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it has yet to be adequately applied as the core concept in AD management&#46; Skin acidification in murine models improved epidermal integrity&#44; transepidermal water loss &#40;TEWL&#41;&#44; accelerated barrier recovery<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> and prevented AD&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">2&#44;5&#44;6</span></a> It prevented emergence of oxazolone-induced AD&#44; reduced Th2-dominant inflammation&#44; normalized expression of antimicrobial peptides and inhibited generation of cytokines&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> Skin barrier and permeability function in normal mice improved with increased activities of &#946;-glucocerebrosidase and sphingomyelinase&#44; and reduction in serine protease dependent degradation of desmogleins&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> Application of the murine skin acidification concept in restoration of physiological skin acidity in AD and its effect on disease severity still requires further investigation&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Our study aimed to determine the effect of pH 4&#46;5 moisturizer in restoration of epidermal barrier in AD&#46; A moisturizer with pH that is more compatible with physiological pH could improve the skin pH in AD and subsequently its disease severity&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">A randomized half-body&#44; double-blind&#44; controlled study comparing a pH-modified moisturizer with a standard commercial moisturizer was performed&#46; Inclusion criteria were patients aged 12&#8211;65 years diagnosed with AD according to the Hanifin&#8211;Radjka Criteria&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> and stable mild to moderate AD for 1 month prior to recruitment&#46; Exclusion criteria were recurrent infections&#44; &#62;1&#37; body surface area with skin erosions&#44; known allergy or irritation reaction to aqueous cream&#44; glycerine&#44; methyl paraben or propyl paraben&#44; change in treatment regime 4 weeks before recruitment&#44; pregnancy and breast feeding&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Half body randomization was performed using sequentially numbered&#44; opaque sealed envelopes &#40;SNOSE&#41;&#46; Investigators and patients were blinded throughout the study&#46; Patients were instructed to apply one moisturizer on one side of the body from the neck below and one moisturizer on the other side twice a day for 6 weeks&#46; All other topical and oral treatments the patients were using prior to study enrollment except moisturizers were continued&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Measurements of skin pH and transepidermal water loss &#40;TEWL&#41; were performed at baseline &#40;week 0&#41;&#44; week 2 and week 6 at 6 pre-determined sites&#44; bilateral forearms&#44; right and left side of abdomen and bilateral anterior shins&#46; Patients rested for at least 20<span class="elsevierStyleHsp" style=""></span>min at 22<span class="elsevierStyleHsp" style=""></span>&#176;C in relative humidity of 55&#8211;60&#37;&#46; Measurements were performed at least 5<span class="elsevierStyleHsp" style=""></span>h after moisturizer and other topical therapy application&#46; Skin pH was assessed by Hanna Instruments H199181&#46; Transepidermal water loss was assessed by Tewameter TM300&#46; Three readings were taken per assessment and an average was obtained&#46; A modified objective SCORing Atopic Dermatitis &#40;SCORAD&#41; was used to determine disease severity&#46; The A component was doubled in the calculation of the final score&#46; The assessment of itch and sleeplessness in component C was excluded as it was difficult to differentiate the severity of itch on each side of the body and impossible to determine the effect of symptoms from half of the body to accounts for sleeplessness&#46; The modified objective SCORAD was calculated as 2 &#40;<span class="elsevierStyleItalic">A</span>&#47;5&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleItalic">B</span>&#47;2&#46; Score of &#60;15 was considered mild&#44; 15&#8211;40 was moderate&#44; while &#62;40 was severe&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">8</span></a> Itch was evaluated using a visual analog score &#40;VAS&#41; of 0&#8211;10 with 0 representing no itch&#44; and 10 representing most severe itch&#46; The Dermatology Life Quality Index Questionnaire &#40;DLQI&#41;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a> were used to determine the disease effect on the patients&#8217; quality of life&#46; SCORAD&#44; itch score and DLQI were determined at baseline &#40;week 0&#41;&#44; week 2 and at week 6&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The standard commercial moisturizer used was aqueous cream manufactured by KCK Pharmaceutical Industries Sdn Bhd&#46; The ingredients include 9&#37; emulsifying wax&#44; 6&#37; liquid paraffin&#44; 15&#37; white soft paraffin&#44; 0&#46;15&#37; methyl paraben and 0&#46;08&#37; propyl paraben&#46; The cream has pH of 7&#46;32&#8211;7&#46;58 measured by LAQUA pH meter by HORIBA Scientific&#46; The pH of this moisturizer was modified to achieve the desired pH of 4&#46;5 by adding citric acid 5&#37;&#46; Citric acid was chosen as it was easily available&#46; Citric acid forms a small component of the natural moisturizing factors and topical application has been shown to be beneficial in ichthyiosis&#44; increased epidermal thickness and increased dermal glycosaminoglycan&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">10&#44;11</span></a> The pH-modified cream remained stable over 3 months at room temperature without changes in color&#44; smell&#44; texture&#44; consistency and pH&#46; Both the standard commercial moisturizer cream and pH-modified cream have similar color&#44; smell&#44; texture and consistency&#46; The study was approved by Research Ethics Committee&#44; the National University of Malaysia research code FF-2018-058&#46; Funding was obtained from the Fundamental Research Grant&#44; National University of Malaysia with the same research code&#46; Sample size was calculated with effect size of 0&#46;2 and standard deviation of the outcome of 0&#46;18 based on the results of Danby et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a> Two-tailed alpha level was set at 0&#46;05&#44; beta level 0&#46;2&#46; Using the formula &#40;1&#47;<span class="elsevierStyleItalic">q</span>1<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1&#47;<span class="elsevierStyleItalic">q</span>0&#41; &#40;<span class="elsevierStyleItalic">Z&#945;</span><span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Z&#946;</span>&#41;<span class="elsevierStyleSup">2</span>&#47;&#40;<span class="elsevierStyleItalic">E</span>&#47;<span class="elsevierStyleItalic">S</span>&#41;<span class="elsevierStyleSup">2</span>&#44; the sample size was 36 with consideration of 20&#37; drop out rate&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> SPSS statistical software was used for statistical analyses&#46; Where there were more than 2 variables compared&#44; <span class="elsevierStyleItalic">p</span>-values were obtained using Friedman test&#46; Wilcoxon test was used to determine changes between baseline&#44; week 2 and week 6&#46; Mann&#8211;Whitney test was used to analyze the differences between standard moisturizer and pH-modified moisturizer groups&#59; <span class="elsevierStyleItalic">p</span>-value &#60;0&#46;05 was considered significant&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">Thirty six patients with AD participated in the study&#46; Thirty patients were females while 6 were males&#46; The age ranged from 12 to 64 years while the median age was 24&#46;5 &#40;28&#46;7&#41; years old&#46; There were 20 &#40;55&#46;6&#37;&#41; Malays&#44; 9 &#40;25&#37;&#41; Chinese&#44; 5 &#40;13&#46;9&#37;&#41; Indians and 2 &#40;5&#46;5&#37;&#41; of other ethnicities&#46; Twenty-one &#40;58&#46;3&#37;&#41; patients had allergic rhinitis or sinusitis&#44; 12 &#40;33&#46;3&#37;&#41; had allergic conjunctivitis and food allergy respectively&#44; and 29 &#40;80&#46;6&#37;&#41; had positive allergy test&#46; Thirty &#40;83&#46;3&#37;&#41; patients were on moisturizers and 31 &#40;86&#46;1&#37;&#41; on topical steroid application&#44; 15 &#40;41&#46;7&#37;&#41; of them required antihistamine&#46; The types of moisturizers used by the patients were&#58; aqueous cream 13 &#40;36&#46;1&#37;&#41;&#44; aqueous cream with glycerin 12 &#40;33&#46;3&#37;&#41;&#44; paraffin 3 &#40;8&#46;3&#37;&#41;&#44; others 2 &#40;5&#46;6&#37;&#41; i&#46;e&#46; 1 oatmeal based and 1 urea based moisturizer while 6 &#40;16&#46;7&#37;&#41; not using any moisturizer&#46; Baseline disease severity assessments revealed modified objective SCORAD median value of 14&#46;3 &#40;10&#46;7&#41;&#44; body surface area &#40;BSA&#41; was 1&#46;0 &#40;1&#46;5&#41;&#44; itch score was 4 &#40;3&#41; and DLQI was 7&#46;5 &#40;5&#46;75&#41;&#46; Characteristics of the study population are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">pH-modified moisturizer</span><p id="par0045" class="elsevierStylePara elsevierViewall">Skin pH decreased from week 0 to week 6 at all sites&#44; greater reduction was observed at week 2&#46; The values increased slightly from week 2 to week 6 but remained lower than baseline &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The pH reductions from week 0 to week 6 were significant at the forearms 5&#46;315 &#40;0&#46;98&#41; at week 0&#44; 4&#46;85 &#40;0&#46;54&#41; at week 2&#44; 5&#46;04 &#40;0&#46;78&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024 and abdomen 5&#46;25 &#40;1&#46;01&#41; at week 0&#44; 4&#46;82 &#40;0&#46;64&#41; at week 2&#44; 5&#46;01 &#40;0&#46;59&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;000 but not at the shins 5&#46;01 &#40;0&#46;80&#41; at week 0&#44; 4&#46;76 &#40;0&#46;49&#41; at week 2&#44; 4&#46;85 &#40;0&#46;79&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;088&#46; TEWL decreased from week 0 to week 6 at all sites&#46; TEWL significantly decreased from 4&#46;60 &#40;2&#46;55&#41; at week 0 to 3&#46;70 &#40;3&#46;10&#41; at week 2 and 3&#46;00 &#40;3&#46;55&#41; at week 6 with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00 at the forearms &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; At the abdomen&#44; TEWL decreased from 3&#46;90 &#40;2&#46;90&#41; at week 0 to 2&#46;40 &#40;3&#46;45&#41; at week 2 but increased slightly to 2&#46;70 &#40;2&#46;25&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; The changes observed over the shins were not significant&#44; TEWL at week 0 was 3&#46;70 &#40;2&#46;30&#41;&#44; 3&#46;50 &#40;2&#46;25&#41; at week 2 and 3&#46;50 &#40;2&#46;85&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;10&#46; The changes in skin pH and TEWL at the pH modified moisturizer application sites are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">table 2</a>&#46; SCORAD improved significantly&#44; median SCORAD was 14&#46;1 &#40;12&#46;75&#41; at week 0&#44; 10&#46;5 &#40;13&#46;25&#41; at week 2 and 7 &#40;12&#46;65&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Standard moisturizer</span><p id="par0050" class="elsevierStylePara elsevierViewall">Similar pattern of reduction in skin pH from week 0 to week 6 with greater reduction at week 2 was observed at standard moisturizer application sites &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The pH reduction was significant at the forearm&#44; 5&#46;29 &#40;0&#46;94&#41; at week 0&#59; 4&#46;84 &#40;0&#46;55&#41; at week 2 and 5&#46;02 &#40;0&#46;70&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00 and the abdomen 5&#46;25 &#40;1&#46;09&#41; at week 0&#44; 4&#46;91&#40;0&#46;63&#41; at week 2&#44; 5&#46;12 &#40;0&#46;66&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#46; There pH changes at the shin were not significant with 4&#46;98 &#40;0&#46;91&#41; at week 0&#44; 4&#46;79 &#40;0&#46;50&#41; at week 2&#44; and 4&#46;93 &#40;0&#46;82&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;432&#46; TEWL at the forearms and shins showed non-significant slight reductions at week 2 followed by an increment at week 6 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; TEWL at the forearm was 4&#46;80 &#40;2&#46;95&#41; at week 0&#44; 4&#46;10 &#40;2&#46;15&#41; at week 2&#44; and 4&#46;60 &#40;3&#46;40&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;67&#46; At the shins&#44; TEWL was 3&#46;80 &#40;1&#46;40&#41; at week 0&#44; 3&#46;50 &#40;2&#46;35&#41; at week 2 and 4&#46;00 &#40;2&#46;50&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;913&#46; TEWL increased transiently and later decreased to below baseline values on the abdomen measuring 3&#46;70 &#40;2&#46;45&#41; at week 0&#44; 4&#46;10 &#40;3&#46;60&#41; at week 2 and 3&#46;40 &#40;2&#46;95&#41; at week 6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;80&#46; Results for pH and TEWL at standard moisturizer applications sites are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">table 2</a>&#46; SCORAD improved significantly with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#44; the median value at week 0 was 14&#46;2 &#40;9&#46;1&#41;&#44; 10&#46;9 &#40;10&#46;65&#41; at week 2 and 10&#46;5 &#40;11&#41; at week 6 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">pH-modified moisturizer vs standard moisturizer</span><p id="par0055" class="elsevierStylePara elsevierViewall">Greater pH reduction was observed at pH-modified moisturizer sites at the abdomen and shin &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; TEWL values were lower at pH-modified moisturizer sites at forearm and abdomen &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; SCORAD were lower at the pH-modified moisturizer sites at week 2 and week 6 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; However&#44; there were no statistically significant differences in the pH&#44; TEWL and SCORAD values between the standard moisturizer and pH-modified moisturizer sites&#46; Improvement in SCORAD was mirrored by significant reduction in itch scores and DLQI &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">One patient developed ipsilateral erythema requiring topical corticosteroid most likely due to a reaction to the pH-modified moisturizer&#46; Two patients developed mild flares which were symmetrical and bilateral&#46; Other side effect reported was hypertrichosis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; over both legs upon completion of the study&#46; Another patient reported mild tingling sensation with pH modified moisturizer application which disappeared after two weeks&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">The clinical and biophysical effects of moisturizers on AD skin are under-explored despite extensive use of various types of moisturizers in standard AD management&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">14&#44;15</span></a> The effects of mineral oils&#44; a common ingredient in moisturizers on the skin barrier in AD patients are poorly documented&#46; Aqueous cream was chosen as the moisturizer in this study as it is the preferred moisturizer in most of our patients&#44; cost-effective and is more amendable to pH modification&#46; Aqueous cream is preferred by our patients as it feels less greasy&#44; an important factor that facilitate compliance in our tropical hot and humid weather&#46; The aqueous cream did not contain sodium laureth sulfate &#40;SLS&#41;&#44; which is the most likely agent responsible for adverse effects reported with aqueous cream&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">16&#44;17&#44;18</span></a> Aqueous cream with SLS caused reduced stratum corneum thickness with increase in TEWL after 4 weeks of regular application&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">15&#44;16</span></a> We observed improvements in both pH and TEWL with aqueous cream &#40;without SLS&#41;&#44; pH values were significantly lower from baseline at 6 weeks while there was no significant changes in TEWL&#46; This suggests that the use of SLS rather than aqueous cream should be prohibited for leave-on or wash-off purposes but further confirmatory evidence is required&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Our results showed that skin pH&#44; TEWL and AD severity improved with moisturizer application irrespective of the pH of the moisturizer used&#46; Inclusion of moisturizers in management of AD has been shown to improved disease severity&#44; reduced flares and decreased the amount of topical corticosteroid requirement compared with no moisturizer&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> These effects were observed with various types of moisturizers&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> The relationship between clinical AD improvement with biophysical parameters like pH&#44; TEWL and hydration are still unclear as these are not evaluated in most moisturizer studies&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a> Reduction in clinical severity scores seemed to be accompanied by improvement in skin hydration with no change in TEWL&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a> Data on effect of moisturizers on skin pH is even more lacking&#46; The effect of a moisturizer with pH 4&#46;92 &#40;Diprobase&#174; cream&#41; was compared with aqueous cream &#40;containing SLS&#41; and another moisturizer with pH 7&#46;13 &#40;Doublebase&#8482; gel&#41; in patients with quiescent AD&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a> Skin pH and hydration increased while TEWL decreased transiently following a single application of all three moisturizers&#46; pH increased significantly with Doublebase&#8482; gel and Diprobase&#174; cream upon 28 days of repeated use&#44; there were no changes in TEWL but hydration was better with Doublebase&#8482; gel&#46; The pH of the moisturizers did not seem to affect skin pH and TEWL differently&#46; The difference in hydration maybe attributed to humectant component of Doublebase&#8482; gel as the other moisturizers contain only occlusive agents&#46; Occlusive dressings have been demonstrated to improve skin hydration&#44; but caused increased pH and TEWL&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">19&#44;20</span></a> Long term use of occlusive moisturizers containing paraffin may result in the same effect&#46; The surface pH changes that results from moisturizer application is most likely inadequate to overcome the effects of the skin&#39;s intrinsic buffering mechanisms&#46; In addition&#44; concomitant use of skin cleansers and topical steroids which are more alkaline in formulation may have overwhelmed the effect of the moisturizer&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">While pH changes with both moisturizers were comparable&#44; we observed significant TEWL improvement at pH-modified moisturizer sites which was not observed at standard moisturizer sites&#46; TEWL reduction is typically not achieved by application of most moisturizers irrespective of its ingredients&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">12&#44;14</span></a> TEWL reduction is seen with topical pharmacological interventions such as corticosteroid and calcineurin inhibitor&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> The benefit of physiologically compatible pH moisturizer may be due to its effect on TEWL rather than skin surface pH&#46; Acidification of AD skin inhibits activity of pH-sensitive serine proteases that is responsible for accelerated desquamation and increase synthesis of lipids for formation of the extracellular lamellar matrix&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a> both are key components of the permeability barrier represented by TEWL&#46; Evaluation of stratum corneum compounds is needed to further investigate this aspect&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Both moisturizers were well tolerated&#44; mild and transient adverse effects were observed&#46; All patients have previously used aqueous cream without experiencing adverse effects&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Limitations of this study include the absence of a washout period of the patients&#8217; moisturizer prior to initiation of the study moisturizer&#46; Baseline pH was obtained at least 5<span class="elsevierStyleHsp" style=""></span>h after the last application of the patients&#8217; routine moisturizer&#46; However&#44; the majority of patients were either moisturizer na&#239;ve&#44; using aqueous cream&#44; or aqueous cream in combination with glycerin&#46; In addition&#44; washout was not performed to avoid triggering disease flare&#46; We did not measure skin hydration&#44; thus is unable to show the relationship between hydration and pH&#46; The status of the study participants&#8217; filaggrin deficiency was not determined&#59; this could affect the interpretation of our results&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conclusion</span><p id="par0090" class="elsevierStylePara elsevierViewall">Standard aqueous cream and pH-modified aqueous cream both improved skin pH&#46; There were no significant differences in pH and TEWL values between the two moisturizers&#46; pH reduction was observed with both moisturizers&#46; There was significant TEWL improvement with pH-modified moisturizer was not observed with standard moisturizer&#46; Application of both moisturizers resulted in improvement of AD&#46; Moisturizer with physiological pH is useful as an adjunct in the treatment of AD&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Financial support</span><p id="par0095" class="elsevierStylePara elsevierViewall">Fundamental research grant from <span class="elsevierStyleGrantSponsor" id="gs1">National University of Malaysia</span>&#44; Malaysia&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Authors&#39; contributions</span><p id="par0100" class="elsevierStylePara elsevierViewall">Goh Siew Wen&#58; Statistic analysis&#59; approval of the final version of the manuscript&#59; conception and planning of the study&#59; elaboration and writing of the manuscript&#59; obtaining&#44; analysis&#44; and interpretation of the data&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Adawiyah Jamil&#58; Approval of the final version of the manuscript&#59; conception and planning of the study&#59; elaboration and writing of the manuscript&#59; obtaining&#44; analysis&#44; and interpretation of the data&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Nazarudin Safian&#58; Statistic analysis&#59; approval of the final version of the manuscript&#59; conception and planning of the study&#59; obtaining&#44; analysis&#44; and interpretation of the data&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Norazirah Md Nor&#58; Statistic analysis&#59; approval of the final version of the manuscript&#59; conception and planning of the study&#59; elaboration and writing of the manuscript&#59; obtaining&#44; analysis&#44; and interpretation of the data&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the manuscript&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Norliza Muhammad&#58; Approval of the final version of the manuscript&#59; conception and planning of the study&#59; elaboration and writing of the manuscript&#59; obtaining&#44; analysis&#44; and interpretation of the data&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the manuscript&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Nur Liyana Saharudin&#58; Approval of the final version of the manuscript&#59; conception and planning of the study&#59; elaboration and writing of the manuscript&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicts of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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          "titulo" => "Results"
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            0 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "pH-modified moisturizer"
            ]
            1 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Standard moisturizer"
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            2 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "pH-modified moisturizer vs standard moisturizer"
            ]
          ]
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        5 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Discussion"
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        6 => array:2 [
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          "titulo" => "Conclusion"
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          "identificador" => "sec0045"
          "titulo" => "Financial support"
        ]
        8 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Authors&#39; contributions"
        ]
        9 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Conflicts of interest"
        ]
        10 => array:2 [
          "identificador" => "xack473882"
          "titulo" => "Acknowledgments"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-05-30"
    "fechaAceptado" => "2019-11-25"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1254927"
          "palabras" => array:3 [
            0 => "Atopic&#44; dermatitis"
            1 => "Eczema"
            2 => "Emollients"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Higher skin pH in atopic dermatitis contributes to impaired epidermal barrier&#46; A moisturizer compatible with physiological pH could improve atopic dermatitis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine the effect of a physiologically compatible pH moisturizer in atopic dermatitis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A randomized half body&#44; double blind&#44; controlled trial involving patients with stable atopic dermatitis was performed&#46; pH-modified moisturizer and standard moisturizer were applied to half body for 6 weeks&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 6 &#40;16&#46;7&#37;&#41; males and 30 &#40;83&#46;3&#37;&#41; females participated&#46; Skin pH reductions from week 0&#44; week 2 and 6 were significant at the forearms &#40;5&#46;315 &#91;0&#46;98&#93; to 4&#46;85 &#91;0&#46;54&#93; to 5&#46;04 &#91;0&#46;78&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; and abdomen &#40;5&#46;25 &#91;1&#46;01&#93;&#44; 4&#46;82 &#91;0&#46;64&#93;&#44; 5&#46;01 &#91;0&#46;59&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41; but not at the shins &#40;5&#46;01 &#91;0&#46;80&#93;&#44; 4&#46;76 &#91;0&#46;49&#93;&#44; 4&#46;85 &#91;0&#46;79&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;09&#41; with pH-modified moisturizer&#46; Transepidermal water loss &#40;TEWL&#41; at the forearms decreased &#40;4&#46;60 &#91;2&#46;55&#93; to 3&#46;70 &#91;3&#46;10&#93; to 3&#46;00 &#91;3&#46;55&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41;&#44; abdomen &#40;3&#46;90 &#91;2&#46;90&#93; to 2&#46;40 &#91;3&#46;45&#93; to 2&#46;70 &#91;2&#46;25&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;046&#41;&#46; SCORAD improved from 14&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;75 to 10&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;25 to 7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;25&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#46; In standard moisturizer group&#44; pH reductions were significant at the forearms &#40;5&#46;29 &#91;0&#46;94&#93; to 4&#46;84 &#91;0&#46;55&#93; to 5&#46;02 &#91;0&#46;70&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41; and abdomen &#40;5&#46;25 &#91;1&#46;09&#93;&#44; 4&#46;91 &#91;0&#46;63&#93;&#44; 5&#46;12 &#91;0&#46;66&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#41;&#46; TEWL at the forearm were &#40;4&#46;80 &#91;2&#46;95&#93;&#44; 4&#46;10 &#91;2&#46;15&#93;&#44; 4&#46;60 &#91;3&#46;40&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;67&#41;&#44; shins &#40;3&#46;80 &#91;1&#46;40&#93;&#44; 3&#46;50 &#91;2&#46;35&#93;&#44; 4&#46;00 &#91;2&#46;50&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;91&#41; and abdomen &#40;3&#46;70 &#91;2&#46;45&#93;&#44; 4&#46;10 &#91;3&#46;60&#93;&#44; 3&#46;40 &#91;2&#46;95&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;80&#41;&#46; SCORAD improved from 14&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;1 to 10&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;65 to 10&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00&#46; Reduction in pH was observed with both moisturizers while TEWL significantly improved with pH-modified moisturizer&#46; pH-modified moisturizer resulted in greater pH&#44; TEWL and SCORAD improvements however the differences were not significant from standard moisturizer&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Study limitation</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Skin hydration was not evaluated&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusion</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Moisturization is beneficial for atopic dermatitis&#59; use of physiologically compatible pH moisturizer is promising&#46;</p></span>"
        "secciones" => array:6 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
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            "identificador" => "abst0015"
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            "identificador" => "abst0020"
            "titulo" => "Results"
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          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Study limitation"
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          5 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Conclusion"
          ]
        ]
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    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">How to cite this article&#58; Wen GS&#44; Jamil A&#44; Safian N&#44; Md Nor M&#44; Muhammad N&#44; Saharudin NL&#46; A randomized half-body&#44; double blind&#44; controlled trial on the effects of a pH-modified moisturizer vs&#46; standard moisturizer in mild to moderate atopic dermatitis&#46; An Bras Dermatol&#46; 2020&#59;95&#58;320&#8211;5&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Study conducted at the Dermatology Unit&#44; Department of Medicine&#44; University Kebangsaan Malaysia Medical Center&#44; Kuala Lumpur&#44; Malaysia&#46;</p>"
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                  \t\t\t\t">6 &#40;16&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Chinese&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">5 &#40;13&#46;9&#37;&#41;&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
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                  \t\t\t\t">2 &#40;5&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">21 &#40;58&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">12 &#40;33&#46;3&#37;&#41;&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  " align="char" valign="\n
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                  \t\t\t\t">12 &#40;33&#46;3&#37;&#41;&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
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                  \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">5 &#40;13&#46;9&#37;&#41;&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"><span class="elsevierStyleHsp" style=""></span>Positive pick&#47;Patch test&#47;serum IgE&nbsp;\t\t\t\t\t\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">29 &#40;80&#46;6&#37;&#41;&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
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>Moisturizer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;83&#46;3&#37;&#41;&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"><span class="elsevierStyleHsp" style=""></span>Topical steroids&nbsp;\t\t\t\t\t\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">31 &#40;86&#46;1&#37;&#41;&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"><span class="elsevierStyleHsp" style=""></span>Systemic immunosuppressant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#37;&#41;&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"><span class="elsevierStyleHsp" style=""></span>Antihistimine&nbsp;\t\t\t\t\t\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">15 &#40;41&#46;7&#37;&#41;&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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Type of moisturizer</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"><span class="elsevierStyleHsp" style=""></span>Aqueous cream&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;36&#46;1&#37;&#41;&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"><span class="elsevierStyleHsp" style=""></span>Aqueous cream with glycerine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;33&#46;3&#37;&#41;&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"><span class="elsevierStyleHsp" style=""></span>Paraffin&nbsp;\t\t\t\t\t\t\n
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                  \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 &#40;8&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>Others&nbsp;\t\t\t\t\t\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 &#40;5&#46;6&#37;&#41;&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"><span class="elsevierStyleHsp" style=""></span>No moisturizer&nbsp;\t\t\t\t\t\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 &#40;16&#46;7&#37;&#41;&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="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Disease severity</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"><span class="elsevierStyleHsp" style=""></span>Modified objective SCORAD&nbsp;\t\t\t\t\t\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;3 &#40;10&#46;7&#41;&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"><span class="elsevierStyleHsp" style=""></span>BSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;0 &#40;1&#46;5&#41;&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"><span class="elsevierStyleHsp" style=""></span>DLQI&nbsp;\t\t\t\t\t\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">7&#46;5 &#40;5&#46;75&#41;&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"><span class="elsevierStyleHsp" style=""></span>Itch score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t\tvoid\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">Parameter&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">Site&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">Week&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">pH-modified moisturizer&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">Standard moisturizer&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"><span class="elsevierStyleItalic">p</span>-Value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pH</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">Forearm</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;32 &#40;0&#46;98&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;29 &#40;0&#46;94&#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  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;90</td></tr><tr title="table-row"><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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;85 &#40;0&#46;54&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;84 &#40;0&#46;55&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;04 &#40;0&#46;78&#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">5&#46;02 &#40;0&#46;70&#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></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Abdomen</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;25 &#40;1&#46;01&#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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;25 &#40;1&#46;09&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;74</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;82 &#40;0&#46;64&#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">4&#46;91 &#40;0&#46;63&#41;&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;01 &#40;0&#46;59&#41;<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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;12 &#40;0&#46;66&#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></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shin</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;01 &#40;0&#46;80&#41;&nbsp;\t\t\t\t\t\t\n
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