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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cow&#39;s milk protein allergy &#40;CMPA&#41; is defined as a reproducible&#44; immunological adverse reaction to one or more cow&#39;s milk &#40;CM&#41; proteins&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> It involves the participation of IgE immunoglobulins &#40;IgE&#41;&#44; cells &#40;T-lymphocytes&#41;&#44; or both&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> It affects 2&#8211;3&#37; of children&#44; representing the most common food allergy in childhood&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">For the diagnosis of IgE-mediated CMPA&#44; detailed clinical history and detection of IgE specific for allergens are important tools&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> However&#44; the double-blind&#44; placebo-controlled oral challenge test &#40;DBPCOCT&#41;&#44; which consists in offering the food without the physician&#39;s or the patient&#39;s knowledge&#44; continues to be considered the gold standard for the diagnosis of CMPA&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#8211;7</span></a> Nonetheless&#44; it has disadvantages related to the time required for its performance&#44; the costs involved&#44; and the need for an adequate physical structure and a multidisciplinary team&#44; which are limiting factors for its broad use in clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Different values of serum-specific IgE and mean papule diameter in the immediate-reading skin test &#40;IRST&#41;&#44; from which the chance of having symptoms at the time of the OCT would be greater than 95&#37; were established&#59; however&#44; the values found were not reproducible in different populations&#44; and differences regarding ethnic-racial characteristics&#44; age&#44; dietary habits&#44; clinical phenotypes&#44; and technical conditions for IRST were presumed&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#8211;15</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The desire to minimize OCTs &#8211; with their inherent risks &#8211; together with the unavailability of an adequate universal cutoff point for all populations&#44; motivated this study&#44; whose objectives are&#58; to compare serum concentrations of specific IgE and mean papule diameter induced by the IRST with CM and its fractions with OCT results&#44; and to establish cutoff points capable of predicting clinical reactivity to CM in patients treated at a referral service&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">This was a prospective&#44; observational&#44; diagnostic study that included 122 children&#44; aged 5 months to 3 years &#40;median 17 months&#41;&#44; with clinical suspicion of IgE-mediated CMPA and evidence of positive IgE specific for CM and&#47;or its fractions&#44; in the first consultation &#40;inclusion criteria&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">After approval by the ethics committee&#44; children consecutively admitted to the Food Allergy Service of Universidade Federal de Sergipe &#40;UFS&#41; between November 2008 and May 2014&#44; and who met the inclusion criteria&#44; were selected&#46; Parents and&#47;or guardians answered a standardized questionnaire regarding symptom history&#44; birth conditions&#44; breastfeeding time&#44; time of the first introduction of CM&#44; triggering volume&#44; time interval between ingestion and symptom onset&#44; in addition to the time of the last reaction and medication used&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Any of the following symptoms described for the skin &#40;hyperemia&#44; urticaria&#44; contact urticaria&#44; and angioedema&#41;&#44; respiratory tract &#40;rhinorrhea&#44; sneezing&#44; nasal obstruction&#44; laryngeal stridor&#44; hoarseness&#44; coughing&#44; dyspnea&#44; and cyanosis&#41;&#44; gastrointestinal tract &#40;perioral hyperemia&#44; tongue and&#47;or uvular edema&#44; vomiting&#44; and diarrhea&#41;&#44; and cardiovascular system &#40;tachycardia&#44; arrhythmias&#44; hypotonia&#44; prostration&#44; and syncope&#41;&#44; clearly observed and triggered up to two hours after food contact were considered suspected objective IgE-mediated CMPA symptoms&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2&#44;3&#44;6&#44;17</span></a> As positive evidence for detection of specific IgE for CM and fractions&#44; IRST results and&#47;or IgE levels brought by the parents&#47;guardians were accepted at the first consultation&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">After being selected&#44; nursing mothers and children were instructed to restrict CM protein and derivatives in their diet for a period of two to four weeks&#44; to not use antihistamines for one week before the OCT&#44; and to have children to fast for two hours before the procedure&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7&#44;19&#44;20</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Printed leaflets containing instructions on CM elimination diet and careful reading of labels were distributed and a questionnaire on compliance with these requirements was applied prior to the OCT&#46; Guidelines on the risks and benefits of the OCT and the implications of a positive or negative test result were also given to the parents&#44; who&#44; after being instructed&#44; signed the informed consent&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">A recent history &#40;less than two years&#41; of anaphylaxis associated with the presence of specific IgE at admission&#44; symptom persistence after the CM exclusion period&#44; low adherence to OCT preparation guidelines&#44; and the presence of an inflammatory and&#47;or infectious process on the day of the procedure were considered the exclusion criteria&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#44;7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">On the day of the OCT&#44; after verifying compliance with the recommendations&#44; the children underwent a careful physical examination&#44; followed by the following tests&#58; peripheral blood collection to determine serum concentrations of total IgE and IgE specific for CM and its fractions&#44; and IRST&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">A peripheral blood sample was collected and centrifuged&#59; the serum was stored and frozen at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C until the analysis&#46; The levels of total and specific IgE to total CM&#44; &#945;-lactalbumin&#44; &#946;-lactoglobulin&#44; and casein were determined using the ImmunoCAP<span class="elsevierStyleSup">&#174;</span> method &#40;Thermo Fisher Scientific&#44; Brazil&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> Serum levels were determined at the Research Laboratory of the Discipline of Nutrology of the Department of Pediatrics of Universidade Federal de S&#227;o Paulo&#46; The results obtained were expressed in kUA&#47;L and considered positive when greater than 0&#46;35<span class="elsevierStyleHsp" style=""></span>kUA&#47;L&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Regarding the IRST&#44; the following extracts were used&#58; total CM &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&#41;&#44; &#945;-lactalbumin &#40;5&#37;&#41;&#44; &#946;-lactoglobulin &#40;5&#37;&#41;&#44; and casein &#40;5&#37;&#41; &#40;IPI-ASAC<span class="elsevierStyleSup">&#174;</span>&#44; Spain&#41;&#44; in addition to controls&#58; negative &#40;diluent&#41; and positive &#40;histamine 1<span class="elsevierStyleHsp" style=""></span>mg&#47;mL&#41;&#46; The appearance of a papule with a mean diameter greater than or equal to 3<span class="elsevierStyleHsp" style=""></span>mm in relation to the negative control&#44; 15<span class="elsevierStyleHsp" style=""></span>min after the IRST by puncture&#44; characterized the result as positive&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Open OCT&#44; a procedure in which only the physician is aware of what is being offered to the patient&#44; was performed in a hospital environment&#44; under the supervision of a multidisciplinary team prepared to treat any clinical reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> Open OCT was chosen because&#44; regarding the presence of objective symptoms in children under three years of age&#44; it was possible to establish the diagnosis&#44; even without performing the DBPCOCT&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The children were given 100<span class="elsevierStyleHsp" style=""></span>mL of CM &#40;13&#37; dilution&#41; administered in increasing doses &#40;1&#44; 4&#44; 10&#44; 15&#44; 20&#44; 25&#44; and 25<span class="elsevierStyleHsp" style=""></span>mL&#41; at 15- to 20-minute intervals&#44; equivalent to 0&#46;03&#44; 0&#46;14&#44; 0&#46;34&#44; 0&#46;51&#44; 0&#46;68&#44; 0&#46;85&#44; and 0&#46;85<span class="elsevierStyleHsp" style=""></span>g of CM protein&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7&#44;8&#44;19&#44;20</span></a> In case of refusal&#44; a palatable vehicle capable of masking the taste of CM was offered&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">When clinical reactions occurred&#44; the test was considered positive and the child was promptly observed&#44; remaining under observation until the manifestations disappeared&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> The reactions were classified according to severity as mild &#40;skin symptoms and&#47;or upper respiratory tract symptoms only&#41;&#44; moderate &#40;gastrointestinal tract symptoms or association of systems excluding lower respiratory tract and&#47;or cardiovascular symptoms&#41;&#44; and severe &#40;laryngeal&#44; lower respiratory tract&#44; and&#47;or cardiovascular symptoms&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">If no manifestation occurred after the intake of the full offered volume within two hours&#44; the test was considered negative&#44; and the patient was excluded from the study and discharged&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Analysis of collected data</span><p id="par0090" class="elsevierStylePara elsevierViewall">The collected data were analyzed using the statistical software SPSS &#40;Released 2008&#46; SPSS Statistics for Windows&#44; Version 17&#46;0&#46; Chicago&#44; USA&#41;&#46; Sensitivity &#40;S&#41;&#44; specificity &#40;Sp&#41;&#44; positive predictive value &#40;PPV&#41;&#44; negative predictive value &#40;NPV&#41;&#44; and positive &#40;PLR&#41; and negative likelihood ratio &#40;NLR&#41; were calculated to assess the accuracy of cutoff points for serum-specific IgE for total CM and fractions&#44; as well as the mean papule diameter in the IRST when compared to the OCT results &#40;the gold standard&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The receiver operating characteristic &#40;ROC&#41; curves were obtained from the ratio between S and Sp&#46; Thus&#44; optimal cutoff points were defined&#44; with the objective of defining allergy&#46; For this purpose&#44; two methods were used&#58; Youden&#39;s index and Sp maximization&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">PPV and NPV were calculated for a cutoff value of 0&#46;35<span class="elsevierStyleHsp" style=""></span>kUA&#47;L&#44; based on previous positivity references and the &#8220;optimal cutoffs&#8221; on the ROC curve&#46; The sample power was calculated so that the cutoff points showed specificity equal to or greater than 70&#37;&#44; as described by Champely in 2017&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">To evaluate the agreement between the fractions &#40;&#945;-lactalbumin&#44; &#946;-lactoglobulin&#44; and casein&#41; and total cow&#39;s milk&#44; Krippendorff&#39;s <span class="elsevierStyleItalic">&#945;</span> was used as the measurement of agreement&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> A value of 1 means there is perfect agreement&#44; 0 indicates absence of agreement&#44; and values lower than 0 indicate systematic disagreement&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The study was approved by the ethics committees of Universidade Federal de Sergipe &#40;UFS&#41; and Universidade Federal de S&#227;o Paulo &#40;UNIFESP&#41;&#44; under the respective numbers CEP&#47;SE N&#46; CAAE &#8211; 0087&#46;0&#46;107&#46;174-08 and CEP&#47;SP &#8211; 1440&#47;11&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0115" class="elsevierStylePara elsevierViewall">Of the 122 children submitted to OCT&#44; 60 &#40;49&#37;&#41; were males&#46; The allergic group consisted of 73 patients &#40;59&#46;8&#37;&#41; and the control group &#40;non-allergic&#41;&#44; of 49 &#40;40&#46;2&#37;&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The most frequently observed symptoms during open OCT were of the skin&#44; in 86&#46;3&#37; &#40;63&#47;73&#41; of the children&#44; followed by respiratory in 23&#46;3&#37; &#40;17&#47;73&#41; and gastrointestinal symptoms in 13&#46;7&#37; &#40;10&#47;73&#41;&#46; There were no cardiovascular symptoms&#46; Urticaria was the most frequent clinical manifestation&#44; affecting 78&#37; of the children&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Serum levels of IgE specific for CM and its fractions &#40;&#945;-lactalbumin&#44; &#946;-lactoglobulin&#44; and casein&#41; were significantly higher in the allergic group compared to non-allergic patients &#40;median 3&#46;39<span class="elsevierStyleHsp" style=""></span>kUA&#47;L <span class="elsevierStyleItalic">vs&#46;</span> 1&#46;16<span class="elsevierStyleHsp" style=""></span>kUA&#47;L&#59; 0&#46;97<span class="elsevierStyleHsp" style=""></span>kUA&#47;L <span class="elsevierStyleItalic">vs</span>&#46; 0&#46;09<span class="elsevierStyleHsp" style=""></span>kUA&#47;L&#59; 1&#46;72<span class="elsevierStyleHsp" style=""></span>kUA&#47;L <span class="elsevierStyleItalic">vs&#46;</span> 0&#46;44<span class="elsevierStyleHsp" style=""></span>kUA&#47;L&#59; and 0&#46;75<span class="elsevierStyleHsp" style=""></span>kUA&#47;L <span class="elsevierStyleItalic">vs&#46;</span> 0&#46;36<span class="elsevierStyleHsp" style=""></span>kUA&#47;L&#44; respectively&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> describes the accuracy of different concentrations of specific IgE and the mean papule diameter for CM and its fractions&#44; according to the OCT results&#46; For IgE concentrations&#44; when the value of 0&#46;35<span class="elsevierStyleHsp" style=""></span>kUA&#47;L was established as the cutoff point for test positivity&#44; the S for the total CM and its fractions varied from 43&#37; to 67&#37;&#44; the Sp from 27&#37; to 39&#37;&#44; and the NPV from 25&#37; to 43&#37;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">The ROC curves constructed from the ratio between S and Sp of the specific IgE levels were discriminatory&#44; with an area under the curve greater than 0&#46;6 for CM and its fractions &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; According to the proposed criterion for establishing an optimal cutoff point&#44; Youden&#39;s index&#44; the specific serum IgE concentration considered optimal for CM was 5&#46;17<span class="elsevierStyleHsp" style=""></span>kUA&#47;L&#44; quite different from that obtained with the Sp maximization criterion &#40;PPV<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100&#37;&#41;&#44; with values of 77&#46;7<span class="elsevierStyleHsp" style=""></span>kUA&#47;L &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">As for the fractions&#44; according to Youden&#39;s index&#44; the following values were considered&#58; 0&#46;95<span class="elsevierStyleHsp" style=""></span>kUA&#47;L for &#945;-lactalbumin&#44; 0&#46;82<span class="elsevierStyleHsp" style=""></span>kUA&#47;L for &#946;-lactoglobulin&#44; and 0&#46;72<span class="elsevierStyleHsp" style=""></span>kUA&#47;L for casein &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; When evaluated alone&#44; the PLR&#44; which represents how much a positive result increases the chance of an individual of being ill&#44; showed low diagnostic accuracy &#40;values between 2 and 5&#41;&#44; being null for &#946;-lactoglobulin &#40;value between 1 and 2&#41; and higher for total CM&#46; The evaluation of the different possible combinations showed that any association has better accuracy than total CM alone&#44; mainly if associated with casein &#40;PLR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#46;53&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The mean papule diameters were significantly higher in the allergic group&#58; CM&#58; median 2&#46;5<span class="elsevierStyleHsp" style=""></span>mm <span class="elsevierStyleItalic">vs&#46;</span> 0<span class="elsevierStyleHsp" style=""></span>mm&#59; &#945;-lactalbumin&#58; 8&#46;75<span class="elsevierStyleHsp" style=""></span>mm <span class="elsevierStyleItalic">vs&#46;</span> 5&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#59; &#946;-lactoglobulin&#58; 9&#46;75<span class="elsevierStyleHsp" style=""></span>mm <span class="elsevierStyleItalic">vs&#46;</span> 8&#46;0<span class="elsevierStyleHsp" style=""></span>mm&#59; and casein&#58; 3&#46;5<span class="elsevierStyleHsp" style=""></span>mm <span class="elsevierStyleItalic">vs</span>&#46; 0<span class="elsevierStyleHsp" style=""></span>mm&#46; When evaluating the performance of different mean papule diameters&#44; when the 3-mm value was established as a cutoff for IRST positivity&#44; the S for total CM and its fractions varied from 15&#37; to 46&#37;&#44; whereas Sp ranged from 15&#37; to 38&#37;&#44; and NPV from 16&#37; to 29&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The ROC curves were adequate&#44; with area under the curve greater than 0&#46;7 for CM and its fractions&#44; except for casein&#44; with an area of 0&#46;697 &#40;0&#46;607&#8211;0&#46;787&#41;&#44; being only discriminatory &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Using Youden&#39;s index&#44; the optimal cutoff point for the mean papule diameter for CM was 3&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#46; With the maximization of Sp &#40;PPV<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100&#37;&#41; the cutoff point for CM was 5&#46;0<span class="elsevierStyleHsp" style=""></span>mm&#44; 15&#46;5<span class="elsevierStyleHsp" style=""></span>mm for &#945;-lactalbumin&#44; 21&#46;5<span class="elsevierStyleHsp" style=""></span>mm for &#946;-lactoglobulin&#44; and 10<span class="elsevierStyleHsp" style=""></span>mm for casein &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The use of the components contributed to improve the diagnosis of those with a negative IRST for total CM &#40;NLR&#58; 0&#46;74&#41;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The power of the established cutoff points was calculated to have a specificity equal to or greater than 70&#37;&#46; The power of the specific serum IgE cutoff point and the skin test for cow&#39;s milk&#44; calculated using Youden&#39;s index&#44; was 99&#46;9&#37; in both&#44; thus considered as having high power&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">In clinical practice&#44; new diagnostic tests are used for different reasons&#58; for screening&#44; to obtain better information&#44; due to lower costs&#44; or as a complement to existing exams&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> Perfect tests do not exist&#44; but it is necessary to know how well a test can differentiate ill individuals from healthy ones&#44; <span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; the diagnostic test accuracy&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">The present study has some advantages&#44; as it is a prospective&#44; cross-sectional study of diagnostic accuracy that evaluated children up to 3 years of age with objective symptoms of CMPA&#44; which allowed the use of open OCT as a diagnostic method&#44; eliminating the need for DBPCOCT&#44; a less feasible procedure&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#44;6</span></a> For the most part&#44; the studies included patients in different age ranges&#44; and some of them included adults&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#8211;15</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">All children were submitted to open OCT regardless of IgE levels and mean papule diameters&#44; minimizing selection bias&#46; The time of the exclusion diet before OCT did not interfere with the results&#46; OCT with symptoms was considered positive &#40;allergic&#41; and&#44; without symptoms&#44; negative &#40;non-allergic or tolerant&#41;&#46; The solely discriminatory performance of the ROC curves is due to the uncertainty regarding the predictive power for allergy and&#47;or tolerance by specific IgE serum levels and mean papule diameter for patients in the assessed age range&#44; non-anaphylactic&#44; and in distinct locations&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The use of ImmunoCAP<span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span>&#44; a technique of quantitative serum-specific IgE detection&#44; allowed the researchers to establish a relationship between IgE levels and a food allergy diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> Published studies that proposed and discussed cutoff point values for CMPA diagnosis described different results between studied populations&#44; pointing to the need to establish values for each specific population&#44; which motivated this study &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#8211;15</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">In Brazil&#44; cutoff points for CM-specific IgE serum concentrations were established for phenotypically distinct populations in S&#227;o Paulo&#44; with different results&#58; 3&#46;06<span class="elsevierStyleHsp" style=""></span>kUA&#47;L for anaphylactic<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> and 11<span class="elsevierStyleHsp" style=""></span>kUA&#47;L for non-anaphylactic cases&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">According to the definition&#44; the cutoff point is considered good when it combines high PPV and Sp&#46; In the present study&#44; the ROC curve showed that the optimal cutoff point for CM &#40;<span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; the point at which the weight of S is equal to that of Sp&#41; using Youden&#39;s index was 5&#46;17<span class="elsevierStyleHsp" style=""></span>kUA&#47;L &#40;Sp&#58; 90&#37; and PPV&#58; 88&#37;&#41;&#46; When trying to find a better cutoff point&#44; <span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; with a higher PPV&#44; establishing the PPV at 90&#37; or 95&#37;&#44; the value provided by the curve was 77&#46;7<span class="elsevierStyleHsp" style=""></span>kUA&#47;L &#40;Sp and PPV of 100&#37;&#59; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In clinical practice&#44; the most appropriate level of specific IgE to indicate whether or not to perform OCT depends on the clinical context&#46; If the challenge may be dangerous to the patient&#44; a low cutoff point would be of interest&#44; even at the cost of misidentifying the patient as allergic&#46; Although the value of 5&#46;17<span class="elsevierStyleHsp" style=""></span>kUA&#47;L did not show such adequate Sp and PPV&#44; accepting 77<span class="elsevierStyleHsp" style=""></span>kUA&#47;L would subject all children to OCT&#44; thus exposing many of them to risk situations &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Some studies have also documented the usefulness of IRST as a predictor of OCT positivity for CMPA diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13&#8211;15</span></a> The optimal cutoff point established for CM in IRST was 3&#46;5<span class="elsevierStyleHsp" style=""></span>mm &#40;Sp<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>90&#37; and PPV<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>87&#37;&#41;&#46; When trying to find a better cutoff point&#44; establishing the PPV at 90&#37; or 95&#37;&#44; the value provided by the ROC curve was 5&#46;0<span class="elsevierStyleHsp" style=""></span>mm &#40;specificity and PPV of 100&#37;&#59; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Although there is no age restriction for IRST&#44; it is assumed that patients younger than 2 years of age may have smaller diameters&#44; because the skin reactivity acquired during childhood reaches its peak from 15 to 25 years of age and progressively declines&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> For this reason&#44; the skin IRST index&#44; the ratio between papule size and the positive control&#44; can be used to predict results of oral provocation tests&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> When establishing a previously determined positive value of 0&#46;6&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> and comparing the accuracy obtained with those of the cutoff points established by Youden&#39;s index and the maximization of Sp&#44; the best measure obtained was the value of 3&#46;5<span class="elsevierStyleHsp" style=""></span>mm &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Some authors correlated their skin index results with those of OCT&#59; however&#44; no usefulness was found in this study&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13&#44;14&#44;29</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0205" class="elsevierStylePara elsevierViewall">If the disease prevalence is high among the population&#44; the PPV and NPV results are influenced&#46; A prevalence adjustment would be impossible due to the lack of knowledge about the prevalence of CMPA in this region and in Brazil and&#44; thus&#44; alternative measures of performance such as PLR and NLR were performed&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">In the diagnostic evaluation of CM-associated component use in the evaluation of children with suspected CMPA&#44; these results would agree with those published by Castro et al&#46;&#44; who demonstrated that there was no increase in the diagnostic evaluation when using the components in addition to CM&#44; if they had been analyzed one by one&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> However&#44; when the different possible combinations are evaluated&#44; it is shown that any association has better accuracy than total CM alone&#46; Garcia-Ara et al&#46; also observed that&#44; when validating their results with OCT&#44; there was an advantage in the diagnosis when the protein fractions were associated&#46; Additionally&#44; the negativity of the fractions excluded CMPA in many cases due to its high NPV&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">To evaluate if the results obtained were associated with the agreement between the fractions &#40;&#945;-lactalbumin&#44; &#946;-lactoglobulin&#44; and casein&#41; and CM&#44; since fractions should be included in the total component of CM&#44; Krippendorf&#39;s <span class="elsevierStyleItalic">&#945;</span> was used as the measure of agreement&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> The observation of levels that were discretely superior to zero allowed us to state that the use of fractions&#44; both for IgE measurements and for papule diameter in the IRST&#44; helps in the diagnosis of CMPA in children under 3 years of age&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">In conclusion&#44; the cutoff level of the specific IgE for CM in children treated at a specialized service showed to be discriminatory for the diagnosis of CMPA&#44; with a value of 5&#46;17<span class="elsevierStyleHsp" style=""></span>kUA&#47;L&#44; as well as a mean papule diameter for CM of 3&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of interest</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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    "fechaRecibido" => "2017-01-19"
    "fechaAceptado" => "2017-04-21"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec984699"
          "palabras" => array:5 [
            0 => "Milk hypersensitivity"
            1 => "Accuracy"
            2 => "Child"
            3 => "Epidemiology"
            4 => "ROC curve"
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          "clase" => "keyword"
          "titulo" => "Palavras-chave"
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          "palabras" => array:5 [
            0 => "Hipersensibilidade a leite"
            1 => "Acur&#225;cia"
            2 => "Crian&#231;a"
            3 => "Epidemiologia"
            4 => "Curva ROC"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To compare serum concentrations of specific IgE and mean papule diameters induced in the immediate skin reactivity test with cow&#39;s milk and its fractions with results of the oral challenge test&#44; and to establish cutoff points capable of predicting clinical reactivity to cow&#39;s milk in patients treated at a referral service&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">One hundred and twenty-two children &#40;median of 17 months&#41; with a history of immediate reactions to cow&#39;s milk and presence of specific IgE for cow&#39;s milk and&#47;or its fractions &#40;positive skin and&#47;or IgE serum tests&#41; were submitted to open oral challenge test with cow&#39;s milk&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The oral challenge test was positive in 59&#46;8&#37; of the children&#44; 49&#37; of whom were males&#46; Serum levels of specific IgE&#44; as well as mean cow&#39;s milk papule diameters&#44; were significantly higher in allergic patients &#40;medians&#58; 3&#46;39<span class="elsevierStyleHsp" style=""></span>kUA&#47;L <span class="elsevierStyleItalic">vs&#46;</span> 1&#46;16<span class="elsevierStyleHsp" style=""></span>kUA&#47;L&#44; 2&#46;5<span class="elsevierStyleHsp" style=""></span>mm <span class="elsevierStyleItalic">vs&#46;</span> 0<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; The optimal cutoff points &#40;Youden&#39;s index&#41; of serum IgE specific for cow&#39;s milk and its fractions capable of predicting cow&#39;s milk reactivity &#40;positive oral challenge test&#41; were&#58; 5&#46;17<span class="elsevierStyleHsp" style=""></span>kUA&#47;L for cow&#39;s milk&#44; 0&#46;95<span class="elsevierStyleHsp" style=""></span>kUA&#47;L for &#945;-lactalbumin&#44; 0&#46;82<span class="elsevierStyleHsp" style=""></span>kUA&#47;L for &#946;-lactoglobulin&#44; and 0&#46;72<span class="elsevierStyleHsp" style=""></span>kUA&#47;L for casein&#44; whereas for papule diameters the cutoff points were 3&#46;5<span class="elsevierStyleHsp" style=""></span>mm for cow&#39;s milk and 6&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#44; 9&#46;0<span class="elsevierStyleHsp" style=""></span>mm&#44; and 3&#46;0<span class="elsevierStyleHsp" style=""></span>mm for the &#945;-lactalbumin&#44; &#946;-lactoglobulin&#44; and casein fractions&#44; respectively&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The cutoff points capable of predicting clinical reactivity to cow&#39;s milk were&#58; 5&#46;17<span class="elsevierStyleHsp" style=""></span>kUA&#47;L for serum-specific IgE and 3&#46;5<span class="elsevierStyleHsp" style=""></span>mm for papule diameter measurement&#44; values considered discriminatory for the diagnosis of cow&#39;s milk allergy&#46;</p></span>"
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          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
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            "titulo" => "Methods"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Comparar concentra&#231;&#245;es s&#233;ricas de IgE espec&#237;fica e di&#226;metros m&#233;dios das p&#225;pulas induzidas no teste cut&#226;neo de leitura imediata com leite de vaca e suas fra&#231;&#245;es com resultados do teste de provoca&#231;&#227;o oral e estabelecer pontos de corte&#44; capazes de predizer reatividade cl&#237;nica ao leite de vaca em pacientes atendidos em um servi&#231;o de refer&#234;ncia&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Cento e vinte e duas crian&#231;as &#40;mediana 17 meses&#41;&#44; com hist&#243;ria de rea&#231;&#245;es imediatas ao leite de vaca e presen&#231;a de IgE espe&#231;&#237;ficas para leite de vaca e&#47;ou fra&#231;&#245;es &#40;testes cut&#226;neos e&#47;ou IgE s&#233;rica positivos&#41; foram submetidas ao teste de provocac&#184;&#227;o oral aberto com leite de vaca&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">O teste de provocac&#184;&#227;o oral foi positivo em 59&#44;8&#37; das crian&#231;as&#44; 49&#37; eram do sexo masculino&#46; Os n&#237;veis s&#233;ricos de IgE espec&#237;fica&#44; assim como os di&#226;metros m&#233;dios das p&#225;pulas para leite de vaca&#44; foram significantemente maiores nos al&#233;rgicos &#40;medianas&#58; 3&#44;39kUA&#47;L <span class="elsevierStyleItalic">vs</span> 1&#44;16 kUA&#47;L&#59; 2&#44;5<span class="elsevierStyleHsp" style=""></span>mm <span class="elsevierStyleItalic">vs</span> 0<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; Os &#8220;pontos de corte &#243;timos&#8221; &#40;&#205;ndice de Youden&#41; das IgE s&#233;ricas espec&#237;ficas para o leite de vaca e suas fra&#231;&#245;es capazes de predizer a reatividade ao leite de vaca &#40;teste de provocac&#184;&#227;o oral positivo&#41; foram&#58; 5&#44;17kUA&#47;L para o leite de vaca&#44; 0&#44;95 kUA&#47;L para &#945;-lactoalbumina&#44; 0&#44;82kUA&#47;L para &#946;-lactoglobulina e 0&#44;72kUA&#47;L para case&#237;na e para os di&#226;metros de p&#225;pulas foram 3&#44;5<span class="elsevierStyleHsp" style=""></span>mm para leite de vaca e 6&#44;5<span class="elsevierStyleHsp" style=""></span>mm&#44; 9&#44;0<span class="elsevierStyleHsp" style=""></span>mm e 3&#44;0<span class="elsevierStyleHsp" style=""></span>mm para as fra&#231;&#245;es &#945;-lactoalbumina&#44; &#946;-lactoglobulina e case&#237;na&#44; respectivamente&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Os n&#237;veis de corte capazes de predizer reatividade cl&#237;nica ao leite de vaca foram&#58; 5&#44;17kUA&#47;L para IgE s&#233;rica espec&#237;fica e 3&#44;5<span class="elsevierStyleHsp" style=""></span>mm para a medida do di&#226;metro da p&#225;pula&#44; valores considerados discriminat&#243;rios para o diagn&#243;stico da alergia ao leite de vaca&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Franco JM&#44; Pinheiro AP&#44; Vieira SC&#44; Barreto &#205;D&#44; Gurgel RQ&#44; Cocco RR&#44; et al&#46; Accuracy of serum IgE concentrations and papule diameter in the diagnosis of cow&#39;s milk allergy&#46; J Pediatr &#40;Rio J&#41;&#46; 2018&#59;94&#58;279&#8211;85&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Study carried out at Universidade Federal de S&#227;o Paulo &#40;UNIFESP&#41;&#44; Escola Paulista de Medicina&#44; S&#227;o Paulo&#44; SP&#59; and Universidade Federal de Sergipe&#44; Aracaju&#44; SE&#44; Brazil&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristic &#40;ROC&#41; curves to obtain optimum levels of specific serum IgE for&#58; &#40;a&#41; total cow&#39;s milk&#44; &#40;b&#41; &#945;-lactalbumin&#44; &#40;c&#41; &#946;-lactoglobulin&#44; &#40;d&#41; casein&#59; and for the mean papule diameter of the immediate reading skin test for&#58; &#40;e&#41; total cow&#39;s milk &#40;f&#41;&#44; &#945;-lactalbumin&#44; &#40;g&#41; &#946;-lactoglobulin&#44; and &#40;h&#41; casein in the open oral challenge test for cow&#39;s milk and its fractions&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">CM&#44; cow&#39;s milk&#59; &#945;&#44; &#945;-lactalbumin&#59; &#946;&#44; &#946;-lactoglobulin&#59; c&#44; casein&#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" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleBold">Serum measurement of specific IgE</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cutoff point of 0&#46;35</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">kUA&#47;L</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sensitivity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Specificity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Study PV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Positive &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Negative &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cutoff point by Youden&#39;s index</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Cutoff point&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sensitivity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Specificity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>PPV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NPV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Maximum specificity</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Cutoff point&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sensitivity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Specificity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>PPV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NPV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleBold">Immediate skin test reactivity</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cutoff point of 3</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mm</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sensitivity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Specificity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>PPV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NPV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cutoff point by Youden&#39;s index</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Cutoff point &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sensitivity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Specificity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>PPV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NPV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Maximum specificity</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Cutoff point &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sensitivity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Specificity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>PPV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NPV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Description of sensitivity &#40;S&#41;&#44; specificity &#40;Sp&#41;&#44; positive predictive values &#40;PPV&#41;&#44; and negative predictive values &#40;NPV&#41; for specific IgE concentrations for cow&#39;s milk and its fractions&#44; and for mean papule diameter in the immediate-reading skin reactivity test in the open oral provocation test&#44; by different criteria&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">P&#44; percentage&#59; Sp&#44; specificity&#59; PPV&#44; positive predictive values&#59; DBPC&#44; double-blinded placebo-controlled&#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" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference&#39;s<br>Author &#40;year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Diagnostic method&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">P &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PPV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cutoff point &#40;kUA&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sp &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cutoff point &#40;kUA&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sampson &#40;1997&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;6&#8211;17 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DBPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Garcia-Ara &#40;2001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;12 m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95<br>99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;5<br>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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Roehr &#40;2001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 m to 11 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DBPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59<br>86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;35<br>17&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38<br>96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;35<br>17&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Saarinen &#40;2001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Median&#58; 6&#46;9 m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92<br>58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;5<br>0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">94<br>49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;5<br>0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sampson &#40;2001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 m to 14 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DBPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100<br>95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">32<br>15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100<br>94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">32<br>15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Celik-Bilgili &#40;2005&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 m to 16 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&#47;DBPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">88&#46;8<br>25&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mehl &#40;2006&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 m to 14 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&#47;DBPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Komata &#40;2007&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;2&#8211;14 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&#47;DBPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95<br>95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&#46;9<br>5&#46;8 &#40;&#60;1 y&#41;<br>57&#46;3 &#40;&#62;2 y&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Van der Gugten &#40;2008&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;2&#8211;15 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DBPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23 &#40;&#60;2&#46;5 y&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Castro &#40;2015&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;9 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&#47;DBPC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Specific serum IgE values &#40;ImmunoCAP<span class="elsevierStyleSup">&#174;</span>&#41; predictive for the diagnosis of cow&#39;s milk allergy &#40;reproduced and modified from Luyt et al&#46;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a></p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">PLR&#44; positive likelihood ratio&#59; NLR&#44; negative likelihood ratio&#59; CI&#44; confidence interval&#46;</p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cow&#39;s milk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Youden&#39;s index &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Maximization of specificity &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Skin index &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cutoff &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sensitivity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Specificity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PLR &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NLR &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Accuracy &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Accuracy of the different cutoff points of the mean papule diameter for total cow&#39;s milk in the open rral provocation tests&#46;</p>"
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