Original Article
Safety of immunotherapy with glutaraldehyde modified allergen extracts in children and adults
M. Guzmán-Fulgencio, R. Caballero, B. Lara, M. Mena, M. Tejera, A. Sastre, J.-L. Subiza, E. Fernández-Caldas, M. Casanovas
Corresponding author
Inmunotek S.L., Parque Tecnológico de Alcalá de Henares, Calle Punto Mobi, 5, 28805 Alcalá de Henares, Madrid, Spain
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Işık, A. Çağlar, B. Eroğlu-Filibeli, Ş. Çağlayan-Sözmen, Z. Arıkan-Ayyıldız, S. Asilsoy, N. Uzuner" "autores" => array:7 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Işık" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Çağlar" ] 2 => array:2 [ "nombre" => "B." "apellidos" => "Eroğlu-Filibeli" ] 3 => array:2 [ "nombre" => "Ş." "apellidos" => "Çağlayan-Sözmen" ] 4 => array:2 [ "nombre" => "Z." "apellidos" => "Arıkan-Ayyıldız" ] 5 => array:2 [ "nombre" => "S." "apellidos" => "Asilsoy" ] 6 => array:2 [ "nombre" => "N." 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"apellidos" => "Lara" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Mena" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Tejera" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Sastre" ] 6 => array:2 [ "nombre" => "J.-L." "apellidos" => "Subiza" ] 7 => array:2 [ "nombre" => "E." "apellidos" => "Fernández-Caldas" ] 8 => array:4 [ "nombre" => "M." "apellidos" => "Casanovas" "email" => array:1 [ 0 => "mcasanovas@inmunotek.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Inmunotek S.L., Parque Tecnológico de Alcalá de Henares, Calle Punto Mobi, 5, 28805 Alcalá de Henares, Madrid, Spain" "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="sect0040">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The efficacy and effectiveness of allergen specific immunotherapy (SIT) has been demonstrated in several double-blind placebo-controlled trials (DBPC) and in open studies.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">1–5</span></a> SIT has been accepted in consensus documents and position papers to be the only aetiological treatment of allergic diseases caused by inhalant allergens and hymenopter venoms,<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">6–10</span></a> always considering that it is effective when appropriate doses of allergens are administered.<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">3–9,11</span></a> The main concern related to this treatment is safety, which has been recognised since early studies<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">12,13</span></a> and has been globally evaluated and reviewed.<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">14–16</span></a> It has also been specifically evaluated in prospective studies,<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">17–23</span></a> assessing the safety of allergen vaccines from a single, or various, manufacturers in large groups of patients.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The vast majority of side effects related to SIT with allergen extracts are mainly due to the intrinsic properties of the allergens (IgE-binding epitopes) and the susceptibility of the allergic patient. These are predictable but they are not necessarily acceptable. Severe side-effects may be acceptable if the degree of benefit is large and the risk of side-effects is minimised and treated promptly and effectively.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">12</span></a> In general, the clinical indications for immunotherapy for allergic rhinitis and asthma are similar for adults and children.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">An important issue is the increasing evidence that polysensitisation to allergically unrelated allergens is more prevalent than monosensitisation.<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">24–26</span></a> The treatment of these patients with immunotherapy is a matter of debate.<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">27</span></a> Two possibilities may arise: the use of a mixture of the relevant allergen extracts to which the patient is allergic,<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a> or the use of a single clinically relevant allergen.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">9</span></a> Single-allergen immunotherapy refers to a single extract, or to extracts containing several allergenically close related allergens, such as a grass-pollen mixture, or <span class="elsevierStyleItalic">Dermatophagoides pteronyssinus</span> and <span class="elsevierStyleItalic">D. farinae</span>. Multi-allergen immunotherapy is the use of allergen mixtures with little, or no allergenic cross-reactivity,<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">24</span></a> such as <span class="elsevierStyleItalic">Olea europaea</span> and grass pollens, <span class="elsevierStyleItalic">Cupressus spp.</span> with other tree species, such as <span class="elsevierStyleItalic">Platanus hybrida</span>, grass mixtures with <span class="elsevierStyleItalic">Salsola kali</span>, or <span class="elsevierStyleItalic">Parietaria Judaica</span>, or <span class="elsevierStyleItalic">D. pteronyssinus</span> and <span class="elsevierStyleItalic">Blomia tropicalis</span>.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Consideration of the following basic principles is necessary when mixing allergen extracts: (1) cross reactivity of allergens, (2) appropriate dose of each constituent and (3) enzymatic degradation of allergens.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a> In the case of multi-allergen immunotherapy, the current procedure is the mixture of the allergen extracts, obtaining a final preparation in which each extract is diluted by a factor which is the number of extracts (i.e. 50% and 50% in the case of two allergens, or 33, 33 and 33% in the cases of three allergens). Therefore, the effective dose of each constituent is decreased.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a> The consideration regarding the maintenance of the appropriate dose in a mixture has a great impact on the issue of safety, because the maintenance of these doses yields a final preparation in which the final allergenic activity is the sum of the activity of each component. This approach, that could be dangerous using native allergen extracts, could be achieved using allergoids.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The modification of natural allergens with glutaraldehyde<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">28,29</span></a> which produces extracts with decreased IgE-binding capacity has proven to be safe and clinically efficacious,<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">30–37</span></a> allowing for the administration of high doses in a short period of time.<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">38</span></a> Furthermore, this modification significantly reduces the proteolytic activity of some native allergen extracts, such as those derived from mites,<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">39</span></a> allowing the mixture with pollen extracts.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The objective of this study was to evaluate the safety of therapeutic vaccines containing modified allergen extracts in a representative cohort of patients and to compare the safety profile regarding the age and the dose of allergen extract administered.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Safety was graded following the criteria of the European Academy of Allergy and Clinical Immunology (EAACI).<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Patient population</span><p id="par0040" class="elsevierStylePara elsevierViewall">The data evaluated were from the medical records of a cohort of 1855 patients (1034 male, 821 female). From these, 699 patients were children (435 males and 264 females) from 0 to 17 years with a mean age of 10.18 years (95% confidence interval 6.7–13.66) and 1156 patients were adults (599 males and 557 females) with a mean age of 34.59 years old (95% confidence interval 23.33–45.85). The epidemiological data of these patients are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. All patients were treated under real life clinical conditions in 48 Clinics/Allergy Services. The age distribution of the patients was: 699 (37.7%) were younger than 18 years. From these, 0.05% (one patient) was 10 months old, 14.6% were between 2 and 10 years and 23% were between 12 and 18 years. Adults were 1156 (62.3%) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Patients were mono or polysensitised to mites (<span class="elsevierStyleItalic">Dermatophagoides pteronyssinus</span>, <span class="elsevierStyleItalic">D. farinae, Blomia tropicalis</span>), pollens (grasses, <span class="elsevierStyleItalic">Olea europaea</span>, <span class="elsevierStyleItalic">Parietaria judaica</span>, <span class="elsevierStyleItalic">Cupressus arizonica</span>, <span class="elsevierStyleItalic">Salsola kali</span>, <span class="elsevierStyleItalic">Artemisia vulgaris, Plantago lanceolata</span> and/or <span class="elsevierStyleItalic">Chenopodium album</span>) and/or danders (cat and/or dog). All patients met the criteria for receiving immunotherapy described in the EAACI and WHO Position Papers on allergen immunotherapy.<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">40,41</span></a> All patients were diagnosed as having rhinoconjunctivitis (RC) (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1002) or rhinoconjunctivitis and asthma (RC-A) (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>883).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Immunotherapy preparation</span><p id="par0045" class="elsevierStylePara elsevierViewall">Each patient received an individualised commercial therapeutic vaccine (Clustoid<span class="elsevierStyleSup">®</span>, Inmunotek, SL, Alcalá de Henares, Spain). Three different preparations were supplied according to the individual medical prescription: Clustoid<span class="elsevierStyleSup">®</span>, Clustoid<span class="elsevierStyleSup">®</span> Max or Clustoid<span class="elsevierStyleSup">®</span> Forte. The characteristics of each preparation are specified in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. All of them contained polymerised allergen extracts prepared as previously described.<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">42</span></a> Each treatment contained vials of a single concentration of the modified extract/s labelled in Therapeutic Units (TU). One TU of the modified extract has the same protein amount as the protein of one Biological Unit (BU) of the corresponding native extract standardised according to the Nordic Guidelines.<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">43</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Major allergen content was determined in the corresponding native preparation before modification and expressed in mcg/mL. The contents in mite extracts was determined by ELISA using monoclonal antibodies (Indoor Biotechnologies Ltd., Charlottesville, VA, USA) and in pollen extracts by means of scanning densitometry.<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">44</span></a> The contents in these major allergens in the native extract needed to produce 10,000 TU of the modified preparation were 4 and 2 mcg of group 1 and group 2 of <span class="elsevierStyleItalic">Dermatophagoides</span>, respectively. In pollen, the figures were 24 mcg of Ole e 1 (<span class="elsevierStyleItalic">O. europaea</span>), and 25 mcg of Phl p1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>Phl p 5 in grasses.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The composition of the treatments is described in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Schedules of administration</span><p id="par0060" class="elsevierStylePara elsevierViewall">Different treatment schedules were used by the clinicians, with the most common being: the conventional, rush and ultra-rush. In conventional schedules, (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>331; 151 children and 180 adults) the patient received an injection of 0.2<span class="elsevierStyleHsp" style=""></span>mL and after one-week 0.5<span class="elsevierStyleHsp" style=""></span>mL. In rush schedule (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1048; 409 children and 639 adults) the first dose of 0.2<span class="elsevierStyleHsp" style=""></span>mL was injected in one arm and 30<span class="elsevierStyleHsp" style=""></span>min later 0.3<span class="elsevierStyleHsp" style=""></span>mL in the other arm. In ultra-rush schedule (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>84; 21 children and 63 adults) the first injection was the maintenance dose of 0.5<span class="elsevierStyleHsp" style=""></span>mL (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). In all schedules, the maintenance dose was 0.5<span class="elsevierStyleHsp" style=""></span>mL monthly. Pre-treatment with drugs (antihistamines or corticosteroids), in order to prevent adverse reactions, was not used. All injections were administered subcutaneously on the extensor surfaces of the upper arms using an insulin syringe with a 26 gauge ½ inch non-removable needle. Following the recommendations of the European Academy of Allergy and Clinical Immunology (EAACI),<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">40</span></a> all patients had a 30<span class="elsevierStyleHsp" style=""></span>minutes waiting period after each injection. Immunotherapy treatments including pollen extract were administered without interruption, or reduction of the planned dose during the corresponding pollen season.</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Ethics, design and sample size calculation</span><p id="par0065" class="elsevierStylePara elsevierViewall">The study was classified as Observational Postauthorization study (EPA-OD) by the Spanish Health Authorities (Agencia Española de Medicamentos y Productos Sanitarios) and was evaluated by the Ethics Committee of the “Comunidad Autonómica de Madrid”. It was conducted in 48 centres in Spain involving 57 specialists in allergy for the safety evaluation of different treatments containing polymerised allergen extracts (Clustoid<span class="elsevierStyleSup">®</span>, Clustoid<span class="elsevierStyleSup">®</span> Forte and Clustoid<span class="elsevierStyleSup">®</span> Max, Inmunotek, Alcalá de Henares, Spain). <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the characteristics of each preparation. The sample size was calculated based on the results obtained by Gastaminza.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a> The rate of systemic reactions (grades 2, 3 and 4) was 0.27% per injection. We considered that the rate of systemic reactions using these polymerised allergen extracts would be reduced by a factor of three. Therefore, the number of injections to be evaluated, for a relative risk of 0.35 and an error protection of 7.84,<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">45</span></a> was 9655. Considering that each patient would receive a mean of six injections, the number of patients to obtain this data was a minimum of 1650 subjects.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Safety assessment</span><p id="par0070" class="elsevierStylePara elsevierViewall">The adverse reactions based on the intrinsic properties of the allergen extracts were categorised as immediate when the onset was during the first 30<span class="elsevierStyleHsp" style=""></span>minutes after the administration and delayed when the onset was afterwards.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">8</span></a> Local reactions were quantified measuring the diameter of the erythema of the reaction. Immediate reactions with a diameter smaller than 5<span class="elsevierStyleHsp" style=""></span>cm and delayed reactions smaller than 10<span class="elsevierStyleHsp" style=""></span>cm were considered as clinically irrelevant.<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">46</span></a> The systemic reactions were graded according to the classification of the EAACI Position Paper on immunotherapy.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">8</span></a> The grading was: grade 0: No symptoms or non-specific symptoms; grade 1: Mild systemic reactions. Symptoms: Localised urticaria, rhinitis or mild asthma (Peak Flow<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>20% decrease from baseline); grade 2: Moderate systemic reactions. Symptoms: Slow onset (>15<span class="elsevierStyleHsp" style=""></span>min) of generalised urticaria and/or moderate asthma (PF<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>40% decrease from baseline); grade 3: Severe (non-life-threatening) systemic reactions. Symptoms: Rapid onset (<15<span class="elsevierStyleHsp" style=""></span>min) of generalised urticaria, angio-oedema, or severe asthma (PF<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>40% decrease from baseline), and grade 4: Anaphylactic shock. Symptoms: Immediate evoked reaction of itching, flushing, erythema, generalised urticaria, stridor (angio-oedema), immediate asthma, hypotension etc.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistics</span><p id="par0075" class="elsevierStylePara elsevierViewall">Fisher's exact test was used to evaluate the differences in the number of side reactions between children and adults, and the build-up and maintenance doses of different mixtures (mites, pollen and mites<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pollen) and between the preparations containing different number of extracts.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Vaccines and number of injections</span><p id="par0080" class="elsevierStylePara elsevierViewall">The composition of the vaccines and schedules of administration in children and adults are shown in <a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3 and 4</a>, respectively. The number of injections administered was 11,753; 4129 (35.1%) corresponded to the children and 7624 (64.9%) to the adults. From these, 3292 (28%) corresponded to the build-up phase (1228 in children and 2064 in adults) and 8461 (72%) to the maintenance dose (2901 in children and 5560 in adults) (data not shown). Each patient received a mean of 6.33 injections (5.9 in children and 6.6 in adults).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Adverse reactions</span><p id="par0085" class="elsevierStylePara elsevierViewall">All reactions were due to the intrinsic properties of the allergen extracts and, therefore, expected. There were no records related to unexpected adverse reactions, such as of toxic or infectious origins.</p><p id="par0090" class="elsevierStylePara elsevierViewall">A total of 132, (98 immediate and 34 delayed) relevant local reactions (1 per 14 patients, and 1 per 89 injections) were recorded. Of them, 48 (0.40% of injections) occurred in children (34 immediate and 14 delayed) and 84 (0.71% of injections) in adults (64 immediate and 20 delayed). There were significant differences between Clustoid<span class="elsevierStyleSup">®</span> Max and both, Clustoid<span class="elsevierStyleSup">®</span> and Clustoid<span class="elsevierStyleSup">®</span> Forte, regarding relevant local reactions (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.017 and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.004 respectively, Fisher exact text; data not shown).</p><p id="par0095" class="elsevierStylePara elsevierViewall">There were 38 systemic reactions in 1855 patients (14 in children and 24 in adults). 11 reactions (8 in adults and 3 in children) were immediate (9 of grade 1 and 2 of grade 2) and 27 delayed (11 in children and 16 in adults, 22 of grade 1 and 5 grade 2) (data not shown). There were 7 systemic reactions of grade 2 (occurred in 0.06% of the injections). All systemic reactions were mild and resolved (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>). No differences between children and adults and between treatments were found in systemic reactions. Two patients withdrew from immunotherapy due to reactions (described in <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>).</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">Retrospective data related to the administration of vaccines containing polymerised allergen extracts, from the medical records of a cohort of 1855 patients, was analysed in order to evaluate the safety of these preparations. A large number of centres (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>48) and physicians (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>57) were included in order to be more representative of real life conditions and to avoid the bias of a single, or few, physicians administering the treatment. All adverse reactions were of allergic nature, expected during the use of specific immunotherapy. In the present study, we detected that 1.12% of the total injections caused local reactions and that 0.06% caused a systemic reaction of grade 2. No grade 3 and 4 systemic reactions were reported.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Maintenance dose was reached the first day using rush schedule, or in one week with just two injections.</p><p id="par0110" class="elsevierStylePara elsevierViewall">We observed that specific immunotherapy (AIT) using modified allergen vaccines with different schedules is safe in both children and adults. In this study we have found a low rate of adverse reactions to AIT in Clustoid<span class="elsevierStyleSup">®</span>, Clustoid<span class="elsevierStyleSup">®</span> Forte and Clustoid<span class="elsevierStyleSup">®</span> Max treatments in both of them. Significant differences between children and adults were not observed with the use of Clustoid<span class="elsevierStyleSup">®</span> Forte, Clustoid<span class="elsevierStyleSup">®</span> Forte and Clustoid<span class="elsevierStyleSup">®</span> Max treatments related to relevant local reactions. These data suggest that these treatments appear to be better-tolerated in children than in adults even at higher concentrations like in Clustoid<span class="elsevierStyleSup">®</span> Forte (30,000<span class="elsevierStyleHsp" style=""></span>TU/mL). To confirm these data will need studies with a larger number of patients.</p><p id="par0115" class="elsevierStylePara elsevierViewall">With the use of unmodified standardised allergen extracts adsorbed to alum, Gastaminza et al.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a> provided data from 1212 patients in which SIT was administered in a single immunotherapy unit. These patients were diagnosed of allergic asthma and/or rhinoconjunctivitis, or hymenoptera venom anaphylaxis, and received a total of 29,754 injections. Seventy-nine systemic reactions (0.3% per injection) occurred in 2.9% of the patients receiving mite extracts, 7.5% of patients with pollen extracts and 6.7% in the case of hymenoptera venoms. No withdrawals were reported.</p><p id="par0120" class="elsevierStylePara elsevierViewall">In a multi-centre study, Moreno et al.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">18</span></a> evaluated 488 patients treated with biologically standardised allergen extracts for respiratory allergies; 433 patients completed the study and four were asked to abandon by the physicians. In three cases, the abandonment was suggested due to recurrent reactions and in one due to a single reaction. Four more patients left the study by their own decision due to local reactions during the build-up phase. The total of injections administered was 17,526 and the number of systemic reactions was 50 (0.3% of the injections): 30 of grade 2 and 21 of grade 3. In this study, the investigators detected more systemic reactions in patients receiving mite extracts.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Winther et al.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">19</span></a> evaluated the side-effects of SIT of a single manufacturer in a multi-centre study involving 1038 patients, treated with extracts of mite, pollen, dog or cat, or with wasp and bee venoms. The total number of injections was 23,047. Forty-one patients (4%) stopped the treatment due to complications (local or systemic reactions, or worsening of allergic symptoms). Twenty-three per cent of the patients treated with one allergen extract did not reach the maximum dose, and 29% when the treatment was with more than one allergen extract. A total of 582 side-effects were reported in 341 patients (2.5% of the injections). Seventy-eight per cent of these reactions were of grade 2, 20% of grade 3, and 1% (eight reactions) of grade 4.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Tabar et al.<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">21</span></a> analysed 419 patients observing that 4.8% of the patients experienced a systemic reaction (0.4% of the injections), being these reactions mainly in patients with asthma and sensitised to <span class="elsevierStyleItalic">D. pteronyssinus</span>. In another study,<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">20</span></a> 239 patients were evaluated in a double-blind placebo-controlled study using an allergen extract of <span class="elsevierStyleItalic">D. petronyssinus</span> from a single manufacturer administered using two types of build-up phases (conventional and cluster). During the incremental phase, there were 19 adverse reactions in 15 patients receiving the allergen extract; eight reactions (0.2% per injection) were systemic (three immediate and five delayed). All reactions were of grade 2. During the maintenance phase, nine delayed adverse reactions (0.5% per injection) were reported in eight patients. Two reactions were local and seven systemic (one with non-specific symptoms and six with asthma). As a consequence, the dose schedule for these patients was modified. Machín et al.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">22</span></a> evaluated the safety in 339 patients carefully treated in an immunotherapy unit, observing 21 systemic reactions in 14 patients (4.1% of the patients, 0.4% of the injections). In other double-blinded, placebo-controlled studies we can observed that pre-seasonal SCIT in the elderly is safe and efficacious comparable to studies in younger patients, although SCIT were safe in both.<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">47</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The tolerability of modified extracts was compared in double-blind studies with the corresponding unmodified preparations.<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">36,37</span></a> Doses 10 times higher than those used in the present study were achieved, and no adverse events were reported with the doses used in normal clinical conditions, confirming the wide therapeutic margin for this chemically-modified allergen vaccine and the safer profile than regular vaccines based on native unmodified extracts.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Although this study was not designed to compare SCIT with the sublingual route of administration, the rate of side reactions described in this study is lower than that described in some studies using sublingual immunotherapy. The safety of sublingual immunotherapy, using drops or tablets, has been reviewed in a study including eight double-blind placebo-controlled (DBPC) trials.<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">48</span></a> A total of 690 patients (347 active and 343 placebo) were studied; 145 adverse events were reported in the active and 79 in the placebo group (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01), with a higher incidence of adverse events in the mouth (18% and 4% of the patients in the active and placebo groups, respectively) and in the gastro-intestinal tract (14% and 4% of the patients in the active and placebo groups, respectively). Two laryngeal oedemas were reported in patients receiving the active treatment (0.6% of the patients).</p><p id="par0145" class="elsevierStylePara elsevierViewall">In DBPC studies using sublingual tablets of <span class="elsevierStyleItalic">Phleum pratense</span><a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">49</span></a> and <span class="elsevierStyleItalic">House Dust Mite</span>,<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">50</span></a> there were a lot of non-explained withdrawals due to adverse events in the groups who received the active tablets. Finally, in a large study using tablets,<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">51</span></a> 855 patients were included and 451 (53%) had adverse events, judged by the investigators as probably, or possibly, related to the treatment; 26 participants (3%) withdrew due to adverse events. Other studies with sublingual immunotherapy tablets describe a high percentage of adverse reactions with grasses and mites.<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">52,53</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Two safety studies<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">23,38</span></a> using modified allergen extracts of another manufacturer involved 1834 patients. One (1068 patients)<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">38</span></a> was regarding the safety of the build-up phase of rush schedule and the other (766 patients) build-up and maintenance. The incidence of relevant local and systemic reactions was low, below 1%, and all systemic reactions were mild and resolved spontaneously without the need for medication. There is some mention of oral immunotherapy with modified allergen extracts and safety. No severe adverse events effects were observed in short-term study.<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">54</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The possibility of adverse reactions of infectious origin has been suggested because of the use of multidose vials. These vials are sterile and contain phenol to avoid further contamination when in use. In this study, no reactions due to infection were recorded. This is in line with previous publications by Balekian et al.<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">55</span></a> and Lay et al.,<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">56</span></a> who evaluated the presence of adverse events of infectious origin after the administration of more than 130,000 injections in more than 3000 patients and more than 26,000 injections in 272 patients, respectively.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Considering the results presented in this study and in the context of the data available in the literature, we can conclude that the SC administration of these modified allergen extracts is safer than the use of unmodified allergen vaccines in all groups of patients. Furthermore, the available published data suggests that the safety profile of these modified allergen vaccines administered subcutaneously could be better than that observed with the sublingual administration of allergen extracts.</p><p id="par0165" class="elsevierStylePara elsevierViewall">In conclusion, specific immunotherapy using modified natural allergen vaccines is safe to treat allergic patients, even at higher doses and in mixtures of unrelated allergen extracts without dilution in the final presentation.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Ethical disclosures</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Confidentiality of data</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Right to privacy and informed consent</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Protection of human subjects and animals in research</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration.</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors declare the following, real or perceived conflicts of interest: The authors work in Inmunotek SL.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres803005" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec801333" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patient population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Immunotherapy preparation" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Schedules of administration" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Ethics, design and sample size calculation" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Safety assessment" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistics" ] ] ] 4 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Vaccines and number of injections" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Adverse reactions" ] ] ] 5 => array:2 [ "identificador" => "sec0060" "titulo" => "Discussion" ] 6 => array:3 [ "identificador" => "sec0065" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Confidentiality of data" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Right to privacy and informed consent" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Protection of human subjects and animals in research" ] ] ] 7 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 8 => array:2 [ "identificador" => "xack269031" "titulo" => "Acknowledgements" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-06-16" "fechaAceptado" => "2016-08-19" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec801333" "palabras" => array:7 [ 0 => "Allergen immunotherapy" 1 => "Mites" 2 => "Pollens" 3 => "Rhinoconjunctivitis" 4 => "Asthma" 5 => "Safety" 6 => "Glutaraldehyde-modified allergen extracts" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Glutaraldehyde-modified natural allergen extracts show significant reduction in the IgE-binding capacity and proteolytic activity. This allows the administration of higher doses in a shorter period of time, and to mix different allergen extracts.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Evaluate the safety of different concentrations and mixtures of glutaraldehyde-modified allergen extracts in a large group of paediatric and adult patients undergoing specific immunotherapy treatment.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">1855 patients (1156 adults and 699 children), suffering from rhinoconjunctivitis and/or asthma, participated in an observational multicentre cohort study, to evaluate the safety of immunotherapy using vaccines containing modified allergen extracts. Patients were monosensitised, or polysensitised, and received a therapeutic vaccine containing polymerised allergen extracts adsorbed onto aluminium hydroxide. Safety was assessed by recording all side reactions related to immunotherapy.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The clinically relevant local reactions totalled 120, (90 immediate and 30 delayed) (1.02% of injections). Of them, 31 (0.26% of injections) occurred in children (26 immediate and 5 delayed) and 89 (0.76% of injections) in adults (64 immediate and 25 delayed). There were 38 systemic reactions. Eleven reactions were immediate (9 of grade 1 and 2 of grade 2) and 27 delayed (22 of grade 1 and 5 of grade 2). There were seven grade 2 systemic reactions (0.06% of the injections). No differences (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05) in the number of reactions were observed between adults and children and between treatments were found in systemic reactions. All systemic reactions were mild and resolved spontaneously without the need of medication.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Specific immunotherapy using natural modified allergen vaccines is safe to treat allergic patients, even at higher doses and in mixtures of unrelated allergen extracts. The percentage of adverse reactions detected is lower than those reported in the literature with native unmodified allergen extracts.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] ] "multimedia" => array:6 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">All \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Children (0–17 years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Children (0–5 years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Children (6–10 years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Children (11–17 years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adults \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1885 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">699 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">244 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">427 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1156 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1034 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">435 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">153 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">262 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">599 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">821 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">264 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">165 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">557 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1347787.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Epidemiological data of patients.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "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"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Concentration \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1855 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Children <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>699 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Children (0–5 years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Children (6–10 years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Children (11–17 years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adults <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1156 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Clustoid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10,000<span class="elsevierStyleHsp" style=""></span>TU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">537 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">251 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">112 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">120 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">286 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Clustoid<br>Forte \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30,000<span class="elsevierStyleHsp" style=""></span>TU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">317 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">206 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Clustoid<br>Max \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Each allergen extract at 10,000<span class="elsevierStyleHsp" style=""></span>TU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">337 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">236 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">664 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">No. injections</td><td class="td" title="table-entry " align="char" valign="top">11,753 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4129 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">122 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1276 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2731 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7624 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1347789.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Concentration and frequency of the treatments administered.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviation</span>: Derm means <span class="elsevierStyleItalic">Dermatophagoides pteronyssinus</span> and <span class="elsevierStyleItalic">Dermatophagoides farinae</span>.</p>" "tablatextoimagen" => array:3 [ 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"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">CLUSTOID \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Adults</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Children</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">286 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">251 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Mites</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">183 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72.91 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Derm</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">166 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Derm</span> and other mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Pollen</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">172 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Grasses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Olea europaea</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Parietaria Judaica</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cupressus arizonica</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pollen mixtures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.96 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Danders</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cat \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dog \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Mixtures</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.99 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mites and pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other mixtures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.39 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1347792.png" ] ] 1 => 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"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">CLUSTOID FORTE \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Adults</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Children</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">206 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Mites</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">144 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75.68 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Derm</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">136 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75.68 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Derm</span> and other mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Pollen</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.32 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Grasses</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20.72 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mixtures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Grasses</span> and <span class="elsevierStyleItalic">Derm</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1347785.png" ] ] 2 => 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"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">CLUSTOID MAX \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Adults</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Children</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">664 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">337 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Mites</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">173 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.38 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Derm</span> and other mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.75 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Derm</span> and grasses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Derm</span>, grasses and other pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.97 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Derm</span> and other pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Derm</span>, mites, cat and/or pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.89 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Derm</span>, mites and pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other mites and pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Pollen</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">441 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">238 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Grasses and other pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">378 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">225 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66.76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Grasses, cat dander and/or other pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.89 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other mixtures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.97 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1347790.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Composition of the vaccines administered to the adult and children patients.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "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"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Schedule \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Build-up</th><th class="td" title="table-head " align="left" valign="top" scope="col">Maintenance \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Day 0 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Day 7 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Each 4 weeks \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Children<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>699 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adults<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1156 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Conventional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.2<span class="elsevierStyleHsp" style=""></span>mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5<span class="elsevierStyleHsp" style=""></span>mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5<span class="elsevierStyleHsp" style=""></span>mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">151 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">180 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.2<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>0.3<span class="elsevierStyleHsp" style=""></span>mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5<span class="elsevierStyleHsp" style=""></span>mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">409 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">639 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ultra-rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5<span class="elsevierStyleHsp" style=""></span>mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">118 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">274 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1347786.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Schedules of administration in children and adults.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviation</span>: ns, not significant.</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"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse reaction \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type reaction \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Children (0–17 years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adults \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="12" align="left" valign="middle" style="border-bottom: 2px solid black">All</td><td class="td" title="table-entry " rowspan="6" align="left" valign="middle" style="border-bottom: 2px solid black">Relevant local reactions</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">ns</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">4.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">5.53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">10.39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1.66 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Delayed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">ns</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">3.73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="6" align="left" valign="middle" style="border-bottom: 2px solid black">Systemic reactions grade 2</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">–</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Delayed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">–</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.72 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="12" align="left" valign="middle" style="border-bottom: 2px solid black">Clustoid</td><td class="td" title="table-entry " rowspan="6" align="left" valign="middle" style="border-bottom: 2px solid black">Relevant Local reactions</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">ns</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">4.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.74 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Delayed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">ns</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.32 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="6" align="left" valign="middle" style="border-bottom: 2px solid black">Systemic reactions grade 2</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">–</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Delayed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">–</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="12" align="left" valign="middle" style="border-bottom: 2px solid black">Clustoid Forte</td><td class="td" title="table-entry " rowspan="6" align="left" valign="middle" style="border-bottom: 2px solid black">Relevant local reactions</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">ns</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1.64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2.84 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Delayed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">ns</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.86 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="6" align="left" valign="middle" style="border-bottom: 2px solid black">Systemic reactions grade 2</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">–</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Delayed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">ns</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="12" align="left" valign="middle" style="border-bottom: 2px solid black">Clustoid Max</td><td class="td" title="table-entry " rowspan="6" align="left" valign="middle" style="border-bottom: 2px solid black">Relevant local reactions</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">ns</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2.73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Delayed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">ns</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2.52 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="6" align="left" valign="middle" style="border-bottom: 2px solid black">Systemic reactions grade 2</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">–</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Delayed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">ns</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">% injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="middle" style="border-bottom: 2px solid black">Total</td><td class="td" title="table-entry " colspan="2" align="center" valign="top" style="border-bottom: 2px solid black">Relevant local reactions</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">132 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="center" valign="top" style="border-bottom: 2px solid black">Patient/Infection rate (%)</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">26/4129 (0.63%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">53/7624 (0.69%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">79/11753 (0.67%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="center" valign="top" style="border-bottom: 2px solid black">Systemic reactions grade 2</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="center" valign="top" style="border-bottom: 2px solid black">Patient/Infection rate</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">3/4129 (0.07%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1/7624 (0.01%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">4/11753 (0.03%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="center" valign="top">Total</td><td class="td" title="table-entry " align="left" valign="top">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">139 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1347788.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Adverse local and systemic relevant reactions by treatment in children and adults.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at6" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviation</span>: Derm, <span class="elsevierStyleItalic">Dermatophagoides pteronyssinus</span> and <span class="elsevierStyleItalic">Dermatophagoides farinae</span>; Dx, diagnosis; RC, rhinoconjuntivitis; RC-A, rhinoconjuntivitis and asthma.</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"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Composition \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dx \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Grade of Systemic Reactions \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total<br>Injections in treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Injection number \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dose (mL) administered<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Description \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="middle" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Clustoid</span></td><td class="td" title="table-entry " rowspan="2" align="left" valign="middle" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Derm</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">+</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">B. tropicalis</span></td><td class="td" title="table-entry " rowspan="2" align="left" valign="middle" style="border-bottom: 2px solid black">RC-A</td><td class="td" title="table-entry " rowspan="2" align="left" valign="middle" style="border-bottom: 2px solid black">1041</td><td class="td" title="table-entry " rowspan="2" align="left" valign="middle" style="border-bottom: 2px solid black">M</td><td class="td" title="table-entry " rowspan="2" align="left" valign="middle" style="border-bottom: 2px solid black">23</td><td class="td" title="table-entry " rowspan="2" align="left" valign="middle" style="border-bottom: 2px solid black">2</td><td class="td" title="table-entry " rowspan="2" align="left" valign="middle" style="border-bottom: 2px solid black">10</td><td class="td" title="table-entry " rowspan="2" align="left" valign="middle" style="border-bottom: 2px solid black">2</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="middle" style="border-bottom: 2px solid black">Bronchospasm and generalized erythema. FEV1 (60%) BD+. Stop IT</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Clustoid Forte</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Derm</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">RC-A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1613 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Bronchospasm crisis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Clustoid Max</span></td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">Grasses<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Olea</span><span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Platanus</span></td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">RC</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">1521</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">F</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">15</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">2</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle" style="border-bottom: 2px solid black">3</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Dyspnoea \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Dyspnoea \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top" style="border-bottom: 2px solid black">Dyspnoea and stop IT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Clustoid Max</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Grasses<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Olea</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2121 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bronquial Asthma. 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This study was sponsored by Inmunotek, S.L.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/03010546/0000004500000002/v1_201702200044/S0301054616301197/v1_201702200044/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/03010546/0000004500000002/v1_201702200044/S0301054616301197/v1_201702200044/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054616301197?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 16 | 2 | 18 |
| 2024 October | 92 | 29 | 121 |
| 2024 September | 86 | 28 | 114 |
| 2024 August | 75 | 27 | 102 |
| 2024 July | 76 | 39 | 115 |
| 2024 June | 49 | 18 | 67 |
| 2024 May | 62 | 20 | 82 |
| 2024 April | 53 | 19 | 72 |
| 2024 March | 74 | 23 | 97 |
| 2024 February | 69 | 20 | 89 |
| 2024 January | 103 | 16 | 119 |
| 2023 December | 81 | 15 | 96 |
| 2023 November | 86 | 17 | 103 |
| 2023 October | 106 | 41 | 147 |
| 2023 September | 72 | 29 | 101 |
| 2023 August | 60 | 7 | 67 |
| 2023 July | 77 | 28 | 105 |
| 2023 June | 81 | 5 | 86 |
| 2023 May | 95 | 9 | 104 |
| 2023 April | 75 | 15 | 90 |
| 2023 March | 94 | 18 | 112 |
| 2023 February | 71 | 14 | 85 |
| 2023 January | 67 | 17 | 84 |
| 2022 December | 76 | 13 | 89 |
| 2022 November | 71 | 20 | 91 |
| 2022 October | 56 | 54 | 110 |
| 2022 September | 62 | 37 | 99 |
| 2022 August | 39 | 21 | 60 |
| 2022 July | 26 | 14 | 40 |
| 2022 June | 28 | 24 | 52 |
| 2022 May | 44 | 22 | 66 |
| 2022 April | 56 | 29 | 85 |
| 2022 March | 70 | 35 | 105 |
| 2022 February | 37 | 21 | 58 |
| 2022 January | 52 | 26 | 78 |
| 2021 December | 61 | 36 | 97 |
| 2021 November | 49 | 31 | 80 |
| 2021 October | 27 | 24 | 51 |
| 2021 September | 28 | 28 | 56 |
| 2021 August | 28 | 18 | 46 |
| 2021 July | 22 | 28 | 50 |
| 2021 June | 54 | 55 | 109 |
| 2021 May | 44 | 46 | 90 |
| 2021 April | 75 | 90 | 165 |
| 2021 March | 175 | 45 | 220 |
| 2021 February | 97 | 38 | 135 |
| 2021 January | 33 | 38 | 71 |
| 2020 December | 1 | 6 | 7 |
| 2020 November | 0 | 12 | 12 |
| 2020 October | 0 | 11 | 11 |
| 2020 September | 0 | 22 | 22 |
| 2020 August | 0 | 12 | 12 |
| 2020 July | 0 | 8 | 8 |
| 2020 June | 0 | 7 | 7 |
| 2020 May | 0 | 19 | 19 |
| 2020 April | 0 | 10 | 10 |
| 2020 March | 0 | 5 | 5 |
| 2020 February | 0 | 7 | 7 |
| 2020 January | 0 | 17 | 17 |
| 2019 December | 0 | 6 | 6 |
| 2019 November | 0 | 8 | 8 |
| 2019 October | 0 | 13 | 13 |
| 2019 September | 0 | 11 | 11 |
| 2019 August | 0 | 12 | 12 |
| 2019 July | 0 | 14 | 14 |
| 2019 June | 0 | 11 | 11 |
| 2019 May | 0 | 17 | 17 |
| 2018 March | 1 | 0 | 1 |
| 2018 February | 12 | 1 | 13 |
| 2018 January | 10 | 2 | 12 |
| 2017 November | 1 | 0 | 1 |
| 2017 February | 3 | 2 | 5 |
| 2016 December | 0 | 2 | 2 |
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