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the Brazilian Ministry of Health introduced RV1&#44; a live attenuated monovalent vaccine derived from human G1P&#91;8&#93; strain&#44; simultaneously in all 27 states&#44; through its National Immunization Program &#40;Programa Nacional de Imuniza&#231;&#227;o &#91;PNI&#93;&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A key issue for rotavirus vaccine immunization programs is the need for safety monitoring with regard to intussusception&#44; a form of intestinal obstruction occurring at a background rate of approximately 50 per 100&#44;000 infants&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">3</span></a> An earlier rotavirus vaccine &#40;Rotashield&#44; Wyeth Vaccines&#44; PA&#44; USA&#41; based on a different &#40;rhesus&#41; strain than the current WHO recommended vaccines was found to be associated with an increased risk of intussusception&#44; with the vaccine causing roughly ten excess cases per 100&#44;000 vaccinated infants&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">4</span></a> Large clinical trials have not detected a risk of intussusception associated with either currently used vaccines<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">5&#44;6</span></a>&#59; however&#44; post-licensure surveillance in Mexico and Australia has observed a small risk of intussusception after the initial dose&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">7&#44;8</span></a> In Mexico&#44; an association was found between RV1 and intussusception&#44; with the vaccine causing one to four excess cases of intussusception per 100&#44;000 vaccinated infants&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">8&#44;9</span></a> In Australia&#44; a possible temporal clustering of intussusception episodes was noted during the seven days after the initial dose of both RV1 and RV5&#44; though there was no increase in overall risk at 12 months of age&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">7</span></a> In Brazil&#44; no increased risk was identified after the first dose&#44; but a potential small risk was identified after the second dose of RV1 &#40;excess of 1&#46;5 cases per 100&#44;000 vaccinated infants&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> No definite increased risk of intussusception has been identified after use of RV5 in the United States&#44; but an excess risk less than one in 65&#44;000 vaccinated infants has not been excluded&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">10</span></a> Marked declines in severe and fatal diarrhea were demonstrated in early adopter countries after the introduction of rotavirus vaccine&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">11</span></a> Because the documented benefits of vaccination have far outweighed the low-level risk of intussusception observed in some settings&#44; regulatory agencies have continued to recommend rotavirus vaccination for all children worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">2</span></a> Ongoing post-licensure monitoring of the safety and effectiveness of rotavirus vaccines is crucial for assessing the risk&#47;benefit profile of rotavirus vaccines&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">This study&#39;s objective was to monitor and characterizes the intussusception events in a subset of participating hospitals and compares the number of intussusceptions cases before and after the introduction of rotavirus vaccine&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Intussusception case definition</span><p id="par0020" class="elsevierStylePara elsevierViewall">Intussusception case-patients were included if registered as State of S&#227;o Paulo residents&#44; aged less than 1 year&#44; and diagnosed with definite intussusception based on Level I of diagnostic certainty as defined by the Brighton Collaboration Intussusception Working Group criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a> Diagnosis of intussusception is classified as Level 1 if confirmed by air or liquid contrast enema&#44; ultrasound &#40;with confirmed reduction on subsequent ultrasound or enema&#41;&#44; or at surgery or autopsy&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Setting and data sources</span><p id="par0025" class="elsevierStylePara elsevierViewall">S&#227;o Paulo is a highly industrialized Brazilian state&#46; It is also the most populous&#58; over 41 million people live there &#40;41&#44;579&#44;695 in 2011&#41;&#46; The newborn cohort has been decreasing in recent years&#46; In 2001&#44; 686&#44;533 children were born in S&#227;o Paulo&#44; while 605&#44;558 were born in 2008&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a> Two-dose rotavirus vaccine coverage among children &#60;1 year of age reached 85&#46;1&#37; in 2007 and 86&#46;3&#37; in 2008&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> In S&#227;o Paulo state&#44; there are 9549 clinical pediatric beds and 1048 pediatric surgery beds distributed across 893 public and private hospitals&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Data on intussusception were obtained from 58 hospitals in S&#227;o Paulo state from 2001 through 2008&#46; These sentinel hospitals were selected from those with pediatric surgery services that served as the primary referral hospital for intestinal obstruction in each metropolitan area or groups of municipalities &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Not all of these hospitals conducted surveillance during the entire 2001&#8211;2008 study period&#46; Thus&#44; for comparison of the pre-vaccine and post-vaccine periods&#44; data was only used from 21 of the 58 hospitals that conducted intussusception surveillance for the entire 2001&#8211;2008 period&#46; These hospitals contain 10&#46;2&#37; of the clinical pediatrics beds and 12&#46;7&#37; of the pediatric surgery beds of S&#227;o Paulo state&#44; but accounted for approximately 30&#37; of the discharge diagnoses of intestinal obstruction identified among children younger than 1 year of age admitted in public hospitals in S&#227;o Paulo during 2001&#8211;2005&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Two approaches were used to ascertain intussusception cases&#46; To establish a pre-vaccine baseline&#44; intussusception cases hospitalized between January 2001 and February 2006 were identified at each sentinel hospital through retrospective review of discharge diagnoses coded as intestinal obstruction &#40;K56&#41;&#44; according to the International Classification of Diseases&#44; 10th edition &#40;ICD-10&#41;&#44; and diagnoses of intussusception in radiology or surgical log-books&#46; The search was conducted during 2006 and data were abstracted from medical records using standardized forms&#46; Cases occurring between March 2006 and December 2008 were identified through a prospective surveillance system that was established in sentinel private and public state hospitals&#46; Medical and surgical staff at sentinel hospitals participated in an initial training in identifying intussusception cases using the validated Brighton Collaboration Level I case definition&#46; Hospital staff&#44; particularly pediatric surgeons&#44; were asked to report cases electronically using a standard data collection form&#46; Periodic visits and calls were made to the hospital to encourage reporting and to address concerns&#46; Periodic review of surgical and radiology logs was conducted to ensure the thoroughness of reporting&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The demographic and clinical characteristics of case-patients from all hospitals were summarized using descriptive statistics&#46; To examine potential seasonal variation and age distribution of intussusception cases&#44; the number of intussusception hospitalizations in S&#227;o Paulo was plotted by year and week of age&#46; For this analysis&#44; cases from all 58 surveillance hospitals were used&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">It was also of interest to monitor changes in number of intussusception cases before and after the introduction of vaccine&#46; Thus&#44; the number of intussusception cases per year was plotted for those 21 hospitals that conducted surveillance during the entire 2001&#8211;2008 period&#46; Because rotavirus vaccine coverage among infants was high after 2006&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> this study compared the number of intussusception events during 2007 and 2008 with the average annual number of cases during the baseline years 2001&#8211;2005&#44; considering 2006 as a transition year when rotavirus vaccine was being introduced&#46; The number of intussusception cases from these 21 hospitals was also plotted by calendar year&#44; according to four age groups&#58; &#60;6 weeks&#44; 6&#8211;14 weeks&#44; 15&#8211;24 weeks&#44; and 25&#8211;52 weeks&#46; All statistical analyses were performed using Epi-Info 3&#46;5&#46;1 &#40;Epi Info&#8482;&#44; GA&#44; USA&#41; and Microsoft Excel 2007 &#40;Microsoft<span class="elsevierStyleSup">&#174;</span>&#44; WA&#44; USA&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethics</span><p id="par0050" class="elsevierStylePara elsevierViewall">The study was approved by the Ethics Committee of Irmandade da Santa Casa de Miseric&#243;rdia de S&#227;o Paulo&#44; registration No&#46; 38053&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinical and demographic characteristics of cases</span><p id="par0055" class="elsevierStylePara elsevierViewall">Between 2001 and 2008&#44; a total of 331 intussusception cases were identified in S&#227;o Paulo state &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Intussusception cases were more likely to be male &#40;59&#46;5&#37;&#41; and had a median age of 26 weeks &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; with peak incidence among those 18&#8211;24 weeks of age &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Only 9&#46;1&#37; of the intussusception events occurred among children &#60;15 weeks of age&#44; when the initial dose of rotavirus vaccines is typically administered in Brazil&#44; whereas 36&#46;6&#37; occurred among those 15&#8211;24 weeks of age&#44; when the second dose of rotavirus vaccine is typically administered&#44; and 54&#46;4&#37; among those 25&#8211;52 weeks of age&#46; Intussusception events occurred year-round&#44; without evidence of a seasonal peak &#40;data not shown&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The most frequently observed signs or symptoms &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; included vomiting &#40;89&#46;4&#37;&#41;&#44; bloody stool &#40;75&#46;5&#37;&#41;&#44; and abdominal distention &#40;71&#46;8&#37;&#41;&#46; Mean duration of symptoms before presenting for medical care was roughly one day&#46; Diagnosis of intussusception was made by ultrasonography&#44; contrast enema&#44; and surgery in 44&#46;1&#37;&#44; 21&#46;5&#37;&#44; and 34&#46;1&#37; of the case-patients&#44; respectively&#46; A majority &#40;92&#46;1&#37;&#41; of the case-patients were surgically treated for intussusception&#44; with at least 31&#46;8&#37; of those who underwent surgery requiring bowel resection&#46; Among the 331 case-patients hospitalized for intussusception during the study period&#44; 13 &#40;3&#46;9&#37;&#41; died&#46; Among those surviving&#44; the mean duration of hospitalization was approximately five days &#40;range&#58; 0&#8211;76 days&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Temporal distribution of cases</span><p id="par0065" class="elsevierStylePara elsevierViewall">Among the 331 case-patients&#44; 246 &#40;74&#46;3&#37;&#41; were from 21 hospitals that identified and reported intussusception during the entire surveillance period&#44; 2001&#8211;2008&#46; The overall demographic and clinical characteristics of cases from these 21 hospitals were similar to those of cases from hospitals that only reported cases for part of the surveillance period &#40;data not shown&#41;&#46; When restricting the analysis to cases at the 21 hospitals with stable reporting during the entire 2001&#8211;2008 surveillance period&#44; no increase was observed in the number of reported intussusception events during the surveillance period after vaccine introduction&#46; The observed number of intussusception events during 2007 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41; and 2008 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41; was somewhat lower than the average annual number of intussusception cases &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32 cases per year&#44; range 24&#8211;42 cases per year&#41; during 2001&#8211;2005 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">Efforts to build capacity for intussusception monitoring by the Division of Immunization of the State of S&#227;o Paulo identified several important lessons for future rotavirus vaccine safety monitoring efforts in Brazil&#46; First&#44; the age distribution of intussusception in S&#227;o Paulo is similar to that in other regions of the world&#44; with &#60;10&#37; of cases occurring among those &#60;15 weeks of age&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">15&#8211;17</span></a> At this age&#44; the first dose of rotavirus vaccine &#8211; the dose with the highest potential risk of intussusception &#8211; is typically administered&#46; This finding indicates that it would be necessary to expand surveillance to a large number of hospitals in order to identify enough cases to assess risk of intussusception after the initial dose of rotavirus vaccination&#46; Identifying a four- to five-fold increase in risk of intussusception relative to background might not be possible when assessing trends of intussusception among all infants under one year of age who typically have background rates of &#8764;40&#8211;50 per 100&#44;000&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> Second&#44; surgery is the most common treatment of intussusception in Brazil&#44; compared with more developed settings where non-surgical treatment with air&#47;contrast enema is used more often&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">19&#8211;21</span></a> This finding has implications for resource-poor settings&#44; in that networking with surgeons and hospitals with surgical centers could enhance surveillance for intussusception after the introduction of vaccine&#46; Third&#44; while cautious interpretation is warranted&#44; this study did not observe a substantial increase in the number of intussusception cases during the post-vaccine introduction period&#44; when some 85&#37; of the infants had received vaccination in Brazil&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Brazil was one of the early adopters of rotavirus vaccine&#44; and has documented large reductions in hospitalizations and deaths related to diarrhea among children under five years age since the introduction of rotavirus vaccines&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> While clinical trials for rotavirus vaccines have not identified a vaccine-associated increased risk of intussusception&#44; large post-licensure evaluations in Mexico and Australia have found a low risk after the first dose of both rotavirus vaccines&#44; amounting to roughly one to four excess cases of intussusception for every 100&#44;000 vaccinated children&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">7&#8211;9</span></a> While a cautious interpretation is warranted&#44; since the present surveillance was not intended to quantify risk of intussusception associated with RV1&#44; it is reassuring that there was no large increase in intussusception cases at a population level following vaccine introduction in the state of S&#227;o Paulo&#44; Brazil&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Trend analysis cannot exclude a risk of similar magnitude to that seen in Mexico and Australia after the initial dose&#44; particularly because background rates of intussusception are very low &#40;&#8764;10&#8211;20 per 100&#44;000 infant years during 6&#8211;12 weeks of age when the first dose is administered in Brazil&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">3&#44;9</span></a> Assessing trends in narrow age windows might be useful&#44; but sample size is typically insufficient for confidently excluding risk&#44; even with national datasets from countries with large birth cohorts&#44; such as the United States&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">3</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Analytic epidemiologic studies&#44; such as those employing the case-series or the case&#8211;control method&#44; would be necessary for assessing a magnitude of risk of one to two excess adverse events per 100&#44;000 vaccinated children&#46; Surveillance platforms similar to that established by the State of S&#227;o Paulo are the backbone for such epidemiologic studies&#44; provided that intussusception case-finding is active and independent of the vaccination status&#46; Indeed&#44; several of these hospitals from S&#227;o Paulo enhanced and continued surveillance as part of a nationwide study in Brazil that assessed risk of intussusception after RV1 using self-controlled case-series and case&#8211;control design&#46; In that nationwide study&#44; no risk of intussusception was found after the first dose of rotavirus vaccine in Brazil&#44; but a low-level risk was detected after the second dose&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> Initiating this type of active hospital based surveillance for specific outcomes such as intussusception would be valuable for safety monitoring in other settings without any existing national safety monitoring platforms&#44; particularly for building capacity for safety monitoring and for obtaining established platforms that can be utilized for specialized studies for assessing risk as new safety concerns arise&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In the present cohort&#44; 90&#37; of the intussusception case-patients required surgery&#46; This is comparable to treatment standards in resource poor settings&#44; while in industrialized countries only 10&#8211;50&#37; of patients require surgical treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">15&#44;19&#8211;21</span></a> The reasons for the high rates of surgical treatment among cases remain a subject for further investigation&#46; Delays in presentation and treatment may also explain the higher in-hospital mortality of 4&#8211;5&#37; in some regions of Brazil<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> and &#8764;12&#8211;13&#37; reported from Africa&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a> compared with 1&#37; in Mexico<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> and &#60;1&#37; in industrialized countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">19&#8211;21</span></a> Improving diagnosis and early intervention with non-invasive reduction techniques have the potential to reduce morbidity and mortality in Brazil&#46; Further studies identifying risk-factors for severe outcomes related to intussusception in Brazil are warranted&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">This evaluation has several limitations&#46; First&#44; this study considered sentinel services&#46; The reported cases do not represent all intussusception cases of S&#227;o Paulo state during the studied period&#46; The selected services have 30&#37; of pediatrics beds of the State of S&#227;o Paulo&#39;s public health system&#44; which covers &#8764;60&#37; the population&#46; Without a precise population denominator&#44; it is not possible to calculate incidences&#46; Results in absolute numbers can be influenced by population changes&#44; such as decrease in birth rate over time&#46; Second&#44; using different surveillance methods before and after the introduction of vaccine limits the ability to confidently compare the rate of events between the two periods&#44; particularly because of differences in methods of ascertaining cases&#46; These results alone cannot be used to refute a casual association between rotavirus vaccination and intussusception&#44; and cannot be directly compared with data from post-licensure monitoring in Mexico and Australia&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">7&#44;8</span></a> Third&#44; vaccination history of cases was not available&#46; Moreover&#44; the completeness and accuracy of data describing the clinical presentation and management of intussusceptions reflects recording completeness in medical records&#46; Fourth&#44; intussusception is a rare event&#44; especially among infants aged &#60;3 months&#59; relatively small changes in absolute numbers in narrower age ranges&#44; such as infants aged 6&#8211;14 weeks&#44; could result an increase or decrease in trend by chance alone&#46; Last&#44; hospital based surveillance may not be representative of all intussusception events&#44; particularly in resource poor settings where access to pediatric diagnostic facilities and treatment is limited&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Since 2006&#44; rotavirus vaccines have been introduced in over 30 countries worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">22</span></a> While the benefits of rotavirus vaccination in terms of reducing severe and fatal diarrhea have far outweighed the low risk of intussusception&#44; the ongoing monitoring of intussusception after the introduction of vaccine is important for ensuring vaccine safety and maintaining public trust in the rotavirus vaccine program&#46; The present experience&#44; establishing intussusception surveillance for monitoring post licensure rotavirus vaccine safety in S&#227;o Paulo&#44; should provide valuable information for other similar countries that are introducing rotavirus vaccine and do not have existing safety monitoring systems&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Intussusception surveillance was initiated after the nationwide introduction of live attenuated monovalent rotavirus vaccine &#40;RV1&#41;&#46; The objective is to assess the epidemiology of intussusception and compare the number of cases before and after the introduction of rotavirus vaccine&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cases of intussusception occurring between March 2006 and January 2008 were identified through a prospective enhanced passive surveillance system established in sentinel state hospitals&#46; Retrospective review of medical records was used to identify cases&#44; which occurred in sentinel hospitals between January 2001 and February 2006&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">From 2001 to 2008&#44; 331 intussusception cases were identified&#44; 59&#46;5&#37; were male&#44; with peak incidence among those 18&#8211;24 weeks of age&#46; Overall &#60;10&#37; of cases were among infants 6&#8211;14 weeks of age &#40;when the first dose of RV1 is administered&#41;&#46; The most frequently observed signs or symptoms of intussusception included vomiting &#40;89&#46;4&#37;&#41;&#44; bloody stool &#40;75&#46;5&#37;&#41;&#44; and abdominal distention &#40;71&#46;8&#37;&#41;&#46; A majority &#40;92&#46;1&#37;&#41; of the case-patients required surgery for treatment&#59; 31&#46;8&#37; of those who underwent surgery required bowel resection&#44; and 13 &#40;3&#46;9&#37;&#41; died&#46; Among the 21 hospitals that reported cases throughout the entire surveillance period &#40;2001&#8211;2008&#41;&#44; the number of intussusception events during 2007 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41; and 2008 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41; was not greater than the average annual number &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>31&#44; range 24&#8211;42&#41; during baseline years 2001&#8211;2005&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Although this analysis did not identify an increase in intussusception cases during the two years after RV1 introduction&#44; these results support the need for special epidemiologic methods to assess the potential link between rotavirus vaccine and this very rare adverse event&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A vigil&#226;ncia da intussuscep&#231;&#227;o foi iniciada ap&#243;s a introdu&#231;&#227;o da vacina monovalente viva atenuada contra rotav&#237;rus &#40;RV1&#41; em todo o pa&#237;s&#46; O objetivo &#233; avaliar a epidemiologia da intussuscep&#231;&#227;o e comparar a quantidade de casos antes e depois da introdu&#231;&#227;o da vacina contra rotav&#237;rus&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Os casos de intussuscep&#231;&#227;o entre mar&#231;o de 2006 e janeiro de 2008 foram identificados por meio de um sistema de vigil&#226;ncia passivo prospectivo aprimorado estabelecido em hospitais-sentinela estaduais&#46; A an&#225;lise retrospectiva de prontu&#225;rios m&#233;dicos foi utilizada para identificar os casos que ocorreram em hospitais-sentinela entre janeiro de 2001 e fevereiro de 2006&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De 2001-2008&#44; identificamos 331 casos de intussuscep&#231;&#227;o&#44; 59&#44;5&#37; dos quais ocorreram em pacientes do sexo masculino&#44; com pico de incid&#234;ncia entre aqueles com 18-24 semanas de idade&#46; Em geral&#44; &#60; 10&#37; dos casos ocorreram entre neonatos com 6-14 semanas de idade &#40;quando a 1&#170; dose de RV1 &#233; administrada&#41;&#46; Os sinais ou sintomas de intussuscep&#231;&#227;o observados com mais frequ&#234;ncia inclu&#237;am v&#244;mito &#40;89&#44;4&#37;&#41;&#44; fezes com sangue &#40;75&#44;5&#37;&#41; e distens&#227;o abdominal &#40;71&#44;8&#37;&#41;&#46; A maioria &#40;92&#44;1&#37;&#41; dos pacientes precisou de cirurgia para o tratamento&#59; 31&#44;8&#37; dos que se submeteram &#224; cirurgia precisaram de ressec&#231;&#227;o intestinal&#44; e 13 &#40;3&#44;9&#37;&#41; vieram a &#243;bito&#46; Entre os 21 hospitais que relataram casos durante todo o per&#237;odo de vigil&#226;ncia &#40;2001-2008&#41;&#44; a quantidade de casos de intussuscep&#231;&#227;o em 2007 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41; e 2008 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41; n&#227;o foi maior que a quantidade m&#233;dia anual &#40;31&#44; faixa de 24-42&#41; durante os anos-base de 2001-2005&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Embora esta an&#225;lise n&#227;o tenha identificado um aumento nos casos de intussuscep&#231;&#227;o nos dois anos ap&#243;s a introdu&#231;&#227;o da RV1&#44; esses resultados justificam a necessidade de m&#233;todos epidemiol&#243;gicos especiais para avaliar a poss&#237;vel associa&#231;&#227;o entre a vacina contra rotav&#237;rus e esse evento adverso muito raro&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclus&#245;es"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Fernandes EG&#44; Leshem E&#44; Patel M&#44; Flannery B&#44; Pellini AC&#44; Veras MA&#44; et al&#46; Hospital-based surveillance of intussusception among infants&#46; J Pediatr &#40;Rio J&#41;&#46; 2016&#59;92&#58;181&#8211;7&#46;</p>"
      ]
    ]
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      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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            "imagen" => "gr1.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Intussusceptions surveillance among infants aged &#60;12 months based on 58 hospitals in S&#227;o Paulo State&#44; Brazil&#44; 2001&#8211;2008&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Age distribution of infants with intussusceptions by week of age from 58 hospitals in S&#227;o Paulo State&#44; 2001&#8211;2008 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>331&#41;&#46;</p>"
        ]
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      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Trends in yearly intussusception hospitalizations among infants aged &#60;12 months between 2001 and 2008&#46; Data are from 21 sentinel hospitals of the hospital-based intussusception surveillance of S&#227;o Paulo State&#44; Brazil &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>246&#41;&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intussusception cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Male sex&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">197 &#40;59&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Age &#8211; &#40;weeks&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Median&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Duration of symptoms before hospitalization &#40;days&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Median&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#8211;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Sign and symptoms&#44; n&#47;total number &#40;&#37;&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vomiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">288&#47;322 &#40;89&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bloody stool<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">191&#47;253 &#40;75&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Abdominal distention&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">183&#47;255 &#40;71&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hematochezia<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">182&#47;293 &#40;62&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Blood detected on rectal exam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">113&#47;202 &#40;55&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pallor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">123&#47;234 &#40;52&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">135&#47;307 &#40;44&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Abdominal mass&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">105&#47;273 &#40;38&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lethargy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">69&#47;223 &#40;30&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rectal mass&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&#47;209 &#40;14&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Method of diagnosis &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ultrasound&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">146 &#40;44&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Contrast enema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">71 &#40;21&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">113 &#40;34&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Necropsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;0&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Definitive treatment &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Air or contrast enema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 &#40;7&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Abdominal surgery</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">305 &#40;92&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Without bowel resection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">159 &#40;52&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>With bowel resection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">97 &#40;31&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Unknown&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49 &#40;16&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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Original article
Hospital-based surveillance of intussusception among infants
Vigilância hospitalar de intussuscepção entre neonatos
Eder Gatti Fernandesa,
Corresponding author
egatti@saude.sp.gov.br

Corresponding author.
, Eyal Leshemb, Manish Patelc, Brendan Flanneryd, Alessandra Cristina Guedes Pellinie, Maria Amelia Verasf, Helena Keico Satog
a Field Epidemiology Training Program/São Paulo State (EPISUS-SP), Secretaria de Estado da Saúde de São Paulo, São Paulo, SP, Brazil
b Epidemic Intelligence Service, Office of Workforce and Career Development, Centers for Diseases Control and Prevention, Atlanta, United States
c Division of Viral Diseases, Centers for Diseases Control and Prevention, Atlanta, United States
d Centers for Diseases Control and Prevention, Atlanta, United States
e Emergency Division of Public Health, Secretaria de Estado da Saúde de São Paulo, São Paulo, SP, Brazil
f Department of Social Medicine, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brazil
g Division of Immunization, Secretaria de Estado da Saúde de São Paulo, São Paulo, SP, Brazil
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Intussusceptions surveillance among infants aged &#60;12 months based on 58 hospitals in S&#227;o Paulo State&#44; Brazil&#44; 2001&#8211;2008&#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">Rotavirus is a leading cause of severe diarrhea&#44; accounting for &#8764;453&#44;000 deaths annually among children &#60;5 years of age worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> The World Health Organization &#40;WHO&#41; has recommended global introduction of one of the two licensed rotavirus vaccines &#91;RotaTeq or RV5 &#40;Merck<span class="elsevierStyleSup">&#174;</span>&#44; PA&#44; USA&#41; and Rotarix or RV1 &#40;Rotarix<span class="elsevierStyleSup">&#174;</span>&#44; GlaxoSmithKline Biologicals&#44; Rixensart&#44; Belgium&#41;&#93; in national immunization programs for preventing severe rotavirus disease&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">2</span></a> In March 2006&#44; the Brazilian Ministry of Health introduced RV1&#44; a live attenuated monovalent vaccine derived from human G1P&#91;8&#93; strain&#44; simultaneously in all 27 states&#44; through its National Immunization Program &#40;Programa Nacional de Imuniza&#231;&#227;o &#91;PNI&#93;&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A key issue for rotavirus vaccine immunization programs is the need for safety monitoring with regard to intussusception&#44; a form of intestinal obstruction occurring at a background rate of approximately 50 per 100&#44;000 infants&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">3</span></a> An earlier rotavirus vaccine &#40;Rotashield&#44; Wyeth Vaccines&#44; PA&#44; USA&#41; based on a different &#40;rhesus&#41; strain than the current WHO recommended vaccines was found to be associated with an increased risk of intussusception&#44; with the vaccine causing roughly ten excess cases per 100&#44;000 vaccinated infants&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">4</span></a> Large clinical trials have not detected a risk of intussusception associated with either currently used vaccines<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">5&#44;6</span></a>&#59; however&#44; post-licensure surveillance in Mexico and Australia has observed a small risk of intussusception after the initial dose&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">7&#44;8</span></a> In Mexico&#44; an association was found between RV1 and intussusception&#44; with the vaccine causing one to four excess cases of intussusception per 100&#44;000 vaccinated infants&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">8&#44;9</span></a> In Australia&#44; a possible temporal clustering of intussusception episodes was noted during the seven days after the initial dose of both RV1 and RV5&#44; though there was no increase in overall risk at 12 months of age&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">7</span></a> In Brazil&#44; no increased risk was identified after the first dose&#44; but a potential small risk was identified after the second dose of RV1 &#40;excess of 1&#46;5 cases per 100&#44;000 vaccinated infants&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> No definite increased risk of intussusception has been identified after use of RV5 in the United States&#44; but an excess risk less than one in 65&#44;000 vaccinated infants has not been excluded&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">10</span></a> Marked declines in severe and fatal diarrhea were demonstrated in early adopter countries after the introduction of rotavirus vaccine&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">11</span></a> Because the documented benefits of vaccination have far outweighed the low-level risk of intussusception observed in some settings&#44; regulatory agencies have continued to recommend rotavirus vaccination for all children worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">2</span></a> Ongoing post-licensure monitoring of the safety and effectiveness of rotavirus vaccines is crucial for assessing the risk&#47;benefit profile of rotavirus vaccines&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">This study&#39;s objective was to monitor and characterizes the intussusception events in a subset of participating hospitals and compares the number of intussusceptions cases before and after the introduction of rotavirus vaccine&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Intussusception case definition</span><p id="par0020" class="elsevierStylePara elsevierViewall">Intussusception case-patients were included if registered as State of S&#227;o Paulo residents&#44; aged less than 1 year&#44; and diagnosed with definite intussusception based on Level I of diagnostic certainty as defined by the Brighton Collaboration Intussusception Working Group criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a> Diagnosis of intussusception is classified as Level 1 if confirmed by air or liquid contrast enema&#44; ultrasound &#40;with confirmed reduction on subsequent ultrasound or enema&#41;&#44; or at surgery or autopsy&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Setting and data sources</span><p id="par0025" class="elsevierStylePara elsevierViewall">S&#227;o Paulo is a highly industrialized Brazilian state&#46; It is also the most populous&#58; over 41 million people live there &#40;41&#44;579&#44;695 in 2011&#41;&#46; The newborn cohort has been decreasing in recent years&#46; In 2001&#44; 686&#44;533 children were born in S&#227;o Paulo&#44; while 605&#44;558 were born in 2008&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a> Two-dose rotavirus vaccine coverage among children &#60;1 year of age reached 85&#46;1&#37; in 2007 and 86&#46;3&#37; in 2008&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> In S&#227;o Paulo state&#44; there are 9549 clinical pediatric beds and 1048 pediatric surgery beds distributed across 893 public and private hospitals&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Data on intussusception were obtained from 58 hospitals in S&#227;o Paulo state from 2001 through 2008&#46; These sentinel hospitals were selected from those with pediatric surgery services that served as the primary referral hospital for intestinal obstruction in each metropolitan area or groups of municipalities &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Not all of these hospitals conducted surveillance during the entire 2001&#8211;2008 study period&#46; Thus&#44; for comparison of the pre-vaccine and post-vaccine periods&#44; data was only used from 21 of the 58 hospitals that conducted intussusception surveillance for the entire 2001&#8211;2008 period&#46; These hospitals contain 10&#46;2&#37; of the clinical pediatrics beds and 12&#46;7&#37; of the pediatric surgery beds of S&#227;o Paulo state&#44; but accounted for approximately 30&#37; of the discharge diagnoses of intestinal obstruction identified among children younger than 1 year of age admitted in public hospitals in S&#227;o Paulo during 2001&#8211;2005&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Two approaches were used to ascertain intussusception cases&#46; To establish a pre-vaccine baseline&#44; intussusception cases hospitalized between January 2001 and February 2006 were identified at each sentinel hospital through retrospective review of discharge diagnoses coded as intestinal obstruction &#40;K56&#41;&#44; according to the International Classification of Diseases&#44; 10th edition &#40;ICD-10&#41;&#44; and diagnoses of intussusception in radiology or surgical log-books&#46; The search was conducted during 2006 and data were abstracted from medical records using standardized forms&#46; Cases occurring between March 2006 and December 2008 were identified through a prospective surveillance system that was established in sentinel private and public state hospitals&#46; Medical and surgical staff at sentinel hospitals participated in an initial training in identifying intussusception cases using the validated Brighton Collaboration Level I case definition&#46; Hospital staff&#44; particularly pediatric surgeons&#44; were asked to report cases electronically using a standard data collection form&#46; Periodic visits and calls were made to the hospital to encourage reporting and to address concerns&#46; Periodic review of surgical and radiology logs was conducted to ensure the thoroughness of reporting&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The demographic and clinical characteristics of case-patients from all hospitals were summarized using descriptive statistics&#46; To examine potential seasonal variation and age distribution of intussusception cases&#44; the number of intussusception hospitalizations in S&#227;o Paulo was plotted by year and week of age&#46; For this analysis&#44; cases from all 58 surveillance hospitals were used&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">It was also of interest to monitor changes in number of intussusception cases before and after the introduction of vaccine&#46; Thus&#44; the number of intussusception cases per year was plotted for those 21 hospitals that conducted surveillance during the entire 2001&#8211;2008 period&#46; Because rotavirus vaccine coverage among infants was high after 2006&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> this study compared the number of intussusception events during 2007 and 2008 with the average annual number of cases during the baseline years 2001&#8211;2005&#44; considering 2006 as a transition year when rotavirus vaccine was being introduced&#46; The number of intussusception cases from these 21 hospitals was also plotted by calendar year&#44; according to four age groups&#58; &#60;6 weeks&#44; 6&#8211;14 weeks&#44; 15&#8211;24 weeks&#44; and 25&#8211;52 weeks&#46; All statistical analyses were performed using Epi-Info 3&#46;5&#46;1 &#40;Epi Info&#8482;&#44; GA&#44; USA&#41; and Microsoft Excel 2007 &#40;Microsoft<span class="elsevierStyleSup">&#174;</span>&#44; WA&#44; USA&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethics</span><p id="par0050" class="elsevierStylePara elsevierViewall">The study was approved by the Ethics Committee of Irmandade da Santa Casa de Miseric&#243;rdia de S&#227;o Paulo&#44; registration No&#46; 38053&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinical and demographic characteristics of cases</span><p id="par0055" class="elsevierStylePara elsevierViewall">Between 2001 and 2008&#44; a total of 331 intussusception cases were identified in S&#227;o Paulo state &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Intussusception cases were more likely to be male &#40;59&#46;5&#37;&#41; and had a median age of 26 weeks &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; with peak incidence among those 18&#8211;24 weeks of age &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Only 9&#46;1&#37; of the intussusception events occurred among children &#60;15 weeks of age&#44; when the initial dose of rotavirus vaccines is typically administered in Brazil&#44; whereas 36&#46;6&#37; occurred among those 15&#8211;24 weeks of age&#44; when the second dose of rotavirus vaccine is typically administered&#44; and 54&#46;4&#37; among those 25&#8211;52 weeks of age&#46; Intussusception events occurred year-round&#44; without evidence of a seasonal peak &#40;data not shown&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The most frequently observed signs or symptoms &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; included vomiting &#40;89&#46;4&#37;&#41;&#44; bloody stool &#40;75&#46;5&#37;&#41;&#44; and abdominal distention &#40;71&#46;8&#37;&#41;&#46; Mean duration of symptoms before presenting for medical care was roughly one day&#46; Diagnosis of intussusception was made by ultrasonography&#44; contrast enema&#44; and surgery in 44&#46;1&#37;&#44; 21&#46;5&#37;&#44; and 34&#46;1&#37; of the case-patients&#44; respectively&#46; A majority &#40;92&#46;1&#37;&#41; of the case-patients were surgically treated for intussusception&#44; with at least 31&#46;8&#37; of those who underwent surgery requiring bowel resection&#46; Among the 331 case-patients hospitalized for intussusception during the study period&#44; 13 &#40;3&#46;9&#37;&#41; died&#46; Among those surviving&#44; the mean duration of hospitalization was approximately five days &#40;range&#58; 0&#8211;76 days&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Temporal distribution of cases</span><p id="par0065" class="elsevierStylePara elsevierViewall">Among the 331 case-patients&#44; 246 &#40;74&#46;3&#37;&#41; were from 21 hospitals that identified and reported intussusception during the entire surveillance period&#44; 2001&#8211;2008&#46; The overall demographic and clinical characteristics of cases from these 21 hospitals were similar to those of cases from hospitals that only reported cases for part of the surveillance period &#40;data not shown&#41;&#46; When restricting the analysis to cases at the 21 hospitals with stable reporting during the entire 2001&#8211;2008 surveillance period&#44; no increase was observed in the number of reported intussusception events during the surveillance period after vaccine introduction&#46; The observed number of intussusception events during 2007 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41; and 2008 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41; was somewhat lower than the average annual number of intussusception cases &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32 cases per year&#44; range 24&#8211;42 cases per year&#41; during 2001&#8211;2005 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">Efforts to build capacity for intussusception monitoring by the Division of Immunization of the State of S&#227;o Paulo identified several important lessons for future rotavirus vaccine safety monitoring efforts in Brazil&#46; First&#44; the age distribution of intussusception in S&#227;o Paulo is similar to that in other regions of the world&#44; with &#60;10&#37; of cases occurring among those &#60;15 weeks of age&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">15&#8211;17</span></a> At this age&#44; the first dose of rotavirus vaccine &#8211; the dose with the highest potential risk of intussusception &#8211; is typically administered&#46; This finding indicates that it would be necessary to expand surveillance to a large number of hospitals in order to identify enough cases to assess risk of intussusception after the initial dose of rotavirus vaccination&#46; Identifying a four- to five-fold increase in risk of intussusception relative to background might not be possible when assessing trends of intussusception among all infants under one year of age who typically have background rates of &#8764;40&#8211;50 per 100&#44;000&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> Second&#44; surgery is the most common treatment of intussusception in Brazil&#44; compared with more developed settings where non-surgical treatment with air&#47;contrast enema is used more often&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">19&#8211;21</span></a> This finding has implications for resource-poor settings&#44; in that networking with surgeons and hospitals with surgical centers could enhance surveillance for intussusception after the introduction of vaccine&#46; Third&#44; while cautious interpretation is warranted&#44; this study did not observe a substantial increase in the number of intussusception cases during the post-vaccine introduction period&#44; when some 85&#37; of the infants had received vaccination in Brazil&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Brazil was one of the early adopters of rotavirus vaccine&#44; and has documented large reductions in hospitalizations and deaths related to diarrhea among children under five years age since the introduction of rotavirus vaccines&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> While clinical trials for rotavirus vaccines have not identified a vaccine-associated increased risk of intussusception&#44; large post-licensure evaluations in Mexico and Australia have found a low risk after the first dose of both rotavirus vaccines&#44; amounting to roughly one to four excess cases of intussusception for every 100&#44;000 vaccinated children&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">7&#8211;9</span></a> While a cautious interpretation is warranted&#44; since the present surveillance was not intended to quantify risk of intussusception associated with RV1&#44; it is reassuring that there was no large increase in intussusception cases at a population level following vaccine introduction in the state of S&#227;o Paulo&#44; Brazil&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Trend analysis cannot exclude a risk of similar magnitude to that seen in Mexico and Australia after the initial dose&#44; particularly because background rates of intussusception are very low &#40;&#8764;10&#8211;20 per 100&#44;000 infant years during 6&#8211;12 weeks of age when the first dose is administered in Brazil&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">3&#44;9</span></a> Assessing trends in narrow age windows might be useful&#44; but sample size is typically insufficient for confidently excluding risk&#44; even with national datasets from countries with large birth cohorts&#44; such as the United States&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">3</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Analytic epidemiologic studies&#44; such as those employing the case-series or the case&#8211;control method&#44; would be necessary for assessing a magnitude of risk of one to two excess adverse events per 100&#44;000 vaccinated children&#46; Surveillance platforms similar to that established by the State of S&#227;o Paulo are the backbone for such epidemiologic studies&#44; provided that intussusception case-finding is active and independent of the vaccination status&#46; Indeed&#44; several of these hospitals from S&#227;o Paulo enhanced and continued surveillance as part of a nationwide study in Brazil that assessed risk of intussusception after RV1 using self-controlled case-series and case&#8211;control design&#46; In that nationwide study&#44; no risk of intussusception was found after the first dose of rotavirus vaccine in Brazil&#44; but a low-level risk was detected after the second dose&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> Initiating this type of active hospital based surveillance for specific outcomes such as intussusception would be valuable for safety monitoring in other settings without any existing national safety monitoring platforms&#44; particularly for building capacity for safety monitoring and for obtaining established platforms that can be utilized for specialized studies for assessing risk as new safety concerns arise&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In the present cohort&#44; 90&#37; of the intussusception case-patients required surgery&#46; This is comparable to treatment standards in resource poor settings&#44; while in industrialized countries only 10&#8211;50&#37; of patients require surgical treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">15&#44;19&#8211;21</span></a> The reasons for the high rates of surgical treatment among cases remain a subject for further investigation&#46; Delays in presentation and treatment may also explain the higher in-hospital mortality of 4&#8211;5&#37; in some regions of Brazil<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> and &#8764;12&#8211;13&#37; reported from Africa&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a> compared with 1&#37; in Mexico<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> and &#60;1&#37; in industrialized countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">19&#8211;21</span></a> Improving diagnosis and early intervention with non-invasive reduction techniques have the potential to reduce morbidity and mortality in Brazil&#46; Further studies identifying risk-factors for severe outcomes related to intussusception in Brazil are warranted&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">This evaluation has several limitations&#46; First&#44; this study considered sentinel services&#46; The reported cases do not represent all intussusception cases of S&#227;o Paulo state during the studied period&#46; The selected services have 30&#37; of pediatrics beds of the State of S&#227;o Paulo&#39;s public health system&#44; which covers &#8764;60&#37; the population&#46; Without a precise population denominator&#44; it is not possible to calculate incidences&#46; Results in absolute numbers can be influenced by population changes&#44; such as decrease in birth rate over time&#46; Second&#44; using different surveillance methods before and after the introduction of vaccine limits the ability to confidently compare the rate of events between the two periods&#44; particularly because of differences in methods of ascertaining cases&#46; These results alone cannot be used to refute a casual association between rotavirus vaccination and intussusception&#44; and cannot be directly compared with data from post-licensure monitoring in Mexico and Australia&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">7&#44;8</span></a> Third&#44; vaccination history of cases was not available&#46; Moreover&#44; the completeness and accuracy of data describing the clinical presentation and management of intussusceptions reflects recording completeness in medical records&#46; Fourth&#44; intussusception is a rare event&#44; especially among infants aged &#60;3 months&#59; relatively small changes in absolute numbers in narrower age ranges&#44; such as infants aged 6&#8211;14 weeks&#44; could result an increase or decrease in trend by chance alone&#46; Last&#44; hospital based surveillance may not be representative of all intussusception events&#44; particularly in resource poor settings where access to pediatric diagnostic facilities and treatment is limited&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Since 2006&#44; rotavirus vaccines have been introduced in over 30 countries worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">22</span></a> While the benefits of rotavirus vaccination in terms of reducing severe and fatal diarrhea have far outweighed the low risk of intussusception&#44; the ongoing monitoring of intussusception after the introduction of vaccine is important for ensuring vaccine safety and maintaining public trust in the rotavirus vaccine program&#46; The present experience&#44; establishing intussusception surveillance for monitoring post licensure rotavirus vaccine safety in S&#227;o Paulo&#44; should provide valuable information for other similar countries that are introducing rotavirus vaccine and do not have existing safety monitoring systems&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Materials and methods"
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              "titulo" => "Intussusception case definition"
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              "titulo" => "Clinical and demographic characteristics of cases"
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              "titulo" => "Temporal distribution of cases"
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    "fechaRecibido" => "2014-11-14"
    "fechaAceptado" => "2015-06-02"
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          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Rotavirus vaccines"
            1 => "Intussusception"
            2 => "Surveillance"
            3 => "Brazil"
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          "clase" => "keyword"
          "titulo" => "Palavras-chave"
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            0 => "Vacina contra rotav&#237;rus"
            1 => "Intussuscep&#231;&#227;o"
            2 => "Vigil&#226;ncia"
            3 => "Brasil"
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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">Intussusception surveillance was initiated after the nationwide introduction of live attenuated monovalent rotavirus vaccine &#40;RV1&#41;&#46; The objective is to assess the epidemiology of intussusception and compare the number of cases before and after the introduction of rotavirus vaccine&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cases of intussusception occurring between March 2006 and January 2008 were identified through a prospective enhanced passive surveillance system established in sentinel state hospitals&#46; Retrospective review of medical records was used to identify cases&#44; which occurred in sentinel hospitals between January 2001 and February 2006&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">From 2001 to 2008&#44; 331 intussusception cases were identified&#44; 59&#46;5&#37; were male&#44; with peak incidence among those 18&#8211;24 weeks of age&#46; Overall &#60;10&#37; of cases were among infants 6&#8211;14 weeks of age &#40;when the first dose of RV1 is administered&#41;&#46; The most frequently observed signs or symptoms of intussusception included vomiting &#40;89&#46;4&#37;&#41;&#44; bloody stool &#40;75&#46;5&#37;&#41;&#44; and abdominal distention &#40;71&#46;8&#37;&#41;&#46; A majority &#40;92&#46;1&#37;&#41; of the case-patients required surgery for treatment&#59; 31&#46;8&#37; of those who underwent surgery required bowel resection&#44; and 13 &#40;3&#46;9&#37;&#41; died&#46; Among the 21 hospitals that reported cases throughout the entire surveillance period &#40;2001&#8211;2008&#41;&#44; the number of intussusception events during 2007 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41; and 2008 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41; was not greater than the average annual number &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>31&#44; range 24&#8211;42&#41; during baseline years 2001&#8211;2005&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Although this analysis did not identify an increase in intussusception cases during the two years after RV1 introduction&#44; these results support the need for special epidemiologic methods to assess the potential link between rotavirus vaccine and this very rare adverse event&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
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            "titulo" => "Methods"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A vigil&#226;ncia da intussuscep&#231;&#227;o foi iniciada ap&#243;s a introdu&#231;&#227;o da vacina monovalente viva atenuada contra rotav&#237;rus &#40;RV1&#41; em todo o pa&#237;s&#46; O objetivo &#233; avaliar a epidemiologia da intussuscep&#231;&#227;o e comparar a quantidade de casos antes e depois da introdu&#231;&#227;o da vacina contra rotav&#237;rus&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Os casos de intussuscep&#231;&#227;o entre mar&#231;o de 2006 e janeiro de 2008 foram identificados por meio de um sistema de vigil&#226;ncia passivo prospectivo aprimorado estabelecido em hospitais-sentinela estaduais&#46; A an&#225;lise retrospectiva de prontu&#225;rios m&#233;dicos foi utilizada para identificar os casos que ocorreram em hospitais-sentinela entre janeiro de 2001 e fevereiro de 2006&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De 2001-2008&#44; identificamos 331 casos de intussuscep&#231;&#227;o&#44; 59&#44;5&#37; dos quais ocorreram em pacientes do sexo masculino&#44; com pico de incid&#234;ncia entre aqueles com 18-24 semanas de idade&#46; Em geral&#44; &#60; 10&#37; dos casos ocorreram entre neonatos com 6-14 semanas de idade &#40;quando a 1&#170; dose de RV1 &#233; administrada&#41;&#46; Os sinais ou sintomas de intussuscep&#231;&#227;o observados com mais frequ&#234;ncia inclu&#237;am v&#244;mito &#40;89&#44;4&#37;&#41;&#44; fezes com sangue &#40;75&#44;5&#37;&#41; e distens&#227;o abdominal &#40;71&#44;8&#37;&#41;&#46; A maioria &#40;92&#44;1&#37;&#41; dos pacientes precisou de cirurgia para o tratamento&#59; 31&#44;8&#37; dos que se submeteram &#224; cirurgia precisaram de ressec&#231;&#227;o intestinal&#44; e 13 &#40;3&#44;9&#37;&#41; vieram a &#243;bito&#46; Entre os 21 hospitais que relataram casos durante todo o per&#237;odo de vigil&#226;ncia &#40;2001-2008&#41;&#44; a quantidade de casos de intussuscep&#231;&#227;o em 2007 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41; e 2008 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41; n&#227;o foi maior que a quantidade m&#233;dia anual &#40;31&#44; faixa de 24-42&#41; durante os anos-base de 2001-2005&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Embora esta an&#225;lise n&#227;o tenha identificado um aumento nos casos de intussuscep&#231;&#227;o nos dois anos ap&#243;s a introdu&#231;&#227;o da RV1&#44; esses resultados justificam a necessidade de m&#233;todos epidemiol&#243;gicos especiais para avaliar a poss&#237;vel associa&#231;&#227;o entre a vacina contra rotav&#237;rus e esse evento adverso muito raro&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Fernandes EG&#44; Leshem E&#44; Patel M&#44; Flannery B&#44; Pellini AC&#44; Veras MA&#44; et al&#46; Hospital-based surveillance of intussusception among infants&#46; J Pediatr &#40;Rio J&#41;&#46; 2016&#59;92&#58;181&#8211;7&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Intussusceptions surveillance among infants aged &#60;12 months based on 58 hospitals in S&#227;o Paulo State&#44; Brazil&#44; 2001&#8211;2008&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Age distribution of infants with intussusceptions by week of age from 58 hospitals in S&#227;o Paulo State&#44; 2001&#8211;2008 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>331&#41;&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Trends in yearly intussusception hospitalizations among infants aged &#60;12 months between 2001 and 2008&#46; Data are from 21 sentinel hospitals of the hospital-based intussusception surveillance of S&#227;o Paulo State&#44; Brazil &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>246&#41;&#46;</p>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intussusception cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Male sex&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">197 &#40;59&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Age &#8211; &#40;weeks&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Median&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Duration of symptoms before hospitalization &#40;days&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Median&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#8211;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Sign and symptoms&#44; n&#47;total number &#40;&#37;&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vomiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">288&#47;322 &#40;89&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bloody stool<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">191&#47;253 &#40;75&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Abdominal distention&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">183&#47;255 &#40;71&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hematochezia<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">182&#47;293 &#40;62&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Blood detected on rectal exam&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">113&#47;202 &#40;55&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pallor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">123&#47;234 &#40;52&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">135&#47;307 &#40;44&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Abdominal mass&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">105&#47;273 &#40;38&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lethargy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">69&#47;223 &#40;30&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rectal mass&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&#47;209 &#40;14&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Method of diagnosis &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ultrasound&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">146 &#40;44&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Contrast enema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">71 &#40;21&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">113 &#40;34&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Necropsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;0&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Definitive treatment &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Air or contrast enema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 &#40;7&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Abdominal surgery</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">305 &#40;92&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Without bowel resection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">159 &#40;52&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>With bowel resection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">97 &#40;31&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Unknown&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">49 &#40;16&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Duration of hospitalization &#8211; days</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Median&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#8211;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Death <span class="elsevierStyleItalic">&#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#47;331 &#40;3&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Hematochezia&#58; passage of fresh blood through the anus&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Demographic and clinical characteristics of hospitalized intussusception cases&#46; State of S&#227;o Paulo&#44; Brazil&#44; 2001&#8211;2008 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>331&#41;&#46;</p>"
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              "identificador" => "bib0115"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global mortality associated with rotavirus disease among children in 2004"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "U&#46;D&#46; Parashar"
                            1 => "A&#46; Burton"
                            2 => "C&#46; Lanata"
                            3 => "C&#46; Boschi-Pinto"
                            4 => "K&#46; Shibuya"
                            5 => "D&#46; Steele"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/605025"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "2009"
                        "volumen" => "200"
                        "paginaInicial" => "S9"
                        "paginaFinal" => "S15"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19817620"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
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              "identificador" => "bib0120"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Meeting of the Strategic Advisory Group of Experts on immunization&#44; October 2009 &#8211; conclusions and recommendations"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Wkly Epidemiol Rec"
                        "fecha" => "2009"
                        "volumen" => "84"
                        "paginaInicial" => "517"
                        "paginaFinal" => "532"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19999831"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            2 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Trends in intussusception hospitalizations among US infants before and after implementation of the rotavirus vaccination program&#44; 2000&#8211;2009"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46; Yen"
                            1 => "J&#46;E&#46; Tate"
                            2 => "C&#46;A&#46; Steiner"
                            3 => "M&#46;M&#46; Cortese"
                            4 => "M&#46;M&#46; Patel"
                            5 => "U&#46;D&#46; Parashar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/infdis/jis314"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "2012"
                        "volumen" => "206"
                        "paginaInicial" => "41"
                        "paginaFinal" => "48"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22539812"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0130"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intussusception among infants given an oral rotavirus vaccine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;V&#46; Murphy"
                            1 => "P&#46;M&#46; Gargiullo"
                            2 => "M&#46;S&#46; Massoudi"
                            3 => "D&#46;B&#46; Nelson"
                            4 => "A&#46;O&#46; Jumaan"
                            5 => "C&#46;A&#46; Okoro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM200102223440804"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2001"
                        "volumen" => "344"
                        "paginaInicial" => "564"
                        "paginaFinal" => "572"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11207352"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
              ]
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            4 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;M&#46; Ruiz-Palacios"
                            1 => "I&#46; P&#233;rez-Schael"
                            2 => "F&#46;R&#46; Vel&#225;zquez"
                            3 => "H&#46; Abate"
                            4 => "T&#46; Breuer"
                            5 => "S&#46;C&#46; Clemens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa052434"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2006"
                        "volumen" => "354"
                        "paginaInicial" => "11"
                        "paginaFinal" => "22"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16394298"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety and efficacy of a pentavalent human-bovine &#40;WC3&#41; reassortant rotavirus vaccine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Vesikari"
                            1 => "D&#46;O&#46; Matson"
                            2 => "P&#46; Dennehy"
                            3 => "P&#46; Van Damme"
                            4 => "M&#46; Santosham"
                            5 => "Z&#46; Rodriguez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa052664"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2006"
                        "volumen" => "354"
                        "paginaInicial" => "23"
                        "paginaFinal" => "33"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16394299"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0145"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intussusception following rotavirus vaccine administration&#58; post-marketing surveillance in the National Immunization Program in Australia"
                      "autores" => array:1 [
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ISSN: 00217557
Original language: English
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2020 January 12 10 22
2019 December 6 7 13
2019 November 4 4 8
2019 October 10 11 21
2019 September 13 9 22
2019 August 8 9 17
2019 July 18 8 26
2019 June 13 11 24
2019 May 16 11 27
2019 April 11 10 21
2019 March 9 6 15
2019 February 7 9 16
2019 January 6 13 19
2018 December 11 7 18
2018 November 35 6 41
2018 October 190 23 213
2018 September 83 18 101
2018 August 26 1 27
2018 July 11 6 17
2018 June 41 3 44
2018 May 24 13 37
2018 April 114 4 118
2018 March 14 5 19
2018 February 3 1 4
2018 January 11 2 13
2017 December 10 1 11
2017 November 4 4 8
2017 October 11 1 12
2017 September 3 2 5
2017 August 3 1 4
2017 July 2 1 3
2017 June 11 3 14
2017 May 5 0 5
2017 April 6 18 24
2017 March 5 11 16
2017 February 4 0 4
2017 January 6 1 7
2016 December 14 6 20
2016 November 14 5 19
2016 October 22 10 32
2016 September 24 5 29
2016 August 20 3 23
2016 July 23 7 30
2016 June 31 11 42
2016 May 51 19 70
2016 April 39 18 57
2016 March 28 17 45
2016 February 12 8 20
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