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Implantación de una prueba rápida de infección estreptocócica: ¿su uso también mejora la adherencia antibiótica?
Introduction of rapid streptococcal antigen test: can its use improve adherence to antibiotic therapy?
Anna Maria Bonet-Estevea,b, Laia Font-Riberac, Judit Dorca-Vilad, Antonia Retamal- Cañize, Pere Roura-Pochf, Josep Vidal-Alaballb,e,g,
Autor para correspondencia
jvidal.cc.ics@gencat.cat

Autor para correspondencia.
a Unitat de Farmàcia Atenció Primària. Gerència Territorial Catalunya Central. Institut Català de la Salut, Sant Fruitós de Bages, España
b Grupo de Investigación PROSAARU (Promoción de la Salud en el Ámbito Rural), Gerència Territorial Catalunya Central. Institut Català de la Salut, Sant Fruitós de Bages, España
c Agencia de Salut Pública de Barcelona, Barcelona
d Xarxa Assistencial Universitària de Manresa, Calle Dr. Joan Soler, 1-3, Manresa 08243, España
e Unitat de Suport a la Recerca de la Catalunya Central, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina, Sant Fruitós de Bages, España
f Servei d’Atenció Primària d’Osona. Gerència Territorial de la Catalunya Central, Institut Català de la Salut, Sant Fruitós de Bages, España
g Facultat de Medicina. Universitat de Vic-Universitat Central de Catalunya, Vic, España
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supone un problema de salud p&#250;blica por la posibilidad emergente de resistencias antibi&#243;ticas&#46; En Espa&#241;a&#44; mueren aproximadamente 3&#46;000 personas al a&#241;o a causa de infecciones hospitalarias provocadas por bacterias resistentes<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">3</span></a> y en el mundo se atribuyen 700&#46;000 muertes anuales a esta causa<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a>&#46; Si no se toman medidas de car&#225;cter urgente&#44; se estima que en 2050 la cifra de muertes anuales atribuibles a infecciones multiresistentes podr&#237;a ascender a los 10 millones a nivel mundial&#44; superando el n&#250;mero actual de muertes anuales por c&#225;ncer<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Seg&#250;n informaci&#243;n de la Base de datos para la Investigaci&#243;n Farmacoepidemiol&#243;gica en Atenci&#243;n Primaria &#40;BIFAP&#41; actualizados en 2008&#44; el diagn&#243;stico primario con mayor prescripci&#243;n de antibi&#243;ticos en Espa&#241;a fue la infecci&#243;n del tracto respiratorio &#40;ITR&#41; y el 49&#37; de los usuarios a los que se les prescribi&#243; antibi&#243;tico fueron diagnosticados con alguna de estas<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">5</span></a>&#46; Entre las ITR&#44; la faringoamigdalitis es una de las m&#225;s frecuentes&#44; con una prevalencia del 18 al 20&#44;4&#37;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;7</span></a>&#46; En atenci&#243;n pedi&#225;trica&#44; el 75&#37; de las faringoamigdalitis son tratadas con antibi&#243;ticos<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a>&#44; y en adultos&#44; el 88&#44;9&#37; de las amigdalitis y el 18&#44;3&#37; de las faringitis agudas<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a>&#44; pese a que estas patolog&#237;as no deber&#237;an tratarse de forma sistem&#225;tica con estos<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a>&#44; ya que &#250;nicamente el 37 al 50&#37; de las faringoamigdalitis en infantes y el 15 al 25&#37; en adultos tienen una etiolog&#237;a bacteriana<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">10&#44;11</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">El est&#225;ndar para el diagn&#243;stico de la faringoamigdalitis consiste en averiguar si es de origen viral o bacteriano siendo el <span class="elsevierStyleItalic">Streptococcus pyogenes &#40;EbhGA&#41;</span> el agente principal causante de la faringoamigdalitis bacteriana&#46; La infecci&#243;n causada por este requiere la prescripci&#243;n de antibi&#243;tico ya que acorta la transmisi&#243;n y diseminaci&#243;n de la bacteria a la comunidad&#44; reduce la sintomatolog&#237;a con respecto al grupo no tratado una media de 16 horas y ayuda a prevenir las complicaciones supurativas y no supurativas<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">La incertidumbre en el proceso del diagn&#243;stico es una de las principales razones de prescripci&#243;n innecesaria de antibi&#243;ticos en atenci&#243;n primaria&#46; Por consiguiente&#44; uno de los objetivos del Plan Nacional frente a la Resistencia a los Antibi&#243;ticos 2019-2021 &#40;PRAN&#41; es promover el uso racional de m&#233;todos de diagn&#243;stico r&#225;pido<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a>&#46; En el documento de consenso del 2011&#44; sobre el diagn&#243;stico y tratamiento de la faringoamigdalitis&#44; las pruebas de detecci&#243;n r&#225;pida de ant&#237;geno estreptoc&#243;cico &#40;PDR&#41; y el cultivo de muestra faringoamigdalar se consideran no definitivas para su detecci&#243;n&#44; ya que el paciente podr&#237;a padecer una infecci&#243;n viral y ser portador de <span class="elsevierStyleItalic">EbhGA</span><a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a>&#46; Debido a lo anterior y&#44; a que el resultado del cultivo puede demorarse 48 a 72 h&#44; en la pr&#225;ctica cl&#237;nica&#44; se utilizan habitualmente los criterios cl&#237;nicos para identificar a los pacientes que necesitan una prueba complementaria y tratamiento antibi&#243;tico<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">En este sentido&#44; para el diagn&#243;stico de la faringoamigdalitis los criterios de Centor son los m&#225;s conocidos y se dividen en cuatro puntos&#58; historia o presencia de fiebre &#8805; 38<span class="elsevierStyleHsp" style=""></span>&#176;<span class="elsevierStyleSmallCaps">C</span>&#44; inflamaci&#243;n o exudado faringoamigdalar&#44; adenopat&#237;as laterocervicales dolorosas y ausencia de tos&#46; Los criterios de McIsaac&#44; basados en los de Centor&#44; incluyen la variable edad entre tres a 14 a&#241;os&#44; ya que la faringitis estreptoc&#243;cica presenta una m&#225;xima incidencia entre los cinco y los 15 a&#241;os<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">16</span></a>&#46; Hay disparidad en cuanto al valor pr&#225;ctico de esta puntuaci&#243;n ya que tiene una elevada especificidad y valor predictivo negativo&#44; pero menor valor predictivo positivo&#46; La probabilidad de faringoamigdalitis estreptoc&#243;cica se estima del 30 al 56&#37; en puntuaciones en la escala de Centor &#8805; 3<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Las escalas de predicci&#243;n cl&#237;nica no deben ser utilizadas para la decisi&#243;n de instaurar antibioterapia emp&#237;rica<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a>&#46; No obstante&#44; seg&#250;n un an&#225;lisis del 2017 que incluy&#243; casos diagnosticados de faringoamigdalitis&#44; de los pacientes menores de 14 a&#241;os a los que se prescribi&#243; antibi&#243;tico &#40;54&#44;69&#37;&#41;&#44; &#250;nicamente se efectu&#243; la PDR al 10&#44;33&#37;&#44; mostrando que algunos pediatras no la realizaban a pesar de que los pacientes obten&#237;an puntuaciones altas en la escala de Centor<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">La mayor parte de estudios sobre adherencia al tratamiento son de patolog&#237;as cr&#243;nicas&#46; En un estudio sobre la asociaci&#243;n de la adherencia terap&#233;utica y la PDR en adultos&#44; se observaron mejores resultados en el grupo de pacientes a los que se les realiz&#243; la PDR<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">18</span></a>&#46; En estudios sobre la adherencia al tratamiento antibi&#243;tico en general en poblaci&#243;n infantil se observ&#243; que el 44&#44;4 al 65&#44;7&#37; de infantes cumplieron correctamente el tratamiento prescrito<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">19&#44;20</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Ante la posibilidad de utilizar una prueba de diagn&#243;stico r&#225;pido del <span class="elsevierStyleItalic">EbhGA</span> para orientar en la toma de decisiones en la pr&#225;ctica cl&#237;nica sobre la etiolog&#237;a y el tratamiento de la patolog&#237;a infecciosa faringoamigdalar&#44; se plante&#243; un programa de implantaci&#243;n de la PDR vinculado a un proyecto de investigaci&#243;n con el fin de estudiar su efectividad cl&#237;nica&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">El objetivo principal de este este estudio fue evaluar la influencia del resultado de la prueba diagn&#243;stica r&#225;pida para identificar el <span class="elsevierStyleItalic">EbhGA</span> en las infecciones faringoamigdalares&#44; en t&#233;rminos de mejora de la adherencia a la terapia antibi&#243;tica&#44; en las consultas de pediatr&#237;a de atenci&#243;n primaria del Instituto Catal&#225;n de la Salud de la Catalu&#241;a Central&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Los objetivos secundarios del estudio fueron&#58; 1&#41; describir la relaci&#243;n entre la puntuaci&#243;n de Centor&#44; el resultado de la prueba diagn&#243;stica r&#225;pida de <span class="elsevierStyleItalic">EbhGA</span> y la prescripci&#243;n de tratamiento antibi&#243;tico&#59; 2&#41; describir el grado de adherencia terap&#233;utica global de la poblaci&#243;n infantil al antibi&#243;tico prescrito en la patolog&#237;a faringoamigdalar y 3&#41; describir los motivos de no adherencia terap&#233;utica al antibi&#243;tico en la poblaci&#243;n del estudio&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Material y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Dise&#241;o del estudio</span><p id="par0055" class="elsevierStylePara elsevierViewall">Se dise&#241;&#243; un ensayo cl&#237;nico comunitario con dos grupos de estudio&#46; Los pacientes participantes se seleccionaron por muestreo consecutivo y la asignaci&#243;n a los grupos fue de forma aleatoria&#46; En el estudio participaron 27 pediatras de diferentes dispositivos y recursos asistenciales de atenci&#243;n primaria pedi&#225;trica del Instituto Catal&#225;n de la Salud adscritos a la Gerencia Territorial de la Catalu&#241;a Central&#46; La participaci&#243;n de los pediatras en el estudio se hizo por conveniencia &#40;se present&#243; el estudio en las reuniones locales de pediatr&#237;a y se les invit&#243; a participar de forma voluntaria y por escrito&#44; acept&#225;ndose a los facultativos cl&#237;nicos interesados&#41;&#46; El estudio se efectu&#243; entre noviembre del 2010 y febrero del 2011&#44; ambos inclusive&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">El estudio fue aprobado por el Comit&#233; de &#201;tica de la Fundaci&#243;n Jordi Gol i Gurina &#40;P10&#47;61&#41; y cuenta con los consentimientos informados por escrito de los padres o tutores legales de los pacientes para su participaci&#243;n en el estudio&#44; as&#237; como el consentimiento informado de los pacientes mayores de 14 a&#241;os&#46; Los datos extra&#237;dos en el estudio son an&#243;nimos y fueron tratados con confidencialidad estricta&#44; siguiendo en todo momento los principios &#233;ticos de la Declaraci&#243;n de Helsinki de 1964&#44; revisados en 2013 por la Organizaci&#243;n Mundial de la Salud &#40;OMS&#41;&#46; El estudio cumple con el Reglamento Europeo de Protecci&#243;n de Datos &#8211; Reglamento &#40;UE&#41; 2016&#47;679 de 27 de abril &#40;GDPR&#41; y la Ley Org&#225;nica 3&#47;2018&#44; de 5 de diciembre&#44; de Protecci&#243;n de Datos Personales y garant&#237;a de los derechos digitales&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Poblaci&#243;n de estudio&#46; Criterios de inclusi&#243;n y exclusi&#243;n</span><p id="par0065" class="elsevierStylePara elsevierViewall">La poblaci&#243;n de estudio fueron pacientes con edades comprendidas entre los tres y 15 a&#241;os&#44; atendidos en las consultas pedi&#225;tricas por sospecha de patolog&#237;a faringoamigdalar de origen infeccioso &#40;odinofagia y fiebre&#41;&#44; en la regi&#243;n de la Catalu&#241;a Central&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Se excluyeron del estudio los sujetos que presentasen una sintomatolog&#237;a catarral sugestiva de virasis&#46; Debido a que el desarrollo del proyecto contempl&#243; un seguimiento telef&#243;nico&#44; se excluyeron los pacientes cuyo padre&#44; madre&#44; tutor o responsable no fuera competente para expresarse en las lenguas propias del pa&#237;s &#40;catal&#225;n&#47;castellano&#41; o no pudiera facilitar un tel&#233;fono donde recibir la llamada de seguimiento&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Tama&#241;o muestral</span><p id="par0075" class="elsevierStylePara elsevierViewall">La determinaci&#243;n del tama&#241;o de la muestra se estim&#243; con la calculadora <span class="elsevierStyleItalic">online</span> GRANMO<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">21</span></a>&#44; con un riesgo alfa de 0&#44;05&#44; un riesgo beta inferior al 0&#44;2 en un contraste bilateral y asumiendo una p&#233;rdida de seguimiento del 20&#37;&#46; Teniendo en cuenta que el grado de adherencia al tratamiento antibi&#243;tico es del 62&#44;2&#37;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a>&#44; se requieren 203 sujetos por grupo para detectar una diferencia igual o superior al 15&#37; entre el grupo control y el grupo intervenci&#243;n&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Metodolog&#237;a</span><p id="par0080" class="elsevierStylePara elsevierViewall">Cuando un pediatra&#44; en el ejercicio de su actividad asistencial cotidiana&#44; identificaba a un paciente susceptible de ser incluido en el estudio&#44; verificaba que cumpl&#237;a los criterios de inclusi&#243;n y en ese punto&#44; proced&#237;a a informar al paciente y su padre&#44; madre o tutor sobre la existencia del estudio y los invitaba a participar y a expresar su consentimiento&#46; Tambi&#233;n se solicit&#243; el consentimiento escrito de los pacientes de entre 12 y 15 a&#241;os&#46; Si aceptaban participar&#44; se les asignaba aleatoriamente al grupo intervenci&#243;n o al grupo control&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">El pediatra fue ciego a la intervenci&#243;n hasta el momento en el que el paciente participaba&#44; pero no lo fue durante la fase de hacer el diagn&#243;stico y finalizaci&#243;n de la visita&#44; debido a las caracter&#237;sticas del dise&#241;o del estudio&#46; La persona que realiz&#243; la evaluaci&#243;n de la adherencia al tratamiento antibi&#243;tico mediante una encuesta telef&#243;nica fue ciega a la intervenci&#243;n&#44; ya que no conoc&#237;a a qu&#233; grupo pertenec&#237;a el paciente&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Los datos se analizaron siguiendo las gu&#237;as CONSORT &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; Se cre&#243; una base de datos con el programa SPSS y se emple&#243; la prueba de <span class="elsevierStyleItalic">X</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span> de Pearson para analizar la relaci&#243;n entre las variables categ&#243;ricas&#46; Se fij&#243; un nivel de significaci&#243;n estad&#237;stica del 5&#37;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Intervenci&#243;n</span><p id="par0095" class="elsevierStylePara elsevierViewall">Con respecto al grupo de control&#44; en la consulta&#44; el pediatra llev&#243; a cabo la pr&#225;ctica cl&#237;nica habitual ante una infecci&#243;n de origen amigdalar &#40;criterios de Centor&#41;&#46; Los pacientes atendidos asignados a este grupo recibieron la informaci&#243;n verbal y el tratamiento habitual en las condiciones habituales de diagn&#243;stico y prescripci&#243;n&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">A los pacientes del grupo de intervenci&#243;n&#44; adem&#225;s del diagn&#243;stico cl&#237;nico cl&#225;sico &#40;criterios de Centor&#41;&#44; tambi&#233;n se les efectu&#243; la PDR&#46; Para la realizaci&#243;n de esta prueba se siguieron las indicaciones del fabricante para la obtenci&#243;n de una muestra del exudado faringoamigdalar&#46; El pediatra mostr&#243; y explic&#243; el significado del resultado obtenido con la prueba a los tutores del infante y reforz&#243; con su palabra las implicaciones derivadas&#44; incidiendo expl&#237;citamente en la recomendaci&#243;n terap&#233;utica antibi&#243;tica cuando fue necesaria&#46; Por este motivo&#44; todos los pediatras que aceptaron participar en el estudio recibieron una formaci&#243;n espec&#237;fica sobre el <span class="elsevierStyleItalic">modus operandi</span> de la prueba y las recomendaciones verbales&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Al finalizar el diagn&#243;stico&#44; tanto en el grupo control como en el de intervenci&#243;n&#44; el pediatra recogi&#243; una serie de datos cl&#237;nicos y sociodemogr&#225;ficos del paciente mediante un cuestionario&#44; adem&#225;s de la informaci&#243;n de contacto para su posterior evaluaci&#243;n &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">A los 12 d&#237;as de la visita&#44; se evalu&#243; la adherencia terap&#233;utica antibi&#243;tica mediante una encuesta telef&#243;nica al padre&#44; madre&#44; tutor o responsable del paciente&#44; al que se le realizaron una serie de preguntas para valorar si el paciente cumpli&#243; el tratamiento antibi&#243;tico indicado por el m&#233;dico en t&#233;rminos de d&#237;as de terapia&#44; n&#250;mero de dosis&#44; per&#237;odo de tiempo entre dosis y cantidad de esta&#46; A los acompa&#241;antes de los pacientes a los que se les indic&#243; tratamiento antibi&#243;tico&#44; se les pregunt&#243; si recordaban la duraci&#243;n y la pauta de terapia indicada en la consulta&#44; si el paciente tom&#243; el antibi&#243;tico prescrito&#44; el n&#250;mero de d&#237;as que este tom&#243; el antibi&#243;tico&#44; si se olvid&#243; alguna dosis&#44; si la cantidad fue la indicada&#44; el motivo de finalizaci&#243;n del tratamiento y si el paciente se visit&#243; de nuevo en una consulta m&#233;dica&#46; A los pacientes a los que no se les indic&#243; tratamiento antibi&#243;tico&#44; tambi&#233;n se les pregunt&#243; si acabaron tomando antibi&#243;tico y el motivo&#46; Si el tutor&#47;a del paciente no respondi&#243; el tel&#233;fono durante el d&#237;a 12&#44; se continu&#243; llamando durante los siguientes tres d&#237;as&#44; y si todav&#237;a no respondi&#243;&#44; se consider&#243; como p&#233;rdida&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Variable de resultado</span><p id="par0115" class="elsevierStylePara elsevierViewall">La variable dependiente fue la adherencia al tratamiento&#46; Es una variable dicot&#243;mica &#40;adherencia o no adherencia&#41;&#44; que se deriva del conjunto de preguntas de la encuesta telef&#243;nica de seguimiento&#46; Se consider&#243; adherente&#44; aquel paciente al que se le indic&#243; antibi&#243;tico y cumpli&#243; los criterios siguientes&#58; 1&#41; tom&#243; el antibi&#243;tico&#59; 2&#41; tom&#243; el antibi&#243;tico durante el n&#250;mero de d&#237;as indicado&#59; 3&#41; tom&#243; el antibi&#243;tico sin olvidar ninguna dosis&#59; 4&#41; no tom&#243; ninguna dosis de m&#225;s&#59; 5&#41; tom&#243; la cantidad indicada y 6&#41; tom&#243; el antibi&#243;tico a las horas indicadas&#46; Se pregunt&#243; al paciente el motivo de no adherencia al tratamiento&#44; si fuese el caso&#44; tanto si se indic&#243; o no terapia antibi&#243;tica&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Resultados</span><p id="par0120" class="elsevierStylePara elsevierViewall">En el estudio se estudiaron 557 pacientes que cumpl&#237;an los criterios de inclusi&#243;n&#46; Conformaron el grupo de intervenci&#243;n 276 &#40;43&#44;18&#37;&#41; pacientes y 243 &#40;46&#44;82&#37;&#41; el grupo de control&#46; La edad media fue de 8&#44;1 a&#241;os y el 47&#37; fueron ni&#241;as&#46; Las caracter&#237;sticas de la poblaci&#243;n de estudio&#44; comparadas por grupos de estudio se expone en la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">Se totalizaron 38 p&#233;rdidas&#44; 19 en cada grupo&#44; siendo la ratio de p&#233;rdidas del 9&#44;3&#37;&#46; Adicionalmente&#44; se excluy&#243; a un paciente debido a que no constaban datos de si hubo indicaci&#243;n de antibi&#243;tico en la consulta pedi&#225;trica &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Grado de adherencia terap&#233;utica al antibi&#243;tico prescrito en la patolog&#237;a faringoamigdalar</span><p id="par0130" class="elsevierStylePara elsevierViewall">De los 340 pacientes a los que el pediatra prescribi&#243; antibi&#243;tico&#44; 217 cumplieron las indicaciones del tratamiento &#40;64&#44;8&#37;&#44; IC 95&#37;&#58; 60&#44;6 a 67&#44;01&#37;&#41;&#46; Se observ&#243; una adherencia superior pero no estad&#237;sticamente significativa en el grupo de intervenci&#243;n &#40;68&#37;&#41; vs&#46; grupo de control &#40;62&#44;9&#37;&#41; &#40;<span class="elsevierStyleItalic">X</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span> &#61; 0&#44;901&#44; p &#61; 0&#44;341&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Las causas principales de no cumplimiento terap&#233;utico fueron que no se sigui&#243; el horario indicado &#40;25&#44;6&#37;&#41;&#44; la duraci&#243;n del tratamiento &#40;22&#44;3&#37;&#41;&#44; que no se cumpli&#243; la pauta &#40;9&#44;8&#37;&#41;&#44; que no se termin&#243; el tratamiento &#40;9&#44;5&#37;&#41;&#44; que no se suministr&#243; la cantidad indicada &#40;1&#44;3&#37;&#41;&#44; que no se inici&#243; el tratamiento &#40;1&#44;1&#37;&#41; y que el paciente no record&#243; la indicaci&#243;n de antibi&#243;tico &#40;0&#44;6&#37;&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Los motivos de finalizaci&#243;n de la terapia antes de la fecha indicada en la consulta pedi&#225;trica &#40;9&#44;5&#37;&#41; fueron por causa voluntaria &#40;63&#44;6&#37;&#41;&#44; por indicaci&#243;n de un m&#233;dico &#40;33&#44;3&#37;&#41; y por indicaci&#243;n de otra persona &#40;3&#37;&#41;&#46; Los pacientes que empezaron tratamiento antibi&#243;tico sin indicaci&#243;n y prescripci&#243;n del pediatra u otro facultativo representaron el 8&#44;5&#37;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Relaci&#243;n entre la adherencia terap&#233;utica y la puntuaci&#243;n Centor</span><p id="par0145" class="elsevierStylePara elsevierViewall">El 88&#44;8&#37; de los pacientes present&#243; fiebre superior a 38<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; el 89&#44;4&#37; inflamaci&#243;n amigdalar&#44; el 80&#44;2&#37; ausencia de tos y el 69&#44;7&#37; adenopat&#237;as&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">La adherencia terap&#233;utica fue inferior en pacientes que cumpl&#237;an uno o dos criterios &#40;59&#44;3&#37;&#41;&#44; vs&#46; los que cumpl&#237;an tres &#40;69&#44;4&#37;&#41; y cuatro criterios &#40;62&#44;1&#37;&#41;&#44; la diferencia no es estad&#237;sticamente significativa &#40;p &#61; 0&#44;337&#41;&#46; Se observ&#243; una diferencia significativa &#40;p &#61; 0&#44;001&#41; entre la puntuaci&#243;n Centor y el cumplimiento de la duraci&#243;n del tratamiento antibi&#243;tico&#44; siendo inferior en pacientes con un puntuaci&#243;n de 4 &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">No se obtuvieron resultados positivos en la PDR en pacientes con un criterio Centor&#46; Los individuos con resultado positivo y dos criterios Centor representaron el 27&#44;5&#37;&#44; con tres criterios el 36&#44;2&#37; y con cuatro el 56&#44;4&#37; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Variables sociodemogr&#225;ficas y adherencia terap&#233;utica al antibi&#243;tico</span><p id="par0160" class="elsevierStylePara elsevierViewall">Se observ&#243; que la adherencia al tratamiento antibi&#243;tico fue superior cuando el acompa&#241;ante era el tutor u otras personas &#40;77&#44;3&#37;&#41;&#44; seguido de si era la madre &#40;65&#44;4&#37;&#41; y finalmente&#44; si era el padre &#40;59&#44;8&#37;&#41;&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Respecto al pa&#237;s de nacimiento del padre y de la madre&#44; se identific&#243; una inferior adherencia terap&#233;utica cuando ambos hab&#237;an nacido fuera de Espa&#241;a &#40;55&#44;2&#37;&#41;&#44; presentando mayores dificultades para comprender y&#47;o recordar la pauta indicada&#59; seguido de si uno de los dos hab&#237;a nacido fuera del pa&#237;s &#40;56&#44;3&#37;&#41; y superior&#44; si ambos progenitores hab&#237;an nacido en Espa&#241;a &#40;65&#44;7&#37;&#41;&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Analizando la adherencia por edades&#44; se expone que el cumplimiento del tratamiento antibi&#243;tico es significativamente inferior en pacientes con edades comprendidas entre los 13 y 15 a&#241;os&#44; incumpliendo especialmente la duraci&#243;n de la terapia&#44; a pesar de ser el grupo de edad que record&#243; mejor la pauta indicada&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">No se ha apreciado una asociaci&#243;n entre el grado de adherencia terap&#233;utica y el nivel de formaci&#243;n de los progenitores&#44; el n&#250;mero de hermanos y la puntuaci&#243;n Centor &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Prescripci&#243;n de antibi&#243;ticos</span><p id="par0180" class="elsevierStylePara elsevierViewall">Se prescribi&#243; antibi&#243;tico al 65&#44;63&#37; de los 519 pacientes&#46; Se observ&#243; una diferencia significativamente superior en el grupo intervenci&#243;n que en el grupo control &#40;88&#44;5 vs&#46; 45&#44;5&#37;&#44; p &#60; 0&#44;001&#41;&#46; Se prescribi&#243; antibi&#243;tico al 100&#37; de los pacientes con resultado positivo en la PDR y &#250;nicamente al 3&#44;85&#37; con resultado negativo&#46; El antibi&#243;tico m&#225;s prescrito fue la amoxicilina &#40;77&#44;1&#37;&#41;&#44; seguido de la penicilina oral &#40;9&#44;4&#37;&#41;&#44; la amoxicilina con &#225;cido clavul&#225;nico &#40;7&#44;4&#37;&#41; y otros &#40;6&#44;2&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46; Un total de 15 pacientes &#40;3&#37;&#41; se catalogaron como al&#233;rgicos a la penicilina&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">Las pautas horarias prescritas por el pediatra con m&#225;s frecuencia fueron cada ocho horas &#40;64&#44;3&#37;&#41; y cada 12 horas &#40;31&#44;3&#37;&#41;&#46; La duraci&#243;n m&#225;s indicada fue ocho d&#237;as &#40;43&#44;1&#37;&#41;&#44; seguido de siete d&#237;as o inferior &#40;37&#44;8&#37;&#41; y 10 d&#237;as &#40;19&#44;1&#37;&#41;&#46; No se observaron diferencias significativas entre las ramas de estudio en cuanto a duraci&#243;n &#40;p &#61; 0&#44;829&#41; y pautas prescritas &#40;p &#61; 0&#44;148&#41;&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">El 8&#44;4&#37; de los pacientes del grupo control visit&#243; de nuevo a un m&#233;dico vs&#46; 11&#44;2&#37; del grupo intervenci&#243;n &#40;p &#61; 0&#44;293&#41;&#46; El 83&#44;6&#37; consult&#243; en un ambulatorio&#44; el 12&#44;7&#37; en un hospital y el 3&#44;6&#37; en una consulta privada&#46; En la nueva visita se prescribi&#243; antibi&#243;tico de manera significativamente mayor &#40;p &#60; 0&#44;001&#41; a los pacientes del grupo de control &#40;88&#44;5&#37;&#41; vs&#46; los del grupo intervenci&#243;n &#40;50&#44;2&#37;&#41;&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Discusi&#243;n</span><p id="par0195" class="elsevierStylePara elsevierViewall">El porcentaje de pacientes con tratamiento antibi&#243;tico para una infecci&#243;n faringoamigdalar que cumpli&#243; el tratamiento correctamente &#40;64&#44;8&#37;&#41; fue muy similar al obtenido en una revisi&#243;n sistem&#225;tica que incluy&#243; 43 estudios &#40;62&#44;2&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">El 90&#37; de los pacientes incluidos en el estudio eran menores de 13 a&#241;os&#44; por lo que la responsabilidad principal de la correcta administraci&#243;n del tratamiento recay&#243; en los padres y los tutores&#46; Los adolescentes de entre 13 y 15 a&#241;os que participaron en el estudio obtuvieron peores resultados en la adherencia terap&#233;utica&#44; tanto en la correcta duraci&#243;n&#44; n&#250;mero de dosis y la hora de administraci&#243;n&#44; a pesar de recordar mejor la pauta&#46; El descenso del cumplimiento de la terapia en adolescentes podr&#237;a ser causado por una mayor libertad y falta de supervisi&#243;n por parte de los padres y una dificultad para cumplir las pautas del tratamiento por parte de los adolescentes&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">El acompa&#241;ante principal del menor fue la madre en el 70&#37; de los casos y el padre en el 23&#37;&#46; Si se comparan los resultados&#44; el grado de adherencia terap&#233;utica fue m&#225;s favorable cuando el acompa&#241;ante era la madre &#40;65&#44;4&#37;&#41; respecto el padre &#40;59&#44;8&#37;&#41;&#44; pese a no existir una significaci&#243;n estad&#237;stica&#46; El grado de adherencia superior fue detectado cuando el acompa&#241;ante era el tutor u otros &#40;77&#44;3&#37;&#41;&#46; Esta diferencia puede estar relacionada con la responsabilidad que se ejerce respecto a un tercero que no es el progenitor directo&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">De igual modo que en un estudio sobre la asociaci&#243;n entre la adherencia terap&#233;utica y la prueba diagn&#243;stica r&#225;pida de <span class="elsevierStyleItalic">EbhGA</span>&#44; tambi&#233;n se obtuvieron mejores resultados en el grupo de intervenci&#243;n y se observ&#243; que la adherencia al tratamiento en menores de 15 a&#241;os es superior que en adultos<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">En este estudio&#44; se ha observado una diferencia significativa en la adherencia a la duraci&#243;n del tratamiento antibi&#243;tico respecto a la puntuaci&#243;n Centor&#44; siendo inferior en pacientes con un puntuaci&#243;n de 4&#46; No hemos encontrado una explicaci&#243;n plausible para este resultado&#44; por lo que podr&#237;a tratarse de un error de registro&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Los pediatras del grupo de control&#44; que no ten&#237;an acceso a la PDR fueron un 43&#37; m&#225;s propensos a prescribir antibi&#243;ticos que aquellos del grupo intervenci&#243;n&#44; siendo este tratamiento muchas veces innecesario&#44; ya que menos de la mitad de los casos detectados en el grupo intervenci&#243;n &#40;43&#44;7&#37;&#41; obtuvieron un resultado positivo para faringitis estreptoc&#243;cica&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">El porcentaje de prescripci&#243;n de antibi&#243;ticos para faringoamigdalitis &#40;65&#44;63&#37;&#41; difiere del registrado en otros estudios 80&#44;9<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a>&#44; 75<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a>&#44; 57&#44;8<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a> y 53&#44;81&#37;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">17</span></a>&#44; esto es debido a que los estudios fueron realizados en distintos a&#241;os y para diferentes rangos de edad&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">El 7&#44;4&#37; de los pediatras eligieron la amoxicilina con &#225;cido clavul&#225;nico como tratamiento de entrada a pesar de no ser recomendada en las gu&#237;as de pr&#225;ctica cl&#237;nicas<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a>&#46; En un estudio del 2013&#44; el porcentaje de prescripciones de amoxicilina con &#225;cido clavul&#225;nico por sospecha de faringoamigdalitis estreptoc&#243;cica fue del 29&#37;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">24</span></a> y en un estudio del a&#241;o 2000&#44; el 44&#37; de los adultos recibieron amoxicilina con &#225;cido clavul&#225;nico para tratar la amigdalitis<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">25</span></a> La posible explicaci&#243;n de su uso es la falta de seguimiento de las recomendaciones de las gu&#237;as de pr&#225;ctica cl&#237;nicas&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">La recogida de los datos se realiz&#243; antes de la implementaci&#243;n generalizada de la prueba r&#225;pida de diagn&#243;stico en los centros de atenci&#243;n primaria de la zona y comprobando que los resultados de la adherencia terap&#233;utica no se vieron influenciados por dicha implementaci&#243;n al no mostrar una asociaci&#243;n significativamente estad&#237;stica&#44; el cumplimiento del tratamiento antibi&#243;tico sigue siendo un reto farmacol&#243;gico en patolog&#237;as agudas&#46; Han transcurrido m&#225;s de 10 a&#241;os desde la implementaci&#243;n generalizada de la prueba r&#225;pida y se requieren estudios futuros que permitan plantear nuevos enfoques y estrategias para mejorar el cumplimiento del tratamiento&#44; as&#237; como hacer un seguimiento en el tiempo de la adherencia terap&#233;utica al tratamiento antibi&#243;tico&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conclusiones</span><p id="par0240" class="elsevierStylePara elsevierViewall">La adherencia terap&#233;utica se ve influenciada por varios factores y proporcionar informaci&#243;n sobre el tratamiento y sus indicaciones es clave para su correcto cumplimiento&#46; Utilizar el resultado de la prueba de diagn&#243;stico r&#225;pida para mejorar la adherencia antibi&#243;tica ha mostrado una posible asociaci&#243;n favorable&#44; aunque no estad&#237;sticamente significativa&#46;<elsevierMultimedia ident="tb0005"></elsevierMultimedia></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Financiaci&#243;n</span><p id="par0265" class="elsevierStylePara elsevierViewall">Este trabajo no ha recibido ning&#250;n tipo de financiaci&#243;n&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Conflicto de intereses</span><p id="par0270" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evaluar la influencia del resultado de la prueba r&#225;pida de diagn&#243;stico para la identificaci&#243;n del ant&#237;geno estreptoc&#243;cico en infecciones faringoamigdalares pedi&#225;tricas&#44; en t&#233;rminos de mejora de la adherencia a la terapia antibi&#243;tica&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Dise&#241;o</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ensayo cl&#237;nico comunitario de dos grupos de estudio con asignaci&#243;n aleatoria&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Emplazamiento</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Centros de atenci&#243;n primaria de Catalu&#241;a Central&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Participantes</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">En el estudio se incluyeron a pacientes de tres a 15 a&#241;os por muestreo consecutivo&#44; que fueron atendidos por sospecha de infecci&#243;n faringoamigdalar en las consultas pedi&#225;tricas entre noviembre del 2010 y febrero del 2011&#46; De 557 pacientes que satisficieron los criterios de inclusi&#243;n&#44; se hizo seguimiento a 519&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Intervenci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El grupo control sigui&#243; el algoritmo diagn&#243;stico y terap&#233;utico habitual&#46; Al grupo de intervenci&#243;n&#44; se le realiz&#243; adicionalmente la prueba diagn&#243;stica r&#225;pida de detecci&#243;n del ant&#237;geno <span class="elsevierStyleItalic">estreptoc&#243;cico</span> y se indic&#243; tratamiento seg&#250;n el resultado&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Mediciones principales</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Evaluaci&#243;n de la adherencia&#44; los motivos de no adherencia y los factores de riesgo sociodemogr&#225;ficos mediante una encuesta telef&#243;nica&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se prescribi&#243; antibi&#243;tico al 65&#44;6&#37; y los pediatras del grupo control fueron m&#225;s propensos a recetar antibi&#243;ticos que los del grupo intervenci&#243;n &#40;88&#44;5 vs&#46; 45&#44;5&#37;&#44; p&#60; 0&#44;001&#41;&#46; El 64&#44;8&#37; de los pacientes sigui&#243; las indicaciones del tratamiento&#44; siendo la causa principal de no adherencia no cumplir el horario &#40;25&#44;6&#37;&#41;&#46; La adherencia terap&#233;utica fue superior en el grupo de intervenci&#243;n &#40;68&#37;&#41; que en el de control &#40;62&#44;9&#37;&#41;&#44; no existiendo una diferencia significativa&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La prueba r&#225;pida del diagn&#243;stico para la identificaci&#243;n de <span class="elsevierStyleItalic">estreptococo</span>&#44; complementaria al uso de los criterios Centor evita la prescripci&#243;n innecesaria de tratamiento antibi&#243;tico&#44; aunque no ha demostrado mejorar la adherencia terap&#233;utica&#46;</p></span>"
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        "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Objective</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">To evaluate the influence of the result of a rapid <span class="elsevierStyleItalic">streptococcal</span> antigen test in paediatric pharyngotonsillitis infections&#44; in terms of improvement of antibiotic therapy adherence&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Design</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Randomized community clinical trial with two study groups&#46;</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Location</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Primary Care Centers in Central Catalonia&#46;</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Participants</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Patients aged from 3 to 15 years&#44; who were attended at paediatric consultations on suspicion of pharyngotonsillitis caused by an infection between November 2010 and February 2011 &#40;both included&#41;&#44; were included in the study on a consecutive basis&#46; 557 patients met the inclusion criteria and 519 were evaluated&#46;</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Intervention</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">The control group received the usual diagnostic-therapeutic algorithm&#46; Rapid <span class="elsevierStyleItalic">streptococcal</span> antigen test was additionally performed to experimental group participants and it was indicated the more convenient treatment&#46;</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Main measurements</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Antibiotic adherence&#44; non-adherence causes and socio-demographic risk factors were evaluated via telephone survey<span class="elsevierStyleItalic">&#46;</span></p></span> <span id="abst0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Antibiotics were prescribed to 65&#46;6&#37; and paediatricians of the control group were more likely to prescribe antibiotic than the ones in the intervention group &#40;88&#46;5&#37; vs 45&#46;5&#37;&#44; p&#60; 0&#46;0001&#41;&#46; 64&#46;8&#37; followed doctor&#39;s treatment orders&#44; being failure following medication scheduling the main cause of non-adherence &#40;25&#46;6&#37;&#41;&#46; Medication adherence was higher in the experimental group &#40;68&#37;&#41; than in the control group &#40;62&#46;9&#37;&#41; but no significant differences were found&#46;</p></span> <span id="abst0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusion</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Rapid strep test&#44; complementing the use of Centor Criteria avoids unnecessary antibiotics prescriptions&#44; but had not been proven to be effective in increasing medication adherence&#46;</p></span>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\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">Section&#47;topic&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">Item No&#46;&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">Checklist item&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">Reported on page&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Title and abstract</span></td></tr><tr title="table-row"><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">1a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Identification as a randomised trial in the title&#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">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Structured summary of trial design&#44; methods&#44; results&#44; and conclusions&#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">4&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Introduction</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Background and objectives</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Scientific background and explanation of rationale&#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">6&#44;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">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Specific objectives or hypotheses&#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&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Methods</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Trial design</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Description of trial design &#40;such as parallel&#44; factorial&#41; including allocation ratio&#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">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">3b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Important changes to methods after trial commencement &#40;such as eligibility criteria&#41;&#44; with reasons&#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">Not applicable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Participants</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eligibility criteria for participants&#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">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">4b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Settings and locations where the data were collected&#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">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"><span class="elsevierStyleHsp" style=""></span>Interventions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">The interventions for each group with sufficient details to allow replication&#44; including how and when they were actually administered&#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">8&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Outcomes</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completely defined pre-specified primary and secondary outcome measures&#44; including how and when they were assessed&#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">Table 210&#44; Table 2&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">6b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Any changes to trial outcomes after the trial commenced&#44; with reasons&#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">Not applicable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sample size</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">How sample size was determined&#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">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">7b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">When applicable&#44; explanation of any interim analyses and stopping guidelines&#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">Not applicable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Randomisation&#58;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sequence generation</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Method used to generate the random allocation sequence&#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">9&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">8b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Type of randomisation&#59; details of any restriction &#40;such as blocking and block size&#41;&#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">8&#44;9&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"><span class="elsevierStyleHsp" style=""></span>Allocation concealment mechanism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">Mechanism used to implement the random allocation sequence &#40;such as sequentially numbered containers&#41;&#44; describing any steps taken to conceal the sequence until interventions were assigned&#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">9&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"><span class="elsevierStyleHsp" style=""></span>Implementation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Who generated the random allocation sequence&#44; who enrolled participants&#44; and who assigned participants to interventions&#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">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Blinding</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">If done&#44; who was blinded after assignment to interventions &#40;for example&#44; participants&#44; care providers&#44; those assessing outcomes&#41; and how&#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">9&#44;10&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">11b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">If relevant&#44; description of the similarity of interventions&#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">Not applicable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Statistical methods</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Statistical methods used to compare groups for primary and secondary outcomes&#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">9&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">12b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Methods for additional analyses&#44; such as subgroup analyses and adjusted analyses&#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">Not applicable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Results</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Participant flow &#40;a diagram is strongly recommended&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">For each group&#44; the numbers of participants who were randomly assigned&#44; received intended treatment&#44; and were analysed for the primary outcome&#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">10&#44; 11&#44; Fig&#46; 1&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">13b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">For each group&#44; losses and exclusions after randomisation&#44; together with reasons&#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">12&#44; Fig&#46; 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Recruitment</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dates defining the periods of recruitment and follow-up&#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">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">14b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Why the trial ended or was stopped&#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">Not applicable&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"><span class="elsevierStyleHsp" style=""></span>Baseline data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">A table showing baseline demographic and clinical characteristics for each group&#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">Table 3&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"><span class="elsevierStyleHsp" style=""></span>Numbers analysed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">For each group&#44; number of participants &#40;denominator&#41; included in each analysis and whether the analysis was by original assigned groups&#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">Table 310&#44; 11&#44; Table 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Outcomes and estimation</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">For each primary and secondary outcome&#44; results for each group&#44; and the estimated effect size and its precision &#40;such as 95&#37; confidence interval&#41;&#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">12&#44;13&#44;14&#44;15&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">17b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">For binary outcomes&#44; presentation of both absolute and relative effect sizes is recommended&#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">Not applicable&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"><span class="elsevierStyleHsp" style=""></span>Ancillary analyses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Results of any other analyses performed&#44; including subgroup analyses and adjusted analyses&#44; distinguishing pre-specified from exploratory&#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">Not applicable&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"><span class="elsevierStyleHsp" style=""></span>Harms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">All important harms or unintended effects in each group&#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">Not applicable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Discussion</span></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"><span class="elsevierStyleHsp" style=""></span>Limitations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Trial limitations&#44; addressing sources of potential bias&#44; imprecision&#44; and&#44; if relevant&#44; multiplicity of analyses&#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">13&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"><span class="elsevierStyleHsp" style=""></span>Generalisability&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Generalisability &#40;external validity&#44; applicability&#41; of the trial findings&#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">Not applicable&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"><span class="elsevierStyleHsp" style=""></span>Interpretation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Interpretation consistent with results&#44; balancing benefits and harms&#44; and considering other relevant evidence&#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">12&#44; 13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Other information</span></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"><span class="elsevierStyleHsp" style=""></span>Registration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Registration number and name of trial registry&#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">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"><span class="elsevierStyleHsp" style=""></span>Protocol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Where the full trial protocol can be accessed&#44; if available&#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">Available on request&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"><span class="elsevierStyleHsp" style=""></span>Funding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Sources of funding and other support &#40;such as supply of drugs&#41;&#44; role of funders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "es" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Lista de &#237;tems CONSORT</p>"
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><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">Grupo de aleatorizaci&#243;n&#58; intervenci&#243;n o control&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">Criterios Centor&#58; historia o presencia de fiebre 38 &#176;C&#44; inflamaci&#243;n o exudado faringoamigdalar&#44; adenopat&#237;as laterocervicales dolorosas y ausencia de tos&#46;&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">Resultado de la prueba r&#225;pida del grupo intervenci&#243;n&#58; positivo&#47;negativo&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">Edad del paciente&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">Datos asistenciales&#58; &#193;rea&#44; fecha de la visita&#44; hora de visita y pediatra que lo ha visitado&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">Nivel de estudios m&#225;s alto de los padres&#58; sin estudios&#47;estudios primarios&#47;estudios secundarios&#47;estudios superiores&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">Lugar de nacimiento del paciente y los padres&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">N&#250;mero de hermanos del paciente&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "es" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Variables independientes del estudio</p>"
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      4 => array:8 [
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            "identificador" => "at3"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \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" style="border-bottom: 2px solid black">&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">Control&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">Intervenci&#243;n&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">Valor p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo</span></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"><span class="elsevierStyleHsp" style=""></span>Ni&#241;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">127 &#40;52&#44;26&#37;&#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">148 &#40;53&#44;62&#37;&#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">0&#44;757&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"><span class="elsevierStyleHsp" style=""></span>Ni&#241;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">116 &#40;47&#44;74&#37;&#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">128 &#40;46&#44;38&#37;&#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="" 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"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">243 &#40;46&#44;82&#37;&#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">276 &#40;53&#44;18&#37;&#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="" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Edad</span></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"><span class="elsevierStyleHsp" style=""></span>0-3&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">30 &#40;12&#44;34&#37;&#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">27 &#40;9&#44;78&#37;&#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">0&#44;656&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"><span class="elsevierStyleHsp" style=""></span>4-6&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
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Pa&#237;s nacimiento padres</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>P y M Espa&#241;a&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>P o M otro&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">28 &#40;10&#44;45&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">A&#241;o llegada padres</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anterior 98&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12 &#40;42&#44;85&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;18&#44;92&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;099&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Entre 98 y 2003&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9 &#40;32&#44;14&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19 &#40;51&#44;35&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Posterior a 2003&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;25&#37;&#41;&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">75 &#40;27&#44;78&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  """
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                  \t\t\t\t">4 &#40;0&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Cefalexina&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">2 &#40;0&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \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
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                  \t\t\t\t">Cefuroxima&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">2 &#40;0&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Lo conocido sobre el tema</span><p id="par0245" class="elsevierStylePara elsevierViewall">El incumplimiento del tratamiento antibi&#243;tico supone un riesgo de salud p&#250;blica que provoca resistencias bacterianas&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Existen estudios cuantitativos que eval&#250;an la adherencia terap&#233;utica y los factores de riesgo que pueden conducir al fracaso terap&#233;utico&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">&#191;Qu&#233; aporta este estudio&#63;</span><p id="par0255" class="elsevierStylePara elsevierViewall">Los hallazgos obtenidos muestran que el 64&#44;8&#37; los pacientes pedi&#225;tricos diagnosticados de faringoamigdalitis cumplieron el tratamiento antibi&#243;tico&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">A pesar de que la adherencia terap&#233;utica fue un 5&#44;1&#37; superior en los pacientes a los que se les realiz&#243; el test de diagn&#243;stico r&#225;pido de detecci&#243;n del ant&#237;geno <span class="elsevierStyleItalic">estreptoc&#243;cico</span>&#44; no se observ&#243; una diferencia significativa&#46;</p></span></span>"
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                      "Revista" => array:5 [
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                      "titulo" => "Prescripci&#243;n de antibi&#243;ticos en las infecciones del tracto respiratorio y factores predictores de su utilizaci&#243;n"
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                        0 => array:2 [
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                      "doi" => "10.1542/peds.2009-2648"
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                      "Revista" => array:3 [
                        "tituloSerie" => "Plan Nacional Frente a la Resistencia a los Antibi&#243;ticos 2019-2021&#46; Agencia Espa&#241;ola Medicam y Prod Sanit &#91;Internet&#93;"
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                        0 => array:2 [
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                            3 => "J&#46;G&#46; De La Iglesia"
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ISSN: 02126567
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es en pt

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