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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Atopic dermatitis &#40;AD&#41; is a prevalent&#44; chronic&#44; relapsing&#44; and inflammatory skin disorder of a multifactorial etiology characterized by intense itching and skin lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a> AD is a global disease that affects individuals across all age groups&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">2</span></a> The prevalence of AD among the pediatric population is notably high&#44; with estimates indicating that 15&#37; up to 30&#37; of children seem to be affected by this disease<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">3&#8211;5</span></a> vs a slightly lower prevalence among the adult population ranging from 7&#37; up to 14&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">2</span></a> The prevalence of AD among Spanish children remains unclear due to the lack of comprehensive&#44; age-specific studies and scarce available data&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">AD in pediatric patients is often associated with a range of comorbidities&#44; including other diseases such as asthma or allergic rhinitis&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a> Additionally&#44; psychiatric and psychological disorders are likely to be more prevalent in this population&#46; In fact&#44; there is evidence of an increased incidence of mental issues&#44; such as attention deficit hyperactivity disorder &#40;ADHD&#41; and depression&#44; which can also manifest as suicide ideation among these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">1&#44;6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The presence of these comorbidities&#44; along with symptoms of AD such as intense pruritus&#44; significantly impairs health-related quality of life &#40;HRQoL&#41;&#44; especially in severe cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">6&#44;8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Due to disease heterogeneity&#44; comorbidities&#44; complexity in treatment care and differences between national or regional health care systems&#44; managing AD in the pediatric population remains challenging&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">9</span></a> Short regimens of topical corticosteroids are the most widely prescribed treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">10</span></a> However&#44; adherence to these conventional therapies is often low&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> and their efficacy in severe cases is also limited&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#44;13</span></a> Fortunately&#44; in recent years&#44; innovative&#44; and highly effective treatments have emerged such as biologic drugs and Janus kinase &#40;JAK&#41; inhibitors&#46; However&#44; their use in children is still restricted in some cases&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">10</span></a> As a matter of fact&#44; the substantial humanistic burden of disease in patients with moderate-to-severe AD suggests potential undertreatment in this group&#44; with few evidence available on new therapies&#44; patient-reported outcomes &#40;PROs&#41;&#44; AD severity and impairment&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> On the other hand&#44; AD represents a substantial economic burden on the health system&#44; as well as on the patients and caregivers&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> The total direct cost was estimated to be nearly &#8364;2700 per patient per year&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> As expected&#44; the severity of the condition had a direct impact on cost&#44; with severe cases resulting in higher costs&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> Specifically&#44; compared with patients with mild and moderate AD&#44; severe AD presented significantly higher total direct costs &#40;&#8364;1512 &#91;SD&#44; 854&#93; and &#8364;1984 &#91;SD&#44; 2093&#93; vs &#8364;5377 &#91;SD&#44; 3&#46;518&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; respectively&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">There is no available comprehensive&#44; updated information on the humanistic&#44; and economic burden associated with children with AD in Spain&#46; This systematic review aims to provide an overview based on the most recent Spanish real-world evidence&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">We conducted a systematic review of observational studies on the humanistic and economic burden associated with pediatric patients with AD over the past 10 years &#40;from March 2013 through March 2023&#41; following the recommendations established by the &#8220;Preferred Reporting Items of Systematic Reviews and Meta-analysis&#8221; &#40;PRISMA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">15</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Data sources and search strategy</span><p id="par0035" class="elsevierStylePara elsevierViewall">The international PubMed&#47;MEDLINE&#44; Cochrane Library&#44; the Spanish national <span class="elsevierStyleItalic">Medicina en Espa&#241;ol</span> &#40;MEDES&#41;&#44; and <span class="elsevierStyleItalic">&#205;ndice Bibliogr&#225;fico Espa&#241;ol en Ciencias de la Salud</span> &#40;IBECS&#41; databases were searched to identify relevant publications for review&#46; Additionally&#44; manual searches in the grey literature &#40;Google and Google Scholar&#41; were conducted to identify documents such as non-indexed articles and conference abstracts published over the past 3 years at key national and European congresses organized by the following medical societies&#58; Spanish Academy of Dermatology and Venerology &#40;AEDV&#41;&#44; Spanish Society of Allergology and Clinical Immunology &#40;SEAIC&#41;&#44; European Academy of Dermatology and Venereology &#40;EADV&#41;&#44; American Academy of Dermatology &#40;AAD&#41; and Society for Pediatric Dermatology &#40;SDP&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The different databases were searched using both free-text and MeSH &#40;medical subject headings&#41; terms&#44; combined with the Boolean connectors OR and AND&#46; The list of terms and search strategy are detailed in <a class="elsevierStyleCrossRef" href="#sec0125">Table S1 of the supplementary data</a>&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Study selection</span><p id="par0045" class="elsevierStylePara elsevierViewall">Two reviewers independently screened all identified articles at two levels &#40;levels 1 and 2&#41;&#46; Level 1 consisted of a broad screening based on article titles and&#47;or abstracts&#44; as available&#46; Level 2 involved two reviewers who independently reviewed the full-text articles and applied the inclusion&#47;exclusion criteria&#46; At both levels&#44; discrepancies were resolved by consensus or with the involvement of a third team member&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Eligibility criteria</span><p id="par0050" class="elsevierStylePara elsevierViewall">Observational studies conducted in Spain including pediatric population &#40;&#60;18 years&#41; with a confirmed diagnosis of AD by dermatologists&#47;physicians published in English or Spanish from March 2013 through March 2023 were eligible&#46; Studies conducted out of Spain were included when specific data from the Spanish population were provided&#46; <a class="elsevierStyleCrossRef" href="#sec0125">Table S2 of the supplementary data</a> lists the inclusion and exclusion criteria&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Data mining and quality assessment</span><p id="par0055" class="elsevierStylePara elsevierViewall">Data mining included data on the epidemiology of the disease &#40;prevalence and incidence&#41;&#44; patients&#8217; characteristics &#40;demographic&#44; comorbidities&#41;&#44; patterns on use of treatment&#44; PROs&#44; impact of the disease on the HRQoL&#44; adherence&#44; use of health care resources&#44; and associated costs&#46; A standardized data mining form was used to draw the data from the selected articles&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The quality of included studies was assessed by two independent reviewers using the Strengthening the Reporting of Observational Studies in Epidemiology &#40;STROBE&#41; statement&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">16</span></a> resolving discrepancies by consensus&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">A total of 133 reports were initially identified &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; After duplicate removal and applying the established inclusion criteria&#44; 11 publications &#40;10 full-text articles and 1 conference abstract&#41; were included in the synthesis&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The main characteristics of selected articles are summarised in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Regarding the study design&#44; 54&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; of the studies were cross-sectional&#44; 27&#46;3&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; retrospective&#44; and 18&#46;2&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; prospective&#46; Inclusion criteria were heterogeneous regarding age range&#44; time from diagnosis&#44; diagnostic criteria&#44; severity&#44; and treatment patterns&#46; The information source included the review of health records or databases in 54&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; reports&#44; whereas in 36&#46;4&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41; of the publications&#44; information was retrieved through interviews conducted with the patients or their parents&#47;caregivers&#46; A total of 27&#46;3&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; of studies were eventually conducted in primary care health care settings&#44; 45&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41; in hospital health care settings&#44; and 18&#46;2&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; in both&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Population characteristics</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Age and gender</span><p id="par0075" class="elsevierStylePara elsevierViewall">Details on the population&#39;s age and gender are detailed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Four studies<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">21&#44;25&#8211;27</span></a> included a broad age spectrum from 6-month infants to younger than 18-year-old patients&#46; In contrast&#44; two studies<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">20&#44;23</span></a> focused on a narrower age range&#44; 12&#8211;15-month-olds&#44; and 6&#8211;7&#47;14&#8211;15-year-olds&#44; respectively&#46; Overall&#44; the most represented age group was from 2- to 15-year-olds&#46; Regarding gender&#44; the male&#47;female proportion was similar&#44; with the female representation varying from 42&#37; up to 54&#46;5&#37; according to different studies and age ranges&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Severity of AD</span><p id="par0080" class="elsevierStylePara elsevierViewall">Six studies<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;21&#44;25&#44;27</span></a> assessed the severity of AD using different tools&#44; including the Investigator&#39;s Global Assessment &#40;IGA&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;19&#44;21</span></a> the SCORing Atopic Dermatitis &#40;SCORAD&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> the Clinical Global Impressions scale &#8211; Severity of Illness &#40;CGI-SI&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> the Patient Global Assessment &#40;PtGA&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">25&#44;27</span></a> the Patient-Oriented Eczema Measure &#40;POEM&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a> and the physician&#39;s perspective<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Three studies focused on moderate-to-severe AD patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">18&#44;19&#44;21</span></a> while the other three studies included patients from all AD severities&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;25&#44;27</span></a> In the latter studies&#44; moderate AD was reported in 28&#46;8&#37; up to 50&#46;3&#37; of patients&#44; and severe AD in 4&#46;1&#37; up to 12&#46;6&#37; of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;25&#44;27</span></a> Mild AD was the most prevalent disease in two of those studies according to PtGA&#47;POEM<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">25&#44;27</span></a>&#59; while moderate AD was the most prevalent in study &#35;3 according to IGA&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Ortiz de Frutos et al&#46; used several tools to assess disease severity&#46; A total of 70&#46;7&#37; of pediatric patients had been initially diagnosed with moderate AD&#44; based on the specialist&#39;s best clinical judgment&#44; and&#44; therefore&#44; had been included in the study&#46; However&#44; at the time of medical consultation&#44; only 53&#46;4&#37; and 50&#46;9&#37; exhibited moderate-to-severe AD according to IGA and CGI-SI respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> Six percent of the patients had been initially included in the study as having moderate-to-severe AD&#44; but obtained a SCORAD score &#60;15&#44; which ended up categorizing their AD as mild&#46; In contrast&#44; Silverberg et al&#46; evaluated disease severity using PtGA and POEM&#44; observing similar rates&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Comorbidities</span><p id="par0095" class="elsevierStylePara elsevierViewall">Five studies<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;21&#44;22&#44;24&#44;27</span></a> provided specific data on comorbidities associated with AD in Spanish pediatric patients &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; An additional study<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a> listed comorbidities without providing prevalence percentages&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">One study presented aggregate data&#44; confirming that 84&#46;4&#37; of pediatric patients with AD had&#44; at least&#44; one comorbidity&#44; for a mean of 2&#46;5 comorbidities per patient&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> In general&#44; respiratory conditions such as asthma and allergies such as allergic rhinitis were the most widely reported conditions in the observational studies reviewed ranging from 2&#46;6&#37; up to 47&#37; and from 7&#46;9&#37; up to 50&#37;&#44; respectively&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Interestingly&#44; in the study conducted by Almenara-Blasco et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a> different gender-related comorbidity patterns were identified&#46; Mental health disorders&#44; dyslipidemia&#44; and respiratory conditions were more common among men&#44; whereas respiratory-allergic&#44; sensitive-digestive&#44; menstrual-dysphoric-metabolic&#44; and cardiometabolic conditions were more common among women &#40;percentages not provided&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a></p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Disease burden</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Epidemiology</span><p id="par0110" class="elsevierStylePara elsevierViewall">Six articles<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">20&#8211;25</span></a> provided epidemiological data&#44; including prevalence &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41; and incidence &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; of AD in the pediatric population of Spain&#46; The reported prevalence rates varied significantly across the studies ranging from 0&#46;01&#37; up to 30&#37; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Sicras-Mainar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a> assessed the prevalence of AD by different age groups&#44; with both overall and severe AD prevalence being higher in 6&#8211;12-year-olds &#40;11&#46;5&#37; vs 6&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; vs 13&#8211;18-year-olds &#40;0&#46;39&#37; vs 0&#46;23&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a> Similarly&#44; Arnedo-Pena et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a> reported a higher prevalence in adolescents older than 12 years vs younger children&#44; as well as in women compared to men in both 2002 and 2012 &#40;29&#46;80&#37; vs 21&#46;50&#37; and 41&#46;40&#37; vs 28&#46;30&#37;&#44; respectively&#41;&#46; This study also reported an increase in the prevalence ratio from 1994 &#40;1&#46;02 &#91;95&#37; CI&#44; 0&#46;86&#8211;1&#46;21&#93;&#41; through 2012 &#40;1&#46;41 &#91;95&#37; CI&#44; 1&#46;21&#8211;1&#46;73&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">For the incidence of AD&#44; data were drawn from two studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">23&#44;24</span></a> Arnedo-Pena et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a> identified a total of 182 new cases of AD from 1994 through 2002&#44; with an incidence rate of 15&#46;9 per 1000 persons years&#46; Darb&#224; and Mars&#224;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a> confirmed an incidence rate of AD from 2000 through 2017 of 5&#46;8 per 100&#44;000 persons&#44; with a higher incidence being reported in children aged 0&#8211;5 years &#40;30&#46;0 per 100&#44;000 persons&#41;&#44; and the overall incidence being stable throughout the study period&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a></p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Treatment patterns</span><p id="par0125" class="elsevierStylePara elsevierViewall">Three studies<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">19&#44;21&#44;22</span></a> assessed treatment patterns in pediatric patients with moderate-to-severe AD in Spain &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">The first-line therapy in children with moderate-to-severe AD was the use of emollients &#40;82&#46;8&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> followed by topical pharmacological treatment &#40;77&#46;6&#37;&#41; including corticosteroids&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> Systemic corticosteroids were also used in children starting at the age of 6 years &#40;37&#46;5&#37; up to 95&#46;4&#37;&#41; being cyclosporine &#40;40&#46;5&#37; up to 50&#37;&#41; and azathioprine &#40;23&#46;8&#37;&#41; the most widely used drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">21&#44;22</span></a> Only a small percentage of patients received biologic drugs &#40;1&#46;5&#37;&#41;&#44; in children older than 6 years&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Despite pediatric patients suffering from moderate-to-severe AD&#44; it was notable that 24&#46;1&#37; of patients reported not using any topical pharmacological treatment or delaying its use&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Patient-reported outcomes</span><p id="par0140" class="elsevierStylePara elsevierViewall">Three articles<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#8211;19</span></a> provided data on PROs covering aspects such as HRQoL &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#8211;19</span></a> treatment satisfaction &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> and treatment adherence &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">18&#44;19</span></a></p><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">HRQoL</span><p id="par0145" class="elsevierStylePara elsevierViewall">The impact of AD on the patients&#8217; HRQoL was evaluated using the children&#39;s version of the Dermatology Life Quality Index &#40;cDLQI&#41;&#44; the Infant&#39;s Dermatitis Quality of Life Index &#40;IDQoL&#41;&#44; and the children&#39;s version of the EADA &#40;<span class="elsevierStyleItalic">Escala de afectaci&#243;n de la dermatitis at&#243;pica</span>&#41; scale&#46; Lower scores represented less impairment and better HRQoL in all questionaries used&#44; with final scores ranging from 0 up to 30 in the cDLQI and IDQoL indexes&#44; and from 0 up to 10 in the EADA scale&#46; A summary of the results has been presented in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Two studies used the cDLQI&#58; one reported an overall score of 6&#46;1&#44; being symptoms and feelings &#40;2&#46;0&#41; and daily activities &#40;1&#46;8&#41; the most affected dimensions<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a>&#59; while the other reported overall mean scores of 3&#46;8&#44; 8&#46;8&#44; and 14&#46;5 based on disease severity &#40;mild&#44; moderate and severe or very severe&#44; respectively&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> Similarly to the cDLQI&#44; global IDQoL and EADA scores showed a moderate impact with mean scores of 7&#46;6 and 2&#46;5&#44; respectively in these moderate-to-severe patients&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Torrelo et al&#46; observed higher levels of emotional&#44; physical&#44; and social impairment in patients with severe AD vs patients with mild AD&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> Consistent with this&#44; in severe compared to mild ones&#44; individual cDLQI domain scores revealed a significantly higher impact on symptoms &#40;mean score&#44; 3&#46;4 &#91;SD&#44; 1&#46;8&#93; vs 1&#46;7 &#91;SD&#44; 1&#46;1&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; activities of daily living &#40;mean score&#44; 2&#46;8 &#91;SD&#44; 1&#46;6&#93; vs 0&#46;4 &#91;SD&#44; 1&#46;7&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; and leisure &#40;mean score&#44; 2&#46;9 &#91;SD&#44; 2&#46;2&#93; vs 0&#46;3 &#91;SD&#44; 0&#46;7&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> Furthermore&#44; AD led to changes in mood &#40;79&#46;9&#37;&#41;&#44; affecting feelings of restlessness &#40;91&#46;6&#37;&#41;&#44; concentration difficulties &#40;35&#46;3&#37;&#41;&#44; and depression &#40;7&#46;6&#37;&#41;&#44; particularly among those with severe AD&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> AD significantly impaired patients&#8217; daily life in all severity groups&#44; with 24&#46;5&#37; of the overall sample experiencing strong or very strong pruritus&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> Sleep was deprived by pruritus&#44; with most patients with moderate-to-severe AD reporting difficulty falling asleep &#40;90&#46;1&#37; with moderate AD and 87&#46;5&#37; with severe AD&#41;&#44; and a proportion of them awakening at night time &#40;76&#46;8&#37; with moderate AD and 97&#46;5&#37; with severe AD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Treatment satisfaction and adherence</span><p id="par0160" class="elsevierStylePara elsevierViewall">Treatment satisfaction and adherence were evaluated in patients using topical pharmacological maintenance treatment for flare-ups prevention&#46; Overall&#44; patients expressed high satisfaction &#40;7&#46;2&#41;&#44; evaluated using a Visual Analogue Scale &#40;VAS 0-10&#41;&#44; with no significant differences regarding disease severity&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> However&#44; treatment adherence&#44; reported by the Morisky&#8211;Green test&#44; was low &#40;18&#46;4&#37;&#41;&#44; with 49&#46;9&#37; of the patients admitting to occasionally forgetting applying treatment&#44; and 34&#46;0&#37; admitting not adhering to it during symptom-free periods&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> In contrast&#44; another study found that most patients adhered to the pharmacological treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> Discrepancies were found between physicians and patients&#8217; perceptions of reported compliance&#46; While dermatologists considered that many of their patients complied with maintenance treatment &#40;88&#46;7&#37;&#41;&#44; the percentage of patients who declared themselves as compliant was lower &#40;18&#46;4&#37; up to 42&#46;6&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> Interestingly enough&#44; patients rated excellent&#44; good&#44; or sufficient disease control in 62&#46;7&#37; of cases while dermatologists did so in 40&#46;5&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a></p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Use of resources and associated costs</span><p id="par0165" class="elsevierStylePara elsevierViewall">Only one report showed data on specialized care resource use and associated costs in pediatric patients &#40;&#60;5 years old&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The study conducted from 2000 through 2017 included 84&#46;3&#37; of ER admissions with a mean length of stay 4&#46;3 days&#46; The most common medical procedures upon admission included blood microscopic examination &#40;30&#46;6&#37;&#41;&#44; steroid injections &#40;18&#46;6&#37;&#41;&#44; antibiotics &#40;12&#46;1&#37;&#41;&#44; and skin biopsies &#40;14&#46;3&#37;&#41;&#46; Additionally&#44; pharmacological interventions registered in primary care centers involved the administration of antibiotics &#40;8&#46;7&#37;&#41;&#44; corticosteroids &#40;topical&#44; 25&#46;7&#37;&#59; systemic&#44; 17&#46;8&#37;&#41;&#44; analgesics &#40;paracetamol&#44; 27&#46;1&#37;&#59; ibuprofen&#44; 20&#46;2&#37;&#59; other&#44; 28&#46;3&#37;&#41;&#44; and antihistamines &#40;14&#46;3&#37;&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The mean annual direct medical costs per patient were estimated at &#8364;2310&#46; These costs were mostly stable within the first half of study period &#40;&#8364;1500&#8211;&#8364;2500&#47;per patient approx&#46;&#44; 2000&#8211;2009&#41;&#44; with a major increase being observed from 2009 through 2010 up to &#8364;4000&#47;per patient &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; followed by a decreasing trend in the 2011&#8211;2017 period&#44; back to 2500&#8364;&#47;per patient approx&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0180" class="elsevierStylePara elsevierViewall">Our systematic review synthesized findings from 11 observational studies providing an overview of the population characteristics&#44; burden of disease&#44; epidemiology&#44; treatment patterns&#44; PROs&#44; use of resources and costs associated with the management of AD in pediatric Spanish patients&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Based on the studies assessing the severity of AD&#44; we could conclude that differences in classification may derive from the use of different instrument measures&#46; The observed results suggested that the use of PRO measures such as PtGA and POEM would correlate well between them&#46; However&#44; the results obtained using clinical measures such IGA or CGI-SI might underestimate the severity vs the results obtained using SCORAD&#44; as it combines the clinical and the patient perspective&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Among the studies included in our review that reported data on comorbidities&#44; respiratory diseases and allergies were found to be the most common&#46; Notably&#44; one of the studies of pediatric patients with severe AD reported a high prevalence &#40;&#62;70&#37;&#41; of mental illnesses&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;21&#44;22&#44;24&#44;27</span></a> In this context&#44; there is evidence of a significant association between AD in children and mental health symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">28</span></a> A longitudinal&#44; population-based birth control cohort study found that children with severe AD were &#62;2-fold more likely to have symptoms of depression vs those without AD&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">28</span></a> Additionally&#44; children with AD were more likely to internalize behaviors&#44; such as anxiety or somatic complaints&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">28</span></a> Moreover&#44; a higher prevalence of ADHD in pediatric AD patients has been reported too&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">29</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">As seen in the three studies included in our review&#44; AD affects not only the emotional domain but also other domains of HRQoL&#44; as physical and social impairment&#44; particularly in severe AD&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#8211;19</span></a> Pruritus is the symptom with the greatest impact on HRQoL&#44; as it negatively interferes with sleep quality&#44; mood swings and restlessness&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">8</span></a> Consistent with this&#44; AD has been pointed out to be the most common skin disease that causes the greatest impairment in HRQoL on account of symptoms such as pruritus and insomnia&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">30</span></a> One study revealed that 79&#37; of children with AD reported sleep disturbances&#44;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">31</span></a> even among patients with mild and inactive disease&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">32</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">The prevalence data from the analyzed studies revealed wide heterogeneity&#46; For instance&#44; significant variability in AD prevalence and incidence was observed across regions and age groups&#46; This variability could be attributed to variations in study methodologies and design&#44; research settings and AD definitions&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">AD prevalence is heterogeneous&#44; generally ranging from 10&#37; up to 30&#37; even for younger children younger than 2 years&#44; suggesting an early onset during childhood&#46; This early onset is usually associated with genetic predisposition and environmental factors&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">33</span></a> Although gender difference patterns seemed nonsignificant&#44; the long study conducted by Arnedo-Pena et al&#46; in a small region of Spain from 1994 though 2012 resulted in women showing a higher prevalence of AD&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a> a trend not yet seen in the real-world global study conducted by Silverberg et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a> including 18 countries&#46; An increasing trend in AD prevalence in Spain was observed from 1994 through 2012&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a> In contrast&#44; a decrease in AD prevalence from 22&#46;8&#37; &#40;1996&#41; down to 21&#46;3&#37; &#40;2006&#41;&#44; and down to 16&#46;3&#37; &#40;2017&#41; was seen&#44; for example&#44; in Sweden&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">34</span></a> highlighting geographical variations&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Regarding AD incidence&#44; in our review a stable trend in children aged 0&#8211;5 years from 2000 through 2017 was observed&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a> Similarly&#44; a study from Denmark and Sweden supports this stability&#44; with consistent incidence rates throughout time&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">35</span></a> This stability suggests unchanged risk factors for AD development in this age group&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">34</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">In Spain&#44; the current AD treatment guidelines for pediatric population suggest an adequate skin hydration and use of topical corticosteroids&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">36</span></a> which is consistent with the treatment patterns reported in the reviewed studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">19&#44;20</span></a> yet we should mention that 24&#46;1&#37; of moderate-to-severe patients delayed initiation&#44; or did not apply topical pharmacological maintenance treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> The treatment adherence was low despite the patient&#39;s expressed satisfaction with treatment<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> and regardless of disease severity&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">37</span></a> We should&#44; also&#44; mention the different perceptions between patients and specialists in the field&#44; with specialists often overestimating the patient&#39;s compliance with the recommendations and prescribed treatment application&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">The use of biologic drugs as the treatment of choice among pediatric patients seemed to be limited&#44; with only 1&#46;5&#37; of patients older than 6 years benefiting from this option&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a> This limited usage of biologics in the Spanish pediatric population may be due to their very recent authorization for use and access barriers that might have prevented their prescription&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">38</span></a> However&#44; biologic drugs may provide adequate control in moderate-to-severe cases&#44; covering an unmet need in this pediatric population&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">39</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Of note the significant gap in the literature on the economic burden of pediatric AD in Spain&#46; While several studies have focused on the economic implications on adult patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">40&#44;41</span></a> pediatric population research is lacking&#44; despite existing research in other European countries highlighting important secondary care use of resources such as outpatient visits and pharmacy dispensations&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">42</span></a> The mean direct medical cost in Sweden &#40;SD&#41; was estimated at &#8364;1111 &#40;3416&#41; and &#8364;1906 &#40;7067&#41; for mild-to-moderate and severe AD&#44; respectively&#44; which is consistent with the Spanish data retrieved in our review&#46; Nonetheless&#44; there is a need for more targeted studies in this area&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">This review presents some limitations&#46; Variations in the definition and severity of AD across different scales had implications for the comparability and generalizability of our findings&#46; Additionally&#44; the heterogeneity in the available data&#44; including differences in study design&#44; data collection methods&#44; and outcome measures&#44; complicated result interpretation&#46; Moreover&#44; the methodologies and target populations also differed across studies&#44; leading to variable results&#46; There was a lack of comprehensive data on the use of resources and costs associated with AD in the pediatric population&#44; which limits our understanding of the economic burden associated with AD&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conclusions</span><p id="par0235" class="elsevierStylePara elsevierViewall">This systematic review provides a comprehensive picture of the clinical&#44; humanistic and economic burden of AD in pediatric patients in Spain&#44; which may be beneficial for physicians and health care decision makers who manage this condition&#44; as well as researchers seeking to determine the gaps in knowledge that remain that need to be addressed in future research studies&#46; The high prevalence and early onset highlight the need for comprehensive&#44; patient-focused care tailored to this subpopulation&#46; Despite the existence of established treatment guidelines&#44; low adherence to treatment indicates a need for developing better and more effective strategies&#46; On the other hand&#44; biological therapy&#44; including newly available treatments and small molecule JAK inhibitors&#44; present a promising opportunity for innovation and expansion in therapeutic interventions&#46; As modern and effective management strategies are developed&#44; these key factors should be considered to improve patient outcomes&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Ethical approval</span><p id="par0240" class="elsevierStylePara elsevierViewall">This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Funding</span><p id="par0245" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleGrantSponsor" id="gs1">Eli Lilly</span> sponsored this study and the publication of this article&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Authors&#8217; contributions</span><p id="par0250" class="elsevierStylePara elsevierViewall">Rosa Moro&#44; Silvia D&#237;az-Cerezo&#44; Luis Liz&#225;n and Mercedes N&#250;&#241;ez contributed to the conception of the work&#44; the design&#44; the acquisition&#44; and analysis of the data&#46; All authors participated in the interpretation of data for the work&#44; the critical revision of the manuscript and approved the final submitted version&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of interest</span><p id="par0255" class="elsevierStylePara elsevierViewall">Antonio Torrelo Fern&#225;ndez is member of the advisory board of Eli Lilly and Viatris&#44; has received speaker fees from Eli Lilly&#44; Viatris&#44; Pfizer&#44; Sanofi&#44; and Novartis&#44; and fees for attending meetings from Sanofi and Pierre Fabre&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Asunci&#243;n Vicente is member of the advisory board of Eli Lilly and Amryt&#44; has received consulting fees from Abbvie&#44; Amgen&#44; Amryt&#44; Boehringer Ingelheim&#44; Bristol-Myers Squibb&#44; Eli Lilly&#44; Novartis&#44; Pierre Fabre and Sanofi Genzyme&#44; speaker fees from Abbvie&#44; Amgen&#44; Amryt&#44; Boehringer Ingelheim&#44; Bristol-Myers Squibb&#44; Ferrer&#44; Galderma&#44; Janssen&#44; Eli Lilly&#44; Novartis&#44; Pierre Fabre&#44; Pfizer&#44; and Sanofi Genzyme and fees for attending meetings from Abbvie&#44; Almirall&#44; Amgen&#44; Amryt&#44; Boehringer Ingelheim&#44; Bristol-Myers Squibb&#44; Ferrer&#44; Galderma&#44; Eli Lilly&#44; Novartis&#44; Pierre Fabre&#44; Pfizer&#44; and Sanofi Genzyme&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Ana Martin-Santiago has received speaker fees from Abbvie&#44; Amgen&#44; Leo-Pharma&#44; Leti&#44; Novartis&#44; Pfizer&#44; and Sanofi&#44; payments for her expert testimony from Abbvie&#44; Amryt&#44; Leo-Pharma&#44; Pfizer&#44; and Sanofi&#44; and fees for attending meetings from Abbvie&#44; Almirall&#44; Janssen&#44; Leo-Pharma&#44; Leti&#44; Eli Lilly&#44; Novartis&#44; Pfizer&#44; Pierre Fabre&#44; Sanofi&#44; UCB and Viatrix&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Ra&#250;l de Lucas Laguna is member of the advisory board of Novartis&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; Sanofi&#44; Leo-Pharma&#44; Johnson &#38; Johnson&#44; UCB&#44; Almirall&#44; Galderma&#44; LetiPharma&#44; has received consulting fees from Novartis&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; Sanofi&#44; Leo-Pharma&#44; Johnson &#38; Johnson&#44; UCB&#44; Almirall&#44; Galderma&#44; and LetiPharma&#44; speaker fees from Novartis&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; Sanofi&#44; LetiPharma&#44; Johnson &#38; Johnson&#44; UCB&#44; Almirall&#44; Galderma&#44; and LetiPharma&#44; payments for his expert testimony from Novartis&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; Sanofi&#44; LetiPharma&#44; Johnson &#38; Johnson&#44; UCB&#44; Almirall&#44; Galderma&#44; and LetiPharma&#44; and support for attending meetings from Novartis&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; Sanofi&#44; Leo-Pharma&#44; Johnson &#38; Johnson&#44; UCB&#44; Almirall&#44; Galderma&#44; and LetiPharma&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Jos&#233; Carlos Armario Hita is member of the advisory board of Abbvie&#44; Novartis&#44; Lilly&#44; Sanofi&#44; Galderma&#44; Leo-Pharma&#44; Janssen&#44; Pfizer&#44; UCB farma&#44; and Almirall&#44; has received consulting fees from Abbvie&#44; Novartis&#44; Lilly&#44; Sanofi&#44; Galderma&#44; Leo-Pharma&#44; Janssen&#44; Pfizer&#44; UCB farma&#44; Almirall&#44; speaker fees from Abbvie&#44; Novartis&#44; Lilly&#44; Sanofi&#44; Galderma&#44; Leo-Pharma&#44; Janssen&#44; Pfizer&#44; UCB farma&#44; Almirall&#44; and fees for attending meetings from Abbvie&#44; Novartis&#44; Lilly&#44; Sanofi&#44; Galderma&#44; Leo-Pharma&#44; Janssen&#44; Pfizer&#44; UCB farma&#44; and Almirall&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Rosa Moro&#44; Silvia D&#237;az-Cerezo and Mercedes N&#250;&#241;ez are employees of Eli Lilly&#46; Luis Liz&#225;n works as an independent scientific consultant &#40;Outcomes&#8217;10&#41; and declared to have received honoraria for conducting the systematic literature review and manuscript drafting tasks&#46;</p></span></span>"
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          "titulo" => "Introduction"
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              "titulo" => "Data sources and search strategy"
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            1 => array:2 [
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Atopic dermatitis &#40;AD&#41; is a chronic&#44; inflammatory skin disease affecting all age groups&#44; particularly children&#46; This systematic review provides an overview of the humanistic and economic disease burden in the pediatric population with AD in Spain&#46; The evidence&#44; collected from 11 observational studies published over the past 10 years&#44; exhibits the most common characteristics of the patients&#44; disease burden&#44; patient-reported outcomes&#44; use of resources&#44; and treatment patterns&#46; The burden of AD extends beyond physical symptoms&#44; with associated comorbidities such as asthma and impaired health-related quality of life and mental health disorders&#44; particularly in severe cases&#46; Traditional therapies&#44; primarily topical corticosteroids&#44; face adherence and efficacy challenges&#46; Despite promising innovative treatments and available biological therapies&#44; their use is still limited in the pediatric population&#46; The findings of the present review highlight the scarce scientific evidence on the economic burden of pediatric AD&#44; as well as the most updated humanistic evidence on this disease&#46; At the same time&#44; the need for individualized care and innovative therapeutic interventions to address the multifaceted challenges of pediatric AD in Spain is evident&#46;</p></span>"
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        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La dermatitis at&#243;pica &#40;DA&#41; es un trastorno cut&#225;neo cr&#243;nico e inflamatorio que afecta a todos los grupos de edad&#44; pero especialmente a los ni&#241;os&#46; Esta revisi&#243;n sistem&#225;tica proporciona una visi&#243;n general de la carga de la enfermedad en la poblaci&#243;n pedi&#225;trica con DA en Espa&#241;a&#46; La evidencia recopilada de 11 estudios observacionales publicados en los &#250;ltimos 10 a&#241;os presenta las caracter&#237;sticas m&#225;s comunes de los pacientes&#44; la carga de la enfermedad&#44; los resultados reportados por los pacientes&#44; el uso de recursos y los patrones de tratamiento m&#225;s frecuentes&#46; La carga de la DA se extiende m&#225;s all&#225; de los s&#237;ntomas f&#237;sicos&#44; con comorbilidades asociadas como el asma&#44; el deterioro de la calidad de vida relacionada con la salud y trastornos de salud mental&#44; particularmente en los casos graves&#46; Los tratamientos tradicionales&#44; principalmente los corticosteroides t&#243;picos&#44; enfrentan desaf&#237;os de adherencia y eficacia&#46; A pesar de las prometedoras innovaciones terap&#233;uticas y la disponibilidad de terapias biol&#243;gicas&#44; su uso permanece limitado en poblaci&#243;n pedi&#225;trica&#46; Los resultados de la presente revisi&#243;n resaltan la escasa evidencia cient&#237;fica sobre la carga econ&#243;mica de la DA pedi&#225;trica&#44; as&#237; como la evidencia human&#237;stica m&#225;s actualizada de la enfermedad&#46; Asimismo&#44; se hace patente la necesidad de una atenci&#243;n personalizada e intervenciones terap&#233;uticas innovadoras para abordar los desaf&#237;os multifac&#233;ticos de la DA pedi&#225;trica en Espa&#241;a&#46;</p></span>"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">PRISMA flow diagram with the selection process of the included publications&#46; IBECS&#44; &#205;ndice Bibliogr&#225;fico Espa&#241;ol en Ciencias de la Salud&#59; MEDES&#44; Medicina en Espa&#241;ol&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1284
            "Ancho" => 3439
            "Tamanyo" => 213139
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AD severity&#46; &#40;A&#41; Studies including mild&#44; moderate and severe patients measured with IGA&#44; PtGA and POEM&#46; &#40;B&#41; Studies restricted to moderate-to-severe patients measured with SCORAD&#44; IGA&#44; CGI-SI&#44; IGA and medical history&#46; NA&#44; not available&#59; <span class="elsevierStyleSup">a</span>IGA has six categories of response and its score ranges from 0 &#40;no illness&#44; with no inflammatory signs of AD&#41; up to 5 &#40;very serious illness&#44; with intense erythema and intense papule&#47;infiltration with crusts&#47;exudation&#41;&#46; Barroso et al&#46; ranged severity from 0 up to 4&#44; considering scores of 3 as moderate and scores of 4 as severe AD&#59; <span class="elsevierStyleSup">b</span>Patient Global Assessment &#40;PtGA&#41;&#44; which asks&#44; &#8220;Please check one answer that best describes the severity of your or your child&#39;s eczema over the past week&#44;&#8221; with responses of clear&#44; mild&#44; moderate&#44; or severe&#59; <span class="elsevierStyleSup">c</span>Patient-Oriented Eczema Measure &#40;POEM&#41;&#44; with a total score ranging from 0 &#40;lower severity&#41; up to 28 &#40;higher severity&#41;&#59; severity groupings have been defined as bands of 0&#8211;7 indicating mild AD&#44; 8&#8211;16 moderate AD&#44; and &#62;16 severe AD&#59; <span class="elsevierStyleSup">d</span>SCORAD takes into account the extent and intensity of the lesions&#44; as well as the symptoms &#40;pruritus and loss of sleep&#41; it causes&#59; extent &#40;A&#41;&#58; the body surface is divided into four segments &#40;head and neck&#44; trunk&#44; upper and lower extremities&#41; to which a percentage is assigned based on the extent represented&#59; intensity &#40;B&#41;&#59; <span class="elsevierStyleSup">e</span>The Clinical Global Impression &#8211; Severity scale &#40;CGI-S&#41; is a valuable tool used by clinicians to assess the severity of a patient&#39;s illness vs their past experience with similar diagnoses&#46; It involves rating the patient&#39;s current condition on a 7-point scale&#44; reflecting different levels of illness severity&#58; &#40;1&#41; normal&#44; not at all ill&#44; &#40;2&#41; borderline mentally ill&#44; &#40;3&#41; mildly ill&#44; &#40;4&#41; moderately ill&#44; &#40;5&#41; markedly ill&#44; &#40;6&#41; severely ill&#44; and &#40;7&#41; extremely ill&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1690
            "Ancho" => 3167
            "Tamanyo" => 225436
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Comorbidities associated with pediatric AD&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1546
            "Ancho" => 2392
            "Tamanyo" => 109554
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Prevalence of pediatric AD in Spanish population by different age groups&#46; Blue dots correspond to overall prevalence while orange dots correspond to severe AD&#59; yr&#44; years&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figure 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 1625
            "Ancho" => 2667
            "Tamanyo" => 162854
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Treatment patterns&#46;</p>"
        ]
      ]
      5 => 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"
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        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">AD&#44; atopic dermatitis&#59; PROs&#44; patient-reported outcomes&#59; HRQoL&#44; health-related quality of life&#59; NA&#44; not available&#59; X marks the reported variables in each study&#46;</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-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Author &#40;year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study characteristics</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Main variables</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Source&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Health care setting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size &#40;<span class="elsevierStyleItalic">N</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Demographic and clinical characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Epidemiology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment patterns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PROs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HRU&#47;costs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#225;nchez-P&#233;rez &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Medical chart review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary care&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#8805;2 to &#60;18 years&#44; &#8805;1 year since AD diagnosis &#40;Hanifin and Rajka criteria&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">151&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- HRQoL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Torrelo &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patient interviews&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#8805;2 to &#60;15 years&#46; Moderate-to-severe AD &#40;Hanifin and Rajka criteria&#41;&#44; &#8805;16-month history of AD&#44; topical treatment &#8805;4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- HRQoL- Satisfaction- Adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ortiz de Frutos &#40;2014&#41;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Medical chart review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#8805;2 to &#60;15 years&#46; Clinically diagnosed moderate-to-severe AD &#40;specialist&#39;s judgment&#44; excluding mild AD&#41;&#44; &#8805;12-month history of AD&#44; IGA &#62;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">116&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- HRQoL- Adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Draaisma &#40;2015&#41;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Parent or caregiver interviews&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary care&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#62;12 to &#60;15 month-old infants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6937&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Barroso &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Electronic health records&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#60;18 years with moderate-to-severe AD &#40;IGA &#62;3&#41;&#44; treatments<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sicras-Mainar &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Review of medical records &#40;computerized databases&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary care and hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#8805;6 years&#44; AD diagnosis &#8805;1 year prior to the index date&#44; prescribed medication&#44; &#8805;2 prescriptions at the follow-up&#44; regular monitoring with &#8805;2 health records&#44; including a visit to the dermatology unit&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#44;374 with AD844 with severe AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Arnedo-Pena &#40;2020&#41;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patient interviews&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3607 &#40;1st survey&#44; 1994&#41;1805 &#40;2nd survey&#44; 2002&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Prevalence- Incidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Darb&#224; &#40;2021&#41;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Database&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary care and hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1266&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Incidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Silverberg &#40;2021&#41;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patient interviews&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#62;6 months to 18 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3465&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Almenara-Blasco &#40;2022&#41;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Medical chart review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary care&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;757&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#225;zaro &#40;2022&#41;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a>&#91;ABSTRACT SEAIC 2022&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#62;6 months to 18 years&#44; diagnosed with AD &#40;criteria-based&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">564&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  <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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Author &#40;year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Sample size &#40;<span class="elsevierStyleItalic">N</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Population age&#44; yr<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</a></th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Mean age&#44; years &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Gender&#44; female &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">0&#46;5&#8211;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2&#8211;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">5&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">15&#8211;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#225;nchez-P&#233;rez &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">151&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;4 &#40;4&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Torrelo &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;7 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ortiz de Frutos &#40;2014&#41;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">161&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;7 &#40;3&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Draaisma &#40;2015&#41;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6937&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#8211;15 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">46&#46;9&#8211;50&#46;1<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Barroso &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#60;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sicras-Mainar &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#44;374 with AD844 with severe AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#8211;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#8211;12 yr&#58; 9&#46;1 &#40;2&#46;0&#41;13&#8211;18 yr&#58; 14&#46;8 &#40;1&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#8211;12 yr&#58; 4213&#8211;18 yr&#58; 51&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Arnedo-Pena &#40;2020&#41;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3607&#40;year 1994&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#8211;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;3 &#40;0&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1805&#40;year 2002&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;4 &#40;0&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Darb&#224; &#40;2021&#41;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1266&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Silverberg &#40;2021&#41;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3465&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5&#8211;&#60;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 mo&#8211;&#60;6 yr&#58; 3&#46;26&#8211;&#60;12 yr&#58; 9&#46;212&#8211;&#60;18 yr&#58; 14&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 mo&#8211;&#60;6yr&#58; 54&#46;56&#8211;&#60;12 yr&#58; 45&#46;112&#8211;&#60;18 yr&#58; 46&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Almenara-Blasco &#40;2022&#41;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;757&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#225;zaro &#40;2022&#41;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">564&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5&#8211;&#60;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3653833.png"
              ]
            ]
          ]
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            0 => array:3 [
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author &#40;year&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Disease severity&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tool &#40;score range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overall score&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Symptoms and feelings&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Activities of daily living&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Leisure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Interpersonal relationships&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#225;nchez-P&#233;rez &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">cDLQI<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a> &#40;0&#8211;30&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;6<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;0<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe or very severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;1<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;8<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;6<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Torrelo &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate-to-severe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">cDLQI<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a> &#40;0&#8211;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EADA<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">b</span></a> &#40;0&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ortiz de Frutos &#40;2014&#41;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate-to-severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EADA<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">b</span></a> &#40;0&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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Review
Humanistic and Economic Burden of Atopic Dermatitis in Pediatric Patients in Spain: A Systematic Review
Carga humanística y económica de la dermatitis atópica en pacientes pediátricos en España: una revisión sistemática
A. Torrelo Fernándeza, A. Vicenteb, A. Martin-Santiagoc, R. de Lucas Lagunad, J.C. Armario-Hitae, R. Morof, S. Díaz-Cerezof, L. Lizáng,h, M. Núñezf,
Autor para correspondencia
nunez_mercedes@lilly.com

Corresponding author.
a Servicio de Dermatología, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
b Servicio de Dermatología, Hospital Sant Joan de Deu Barcelona, Universidad de Barcelona, Esplugues de Llobregat, Barcelona, Spain
c Servicio de Dermatología, Hospital Universitario Son Espases, Palma de Mallorca, Islas Baleares, Spain
d Servicio de Dermatología, Hospital Universitario La Paz, Madrid, Spain
e Servicio de Dermatología, Hospital Punta de Europa, Algeciras, Universidad de Cádiz, Cádiz, Spain
f Eli Lilly and Company, Madrid, Spain
g Outcomes’10, S.L., Castellón de la Plana, Spain
h Departamento de Medicina, Universidad Jaume I, Castellón de la Plana, Spain
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            "entidad" => "Servicio de Dermatolog&#237;a&#44; Hospital Sant Joan de Deu Barcelona&#44; Universidad de Barcelona&#44; Esplugues de Llobregat&#44; Barcelona&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Servicio de Dermatolog&#237;a&#44; Hospital Universitario Son Espases&#44; Palma de Mallorca&#44; Islas Baleares&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Servicio de Dermatolog&#237;a&#44; Hospital Universitario La Paz&#44; Madrid&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
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          4 => array:3 [
            "entidad" => "Servicio de Dermatolog&#237;a&#44; Hospital Punta de Europa&#44; Algeciras&#44; Universidad de C&#225;diz&#44; C&#225;diz&#44; Spain"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Eli Lilly and Company&#44; Madrid&#44; Spain"
            "etiqueta" => "f"
            "identificador" => "aff0030"
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            "entidad" => "Outcomes&#8217;10&#44; S&#46;L&#46;&#44; Castell&#243;n de la Plana&#44; Spain"
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            "identificador" => "aff0035"
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            "entidad" => "Departamento de Medicina&#44; Universidad Jaume I&#44; Castell&#243;n de la Plana&#44; Spain"
            "etiqueta" => "h"
            "identificador" => "aff0040"
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        "titulo" => "Carga human&#237;stica y econ&#243;mica de la dermatitis at&#243;pica en pacientes pedi&#225;tricos en Espa&#241;a&#58; una revisi&#243;n sistem&#225;tica"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Atopic dermatitis &#40;AD&#41; is a prevalent&#44; chronic&#44; relapsing&#44; and inflammatory skin disorder of a multifactorial etiology characterized by intense itching and skin lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a> AD is a global disease that affects individuals across all age groups&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">2</span></a> The prevalence of AD among the pediatric population is notably high&#44; with estimates indicating that 15&#37; up to 30&#37; of children seem to be affected by this disease<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">3&#8211;5</span></a> vs a slightly lower prevalence among the adult population ranging from 7&#37; up to 14&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">2</span></a> The prevalence of AD among Spanish children remains unclear due to the lack of comprehensive&#44; age-specific studies and scarce available data&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">AD in pediatric patients is often associated with a range of comorbidities&#44; including other diseases such as asthma or allergic rhinitis&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">1</span></a> Additionally&#44; psychiatric and psychological disorders are likely to be more prevalent in this population&#46; In fact&#44; there is evidence of an increased incidence of mental issues&#44; such as attention deficit hyperactivity disorder &#40;ADHD&#41; and depression&#44; which can also manifest as suicide ideation among these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">1&#44;6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The presence of these comorbidities&#44; along with symptoms of AD such as intense pruritus&#44; significantly impairs health-related quality of life &#40;HRQoL&#41;&#44; especially in severe cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">6&#44;8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Due to disease heterogeneity&#44; comorbidities&#44; complexity in treatment care and differences between national or regional health care systems&#44; managing AD in the pediatric population remains challenging&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">9</span></a> Short regimens of topical corticosteroids are the most widely prescribed treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">10</span></a> However&#44; adherence to these conventional therapies is often low&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> and their efficacy in severe cases is also limited&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#44;13</span></a> Fortunately&#44; in recent years&#44; innovative&#44; and highly effective treatments have emerged such as biologic drugs and Janus kinase &#40;JAK&#41; inhibitors&#46; However&#44; their use in children is still restricted in some cases&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">10</span></a> As a matter of fact&#44; the substantial humanistic burden of disease in patients with moderate-to-severe AD suggests potential undertreatment in this group&#44; with few evidence available on new therapies&#44; patient-reported outcomes &#40;PROs&#41;&#44; AD severity and impairment&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> On the other hand&#44; AD represents a substantial economic burden on the health system&#44; as well as on the patients and caregivers&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> The total direct cost was estimated to be nearly &#8364;2700 per patient per year&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> As expected&#44; the severity of the condition had a direct impact on cost&#44; with severe cases resulting in higher costs&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">14</span></a> Specifically&#44; compared with patients with mild and moderate AD&#44; severe AD presented significantly higher total direct costs &#40;&#8364;1512 &#91;SD&#44; 854&#93; and &#8364;1984 &#91;SD&#44; 2093&#93; vs &#8364;5377 &#91;SD&#44; 3&#46;518&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; respectively&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">There is no available comprehensive&#44; updated information on the humanistic&#44; and economic burden associated with children with AD in Spain&#46; This systematic review aims to provide an overview based on the most recent Spanish real-world evidence&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">We conducted a systematic review of observational studies on the humanistic and economic burden associated with pediatric patients with AD over the past 10 years &#40;from March 2013 through March 2023&#41; following the recommendations established by the &#8220;Preferred Reporting Items of Systematic Reviews and Meta-analysis&#8221; &#40;PRISMA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">15</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Data sources and search strategy</span><p id="par0035" class="elsevierStylePara elsevierViewall">The international PubMed&#47;MEDLINE&#44; Cochrane Library&#44; the Spanish national <span class="elsevierStyleItalic">Medicina en Espa&#241;ol</span> &#40;MEDES&#41;&#44; and <span class="elsevierStyleItalic">&#205;ndice Bibliogr&#225;fico Espa&#241;ol en Ciencias de la Salud</span> &#40;IBECS&#41; databases were searched to identify relevant publications for review&#46; Additionally&#44; manual searches in the grey literature &#40;Google and Google Scholar&#41; were conducted to identify documents such as non-indexed articles and conference abstracts published over the past 3 years at key national and European congresses organized by the following medical societies&#58; Spanish Academy of Dermatology and Venerology &#40;AEDV&#41;&#44; Spanish Society of Allergology and Clinical Immunology &#40;SEAIC&#41;&#44; European Academy of Dermatology and Venereology &#40;EADV&#41;&#44; American Academy of Dermatology &#40;AAD&#41; and Society for Pediatric Dermatology &#40;SDP&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The different databases were searched using both free-text and MeSH &#40;medical subject headings&#41; terms&#44; combined with the Boolean connectors OR and AND&#46; The list of terms and search strategy are detailed in <a class="elsevierStyleCrossRef" href="#sec0125">Table S1 of the supplementary data</a>&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Study selection</span><p id="par0045" class="elsevierStylePara elsevierViewall">Two reviewers independently screened all identified articles at two levels &#40;levels 1 and 2&#41;&#46; Level 1 consisted of a broad screening based on article titles and&#47;or abstracts&#44; as available&#46; Level 2 involved two reviewers who independently reviewed the full-text articles and applied the inclusion&#47;exclusion criteria&#46; At both levels&#44; discrepancies were resolved by consensus or with the involvement of a third team member&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Eligibility criteria</span><p id="par0050" class="elsevierStylePara elsevierViewall">Observational studies conducted in Spain including pediatric population &#40;&#60;18 years&#41; with a confirmed diagnosis of AD by dermatologists&#47;physicians published in English or Spanish from March 2013 through March 2023 were eligible&#46; Studies conducted out of Spain were included when specific data from the Spanish population were provided&#46; <a class="elsevierStyleCrossRef" href="#sec0125">Table S2 of the supplementary data</a> lists the inclusion and exclusion criteria&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Data mining and quality assessment</span><p id="par0055" class="elsevierStylePara elsevierViewall">Data mining included data on the epidemiology of the disease &#40;prevalence and incidence&#41;&#44; patients&#8217; characteristics &#40;demographic&#44; comorbidities&#41;&#44; patterns on use of treatment&#44; PROs&#44; impact of the disease on the HRQoL&#44; adherence&#44; use of health care resources&#44; and associated costs&#46; A standardized data mining form was used to draw the data from the selected articles&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The quality of included studies was assessed by two independent reviewers using the Strengthening the Reporting of Observational Studies in Epidemiology &#40;STROBE&#41; statement&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">16</span></a> resolving discrepancies by consensus&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">A total of 133 reports were initially identified &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; After duplicate removal and applying the established inclusion criteria&#44; 11 publications &#40;10 full-text articles and 1 conference abstract&#41; were included in the synthesis&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The main characteristics of selected articles are summarised in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Regarding the study design&#44; 54&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; of the studies were cross-sectional&#44; 27&#46;3&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; retrospective&#44; and 18&#46;2&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; prospective&#46; Inclusion criteria were heterogeneous regarding age range&#44; time from diagnosis&#44; diagnostic criteria&#44; severity&#44; and treatment patterns&#46; The information source included the review of health records or databases in 54&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; reports&#44; whereas in 36&#46;4&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41; of the publications&#44; information was retrieved through interviews conducted with the patients or their parents&#47;caregivers&#46; A total of 27&#46;3&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; of studies were eventually conducted in primary care health care settings&#44; 45&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41; in hospital health care settings&#44; and 18&#46;2&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; in both&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Population characteristics</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Age and gender</span><p id="par0075" class="elsevierStylePara elsevierViewall">Details on the population&#39;s age and gender are detailed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Four studies<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">21&#44;25&#8211;27</span></a> included a broad age spectrum from 6-month infants to younger than 18-year-old patients&#46; In contrast&#44; two studies<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">20&#44;23</span></a> focused on a narrower age range&#44; 12&#8211;15-month-olds&#44; and 6&#8211;7&#47;14&#8211;15-year-olds&#44; respectively&#46; Overall&#44; the most represented age group was from 2- to 15-year-olds&#46; Regarding gender&#44; the male&#47;female proportion was similar&#44; with the female representation varying from 42&#37; up to 54&#46;5&#37; according to different studies and age ranges&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Severity of AD</span><p id="par0080" class="elsevierStylePara elsevierViewall">Six studies<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;21&#44;25&#44;27</span></a> assessed the severity of AD using different tools&#44; including the Investigator&#39;s Global Assessment &#40;IGA&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;19&#44;21</span></a> the SCORing Atopic Dermatitis &#40;SCORAD&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> the Clinical Global Impressions scale &#8211; Severity of Illness &#40;CGI-SI&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> the Patient Global Assessment &#40;PtGA&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">25&#44;27</span></a> the Patient-Oriented Eczema Measure &#40;POEM&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a> and the physician&#39;s perspective<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Three studies focused on moderate-to-severe AD patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">18&#44;19&#44;21</span></a> while the other three studies included patients from all AD severities&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;25&#44;27</span></a> In the latter studies&#44; moderate AD was reported in 28&#46;8&#37; up to 50&#46;3&#37; of patients&#44; and severe AD in 4&#46;1&#37; up to 12&#46;6&#37; of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;25&#44;27</span></a> Mild AD was the most prevalent disease in two of those studies according to PtGA&#47;POEM<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">25&#44;27</span></a>&#59; while moderate AD was the most prevalent in study &#35;3 according to IGA&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Ortiz de Frutos et al&#46; used several tools to assess disease severity&#46; A total of 70&#46;7&#37; of pediatric patients had been initially diagnosed with moderate AD&#44; based on the specialist&#39;s best clinical judgment&#44; and&#44; therefore&#44; had been included in the study&#46; However&#44; at the time of medical consultation&#44; only 53&#46;4&#37; and 50&#46;9&#37; exhibited moderate-to-severe AD according to IGA and CGI-SI respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> Six percent of the patients had been initially included in the study as having moderate-to-severe AD&#44; but obtained a SCORAD score &#60;15&#44; which ended up categorizing their AD as mild&#46; In contrast&#44; Silverberg et al&#46; evaluated disease severity using PtGA and POEM&#44; observing similar rates&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Comorbidities</span><p id="par0095" class="elsevierStylePara elsevierViewall">Five studies<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;21&#44;22&#44;24&#44;27</span></a> provided specific data on comorbidities associated with AD in Spanish pediatric patients &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; An additional study<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a> listed comorbidities without providing prevalence percentages&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">One study presented aggregate data&#44; confirming that 84&#46;4&#37; of pediatric patients with AD had&#44; at least&#44; one comorbidity&#44; for a mean of 2&#46;5 comorbidities per patient&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> In general&#44; respiratory conditions such as asthma and allergies such as allergic rhinitis were the most widely reported conditions in the observational studies reviewed ranging from 2&#46;6&#37; up to 47&#37; and from 7&#46;9&#37; up to 50&#37;&#44; respectively&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Interestingly&#44; in the study conducted by Almenara-Blasco et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a> different gender-related comorbidity patterns were identified&#46; Mental health disorders&#44; dyslipidemia&#44; and respiratory conditions were more common among men&#44; whereas respiratory-allergic&#44; sensitive-digestive&#44; menstrual-dysphoric-metabolic&#44; and cardiometabolic conditions were more common among women &#40;percentages not provided&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a></p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Disease burden</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Epidemiology</span><p id="par0110" class="elsevierStylePara elsevierViewall">Six articles<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">20&#8211;25</span></a> provided epidemiological data&#44; including prevalence &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41; and incidence &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; of AD in the pediatric population of Spain&#46; The reported prevalence rates varied significantly across the studies ranging from 0&#46;01&#37; up to 30&#37; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Sicras-Mainar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a> assessed the prevalence of AD by different age groups&#44; with both overall and severe AD prevalence being higher in 6&#8211;12-year-olds &#40;11&#46;5&#37; vs 6&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; vs 13&#8211;18-year-olds &#40;0&#46;39&#37; vs 0&#46;23&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a> Similarly&#44; Arnedo-Pena et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a> reported a higher prevalence in adolescents older than 12 years vs younger children&#44; as well as in women compared to men in both 2002 and 2012 &#40;29&#46;80&#37; vs 21&#46;50&#37; and 41&#46;40&#37; vs 28&#46;30&#37;&#44; respectively&#41;&#46; This study also reported an increase in the prevalence ratio from 1994 &#40;1&#46;02 &#91;95&#37; CI&#44; 0&#46;86&#8211;1&#46;21&#93;&#41; through 2012 &#40;1&#46;41 &#91;95&#37; CI&#44; 1&#46;21&#8211;1&#46;73&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">For the incidence of AD&#44; data were drawn from two studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">23&#44;24</span></a> Arnedo-Pena et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a> identified a total of 182 new cases of AD from 1994 through 2002&#44; with an incidence rate of 15&#46;9 per 1000 persons years&#46; Darb&#224; and Mars&#224;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a> confirmed an incidence rate of AD from 2000 through 2017 of 5&#46;8 per 100&#44;000 persons&#44; with a higher incidence being reported in children aged 0&#8211;5 years &#40;30&#46;0 per 100&#44;000 persons&#41;&#44; and the overall incidence being stable throughout the study period&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a></p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Treatment patterns</span><p id="par0125" class="elsevierStylePara elsevierViewall">Three studies<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">19&#44;21&#44;22</span></a> assessed treatment patterns in pediatric patients with moderate-to-severe AD in Spain &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">The first-line therapy in children with moderate-to-severe AD was the use of emollients &#40;82&#46;8&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> followed by topical pharmacological treatment &#40;77&#46;6&#37;&#41; including corticosteroids&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a> Systemic corticosteroids were also used in children starting at the age of 6 years &#40;37&#46;5&#37; up to 95&#46;4&#37;&#41; being cyclosporine &#40;40&#46;5&#37; up to 50&#37;&#41; and azathioprine &#40;23&#46;8&#37;&#41; the most widely used drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">21&#44;22</span></a> Only a small percentage of patients received biologic drugs &#40;1&#46;5&#37;&#41;&#44; in children older than 6 years&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Despite pediatric patients suffering from moderate-to-severe AD&#44; it was notable that 24&#46;1&#37; of patients reported not using any topical pharmacological treatment or delaying its use&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Patient-reported outcomes</span><p id="par0140" class="elsevierStylePara elsevierViewall">Three articles<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#8211;19</span></a> provided data on PROs covering aspects such as HRQoL &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#8211;19</span></a> treatment satisfaction &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> and treatment adherence &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">18&#44;19</span></a></p><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">HRQoL</span><p id="par0145" class="elsevierStylePara elsevierViewall">The impact of AD on the patients&#8217; HRQoL was evaluated using the children&#39;s version of the Dermatology Life Quality Index &#40;cDLQI&#41;&#44; the Infant&#39;s Dermatitis Quality of Life Index &#40;IDQoL&#41;&#44; and the children&#39;s version of the EADA &#40;<span class="elsevierStyleItalic">Escala de afectaci&#243;n de la dermatitis at&#243;pica</span>&#41; scale&#46; Lower scores represented less impairment and better HRQoL in all questionaries used&#44; with final scores ranging from 0 up to 30 in the cDLQI and IDQoL indexes&#44; and from 0 up to 10 in the EADA scale&#46; A summary of the results has been presented in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Two studies used the cDLQI&#58; one reported an overall score of 6&#46;1&#44; being symptoms and feelings &#40;2&#46;0&#41; and daily activities &#40;1&#46;8&#41; the most affected dimensions<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a>&#59; while the other reported overall mean scores of 3&#46;8&#44; 8&#46;8&#44; and 14&#46;5 based on disease severity &#40;mild&#44; moderate and severe or very severe&#44; respectively&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> Similarly to the cDLQI&#44; global IDQoL and EADA scores showed a moderate impact with mean scores of 7&#46;6 and 2&#46;5&#44; respectively in these moderate-to-severe patients&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Torrelo et al&#46; observed higher levels of emotional&#44; physical&#44; and social impairment in patients with severe AD vs patients with mild AD&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> Consistent with this&#44; in severe compared to mild ones&#44; individual cDLQI domain scores revealed a significantly higher impact on symptoms &#40;mean score&#44; 3&#46;4 &#91;SD&#44; 1&#46;8&#93; vs 1&#46;7 &#91;SD&#44; 1&#46;1&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; activities of daily living &#40;mean score&#44; 2&#46;8 &#91;SD&#44; 1&#46;6&#93; vs 0&#46;4 &#91;SD&#44; 1&#46;7&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; and leisure &#40;mean score&#44; 2&#46;9 &#91;SD&#44; 2&#46;2&#93; vs 0&#46;3 &#91;SD&#44; 0&#46;7&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> Furthermore&#44; AD led to changes in mood &#40;79&#46;9&#37;&#41;&#44; affecting feelings of restlessness &#40;91&#46;6&#37;&#41;&#44; concentration difficulties &#40;35&#46;3&#37;&#41;&#44; and depression &#40;7&#46;6&#37;&#41;&#44; particularly among those with severe AD&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> AD significantly impaired patients&#8217; daily life in all severity groups&#44; with 24&#46;5&#37; of the overall sample experiencing strong or very strong pruritus&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a> Sleep was deprived by pruritus&#44; with most patients with moderate-to-severe AD reporting difficulty falling asleep &#40;90&#46;1&#37; with moderate AD and 87&#46;5&#37; with severe AD&#41;&#44; and a proportion of them awakening at night time &#40;76&#46;8&#37; with moderate AD and 97&#46;5&#37; with severe AD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Treatment satisfaction and adherence</span><p id="par0160" class="elsevierStylePara elsevierViewall">Treatment satisfaction and adherence were evaluated in patients using topical pharmacological maintenance treatment for flare-ups prevention&#46; Overall&#44; patients expressed high satisfaction &#40;7&#46;2&#41;&#44; evaluated using a Visual Analogue Scale &#40;VAS 0-10&#41;&#44; with no significant differences regarding disease severity&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> However&#44; treatment adherence&#44; reported by the Morisky&#8211;Green test&#44; was low &#40;18&#46;4&#37;&#41;&#44; with 49&#46;9&#37; of the patients admitting to occasionally forgetting applying treatment&#44; and 34&#46;0&#37; admitting not adhering to it during symptom-free periods&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> In contrast&#44; another study found that most patients adhered to the pharmacological treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> Discrepancies were found between physicians and patients&#8217; perceptions of reported compliance&#46; While dermatologists considered that many of their patients complied with maintenance treatment &#40;88&#46;7&#37;&#41;&#44; the percentage of patients who declared themselves as compliant was lower &#40;18&#46;4&#37; up to 42&#46;6&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> Interestingly enough&#44; patients rated excellent&#44; good&#44; or sufficient disease control in 62&#46;7&#37; of cases while dermatologists did so in 40&#46;5&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a></p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Use of resources and associated costs</span><p id="par0165" class="elsevierStylePara elsevierViewall">Only one report showed data on specialized care resource use and associated costs in pediatric patients &#40;&#60;5 years old&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The study conducted from 2000 through 2017 included 84&#46;3&#37; of ER admissions with a mean length of stay 4&#46;3 days&#46; The most common medical procedures upon admission included blood microscopic examination &#40;30&#46;6&#37;&#41;&#44; steroid injections &#40;18&#46;6&#37;&#41;&#44; antibiotics &#40;12&#46;1&#37;&#41;&#44; and skin biopsies &#40;14&#46;3&#37;&#41;&#46; Additionally&#44; pharmacological interventions registered in primary care centers involved the administration of antibiotics &#40;8&#46;7&#37;&#41;&#44; corticosteroids &#40;topical&#44; 25&#46;7&#37;&#59; systemic&#44; 17&#46;8&#37;&#41;&#44; analgesics &#40;paracetamol&#44; 27&#46;1&#37;&#59; ibuprofen&#44; 20&#46;2&#37;&#59; other&#44; 28&#46;3&#37;&#41;&#44; and antihistamines &#40;14&#46;3&#37;&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The mean annual direct medical costs per patient were estimated at &#8364;2310&#46; These costs were mostly stable within the first half of study period &#40;&#8364;1500&#8211;&#8364;2500&#47;per patient approx&#46;&#44; 2000&#8211;2009&#41;&#44; with a major increase being observed from 2009 through 2010 up to &#8364;4000&#47;per patient &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; followed by a decreasing trend in the 2011&#8211;2017 period&#44; back to 2500&#8364;&#47;per patient approx&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0180" class="elsevierStylePara elsevierViewall">Our systematic review synthesized findings from 11 observational studies providing an overview of the population characteristics&#44; burden of disease&#44; epidemiology&#44; treatment patterns&#44; PROs&#44; use of resources and costs associated with the management of AD in pediatric Spanish patients&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Based on the studies assessing the severity of AD&#44; we could conclude that differences in classification may derive from the use of different instrument measures&#46; The observed results suggested that the use of PRO measures such as PtGA and POEM would correlate well between them&#46; However&#44; the results obtained using clinical measures such IGA or CGI-SI might underestimate the severity vs the results obtained using SCORAD&#44; as it combines the clinical and the patient perspective&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Among the studies included in our review that reported data on comorbidities&#44; respiratory diseases and allergies were found to be the most common&#46; Notably&#44; one of the studies of pediatric patients with severe AD reported a high prevalence &#40;&#62;70&#37;&#41; of mental illnesses&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#44;21&#44;22&#44;24&#44;27</span></a> In this context&#44; there is evidence of a significant association between AD in children and mental health symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">28</span></a> A longitudinal&#44; population-based birth control cohort study found that children with severe AD were &#62;2-fold more likely to have symptoms of depression vs those without AD&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">28</span></a> Additionally&#44; children with AD were more likely to internalize behaviors&#44; such as anxiety or somatic complaints&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">28</span></a> Moreover&#44; a higher prevalence of ADHD in pediatric AD patients has been reported too&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">29</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">As seen in the three studies included in our review&#44; AD affects not only the emotional domain but also other domains of HRQoL&#44; as physical and social impairment&#44; particularly in severe AD&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">17&#8211;19</span></a> Pruritus is the symptom with the greatest impact on HRQoL&#44; as it negatively interferes with sleep quality&#44; mood swings and restlessness&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">8</span></a> Consistent with this&#44; AD has been pointed out to be the most common skin disease that causes the greatest impairment in HRQoL on account of symptoms such as pruritus and insomnia&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">30</span></a> One study revealed that 79&#37; of children with AD reported sleep disturbances&#44;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">31</span></a> even among patients with mild and inactive disease&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">32</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">The prevalence data from the analyzed studies revealed wide heterogeneity&#46; For instance&#44; significant variability in AD prevalence and incidence was observed across regions and age groups&#46; This variability could be attributed to variations in study methodologies and design&#44; research settings and AD definitions&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">AD prevalence is heterogeneous&#44; generally ranging from 10&#37; up to 30&#37; even for younger children younger than 2 years&#44; suggesting an early onset during childhood&#46; This early onset is usually associated with genetic predisposition and environmental factors&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">33</span></a> Although gender difference patterns seemed nonsignificant&#44; the long study conducted by Arnedo-Pena et al&#46; in a small region of Spain from 1994 though 2012 resulted in women showing a higher prevalence of AD&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a> a trend not yet seen in the real-world global study conducted by Silverberg et al&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a> including 18 countries&#46; An increasing trend in AD prevalence in Spain was observed from 1994 through 2012&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a> In contrast&#44; a decrease in AD prevalence from 22&#46;8&#37; &#40;1996&#41; down to 21&#46;3&#37; &#40;2006&#41;&#44; and down to 16&#46;3&#37; &#40;2017&#41; was seen&#44; for example&#44; in Sweden&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">34</span></a> highlighting geographical variations&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Regarding AD incidence&#44; in our review a stable trend in children aged 0&#8211;5 years from 2000 through 2017 was observed&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a> Similarly&#44; a study from Denmark and Sweden supports this stability&#44; with consistent incidence rates throughout time&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">35</span></a> This stability suggests unchanged risk factors for AD development in this age group&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">34</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">In Spain&#44; the current AD treatment guidelines for pediatric population suggest an adequate skin hydration and use of topical corticosteroids&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">36</span></a> which is consistent with the treatment patterns reported in the reviewed studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">19&#44;20</span></a> yet we should mention that 24&#46;1&#37; of moderate-to-severe patients delayed initiation&#44; or did not apply topical pharmacological maintenance treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a> The treatment adherence was low despite the patient&#39;s expressed satisfaction with treatment<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a> and regardless of disease severity&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">37</span></a> We should&#44; also&#44; mention the different perceptions between patients and specialists in the field&#44; with specialists often overestimating the patient&#39;s compliance with the recommendations and prescribed treatment application&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">The use of biologic drugs as the treatment of choice among pediatric patients seemed to be limited&#44; with only 1&#46;5&#37; of patients older than 6 years benefiting from this option&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a> This limited usage of biologics in the Spanish pediatric population may be due to their very recent authorization for use and access barriers that might have prevented their prescription&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">38</span></a> However&#44; biologic drugs may provide adequate control in moderate-to-severe cases&#44; covering an unmet need in this pediatric population&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">39</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Of note the significant gap in the literature on the economic burden of pediatric AD in Spain&#46; While several studies have focused on the economic implications on adult patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">40&#44;41</span></a> pediatric population research is lacking&#44; despite existing research in other European countries highlighting important secondary care use of resources such as outpatient visits and pharmacy dispensations&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">42</span></a> The mean direct medical cost in Sweden &#40;SD&#41; was estimated at &#8364;1111 &#40;3416&#41; and &#8364;1906 &#40;7067&#41; for mild-to-moderate and severe AD&#44; respectively&#44; which is consistent with the Spanish data retrieved in our review&#46; Nonetheless&#44; there is a need for more targeted studies in this area&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">This review presents some limitations&#46; Variations in the definition and severity of AD across different scales had implications for the comparability and generalizability of our findings&#46; Additionally&#44; the heterogeneity in the available data&#44; including differences in study design&#44; data collection methods&#44; and outcome measures&#44; complicated result interpretation&#46; Moreover&#44; the methodologies and target populations also differed across studies&#44; leading to variable results&#46; There was a lack of comprehensive data on the use of resources and costs associated with AD in the pediatric population&#44; which limits our understanding of the economic burden associated with AD&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conclusions</span><p id="par0235" class="elsevierStylePara elsevierViewall">This systematic review provides a comprehensive picture of the clinical&#44; humanistic and economic burden of AD in pediatric patients in Spain&#44; which may be beneficial for physicians and health care decision makers who manage this condition&#44; as well as researchers seeking to determine the gaps in knowledge that remain that need to be addressed in future research studies&#46; The high prevalence and early onset highlight the need for comprehensive&#44; patient-focused care tailored to this subpopulation&#46; Despite the existence of established treatment guidelines&#44; low adherence to treatment indicates a need for developing better and more effective strategies&#46; On the other hand&#44; biological therapy&#44; including newly available treatments and small molecule JAK inhibitors&#44; present a promising opportunity for innovation and expansion in therapeutic interventions&#46; As modern and effective management strategies are developed&#44; these key factors should be considered to improve patient outcomes&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Ethical approval</span><p id="par0240" class="elsevierStylePara elsevierViewall">This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Funding</span><p id="par0245" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleGrantSponsor" id="gs1">Eli Lilly</span> sponsored this study and the publication of this article&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Authors&#8217; contributions</span><p id="par0250" class="elsevierStylePara elsevierViewall">Rosa Moro&#44; Silvia D&#237;az-Cerezo&#44; Luis Liz&#225;n and Mercedes N&#250;&#241;ez contributed to the conception of the work&#44; the design&#44; the acquisition&#44; and analysis of the data&#46; All authors participated in the interpretation of data for the work&#44; the critical revision of the manuscript and approved the final submitted version&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of interest</span><p id="par0255" class="elsevierStylePara elsevierViewall">Antonio Torrelo Fern&#225;ndez is member of the advisory board of Eli Lilly and Viatris&#44; has received speaker fees from Eli Lilly&#44; Viatris&#44; Pfizer&#44; Sanofi&#44; and Novartis&#44; and fees for attending meetings from Sanofi and Pierre Fabre&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Asunci&#243;n Vicente is member of the advisory board of Eli Lilly and Amryt&#44; has received consulting fees from Abbvie&#44; Amgen&#44; Amryt&#44; Boehringer Ingelheim&#44; Bristol-Myers Squibb&#44; Eli Lilly&#44; Novartis&#44; Pierre Fabre and Sanofi Genzyme&#44; speaker fees from Abbvie&#44; Amgen&#44; Amryt&#44; Boehringer Ingelheim&#44; Bristol-Myers Squibb&#44; Ferrer&#44; Galderma&#44; Janssen&#44; Eli Lilly&#44; Novartis&#44; Pierre Fabre&#44; Pfizer&#44; and Sanofi Genzyme and fees for attending meetings from Abbvie&#44; Almirall&#44; Amgen&#44; Amryt&#44; Boehringer Ingelheim&#44; Bristol-Myers Squibb&#44; Ferrer&#44; Galderma&#44; Eli Lilly&#44; Novartis&#44; Pierre Fabre&#44; Pfizer&#44; and Sanofi Genzyme&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Ana Martin-Santiago has received speaker fees from Abbvie&#44; Amgen&#44; Leo-Pharma&#44; Leti&#44; Novartis&#44; Pfizer&#44; and Sanofi&#44; payments for her expert testimony from Abbvie&#44; Amryt&#44; Leo-Pharma&#44; Pfizer&#44; and Sanofi&#44; and fees for attending meetings from Abbvie&#44; Almirall&#44; Janssen&#44; Leo-Pharma&#44; Leti&#44; Eli Lilly&#44; Novartis&#44; Pfizer&#44; Pierre Fabre&#44; Sanofi&#44; UCB and Viatrix&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Ra&#250;l de Lucas Laguna is member of the advisory board of Novartis&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; Sanofi&#44; Leo-Pharma&#44; Johnson &#38; Johnson&#44; UCB&#44; Almirall&#44; Galderma&#44; LetiPharma&#44; has received consulting fees from Novartis&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; Sanofi&#44; Leo-Pharma&#44; Johnson &#38; Johnson&#44; UCB&#44; Almirall&#44; Galderma&#44; and LetiPharma&#44; speaker fees from Novartis&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; Sanofi&#44; LetiPharma&#44; Johnson &#38; Johnson&#44; UCB&#44; Almirall&#44; Galderma&#44; and LetiPharma&#44; payments for his expert testimony from Novartis&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; Sanofi&#44; LetiPharma&#44; Johnson &#38; Johnson&#44; UCB&#44; Almirall&#44; Galderma&#44; and LetiPharma&#44; and support for attending meetings from Novartis&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; Sanofi&#44; Leo-Pharma&#44; Johnson &#38; Johnson&#44; UCB&#44; Almirall&#44; Galderma&#44; and LetiPharma&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Jos&#233; Carlos Armario Hita is member of the advisory board of Abbvie&#44; Novartis&#44; Lilly&#44; Sanofi&#44; Galderma&#44; Leo-Pharma&#44; Janssen&#44; Pfizer&#44; UCB farma&#44; and Almirall&#44; has received consulting fees from Abbvie&#44; Novartis&#44; Lilly&#44; Sanofi&#44; Galderma&#44; Leo-Pharma&#44; Janssen&#44; Pfizer&#44; UCB farma&#44; Almirall&#44; speaker fees from Abbvie&#44; Novartis&#44; Lilly&#44; Sanofi&#44; Galderma&#44; Leo-Pharma&#44; Janssen&#44; Pfizer&#44; UCB farma&#44; Almirall&#44; and fees for attending meetings from Abbvie&#44; Novartis&#44; Lilly&#44; Sanofi&#44; Galderma&#44; Leo-Pharma&#44; Janssen&#44; Pfizer&#44; UCB farma&#44; and Almirall&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Rosa Moro&#44; Silvia D&#237;az-Cerezo and Mercedes N&#250;&#241;ez are employees of Eli Lilly&#46; Luis Liz&#225;n works as an independent scientific consultant &#40;Outcomes&#8217;10&#41; and declared to have received honoraria for conducting the systematic literature review and manuscript drafting tasks&#46;</p></span></span>"
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    "fechaRecibido" => "2024-06-03"
    "fechaAceptado" => "2024-06-25"
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            0 => "Dermatitis at&#243;pica"
            1 => "Ni&#241;os"
            2 => "Epidemiolog&#237;a"
            3 => "Calidad de Vida Relacionada con la Salud"
            4 => "Patrones de tratamiento"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Atopic dermatitis &#40;AD&#41; is a chronic&#44; inflammatory skin disease affecting all age groups&#44; particularly children&#46; This systematic review provides an overview of the humanistic and economic disease burden in the pediatric population with AD in Spain&#46; The evidence&#44; collected from 11 observational studies published over the past 10 years&#44; exhibits the most common characteristics of the patients&#44; disease burden&#44; patient-reported outcomes&#44; use of resources&#44; and treatment patterns&#46; The burden of AD extends beyond physical symptoms&#44; with associated comorbidities such as asthma and impaired health-related quality of life and mental health disorders&#44; particularly in severe cases&#46; Traditional therapies&#44; primarily topical corticosteroids&#44; face adherence and efficacy challenges&#46; Despite promising innovative treatments and available biological therapies&#44; their use is still limited in the pediatric population&#46; The findings of the present review highlight the scarce scientific evidence on the economic burden of pediatric AD&#44; as well as the most updated humanistic evidence on this disease&#46; At the same time&#44; the need for individualized care and innovative therapeutic interventions to address the multifaceted challenges of pediatric AD in Spain is evident&#46;</p></span>"
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        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La dermatitis at&#243;pica &#40;DA&#41; es un trastorno cut&#225;neo cr&#243;nico e inflamatorio que afecta a todos los grupos de edad&#44; pero especialmente a los ni&#241;os&#46; Esta revisi&#243;n sistem&#225;tica proporciona una visi&#243;n general de la carga de la enfermedad en la poblaci&#243;n pedi&#225;trica con DA en Espa&#241;a&#46; La evidencia recopilada de 11 estudios observacionales publicados en los &#250;ltimos 10 a&#241;os presenta las caracter&#237;sticas m&#225;s comunes de los pacientes&#44; la carga de la enfermedad&#44; los resultados reportados por los pacientes&#44; el uso de recursos y los patrones de tratamiento m&#225;s frecuentes&#46; La carga de la DA se extiende m&#225;s all&#225; de los s&#237;ntomas f&#237;sicos&#44; con comorbilidades asociadas como el asma&#44; el deterioro de la calidad de vida relacionada con la salud y trastornos de salud mental&#44; particularmente en los casos graves&#46; Los tratamientos tradicionales&#44; principalmente los corticosteroides t&#243;picos&#44; enfrentan desaf&#237;os de adherencia y eficacia&#46; A pesar de las prometedoras innovaciones terap&#233;uticas y la disponibilidad de terapias biol&#243;gicas&#44; su uso permanece limitado en poblaci&#243;n pedi&#225;trica&#46; Los resultados de la presente revisi&#243;n resaltan la escasa evidencia cient&#237;fica sobre la carga econ&#243;mica de la DA pedi&#225;trica&#44; as&#237; como la evidencia human&#237;stica m&#225;s actualizada de la enfermedad&#46; Asimismo&#44; se hace patente la necesidad de una atenci&#243;n personalizada e intervenciones terap&#233;uticas innovadoras para abordar los desaf&#237;os multifac&#233;ticos de la DA pedi&#225;trica en Espa&#241;a&#46;</p></span>"
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            "titulo" => "Supplementary data"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">PRISMA flow diagram with the selection process of the included publications&#46; IBECS&#44; &#205;ndice Bibliogr&#225;fico Espa&#241;ol en Ciencias de la Salud&#59; MEDES&#44; Medicina en Espa&#241;ol&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AD severity&#46; &#40;A&#41; Studies including mild&#44; moderate and severe patients measured with IGA&#44; PtGA and POEM&#46; &#40;B&#41; Studies restricted to moderate-to-severe patients measured with SCORAD&#44; IGA&#44; CGI-SI&#44; IGA and medical history&#46; NA&#44; not available&#59; <span class="elsevierStyleSup">a</span>IGA has six categories of response and its score ranges from 0 &#40;no illness&#44; with no inflammatory signs of AD&#41; up to 5 &#40;very serious illness&#44; with intense erythema and intense papule&#47;infiltration with crusts&#47;exudation&#41;&#46; Barroso et al&#46; ranged severity from 0 up to 4&#44; considering scores of 3 as moderate and scores of 4 as severe AD&#59; <span class="elsevierStyleSup">b</span>Patient Global Assessment &#40;PtGA&#41;&#44; which asks&#44; &#8220;Please check one answer that best describes the severity of your or your child&#39;s eczema over the past week&#44;&#8221; with responses of clear&#44; mild&#44; moderate&#44; or severe&#59; <span class="elsevierStyleSup">c</span>Patient-Oriented Eczema Measure &#40;POEM&#41;&#44; with a total score ranging from 0 &#40;lower severity&#41; up to 28 &#40;higher severity&#41;&#59; severity groupings have been defined as bands of 0&#8211;7 indicating mild AD&#44; 8&#8211;16 moderate AD&#44; and &#62;16 severe AD&#59; <span class="elsevierStyleSup">d</span>SCORAD takes into account the extent and intensity of the lesions&#44; as well as the symptoms &#40;pruritus and loss of sleep&#41; it causes&#59; extent &#40;A&#41;&#58; the body surface is divided into four segments &#40;head and neck&#44; trunk&#44; upper and lower extremities&#41; to which a percentage is assigned based on the extent represented&#59; intensity &#40;B&#41;&#59; <span class="elsevierStyleSup">e</span>The Clinical Global Impression &#8211; Severity scale &#40;CGI-S&#41; is a valuable tool used by clinicians to assess the severity of a patient&#39;s illness vs their past experience with similar diagnoses&#46; It involves rating the patient&#39;s current condition on a 7-point scale&#44; reflecting different levels of illness severity&#58; &#40;1&#41; normal&#44; not at all ill&#44; &#40;2&#41; borderline mentally ill&#44; &#40;3&#41; mildly ill&#44; &#40;4&#41; moderately ill&#44; &#40;5&#41; markedly ill&#44; &#40;6&#41; severely ill&#44; and &#40;7&#41; extremely ill&#46;</p>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Comorbidities associated with pediatric AD&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Prevalence of pediatric AD in Spanish population by different age groups&#46; Blue dots correspond to overall prevalence while orange dots correspond to severe AD&#59; yr&#44; years&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HRU&#47;costs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#225;nchez-P&#233;rez &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Medical chart review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary care&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#8805;2 to &#60;18 years&#44; &#8805;1 year since AD diagnosis &#40;Hanifin and Rajka criteria&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">151&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- HRQoL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Torrelo &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patient interviews&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#8805;2 to &#60;15 years&#46; Moderate-to-severe AD &#40;Hanifin and Rajka criteria&#41;&#44; &#8805;16-month history of AD&#44; topical treatment &#8805;4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- HRQoL- Satisfaction- Adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ortiz de Frutos &#40;2014&#41;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Medical chart review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#8805;2 to &#60;15 years&#46; Clinically diagnosed moderate-to-severe AD &#40;specialist&#39;s judgment&#44; excluding mild AD&#41;&#44; &#8805;12-month history of AD&#44; IGA &#62;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">116&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- HRQoL- Adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Draaisma &#40;2015&#41;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Parent or caregiver interviews&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary care&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#62;12 to &#60;15 month-old infants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6937&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Barroso &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Electronic health records&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#60;18 years with moderate-to-severe AD &#40;IGA &#62;3&#41;&#44; treatments<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sicras-Mainar &#40;2019&#41;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Review of medical records &#40;computerized databases&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary care and hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#8805;6 years&#44; AD diagnosis &#8805;1 year prior to the index date&#44; prescribed medication&#44; &#8805;2 prescriptions at the follow-up&#44; regular monitoring with &#8805;2 health records&#44; including a visit to the dermatology unit&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#44;374 with AD844 with severe AD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Arnedo-Pena &#40;2020&#41;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patient interviews&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3607 &#40;1st survey&#44; 1994&#41;1805 &#40;2nd survey&#44; 2002&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Prevalence- Incidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Darb&#224; &#40;2021&#41;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Database&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary care and hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1266&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Incidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Silverberg &#40;2021&#41;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patient interviews&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#62;6 months to 18 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3465&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X- Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Almenara-Blasco &#40;2022&#41;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Medical chart review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary care&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;757&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#225;zaro &#40;2022&#41;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a>&#91;ABSTRACT SEAIC 2022&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cross-sectional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#62;6 months to 18 years&#44; diagnosed with AD &#40;criteria-based&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">564&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">First 3 ISAAC &#40;International Study of Asthma and Allergies in Childhood&#41; criteria<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>medical diagnosis reported by the patient<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>additional criteria for children &#60;6 years old&#46;</p>"
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                  <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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Author &#40;year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Sample size &#40;<span class="elsevierStyleItalic">N</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Population age&#44; yr<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</a></th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Mean age&#44; years &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Gender&#44; female &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">0&#46;5&#8211;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2&#8211;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">5&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">15&#8211;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">S&#225;nchez-P&#233;rez &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Torrelo &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Ortiz de Frutos &#40;2014&#41;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Draaisma &#40;2015&#41;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14&#46;4 &#40;0&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Silverberg &#40;2021&#41;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 mo&#8211;&#60;6 yr&#58; 3&#46;26&#8211;&#60;12 yr&#58; 9&#46;212&#8211;&#60;18 yr&#58; 14&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">6 mo&#8211;&#60;6yr&#58; 54&#46;56&#8211;&#60;12 yr&#58; 45&#46;112&#8211;&#60;18 yr&#58; 46&#46;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">L&#225;zaro &#40;2022&#41;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">X&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;7<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#46;6<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;0<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Severe or very severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">14&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#46;1<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">2&#46;8<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;6<a class="elsevierStyleCrossRef" href="#tblfn0035">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">Torrelo &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">18</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">Moderate-to-severe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">cDLQI<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a> &#40;0&#8211;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">6&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">EADA<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">b</span></a> &#40;0&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Ortiz de Frutos &#40;2014&#41;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Moderate-to-severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">EADA<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">b</span></a> &#40;0&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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        "texto" => "<p id="par0285" class="elsevierStylePara elsevierViewall">Assistance in the methodology and editorial preparation of this article was provided by Outcomes&#8217;10&#46; The authors hereby wish to thank Patricia Felip&#44; Ana Causanilles and H&#233;ctor David de Paz for their help during data analysis and medical drafting tasks&#46;</p>"
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Información del artículo
ISSN: 00017310
Idioma original: Inglés
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año/Mes Html Pdf Total
2024 Noviembre 25 15 40
2024 Octubre 183 83 266
2024 Septiembre 235 93 328
2024 Agosto 226 90 316
2024 Julio 86 54 140

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

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