was read the article
array:23 [ "pii" => "S0301054613001110" "issn" => "03010546" "doi" => "10.1016/j.aller.2013.02.011" "estado" => "S300" "fechaPublicacion" => "2014-07-01" "aid" => "510" "copyright" => "SEICAP" "copyrightAnyo" => "2012" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Allergol Immunopathol (Madr). 2014;42:342-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 658 "formatos" => array:3 [ "EPUB" => 5 "HTML" => 428 "PDF" => 225 ] ] "itemSiguiente" => array:18 [ "pii" => "S0301054613002371" "issn" => "03010546" "doi" => "10.1016/j.aller.2013.08.001" "estado" => "S300" "fechaPublicacion" => "2014-07-01" "aid" => "555" "copyright" => "SEICAP" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Allergol Immunopathol (Madr). 2014;42:348-54" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 848 "formatos" => array:3 [ "EPUB" => 9 "HTML" => 455 "PDF" => 384 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Perioperative allergic reactions: Experience in a Flemish referral centre" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "348" "paginaFinal" => "354" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1411 "Ancho" => 1622 "Tamanyo" => 130114 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Basal (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>90) and acute phase tryptase levels (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>59). Tryptase levels were measured with an immunoassay. Results did not follow a Gaussian distribution (D’Agostino and Pearson omnibus normality test). Significance was calculated after logarithmic scale conversion, by using paired <span class="elsevierStyleItalic">t</span>-test (basal versus acute phase levels in both IgE and non-IgE-reactions) and unpaired <span class="elsevierStyleItalic">t</span>-test (basal and acute phase levels in IgE-mediated reactions versus non-IgE-reactions).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Antunes, A.-M. Kochuyt, J.L. Ceuppens" "autores" => array:3 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Antunes" ] 1 => array:2 [ "nombre" => "A.-M." "apellidos" => "Kochuyt" ] 2 => array:2 [ "nombre" => "J.L." "apellidos" => "Ceuppens" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054613002371?idApp=UINPBA00004N" "url" => "/03010546/0000004200000004/v1_201407030035/S0301054613002371/v1_201407030035/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0301054613001043" "issn" => "03010546" "doi" => "10.1016/j.aller.2013.02.004" "estado" => "S300" "fechaPublicacion" => "2014-07-01" "aid" => "503" "copyright" => "SEICAP" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Allergol Immunopathol (Madr). 2014;42:336-41" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 845 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 407 "PDF" => 428 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Investigation of underlying primary immunodeficiencies in patients with severe atopic dermatitis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "336" "paginaFinal" => "341" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Aghamohammadi, Z.Gholizadeh Moghaddam, H. Abolhassani, Z. Hallaji, H. Mortazavi, S. Pourhamdi, P. Mohammadinejad, N. Rezaei" "autores" => array:8 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Aghamohammadi" ] 1 => array:2 [ "nombre" => "Z.Gholizadeh" "apellidos" => "Moghaddam" ] 2 => array:2 [ "nombre" => "H." "apellidos" => "Abolhassani" ] 3 => array:2 [ "nombre" => "Z." "apellidos" => "Hallaji" ] 4 => array:2 [ "nombre" => "H." "apellidos" => "Mortazavi" ] 5 => array:2 [ "nombre" => "S." "apellidos" => "Pourhamdi" ] 6 => array:2 [ "nombre" => "P." "apellidos" => "Mohammadinejad" ] 7 => array:2 [ "nombre" => "N." "apellidos" => "Rezaei" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054613001043?idApp=UINPBA00004N" "url" => "/03010546/0000004200000004/v1_201407030035/S0301054613001043/v1_201407030035/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Off-label prescribing for allergic diseases in pre-school children" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "342" "paginaFinal" => "347" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Morais-Almeida, A.J. Cabral" "autores" => array:2 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Morais-Almeida" "email" => array:1 [ 0 => "mmoraisalmeida@netcabo.pt" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A.J." "apellidos" => "Cabral" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Immunoallergy Department, CUF Descobertas Hospital, Lisbon, Portugal" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Many drugs used in the treatment of allergic diseases are not appropriately studied in the paediatric population, especially in infants and younger children. Nonetheless, their off-label use, i.e. use outside the formal indications authorised by the regulatory authorities, in a different age group, dose, or indication<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> is common in many paediatric illnesses like allergic disease. This happens because of practical and ethical considerations in carrying out clinical trials in this population.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In general, off-label prescription rates range from 11% to 37% in children treated in the community setting, and in up to 62% of children in paediatric hospital wards.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The major concern with this off-label use is the increased risk of adverse drug reactions.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Additionally, younger children and infants have a considerably increased risk of prescription errors, especially dosage errors.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">However, off-label prescriptions are not necessarily incorrect,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and may even be appropriate in certain clinical situations provided there is no alternative treatment, and when the likely benefits outweigh the potential risks,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> such as when conventional treatments are unable to achieve control of the disease. The potential advantages of off-label prescribing, apart from the probable benefit to the individual patient, are that new therapeutic uses may be described, and data on the efficacy and safety of the drug being used in new settings may be collected.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> With off-label prescriptions, the physician must act as an enlightened intermediary. On the one hand, managing the regulatory data aimed at ensuring the effectiveness and safety of the prescription, and on the other hand, putting all his or her knowledge into serving the interests of the patient.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Several studies have consistently shown that off-label use in children is common. A population-based cohort study carried out in primary care units in Holland assessed the prescribing of respiratory drugs in 2502 children, showing that almost 37% were off-label, and 39% in this group were prescriptions for asthma.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The TEDDY study, comparing the use of anti-asthmatic drugs in children in Holland, Italy, and the United Kingdom, established that off-label use of β2-agonists and inhaled corticosteroids is frequent, including up to 80% of the inhaled budesonide prescriptions in Italy.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In Portugal, few studies exist concerning off-label use of drugs in paediatric populations, and none are specifically related to drugs for the treatment of allergic disease. This study aimed to characterise off-label prescribing of drugs used in the treatment and control of asthma, allergic rhinitis, and atopic eczema in a significant sample of pre-school aged children followed by allergy specialists at a reference allergology consultation.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">The clinical files of children aged ≤6 years followed in our allergology consultation who were diagnosed with current asthma, allergic rhinitis, and/or atopic eczema phenotypes, with predominantly moderate to severe clinical presentations, were systematically reviewed. Consecutive medical visits were analysed from the beginning of January 2012 until the inclusion of a total of 500 patients (June 2012).</p><p id="par0030" class="elsevierStylePara elsevierViewall">The data collected included gender, age, diagnosis, and drugs prescribed for the control of allergic diseases that were used for a minimum period of two weeks, as well as the respective dosages. Drugs used for acute treatment were not considered. The drugs included were classified as follows: (1) inhaled corticosteroids (IC); (2) nasal topical corticosteroids (NC); (3) long acting β2 agonists (LABA); (4) oral antihistamines (AH); (5) oral antileukotrienes (AL); (6) topical immunomodulators (TI).</p><p id="par0035" class="elsevierStylePara elsevierViewall">The formal indications for each drug were available from <span class="elsevierStyleItalic">Infarmed – Autoridade Nacional do Medicamento e Produtos, I.P</span>. (Infarmed),<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> the national authority on drug control and authorisation, and were confirmed by the pharmaceutical companies responsible for their production and distribution; these indications were systematically compared by the authors, who found no discrepancies (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The age groups were classified according to the paediatric age definitions provided by the <span class="elsevierStyleItalic">European Medicines Agency</span> (EMA).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> As such, the sample was divided as follows: age<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>2 years, and age 2–6 years. Although EMA considers an age group for newborns “younger than one month old”, the sample did not include any patients in this age group.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The study was approved by the ethical committee of the institution.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Statistical comparisons (chi-square) were performed using the statistical program IBM SPSS Statistics version 19.0.0 (2010, Chicago, IL, USA), and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 was considered statistically significant.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">A total of 500 patient files were verified (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>), corresponding to 1224 prescriptions used to control the previously mentioned pathologies. The most prescribed drugs were oral antihistamines (34.6%), followed by antileukotrienes (22.6%), nasal topical corticosteroids (20.3%), inhaled corticosteroids (17.7%), association of inhaled corticosteroids and LABA (4.6%), and, finally, topic immunomodulators (0.2%). The most often used drugs were montelukast (22.6%), levocetirizine (17.1%), mometasone (17.1%), and fluticasone (17.0%) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Of all the prescriptions, 802 (65.5%) were authorised for use in children and were used according to the formally approved indication. The remaining 422 (34.5%) drugs were used off-label, outside the approvals for age (62.6%), dosage (31.7%), or clinical indication (5.7%). Mometasone, fluticasone, and levocetirizine were the drugs most frequently prescribed in this fashion (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). In Portugal, as in several other European countries, mometasone is authorised solely for children aged >6 years and is therefore frequently used off-label. The same occurs with levocetirizine, which is authorised only for children aged >2 years. As for fluticasone, its off-label use was related to prescribing doses greater than the approved dosage. Only montelukast was prescribed outside of its clinical indication since, in Portugal as in other countries, it can only be used as adjunctive therapy in the preventive treatment of asthma in children age <2 years, being not authorised as a single therapy,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> with the exception if it is not possible to use inhaled steroids as controller medication.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Dividing the prescriptions into categories, we highlight the off-label use of nasal topical corticoids in over 75% of the total prescription (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>), which was always due to the age limitation. We also note the off-label use of pimecrolimus due to age in cases of severe atopic eczema, despite its reduced prescribing in three patients aged 8, 10, and 12 months, respectively.</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Although the overall prescribing for children aged <2 years was lower than in older children, off-label use was relatively much more frequent. Up to 73.5% of prescriptions in this age group were off-label compared with 27.7% in the oldest age group (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). This difference was statistically significant (p <0.001). Note that, with one exception, all children aged <2 years received at least one off-label prescription.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">This study provides detailed and original information about national off-label prescribing for the allergic diseases asthma, allergic rhinitis, and atopic eczema in the paediatric population.</p><p id="par0080" class="elsevierStylePara elsevierViewall">We found that, in pre-school children, the use of drugs for these conditions in moderate to severe forms is frequent (34.5%), particularly in children aged <2 years, with more than 73% of prescriptions made for this group. This is probably due to the absence of data on the safety and efficacy of drugs at this age group, owing to the lack of clinical trials.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The lack of clinical research in the paediatric population, mainly in infants, results from a combination of factors that can contribute to this age group being the last to benefit from medical progress.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,13</span></a> Pharmaceutical companies, which can never promote or recommend off-label use of their drugs, apparently view the approval of drugs in children as a market that would bring small financial benefit, with only a few drugs representing a large enough economic interest. As such, it is not surprising that the drugs that have been adequately studied in children are anti-infectious vaccines and some antibiotics. Specific medical techniques and appropriate equipment are also necessary for clinical investigation in the paediatric population; technical procedures that seem simple in adults, such as drawing blood, among other minimally invasive interventions, can be difficult to execute or even authorise in children. Lastly, the ethical implications in children are more complex, with potential risks associated with the intervention, and significantly hinder clinical trials in this population.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The clinical investigation of drugs in the paediatric population is regulated by international standards (ICH E11), including European (EC no. 1902/2006), which set out specific requirements for the protection of children in clinical trials.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,16</span></a> However, the current EMA regulations encourage research and development of drugs in the paediatric population to improve the available information on these drugs, by assigning benefits to the pharmaceutical industry like extending the period of patent exclusivity.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,18</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Nonetheless, most drugs available on the market are not specifically tested in children, particularly younger children. In Portugal, Infarmed has specialised committees, namely the Committee for the Evaluation of Medicinal Products, which is responsible for issuing opinions on the quality, safety, and efficacy of drugs within their marketing authorisations (AIM). They have the responsibility for reviewing and approving the Summaries of Product Characteristics (RCM). However, the use of drugs outside their authorised RCM is not the concern of authorities and is the sole responsibility of the prescriber.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">This study showed a great number of off-label prescriptions, although it can be overestimated related with the severity of the clinical manifestations of the included children; these values must be interpreted with caution, however, as they may suggest inadequate or inappropriate use. Off-label prescribing is not necessarily incorrect<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and is contemplated in several therapeutic guidelines that include paediatric populations, but remarkably with no indication that some of the drugs are being recommended for unlicensed and off-label use.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In fact, indications for drug use in therapeutic guidelines do not clinically or legally authorise their use, even if the guidelines support it.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Off-label prescribing is frequently necessary, but should be evaluated according to clinical indications, therapeutic alternatives, and risk-benefit considerations, and off-label use implies obtaining informed consent from the patient or guardian. However, if off-label use of drugs does not require a signed informed consent by the patient or his or her legal representative, is oral consent enough? In the prescriptions studied, off-label drug use was systematically indicated and justified to the parents or caretakers as well as the clinical necessity for the drug's use, which was invariably authorised after the requested clarifications, increasing the compliance to the indicated treatments. This type of information is very important for patient and caregiver adherence, but it is often omitted. A survey conducted in the UK found that most paediatricians did not obtain informed consent, or inform the children's parents that the drug's use was off-label, which could indicate poor medical practice.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">From the prescriptions studies, we note the very frequent off-label use of a very safe topical nasal corticosteroid, mometasone. The reason for off-label use was entirely due to its use outside the authorised age group, as it is only approved for children aged ≥6 years. This imposition is made by EMA, whereas the U.S. Food and Drug Administration (FDA) already allows the use of this drug in younger children, i.e. those aged >2 years.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Despite the discrepancy in permissions, the fact that the FDA, which is responsible for the regulation of drugs in the United States, has already authorised broader use of this drug offers additional security for prescribing it off-label in Europe. If the authorisations were identical, off-label use of mometasone would be only 4.3%.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The same can be said of the use of some antihistamines, in particular levocetirizine, whose off-label use was approximately 25%, and almost entirely due to its use in children aged under the authorised age. As of 2009, the FDA approved prescribing this drug for children and infants from six months of age<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> after publication of long-term trials that demonstrated its safety and efficacy in this paediatric population.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> In our pharmaceutical market, levocetirizine is still only approved for children aged >2 years.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> As in the above-mentioned case, if the indications were the same on both continents, off-label prescribing of this drug would have been irrelevant.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Regarding topical immunomodulators, pimecrolimus was prescribed for only three cases of atopic eczema, but always off-label for age, despite its use being justified by clinical severity. This pathology appears in over 60% of patients before the age of 12 months;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> however, these drugs are only approved for children aged >2 years by both the FDA and EMA.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,22,25</span></a> This limitation was imposed because there are no current studies of long-term safety that are deemed sufficient for approval in younger children. The concerns of the regulatory authorities are based on the theoretical risk of systemic immunosuppression derived from the use of oral calcineurin inhibitors such as pimecrolimus or tacrolimus in transplant recipients, and the existence of rare instances of malignancy associated with their use.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> However, pharmacokinetic data obtained from clinical trials in children aged <2 years did not suggest concentrations high enough to cause systemic immunosuppression, unlike oral administration, or demonstrate a correlation between systemic concentrations and percentage body surface area treated or the duration of treatment.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Likewise, there was no interference with the development of normal immune responses to vaccinations.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Besides demonstrating extreme efficacy, these trials demonstrate safety data for IT use in atopic eczema, but more extensive surveillance is needed to determine long-term safety. Nonetheless, since its introduction on the market in 2001, no definite causal relationship between the use of IT and malignancy has been established.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In this study, we confirmed that the off-label use of anti-allergic drugs in pre-school-aged children for the treatment of moderate to severe allergic diseases is high. With few studies of long-term safety, the implications inherent in this type of use become evident. The Paediatric Committee of the EMA has issued a list of drugs currently administered to children for which information on pharmacokinetics, efficacy, and safety are urgently needed; fluticasone and montelukast, among others, were included.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> The standard method consists of performing randomised controlled trials, which are limited by methodological difficulties, hence the need to develop sufficiently extensive post-marketing observational studies in order to obtain sufficient data to evaluate the safety and efficacy of drugs used in paediatric populations.</p><p id="par0130" class="elsevierStylePara elsevierViewall">In some emerging diseases in our area of expertise the majority of drugs available that provide the best results are used off-label regardless of age.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The presence of complete and updated records with detailed information on the drugs used, dosages, routes of administration, and adverse effects are important in obtaining reliable data essential for further evaluation of the safety and efficacy of drugs in which more complex studies in children are not feasible for practical and/or ethical reasons. As with other populations with unique characteristics, such as pregnant women and the elderly, publication and distribution of this information by the scientific community is critical for the acquisition of new safety data, allowing the approval of new dosages, clinical indications, and/or prescribing for younger children, reducing off-label drug use that, although often appropriate, is not without risks.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Finally, this study should increase clinicians’ awareness of prescribing drugs off-label such that they are available at any time to discuss use of the drugs with patients and their families, as well as provide the motives that justify their use, valuing benefits versus risks, increasing compliance and contributing to achieve better outcomes.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Ethical disclosures</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Protection of human subjects and animals in research</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Confidentiality of data</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Right to privacy and informed consent</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflict of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">None to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:2 [ "identificador" => "xres349796" "titulo" => array:5 [ 0 => "Abstract" 1 => "Background" 2 => "Methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec331459" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] ] ] 4 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Protection of human subjects and animals in research" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Right to privacy and informed consent" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-12-29" "fechaAceptado" => "2013-02-02" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec331459" "palabras" => array:6 [ 0 => "Asthma" 1 => "Atopic eczema" 2 => "Infant" 3 => "Off-label prescription" 4 => "Pre-school children" 5 => "Rhinitis" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Several studies have demonstrated that medication is commonly used off-label in children with allergic diseases. The aim of this study was to characterise off-label use of prescriptions for allergic diseases in pre-school children from an allergology outpatient unit.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The clinical files of children aged ≤6 years seen in a reference allergology consultation with asthma, allergic rhinitis, and/or atopic eczema were reviewed. A total of 500 patients were consecutively observed from January to June 2012. The data collected included gender, age, diagnosis, and prescriptions with the respective daily dosage.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 1224 prescriptions were registered. The most prescribed medications were oral antihistamines (34.6%), antileukotrienes (22.6%), topical nasal corticosteroids (20.3%), and inhaled corticosteroids (17.7%). From all prescriptions, 422 (34.5%) were considered off-label for age (62.6%), dosage (31.7%), or clinical indication (5.7%). Off-label use was more frequent in children aged <2 years, with 73.5% prescribed for children of this age.</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Off-label use of drugs for the treatment of paediatric allergic diseases is high. However, these prescriptions are not necessarily wrong, and are recommended in many guidelines. Randomised controlled studies are limited by methodological difficulties creating the need for more observational studies in order to further evaluate the safety and efficacy of drugs used in children.</p>" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "<span class="elsevierStyleItalic">Source</span>: Infarmed, I.P.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>" "tabla" => array:3 [ "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">IC: inhaled corticoids; NC: nasal topic corticoids; LABA: long acting β2 agonists; AH: oral antihistamines; AL: anti-leukotriene; TI: topic immunomodulator.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">Category \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Minimum age \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Maximum dose \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IC</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">Budesonide \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 years \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">400<span class="elsevierStyleHsp" style=""></span>μg/day – 2 to 7 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluticasone \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 months \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<span class="elsevierStyleHsp" style=""></span>μg/day – 1 to 4 years; 400<span class="elsevierStyleHsp" style=""></span>μg/day – 4 to 16 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NC</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">Budesonide \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 years \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">400<span class="elsevierStyleHsp" style=""></span>μg/day \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluticasone furoate \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 years \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">55<span class="elsevierStyleHsp" style=""></span>μg/day \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mometasone \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 years \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">100<span class="elsevierStyleHsp" style=""></span>μg/day \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LABA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">Salmeterol \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 years \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">100<span class="elsevierStyleHsp" style=""></span>μg/day \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AH</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">Cetirizine \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5<span class="elsevierStyleHsp" style=""></span>mg/day – 2 to 6 years; 10<span class="elsevierStyleHsp" style=""></span>mg/day – 6 to 18 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Levocetirizine \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 years \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">2.5<span class="elsevierStyleHsp" style=""></span>mg/day – 2 to 6 years; 5<span class="elsevierStyleHsp" style=""></span>mg/day – older than 6 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Loratadine \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5<span class="elsevierStyleHsp" style=""></span>mg/day – 2 to 6 years; 10<span class="elsevierStyleHsp" style=""></span>mg/day – 6 to 18 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Desloratadine \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 months \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">1.25<span class="elsevierStyleHsp" style=""></span>mg/day – 1 to 5 years; 2.5<span class="elsevierStyleHsp" style=""></span>mg/day – 6 to 12 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ebastine \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 years \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">2.5<span class="elsevierStyleHsp" style=""></span>mg/day – 2 to 5 years; 5<span class="elsevierStyleHsp" style=""></span>mg/day – 6 to 11 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ketotifen \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 months \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">0.1<span class="elsevierStyleHsp" style=""></span>mg/kg/day - 6 months to 3 years; 2<span class="elsevierStyleHsp" style=""></span>mg/day – older than 3 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AL \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">Montelukast \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4<span class="elsevierStyleHsp" style=""></span>mg/day – 6 months to 5 years; 5<span class="elsevierStyleHsp" style=""></span>mg/day – 6 to 14 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TI \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">Pimecrolimus \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 years \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"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab522865.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Always used in combination with fluticasone – authorisations identical to isolated use.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Drugs used for treatment of asthma, allergic rhinitis, and atopic eczema, and their authorizations for use according to age and dose.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Total (%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Gender</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Female \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">195 (61) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">305 (39) \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Age</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span><2 years \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 (16) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2–6 years \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">420 (84) \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="2" 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="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Diagnosis</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Asthma \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">238 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Allergic rhinitis \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">350 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Atopic eczema \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab522868.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Characterisation of the study population.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Results in <span class="elsevierStyleItalic">n</span>, except when pointed out. IC: inhaled corticoids; NC: nasal topic corticoids; LABA: long acting β2 agonist; AH: oral antihistamines; AL: anti-leukotriene; TI: topic immunomodulator.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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">Category \t\t\t\t\t\t\n \t\t\t\t</td><td 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">Drug \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="6" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Prescriptions</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Off-label</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Total \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Dose \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Indication \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IC</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">Budesonide \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluticasone \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">208 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.2 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="8" 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 " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NC</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">Budesonide \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluticasone furoate \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mometasone \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">209 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">168 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">168 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="8" 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LABA \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">Salmeterol \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="8" 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 " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AH</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">Cetirizine \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">115 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Levocetirizine \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">209 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Loratadine \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Desloratadine \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ebastine \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ketotifen \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.6 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="8" 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AL \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">Montelukast \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">277 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \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="8" 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TI \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">Pimecrolimus \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="8" 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Totals \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"> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1224 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">422 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34.5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">264 (62.6%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">134 (31.7%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (5.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab522867.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Total number of prescriptions studied.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Results in <span class="elsevierStyleItalic">n</span>, except when pointed out. IC: inhaled corticoids; NC: nasal topic corticoids; LABA: long acting β2 agonist; AH: oral antihistamines; AL: anti-leukotriene; TI: topic immunomodulator.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Authorised</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="5" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Off-label</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Total \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Total \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Dose \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Indication \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Age group (years)</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span><2 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">181 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">133 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73.5<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">*</span></a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2–6 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1043 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">754 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">289 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.5<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">*</span></a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">195 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="9" 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="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Drug category</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>IC \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">217 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">122 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.2 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>NC \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">248 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">189 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">76.2 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">189 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LABA \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69.6 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.4 \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">100 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab522866.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0010"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Prescriptions according to age and drug category.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Off-label use of medicines: consensus recommendations for evaluating appropriateness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Gazarian" 1 => "M. Kelly" 2 => "J.R. McPhee" 3 => "L.V. Graudins" 4 => "R.L. Ward" 5 => "T.J. Campbell" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Med J Aust" "fecha" => "2006" "volumen" => "185" "paginaInicial" => "544" "paginaFinal" => "548" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17115966" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Research in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.P. Burns" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.CCM.0000054905.39382.58" "Revista" => array:7 [ "tituloSerie" => "Crit Care Med" "fecha" => "2003" "volumen" => "31" "numero" => "Suppl. 3" "paginaInicial" => "S131" "paginaFinal" => "S136" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12626958" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A literature review on off-label drug use in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Pandolfini" 1 => "M. Bonati" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00431-005-1698-8" "Revista" => array:6 [ "tituloSerie" => "Eur J Pediatr" "fecha" => "2005" "volumen" => "164" "paginaInicial" => "552" "paginaFinal" => "558" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15912383" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Unlicensed and off-label drug use in children: implications for safety" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "I. Choonara" 1 => "S. Conroy" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Drug Saf" "fecha" => "2002" "volumen" => "25" "paginaInicial" => "1" "paginaFinal" => "5" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11820908" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review of medication errors in pediatric patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.A. Ghaleb" 1 => "N. Barber" 2 => "B.D. Franklin" 3 => "V.W. Yeung" 4 => "Z.F. Khaki" 5 => "I.C. Wong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1345/aph.1G717" "Revista" => array:6 [ "tituloSerie" => "Ann Pharmacother" "fecha" => "2006" "volumen" => "40" "paginaInicial" => "1766" "paginaFinal" => "1776" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16985096" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paediatric prescribing: using unlicensed drugs and medicines outside their licensed indications" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Collier" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Clin Pharmacol" "fecha" => "1999" "volumen" => "48" "paginaInicial" => "5" "paginaFinal" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10383552" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Uses of drugs not described in the package insert (off-label uses)" ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pediatrics" "fecha" => "2002" "volumen" => "110" "paginaInicial" => "181" "paginaFinal" => "183" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12093968" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Off-label use of approved drugs: therapeutic opportunity and challenges" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "W.M. Bennett" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2004" "volumen" => "15" "paginaInicial" => "830" "paginaFinal" => "831" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14978188" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Unlicensed and off-label prescription of respiratory drugs to children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "G.W. t Jong" 1 => "I.A. Eland" 2 => "M.C. Sturkenboom" 3 => "J.N. van den Anker" 4 => "B.H. Strickerf" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2004" "volumen" => "23" "paginaInicial" => "310" "paginaFinal" => "313" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14979509" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Assessment of pediatric asthma drug use in three European countries; a TEDDY study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.F. Sen" 1 => "K.M. Verhamme" 2 => "A. Neubert" 3 => "Y. Hsia" 4 => "M. Murray" 5 => "M. Felisi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00431-010-1275-7" "Revista" => array:6 [ "tituloSerie" => "Eur J Pediatr" "fecha" => "2011" "volumen" => "170" "paginaInicial" => "81" "paginaFinal" => "92" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20811908" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Information about authorized drugs use; 2012. Available at: <a id="intr0005" class="elsevierStyleInterRef" href="http://www.infarmed.pt/infomed/inicio.php">www.infarmed.pt/infomed/inicio.php</a> [accessed 20.06.12]." ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Note for guidance on clinical investigation of medicinal products in children" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "1997" "editorial" => "European Agency for the Evaluation of Medicinal Products HMEU" "editorialLocalizacion" => "London" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug research and children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. Meadows" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "FDA Consum" "fecha" => "2003" "volumen" => "37" "paginaInicial" => "12" "paginaFinal" => "17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14666900" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Testing medications in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R. Steinbrook" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMhpr021646" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2002" "volumen" => "347" "paginaInicial" => "1462" "paginaFinal" => "1470" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12409558" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "ICH Guidance E11: Note for guidance on clinical investigation of medicinal products in the paediatric population (CPMP/ICH/2711/99); 2012 (June). Available from: <a id="intr0010" class="elsevierStyleInterRef" href="http://www.ema.europa.eu/pdfs/human/ich/271199en.pdf">http://www.ema.europa.eu/pdfs/human/ich/271199en.pdf</a> [on-line]." ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Amending Regulation EC No. 1902/2006 on medicinal products for paediatric use; 2012 (June). Available from: <a id="intr0015" class="elsevierStyleInterRef" href="http://ec.europa.eu/health/files/eudralex/vol-1/reg_2006_1902/reg_2006_1902_en.pdf">http://ec.europa.eu/health/files/eudralex/vol-1/reg_2006_1902/reg_2006_1902_en.pdf</a> [online]." ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The European Regulation on medicines for paediatric use" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Dunne" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.prrv.2007.04.004" "Revista" => array:6 [ "tituloSerie" => "Paediatr Respir Rev" "fecha" => "2007" "volumen" => "8" "paginaInicial" => "177" "paginaFinal" => "183" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17574163" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "What is happening to improve drug therapy in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H.M. Sammons" 1 => "I. Choonara" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Paediatr Child Health" "fecha" => "2007" "volumen" => "17" "paginaInicial" => "108" "paginaFinal" => "110" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Utilização de medicamentos off-label" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Infarmed" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "fecha" => "2010" "editorial" => "Infarmed" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of unlabelled and off licence drugs in children. Use of unlicensed drugs may be recommended in guidelines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F.A. Riordan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "BMJ" "fecha" => "2000" "volumen" => "320" "paginaInicial" => "1210" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10836830" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A prospective questionnaire assessment of attitudes and experiences of off label prescribing among hospital based paediatricians" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.S. McLay" 1 => "M. Tanaka" 2 => "S. Ekins-Daukes" 3 => "P.J. Helms" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/adc.2005.081828" "Revista" => array:6 [ "tituloSerie" => "Arch Dis Child" "fecha" => "2006" "volumen" => "91" "paginaInicial" => "584" "paginaFinal" => "587" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16443615" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Informations about authorized drugs use obtained on U.S. Food and Drug Administration (FDA) site; 2012. FDA. Available online at: <a id="intr0020" class="elsevierStyleInterRef" href="http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm">http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm</a> [accessed 20.06.12]." ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety of levocetirizine treatment in young atopic children: an 18-month study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F.E. Simons" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1399-3038.2007.00558.x" "Revista" => array:6 [ "tituloSerie" => "Pediatr Allergy Immunol" "fecha" => "2007" "volumen" => "18" "paginaInicial" => "535" "paginaFinal" => "542" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17561929" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The atopic eczema/dermatitis syndrome. Epidemiology, natural course, and immunology of the IgE-associated (extrinsic) and the nonallergic (intrinsic) AEDS" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Wuthrich" 1 => "P. Schmid-Grendelmeier" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Investig Allergol Clin Immunol" "fecha" => "2003" "volumen" => "13" "paginaInicial" => "1" "paginaFinal" => "5" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12861844" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Informations about authorized drugs use obtained on European Medicines Agency (EMA) site; 2012. EMA. Available online at: <a id="intr0025" class="elsevierStyleInterRef" href="http://www.ema.europa.eu/ema/index.jsp%3Fcurl=/pages/medicines/landing/epar_search.jsp%26mid=WC0b01ac058001d124">http://www.ema.europa.eu/ema/index.jsp?curl=/pages/medicines/landing/epar_search.jsp∣=WC0b01ac058001d124</a> [assessed 26.06.12]." ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety of topical calcineurin inhibitors for the treatment of atopic dermatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P.J. Munzenberger" 1 => "J.M. Montejo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1592/phco.27.7.1020" "Revista" => array:6 [ "tituloSerie" => "Pharmacotherapy" "fecha" => "2007" "volumen" => "27" "paginaInicial" => "1020" "paginaFinal" => "1028" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17594208" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The safety and efficacy of tacrolimus therapy in patients younger than 2 years with atopic dermatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.R. Patel" 1 => "M.R. Vander Straten" 2 => "N.J. Korman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archderm.139.9.1184" "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2003" "volumen" => "139" "paginaInicial" => "1184" "paginaFinal" => "1186" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12975161" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term treatment of atopic dermatitis with pimecrolimus cream 1% in infants does not interfere with the development of protective antibodies after vaccination" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.A. Papp" 1 => "K. Breuer" 2 => "M. Meurer" 3 => "J.P. Ortonne" 4 => "P.C. Potter" 5 => "Y. de Prost" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2004.08.046" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2005" "volumen" => "52" "paginaInicial" => "247" "paginaFinal" => "253" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15692469" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "List of paediatrics needs (as established by the Paediatric Working Party); 2012 (June). Available from: <a id="intr0030" class="elsevierStyleInterRef" href="http://www.emea.europa.eu/docs/en_GB/document_library/Other/2009/10/WC500004058.pdf">http://www.emea.europa.eu/docs/en_GB/document_library/Other/2009/10/WC500004058.pdf</a>" ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eosinophilic esophagitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.H. Blatman" 1 => "A.M. Ditto" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Allergy Asthma Proc" "fecha" => "2012" "volumen" => "33" "numero" => "Suppl. 1" "paginaInicial" => "88" "paginaFinal" => "90" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/03010546/0000004200000004/v1_201407030035/S0301054613001110/v1_201407030035/en/main.assets" "Apartado" => array:4 [ "identificador" => "5554" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03010546/0000004200000004/v1_201407030035/S0301054613001110/v1_201407030035/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054613001110?idApp=UINPBA00004N" ]
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2024 November | 4 | 0 | 4 |
2024 October | 44 | 3 | 47 |
2024 September | 60 | 10 | 70 |
2024 August | 56 | 6 | 62 |
2024 July | 97 | 7 | 104 |
2024 June | 68 | 2 | 70 |
2024 May | 58 | 4 | 62 |
2024 April | 58 | 10 | 68 |
2024 March | 70 | 8 | 78 |
2024 February | 50 | 9 | 59 |
2024 January | 64 | 5 | 69 |
2023 December | 60 | 10 | 70 |
2023 November | 65 | 7 | 72 |
2023 October | 78 | 16 | 94 |
2023 September | 62 | 10 | 72 |
2023 August | 52 | 0 | 52 |
2023 July | 85 | 10 | 95 |
2023 June | 85 | 8 | 93 |
2023 May | 113 | 7 | 120 |
2023 April | 90 | 10 | 100 |
2023 March | 57 | 4 | 61 |
2023 February | 46 | 8 | 54 |
2023 January | 35 | 12 | 47 |
2022 December | 30 | 17 | 47 |
2022 November | 33 | 7 | 40 |
2022 October | 38 | 11 | 49 |
2022 September | 25 | 33 | 58 |
2022 August | 18 | 13 | 31 |
2022 July | 27 | 5 | 32 |
2022 June | 22 | 9 | 31 |
2022 May | 54 | 13 | 67 |
2022 April | 36 | 10 | 46 |
2022 March | 45 | 10 | 55 |
2022 February | 41 | 12 | 53 |
2022 January | 46 | 11 | 57 |
2021 December | 44 | 24 | 68 |
2021 November | 38 | 14 | 52 |
2021 October | 28 | 10 | 38 |
2021 September | 28 | 11 | 39 |
2021 August | 28 | 9 | 37 |
2021 July | 15 | 9 | 24 |
2021 June | 21 | 9 | 30 |
2021 May | 28 | 9 | 37 |
2021 April | 53 | 13 | 66 |
2021 March | 30 | 10 | 40 |
2021 February | 16 | 11 | 27 |
2021 January | 11 | 3 | 14 |
2020 December | 1 | 0 | 1 |
2020 August | 0 | 1 | 1 |
2020 July | 0 | 1 | 1 |
2020 May | 0 | 3 | 3 |
2019 June | 0 | 1 | 1 |
2019 May | 0 | 9 | 9 |
2018 February | 5 | 1 | 6 |
2018 January | 10 | 0 | 10 |
2017 December | 8 | 3 | 11 |
2017 November | 3 | 3 | 6 |
2017 October | 9 | 3 | 12 |
2017 September | 14 | 1 | 15 |
2017 August | 10 | 5 | 15 |
2017 July | 17 | 10 | 27 |
2017 June | 20 | 24 | 44 |
2017 May | 27 | 18 | 45 |
2017 April | 20 | 22 | 42 |
2017 March | 32 | 7 | 39 |
2017 February | 16 | 0 | 16 |
2017 January | 21 | 1 | 22 |
2016 December | 16 | 6 | 22 |
2016 November | 14 | 1 | 15 |
2016 October | 25 | 8 | 33 |
2016 September | 11 | 2 | 13 |
2016 August | 10 | 3 | 13 |
2016 July | 9 | 1 | 10 |
2016 June | 22 | 3 | 25 |
2016 May | 9 | 6 | 15 |
2016 April | 14 | 9 | 23 |
2016 March | 8 | 8 | 16 |
2016 February | 10 | 7 | 17 |
2016 January | 14 | 10 | 24 |
2015 December | 7 | 6 | 13 |
2015 November | 3 | 5 | 8 |
2015 October | 17 | 6 | 23 |
2015 September | 7 | 3 | 10 |
2015 August | 9 | 5 | 14 |
2015 July | 4 | 8 | 12 |
2015 April | 1 | 2 | 3 |
2015 March | 0 | 2 | 2 |
2015 February | 0 | 2 | 2 |
2015 January | 0 | 1 | 1 |
2014 December | 0 | 1 | 1 |
2014 November | 3 | 2 | 5 |
2014 October | 1 | 2 | 3 |
2014 August | 1 | 2 | 3 |
2014 July | 1 | 6 | 7 |