<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0185-3325</journal-id>
<journal-title><![CDATA[Salud mental]]></journal-title>
<abbrev-journal-title><![CDATA[Salud Ment]]></abbrev-journal-title>
<issn>0185-3325</issn>
<publisher>
<publisher-name><![CDATA[Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0185-33252008000600008</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Impacto de la duración de la psicosis no tratada (DPNT) en el curso y pronóstico de la esquizofrenia]]></article-title>
<article-title xml:lang="en"><![CDATA[Impact of Duration of Untreated Psychosis (DUP) in the course and outcome of schizophrenia]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[García]]></surname>
<given-names><![CDATA[Isis]]></given-names>
</name>
<xref ref-type="aff" rid="A01"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Fresán]]></surname>
<given-names><![CDATA[Ana]]></given-names>
</name>
<xref ref-type="aff" rid="A02"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Medina-Mora]]></surname>
<given-names><![CDATA[María Elena]]></given-names>
</name>
<xref ref-type="aff" rid="A03"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ruiz]]></surname>
<given-names><![CDATA[Gabriela Mariana]]></given-names>
</name>
</contrib>
</contrib-group>
<aff id="A01">
<institution><![CDATA[,Universidad Nacional Autónoma de México Facultad de Psicología ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<aff id="A02">
<institution><![CDATA[,Instituto Nacional de Psiquiatría Ramón de la Fuente Subdirección de Investigaciones Clínicas ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<aff id="A03">
<institution><![CDATA[,Instituto Nacional de Psiquiatría Ramón de la Fuente Dirección de Investigaciones Epidemiológicas y Psicosociales ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>12</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>12</month>
<year>2008</year>
</pub-date>
<volume>31</volume>
<numero>6</numero>
<fpage>479</fpage>
<lpage>485</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_arttext&amp;pid=S0185-33252008000600008&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_abstract&amp;pid=S0185-33252008000600008&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_pdf&amp;pid=S0185-33252008000600008&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[The duration of Untreated Psychosis (DUP), defined as the period of time between the onset of psychotic symptoms, such as hallucinations and delusions, and the first effective treatment, has been associated to prognosis of schizophrenia. It has been demonstrated that although psychotic symptoms are initially detected by relatives of patients with schizophrenia, they take a long time to seek specialized attention, which in turn leads to a delay in the diagnosis and treatment of the disorder. Schizophrenia has been considered by the World Health Organization as a public health problem and has been placed as the ninth cause of incapacity in the world. Thus, DUP represents part of this public health problem. In Mexico, the average DUP lasts 64 weeks, which is very similar to the average observed in other countries, where the mean DUP in psychotic patients varies between one and two years. One of the main reasons of a prolonged DUP is that patients and their families first assist with a general practitioner which, in many cases, does not perform an adequate diagnosis with the subsequent referral to a psychiatric facility, and the treatment given for the patient is based on sedative medication. This is also Mexico's case, where seeking help primarily involves religious groups, with very few referrals to psychiatric facilities and with inadequate treatment support, which delays care in specialized services. It has been established that early treatment is related to a better prognosis and outcome, while treatment delay has been related to a longer time to achieve symptom remission. These results support the hypothesis that the presence of psychotic symptoms for a long period of time may predispose to biological damage, which may in turn lead to predominant negative symptoms and severe cognitive deficits after the first psychotic episode. Also, some studies have found that a longer DUP is related to a more insidious illness onset, frequent relapses and psychiatric hospitalizations during the course of the disorder, with a poor response to antipsychotic medication. Through the use of neuroimaging, several studies have found the relation between DUP and brain morphology in patients with schizophrenia. Studies using Magnetic Resonance Imaging (MRI) have reported that patients with longer DUP show a significant reduction in the gray matter of the temporal planum, in the left middle, inferior temporal, left occipital and left fusiform cortices, with an increase of grey matter in the left basal ganglia, and a volume reduction of the caudate nucleus. These results may be related to the clinical course of the disorder in terms of a higher symptom severity and poor treatment response. In regard to psychosocial variables related to DUP, it has been observed that men have a longer DUP when compared to women and patients that are single and unemployed also have a longer DUP. Consequently, it has been found that there is a relationship between DUP and premorbid adjustment in patients with schizophrenia. Premorbid adjustment is defined as the psychosocial functioning in the educational, occupational, social and interpersonal relations areas before the evidence of positive characteristic symptomatology, where symptoms are not secondary to an organic cause and cover a period of six months before the first psychiatric hospitalization or contact with a psychiatric facility. In addition, it has been found that a prolonged DUP is related to a poor premorbid adjustment, especially during late adolescence and adulthood. This association may suggest the presence of prodromic symptoms secondary to the physiopathological process of psychosis. Consequently, if a patient shows some of the initial symptoms of the disorder, including psychosocial impairment, his/her abilities to be aware of the symptoms may be limited to seek for medical care, which may in turn increase DUP. Furthermore, some authors have reported that some variables related to the patient's environment are related with DUP. The main variable pointed out is: the previous experience with mental disorders and psychiatric facilities. Patients whose families had previous experience of a mentally ill relative, report a shorter DUP when compared to families with no previous history of an ill relative. Also, it has been analised that patients with an adequate social network have a shorter DUP compared to those patients whose social network is inadequate or limited. Based on these results, some authors have proposed two phenotypes for psychotic disorders: the first one characterized by males, poor premorbid adjustment, long DUP, insidious onset of the disorder and a stable pattern of negative symptoms. The second phenotype was one characterized by the following variables: females, good premorbid adjustment, a shorter DUP, acute illness onset and absence of a stable pattern of negative symptoms. This definition may be useful to determine the course of the disorder in patients with schizophrenia and may be able to predict the clinical outcome. Thus, DUP can be used as an indicator of prognosis in patients with schizophrenia and its evaluation should be promoted. Although these two phenotypes are very useful, caution should be warranted in their use to avoid generalization. By and large, the studies related to the clinical impact of DUP emphasized the need to reduce DUP through early detection programs, including psychoeducation. We believe that this approach will be useful to identify individuals at an early development of a psychotic illness so that interventions can begin before symptoms have reached a level of significant impairment for the patient and warranting referrals by the family, school or health providers. Based on the studies reviewed above, we can conclude that DUP has a definitive impact on the prognosis of patients with schizophrenia and that future studies should be performed including it not only as a predictor of clinical outcome, but also as an specific clinical target for mental health research. Increasing the knowledge about the relationship between DUP and clinical course of schizophrenia is crucial to create and promote early detection and intervention programs such as the ones that have started all over the world, where the main objective is to identify young people who are at risk of developing psychotic disorders, specially schizophrenia.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[La duración de la psicosis no tratada (DPNT), definida como el período de tiempo entre la aparición de los síntomas psicóticos y el inicio de un tratamiento adecuado, está asociada al pronóstico de la esquizofrenia, enfermedad que ha sido considerada por la Organización Mundial de la Salud, como un problema de salud pública. El atraso en la búsqueda de tratamiento especializado conlleva a un retraso en el diagnóstico y tratamiento adecuados de la enfermedad. En México, el promedio de la DPNT es de 64 semanas, siendo éste similar al reportado en otros países, donde la media varía entre uno y dos años. Se ha comprobado que el retraso en el tratamiento adecuado del padecimiento está relacionado con un pobre pronóstico, lo cual apoya la hipótesis de que la presencia de síntomas psicóticos durante un largo período de tiempo puede predisponer a un daño biológico, generando así un predominio de síntomas negativos y mayores déficit cognitivos después del primer episodio psicótico. Además, se ha encontrado que una DPNT larga se relaciona con un inicio insidioso de la enfermedad, mayor número de recaídas y rehospitalizaciones psiquiátricas durante el curso de la enfermedad, además de una pobre respuesta al tratamiento farmacológico con antipsicóticos. En cuanto a las variables demográficas y psicosociales que se asocian con una DPNT prolongada encontramos: al sexo masculino, el no tener pareja u ocupación laboral. Asimismo, se ha reportado que los pacientes que presentan un mayor deterioro en su funcionamiento premórbido, son aquellos que muestran una mayor DPNT. Esta asociación sugiere que los pacientes con esquizofrenia pueden presentar síntomas prodrómicos mucho tiempo antes de que su funcionamiento se vea totalmente afectado por el proceso fisiopatológico de la psicosis. Asimismo, se han reportado variables relacionadas con el entorno del paciente asociadas a la DPNT. Entre ellas, destacan la experiencia previa con trastornos mentales y las redes sociales. Se ha observado que los pacientes de familias que han tenido una experiencia previa con otro familiar diagnosticado con alguna enfermedad mental, muestran una menor DPNT en contraste con aquellos cuyas familias no han tenido experiencias previas de enfermedades mentales. De igual forma, se ha informado que pacientes con una adecuada red social tienen una menor DPNT, comparados con aquellos cuya red social es limitada. A partir de estos hallazgos se han propuesto dos fenotipos para los trastornos psicóticos cuya definición puede ser útil para determinar el curso clínico de la enfermedad en pacientes con esquizofrenia. En este sentido, la DPNT se puede utilizar como un indicador para el pronóstico de pacientes con esquizofrenia, por lo que se sugiere promover su evaluación. Los estudios que se han llevado a cabo sobre el impacto clínico de la DPNT enfatizan la necesidad de reducirla mediante programas de detección temprana. Estos programas serían útiles para identificar personas en etapas iniciales de un trastorno psicótico y se podría realizar una intervención profesional antes de que los síntomas alcancen un nivel de deterioro significativo para el paciente. Con base en lo anterior, se puede concluir que la DPNT tiene un fuerte impacto sobre el pronóstico de los pacientes con esquizofrenia y que en el futuro se deben realizar estudios que la incluyan no sólo como un factor pronóstico, sino como un objetivo clínico específico de la investigación en salud mental, ya que la información que se genere puede ser la base para la creación y promoción de programas de detección e intervención tempranas.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Duration of untreated psychosis]]></kwd>
<kwd lng="en"><![CDATA[schizophrenia]]></kwd>
<kwd lng="en"><![CDATA[psychosis]]></kwd>
<kwd lng="en"><![CDATA[early detection]]></kwd>
<kwd lng="es"><![CDATA[Duración de la psicosis no tratada]]></kwd>
<kwd lng="es"><![CDATA[esquizofrenia]]></kwd>
<kwd lng="es"><![CDATA[psicosis]]></kwd>
<kwd lng="es"><![CDATA[detección temprana]]></kwd>
</kwd-group>
</article-meta>
</front><body><![CDATA[ <p align="justify"><font face="verdana" size="4">Actualizaci&oacute;n por temas</font></p>     <p align="center"><font face="verdana" size="2">&nbsp;</font></p>     <p align="center"><font face="verdana" size="4"><b>Impacto de la duraci&oacute;n de la psicosis no tratada (DPNT) en el curso y pron&oacute;stico de la esquizofrenia</b></font></p>     <p align="center"><font face="verdana" size="2">&nbsp;</font></p>     <p align="center"><font face="verdana" size="3"><b>Impact of Duration of Untreated Psychosis (DUP) in the course and outcome of schizophrenia</b></font></p>     <p align="center"><font face="verdana" size="2">&nbsp;</font></p>     <p align="center"><font face="verdana" size="2"><b>Isis Garc&iacute;a,<sup>1</sup> Ana Fres&aacute;n,<sup>2* </sup>Mar&iacute;a Elena Medina&#150;Mora,<sup>3</sup> Gabriela Mariana Ruiz</b></font></p>     <p align="justify"><font face="verdana" size="2">&nbsp;</font></p>     <p align="justify"><font face="verdana" size="2"><i><sup>1 </sup>Facultad de Psicolog&iacute;a, Universidad Nacional Aut&oacute;noma de M&eacute;xico.</i></font></p>     <p align="justify"><font face="verdana" size="2"><i><sup>2 </sup>Subdirecci&oacute;n de Investigaciones Cl&iacute;nicas, Instituto Nacional de Psiquiatr&iacute;a Ram&oacute;n de la Fuente.</i></font></p>     ]]></body>
<body><![CDATA[<p align="justify"><font face="verdana" size="2"><i><sup>3 </sup>Direcci&oacute;n de Investigaciones Epidemiol&oacute;gicas y Psicosociales, Instituto Nacional de Psiquiatr&iacute;a Ram&oacute;n de la Fuente.</i></font></p>     <p align="justify"><font face="verdana" size="2">&nbsp;</font></p>     <p align="justify"><font face="verdana" size="2">*<b>Correspondencia:</b>    <br>     <i>Dra. Ana Fres&aacute;n.    <br>     Subdirecci&oacute;n de Investigaciones Cl&iacute;nicas.    <br>     Instituto Nacional de Psiquiatr&iacute;a Ram&oacute;n de la Fuente.    <br>     Calz. M&eacute;xico&#150;Xochimilco 101, Tlalpan,    <br>  	14370, M&eacute;xico, DF.    <br>   Tel: 5655 2811 ext. 204, Fax: 5513 3722</i></font></p>     <p align="justify"><font face="verdana" size="2">&nbsp;</font></p>     ]]></body>
<body><![CDATA[<p align="justify"><font face="verdana" size="2">Recibido primera versi&oacute;n: 29 de febrero de 2008.    <br>   Segunda versi&oacute;n: 11 de julio de 2008.    <br>   Aceptado: 7 de agosto de 2008.</font></p>     <p align="justify"><font face="verdana" size="2">&nbsp;</font></p>     <p align="justify"><font face="verdana" size="2"><b>Abstract</b></font></p>     <p align="justify"><font face="verdana" size="2">The duration of Untreated Psychosis (DUP), defined as the period of time between the onset of psychotic symptoms, such as hallucinations and delusions, and the first effective treatment, has been associated to prognosis of schizophrenia.</font></p>     <p align="justify"><font face="verdana" size="2">It has been demonstrated that although psychotic symptoms are initially detected by relatives of patients with schizophrenia, they take a long time to seek specialized attention, which in turn leads to a delay in the diagnosis and treatment of the disorder.</font></p>     <p align="justify"><font face="verdana" size="2">Schizophrenia has been considered by the World Health Organization as a public health problem and has been placed as the ninth cause of incapacity in the world. Thus, DUP represents part of this public health problem. In Mexico, the average DUP lasts 64 weeks, which is very similar to the average observed in other countries, where the mean DUP in psychotic patients varies between one and two years.</font></p>     <p align="justify"><font face="verdana" size="2">One of the main reasons of a prolonged DUP is that patients and their families first assist with a general practitioner which, in many cases, does not perform an adequate diagnosis with the subsequent referral to a psychiatric facility, and the treatment given for the patient is based on sedative medication. This is also Mexico's case, where seeking help primarily involves religious groups, with very few referrals to psychiatric facilities and with inadequate treatment support, which delays care in specialized services.</font></p>     <p align="justify"><font face="verdana" size="2">It has been established that early treatment is related to a better prognosis and outcome, while treatment delay has been related to a longer time to achieve symptom remission. These results support the hypothesis that the presence of psychotic symptoms for a long period of time may predispose to biological damage, which may in turn lead to predominant negative symptoms and severe cognitive deficits after the first psychotic episode.</font></p>     ]]></body>
<body><![CDATA[<p align="justify"><font face="verdana" size="2">Also, some studies have found that a longer DUP is related to a more insidious illness onset, frequent relapses and psychiatric hospitalizations during the course of the disorder, with a poor response to antipsychotic medication.</font></p>     <p align="justify"><font face="verdana" size="2">Through the use of neuroimaging, several studies have found the relation between DUP and brain morphology in patients with schizophrenia. Studies using Magnetic Resonance Imaging (MRI) have reported that patients with longer DUP show a significant reduction in the gray matter of the temporal planum, in the left middle, inferior temporal, left occipital and left fusiform cortices, with an increase of grey matter in the left basal ganglia, and a volume reduction of the caudate nucleus. These results may be related to the clinical course of the disorder in terms of a higher symptom severity and poor treatment response.</font></p>     <p align="justify"><font face="verdana" size="2">In regard to psychosocial variables related to DUP, it has been observed that men have a longer DUP when compared to women and patients that are single and unemployed also have a longer DUP.</font></p>     <p align="justify"><font face="verdana" size="2">Consequently, it has been found that there is a relationship between DUP and premorbid adjustment in patients with schizophrenia. Premorbid adjustment is defined as the psychosocial functioning in the educational, occupational, social and interpersonal relations areas before the evidence of positive characteristic symptomatology, where symptoms are not secondary to an organic cause and cover a period of six months before the first psychiatric hospitalization or contact with a psychiatric facility. In addition, it has been found that a prolonged DUP is related to a poor premorbid adjustment, especially during late adolescence and adulthood. This association may suggest the presence of prodromic symptoms secondary to the physiopathological process of psychosis. Consequently, if a patient shows some of the initial symptoms of the disorder, including psychosocial impairment, his/her abilities to be aware of the symptoms may be limited to seek for medical care, which may in turn increase DUP.</font></p>     <p align="justify"><font face="verdana" size="2">Furthermore, some authors have reported that some variables related to the patient's environment are related with DUP. The main variable pointed out is: the previous experience with mental disorders and psychiatric facilities. Patients whose families had previous experience of a mentally ill relative, report a shorter DUP when compared to families with no previous history of an ill relative. Also, it has been analised that patients with an adequate social network have a shorter DUP compared to those patients whose social network is inadequate or limited.</font></p>     <p align="justify"><font face="verdana" size="2">Based on these results, some authors have proposed two phenotypes for psychotic disorders: the first one characterized by males, poor premorbid adjustment, long DUP, insidious onset of the disorder and a stable pattern of negative symptoms. The second phenotype was one characterized by the following variables: females, good premorbid adjustment, a shorter DUP, acute illness onset and absence of a stable pattern of negative symptoms. This definition may be useful to determine the course of the disorder in patients with schizophrenia and may be able to predict the clinical outcome. Thus, DUP can be used as an indicator of prognosis in patients with schizophrenia and its evaluation should be promoted. Although these two phenotypes are very useful, caution should be warranted in their use to avoid generalization.</font></p>     <p align="justify"><font face="verdana" size="2">By and large, the studies related to the clinical impact of DUP emphasized the need to reduce DUP through early detection programs, including psychoeducation. We believe that this approach will be useful to identify individuals at an early development of a psychotic illness so that interventions can begin before symptoms have reached a level of significant impairment for the patient and warranting referrals by the family, school or health providers.</font></p>     <p align="justify"><font face="verdana" size="2">Based on the studies reviewed above, we can conclude that DUP has a definitive impact on the prognosis of patients with schizophrenia and that future studies should be performed including it not only as a predictor of clinical outcome, but also as an specific clinical target for mental health research.</font></p>     <p align="justify"><font face="verdana" size="2">Increasing the knowledge about the relationship between DUP and clinical course of schizophrenia is crucial to create and promote early detection and intervention programs such as the ones that have started all over the world, where the main objective is to identify young people who are at risk of developing psychotic disorders, specially schizophrenia.</font></p>     <p align="justify"><font face="verdana" size="2"><b>Key words: </b>Duration of untreated psychosis, schizophrenia, psychosis, early detection.</font></p>     ]]></body>
<body><![CDATA[<p align="justify"><font face="verdana" size="2">&nbsp;</font></p>     <p align="justify"><font face="verdana" size="2"><b>Resumen</b></font></p>     <p align="justify"><font face="verdana" size="2">La duraci&oacute;n de la psicosis no tratada (DPNT), definida como el per&iacute;odo de tiempo entre la aparici&oacute;n de los s&iacute;ntomas psic&oacute;ticos y el inicio de un tratamiento adecuado, est&aacute; asociada al pron&oacute;stico de la esquizofrenia, enfermedad que ha sido considerada por la Organizaci&oacute;n Mundial de la Salud, como un problema de salud p&uacute;blica.</font></p>     <p align="justify"><font face="verdana" size="2">El atraso en la b&uacute;squeda de tratamiento especializado conlleva a un retraso en el diagn&oacute;stico y tratamiento adecuados de la enfermedad. En M&eacute;xico, el promedio de la DPNT es de 64 semanas, siendo &eacute;ste similar al reportado en otros pa&iacute;ses, donde la media var&iacute;a entre uno y dos a&ntilde;os.</font></p>     <p align="justify"><font face="verdana" size="2">Se ha comprobado que el retraso en el tratamiento adecuado del padecimiento est&aacute; relacionado con un pobre pron&oacute;stico, lo cual apoya la hip&oacute;tesis de que la presencia de s&iacute;ntomas psic&oacute;ticos durante un largo per&iacute;odo de tiempo puede predisponer a un da&ntilde;o biol&oacute;gico, generando as&iacute; un predominio de s&iacute;ntomas negativos y mayores d&eacute;ficit cognitivos despu&eacute;s del primer episodio psic&oacute;tico. Adem&aacute;s, se ha encontrado que una DPNT larga se relaciona con un inicio insidioso de la enfermedad, mayor n&uacute;mero de reca&iacute;das y rehospitalizaciones psiqui&aacute;tricas durante el curso de la enfermedad, adem&aacute;s de una pobre respuesta al tratamiento farmacol&oacute;gico con antipsic&oacute;ticos.</font></p>     <p align="justify"><font face="verdana" size="2">En cuanto a las variables demogr&aacute;ficas y psicosociales que se asocian con una DPNT prolongada encontramos: al sexo masculino, el no tener pareja u ocupaci&oacute;n laboral. Asimismo, se ha reportado que los pacientes que presentan un mayor deterioro en su funcionamiento prem&oacute;rbido, son aquellos que muestran una mayor DPNT. Esta asociaci&oacute;n sugiere que los pacientes con esquizofrenia pueden presentar s&iacute;ntomas prodr&oacute;micos mucho tiempo antes de que su funcionamiento se vea totalmente afectado por el proceso fisiopatol&oacute;gico de la psicosis.</font></p>     <p align="justify"><font face="verdana" size="2">Asimismo, se han reportado variables relacionadas con el entorno del paciente asociadas a la DPNT. Entre ellas, destacan la experiencia previa con trastornos mentales y las redes sociales. Se ha observado que los pacientes de familias que han tenido una experiencia previa con otro familiar diagnosticado con alguna enfermedad mental, muestran una menor DPNT en contraste con aquellos cuyas familias no han tenido experiencias previas de enfermedades mentales. De igual forma, se ha informado que pacientes con una adecuada red social tienen una menor DPNT, comparados con aquellos cuya red social es limitada.</font></p>     <p align="justify"><font face="verdana" size="2">A partir de estos hallazgos se han propuesto dos fenotipos para los trastornos psic&oacute;ticos cuya definici&oacute;n puede ser &uacute;til para determinar el curso cl&iacute;nico de la enfermedad en pacientes con esquizofrenia. En este sentido, la DPNT se puede utilizar como un indicador para el pron&oacute;stico de pacientes con esquizofrenia, por lo que se sugiere promover su evaluaci&oacute;n.</font></p>     <p align="justify"><font face="verdana" size="2">Los estudios que se han llevado a cabo sobre el impacto cl&iacute;nico de la DPNT enfatizan la necesidad de reducirla mediante programas de detecci&oacute;n temprana. Estos programas ser&iacute;an &uacute;tiles para identificar personas en etapas iniciales de un trastorno psic&oacute;tico y se podr&iacute;a realizar una intervenci&oacute;n profesional antes de que los s&iacute;ntomas alcancen un nivel de deterioro significativo para el paciente.</font></p>     <p align="justify"><font face="verdana" size="2">Con base en lo anterior, se puede concluir que la DPNT tiene un fuerte impacto sobre el pron&oacute;stico de los pacientes con esquizofrenia y que en el futuro se deben realizar estudios que la incluyan no s&oacute;lo como un factor pron&oacute;stico, sino como un objetivo cl&iacute;nico espec&iacute;fico de la investigaci&oacute;n en salud mental, ya que la informaci&oacute;n que se genere puede ser la base para la creaci&oacute;n y promoci&oacute;n de programas de detecci&oacute;n e intervenci&oacute;n tempranas.</font></p>     ]]></body>
<body><![CDATA[<p align="justify"><font face="verdana" size="2"><b>Palabras clave: </b>Duraci&oacute;n de la psicosis no tratada, esquizofrenia, psicosis, detecci&oacute;n temprana.</font></p>     <p align="justify"><font face="verdana" size="2">&nbsp;</font></p>     <p align="justify"><font face="verdana" size="2">La duraci&oacute;n de la psicosis no tratada (DPNT), definida como el intervalo de tiempo entre la aparici&oacute;n de los s&iacute;ntomas psic&oacute;ticos y el inicio de un tratamiento farmacol&oacute;gico adecuado, es un factor asociado al pron&oacute;stico de la esquizofrenia. La importancia de su estudio se relaciona con una grave situaci&oacute;n a la que se enfrenta la poblaci&oacute;n: el retraso en la b&uacute;squeda de tratamiento especializado. A este respecto, se ha demostrado que las personas tardan mucho tiempo en buscar ayuda especializada una vez que comienzan los s&iacute;ntomas psic&oacute;ticos, siendo los familiares los primeros en reconocer dichos s&iacute;ntomas.<sup>1</sup></font></p>     <p align="justify"><font face="verdana" size="2">Se ha observado que una de las principales causas por las que la DPNT se alarga, es que la primera ayuda que reciben los pacientes proviene del m&eacute;dico general, el cual no realiza un diagn&oacute;stico oportuno ni la correspondiente canalizaci&oacute;n al servicio de psiquiatr&iacute;a. Esto retrasa el inicio del tratamiento adecuado.<sup>1,2</sup> Es importante se&ntilde;alar que en pa&iacute;ses en los que el primer nivel de atenci&oacute;n est&aacute; capacitado para la detecci&oacute;n oportuna, no se observa el mismo patr&oacute;n de retraso.<sup>3,4</sup> Adem&aacute;s se ha visto que los pacientes que mantienen contacto con el m&eacute;dico general, en comparaci&oacute;n con aquellos que no lo tienen, presentan una DPNT m&aacute;s corta.<sup>5</sup></font></p>     <p align="justify"><font face="verdana" size="2">Actualmente se considera que la DPNT es m&aacute;s larga de lo que se suele reconocer, es por eso que representa un problema de salud p&uacute;blica importante.<sup>1</sup> Seg&uacute;n el Estudio Mexicano del Primer Episodio Psic&oacute;tico, la DPNT promedio de los pacientes es de 64 semanas, esto es similar al reportado en diferentes estudios alrededor del mundo en los que se establece que el promedio de DPNT es de entre uno y dos a&ntilde;os, con una mediana de alrededor de seis meses.<sup>1,3,4,6&#150;10</sup></font></p>     <p align="justify"><font face="verdana" size="2">En 1988 la Organizaci&oacute;n Mundial de la Salud (OMS) realiz&oacute; un estudio multic&eacute;ntrico para evaluar la trayectoria que siguen los pacientes en la b&uacute;squeda de atenci&oacute;n antes de llegar a un servicio especializado de psiquiatr&iacute;a. En general, se observ&oacute; que el retraso en la b&uacute;squeda de atenci&oacute;n fue menor en los pa&iacute;ses que cuentan con servicios descentralizados de psiquiatr&iacute;a y mayor en aquellos en los que hay m&aacute;s curanderos y se recurre a la medicina alternativa.<sup>11</sup> Igualmente, se mostr&oacute; que las principales fuentes de referencia son los m&eacute;dicos generales y los hospitales de segundo nivel. De acuerdo con los resultados de este estudio las principales causas del retraso en la b&uacute;squeda de atenci&oacute;n en M&eacute;xico son: la carencia de recursos econ&oacute;micos y la b&uacute;squeda de atenci&oacute;n con alg&uacute;n otro profesional de la salud mental (psic&oacute;logo y trabajador social) diferente al psiquiatra, principalmente en los pacientes provenientes de los Centros de Salud. Tambi&eacute;n se observ&oacute; que los pacientes del Seguro Social mostraron retraso en el contacto con el psiquiatra debido a tratamientos incorrectos y demora en la canalizaci&oacute;n al servicio de psiquiatr&iacute;a.<sup>11</sup></font></p>     <p align="justify"><font face="verdana" size="2">En otro estudio realizado por la OMS,<sup>12</sup> en el cual fue incluido M&eacute;xico, se evaluaron los caminos que siguen los pacientes antes de llegar a un servicio especializado de psiquiatr&iacute;a y se encontr&oacute;, entre otras cosas, que los pacientes mexicanos buscan ayuda principalmente por medio de grupos religiosos, por lo que rechazan otro tipo de tratamiento, lo cual retrasa la atenci&oacute;n en servicios especializados e incluso se reporta que algunos pacientes no llegan a tener contacto con este tipo de servicios. En este estudio tambi&eacute;n se menciona que el retraso de tiempo en la b&uacute;squeda de tratamiento psiqui&aacute;trico en las poblaciones estudiadas var&iacute;a entre cinco y veinte a&ntilde;os. Adem&aacute;s, la mediana del retraso entre el primer contacto de atenci&oacute;n y la canalizaci&oacute;n a un servicio especializado de salud mental, en M&eacute;xico, fue de 32 semanas, la cual es muy alta en comparaci&oacute;n con otros pa&iacute;ses como Kenia (Nairobi), donde fue de una semana.</font></p>     <p align="justify"><font face="verdana" size="2">Otro punto relevante del estudio se refiere al tipo de tratamiento inicial que reciben los pacientes, el cual, en la mayor&iacute;a de los pa&iacute;ses evaluados, fue prescrito por m&eacute;dicos generales y consisti&oacute; principalmente en medicaci&oacute;n sedante. En M&eacute;xico, se observ&oacute; un desconocimiento en relaci&oacute;n a los s&iacute;ntomas de los padecimientos psiqui&aacute;tricos, ya que los pacientes acudieron a recibir atenci&oacute;n m&eacute;dica principalmente para el tratamiento de s&iacute;ntomas de enfermedades no psiqui&aacute;tricas.<sup>12</sup></font></p>     <p align="justify"><font face="verdana" size="2">En un estudio realizado en M&eacute;xico<sup>13</sup> en una muestra de hogares a nivel nacional, sobre la utilizaci&oacute;n de servicios tanto formales como informales de salud, se encontr&oacute; que los familiares y amigos constituyen el primer recurso (54%) al que acude la poblaci&oacute;n cuando padece problemas emocionales, s&iacute;ntomas depresivos e ideaci&oacute;n suicida, seguido por la automedicaci&oacute;n (15%) y los sacerdotes (10%). Lo anterior ejemplifica que las razones por las cuales las personas no solicitan ayuda especializada son de tipo personal (relacionadas con prejuicios) y por desconocimiento de los servicios especializados de salud mental.<sup>13</sup></font></p>     <p align="justify"><font face="verdana" size="2">Por otro lado, se ha observado que la utilizaci&oacute;n de los servicios de salud mental en las zonas rurales es muy limitada debido a la carencia de &eacute;stos en dichas zonas, por lo que las personas suelen acudir a servicios alternativos, como amistades, sacerdotes o al empleo de remedios caseros para la reducci&oacute;n o eliminaci&oacute;n de los s&iacute;ntomas.<sup>14</sup></font></p>     ]]></body>
<body><![CDATA[<p align="justify"><font face="verdana" size="2">La DPNT se ha establecido como un factor pron&oacute;stico en pacientes con esquizofrenia. Diversos estudios han mostrado que una DPNT corta se relaciona con una menor severidad de los s&iacute;ntomas positivos,<sup>15&#150;17</sup> y que una DPNT larga est&aacute; relacionada con la presencia de s&iacute;ntomas negativos m&aacute;s pronunciados a lo largo del padecimiento.<sup>7,18,19</sup> As&iacute;, la DPNT puede predecir el curso de los s&iacute;ntomas negativos.<sup>20&#150;23</sup> No obstante, existen hallazgos contradictorios en los cuales no se ha encontrado alguna asociaci&oacute;n entre la DPNT y la severidad de los s&iacute;ntomas negativos;<sup>24</sup> incluso, se ha reportado que una DPNT corta se asocia con un mejor pron&oacute;stico en los s&iacute;ntomas negativos, pero no con un mejor pron&oacute;stico de los positivos.<sup>25</sup> Igualmente, se ha observado que los s&iacute;ntomas negativos y la DPNT son dos predictores significativos de discapacidad psicosocial.<sup>26</sup> Las diferencias encontradas entre estos estudios pueden ser secundarias a otras diferencias en la metodolog&iacute;a empleada. Asimismo, una DPNT larga se ha relacionado con una deficiente respuesta y remisi&oacute;n de s&iacute;ntomas de la esquizofrenia, as&iacute; como con un peor pron&oacute;stico.<sup>27&#150;33</sup></font></p>     <p align="justify"><font face="verdana" size="2">Adem&aacute;s, se ha observado que aquellos pacientes con una DPNT larga son m&aacute;s propensos a estados depresivos, ansiedad, s&iacute;ntomas compulsivos y a mostrar alteraciones en la percepci&oacute;n corporal.<sup>34</sup></font></p>     <p align="justify"><font face="verdana" size="2">Por otro lado, la DPNT se ha relacionado con el n&uacute;mero de reca&iacute;das, mientras que el retraso en la b&uacute;squeda de tratamiento psicosocial se ha asociado con un mayor n&uacute;mero de hospitalizaciones.<sup>18,35</sup> Aunque en algunos casos no se han observado diferencias en la DPNT entre pacientes con y sin reca&iacute;das, se ha observado que las m&uacute;ltiples reca&iacute;das se asocian con una DPNT larga en comparaci&oacute;n con los pacientes que no las presentan. Adem&aacute;s, el tiempo entre el alta hospitalaria y la rehospitalizaci&oacute;n es m&aacute;s corto en pacientes con DPNT larga.<sup>36</sup></font></p>     <p align="justify"><font face="verdana" size="2">En cuanto a la respuesta al tratamiento farmacol&oacute;gico, se ha observado que la DPNT puede ser un importante predictor de respuesta,<sup>10,22</sup> de modo que una DPNT larga est&aacute; relacionada con una menor probabilidad de respuesta.<sup>7,37,38</sup></font></p>     <p align="justify"><font face="verdana" size="2">Tambi&eacute;n se ha estudiado la asociaci&oacute;n entre la DPNT y la funci&oacute;n cognitiva, encontr&aacute;ndose que una DPNT larga est&aacute; relacionada con un mayor deterioro cognitivo despu&eacute;s del primer episodio psic&oacute;tico o por lo menos lo predice,<sup>39,40 </sup>aunque los hallazgos sobre el tema no pueden explicar si la DPNT es causa o consecuencia de esta pobre ejecuci&oacute;n. A pesar de la evidencia que se ha encontrado sobre la relaci&oacute;n que hay entre la DPNT y la funci&oacute;n cognitiva, &eacute;sta no es del todo apoyada, pues tambi&eacute;n se han encontrado estudios en los que no existe dicha relaci&oacute;n.<sup>20,41</sup></font></p>     <p align="justify"><font face="verdana" size="2">Adem&aacute;s se han realizado estudios sobre la relaci&oacute;n entre la DPNT y la morfolog&iacute;a cerebral en pacientes con esquizofrenia; por medio del uso de imagen por resonancia magn&eacute;tica (IRM) se ha encontrado que la DPNT se correlaciona negativamente con el volumen de la materia gris en el plano temporal izquierdo, independientemente de la edad, de la edad de inicio de la enfermedad y de la duraci&oacute;n y dosis de la medicaci&oacute;n neurol&eacute;ptica. Los sujetos con una DPNT larga presentan una reducci&oacute;n de la materia gris en el plano temporal en contraste con los pacientes con una DPNT corta. Estos datos indican que existe un proceso patol&oacute;gico progresivo en la materia gris en el plano temporal izquierdo durante la fase inicial no tratada de la esquizofrenia.<sup>42</sup> Con el uso de la misma t&eacute;cnica, se ha observado que una DPNT larga se asocia con una reducci&oacute;n de la materia gris en la corteza izquierda media e inferior temporal, occipital y fusiforme, y con un exceso de materia gris en los ganglios basales izquierdos.<sup>43</sup> Tambi&eacute;n se ha encontrado, mediante el uso del BRAINS2 (software utilizado para el an&aacute;lisis de neuroim&aacute;genes), que los n&uacute;cleos caudados derecho, izquierdo y total no difieren significativamente entre pacientes que cursan su primer episodio de psicosis no afectiva y sujetos controles. Sin embargo, los pacientes con una DPNT larga presentan menor volumen de los n&uacute;cleos caudados, por lo que estas estructuras podr&iacute;an estar relacionadas con la severidad de la sintomatolog&iacute;a psic&oacute;tica.<sup>44</sup></font></p>     <p align="justify"><font face="verdana" size="2">Asimismo, se ha reportado que una DPNT larga se asocia con un inicio insidioso del padecimiento y que la participaci&oacute;n familiar en la b&uacute;squeda de ayuda se asocia con una DPNT corta. De esta forma, se ha considerado que en la DPNT influyen determinantes sociales.<sup>45</sup></font></p>     <p align="justify"><font face="verdana" size="2">En cuanto a las variables psicosociales relacionadas con la DPNT se ha encontrando una asociaci&oacute;n entre una DPNT larga y el sexo masculino y una DPNT corta y el sexo femenino.<sup>17,19,26,28,39,46&#150;48</sup> Estos hallazgos han sido contradictorios, pues existen estudios en los que no se encuentra dicha relaci&oacute;n.<sup>49</sup> Tambi&eacute;n se ha observado que variables como el estado civil y la ocupaci&oacute;n se relacionan con la DPNT. As&iacute;, por ejemplo, el ser soltero y desempleado, se relaciona significativamente con una DPNT larga.<sup>9,50</sup></font></p>     <p align="justify"><font face="verdana" size="2">Por otro lado, se ha encontrado que una DPNT larga se asocia a un bajo ajuste prem&oacute;rbido, en especial durante la adolescencia tard&iacute;a y la edad adulta.<sup>36,37</sup> El ajuste prem&oacute;rbido ha sido tradicionalmente definido como el funcionamiento psicosocial que presenta el sujeto en las &aacute;reas escolar, laboral y de relaciones interpersonales antes de la aparici&oacute;n de s&iacute;ntomas psic&oacute;ticos evidentes, como alucinaciones, delirios, trastornos del pensamiento o del comportamiento, en donde los s&iacute;ntomas no son producto de una causa org&aacute;nica y abarca un periodo de seis meses antes de la primera hospitalizaci&oacute;n o contacto con un servicio psiqui&aacute;trico especializado.<sup>51</sup> No obstante, la definici&oacute;n tradicional de la fase prem&oacute;rbida de la esquizofrenia tambi&eacute;n incluye la fase prodr&oacute;mica de la enfermedad. Esta fase se define como el per&iacute;odo de tiempo en donde se presentan s&iacute;ntomas no espec&iacute;ficos y un deterioro funcional progresivo que precede a la aparici&oacute;n del cuadro psic&oacute;tico caracter&iacute;stico de la esquizofrenia.<sup>52,53</sup> De esta forma, la relaci&oacute;n encontrada entre un bajo ajuste prem&oacute;rbido en la adolescencia tard&iacute;a y la edad adulta con una DPNT larga, puede ser secundaria a la presencia de s&iacute;ntomas prodr&oacute;micos. Estos s&iacute;ntomas pudieran provocar a su vez que los pacientes se vean incapacitados para solicitar atenci&oacute;n especializada debido al deterioro conferido por los primeros s&iacute;ntomas, lo que aumentar&iacute;a la DPNT.</font></p>     <p align="justify"><font face="verdana" size="2">Existen otras variables relacionadas al entorno del paciente que se han asociado con la DPNT. Por ejemplo, se ha observado que la experiencia familiar previa de enfermedad mental puede ser un predictor significativo de una DPNT corta.<sup>54</sup> Esto se debe a un reconocimiento m&aacute;s temprano de los s&iacute;ntomas y a que los familiares acudan m&aacute;s pronto a buscar ayuda especializada. Del mismo modo, se ha visto que la decisi&oacute;n de buscar ayuda por parte de los familiares de los pacientes que no han tenido contacto previo con alg&uacute;n enfermo, se reafirma s&oacute;lo despu&eacute;s de presentarse una emergencia, ya sea porque los s&iacute;ntomas psic&oacute;ticos se vuelven insoportables para ellos o porque el paciente presenta conductas disruptivas.<sup>8</sup> En este punto, cabe mencionar que la esquizofrenia no s&oacute;lo afecta a la persona que la padece, sino a aquellos que mantienen contacto estrecho con el paciente, principalmente el cuidador primario, deterior&aacute;ndose as&iacute; no s&oacute;lo la calidad de vida del pacientes sino la de los familiares responsables de su cuidado.</font></p>     ]]></body>
<body><![CDATA[<p align="justify"><font face="verdana" size="2">La participaci&oacute;n del factor social ha sido apoyada por otros estudios, en los que se ha observado que la carencia de una adecuada red social se asocia con una DPNT larga en pacientes con un primer episodio psic&oacute;tico.<sup>48</sup></font></p>     <p align="justify"><font face="verdana" size="2">A partir de diversos hallazgos reportados en las investigaciones sobre DPNT y otras variables asociadas al pron&oacute;stico, algunos autores consideran que existen dos fenotipos para los trastornos psic&oacute;ticos: el primero caracterizado por el sexo masculino, un pobre ajuste prem&oacute;rbido, una DPNT m&aacute;s prolongada, el inicio insidioso de la enfermedad y un patr&oacute;n estable de s&iacute;ntomas negativos; mientras que el segundo est&aacute; caracterizado por el sexo femenino, un buen ajuste prem&oacute;rbido, un per&iacute;odo m&aacute;s corto de psicosis no tratada, el inicio agudo del padecimiento y ausencia de un patr&oacute;n de s&iacute;ntomas negativos estable.<sup>46,55</sup> La diferenciaci&oacute;n entre estos dos fenotipos es &uacute;til para conocer el patr&oacute;n de desarrollo de la esquizofrenia desde la fase prem&oacute;rbida hasta la fase residual y tal vez poder predecir el pron&oacute;stico de los pacientes. Sin embargo, no deben ser considerados como modelos para basar el tratamiento de los pacientes y deben manejarse con cautela para evitar hacer una generalizaci&oacute;n del padecimiento.</font></p>     <p align="justify"><font face="verdana" size="2">En general, todos los estudios enfatizan en la necesidad de disminuir la DPNT mediante la implementaci&oacute;n de programas de detecci&oacute;n oportuna temprana de los s&iacute;ntomas psic&oacute;ticos.<sup>1&#150;55</sup> Por ejemplo, los programas de psicoeducaci&oacute;n &#151;dirigidos en su mayor&iacute;a a los familiares, pero que pueden ser orientados a especialistas en salud, salud mental y poblaci&oacute;n general&#151; tienen la finalidad de dar informaci&oacute;n acerca de lo referente a la enfermedad y al trato del enfermo. Estos programas podr&iacute;an ser impartidos a personas que no tienen contacto con la enfermedad mental o a los servicios de salud de primer nivel. Esto ayudar&iacute;a a un mayor reconocimiento de los s&iacute;ntomas, una detecci&oacute;n temprana de la enfermedad, a una reducci&oacute;n de la DPNT y por ende a una probable mejor&iacute;a del pron&oacute;stico de los pacientes.</font></p>     <p align="justify"><font face="verdana" size="2">A pesar de las diferencias entre los hallazgos reportados por la bibliograf&iacute;a, existe una evidencia clara de que la DPNT por s&iacute; sola o acompa&ntilde;ada por otras variables, es un factor que influye en el pron&oacute;stico de los pacientes que presentan su primer episodio de esquizofrenia.</font></p>     <p align="justify"><font face="verdana" size="2">Dado que la esquizofrenia es una de las enfermedades mentales que ocasiona m&aacute;s discapacidad a nivel mundial, el noveno lugar, seg&uacute;n la OMS,<sup>28</sup> es de suma importancia el estudio de los factores asociados a su presentaci&oacute;n, evoluci&oacute;n y pron&oacute;stico. De esta forma la investigaci&oacute;n sobre la DPNT como factor pron&oacute;stico resulta relevante para el &aacute;rea de la salud, pues al lograr la reducci&oacute;n del tiempo de psicosis no tratada se disminuye el impacto personal y psicosocial que acompa&ntilde;an al padecimiento.</font></p>     <p align="justify"><font face="verdana" size="2">Del mismo modo, independientemente de los resultados de cada estudio, todos los autores concuerdan con la realizaci&oacute;n de programas de detecci&oacute;n temprana de los s&iacute;ntomas psic&oacute;ticos/prodr&oacute;micos, con la finalidad de reducir la DPNT. As&iacute; pues se ha observado que las personas que mantienen mayor contacto con el m&eacute;dico, aunque no sea especialista, presentan per&iacute;odos m&aacute;s cortos de DPNT, al igual que aquellas que viven en pa&iacute;ses en donde los m&eacute;dicos que brindan atenci&oacute;n primaria est&aacute;n mejor capacitados para realizar la detecci&oacute;n y con ello la pronta canalizaci&oacute;n a los servicios especializados. Por esta raz&oacute;n resulta de primordial necesidad la capacitaci&oacute;n del personal de los servicios de salud de primer nivel, pues es &eacute;ste el m&aacute;s concurrido en cuanto a la b&uacute;squeda de ayuda por parte de la poblaci&oacute;n general y debe ser el encargado de la detecci&oacute;n temprana y de la canalizaci&oacute;n al servicio de psiquiatr&iacute;a. De igual forma, dado el contacto que mantienen con las personas, ser&iacute;a conveniente que en ellos recaiga la tarea de informarles sobre los s&iacute;ntomas caracter&iacute;sticos de la esquizofrenia. As&iacute;, ser&iacute;an capaces de reconocer los primeros s&iacute;ntomas psic&oacute;ticos y de esta manera se reducir&iacute;a la DPNT.</font></p>     <p align="justify"><font face="verdana" size="2">Como se puede observar en los reportes de la bibliograf&iacute;a revisada, no existe un hallazgo contundente acerca de la evoluci&oacute;n de la esquizofrenia debido a que es una patolog&iacute;a multicausal o por lo menos para la cual, en la actualidad, no se ha detectado una causa &uacute;nica, pues se le ha asociado igual con causas sociofamiliares que con factores neuroanat&oacute;micos y neurofuncionales y con variables cl&iacute;nicas. Por eso es de gran relevancia continuar con el estudio de los factores con los que se le asocian, no con la finalidad de encontrar una explicaci&oacute;n, sino con la de disminuir las consecuencias que conlleva padecerla y as&iacute; poder mejorar la calidad de vida de los pacientes.</font></p>     <p align="justify"><font face="verdana" size="2">Por &uacute;ltimo, cabe mencionar que la DPNT es una variable que seg&uacute;n se reporta en la bibliograf&iacute;a tiene un fuerte impacto sobre el pron&oacute;stico de la esquizofrenia. Sin embargo, la detecci&oacute;n oportuna de los s&iacute;ntomas conllevar&iacute;a a una reducci&oacute;n en la DPNT y su impacto sobre el curso y pron&oacute;stico de la enfermedad ser&iacute;a m&iacute;nimo.</font></p>     <p align="justify"><font face="verdana" size="2">A partir de esta revisi&oacute;n, se puede tener un panorama m&aacute;s claro del papel de la DPNT en la esquizofrenia y da pie a la futura realizaci&oacute;n de estudios en los que las mediciones, las muestras y las definiciones sean m&aacute;s homog&eacute;neas. Esto conllevar&iacute;a a lograr una generalizaci&oacute;n de los hallazgos para conocer mejor la enfermedad y de esta manera, poder mejorar las condiciones de vida de las personas que la padecen y m&aacute;s a&uacute;n de las que puedan llegar a padecerla.</font></p>     <p align="justify"><font face="verdana" size="2">&nbsp;</font></p>     ]]></body>
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