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Persistencia al tratamiento con metformina de marca vs. genérica en monoterapia para la diabetes tipo 2: estudio retrospectivo de vida real mediante propensity score matching
Treatment persistence with brand-name vs. generic metformin in monotherapy for type 2 diabetes: real-life retrospective study using the propensity matching score
A. Sicras-Mainar
Autor para correspondencia
ansicras@atrysheath.com

Autor para correspondencia.
, A. Sicras-Navarro
Dirección científica, Atrys Health, Barcelona, España
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si tras un periodo de entre 3 y 6 meses con tratamiento no farmacol&#243;gico no se consiguen los objetivos metab&#243;licos&#44; se debe iniciar un tratamiento farmacol&#243;gico<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1&#44;2&#44;6</span></a>&#46; En la actualidad&#44; est&#225;n disponibles una serie de f&#225;rmacos para el tratamiento de la DM2&#44; como metformina &#40;biguanidas&#41;&#44; sulfonilureas&#44; glinidas&#44; glitazonas&#44; inhibidores de las disacaridasas&#44; inhibidores de la dipeptidilpeptidasa 4 &#40;iDPP4&#41;&#44; inhibidores del cotransportador de sodio-glucosa tipo 2 &#40;iSGLT2&#41; y agonistas del receptor del GLP-1 &#40;AR GLP-1&#41;&#44; que al igual que la insulina&#44; pueden utilizarse en monoterapia o en combinaci&#243;n<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">2&#44;6&#44;7</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Metformina es un f&#225;rmaco de primera elecci&#243;n en el tratamiento de la DM2&#44; tal como reconocen las principales gu&#237;as de pr&#225;ctica cl&#237;nica<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1&#44;2&#44;7</span></a>&#46; Sus beneficios&#44; en cuanto a las complicaciones cardiovasculares y la mortalidad&#44; la hacen prioritaria en los pacientes con DM2<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">8</span></a>&#46; No obstante&#44; metformina no deber&#237;a prescribirse en caso de insuficiencia renal severa &#40;filtrado glomerular &#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#41; o insuficiencia card&#237;aca avanzada<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">8&#44;9</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Varios estudios han demostrado que la discontinuaci&#243;n &#40;falta de adherencia&#41; al tratamiento con metformina se sit&#250;a&#44; al a&#241;o de seguimiento&#44; entre el 50 y 70&#37;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">10&#8211;12</span></a>&#46; La falta de adherencia al tratamiento es uno de los problemas m&#225;s importantes en la pr&#225;ctica diaria&#44; ya que ocasiona una menor efectividad cl&#237;nica&#44; una falta de consecuci&#243;n de los objetivos del tratamiento y un posible aumento de los recursos sanitarios<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">10&#8211;13</span></a>&#46; En la terapia farmacol&#243;gica existen presentaciones de especialidades farmac&#233;uticas de marca y gen&#233;rica &#40;equivalente farmac&#233;utico gen&#233;rico &#91;EFG&#93;&#41;&#46; Los EFG son medicamentos con la misma eficacia&#44; seguridad y calidad&#44; y son bioequivalentes a la marca original<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">14&#8211;18</span></a>&#46; Diversos estudios han demostrado que los cambios en la bioapariencia de un mismo principio activo &#40;forma&#44; color&#44; tama&#241;o&#44; bl&#237;ster o cartonaje&#41; pueden interferir en la adherencia terap&#233;utica de los pacientes<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a>&#44; favoreciendo la falta de control de la enfermedad y el riesgo de complicaciones<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Con m&#250;ltiples EFG&#44; los envases de medicamentos dispensados en la oficina de farmacia comunitaria pueden tener apariencias diferentes&#44; circunstancia que puede ocasionar una mayor complejidad a la continuidad del tratamiento &#40;confusi&#243;n de los pacientes&#41;&#44; especialmente en algunos colectivos de pacientes mayores y polimedicados<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a>&#46; Por otra parte&#44; las evidencias disponibles acerca de la relaci&#243;n entre estas variables son escasas en la vida real&#44; tanto en la literatura internacional como en nuestro entorno sanitario&#44; por lo que la realizaci&#243;n de este estudio puede ser de inter&#233;s&#46; El objetivo de este estudio fue analizar la persistencia al tratamiento en sujetos &#8805;<span class="elsevierStyleHsp" style=""></span>50 a&#241;os con DM2&#44; polimedicados&#44; a quienes se les administra &#40;inicio de la medicaci&#243;n&#41; metformina 850<span class="elsevierStyleHsp" style=""></span>mg de marca vs&#46; EFG en situaci&#243;n de pr&#225;ctica cl&#237;nica habitual&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Dise&#241;o y poblaci&#243;n de estudio</span><p id="par0030" class="elsevierStylePara elsevierViewall">Se efectu&#243; un estudio observacional&#44; multic&#233;ntrico y longitudinal &#40;de car&#225;cter retrospectivo&#41;&#44; realizado a partir de la revisi&#243;n de los registros m&#233;dicos &#40;bases de datos informatizadas&#44; con datos disociados&#41;&#46; La poblaci&#243;n de estudio se obtuvo a partir de los registros sanitarios de proveedores de salud de diversos centros de atenci&#243;n primaria y hospitalarios espa&#241;oles &#40;unificados en la base de datos anonimizada BIG-PAC&#41;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a>&#46; Los datos procedieron de diversas historias cl&#237;nicas informatizadas y de otras bases de datos complementarias de financiaci&#243;n&#47;provisi&#243;n de servicios p&#250;blicos&#44; de 7 comunidades aut&#243;nomas espa&#241;olas &#40;1&#44;8 millones de pacientes&#41;&#46; Se respet&#243; la confidencialidad de los registros &#40;an&#243;nimos&#41; seg&#250;n 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="sect0080">Criterios de inclusi&#243;n y exclusi&#243;n</span><p id="par0035" class="elsevierStylePara elsevierViewall">Se incluyeron en el estudio los pacientes polimedicados &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>3 principios activos&#41; que demandaron atenci&#243;n y que iniciaron un nuevo tratamiento con metformina &#40;marca o EFG&#41; entre el 01&#47;01&#47;2016 y el 31&#47;12&#47;2017 &#40;periodo de reclutamiento&#44; fecha &#237;ndice&#41;&#44; para el tratamiento de la DM2&#46; Debieron reunir las siguientes caracter&#237;sticas&#58; a&#41; edad &#8805;<span class="elsevierStyleHsp" style=""></span>50 a&#241;os&#59; b&#41; pacientes activos en la base de datos un m&#237;nimo de 12 meses antes de iniciar el estudio&#59; c&#41; estar en el programa de prescripciones cr&#243;nicas para la obtenci&#243;n de las recetas m&#233;dicas &#40;con registro constatado de la dosis diaria&#44; el intervalo de tiempo y la duraci&#243;n de cada tratamiento administrado&#59; &#8805;<span class="elsevierStyleHsp" style=""></span>2 recetas durante el periodo de seguimiento&#41;&#44; y d&#41; que se pudiera garantizar el seguimiento regular de los pacientes &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>2 registros sanitarios en el sistema inform&#225;tico&#41;&#46; Fueron excluidos&#58; a&#41; los sujetos trasladados a otros centros&#44; los desplazados o fuera de zona&#59; b&#41; los pacientes institucionalizados permanentemente&#59; c&#41; los que cambiaron de tratamiento &#40;marca vs&#46; EFG y viceversa&#41;&#44; y d&#41; con enfermedad mental severa&#44; terminal y&#47;o en di&#225;lisis&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Grupos de estudio y seguimiento</span><p id="par0040" class="elsevierStylePara elsevierViewall">Se diferenciaron 2 grupos de estudio en funci&#243;n del tratamiento inicial dispensado&#58; a&#41; metformina 850<span class="elsevierStyleHsp" style=""></span>mg de marca y b&#41; metformina 850<span class="elsevierStyleHsp" style=""></span>mg EFG&#59; en monoterapia&#46; El periodo de seguimiento&#44; a partir de la fecha de inclusi&#243;n del paciente&#44; fue de 2 a&#241;os&#46; Cada paciente del grupo de marca &#40;referencia&#41; se emparej&#243; &#40;1&#58;1&#41; con otro del grupo de EFG mediante <span class="elsevierStyleItalic">propensity score matching</span> &#40;PSM&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Definici&#243;n del diagn&#243;stico</span><p id="par0045" class="elsevierStylePara elsevierViewall">Los registros de los pacientes con DM2 se obtuvieron a partir de la Clasificaci&#243;n Internacional de Enfermedades &#40;novena edici&#243;n&#41; Modificaci&#243;n Cl&#237;nica &#40;CIE-09-MC&#59; c&#243;digos&#58; 250&#46;00&#44; 250&#46;02&#59; <a href="https://eciemaps.mscbs.gob.es/">https&#58;&#47;&#47;eciemaps&#46;mscbs&#46;gob&#46;es</a>&#41;&#46; Los criterios seguidos siempre fueron a juicio del m&#233;dico responsable de la asistencia&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Variables demogr&#225;ficas y comorbilidades</span><p id="par0050" class="elsevierStylePara elsevierViewall">Las variables sociodemogr&#225;ficas y de comorbilidad &#40;CIE-09-MC&#41; fueron las siguientes&#58; edad &#40;continua y por rangos&#41; y g&#233;nero&#44; as&#237; como los antecedentes personales de hipertensi&#243;n arterial&#44; dislipemia&#44; obesidad&#44; fumadores activos&#44; infarto de miocardio&#44; ictus&#44; enfermedad arterial perif&#233;rica&#44; insuficiencia card&#237;aca&#44; insuficiencia renal&#44; asma&#44; EPOC&#44; neuropat&#237;as&#44; s&#237;ndrome depresivo y neoplasias malignas&#46; Como variable resumen de la comorbilidad general&#44; para cada paciente atendido&#44; se utiliz&#243;&#58; a&#41; el &#237;ndice de comorbilidad de Charlson<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a> como una aproximaci&#243;n a la gravedad del paciente y b&#41; el n&#250;mero de comorbilidades cr&#243;nicas&#46; Estas variables se obtuvieron al inicio del estudio &#40;situaci&#243;n basal&#41;&#46; Se obtuvo el tratamiento administrado en situaci&#243;n basal&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Medicaci&#243;n administrada y persistencia al tratamiento</span><p id="par0055" class="elsevierStylePara elsevierViewall">La informaci&#243;n se obtuvo de los registros procedentes de la dispensaci&#243;n farmacol&#243;gica de medicamentos&#44; seg&#250;n la <span class="elsevierStyleItalic">Anatomical Therapeutic Chemical Classification System</span> &#40;c&#243;digo&#58; ATC&#58; A10BA02&#41;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">23</span></a>&#46; La prescripci&#243;n de marca o gen&#233;rica a un paciente en concreto fue a criterio del m&#233;dico &#40;pr&#225;ctica cl&#237;nica&#41;&#46; La persistencia o duraci&#243;n del tratamiento con metformina 850<span class="elsevierStyleHsp" style=""></span>mg se defini&#243; como el tiempo&#44; medido en d&#237;as&#44; sin abandono del tratamiento inicial o sin cambio a otra medicaci&#243;n al menos 30 d&#237;as despu&#233;s de la dispensaci&#243;n inicial&#46; Este se calcul&#243; desde la fecha de inicio hasta la fecha de discontinuaci&#243;n &#40;en d&#237;as&#41;&#46; La fecha de inicio fue la de inicio del tratamiento con metformina&#44; mientras que la fecha de discontinuaci&#243;n fue la que sucedi&#243; primero entre&#58; a&#41; la fecha de finalizaci&#243;n del periodo de seguimiento &#40;2 a&#241;os&#41;&#44; b&#41; fallecimiento&#44; c&#41; cambio a otro tratamiento antidiab&#233;tico&#44; y d&#41; interrumpe&#47;abandona la medicaci&#243;n &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>60 d&#237;as sin renovar la medicaci&#243;n y&#47;o &#8805;<span class="elsevierStyleHsp" style=""></span>2 recetas&#41;&#46; La persistencia al tratamiento se obtuvo a los 6&#44; 12 y 24 meses de seguimiento&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Se obtuvo el n&#250;mero de medicamentos cardiovasculares y la especialidad m&#233;dica responsable de la primera prescripci&#243;n &#40;medicina de familia o especialista hospitalario de referencia&#41;&#46; Se consider&#243; medicaci&#243;n cardiovascular la relacionada con los siguientes grupos terap&#233;uticos &#40;ATC&#41;&#58; antihipertensivos&#44; diur&#233;ticos&#44; betabloqueantes&#44; bloqueantes del canal de calcio&#44; agentes activos sobre el sistema renina-angiotensina&#44; agentes reductores de l&#237;pidos&#44; otros antidiab&#233;ticos orales&#44; agentes antitromb&#243;ticos y &#225;cido acetilsalic&#237;lico&#46; Tambi&#233;n se obtuvo el n&#250;mero de cambios de marca comercial realizados en la oficina de farmacia comunitaria &#40;marca y EFG&#41;&#44; la posolog&#237;a&#47;d&#237;a de metformina &#40;1&#44; 2 o 3 al d&#237;a&#41; y la dosis diaria total prescrita&#46; Esta informaci&#243;n se obtuvo durante el seguimiento de los pacientes&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Consecuencias cl&#237;nicas</span><p id="par0065" class="elsevierStylePara elsevierViewall">Como una aproximaci&#243;n a la efectividad cl&#237;nica se cuantific&#243;&#58; a&#41; el cambio inicial-final de la hemoglobina glicosilada &#40;HbA1c&#41; y b&#41; el porcentaje de ingresos hospitalarios por descompensaci&#243;n de la diabetes y&#47;o complicaciones macrovasculares &#40;incluye&#58; cardiopat&#237;a isqu&#233;mica &#91;infarto agudo de miocardio&#44; angina estable&#47;inestable&#93;&#44; accidente vasculocerebral &#91;ictus&#44; accidente isqu&#233;mico transitorio&#44; arteriopat&#237;a perif&#233;rica&#93;&#44; e insuficiencia renal&#41; durante el periodo de seguimiento &#40;2 a&#241;os&#41;&#46; Se obtuvieron los fallecimientos por todas las causas&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">An&#225;lisis estad&#237;stico</span><p id="par0070" class="elsevierStylePara elsevierViewall">Los criterios de b&#250;squeda en la base de datos fueron a partir de sentencias inform&#225;ticas &#40;SQL script&#41;&#46; Se revisaron cuidadosamente los datos&#44; mediante an&#225;lisis exploratorio y preparaci&#243;n de estos para el an&#225;lisis&#44; observando sus distribuciones de frecuencia y buscando posibles errores de registro o de codificaci&#243;n&#46; Para minimizar las posibles variables de confusi&#243;n se realiz&#243; un PSM &#40;1&#58;1&#59; metformina de marca vs&#46; metformina EFG&#41;&#46; Las variables incluidas para el apareamiento fueron&#58; edad&#44; sexo&#44; &#237;ndice de Charlson &#40;comorbilidad&#41;&#44; tiempo desde el diagn&#243;stico&#44; HbA1c inicial&#44; dosis de metformina inicial y la medicaci&#243;n basal&#46; Procedimiento&#58; vecino m&#225;s pr&#243;ximo <span class="elsevierStyleItalic">&#40;greedy nearest neighbour algorithm&#41;</span>&#46; Se proporcionaron los coeficientes estandarizados &#40;CE&#41;&#46; Se efectu&#243; un an&#225;lisis estad&#237;stico descriptivo-univariante&#46; Para los datos cualitativos&#58; frecuencias absolutas y relativas&#46; Para los datos cuantitativos&#58; el uso de media&#44; desviaci&#243;n est&#225;ndar &#40;DE&#41;&#44; mediana y percentiles 25 y 75 de la distribuci&#243;n &#40;amplitud intercuartil&#41;&#46; Los intervalos de confianza &#40;IC&#41; del 95&#37; para la estimaci&#243;n de par&#225;metros se basaron en el n&#250;mero total de sujetos con valores no perdidos&#46; La medida de la persistencia al tratamiento se analiz&#243; mediante un an&#225;lisis de supervivencia de Kaplan-Meier &#40;procedimiento&#58; log-rank test&#41;&#46; Se realiz&#243; un modelo de regresi&#243;n de riesgos proporcionales de Cox para la correcci&#243;n del tiempo de persistencia al tratamiento&#46; Adem&#225;s&#44; se efectu&#243; un modelo de regresi&#243;n log&#237;stica &#40;procedimiento&#58; enter&#59; estad&#237;stico&#58; Wald&#41; para evaluar la asociaci&#243;n entre&#58; a&#41; el control metab&#243;lico &#40;reducci&#243;n de la HbA1c&#41; y b&#41; los ingresos hospitalarios&#59; con respecto a metformina &#40;marca vs&#46; ECG&#41;&#46; Las covariables incluidas en los modelos multivariantes fueron las mencionadas con anterioridad en el apareamiento &#40;PSM&#41;&#46; Se utiliz&#243; el programa SPSSWIN versi&#243;n 23&#44; estableci&#233;ndose una significaci&#243;n estad&#237;stica para valores de p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Resultados</span><p id="par0075" class="elsevierStylePara elsevierViewall">De una selecci&#243;n inicial de 980&#46;682 sujetos &#8805;<span class="elsevierStyleHsp" style=""></span>18 a&#241;os asignados a los centros&#44; se reclutaron 5&#46;488 pacientes que reun&#237;an los criterios de selecci&#243;n para ser incluidos en el estudio &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Se compararon los pacientes en tratamiento con&#58; a&#41; metformina de marca &#40;N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>863&#59; 15&#44;7&#37;&#41; vs&#46; b&#41; EFG &#40;N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;625&#59; 84&#44;3&#37;&#41;&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se muestran las caracter&#237;sticas basales de la serie estudiada seg&#250;n los grupos de estudio&#46; La media de edad fue de 61&#44;7 &#40;DE&#58; 9&#44;7&#41; a&#241;os y el 51&#44;9&#37; fueron mujeres&#46; Del conjunto de pacientes&#44; el 59&#44;7&#37; presentaron hipertensi&#243;n arterial&#44; el 57&#44;1&#37; dislipemia y el 31&#44;7&#37; obesidad&#46; El promedio del &#237;ndice de Charlson fue de 1&#44;8 puntos&#44; mientras que el promedio de medicaci&#243;n en situaci&#243;n basal fue de 3&#44;5 &#40;1&#44;6&#41; medicamentos&#46; Hubo una aceptable comparabilidad basal entre los grupos de marca vs&#46; EFG&#46; Los 863 pacientes con metformina de marca se emparejaron en una relaci&#243;n 1&#58;1 con EFG&#46; Las caracter&#237;sticas basales de la serie estudiada despu&#233;s de realizar el PSM se muestran en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#46; La media de edad fue de 60&#44;8 &#40;DE&#58; 8&#44;8&#41; a&#241;os y el 52&#44;6&#37; fueron mujeres&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a> se detalla la persistencia al tratamiento&#44; la medicaci&#243;n cardiovascular y otras variables de inter&#233;s&#46; Con metformina de marca&#44; la duraci&#243;n media del tratamiento &#40;595 vs&#46; 554 d&#237;as&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y la persistencia a los 12 meses &#40;75&#44;7&#37; vs&#46; 68&#44;4&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y a los 24 meses de seguimiento &#40;63&#44;2&#37; vs&#46; 58&#44;2&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;034&#41; fue superior a la del EFG&#46; El hazard ratio relativo a la marca fue del 0&#44;83 &#40;IC del 95&#37;&#58; 0&#44;71-0&#44;96&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;013&#41;&#44; lo que implicar&#237;a que la prescripci&#243;n y&#47;o dispensaci&#243;n de marca reduce un 17&#37; el riesgo de discontinuar el tratamiento&#46; Por el contrario&#44; la persistencia al tratamiento a los 6 meses fue similar &#40;80&#44;6&#37; vs&#46; 78&#44;1&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;191&#41;&#46; En la <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a> se detallan las curvas de Kaplan-Meier de persistencia y probabilidad acumulada de permanecer con el tratamiento a los 24 meses de seguimiento&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">La medicaci&#243;n &#40;cardiovascular&#44; <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41; administrada durante el periodo de seguimiento fue ligeramente superior con metformina EFG &#40;2&#44;4 vs&#46; 2&#44;5&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;237&#41;&#44; aunque sin alcanzar la significaci&#243;n estad&#237;stica&#46; El promedio de dosis diaria administrada con metformina de marca vs&#46; EFG &#40;1&#46;406<span class="elsevierStyleHsp" style=""></span>mg vs&#46; 1&#46;368<span class="elsevierStyleHsp" style=""></span>mg&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;104&#41;&#44; as&#237; como el n&#250;mero de comprimidos&#47;d&#237;a &#40;2 comprimidos&#58; 56&#44;5&#37; vs&#46; 53&#44;1&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;246&#41; y el especialista que inicia la prescripci&#243;n &#40;medicina de familia&#58; 88&#44;4&#37; vs&#46; 90&#44;5&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;402&#41;&#44; respectivamente&#44; mostraron resultados parecidos&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Las consecuencias cl&#237;nicas &#40;efectividad&#41; seg&#250;n los grupos de estudio se detallan en la <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#46; Durante el seguimiento hubo una mayor reducci&#243;n porcentual de la HbA1c de marca vs&#46; EFG &#40;&#8722;6&#44;8&#37; vs&#46; &#8722;4&#44;1&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;013&#41;&#59; mientras que la reducci&#243;n de los ingresos hospitalarios fue un 19&#44;1&#37; superior en el caso de la marca &#40;8&#44;9&#37; vs&#46; 11&#44;0&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;148&#41;&#44; aunque sin alcanzar la significaci&#243;n estad&#237;stica&#46; Los fallecimientos fueron superiores con metformina EFG&#44; aunque sin alcanzar la significaci&#243;n estad&#237;stica &#40;1&#44;4&#37; vs&#46; 2&#44;1&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;258&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a> se detalla la persistencia al tratamiento&#44; ingresos hospitalarios y valores de hemoglobina glicosilada por grupos de estudio y rangos de edad &#40;subgrupos&#41;&#46; Durante el periodo de seguimiento &#40;24 meses&#41;&#44; no se observan diferencias destacadas&#44; respecto a los datos analizados con anterioridad&#46; Adem&#225;s&#44; en el modelo de regresi&#243;n log&#237;stica &#40;corregido por covariables&#41; se pudo comprobar que hubo una asociaci&#243;n entre el grado de control metab&#243;lico &#40;reducci&#243;n de HbA1c&#41; con respecto al uso de metformina de marca vs&#46; EFG &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;75&#59; IC del 95&#37;&#58; 0&#44;67-0&#44;84&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En cuanto a los ingresos hospitalarios&#44; no mostraron resultados concluyentes &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;26&#59; IC del 95&#37;&#58; 0&#44;92-1&#44;7&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;149&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">La persistencia al tratamiento a los 24 meses se asoci&#243; a la medicaci&#243;n de marca &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#44;253&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y a la posolog&#237;a&#47;d&#237;a administrada &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#44;209&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#46; La persistencia no se asoci&#243; al especialista m&#233;dico que inicia la prescripci&#243;n &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;057&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;537&#41;&#46; Adem&#225;s&#44; cabe destacar que el promedio de cambios de &#171;marca comercial&#187; en prescripciones gen&#233;ricas &#40;promedio&#58; 2&#44;5 cambios&#47;paciente&#59; r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#44;306&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; se asoci&#243; con un aumento en la discontinuaci&#243;n del tratamiento&#46; Al 58&#44;2&#37; de los sujetos &#40;N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>502&#47;863&#41; se les dispensaron 2&#43; &#171;marcas comerciales&#187; diferentes durante el periodo de seguimiento&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discusi&#243;n</span><p id="par0105" class="elsevierStylePara elsevierViewall">Los resultados del estudio ponen de manifiesto que los pacientes polimedicados &#8805;<span class="elsevierStyleHsp" style=""></span>50 a&#241;os que inician tratamiento con metformina de marca frente a EFG en monoterapia se asocian a una mayor persistencia al tratamiento&#44; repercutiendo en un mejor grado de control metab&#243;lico &#40;HbA1c&#41;&#46; Aunque&#44; cabe destacar la falta de estudios observacionales en condiciones de vida real en la bibliograf&#237;a revisada&#44; circunstancia que dificulta la comparaci&#243;n de los resultados&#44; pero que&#44; por otra parte&#44; realzan la singularidad de este estudio&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Un medicamento EFG tiene la misma composici&#243;n cualitativa&#47;cuantitativa en principio activo y forma farmac&#233;utica&#44; con una bioequivalencia demostrada &#40;biodisponibilidad&#41; con el medicamento de referencia &#40;marca&#41;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">14&#44;15</span></a>&#46; En nuestro pa&#237;s&#44; la entrada al mercado de estos f&#225;rmacos contribuy&#243; a una reducci&#243;n del gasto farmac&#233;utico en la sanidad p&#250;blica&#44; aunque en la actualidad&#44; tanto los medicamentos gen&#233;ricos como los de marca presentan el mismo coste de adquisici&#243;n debido a la existencia de un sistema de precios de referencia y de agrupaciones homog&#233;neas que impone la igualdad de precios entre marcas y gen&#233;ricos&#46; Ante este escenario&#44; no deber&#237;an existir argumentos farmacol&#243;gicos&#44; ni econ&#243;micos&#44; que impidan indistintamente la prescripci&#243;n de medicamentos de marca o EFG&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">En los medicamentos EFG&#44; pueden existir diferencias en la composici&#243;n de los excipientes y en su apariencia externa&#44; circunstancia que puede repercutir en problemas de bioapariencia &#40;tipo de envase&#44; forma del comprimido&#44; etc&#46;&#41;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">19&#44;20</span></a>&#46; Los resultados globales del estudio est&#225;n en consonancia con los estudios que apoyan la posibilidad de que un cambio en la apariencia del medicamento&#44; en la dispensaci&#243;n de una receta&#44; puede crear confusi&#243;n a los pacientes&#44; y reducir la adherencia &#40;persistencia al tratamiento&#41;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">19&#44;20&#44;24</span></a>&#46; Kesselheim et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> mostraron que los cambios en los colores y formas de los comprimidos&#47;c&#225;psulas aumentan el riesgo en la discontinuaci&#243;n en pacientes epil&#233;pticos&#46; Los autores detallan que los cambios entre diferentes EFG pueden conllevar un riesgo para la salud de los pacientes&#44; especialmente si presentan enfermedades cr&#243;nicas&#46; Goldszmidt et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a> describieron que los cambios de medicamentos EFG &#40;diferentes nombres comerciales&#41; pueden afectar al cumplimiento terap&#233;utico y a la efectividad cl&#237;nica&#46; Colombo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a> describen que la adherencia al tratamiento es un factor importante para el control metab&#243;lico y la prevenci&#243;n de la progresi&#243;n de la enfermedad&#46; El envejecimiento&#44; las comorbilidades y la polifarmacia pueden afectar la adherencia e influir en el resultado de los tratamientos&#46; Nuestros resultados parecen estar en consonancia con estas observaciones&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Los resultados del estudio muestran que la persistencia a los 24 meses de metformina de marca fue superior a la EFG &#40;63&#44;2&#37; vs&#46; 58&#44;2&#37;&#59; HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;83&#41;&#46; Flory et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a>&#44; en una cohorte de 1&#46;259 individuos&#44; muestran una tasa de discontinuaci&#243;n temprana del 20&#44;3&#37;&#46; Los autores detallan que la prescripci&#243;n de dosis iniciales bajas de metformina mejora la persistencia de la medicaci&#243;n&#46; Otros autores describen una persistencia al a&#241;o de seguimiento inferior al 70&#37;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">10&#8211;12</span></a>&#46; En cuanto a la comparaci&#243;n de diferentes antidiab&#233;ticos de marca vs&#46; EFG&#44; el estudio de Trotta et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">29</span></a> detalla que de los pacientes que recibieron EFG&#44; el 61&#44;0&#37; tom&#243; la misma marca comercial&#44; el 23&#44;3&#37; experiment&#243; un solo cambio y el 15&#44;7&#37; m&#250;ltiples&#46; Los autores manifiestan que en pacientes de edad avanzada tratados con antidiab&#233;ticos la adherencia fue similar entre los grupos &#40;marca vs&#46; EFG&#41;&#46; No obstante&#44; el efecto en la adherencia de los pacientes con m&#250;ltiples cambios de EFG debe tenerse en cuenta &#40;discontinuaci&#243;n&#41;&#46; Nuestros resultados de persistencia al tratamiento son ligeramente superiores a los reportados por estos autores&#46; Esta circunstancia podr&#237;a explicarse por varias razones&#58; a&#41; el m&#233;todo de medida de la persistencia&#44; b&#41; es un estudio m&#225;s reciente&#44; y&#47;o c&#41; son pacientes que acuden regularmente a los controles y est&#225;n sujetos a un seguimiento espec&#237;fico por parte de enfermer&#237;a&#46; Nuestros resultados son consistentes con estas observaciones&#44; aunque no hemos encontrado ning&#250;n estudio similar al nuestro&#44; que compare metformina de marca vs&#46; EFG&#46; En este sentido&#44; adem&#225;s de las conocidas razones de incumplimiento&#44; que pueden ser <span class="elsevierStyleItalic">intencionadas</span> &#40;factores sociodemogr&#225;ficos&#44; efectos secundarios&#44; falta de comprensi&#243;n del tratamiento o del estado de salud&#44; etc&#46;&#41; o <span class="elsevierStyleItalic">no intencionadas</span> &#40;olvido de c&#243;mo tomar la medicaci&#243;n correctamente&#44; etc&#46;&#41;&#44; los resultados del estudio muestran que la prescripci&#243;n gen&#233;rica podr&#237;a considerarse un factor m&#225;s a tener en cuenta en este colectivo de pacientes&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">En otros estudios en los que se compara marca con EFG&#44; se observan resultados contradictorios&#46; En general &#40;conjunto de pacientes&#41;&#44; en el uso de medicamentos EFG en enfermedades cardiovasculares no se encuentran discrepancias entre la adherencia&#47;persistencia al tratamiento entre estos dos grupos de medicamentos<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">16</span></a>&#46; Sin embargo&#44; en neurolog&#237;a y en psicolog&#237;a los datos son m&#225;s conflictivos y dependen de la enfermedad tratada<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a>&#46; Aunque las discrepancias son manifiestas&#44; en funci&#243;n de la metodolog&#237;a utilizada&#44; la poblaci&#243;n de estudio y otros factores relacionados con los proveedores y los pacientes<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">30&#44;31</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Durante el seguimiento hubo una mayor reducci&#243;n porcentual de la HbA1c de marca vs&#46; gen&#233;rica&#59; mientras que la reducci&#243;n de los ingresos hospitalarios fue del &#8722;19&#44;1&#37;&#44; aunque sin alcanzar la significaci&#243;n estad&#237;stica &#40;escaso tama&#241;o muestral&#41;&#46; La asociaci&#243;n entre la adherencia al tratamiento y la consecuci&#243;n de los objetivos terap&#233;uticos de control y el riesgo de complicaciones en la progresi&#243;n de la enfermedad est&#225;n fuera de toda duda&#46; En este sentido&#44; nuestros resultados son consistentes con las evidencias disponibles en la literatura<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">25&#8211;28&#44;30&#8211;33</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Algunos autores recomiendan resaltar el nombre del principio activo en la etiqueta de los envases de los medicamentos EFG y alertan de las consecuencias que puede tener&#44; en la adherencia de los pacientes&#44; cambiar la apariencia del envase cada vez que se dispensa una nueva receta<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">34</span></a>&#46; Nuestros resultados podr&#237;an respaldar estas aportaciones&#46; En este sentido&#44; a igualdad de eficacia y bioequivalencia entre el medicamento de marca y el EFG&#44; los hallazgos de este estudio sugieren que los cambios en la <span class="elsevierStyleItalic">apariencia</span> del f&#225;rmaco pueden repercutir en la seguridad del paciente&#44; especialmente en enfermedades cr&#243;nicas&#44; pacientes mayores y&#47;o polimedicados&#46; La reducci&#243;n de la variabilidad en la apariencia &#40;imagen del medicamento o similar&#41; entre medicamentos qu&#237;micamente id&#233;nticos podr&#237;a ayudar a promover la falta de discontinuaci&#243;n del tratamiento y mejorar la adherencia de este&#44; aunque es t&#233;cnicamente complicado de conseguir&#46; Por tanto&#44; o bien regulamos la normalizaci&#243;n de la bioapariencia&#44; o mejor a&#250;n&#44; evaluamos el impacto que supone la falta de bioapariencia&#44; como se ha puesto de manifiesto en este estudio<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Las posibles limitaciones del estudio inciden en las propias de los estudios retrospectivos&#44; como por ejemplo el infrarregistro de la enfermedad o la posible variabilidad de los profesionales y de los pacientes al ser un dise&#241;o observacional&#44; o incluso al sistema de medida empleado para las principales variables del estudio&#44; o a la posibilidad de la existencia de un sesgo de clasificaci&#243;n&#46; En este aspecto&#44; la posible inexactitud de la codificaci&#243;n diagn&#243;stica en cuanto al diagn&#243;stico&#44; o bien la falta de alguna variable que pudiera influir en los resultados finales &#40;nivel socioecon&#243;mico de los pacientes&#44; evoluci&#243;n de la dosis farmacol&#243;gica prescrita&#44; obtenci&#243;n de la medicaci&#243;n&#44; reacciones adversas&#44; etc&#46;&#41;&#44; deben considerarse como una limitaci&#243;n del estudio&#46; Aunque&#44; a nuestro entender&#44; la principal objeci&#243;n al estudio fue el sesgo de selecci&#243;n por parte del m&#233;dico responsable a la hora de iniciar un tratamiento de marca o EFG&#44; puesto que no se realiz&#243; de forma aleatoria&#44; como es habitual en situaci&#243;n de vida real&#46; No obstante&#44; este posible sesgo no debe repercutir en los resultados del estudio&#46; Cabe destacar que hubiera sido de indudable inter&#233;s analizar los diferentes motivos de suspensi&#243;n del f&#225;rmaco&#44; puesto que no es lo mismo por ausencia de efectividad que por tolerancia&#59; lamentablemente esta informaci&#243;n no estuvo disponible en la base de datos&#46; A pesar de que en el estudio los pacientes inician un nuevo tratamiento con metformina 850<span class="elsevierStyleHsp" style=""></span>mg en monoterapia&#44; no podemos descartar la existencia de un sesgo de selecci&#243;n&#46; En primer lugar&#44; porque los niveles iniciales de HbA1c quiz&#225;s fueron sensiblemente bajos&#59; y&#44; en segundo lugar&#44; por el escaso tama&#241;o muestral conseguido&#46; No obstante&#44; este potencial sesgo deber&#237;a de estar distribuido por igual en los dos grupos de estudio&#44; circunstancia que no deber&#237;a afectar a los resultados obtenidos&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Las perspectivas futuras se centran en replicar este estudio en otras instituciones sanitarias y en promover estrategias de intervenci&#243;n orientadas a fomentar la adherencia de los pacientes a los tratamientos prescritos por sus m&#233;dicos&#46; En conclusi&#243;n&#44; los pacientes polimedicados que iniciaron un nuevo tratamiento con metformina de marca vs&#46; gen&#233;rica para la DM2 se asociaron a un mayor grado de persistencia al tratamiento&#44; repercutiendo en un mejor grado de control metab&#243;lico &#40;reducci&#243;n porcentual de HbA1c&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Financiaci&#243;n</span><p id="par0150" class="elsevierStylePara elsevierViewall">Estudio patrocinado por FarmaIndustria&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Autor&#237;a</span><p id="par0155" class="elsevierStylePara elsevierViewall">Los autores han contribuido en los siguientes aspectos&#58; &#40;1&#41; la concepci&#243;n y el dise&#241;o del estudio&#44; o la adquisici&#243;n de datos&#44; o el an&#225;lisis y la interpretaci&#243;n de los datos&#44; &#40;2&#41; el borrador del art&#237;culo o la revisi&#243;n cr&#237;tica del contenido intelectual&#44; y &#40;3&#41; la aprobaci&#243;n definitiva de la versi&#243;n que se presenta&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicto de intereses</span><p id="par0160" class="elsevierStylePara elsevierViewall">ASM y ASN son consultores independientes &#40;Atrys Health&#41; en relaci&#243;n con el desarrollo de este estudio&#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 persistencia al tratamiento en sujetos con diabetes tipo 2 &#40;DM2&#41; polimedicados que se les administra un nuevo tratamiento con metformina 850<span class="elsevierStyleHsp" style=""></span>mg de marca vs&#46; gen&#233;rica en situaci&#243;n de pr&#225;ctica cl&#237;nica habitual&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional-retrospectivo&#44; realizado a partir de los registros m&#233;dicos de pacientes &#8805;<span class="elsevierStyleHsp" style=""></span>50 a&#241;os&#44; que iniciaron tratamiento con metformina &#40;marca vs&#46; gen&#233;rico&#41; entre el 01&#47;01&#47;2016 y el 31&#47;12&#47;2017&#46; El seguimiento de los pacientes fue de 2 a&#241;os&#46; Principales medidas&#58; persistencia al tratamiento y consecuencias cl&#237;nicas &#40;control metab&#243;lico &#91;HbA1c&#93; e ingresos hospitalarios&#41;&#46; Cada paciente del grupo de marca &#40;referencia&#41; se emparej&#243; con otro del grupo gen&#233;rico mediante <span class="elsevierStyleItalic">propensity score matching</span>&#46; Se realiz&#243; un modelo de riesgos proporcionales de Cox&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se emparejaron 863 pacientes con metformina de marca vs&#46; gen&#233;rica &#40;relaci&#243;n 1&#58;1&#41;&#46; La media de edad fue de 60&#44;8 &#40;DE&#58; 8&#44;8&#41; a&#241;os y el 52&#44;6&#37; fueron mujeres&#46; Con metformina de marca&#44; la persistencia a los 24 meses de seguimiento fue un 8&#44;6&#37; superior a la gen&#233;rica &#40;63&#44;2&#37; vs&#46; 58&#44;2&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;034&#41;&#46; El hazard ratio relativo a la marca fue del 0&#44;83 &#40;IC 95&#37;&#58; 0&#44;71-0&#44;96&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;013&#41;&#46; Durante el seguimiento hubo una mayor reducci&#243;n porcentual de la HbA1c de marca vs&#46; gen&#233;rica &#40;&#8722;6&#44;8&#37; vs&#46; &#8722;4&#44;1&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;013&#41;&#46; Hubo una reducci&#243;n del 19&#44;1&#37; en los ingresos hospitalarios superior con metformina de marca vs&#46; gen&#233;rica &#40;8&#44;9&#37; vs&#46; 11&#44;0&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;148&#41;&#44; aunque sin alcanzar la significaci&#243;n estad&#237;stica&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Los pacientes polimedicados que iniciaron un nuevo tratamiento con metformina de marca para la DM2 se asociaron a un mayor grado de persistencia al tratamiento que los que lo iniciaron con metformina gen&#233;rica&#44; repercutiendo en un mejor grado de control metab&#243;lico &#40;reducci&#243;n porcentual de HbA1c&#41;&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To evaluate treatment persistence in patients with polymedicated type 2 diabetes &#40;DM2&#41; receiving new treatment with brand-name vs&#46; generic metformin 850<span class="elsevierStyleHsp" style=""></span>mg in usual clinical practice&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Observational&#44; retrospective study based on the medical records of patients aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years who initiated metformin treatment &#40;brand-name vs&#46; generic&#41; between 01&#47;01&#47;2016 and 31&#47;12&#47;2017&#46; The follow up was two years&#46; Main measures&#58; treatment persistence and clinical consequences &#40;metabolic control &#91;HbA1c&#93; and hospital admissions&#41;&#46; Each patient in the brand-name group &#40;reference&#41; was paired with a patient from the generic group using propensity score matching&#46; A Cox proportional risk model was constructed &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">863 patients receiving brand-name metformin were matched &#40;ratio 1&#58;1&#41; with patients receiving generic metformin&#46; The median age was 60&#46;8 years &#40;SD&#58; 8&#46;8&#41; years and 52&#46;6&#37; were female&#46; Persistence at 24 months was 8&#46;6&#37; higher for brand-name vs&#46; generic metformin &#40;63&#46;2&#37; vs&#46; 58&#46;2&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#41;&#46; The hazard ratio for brand-name metformin was 0&#46;83 &#40;95&#37; CI&#58; 0&#46;71-0&#46;96&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;013&#41;&#46; During the follow-up there was a greater percentage reduction of HbA1c in the brand-name vs&#46; generic group &#40;&#8722;6&#46;8&#37; vs&#46; &#8722;4&#46;1&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;013&#41;&#46; There was a non-significant 19&#46;1&#37; reduction in hospital admissions in the brand-name vs&#46; generic group &#40;8&#46;9&#37; vs&#46; 11&#46;0&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;148&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Polymedicated patients who initiated new brand-name metformin treatment for DM2 had greater treatment persistence than those who initiated it with generic metformin and had better metabolic control &#40;percentage reduction in HbA1c&#41;&#46;</p></span>"
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                  \t\t\t\t" scope="col">Grupos de estudio&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#250;mero de pacientes&#44; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#46;625&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">61&#44;7 &#40;9&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;011&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">453 &#40;52&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;395 &#40;51&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;848 &#40;51&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;703&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">2&#44;3 &#40;1&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;4 &#40;1&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;4 &#40;1&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;012&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#205;ndice de Charlson &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;8 &#40;1&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;8 &#40;1&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#44;8 &#40;1&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;247&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  " colspan="5" align="left" valign="\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="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Comorbilidades asociadas&#59; N &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hipertensi&#243;n arterial&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">486 &#40;56&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;790 &#40;60&#44;3&#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">3&#46;276 &#40;59&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;028&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dislipemia&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">461 &#40;53&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;674 &#40;57&#44;8&#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
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                  \t\t\t\t">3&#46;135 &#40;57&#44;1&#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
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                  \t\t\t\t">0&#44;017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Obesidad&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">264 &#40;30&#44;6&#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">1&#46;475 &#40;31&#44;9&#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">1&#46;739 &#40;31&#44;7&#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;451&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>Fumadores activos&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">85 &#40;9&#44;8&#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
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                  \t\t\t\t">506 &#40;10&#44;9&#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">591 &#40;10&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;342&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infarto de miocardio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90 &#40;10&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">458 &#40;9&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">548 &#40;10&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;636&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>Ictus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">58 &#40;6&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">316 &#40;6&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">374 &#40;6&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;905&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>Enfermedad arterial perif&#233;rica&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">47 &#40;5&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">286 &#40;6&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">333 &#40;6&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;405&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Insuficiencia card&#237;aca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">73 &#40;8&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">415 &#40;9&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">488 &#40;8&#44;9&#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
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                  \t\t\t\t">0&#44;626&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>Insuficiencia renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">67 &#40;7&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">398 &#40;8&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">465 &#40;8&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;415&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Asma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">50 &#40;5&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">276 &#40;6&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">326 &#40;5&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;843&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>EPOC&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">79 &#40;9&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">421 &#40;9&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">500 &#40;9&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;962&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Neuropat&#237;as&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">18 &#40;2&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">78 &#40;1&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">96 &#40;1&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;411&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome depresivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">73 &#40;8&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">343 &#40;7&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">416 &#40;7&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;288&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>Neoplasias malignas&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">112 &#40;13&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">656 &#40;14&#44;2&#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
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                  \t\t\t\t">768 &#40;14&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;349&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="5" 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="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Otras variables</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>Tiempo desde el diagn&#243;stico &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">13&#44;1 &#40;0&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">13&#44;0 &#40;0&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13&#44;0 &#40;0&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;267&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>Dosis diaria de metformina &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;405&#44;5 &#40;477&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;364&#44;8 &#40;490&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#46;371&#44;2 &#40;488&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;267&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>HbA1c inicial&#44; &#37; &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">7&#44;3 &#40;1&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">7&#44;3 &#40;2&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">7&#44;3 &#40;2&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;863&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="5" align="left" valign="\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
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t">3&#44;4 &#40;1&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;5 &#40;1&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;5 &#40;1&#44;6&#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;087&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
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">324 &#40;37&#44;5&#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">1&#46;665 &#40;36&#44;0&#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">1&#46;989 &#40;36&#44;2&#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;401&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>Sangre y &#243;rganos hematopoy&#233;ticos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">221 &#40;25&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;087 &#40;23&#44;5&#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">1&#46;308 &#40;23&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;204&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sistema cardiovascular&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">334 &#40;38&#44;7&#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">1&#46;906 &#40;41&#44;2&#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">2&#46;240 &#40;40&#44;8&#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;099&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>Dermatol&#243;gicos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">121 &#40;14&#44;0&#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">731 &#40;15&#44;8&#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">852 &#40;15&#44;5&#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;138&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>Sistema m&#250;sculo-esquel&#233;tico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">356 &#40;41&#44;2&#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">1&#46;767 &#40;38&#44;2&#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">2&#46;123 &#40;38&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;068&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">312 &#40;36&#44;1&#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">1&#46;651 &#40;35&#44;7&#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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;963 &#40;35&#44;8&#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;333&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>Sistema respiratorio&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">158 &#40;18&#44;3&#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
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                  \t\t\t\t">902 &#40;19&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#46;060 &#40;19&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;272&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Otros medicamentos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">249 &#40;28&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#46;420 &#40;30&#44;7&#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">1&#46;669 &#40;30&#44;4&#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;238&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">EFG&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">CE&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>863&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Promedio de edad&#44; a&#241;os &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">61&#44;0 &#40;9&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">60&#44;6 &#40;8&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;354&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;022&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sexo &#40;mujeres&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">453 &#40;52&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">455 &#40;52&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;923&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\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
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Comorbilidad general</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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Promedio de diagn&#243;sticos &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;3 &#40;1&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#44;4 &#40;1&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;035&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Promedio &#237;ndice de Charlson &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#44;8 &#40;1&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;8 &#40;1&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;856&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;004&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\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
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Comorbilidades asociadas&#59; N &#40;&#37;&#41;</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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hipertensi&#243;n arterial&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">486 &#40;56&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">519 &#40;60&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;107&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;039&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dislipemia&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">461 &#40;53&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">570 &#40;54&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;029&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Obesidad&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">264 &#40;30&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">262 &#40;30&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;917&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fumadores activos&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">85 &#40;9&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">107 &#40;12&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;092&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;041&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infarto de miocardio&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">90 &#40;10&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">93 &#40;10&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;815&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;006&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>Ictus&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">58 &#40;6&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">43 &#40;5&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;124&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;037&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Enfermedad arterial perif&#233;rica&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">47 &#40;5&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">57 &#40;6&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;312&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;024&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Insuficiencia card&#237;aca&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">73 &#40;8&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">58 &#40;6&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;173&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;033&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>Insuficiencia renal&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">67 &#40;7&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">60 &#40;7&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;519&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Asma&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">50 &#40;5&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">50 &#40;5&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;999&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">67 &#40;7&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;299&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Neoplasias malignas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;041&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Endocrinolog&#237;a&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35 &#40;4&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">21 &#40;2&#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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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Otras especialidades&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">38 &#40;4&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26 &#40;3&#44;0&#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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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Metformina&#58; dosis diaria&#44; mg &#40;promedio&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;405&#44;5 &#40;477&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;368&#44;1 &#40;478&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;104&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;039&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 comprimido&#47;d&#237;a&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">337 &#40;39&#44;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">371 &#40;43&#44;0&#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;246&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Tiempo desde el diagn&#243;stico&#44; a&#241;os</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;P25-P75&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Duraci&#243;n del tratamiento&#44; meses</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">725 &#40;481-70&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Medicaci&#243;n cardiovascular &#40;promedio&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Antihipertensivos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Betabloqueantes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">228 &#40;26&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bloqueantes del canal de calcio&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">169 &#40;19&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Agentes del sistema renina-angiotensina&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">550 &#40;63&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">564 &#40;65&#44;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Agentes reductores de l&#237;pidos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">450 &#40;52&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;010&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>Otros antidiab&#233;ticos orales&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;3&#44;4&#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">23 &#40;2&#44;7&#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">0&#44;398&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;020&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>Agentes antitromb&#243;ticos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">225 &#40;26&#44;1&#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">200 &#40;23&#44;2&#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;119&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;023&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>&#193;cido acetilsalic&#237;lico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72 &#40;8&#44;3&#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">83 &#40;9&#44;6&#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;354&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;022&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="5" 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="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Persistencia al tratamiento</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>6 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;191&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;032&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><span class="elsevierStyleHsp" style=""></span>Hazard ratio relativo a la marca<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\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">0&#44;84 &#40;IC&#58; 0&#44;68-1&#44;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;101&nbsp;\t\t\t\t\t\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>12 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#44;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;091&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><span class="elsevierStyleHsp" style=""></span>Hazard ratio relativo a la marca<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\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">0&#44;73 &#40;IC&#58; 0&#44;61-0&#44;67&#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">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&nbsp;\t\t\t\t\t\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>24 meses&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">58&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;034&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;081&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><span class="elsevierStyleHsp" style=""></span>Hazard ratio relativo a la marca<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;83 &#40;IC&#58; 0&#44;71-0&#44;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Grupos de estudio&#44; PSM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">Marca&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">EFG&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><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">N&#250;mero de pacientes&#44; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>863&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>863&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Consecuencias cl&#237;nicas</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>HbA1c inicial&#44; &#37; &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;3 &#40;1&#44;7&#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">7&#44;3 &#40;1&#44;4&#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
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                  \t\t\t\t">18&#44;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#44;0&#37;&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  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Valores de HbA1c</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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">50-64 a&#241;os</span>&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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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&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">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>HbA1c inicial&#44; &#37; &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&#44;4 &#40;1&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&#44;4 &#40;1&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;0&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><span class="elsevierStyleHsp" style=""></span>HbA1c final&#44; &#37; &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#44;9 &#40;1&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Diferencia&#58; HbA1c final - inicial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8722;0&#44;5 &#40;1&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8722;0&#44;3 &#40;1&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Significaci&#243;n estad&#237;stica &#40;diferencia&#41;</span>&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"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#44;001</span>&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"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#44;001</span>&nbsp;\t\t\t\t\t\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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">65-79 a&#241;os</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><span class="elsevierStyleHsp" style=""></span>HbA1c inicial&#44; &#37; &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&#44;1 &#40;1&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&#44;1 &#40;1&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>HbA1c final&#44; &#37; &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#44;6 &#40;1&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#44;9 &#40;1&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;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><span class="elsevierStyleHsp" style=""></span>Diferencia&#58; HbA1c final - inicial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8722;0&#44;5 &#40;1&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8722;0&#44;2 &#40;1&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Significaci&#243;n estad&#237;stica &#40;diferencia&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#44;001</span>&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"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#44;102</span>&nbsp;\t\t\t\t\t\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
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                  \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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">80&#43; a&#241;os</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><span class="elsevierStyleHsp" style=""></span>HbA1c inicial&#44; &#37; &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#44;9 &#40;1&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&#44;2 &#40;1&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;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><span class="elsevierStyleHsp" style=""></span>HbA1c final&#44; &#37; &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#44;4 &#40;1&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&#44;1 &#40;1&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Diferencia&#58; HbA1c final - inicial&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">&#8722;0&#44;1 &#40;1&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Significaci&#243;n estad&#237;stica &#40;diferencia&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
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ISSN: 11383593
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es en pt

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

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

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