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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">Prednisolone &#40;PDN&#41; has changed the prognosis of nephrotic syndrome &#40;NS&#41; since 1950&#46; Nearly 12&#8211;24&#37; of patients are steroid-resistant and about 70&#37; experience at least one episode of relapse&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> Besides the great benefits&#44; there are many concerns about the disadvantages of PDN&#44; particularly about its negative effects on linear growth&#46; Several mechanisms have been proposed regarding the effects of NS on growth&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Some studies have confirmed the short-time inhibitory effects of PDN on growth by comparing height <span class="elsevierStyleItalic">Z</span>-score &#40;Ht&#46;<span class="elsevierStyleItalic">Z</span>s&#41; before and after treatment between frequent and infrequent relapsers&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;3</span></a> Other studies have investigated its negative impact in long-term use&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">4&#44;5</span></a> some others have followed patients longitudinally to compare their final height with their peers&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">6&#44;7</span></a> and finally&#44; some have used a combination of methods&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Theoretically&#44; growth potential can be evaluated using final height prediction in childhood&#46; Several methods have been proposed for this purpose&#46; The chronological age &#40;CA&#41;-based system decreases the prediction as bone age &#40;BA&#41; increases&#46; However&#44; the bone age-based system does not do this&#46; In the BA-based system&#44; the predictions are less affected by bone age discrepancies&#44; but the effect is not symmetrical&#46; Greulich-Pyle &#40;GP&#41; and Tanner-Whitehouse &#40;TW&#41; methods for skeletal age determination can be used for predicting adult height&#44; which is helpful in diagnosing and evaluating the effects of treatment&#46; In this method&#44; the predicted adult height &#40;PAHt&#46;&#41; is compared to the expected adult height &#40;target range of height&#59; target height &#91;THt&#46;&#93;&#44; calculated as mid-parental height &#91;MPHt&#46;&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">By newer TW Mark systems&#44; the errors of prediction are generally a little smaller than those arising from the Bayley-Pinneau predictions&#44; and considerably smaller in the case of postmenarcheal girls&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of this study was to evaluate potential short-term and long-term effects of PDN on linear growth by comparing&#58; &#40;a&#41; Ht&#46;<span class="elsevierStyleItalic">Z</span>s before and after treatment&#44; &#40;b&#41; post-treatment predicted final height compared with &#40;potential pre-treatment&#41; mid-parental target height&#44; and &#40;c&#41; low and high total cumulative doses of PDN according to the growth variables&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Method</span><p id="par0030" class="elsevierStylePara elsevierViewall">This cross-sectional study was conducted on all children &#40;&#62;2 yr&#46;&#41; and adolescents with the diagnosis of idiopathic nephrotic syndrome &#40;INS&#41; registered to the pediatric nephrology department at the main tertiary &#40;Abuzar&#41; children&#39;s hospital in Southwestern Iran from January 2011 to December 2012&#46; All new admissions and recurrences were treated in the in-patient ward and were followed at the out-patient clinic at the same center&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Definitions&#58; INS was diagnosed if urine protein was &#62;40<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#47;hr&#46;&#44; serum protein &#60;2&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; edema&#44; hyperlipidemia &#40;more than age-appropriate limit&#41; with the absence of gross hematuria&#44; renal failure&#44; prolonged hypertension&#44; and normal complement&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">11</span></a> Relapse was defined as reappearance of proteinuria &#8805;2&#43; by dipstick for three consecutive days&#46; Patients who responded during 8 weeks of PDN treatment &#40;and did not relapse frequently before 3 months of drug discontinuation&#41; were defined as SSNS &#40;steroid-sensitive nephrotic syndrome&#41;&#46; They were considered as SRNS &#40;steroid-resistant nephrotic syndrome&#41; if there was no response during this period&#46; SDNS &#40;steroid-dependent nephrotic syndrome&#41; was defined if recurrence occurred during the alternate-day treatment or 3 months after discontinuation of treatment&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Inclusion criteria were&#58; age &#60;12 yr&#46; for boys and &#60;10 yr&#46; for girls&#44; more than 6 months having passed the beginning of treatment&#44; receiving at least 152<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#8211; equal to a complete initial course of treatment&#44; and parental agreement&#46; The exclusion criteria were&#58; abnormal blood pressure&#44; chronic kidney disease&#44; any sign of pubertal development&#44; and the presence of any other substantial disease affecting linear growth&#44; such as hypothyroidism and celiac disease &#40;discovered by a full history taking&#44; precise physical examination&#44; and a basic laboratory panel obtained during the first assessment&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">All subjects were initially treated with 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d of PDN with a maximum of 80<span class="elsevierStyleHsp" style=""></span>mg&#47;day over 4&#8211;6 weeks&#44; followed by 4 weeks of the same steroid dose given on alternate days&#44; and then the dose was tapered over about 3 months&#46; Relapses were treated with PDN 40&#8211;60<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d up to 5 days after disappearance of proteinuria&#44; and then were tapered during the next 8 weeks&#46; SDNS and SRNS patients also received other immunosuppressive drugs&#44; including levamisole&#44; cyclophosphamide&#44; mycophenolate mofetil&#44; and cyclosporine&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The following data were prepared for analysis&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Date of birth&#44; to calculate exact chronological age &#40;CA&#41; at each visit&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Age at diagnosis and the time passed after the diagnosis&#46;</p></li></ul></p><p id="par0065" class="elsevierStylePara elsevierViewall">The first and the last weight and height &#40;before and after treatment&#41; measured by a clinic nurse using instruments with an accuracy of 0&#46;1<span class="elsevierStyleHsp" style=""></span>kg and 0&#46;1<span class="elsevierStyleHsp" style=""></span>cm&#44; respectively &#40;Seca&#174;&#44; SP&#44; USA&#41;&#46; Height measurements were expressed as height standard deviation score &#40;Ht&#46;-SDS&#41; based on the Tanner-Whitehouse reference growth curves&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Parents&#8217; heights at the beginning of treatment were used to calculate MPHt&#46; as pre-treatment Ht&#46; prediction&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Bone age&#58; radiographs of the left hand and wrist were taken and rated according to the GP system&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a> All bone X-rays were reviewed by two radiologists separately and the mean values were used as the final report&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Medications&#44; duration&#44; and doses</span><p id="par0080" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><p id="par0085" class="elsevierStylePara elsevierViewall">Number of relapses&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><p id="par0090" class="elsevierStylePara elsevierViewall">Total cumulative dose of PDN was considered as the sum of 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg for initial treatment and 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg for each relapse for SSNS subjects&#46; For SDNS and SRNS individuals&#44; all doses of PDN used between the relapses were also added to the calculation&#46; Based on this variable&#44; to assess the possible relation of total PDN dose and linear growth&#44; patients were divided into two groups&#58; less than 550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#91;150<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#40;3<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>100&#41;&#93; equal to three or fewer relapses&#59; and patients with &#8805;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg equal to four or more relapses&#46;</p></li></ul></p><p id="par0095" class="elsevierStylePara elsevierViewall">Secondary variables were calculated as follows&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Height standard deviation score &#40;Ht&#46;-SDS&#41;</span> was calculated as&#58; Ht&#46;SDS&#61;&#40;x&#8722;x&#175;&#41;&#47;SD&#44; where &#34;x&#175;&#34; and &#8220;SD&#8221; are the age-matched population mean height and standard deviation&#44; respectively&#44; and &#8220;<span class="elsevierStyleItalic">x</span>&#8221; is the patient&#39;s height &#40;population data according to Tanner et al&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a>&#41;&#46; For example&#44; based on CDC charts&#44; the 50th percentiles for boys and girls at 20 years of age &#40;used for parental Ht&#46;-SDS determination&#41; were considered as 177<span class="elsevierStyleHsp" style=""></span>cm and 163&#46;3<span class="elsevierStyleHsp" style=""></span>cm&#44; respectively&#46; The Ht&#46;-SDSs at this age were 7&#46;0<span class="elsevierStyleHsp" style=""></span>cm and 6&#46;5<span class="elsevierStyleHsp" style=""></span>cm&#44; respectively&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">MPHt&#46;</span> was calculated as the target height &#40;the potential height range that a child is expected to reach if no postnatal disorder or environmental factor has interacted with the genetic height potential&#41;&#46; <span class="elsevierStyleItalic">THt&#46;</span> was calculated as&#58; mean parental height<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>6&#46;5<span class="elsevierStyleHsp" style=""></span>cm in males and mean parental height<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>6&#46;5<span class="elsevierStyleHsp" style=""></span>cm in females&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">PAHt&#46;</span> was calculated using TW mark-2 equations&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> The variables Ht&#46;&#44; CA&#44; BA&#44; and MPHt&#46; are used in this equation&#46;</p></li></ul><elsevierMultimedia ident="eq0005"></elsevierMultimedia>where <span class="elsevierStyleItalic">a</span>&#44; height coefficient&#59; <span class="elsevierStyleItalic">b</span>&#44; age coefficient&#59; <span class="elsevierStyleItalic">c</span>&#44; bone age coefficient&#59; <span class="elsevierStyleItalic">d</span>&#44; a constant&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The equations permit a prediction of adult height&#44; which&#44; in 95&#37; of instances&#44; is within &#177;7<span class="elsevierStyleHsp" style=""></span>cm of true adult height in boys aged 4&#8211;12 and &#177;6<span class="elsevierStyleHsp" style=""></span>cm in girls aged 4&#8211;11&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">With this equation&#44; only two coefficients are provided for each chronological year &#40;<span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; for 6&#44; 6&#46;5&#44; 7&#44; 7&#46;5&#44; etc&#46;&#41;&#46; Therefore&#44; the coefficient of each child referring to the nearest half-year point has been used in this study&#46; This system was limited to the ages more than 6 years&#46; Consequently&#44; their previous coefficients &#40;TW mark-1&#41; were used<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">10</span></a> for younger subjects&#46; In comparison with the 1975 system &#40;TW mark-1&#41; and with the newer version&#44; the standard errors of prediction &#40;actual fewer estimates&#41; are about the same or&#44; on occasion&#44; larger &#40;near half a centimeter&#41;&#46; Recent standard errors are therefore preferred&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">For assessment of short-time side-effects of PDN on linear growth&#44; statistical differences between the first and the last Ht&#46;-SDS were analyzed by comparing 95&#37; confidence intervals&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Finally&#44; predicted adult height &#40;&#177;3&#46;5<span class="elsevierStyleHsp" style=""></span>cm as the standard errors of prediction&#41; and the mid-parental target height of each patient were compared&#59; less values of predicted heights will be expressed as the negative effect of PDN on the potential linear growth&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Delta Ht&#46;</span><span class="elsevierStyleUnderline"><span class="elsevierStyleItalic">Z</span>-score</span> and <span class="elsevierStyleUnderline">Delta Ht&#46; Prediction</span> were calculated as follow&#58;<elsevierMultimedia ident="eq0010"></elsevierMultimedia><elsevierMultimedia ident="eq0015"></elsevierMultimedia></p><p id="par0140" class="elsevierStylePara elsevierViewall">All variables including numbers of relapses &#40;cumulative PDN dose&#41; were compared between the different types of NS&#44; and between the boys and girls&#46; Student&#39;s <span class="elsevierStyleItalic">t</span>-test was used to compare &#916;Ht&#46;<span class="elsevierStyleItalic">Z</span>s in different groups&#46; Correlation between height changes and prednisolone doses was evaluated by Pearson&#39;s correlation test&#46; Data were expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; All <span class="elsevierStyleItalic">p</span>-values were two-sided and considered statistically significant for &#60;0&#46;05&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">This study was approved by the research ethics committee of Ahvaz Jundishapur University of Medical Sciences &#40;U-91156&#41;&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0150" class="elsevierStylePara elsevierViewall">Ninety-seven patients were enrolled &#40;68&#37; male&#59; male&#47;female ratio<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;1&#41;&#46; The patients were aged 1&#8211;11 yr&#46; &#40;3&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;0 yr&#46;&#41; at the onset of disease and 2&#46;5&#8211;11&#46;8 yr&#46; &#40;6&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;41 yr&#46;&#41; at the end of the study &#40;only one pre-pubertal 14-year-old boy was included&#41;&#46; Mean duration of the follow-up was 2&#46;87 years &#40;ranging from 8 months to 9&#46;9 years&#41;&#46; This mean was 3&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8 yr&#46; for SDNS and SRNS patients&#46; All collected and calculated data are shown in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">In the SSNS group&#44; 26 patients had several episodes of relapses and the remaining 37 patients had none &#40;six were new cases and before 10-month follow up&#41;&#46; The median for relapse rate was two &#40;1&#8211;6 relapses&#41; in the SSNS group and five &#40;3&#8211;24 relapses&#41; in the SDNS group&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The mean PDN cumulative dosage was 452&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and the median was 350<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46; The mean PDN cumulative dosages in SSNS&#44; SDNS&#44; and SRNS groups were 272&#44; 757&#44; and 793<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; respectively&#46; Thirty-six patients &#40;36&#46;3&#37;&#41; needed other immunosuppressive drugs&#44; such as steroid sparing agents &#40;SSA&#41;&#58; levamisole &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41;&#44; cyclophosphamide &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#44; MMF &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; and cyclosporine &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Effect of cumulative dosage of prednisolone on height</span><p id="par0165" class="elsevierStylePara elsevierViewall">Seventy-one &#40;66&#37;&#41; of all 97 patients had less than four relapses &#40;&#60;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg PDN&#59; group 1&#41; and the remaining 33 subjects&#44; group 2&#44; had four or more relapses&#46; The second group &#40;frequent relapsers&#41; showed more decrease in mean Ht&#46;<span class="elsevierStyleItalic">Z</span>s compared to the first group &#40;&#8722;0&#46;84 <span class="elsevierStyleItalic">vs&#46;</span> &#8722;0&#46;28&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The cumulative dosage of PDN had a meaningful relationship &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; with the deterioration of &#916;Ht&#46;<span class="elsevierStyleItalic">Z</span>s &#40;the difference between post- and pre-treatment Ht&#46;<span class="elsevierStyleItalic">Z</span>s&#41;&#46; This deterioration was larger in female patients &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">Compared to the mean of target Ht&#46;<span class="elsevierStyleItalic">Z</span>s &#40;pre-treatment predicted height&#41;&#44; the mean of post-treatment predicted Ht&#46;<span class="elsevierStyleItalic">Z</span>s was increased to almost 0&#46;4 SD&#44; but again more PDN cumulative dosages were associated with greater decrease in the post-treatment prediction compared to the pre-treatment level&#46; However&#44; statistical significance was found only in male patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#59; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">As is clear in the figures&#44; these two variables &#40;&#916;Ht&#46;<span class="elsevierStyleItalic">Z</span>s and &#916;Ht&#46; prediction&#41; differed by sex&#46; Pearson&#39;s test revealed a higher correlation of prednisolone cumulative dose &#40;PCD&#41; and &#916;Ht&#46;<span class="elsevierStyleItalic">Z</span> score in girls than boys&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002 <span class="elsevierStyleItalic">vs</span>&#46; 0&#46;088&#46; Regarding the &#916;prediction&#44; there was higher correlation in boys than girls&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003 <span class="elsevierStyleItalic">vs</span>&#46; 0&#46;111&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Patients who needed other immunosuppressive drugs had lower values of &#916;Ht&#46;<span class="elsevierStyleItalic">Z</span>s &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;047&#41;&#44; and this effect was more significant in the group of four or more relapses &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#46; In those with less than four relapses&#44; the cumulative dosage of PDN did not have any meaningful relationship with the outcome measures&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Deterioration of the mean <span class="elsevierStyleItalic">Z</span>-score had no meaningful relationship with the type of nephrotic syndrome &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; allergy &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; family history of renal and non-renal diseases &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; presence of hypertension &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; and parental consanguinity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0195" class="elsevierStylePara elsevierViewall">This study was designed to assess the possible short- and long-term effects of steroids on the linear growth of pre-pubertal children with nephrotic syndrome&#46; Results showed its negative effect on patients with SDNS and four or more relapses&#46; While the effect was more noticeable in girls over the short term&#44; it was more noticeable in boys over the long term&#46; The results of this study were similar to previous ones in many aspects&#46; This study showed that the post-treatment Ht&#46;<span class="elsevierStyleItalic">Z</span>s of patients receiving PDN &#8805;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg had reduced significantly&#44; and that the deterioration of Ht&#46;<span class="elsevierStyleItalic">Z</span>s was associated with an increase in cumulative PDN dose&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">The study by Donatti et al&#46; on 85 SSNS patients&#44; over all&#44; did not show any significant alterations in the Ht&#46;<span class="elsevierStyleItalic">Z</span>s and the mean height percentile between the first and last visit&#59; by dividing patients into two groups&#44; however&#44; if they had improved Ht&#46;<span class="elsevierStyleItalic">Z</span>s&#44; the total dose and duration of PDN&#44; and the chronological age were higher in the last group&#46; This group also had retarded growth and puberty&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">16</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">In an opposite direction&#44; Adhikari et al&#46;&#44; in a study on an African&#47;Indian population&#44; did not found any significant difference between treated and untreated &#40;symptomatically managed&#41; children in mean Ht&#46;-SDS&#46; They then concluded that courses of daily steroids or persistent proteinuria did not inhibit linear growth&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">17</span></a> That study had not considered the effect of cumulative PDN dose or relapse rate in their evaluation&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Non-uniform results seen in previous studies could mostly be due to differences in their methodologies&#44; and since a cut-off has been used for high- <span class="elsevierStyleItalic">vs&#46;</span> low-dose PDN exposures in this study&#44; it is hard to compare this study with the previous ones&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The suppression of osteoblastogenesis in bone marrow and the promotion of osteocyte and osteoblast apoptosis are consequences of steroids&#44; which lead to a decrease in bone formation&#46; The accumulation of apoptotic osteocytes could account for some definitions&#44; such as osteonecrosis&#44; aseptic necrosis&#44; or avascular necrosis&#46; The negative effect of steroid use on bone mass and short-term growth depends on the type and dose of steroid&#44; and occurs mostly during the first 6 months of treatment&#46; The common belief is that trabecular bones are affected more than cortical ones&#46; However&#44; a recent study in patients with acute lymphoblastic leukemia found a high incidence of cortical bone involvement after glucocorticoid treatment&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">However&#44; there is some evidence indicating that steroids induce bone resorption by prolonging osteoclast lifespan&#46; Besides&#44; they promote calcium loss through the kidneys and intestine&#44; producing a negative balance in calcium metabolism that induces more osteoclastic activity due to secondary hyperparathyroidism&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">2&#44;18</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">The effect of PDN cumulative dose on linear growth is shown better with longitudinal studies&#46; For example&#44; the study by Emma et al&#46; on children with SDNS &#40;mean follow up<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5 years&#41; showed loss of almost 0&#46;5 SD of Ht&#46;-SDS during the pre-pubertal period&#44; and 0&#46;7 SD of their target Ht&#46; &#40;only in male subjects&#41; when they reached their final height&#46; More prolonged treatment was associated with higher risk of Ht&#46;-SDS loss&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">6</span></a> These findings were similar to the present results in that this study also discovered long-term negative effects &#40;lower values for Ht&#46; prediction after treatment&#41; limited to boys&#46; In comparison with the study by Emma et al&#46;&#44; using a cut off makes the present approach different&#44; but looking at PDN impact on &#916;Ht&#46;<span class="elsevierStyleItalic">Z</span>s and height prediction using MPHt&#46;<span class="elsevierStyleItalic">Z</span> could be a point of strength in the present study&#46; It was also shown in the study by Ribeiro et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">4</span></a> that long-term PDN&#44; particularly in higher doses&#44; affects height SDS as well as spinal bone density&#46; A longitudinal study by Rees et al&#46; on 41 patients &#40;29 boys&#41; with SSNS also showed a decrease in Ht&#46;-SDS in boys &#40;only after 10 years&#44; and it was associated with delay in puberty&#41; but not in girls&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">3</span></a> This finding requires further research for explanation&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Simmonds et al&#46; determined a cut-off point in which lower cumulative PDN dose was compatible with normal growth&#46; By calculating daily PDN dose and Ht&#46;-SDS velocity between clinics&#44; they found no negative effect on growth at doses of PDN &#60;0&#46;75<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#59; with higher doses&#44; there was a small decline in Ht&#46; SDS velocity&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a> In the present study&#44; a similar relationship with the cumulative doses of PDN &#8805;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg was found&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Under high-dose steroid treatment&#44; the physiological secretion of growth hormone may be reduced or mediated by somatostatin and&#44; in some cases&#44; growth hormone stimulation tests are unable to produce an appropriate response&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">20</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">Attainment of peak bone mass and growth may also be impaired by steroid use because of an altered pituitary-gonadal axis&#46; A reversible hypo-gonadotropic hypogonadism is shown in studies in adults using steroid therapy&#46; Adrenal insufficiency following chronic glucocorticoid therapy may also be associated with depressed levels of other sex steroids&#44; such as androstenedione and estrogen&#46; Steroids may also impair FSH and cause reduction in estrogen secretion&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">Puberty occurs between childhood and the time when final height is obtained&#46; Its beginning time varies according to the ethnic and familial genetic basis&#44; and it may last 2&#8211;6 years to complete&#46; For each family and sibling&#44; it has an individual pattern of progress regarding the overall rate and stages intervals&#46; Even in a healthy child&#44; the exact prediction of pubertal onset and its growth spurt is not possible&#46; With steroid exposure and its negative effects on pubertal process and bone formation&#44; such predictions become more difficult&#46; Accordingly&#44; the present study completely excluded pubertal stages from follow-up analysis&#46; Longitudinal follow-up of patients after completion of puberty can solve this problem when they have reached the final height&#46; Finding a sex difference in short-term and long-term negative PDN impacts &#40;in girls and boys&#44; respectively&#41; matches with the shorter pre-pubertal years in girls than in the boys&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Finally&#44; it was better to compare pre-treatment and post-treatment PAHt&#46;<span class="elsevierStyleItalic">Z</span>&#44; but because pre-treatment bone ages were not available in subjects&#44; MPHt&#46;<span class="elsevierStyleItalic">Z</span> was used as the basic potential target height&#44; which&#44; theoretically&#44; must not change from childhood to adolescence&#46; Comparing different items before and after treatment to evaluate PDN side effects can cause some errors&#46; Although the number of patients in this study was greater than in the previous ones&#44; a much larger population in a multicenter study for longer period would give better results&#46; Short duration &#40;&#60;2&#46;5 yr&#46;&#41; of follow-up in more than half of the patients may affect the results&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Moreover&#44; the equations used in this study were obtained based on data from a British population&#46; However&#44; they have been checked in a Japanese population&#46; Still&#44; they need to match with the raw data of each population to assess applicability&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Finally&#44; the authors were more familiar with the GP system for bone age assessment&#44; and then it was used as a part of TW mark-2 system for height prediction&#46; In fact&#44; the original method for bone age rating in TW formula is their own system&#44; and not that of GP&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">This study showed the negative effect of cumulative PDN dose on linear growth in nephrotic syndrome&#59; fortunately&#44; it happened mostly in prolonged disease with four or more relapses&#46; This finding is important for giving parental assurance about relative safety of this lifesaving drug&#46; Finally&#44; the importance of earlier growth intervention in frequent relapses is warranted&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding</span><p id="par0270" class="elsevierStylePara elsevierViewall">This study was supported by Vice chancellor for research of the Ahvaz Jundishapur University of Medical Sciences&#44; Ahvaz&#44; Iran&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0275" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Effect of cumulative dosage of prednisolone on height"
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            0 => "Prednisolone"
            1 => "Linear growth"
            2 => "Children"
            3 => "Nephrotic syndrome"
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          "clase" => "keyword"
          "titulo" => "Palavras-chave"
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            0 => "Prednisolona"
            1 => "Crescimento linear"
            2 => "Crian&#231;as"
            3 => "S&#237;ndrome nefr&#243;tica"
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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">This study aims at determining the relationship between prednisolone cumulative dose and linear growth in pre-pubertal children with idiopathic nephrotic syndrome&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This cross-sectional study was conducted on all children with idiopathic nephrotic syndrome registered to the pediatric nephrology department at the main referral children&#39;s hospital in Southwestern Iran&#46; Inclusion criteria included age &#40;males &#60;12 years&#59; females &#60;10 years&#41;&#44; &#62;6 months of use&#44; and the minimum prednisolone cumulative dose of 152<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46; The exclusion criteria were individuals who had entered puberty or had other diseases affecting linear growth&#46; Based on the prednisolone cumulative dose of &#8805;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#40;four or more relapses&#41;&#44; the children were divided into two groups&#46; All data regarding age&#44; height&#44; and weight at disease onset and the last visit&#44; bone age&#44; and the parents&#8217; height were collected&#46; Secondary variables including mid-parental target height and predicted adult height were also calculated&#46; Height data were compared between the different rates of relapse&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 97 children &#40;68&#37; male&#41; were enrolled&#46; Their post-treatment mean height <span class="elsevierStyleItalic">Z</span>-score was less than that obtained before treatment &#40;&#8722;0&#46;584 <span class="elsevierStyleItalic">vs&#46;</span> &#8722;0&#46;158&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Subjects with higher prednisolone cumulative doses were found to have more reduction in height <span class="elsevierStyleItalic">Z</span>-score &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Post-treatment height prediction also showed less growth potential compared to pre-treatment target height &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#46; Thirty-three children &#40;34&#46;4&#37;&#41; had four or more relapses&#44; among whom more mean-height <span class="elsevierStyleItalic">Z</span>-score decreases were found compared to those with less-frequent relapses &#40;&#8722;0&#46;84 <span class="elsevierStyleItalic">vs&#46;</span> &#8722;0&#46;28&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This study showed the negative effect of cumulative dosages of prednisolone on linear growth&#44; which was greater in children with four or more relapses&#46;</p></span>"
        "secciones" => array:4 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Determinar a rela&#231;&#227;o entre a dose cumulativa de prednisolona e o crescimento linear em crian&#231;as pr&#233;-p&#250;beres com s&#237;ndrome nefr&#243;tica idiop&#225;tica&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudo transversal conduzido em todas as crian&#231;as com s&#237;ndrome nefr&#243;tica idiop&#225;tica registradas no departamento de nefrologia pedi&#225;trica no principal hospital infantil para encaminhamento no sudoeste do Ir&#227;&#46; Os crit&#233;rios de inclus&#227;o inclu&#237;ram idade &#40;meninos<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>12 anos&#59; meninas<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10 anos&#41;&#44; &#62;6 meses e a dose cumulativa de prednisolona m&#237;nima de 152<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46; Os crit&#233;rios de exclus&#227;o foram indiv&#237;duos que entraram na puberdade ou tinham outras doen&#231;as que afetam o crescimento linear&#46; Com base na dose cumulativa de prednisolona de &#8805;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#40;&#8805;4 recidivas&#41;&#44; as crian&#231;as foram divididas em dois grupos&#46; Foram coletados todos os dados relacionados a idade&#44; estatura e peso no in&#237;cio da doen&#231;a e na &#250;ltima visita&#44; idade &#243;ssea e estatura dos pais&#46; Tamb&#233;m foram calculadas as vari&#225;veis secund&#225;rias&#44; inclusive estatura-alvo e estatura adulta prevista&#46; Os dados de estatura foram comparados entre as diferentes taxas de recidivas&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Foram inscritas 97 crian&#231;as &#40;68&#37; do sexo masculino&#41;&#46; Seu escore z de estatura m&#233;dia p&#243;s-tratamento foi inferior ao obtido antes do tratamento &#40;&#8722;0&#44;584 em compara&#231;&#227;o com &#8722;0&#44;158&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Os indiv&#237;duos com maiores doses cumulativas de prednisolona mostraram maior redu&#231;&#227;o no escore z para estatura &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; A estatura p&#243;s-tratamento tamb&#233;m foi preditiva de menor potencial de crescimento em compara&#231;&#227;o com a estatura-alvo pr&#233;-tratamento &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;006&#41;&#59; 33 crian&#231;as &#40;34&#44;4&#37;&#41; apresentaram &#8805;4 recidivas&#44; entre as quais foram encontradas mais redu&#231;&#245;es m&#233;dias no escore z para estatura em compara&#231;&#227;o com as recidivas menos frequentes &#40;&#8722;0&#44;84 em compara&#231;&#227;o com &#8722;0&#44;28&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#227;o</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este estudo mostrou o efeito negativo das doses cumulativas de prednisolona sobre o crescimento linear&#44; que foi maior em crian&#231;as com &#8805;4 recidivas&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as&#58; Valavi E&#44; Aminzadeh M&#44; Amouri P&#44; Rezazadeh A&#44; Beladi-Mousavi M&#46; Effect of prednisolone on linear growth in children with nephrotic syndrome&#46; J Pediatr &#40;Rio J&#41;&#46; 2020&#59;96&#58;117&#8211;24&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Correlation of height prediction <span class="elsevierStyleItalic">Z</span>-score worsening &#40;post-treatment vs&#46; pre-treatment&#41; with prednisolone cumulative dose &#40;in mg&#41; in 90 children with nephrotic syndrome&#46; 1&#58; all patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#59; 2&#58; boys &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#59; 3&#58; girls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;111&#41;&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Height <span class="elsevierStyleItalic">Z</span>-scores of 99 children treated for different types of nephrotic syndrome&#46;</p>"
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    "bibliografia" => array:2 [
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The effect of long-term steroid therapy on linear growth of nephrotic children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Madani"
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                            2 => "R&#46; Taghaodi"
                            3 => "N&#46; Hajizadeh"
                            4 => "A&#46; Rabbani"
                            5 => "H&#46; Z-Mehrjardi"
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                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Iran J Pediatr"
                        "fecha" => "2011"
                        "volumen" => "21"
                        "paginaInicial" => "21"
                        "paginaFinal" => "27"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23056759"
                            "web" => "Medline"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The impact of corticosteroids on growth and bone health"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46; Mushtaq"
                            1 => "S&#46;F&#46; Ahmed"
                          ]
                        ]
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Original article
Effect of prednisolone on linear growth in children with nephrotic syndrome
Efeito da prednisolona sobre o crescimento linear em crianças com síndrome nefrótica
Ehsan Valavia, Majid Aminzadehb,
Corresponding author
, Parisa Amouria, Afshin Rezazadehc, Maedeh Beladi-Mousavid
a Ahvaz Jundishapur University of Medical Sciences, Chronic Renal Failure Research Center, Ahvaz, Iran
b Ahvaz Jundishapur University of Medical Sciences, Diabetes Research Center, Ahvaz, Iran
c Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
d Ahvaz Jundishapur University of Medical Sciences, Faculty of Medicine, Ahvaz, Iran
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            "entidad" => "Ahvaz Jundishapur University of Medical Sciences&#44; Faculty of Medicine&#44; Ahvaz&#44; Iran"
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        "titulo" => "Efeito da prednisolona sobre o crescimento linear em crian&#231;as com s&#237;ndrome nefr&#243;tica"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Correlation of height <span class="elsevierStyleItalic">Z</span>-score worsening &#40;post-treatment vs&#46; pre-treatment&#41; with prednisolone cumulative dose &#40;in mg&#41; in 90 children with nephrotic syndrome&#46; 1&#58; all patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#59; 2&#58; boys &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;088&#41;&#59; 3&#58; girls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46;</p>"
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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">Prednisolone &#40;PDN&#41; has changed the prognosis of nephrotic syndrome &#40;NS&#41; since 1950&#46; Nearly 12&#8211;24&#37; of patients are steroid-resistant and about 70&#37; experience at least one episode of relapse&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> Besides the great benefits&#44; there are many concerns about the disadvantages of PDN&#44; particularly about its negative effects on linear growth&#46; Several mechanisms have been proposed regarding the effects of NS on growth&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Some studies have confirmed the short-time inhibitory effects of PDN on growth by comparing height <span class="elsevierStyleItalic">Z</span>-score &#40;Ht&#46;<span class="elsevierStyleItalic">Z</span>s&#41; before and after treatment between frequent and infrequent relapsers&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;3</span></a> Other studies have investigated its negative impact in long-term use&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">4&#44;5</span></a> some others have followed patients longitudinally to compare their final height with their peers&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">6&#44;7</span></a> and finally&#44; some have used a combination of methods&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Theoretically&#44; growth potential can be evaluated using final height prediction in childhood&#46; Several methods have been proposed for this purpose&#46; The chronological age &#40;CA&#41;-based system decreases the prediction as bone age &#40;BA&#41; increases&#46; However&#44; the bone age-based system does not do this&#46; In the BA-based system&#44; the predictions are less affected by bone age discrepancies&#44; but the effect is not symmetrical&#46; Greulich-Pyle &#40;GP&#41; and Tanner-Whitehouse &#40;TW&#41; methods for skeletal age determination can be used for predicting adult height&#44; which is helpful in diagnosing and evaluating the effects of treatment&#46; In this method&#44; the predicted adult height &#40;PAHt&#46;&#41; is compared to the expected adult height &#40;target range of height&#59; target height &#91;THt&#46;&#93;&#44; calculated as mid-parental height &#91;MPHt&#46;&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">By newer TW Mark systems&#44; the errors of prediction are generally a little smaller than those arising from the Bayley-Pinneau predictions&#44; and considerably smaller in the case of postmenarcheal girls&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of this study was to evaluate potential short-term and long-term effects of PDN on linear growth by comparing&#58; &#40;a&#41; Ht&#46;<span class="elsevierStyleItalic">Z</span>s before and after treatment&#44; &#40;b&#41; post-treatment predicted final height compared with &#40;potential pre-treatment&#41; mid-parental target height&#44; and &#40;c&#41; low and high total cumulative doses of PDN according to the growth variables&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Method</span><p id="par0030" class="elsevierStylePara elsevierViewall">This cross-sectional study was conducted on all children &#40;&#62;2 yr&#46;&#41; and adolescents with the diagnosis of idiopathic nephrotic syndrome &#40;INS&#41; registered to the pediatric nephrology department at the main tertiary &#40;Abuzar&#41; children&#39;s hospital in Southwestern Iran from January 2011 to December 2012&#46; All new admissions and recurrences were treated in the in-patient ward and were followed at the out-patient clinic at the same center&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Definitions&#58; INS was diagnosed if urine protein was &#62;40<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#47;hr&#46;&#44; serum protein &#60;2&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; edema&#44; hyperlipidemia &#40;more than age-appropriate limit&#41; with the absence of gross hematuria&#44; renal failure&#44; prolonged hypertension&#44; and normal complement&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">11</span></a> Relapse was defined as reappearance of proteinuria &#8805;2&#43; by dipstick for three consecutive days&#46; Patients who responded during 8 weeks of PDN treatment &#40;and did not relapse frequently before 3 months of drug discontinuation&#41; were defined as SSNS &#40;steroid-sensitive nephrotic syndrome&#41;&#46; They were considered as SRNS &#40;steroid-resistant nephrotic syndrome&#41; if there was no response during this period&#46; SDNS &#40;steroid-dependent nephrotic syndrome&#41; was defined if recurrence occurred during the alternate-day treatment or 3 months after discontinuation of treatment&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Inclusion criteria were&#58; age &#60;12 yr&#46; for boys and &#60;10 yr&#46; for girls&#44; more than 6 months having passed the beginning of treatment&#44; receiving at least 152<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#8211; equal to a complete initial course of treatment&#44; and parental agreement&#46; The exclusion criteria were&#58; abnormal blood pressure&#44; chronic kidney disease&#44; any sign of pubertal development&#44; and the presence of any other substantial disease affecting linear growth&#44; such as hypothyroidism and celiac disease &#40;discovered by a full history taking&#44; precise physical examination&#44; and a basic laboratory panel obtained during the first assessment&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">All subjects were initially treated with 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d of PDN with a maximum of 80<span class="elsevierStyleHsp" style=""></span>mg&#47;day over 4&#8211;6 weeks&#44; followed by 4 weeks of the same steroid dose given on alternate days&#44; and then the dose was tapered over about 3 months&#46; Relapses were treated with PDN 40&#8211;60<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d up to 5 days after disappearance of proteinuria&#44; and then were tapered during the next 8 weeks&#46; SDNS and SRNS patients also received other immunosuppressive drugs&#44; including levamisole&#44; cyclophosphamide&#44; mycophenolate mofetil&#44; and cyclosporine&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The following data were prepared for analysis&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Date of birth&#44; to calculate exact chronological age &#40;CA&#41; at each visit&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Age at diagnosis and the time passed after the diagnosis&#46;</p></li></ul></p><p id="par0065" class="elsevierStylePara elsevierViewall">The first and the last weight and height &#40;before and after treatment&#41; measured by a clinic nurse using instruments with an accuracy of 0&#46;1<span class="elsevierStyleHsp" style=""></span>kg and 0&#46;1<span class="elsevierStyleHsp" style=""></span>cm&#44; respectively &#40;Seca&#174;&#44; SP&#44; USA&#41;&#46; Height measurements were expressed as height standard deviation score &#40;Ht&#46;-SDS&#41; based on the Tanner-Whitehouse reference growth curves&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Parents&#8217; heights at the beginning of treatment were used to calculate MPHt&#46; as pre-treatment Ht&#46; prediction&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Bone age&#58; radiographs of the left hand and wrist were taken and rated according to the GP system&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a> All bone X-rays were reviewed by two radiologists separately and the mean values were used as the final report&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Medications&#44; duration&#44; and doses</span><p id="par0080" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><p id="par0085" class="elsevierStylePara elsevierViewall">Number of relapses&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><p id="par0090" class="elsevierStylePara elsevierViewall">Total cumulative dose of PDN was considered as the sum of 150<span class="elsevierStyleHsp" style=""></span>mg&#47;kg for initial treatment and 100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg for each relapse for SSNS subjects&#46; For SDNS and SRNS individuals&#44; all doses of PDN used between the relapses were also added to the calculation&#46; Based on this variable&#44; to assess the possible relation of total PDN dose and linear growth&#44; patients were divided into two groups&#58; less than 550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#91;150<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#40;3<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>100&#41;&#93; equal to three or fewer relapses&#59; and patients with &#8805;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg equal to four or more relapses&#46;</p></li></ul></p><p id="par0095" class="elsevierStylePara elsevierViewall">Secondary variables were calculated as follows&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Height standard deviation score &#40;Ht&#46;-SDS&#41;</span> was calculated as&#58; Ht&#46;SDS&#61;&#40;x&#8722;x&#175;&#41;&#47;SD&#44; where &#34;x&#175;&#34; and &#8220;SD&#8221; are the age-matched population mean height and standard deviation&#44; respectively&#44; and &#8220;<span class="elsevierStyleItalic">x</span>&#8221; is the patient&#39;s height &#40;population data according to Tanner et al&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a>&#41;&#46; For example&#44; based on CDC charts&#44; the 50th percentiles for boys and girls at 20 years of age &#40;used for parental Ht&#46;-SDS determination&#41; were considered as 177<span class="elsevierStyleHsp" style=""></span>cm and 163&#46;3<span class="elsevierStyleHsp" style=""></span>cm&#44; respectively&#46; The Ht&#46;-SDSs at this age were 7&#46;0<span class="elsevierStyleHsp" style=""></span>cm and 6&#46;5<span class="elsevierStyleHsp" style=""></span>cm&#44; respectively&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">MPHt&#46;</span> was calculated as the target height &#40;the potential height range that a child is expected to reach if no postnatal disorder or environmental factor has interacted with the genetic height potential&#41;&#46; <span class="elsevierStyleItalic">THt&#46;</span> was calculated as&#58; mean parental height<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>6&#46;5<span class="elsevierStyleHsp" style=""></span>cm in males and mean parental height<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>6&#46;5<span class="elsevierStyleHsp" style=""></span>cm in females&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">PAHt&#46;</span> was calculated using TW mark-2 equations&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> The variables Ht&#46;&#44; CA&#44; BA&#44; and MPHt&#46; are used in this equation&#46;</p></li></ul><elsevierMultimedia ident="eq0005"></elsevierMultimedia>where <span class="elsevierStyleItalic">a</span>&#44; height coefficient&#59; <span class="elsevierStyleItalic">b</span>&#44; age coefficient&#59; <span class="elsevierStyleItalic">c</span>&#44; bone age coefficient&#59; <span class="elsevierStyleItalic">d</span>&#44; a constant&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The equations permit a prediction of adult height&#44; which&#44; in 95&#37; of instances&#44; is within &#177;7<span class="elsevierStyleHsp" style=""></span>cm of true adult height in boys aged 4&#8211;12 and &#177;6<span class="elsevierStyleHsp" style=""></span>cm in girls aged 4&#8211;11&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">With this equation&#44; only two coefficients are provided for each chronological year &#40;<span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; for 6&#44; 6&#46;5&#44; 7&#44; 7&#46;5&#44; etc&#46;&#41;&#46; Therefore&#44; the coefficient of each child referring to the nearest half-year point has been used in this study&#46; This system was limited to the ages more than 6 years&#46; Consequently&#44; their previous coefficients &#40;TW mark-1&#41; were used<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">10</span></a> for younger subjects&#46; In comparison with the 1975 system &#40;TW mark-1&#41; and with the newer version&#44; the standard errors of prediction &#40;actual fewer estimates&#41; are about the same or&#44; on occasion&#44; larger &#40;near half a centimeter&#41;&#46; Recent standard errors are therefore preferred&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">For assessment of short-time side-effects of PDN on linear growth&#44; statistical differences between the first and the last Ht&#46;-SDS were analyzed by comparing 95&#37; confidence intervals&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Finally&#44; predicted adult height &#40;&#177;3&#46;5<span class="elsevierStyleHsp" style=""></span>cm as the standard errors of prediction&#41; and the mid-parental target height of each patient were compared&#59; less values of predicted heights will be expressed as the negative effect of PDN on the potential linear growth&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Delta Ht&#46;</span><span class="elsevierStyleUnderline"><span class="elsevierStyleItalic">Z</span>-score</span> and <span class="elsevierStyleUnderline">Delta Ht&#46; Prediction</span> were calculated as follow&#58;<elsevierMultimedia ident="eq0010"></elsevierMultimedia><elsevierMultimedia ident="eq0015"></elsevierMultimedia></p><p id="par0140" class="elsevierStylePara elsevierViewall">All variables including numbers of relapses &#40;cumulative PDN dose&#41; were compared between the different types of NS&#44; and between the boys and girls&#46; Student&#39;s <span class="elsevierStyleItalic">t</span>-test was used to compare &#916;Ht&#46;<span class="elsevierStyleItalic">Z</span>s in different groups&#46; Correlation between height changes and prednisolone doses was evaluated by Pearson&#39;s correlation test&#46; Data were expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; All <span class="elsevierStyleItalic">p</span>-values were two-sided and considered statistically significant for &#60;0&#46;05&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">This study was approved by the research ethics committee of Ahvaz Jundishapur University of Medical Sciences &#40;U-91156&#41;&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0150" class="elsevierStylePara elsevierViewall">Ninety-seven patients were enrolled &#40;68&#37; male&#59; male&#47;female ratio<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;1&#41;&#46; The patients were aged 1&#8211;11 yr&#46; &#40;3&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;0 yr&#46;&#41; at the onset of disease and 2&#46;5&#8211;11&#46;8 yr&#46; &#40;6&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;41 yr&#46;&#41; at the end of the study &#40;only one pre-pubertal 14-year-old boy was included&#41;&#46; Mean duration of the follow-up was 2&#46;87 years &#40;ranging from 8 months to 9&#46;9 years&#41;&#46; This mean was 3&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8 yr&#46; for SDNS and SRNS patients&#46; All collected and calculated data are shown in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">In the SSNS group&#44; 26 patients had several episodes of relapses and the remaining 37 patients had none &#40;six were new cases and before 10-month follow up&#41;&#46; The median for relapse rate was two &#40;1&#8211;6 relapses&#41; in the SSNS group and five &#40;3&#8211;24 relapses&#41; in the SDNS group&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The mean PDN cumulative dosage was 452&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and the median was 350<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46; The mean PDN cumulative dosages in SSNS&#44; SDNS&#44; and SRNS groups were 272&#44; 757&#44; and 793<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; respectively&#46; Thirty-six patients &#40;36&#46;3&#37;&#41; needed other immunosuppressive drugs&#44; such as steroid sparing agents &#40;SSA&#41;&#58; levamisole &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41;&#44; cyclophosphamide &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#44; MMF &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; and cyclosporine &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Effect of cumulative dosage of prednisolone on height</span><p id="par0165" class="elsevierStylePara elsevierViewall">Seventy-one &#40;66&#37;&#41; of all 97 patients had less than four relapses &#40;&#60;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg PDN&#59; group 1&#41; and the remaining 33 subjects&#44; group 2&#44; had four or more relapses&#46; The second group &#40;frequent relapsers&#41; showed more decrease in mean Ht&#46;<span class="elsevierStyleItalic">Z</span>s compared to the first group &#40;&#8722;0&#46;84 <span class="elsevierStyleItalic">vs&#46;</span> &#8722;0&#46;28&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The cumulative dosage of PDN had a meaningful relationship &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; with the deterioration of &#916;Ht&#46;<span class="elsevierStyleItalic">Z</span>s &#40;the difference between post- and pre-treatment Ht&#46;<span class="elsevierStyleItalic">Z</span>s&#41;&#46; This deterioration was larger in female patients &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">Compared to the mean of target Ht&#46;<span class="elsevierStyleItalic">Z</span>s &#40;pre-treatment predicted height&#41;&#44; the mean of post-treatment predicted Ht&#46;<span class="elsevierStyleItalic">Z</span>s was increased to almost 0&#46;4 SD&#44; but again more PDN cumulative dosages were associated with greater decrease in the post-treatment prediction compared to the pre-treatment level&#46; However&#44; statistical significance was found only in male patients &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#59; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">As is clear in the figures&#44; these two variables &#40;&#916;Ht&#46;<span class="elsevierStyleItalic">Z</span>s and &#916;Ht&#46; prediction&#41; differed by sex&#46; Pearson&#39;s test revealed a higher correlation of prednisolone cumulative dose &#40;PCD&#41; and &#916;Ht&#46;<span class="elsevierStyleItalic">Z</span> score in girls than boys&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002 <span class="elsevierStyleItalic">vs</span>&#46; 0&#46;088&#46; Regarding the &#916;prediction&#44; there was higher correlation in boys than girls&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003 <span class="elsevierStyleItalic">vs</span>&#46; 0&#46;111&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Patients who needed other immunosuppressive drugs had lower values of &#916;Ht&#46;<span class="elsevierStyleItalic">Z</span>s &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;047&#41;&#44; and this effect was more significant in the group of four or more relapses &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#46; In those with less than four relapses&#44; the cumulative dosage of PDN did not have any meaningful relationship with the outcome measures&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Deterioration of the mean <span class="elsevierStyleItalic">Z</span>-score had no meaningful relationship with the type of nephrotic syndrome &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; allergy &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; family history of renal and non-renal diseases &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; presence of hypertension &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; and parental consanguinity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0195" class="elsevierStylePara elsevierViewall">This study was designed to assess the possible short- and long-term effects of steroids on the linear growth of pre-pubertal children with nephrotic syndrome&#46; Results showed its negative effect on patients with SDNS and four or more relapses&#46; While the effect was more noticeable in girls over the short term&#44; it was more noticeable in boys over the long term&#46; The results of this study were similar to previous ones in many aspects&#46; This study showed that the post-treatment Ht&#46;<span class="elsevierStyleItalic">Z</span>s of patients receiving PDN &#8805;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg had reduced significantly&#44; and that the deterioration of Ht&#46;<span class="elsevierStyleItalic">Z</span>s was associated with an increase in cumulative PDN dose&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">The study by Donatti et al&#46; on 85 SSNS patients&#44; over all&#44; did not show any significant alterations in the Ht&#46;<span class="elsevierStyleItalic">Z</span>s and the mean height percentile between the first and last visit&#59; by dividing patients into two groups&#44; however&#44; if they had improved Ht&#46;<span class="elsevierStyleItalic">Z</span>s&#44; the total dose and duration of PDN&#44; and the chronological age were higher in the last group&#46; This group also had retarded growth and puberty&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">16</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">In an opposite direction&#44; Adhikari et al&#46;&#44; in a study on an African&#47;Indian population&#44; did not found any significant difference between treated and untreated &#40;symptomatically managed&#41; children in mean Ht&#46;-SDS&#46; They then concluded that courses of daily steroids or persistent proteinuria did not inhibit linear growth&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">17</span></a> That study had not considered the effect of cumulative PDN dose or relapse rate in their evaluation&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Non-uniform results seen in previous studies could mostly be due to differences in their methodologies&#44; and since a cut-off has been used for high- <span class="elsevierStyleItalic">vs&#46;</span> low-dose PDN exposures in this study&#44; it is hard to compare this study with the previous ones&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The suppression of osteoblastogenesis in bone marrow and the promotion of osteocyte and osteoblast apoptosis are consequences of steroids&#44; which lead to a decrease in bone formation&#46; The accumulation of apoptotic osteocytes could account for some definitions&#44; such as osteonecrosis&#44; aseptic necrosis&#44; or avascular necrosis&#46; The negative effect of steroid use on bone mass and short-term growth depends on the type and dose of steroid&#44; and occurs mostly during the first 6 months of treatment&#46; The common belief is that trabecular bones are affected more than cortical ones&#46; However&#44; a recent study in patients with acute lymphoblastic leukemia found a high incidence of cortical bone involvement after glucocorticoid treatment&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">However&#44; there is some evidence indicating that steroids induce bone resorption by prolonging osteoclast lifespan&#46; Besides&#44; they promote calcium loss through the kidneys and intestine&#44; producing a negative balance in calcium metabolism that induces more osteoclastic activity due to secondary hyperparathyroidism&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">2&#44;18</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">The effect of PDN cumulative dose on linear growth is shown better with longitudinal studies&#46; For example&#44; the study by Emma et al&#46; on children with SDNS &#40;mean follow up<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5 years&#41; showed loss of almost 0&#46;5 SD of Ht&#46;-SDS during the pre-pubertal period&#44; and 0&#46;7 SD of their target Ht&#46; &#40;only in male subjects&#41; when they reached their final height&#46; More prolonged treatment was associated with higher risk of Ht&#46;-SDS loss&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">6</span></a> These findings were similar to the present results in that this study also discovered long-term negative effects &#40;lower values for Ht&#46; prediction after treatment&#41; limited to boys&#46; In comparison with the study by Emma et al&#46;&#44; using a cut off makes the present approach different&#44; but looking at PDN impact on &#916;Ht&#46;<span class="elsevierStyleItalic">Z</span>s and height prediction using MPHt&#46;<span class="elsevierStyleItalic">Z</span> could be a point of strength in the present study&#46; It was also shown in the study by Ribeiro et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">4</span></a> that long-term PDN&#44; particularly in higher doses&#44; affects height SDS as well as spinal bone density&#46; A longitudinal study by Rees et al&#46; on 41 patients &#40;29 boys&#41; with SSNS also showed a decrease in Ht&#46;-SDS in boys &#40;only after 10 years&#44; and it was associated with delay in puberty&#41; but not in girls&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">3</span></a> This finding requires further research for explanation&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Simmonds et al&#46; determined a cut-off point in which lower cumulative PDN dose was compatible with normal growth&#46; By calculating daily PDN dose and Ht&#46;-SDS velocity between clinics&#44; they found no negative effect on growth at doses of PDN &#60;0&#46;75<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#59; with higher doses&#44; there was a small decline in Ht&#46; SDS velocity&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a> In the present study&#44; a similar relationship with the cumulative doses of PDN &#8805;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg was found&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Under high-dose steroid treatment&#44; the physiological secretion of growth hormone may be reduced or mediated by somatostatin and&#44; in some cases&#44; growth hormone stimulation tests are unable to produce an appropriate response&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">20</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">Attainment of peak bone mass and growth may also be impaired by steroid use because of an altered pituitary-gonadal axis&#46; A reversible hypo-gonadotropic hypogonadism is shown in studies in adults using steroid therapy&#46; Adrenal insufficiency following chronic glucocorticoid therapy may also be associated with depressed levels of other sex steroids&#44; such as androstenedione and estrogen&#46; Steroids may also impair FSH and cause reduction in estrogen secretion&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">Puberty occurs between childhood and the time when final height is obtained&#46; Its beginning time varies according to the ethnic and familial genetic basis&#44; and it may last 2&#8211;6 years to complete&#46; For each family and sibling&#44; it has an individual pattern of progress regarding the overall rate and stages intervals&#46; Even in a healthy child&#44; the exact prediction of pubertal onset and its growth spurt is not possible&#46; With steroid exposure and its negative effects on pubertal process and bone formation&#44; such predictions become more difficult&#46; Accordingly&#44; the present study completely excluded pubertal stages from follow-up analysis&#46; Longitudinal follow-up of patients after completion of puberty can solve this problem when they have reached the final height&#46; Finding a sex difference in short-term and long-term negative PDN impacts &#40;in girls and boys&#44; respectively&#41; matches with the shorter pre-pubertal years in girls than in the boys&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Finally&#44; it was better to compare pre-treatment and post-treatment PAHt&#46;<span class="elsevierStyleItalic">Z</span>&#44; but because pre-treatment bone ages were not available in subjects&#44; MPHt&#46;<span class="elsevierStyleItalic">Z</span> was used as the basic potential target height&#44; which&#44; theoretically&#44; must not change from childhood to adolescence&#46; Comparing different items before and after treatment to evaluate PDN side effects can cause some errors&#46; Although the number of patients in this study was greater than in the previous ones&#44; a much larger population in a multicenter study for longer period would give better results&#46; Short duration &#40;&#60;2&#46;5 yr&#46;&#41; of follow-up in more than half of the patients may affect the results&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Moreover&#44; the equations used in this study were obtained based on data from a British population&#46; However&#44; they have been checked in a Japanese population&#46; Still&#44; they need to match with the raw data of each population to assess applicability&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Finally&#44; the authors were more familiar with the GP system for bone age assessment&#44; and then it was used as a part of TW mark-2 system for height prediction&#46; In fact&#44; the original method for bone age rating in TW formula is their own system&#44; and not that of GP&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">This study showed the negative effect of cumulative PDN dose on linear growth in nephrotic syndrome&#59; fortunately&#44; it happened mostly in prolonged disease with four or more relapses&#46; This finding is important for giving parental assurance about relative safety of this lifesaving drug&#46; Finally&#44; the importance of earlier growth intervention in frequent relapses is warranted&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding</span><p id="par0270" class="elsevierStylePara elsevierViewall">This study was supported by Vice chancellor for research of the Ahvaz Jundishapur University of Medical Sciences&#44; Ahvaz&#44; Iran&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0275" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Effect of cumulative dosage of prednisolone on height"
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            0 => "Prednisolone"
            1 => "Linear growth"
            2 => "Children"
            3 => "Nephrotic syndrome"
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          "titulo" => "Palavras-chave"
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            0 => "Prednisolona"
            1 => "Crescimento linear"
            2 => "Crian&#231;as"
            3 => "S&#237;ndrome nefr&#243;tica"
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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">This study aims at determining the relationship between prednisolone cumulative dose and linear growth in pre-pubertal children with idiopathic nephrotic syndrome&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This cross-sectional study was conducted on all children with idiopathic nephrotic syndrome registered to the pediatric nephrology department at the main referral children&#39;s hospital in Southwestern Iran&#46; Inclusion criteria included age &#40;males &#60;12 years&#59; females &#60;10 years&#41;&#44; &#62;6 months of use&#44; and the minimum prednisolone cumulative dose of 152<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46; The exclusion criteria were individuals who had entered puberty or had other diseases affecting linear growth&#46; Based on the prednisolone cumulative dose of &#8805;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#40;four or more relapses&#41;&#44; the children were divided into two groups&#46; All data regarding age&#44; height&#44; and weight at disease onset and the last visit&#44; bone age&#44; and the parents&#8217; height were collected&#46; Secondary variables including mid-parental target height and predicted adult height were also calculated&#46; Height data were compared between the different rates of relapse&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 97 children &#40;68&#37; male&#41; were enrolled&#46; Their post-treatment mean height <span class="elsevierStyleItalic">Z</span>-score was less than that obtained before treatment &#40;&#8722;0&#46;584 <span class="elsevierStyleItalic">vs&#46;</span> &#8722;0&#46;158&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Subjects with higher prednisolone cumulative doses were found to have more reduction in height <span class="elsevierStyleItalic">Z</span>-score &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Post-treatment height prediction also showed less growth potential compared to pre-treatment target height &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#46; Thirty-three children &#40;34&#46;4&#37;&#41; had four or more relapses&#44; among whom more mean-height <span class="elsevierStyleItalic">Z</span>-score decreases were found compared to those with less-frequent relapses &#40;&#8722;0&#46;84 <span class="elsevierStyleItalic">vs&#46;</span> &#8722;0&#46;28&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This study showed the negative effect of cumulative dosages of prednisolone on linear growth&#44; which was greater in children with four or more relapses&#46;</p></span>"
        "secciones" => array:4 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Determinar a rela&#231;&#227;o entre a dose cumulativa de prednisolona e o crescimento linear em crian&#231;as pr&#233;-p&#250;beres com s&#237;ndrome nefr&#243;tica idiop&#225;tica&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudo transversal conduzido em todas as crian&#231;as com s&#237;ndrome nefr&#243;tica idiop&#225;tica registradas no departamento de nefrologia pedi&#225;trica no principal hospital infantil para encaminhamento no sudoeste do Ir&#227;&#46; Os crit&#233;rios de inclus&#227;o inclu&#237;ram idade &#40;meninos<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>12 anos&#59; meninas<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10 anos&#41;&#44; &#62;6 meses e a dose cumulativa de prednisolona m&#237;nima de 152<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46; Os crit&#233;rios de exclus&#227;o foram indiv&#237;duos que entraram na puberdade ou tinham outras doen&#231;as que afetam o crescimento linear&#46; Com base na dose cumulativa de prednisolona de &#8805;550<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#40;&#8805;4 recidivas&#41;&#44; as crian&#231;as foram divididas em dois grupos&#46; Foram coletados todos os dados relacionados a idade&#44; estatura e peso no in&#237;cio da doen&#231;a e na &#250;ltima visita&#44; idade &#243;ssea e estatura dos pais&#46; Tamb&#233;m foram calculadas as vari&#225;veis secund&#225;rias&#44; inclusive estatura-alvo e estatura adulta prevista&#46; Os dados de estatura foram comparados entre as diferentes taxas de recidivas&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Foram inscritas 97 crian&#231;as &#40;68&#37; do sexo masculino&#41;&#46; Seu escore z de estatura m&#233;dia p&#243;s-tratamento foi inferior ao obtido antes do tratamento &#40;&#8722;0&#44;584 em compara&#231;&#227;o com &#8722;0&#44;158&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Os indiv&#237;duos com maiores doses cumulativas de prednisolona mostraram maior redu&#231;&#227;o no escore z para estatura &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; A estatura p&#243;s-tratamento tamb&#233;m foi preditiva de menor potencial de crescimento em compara&#231;&#227;o com a estatura-alvo pr&#233;-tratamento &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;006&#41;&#59; 33 crian&#231;as &#40;34&#44;4&#37;&#41; apresentaram &#8805;4 recidivas&#44; entre as quais foram encontradas mais redu&#231;&#245;es m&#233;dias no escore z para estatura em compara&#231;&#227;o com as recidivas menos frequentes &#40;&#8722;0&#44;84 em compara&#231;&#227;o com &#8722;0&#44;28&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#227;o</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este estudo mostrou o efeito negativo das doses cumulativas de prednisolona sobre o crescimento linear&#44; que foi maior em crian&#231;as com &#8805;4 recidivas&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as&#58; Valavi E&#44; Aminzadeh M&#44; Amouri P&#44; Rezazadeh A&#44; Beladi-Mousavi M&#46; Effect of prednisolone on linear growth in children with nephrotic syndrome&#46; J Pediatr &#40;Rio J&#41;&#46; 2020&#59;96&#58;117&#8211;24&#46;</p>"
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Article information
ISSN: 00217557
Original language: English
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