#44; al&#233;m de apresentar distribui&#231;&#227;o desproporcional entre os grupos&#44; o que compromete a validade dos dados&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">O presente ECR n&#227;o mostrou efic&#225;cia superior do protetor solar contendo fotoliase no tratamento de QAs no antebra&#231;o em pacientes imunocompetentes&#44; o que contradiz os resultados de estudos anteriores&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">O uso de subst&#226;ncias antioxidantes associadas ao protetor solar tem se tornado frequente&#44; uma vez que v&#225;rios estudos t&#234;m demonstrado efeito fotoprotetor ao reduzir o eritema induzido pela RUV&#44; diminuindo a express&#227;o de p53&#44; diminuindo a forma&#231;&#227;o de &#8220;sunburns cells&#8221; e diminuindo a express&#227;o de citocinas imunossupressoras&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">14</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">A vitamina C neutraliza os radicais livres nos compartimentos aquosos da pele&#44; al&#233;m de desempenhar um papel importante na regenera&#231;&#227;o da vitamina E&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">12&#44;13</span></a> A principal fun&#231;&#227;o da vitamina E &#233; proteger as membranas celulares do estresse oxidativo&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">A associa&#231;&#227;o de &#225;cido L&#8208;asc&#243;rbico 15&#37; com alfa&#8208;tocoferol 1&#37; demonstrou que eles t&#234;m efeito sin&#233;rgico na pele&#46; Quando o alfa&#8208;tocoferol neutraliza o estresse oxidativo nos l&#237;pides&#44; seus produtos oxidados podem ser regenerados pelo &#225;cido L&#8208;asc&#243;rbico&#46; Essa intera&#231;&#227;o ajuda a renovar a prote&#231;&#227;o antioxidante nos tecidos&#46; A formula&#231;&#227;o contendo os dois produtos dobrou a prote&#231;&#227;o UV para a pele quando comparada ao &#225;cido L&#8208;asc&#243;rbico isoladamente&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">23&#44;24</span></a> Lin et al&#46; demonstraram que a adi&#231;&#227;o de &#225;cido fer&#250;lico a 0&#44;5&#37; aumentou tanto a estabilidade da f&#243;rmula quanto dobrou a prote&#231;&#227;o UV para a pele&#46; &#201; postulado que o &#225;cido fer&#250;lico protege o &#225;cido L&#8208;asc&#243;rbico e o alfa&#8208;tocoferol&#44; sofrendo oxida&#231;&#227;o antes dos outros na f&#243;rmula&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">25</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">N&#227;o h&#225; estudos avaliando o uso de antioxidantes t&#243;picos para o tratamento de QAs e CCC&#46; O presente estudo demonstrou efeito ben&#233;fico e seguro da combina&#231;&#227;o de &#225;cido L&#8208;asc&#243;rbico 15&#37;&#44; alfa&#8208;tocoferol 1&#37; e &#225;cido fer&#250;lico 0&#44;5&#37; na redu&#231;&#227;o do n&#250;mero de QAs&#44; consequentemente controlando a atividade do CCC&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Uma das limita&#231;&#245;es do presente estudo foi a aus&#234;ncia da compara&#231;&#227;o direta entre os grupos utilizando protetor solar comum e protetor solar com fotoliase&#44; tornando essa compara&#231;&#227;o inferior &#224; compara&#231;&#227;o entre antioxidante t&#243;pico <span class="elsevierStyleItalic">versus</span> placebo&#46; Al&#233;m disso&#44; o estudo incluiu apenas pacientes com contagens de QAs entre tr&#234;s e dez&#44; e os resultados podem n&#227;o se aplicar aos pacientes com maior n&#250;mero de les&#245;es&#44; bem como em pacientes imunossuprimidos&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Reconhecemos que o intervalo de seguimento de 60 dias pode estar relacionado fracos resultados apresentados no grupo que utilizou a fotoliase&#46; Talvez para obter melhores resultados&#44; seu uso deva ser prolongado&#46; No entanto&#44; mais estudos devem ser realizados para confirmar essa hip&#243;tese&#46; Al&#233;m disso&#44; como demonstrado por Eibenschutz et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">22</span></a> &#233; poss&#237;vel que a fotoliase tenha a melhor indica&#231;&#227;o para evitar a recorr&#234;ncia de QAs tratadas por outros m&#233;todos&#44; sendo uma alternativa para estabilizar&#44; mas n&#227;o tratar o CCC&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Tamb&#233;m acredita&#8208;se que o uso prolongado de antioxidantes t&#243;picos possa melhorar outros sinais de fotoenvelhecimento&#44; uma vez que estudos mostraram que a redu&#231;&#227;o na transcri&#231;&#227;o da metaloproteinase&#8208;1<span class="elsevierStyleHsp" style=""></span>da matriz inibe a forma&#231;&#227;o de d&#237;meros de timina&#44; reduzindo o processo de degrada&#231;&#227;o do col&#225;geno e a carcinog&#234;nese&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">26</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">O ponto forte deste estudo foi a possibilidade de avaliar os efeitos de tr&#234;s interven&#231;&#245;es em um desenho de estudo fatorial&#44; em um grupo de pacientes imunocompetentes que frequentemente apresentam QAs em antebra&#231;o&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclus&#245;es</span><p id="par0250" class="elsevierStylePara elsevierViewall">O protetor solar &#40;FPS 99&#41; contendo fotoliase n&#227;o foi superior ao protetor solar comum &#40;FPS 99&#41; nos desfechos estudados&#44; ap&#243;s oito semanas&#46; O uso da f&#243;rmula antioxidante t&#243;pica &#233; seguro&#44; toler&#225;vel e tamb&#233;m demonstrou maior efic&#225;cia na redu&#231;&#227;o da contagem de QAs em antebra&#231;os quando associada ao protetor solar comum ou protetor solar com fotoliase&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Suporte financeiro</span><p id="par0255" class="elsevierStylePara elsevierViewall">Este estudo recebeu suporte financeiro do Fundo de Amparo &#224; Dermatologia do Estado de S&#227;o Paulo &#8208; Sebasti&#227;o Sampaio &#40;FUNADERSP&#41;&#44; n&#176; 73&#8208;2018&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Contribui&#231;&#245;es dos autores</span><p id="par0260" class="elsevierStylePara elsevierViewall">Bruno Augusto Alvares&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o dos dados&#44; ou an&#225;lise e interpreta&#231;&#227;o dos dados&#59; an&#225;lise estat&#237;stica&#59; reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica dos casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Anna Carolina Miolla&#58; Reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e &#47;ou terap&#234;utica dos casos estudados&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Juliano Vilaverde Schimitt&#58; Concep&#231;&#227;o e planejamento do estudo&#59; an&#225;lise estat&#237;stica&#59; reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e &#47; ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Helio Amante Miot&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o dos dados&#44; ou an&#225;lise e interpreta&#231;&#227;o dos dados&#59; an&#225;lise estat&#237;stica&#59; reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e &#47; ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Luciana Patricia Fernandes Abbade&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o dos dados&#44; ou an&#225;lise e interpreta&#231;&#227;o dos dados&#59; an&#225;lise estat&#237;stica&#59; reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e &#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflito de interesses</span><p id="par0285" 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">V&#225;rios tratamentos est&#227;o dispon&#237;veis para a pele com fotodano avan&#231;ado&#44; que se caracteriza pela presen&#231;a de queratoses act&#237;nicas &#40;QAs&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar a efic&#225;cia do uso de protetor solar com fotoliase em compara&#231;&#227;o ao protetor solar comum&#44; bem como comparar a combina&#231;&#227;o de formula&#231;&#227;o t&#243;pica de antioxidantes <span class="elsevierStyleItalic">versus</span> placebo no tratamento do fotodano avan&#231;ado&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Este foi um ensaio cl&#237;nico fatorial randomizado&#44; duplo&#8208;cego&#46; Os participantes com QAs nos antebra&#231;os foram randomizados para aplicar protetor solar &#40;PS&#41; comum ou protetor solar com fotoliase &#40;PS &#43; F&#41; em ambos os antebra&#231;os durante o dia&#46; Um dos antebra&#231;os em cada grupo foi randomizado novamente para receber antioxidantes t&#243;picos &#40;AOx&#41;&#44; e o outro antebra&#231;o recebeu creme placebo &#40;ambos para aplica&#231;&#227;o noturna&#41;&#46; Os quatro grupos foram PS&#47;AOx&#44; PS&#47;placebo&#44; PS &#43; F&#47;AOx e PS &#43; F&#47;placebo&#46; A dura&#231;&#227;o do tratamento foi de oito semanas&#46; Os desfechos prim&#225;rios foram elimina&#231;&#227;o total de QAs e redu&#231;&#227;o da escala de fotoenvelhecimento do antebra&#231;o &#40;FPS&#41; e do escore de gravidade de QA&#46; Os desfechos secund&#225;rios foram redu&#231;&#227;o na contagem de QAs&#44; a taxa de elimina&#231;&#227;o parcial e a seguran&#231;a&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Quarenta participantes &#40;80 antebra&#231;os&#41; foram inclu&#237;dos&#46; Todos os grupos mostraram melhoras significativas nos resultados na oitava semana&#46; N&#227;o houve diferen&#231;as significantes entre PS e PS &#43; F para nenhum dos resultados&#46; O uso de AOx levou &#224; redu&#231;&#227;o significante na contagem de QAs &#40;22&#37;&#59; p &#60; 0&#44;05&#41;&#46; Elimina&#231;&#227;o parcial foi obtida em 18 &#40;47&#44;4&#37;&#41; antebra&#231;os tratados com AOx e em nove &#40;23&#44;7&#37;&#41; tratados com placebo &#40;p &#60; 0&#44;05&#41;&#46; Todos os grupos reduziram o escore FPS&#44; sem diferen&#231;as significantes entre eles&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Limita&#231;&#245;es do estudo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">O curto per&#237;odo de seguimento e a aus&#234;ncia de reavalia&#231;&#227;o livre de tratamento foram limita&#231;&#245;es do presente estudo&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclus&#245;es</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">N&#227;o h&#225; diferen&#231;a no tratamento do fotodano avan&#231;ado da pele ao comparar o uso de protetor solar com fotoliase e protetor solar comum&#59; os antioxidantes t&#243;picos tiveram mais efic&#225;cia na redu&#231;&#227;o da contagem de QAs do que o placebo&#46;</p></span>"
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          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Contagem de QAs em T0 e T60&#46;</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">QAs&#44; queratoses act&#237;nicas&#59; PS&#44; protetor solar comum FPS 99&#59; PS&#43;F&#44; protetor solar contendo fotoliase FPS 99&#59; AOX&#44; creme composto por agentes antioxidantes&#46; &#42;p &#60;0&#44;05&#46;</p>"
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                  \t\t\t\t">41 &#40;35&#8211;47&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;4 &#40;1&#46;9&#8211;2&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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