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    "textoCompleto" => "<p class="elsevierStylePara">Considering recent epidemiologic data we find strong evidence suggesting the advantage of starting the asthma therapy with controllers or preventive drugs very early on life&#44; better in the first 5 years of age&#46; The epidemiologic studies supporting that idea are&#58; first able around 80 &#37; of asthmatics start their disease in the first 12 years of age <span class="elsevierStyleSup">1</span>&#44; second the cohort study from Melbourne <span class="elsevierStyleSup">2</span> shows that asthma is a &#34;tracking disease&#34; in symptoms and pulmonary function&#44; meaning that a person that as a child have certain severity of disease and pulmonary function compromised will have the same compromise when he or she become an adult and third the cohort study from Tucson <span class="elsevierStyleSup">3</span> demonstrates that the asthmatic suffer the major loosing in pulmonary function in the first 5 years of age&#46;</p><p class="elsevierStylePara">Besides those epidemiologic data&#44; studies in asthmatic children where bronchoalverolar lavage were done demonstrated the presence of inflammation in the air way in children 8 years old <span class="elsevierStyleSup">4</span> and even in infants as little as 15 months of age with persistent wheezing <span class="elsevierStyleSup">5</span>&#46; There are also studies which demonstrate airway remodeling in asthmatic children <span class="elsevierStyleSup">6-7</span> and the most amazing finding is the fact of the thickness of the basal membrane of the airway in asthmatic children without controlled of their disease is very similar to severe asthmatic adults and it is not related either with the duration of the disease <span class="elsevierStyleSup">8</span>&#46; Therefore&#44; we end up once more to the same conclusion that is essential to start the treatment of asthma with controllers or preventing drugs at infancy&#46;</p><p class="elsevierStylePara">The only drugs which have been demonstrated to be useful to stop the airway remodeling in humans are the inhaled corticosteroids &#40;ICS&#41; like beclomethasone <span class="elsevierStyleSup">9</span>&#44; budesonide <span class="elsevierStyleSup">10</span> and fluticasone <span class="elsevierStyleSup"> 11</span> and the long active beta agonists like salmeterol <span class="elsevierStyleSup"> 12</span>&#46; The ICS that needs lower doses and less time to decrease the thickness of the basal membrane of the airway in asthmatics was fluticasone <span class="elsevierStyleSup">11</span>&#46; There is no evidence in the scientific literature that other type of drugs use for asthma like chromones&#44; theophyllines or leukotriene receptor antagonists have any effect in stopping the airway remodeling in humans&#46; These anti-inflammatory and anti-remodeling effects that the ICS has demonstrated besides their already well know utility in improving symptoms and pulmonary function <span class="elsevierStyleSup">13</span> make ICS become the first controller drug in asthma&#46; This should be use very early on life &#40;in the first 5 years&#41; otherwise the results will not be satisfactory&#44; like Childhood Asthma Management Program &#40;CAMP&#41; study <span class="elsevierStyleSup">14</span> demonstrated&#46; In that study the children did not improve their pulmonary function maybe because the ICS treatment started after that age&#46;</p><p class="elsevierStylePara">The problem is that in the first 5 years of age coexisting at least three phenotypes of wheezing in children &#40;transitory&#44; late and persistent or classic asthmatic&#41;&#46; One way to differentiate which infant with recurrent wheezing will become asthmatic in order to early start ICS therapy is using the asthma predictive value &#40;API&#41; <span class="elsevierStyleSup">15</span>&#46; Those infants with recurrent wheezing in the Tucson cohort who had a positive API had 7 times more risk to become asthmatic at school age&#46; In other words&#44; if an infant with recurrent wheezing come to the office and we apply the API and the result is positive we can tell the mother with 77 &#37; of certain that the infant will became asthmatic at school age and start controller drugs will be more effective&#46; In the other hand&#44; if the API is negative we can tell the mother with 70 &#37; of certain that the child will stop wheezing when he or she reaches school age&#46;</p><p class="elsevierStylePara">All of us who are involve in asthma management try to have our asthmatic children free of exacerbations&#44; emergency consults&#44; symptoms with exercise&#44; improved their pulmonary function and quality of life&#44; in other words&#44; stop feeling asthmatic or have a normal life&#46; However&#44; epidemiologic questionnaires done in several parts of the world <span class="elsevierStyleSup">16-18</span> have shown that around 95 &#37; of the asthmatic do not reach the control of their disease according to international guidelines <span class="elsevierStyleSup">19&#44;20</span>&#46;</p><p class="elsevierStylePara">One of the more remarkable issues is that most of the clinical trials done to investigate the efficacy of different drugs in asthma consider as the outcome only one parameter &#40;either clinical&#44; laboratory or pulmonary function&#41; and therefore&#44; besides overestimating the level of asthma control <span class="elsevierStyleSup">21</span>&#46; They do not consider that an asthmatic patient like other chronic patient need to be controlled in not only one parameter but also in a group of several parameters&#46;</p><p class="elsevierStylePara">Few months ago&#44; Bateman et al <span class="elsevierStyleSup">22</span> published the results of the GOAL study <span class="elsevierStyleItalic">&#40;The Gaining Optimal Asthma Control Study&#41;</span>&#46; GOAL was a 1-year&#44; stratified&#44; randomized&#44; double-blind&#44; parallel-group study comparing the efficacy and safety of individual&#44; predefined&#44; stepwise increases of salmeterol&#47;fluticasone with fluticasone alone in achieving two predefined composite measures of asthma control &#40;&#34;well control&#34; and &#34;total control&#34;&#41;&#46; Those outcomes are new and involve many clinical and pulmonary functions criteria as a whole&#46;</p><p class="elsevierStylePara">The GOAL <span class="elsevierStyleSup"> 22</span> study defined that a patient reaches &#34;total control&#34; of asthma if in 7 out of 8 weeks fulfills all of the following criteria&#58; without symptoms in the day&#44; no rescue medication use&#44; normal pulmonary function &#40;peak expiratory flow &#91;PEF&#93; am &#62; 80 &#37;&#41;&#44; no wake-ups at night&#44; no exacerbations&#44; no emergency visits and without secondary effects&#46; We can say that &#34;total control&#34; means clinical remission of asthma and that objective was more stringent than the one that Global Iniciative for Asthma &#40;GINA&#41; <span class="elsevierStyleSup">19</span> proposed&#46; The &#34;well control&#34; was defined as the fact that in 7 out of 8 weeks the patient fulfills the criteria&#58; no wake-ups at night&#44; no exacerbations&#44; no emergency visits and no secondary effects <span class="elsevierStyleItalic">PLUS</span> at least more than two of the follows criteria&#58; &#8804; 2 days with light symptoms&#44; use of rescue medications in &#8804; 2 days and &#8804;  4 times&#47;week and normal pulmonary function &#40;PEF am  &#62; 80 &#37;&#41;&#46;</p><p class="elsevierStylePara">From a total of 5068 patients &#40;between 12 and 80 years of age&#41; recruited in 44 countries&#44; 3421 patients fulfilled the inclusion criteria&#46; Interesting 10 &#37; of them were adolescents &#40;12-17 years-old&#41;&#46; At the beginning of the study the patients were separate in three strata- according to the ICS uses- and were randomized to received salmeterol&#47;fluticasone or fluticasone alone&#46; In each strata&#44; the percentage of patients who reached the &#34;well control&#34; and the &#34;total control&#34; definition were statistical more frequent in the salmeterol&#47;fluticasone group vs&#46; fluticasone&#46; And at the end of the year considerable proportion of patients &#40;41 &#37;&#59; all strata&#41; in the salmeterol&#47;fluticasone group reach the &#34;total control&#34;&#46; Moreover&#44; those patient in the salmeterol&#47;fluticasone group reach the &#34;total control&#34; with 60 &#37; less dose of ICS and earlier than those in the fluticasone group&#46; In the other hand&#44; the patients in the salmeterol&#47; fluticasone group had better quality of life - according to Asthma Quality of Life Questionnaire &#40;AQLQ&#41; scale- than those in the fluticasone group and without differences in adverse events&#46; This study demonstrated&#44; for the first time&#44; the fact that &#34;total control&#34; in asthma can be reach and that is a challenge that physicians and patients have to struggle for&#46;</p><p class="elsevierStylePara">According to the evidence mentioned at the beginning of this editorial&#44; the main question in pediatrics is if the GOAL results can be apply to asthmatic children under 12 years of age&#46; Unfortunately&#44; there is no clinical trial done for that age with the same design&#44; however institutions like NAEPP <span class="elsevierStyleSup">23</span> in the US and in the British Thoracic Society in UK have has in their guidelines the uses of ICS plus long active beta agonist for asthmatic children under 5 years of age with moderate to severe persistent asthma&#46;</p><p class="elsevierStylePara">Moreover&#44; there are some clinical trials which proved the efficacy of salmeterol&#47;fluticasone in asthmatic children less than 12 years of age&#46; For example&#44; Van der Berg et al <span class="elsevierStyleSup">24</span> in a multicenter&#44; randomized&#44; double blind and parallel-group study compared the clinical efficacy of salmeterol &#40;50 &#956;g bid&#41; plus fluticasone &#40;100 &#956;g bid&#41; administrated in one single inhaler &#40;combination therapy with Accuhaler &#174;&#41; vs&#46; concurrently in two separate Accuhaler &#174;  inhalers&#46; From a total of 257 asthmatic children &#40;aged 4-11 years&#41; who remained symptomatic on ICS alone &#40;200-500 &#956;g beclomenthasone or budesonide&#41; were randomized to one of each group&#46; After 12 weeks of treatment both groups of children &#40;combination and separate therapy&#41; were similar in improve PEF&#44; clinical score&#44; less use of rescue drugs&#44; well tolerate therapy and few secondary effects&#46; Bracamonte et al <span class="elsevierStyleSup"> 25</span> in a multicenter&#44; randomized study compared 428 asthmatic children &#40;4-11 years&#41; who remained symptomatic on moderate doses of ICS &#40;&#8804;  500 &#956;g beclomethasone or budesonide&#41;&#46; One group received salmeterol&#47;fluticasone in a MDI free of CFC &#40;25&#47;50 &#956;g two inhalations bid&#41; and the other salmeterol&#47;fluticasone in Accuhaler &#174; device &#40;50&#47;100 &#956;g one inhalation bid&#41; for 12 weeks&#46; Clinical improve was reached in 90 &#37; and 86 &#37; of the children in each group&#44; respectively&#46; Finally&#44; Sekhsaria S&#46; et al <span class="elsevierStyleSup">26</span> in a retrospective study with 50 children &#40;5-60 months of age&#41; with recurrent wheezing demonstrated clinical improve &#40;decrease emergency visits&#44; hospitalization and exacerbations&#41; when they started the treatment with salmeterol&#47;fluticasone&#46;</p><p class="elsevierStylePara">Even though these clinical trials with salmeterol&#47;fluticasone in children under 12 years of age are not big in number of children enrolled and have different design to the GOAL study&#44; their results are promising&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> Competing interest statement</span></p><p class="elsevierStylePara">JACR&#58; in the past five years has been received reimbursement for attending conferences from Gr&#252;nenthal&#44; Merck&#44; GlaxoSmithKline and Andromaco&#44; at the present he is medical advisor for GSK&#46; The position of this paper is a personal opinion and does not express the opinion of any pharmaceutical company</p>"
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Applications of the GOAL study in childhood asthma
Implicaciones del estudio GOAL en el asma infantil
JA. Castro-Rodrígueza
a Departamento de Medicina Respiratoria Infantil. Facultad de Ciencias Médicas.Universidad de Santiago de Chile. Chile.
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    "textoCompleto" => "<p class="elsevierStylePara">Considering recent epidemiologic data we find strong evidence suggesting the advantage of starting the asthma therapy with controllers or preventive drugs very early on life&#44; better in the first 5 years of age&#46; The epidemiologic studies supporting that idea are&#58; first able around 80 &#37; of asthmatics start their disease in the first 12 years of age <span class="elsevierStyleSup">1</span>&#44; second the cohort study from Melbourne <span class="elsevierStyleSup">2</span> shows that asthma is a &#34;tracking disease&#34; in symptoms and pulmonary function&#44; meaning that a person that as a child have certain severity of disease and pulmonary function compromised will have the same compromise when he or she become an adult and third the cohort study from Tucson <span class="elsevierStyleSup">3</span> demonstrates that the asthmatic suffer the major loosing in pulmonary function in the first 5 years of age&#46;</p><p class="elsevierStylePara">Besides those epidemiologic data&#44; studies in asthmatic children where bronchoalverolar lavage were done demonstrated the presence of inflammation in the air way in children 8 years old <span class="elsevierStyleSup">4</span> and even in infants as little as 15 months of age with persistent wheezing <span class="elsevierStyleSup">5</span>&#46; There are also studies which demonstrate airway remodeling in asthmatic children <span class="elsevierStyleSup">6-7</span> and the most amazing finding is the fact of the thickness of the basal membrane of the airway in asthmatic children without controlled of their disease is very similar to severe asthmatic adults and it is not related either with the duration of the disease <span class="elsevierStyleSup">8</span>&#46; Therefore&#44; we end up once more to the same conclusion that is essential to start the treatment of asthma with controllers or preventing drugs at infancy&#46;</p><p class="elsevierStylePara">The only drugs which have been demonstrated to be useful to stop the airway remodeling in humans are the inhaled corticosteroids &#40;ICS&#41; like beclomethasone <span class="elsevierStyleSup">9</span>&#44; budesonide <span class="elsevierStyleSup">10</span> and fluticasone <span class="elsevierStyleSup"> 11</span> and the long active beta agonists like salmeterol <span class="elsevierStyleSup"> 12</span>&#46; The ICS that needs lower doses and less time to decrease the thickness of the basal membrane of the airway in asthmatics was fluticasone <span class="elsevierStyleSup">11</span>&#46; There is no evidence in the scientific literature that other type of drugs use for asthma like chromones&#44; theophyllines or leukotriene receptor antagonists have any effect in stopping the airway remodeling in humans&#46; These anti-inflammatory and anti-remodeling effects that the ICS has demonstrated besides their already well know utility in improving symptoms and pulmonary function <span class="elsevierStyleSup">13</span> make ICS become the first controller drug in asthma&#46; This should be use very early on life &#40;in the first 5 years&#41; otherwise the results will not be satisfactory&#44; like Childhood Asthma Management Program &#40;CAMP&#41; study <span class="elsevierStyleSup">14</span> demonstrated&#46; In that study the children did not improve their pulmonary function maybe because the ICS treatment started after that age&#46;</p><p class="elsevierStylePara">The problem is that in the first 5 years of age coexisting at least three phenotypes of wheezing in children &#40;transitory&#44; late and persistent or classic asthmatic&#41;&#46; One way to differentiate which infant with recurrent wheezing will become asthmatic in order to early start ICS therapy is using the asthma predictive value &#40;API&#41; <span class="elsevierStyleSup">15</span>&#46; Those infants with recurrent wheezing in the Tucson cohort who had a positive API had 7 times more risk to become asthmatic at school age&#46; In other words&#44; if an infant with recurrent wheezing come to the office and we apply the API and the result is positive we can tell the mother with 77 &#37; of certain that the infant will became asthmatic at school age and start controller drugs will be more effective&#46; In the other hand&#44; if the API is negative we can tell the mother with 70 &#37; of certain that the child will stop wheezing when he or she reaches school age&#46;</p><p class="elsevierStylePara">All of us who are involve in asthma management try to have our asthmatic children free of exacerbations&#44; emergency consults&#44; symptoms with exercise&#44; improved their pulmonary function and quality of life&#44; in other words&#44; stop feeling asthmatic or have a normal life&#46; However&#44; epidemiologic questionnaires done in several parts of the world <span class="elsevierStyleSup">16-18</span> have shown that around 95 &#37; of the asthmatic do not reach the control of their disease according to international guidelines <span class="elsevierStyleSup">19&#44;20</span>&#46;</p><p class="elsevierStylePara">One of the more remarkable issues is that most of the clinical trials done to investigate the efficacy of different drugs in asthma consider as the outcome only one parameter &#40;either clinical&#44; laboratory or pulmonary function&#41; and therefore&#44; besides overestimating the level of asthma control <span class="elsevierStyleSup">21</span>&#46; They do not consider that an asthmatic patient like other chronic patient need to be controlled in not only one parameter but also in a group of several parameters&#46;</p><p class="elsevierStylePara">Few months ago&#44; Bateman et al <span class="elsevierStyleSup">22</span> published the results of the GOAL study <span class="elsevierStyleItalic">&#40;The Gaining Optimal Asthma Control Study&#41;</span>&#46; GOAL was a 1-year&#44; stratified&#44; randomized&#44; double-blind&#44; parallel-group study comparing the efficacy and safety of individual&#44; predefined&#44; stepwise increases of salmeterol&#47;fluticasone with fluticasone alone in achieving two predefined composite measures of asthma control &#40;&#34;well control&#34; and &#34;total control&#34;&#41;&#46; Those outcomes are new and involve many clinical and pulmonary functions criteria as a whole&#46;</p><p class="elsevierStylePara">The GOAL <span class="elsevierStyleSup"> 22</span> study defined that a patient reaches &#34;total control&#34; of asthma if in 7 out of 8 weeks fulfills all of the following criteria&#58; without symptoms in the day&#44; no rescue medication use&#44; normal pulmonary function &#40;peak expiratory flow &#91;PEF&#93; am &#62; 80 &#37;&#41;&#44; no wake-ups at night&#44; no exacerbations&#44; no emergency visits and without secondary effects&#46; We can say that &#34;total control&#34; means clinical remission of asthma and that objective was more stringent than the one that Global Iniciative for Asthma &#40;GINA&#41; <span class="elsevierStyleSup">19</span> proposed&#46; The &#34;well control&#34; was defined as the fact that in 7 out of 8 weeks the patient fulfills the criteria&#58; no wake-ups at night&#44; no exacerbations&#44; no emergency visits and no secondary effects <span class="elsevierStyleItalic">PLUS</span> at least more than two of the follows criteria&#58; &#8804; 2 days with light symptoms&#44; use of rescue medications in &#8804; 2 days and &#8804;  4 times&#47;week and normal pulmonary function &#40;PEF am  &#62; 80 &#37;&#41;&#46;</p><p class="elsevierStylePara">From a total of 5068 patients &#40;between 12 and 80 years of age&#41; recruited in 44 countries&#44; 3421 patients fulfilled the inclusion criteria&#46; Interesting 10 &#37; of them were adolescents &#40;12-17 years-old&#41;&#46; At the beginning of the study the patients were separate in three strata- according to the ICS uses- and were randomized to received salmeterol&#47;fluticasone or fluticasone alone&#46; In each strata&#44; the percentage of patients who reached the &#34;well control&#34; and the &#34;total control&#34; definition were statistical more frequent in the salmeterol&#47;fluticasone group vs&#46; fluticasone&#46; And at the end of the year considerable proportion of patients &#40;41 &#37;&#59; all strata&#41; in the salmeterol&#47;fluticasone group reach the &#34;total control&#34;&#46; Moreover&#44; those patient in the salmeterol&#47;fluticasone group reach the &#34;total control&#34; with 60 &#37; less dose of ICS and earlier than those in the fluticasone group&#46; In the other hand&#44; the patients in the salmeterol&#47; fluticasone group had better quality of life - according to Asthma Quality of Life Questionnaire &#40;AQLQ&#41; scale- than those in the fluticasone group and without differences in adverse events&#46; This study demonstrated&#44; for the first time&#44; the fact that &#34;total control&#34; in asthma can be reach and that is a challenge that physicians and patients have to struggle for&#46;</p><p class="elsevierStylePara">According to the evidence mentioned at the beginning of this editorial&#44; the main question in pediatrics is if the GOAL results can be apply to asthmatic children under 12 years of age&#46; Unfortunately&#44; there is no clinical trial done for that age with the same design&#44; however institutions like NAEPP <span class="elsevierStyleSup">23</span> in the US and in the British Thoracic Society in UK have has in their guidelines the uses of ICS plus long active beta agonist for asthmatic children under 5 years of age with moderate to severe persistent asthma&#46;</p><p class="elsevierStylePara">Moreover&#44; there are some clinical trials which proved the efficacy of salmeterol&#47;fluticasone in asthmatic children less than 12 years of age&#46; For example&#44; Van der Berg et al <span class="elsevierStyleSup">24</span> in a multicenter&#44; randomized&#44; double blind and parallel-group study compared the clinical efficacy of salmeterol &#40;50 &#956;g bid&#41; plus fluticasone &#40;100 &#956;g bid&#41; administrated in one single inhaler &#40;combination therapy with Accuhaler &#174;&#41; vs&#46; concurrently in two separate Accuhaler &#174;  inhalers&#46; From a total of 257 asthmatic children &#40;aged 4-11 years&#41; who remained symptomatic on ICS alone &#40;200-500 &#956;g beclomenthasone or budesonide&#41; were randomized to one of each group&#46; After 12 weeks of treatment both groups of children &#40;combination and separate therapy&#41; were similar in improve PEF&#44; clinical score&#44; less use of rescue drugs&#44; well tolerate therapy and few secondary effects&#46; Bracamonte et al <span class="elsevierStyleSup"> 25</span> in a multicenter&#44; randomized study compared 428 asthmatic children &#40;4-11 years&#41; who remained symptomatic on moderate doses of ICS &#40;&#8804;  500 &#956;g beclomethasone or budesonide&#41;&#46; One group received salmeterol&#47;fluticasone in a MDI free of CFC &#40;25&#47;50 &#956;g two inhalations bid&#41; and the other salmeterol&#47;fluticasone in Accuhaler &#174; device &#40;50&#47;100 &#956;g one inhalation bid&#41; for 12 weeks&#46; Clinical improve was reached in 90 &#37; and 86 &#37; of the children in each group&#44; respectively&#46; Finally&#44; Sekhsaria S&#46; et al <span class="elsevierStyleSup">26</span> in a retrospective study with 50 children &#40;5-60 months of age&#41; with recurrent wheezing demonstrated clinical improve &#40;decrease emergency visits&#44; hospitalization and exacerbations&#41; when they started the treatment with salmeterol&#47;fluticasone&#46;</p><p class="elsevierStylePara">Even though these clinical trials with salmeterol&#47;fluticasone in children under 12 years of age are not big in number of children enrolled and have different design to the GOAL study&#44; their results are promising&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> Competing interest statement</span></p><p class="elsevierStylePara">JACR&#58; in the past five years has been received reimbursement for attending conferences from Gr&#252;nenthal&#44; Merck&#44; GlaxoSmithKline and Andromaco&#44; at the present he is medical advisor for GSK&#46; The position of this paper is a personal opinion and does not express the opinion of any pharmaceutical company</p>"
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Información del artículo
ISSN: 16954033
Idioma original: Inglés
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2020 Septiembre 15 15 30
2020 Agosto 20 18 38
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2020 Mayo 36 14 50
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2020 Marzo 20 12 32
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2020 Enero 28 6 34
2019 Diciembre 40 16 56
2019 Noviembre 23 7 30
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2019 Septiembre 20 13 33
2019 Agosto 26 17 43
2019 Julio 18 16 34
2019 Junio 42 13 55
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2019 Abril 36 19 55
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2019 Febrero 31 9 40
2019 Enero 24 19 43
2018 Diciembre 27 19 46
2018 Noviembre 43 27 70
2018 Octubre 51 19 70
2018 Septiembre 28 16 44
2018 Agosto 1 0 1
2018 Julio 5 0 5
2018 Junio 3 0 3
2018 Mayo 7 0 7
2018 Abril 24 0 24
2018 Marzo 30 0 30
2018 Febrero 29 0 29
2018 Enero 16 0 16
2017 Diciembre 26 0 26
2017 Noviembre 13 0 13
2017 Octubre 14 0 14
2017 Septiembre 20 0 20
2017 Agosto 16 0 16
2017 Julio 24 0 24
2017 Junio 31 14 45
2017 Mayo 22 11 33
2017 Abril 18 9 27
2017 Marzo 12 2 14
2017 Febrero 15 6 21
2017 Enero 9 4 13
2016 Diciembre 31 15 46
2016 Noviembre 40 8 48
2016 Octubre 45 6 51
2016 Septiembre 41 5 46
2016 Agosto 10 2 12
2016 Julio 9 0 9
2016 Febrero 2 0 2
2015 Diciembre 4 0 4
2015 Septiembre 0 6 6
2015 Agosto 1 0 1
2015 Julio 15 1 16
2015 Junio 16 0 16
2015 Mayo 26 0 26
2015 Abril 24 2 26
2015 Marzo 28 1 29
2015 Febrero 20 3 23
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2014 Diciembre 33 3 36
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2014 Abril 79 3 82
2014 Marzo 97 20 117
2014 Febrero 65 13 78
2014 Enero 63 12 75
2013 Diciembre 106 14 120
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2013 Octubre 96 18 114
2013 Septiembre 68 18 86
2013 Agosto 97 19 116
2013 Julio 58 9 67
2013 Junio 14 4 18
2013 Mayo 24 6 30
2013 Abril 26 5 31
2013 Marzo 33 4 37
2013 Febrero 45 11 56
2013 Enero 46 1 47
2012 Diciembre 57 6 63
2012 Noviembre 41 8 49
2012 Octubre 24 0 24
2012 Septiembre 7 2 9
2012 Agosto 3 2 5
2005 Mayo 3357 0 3357
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