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Strategies for Surveillance of Pediatric Hemolytic Uremic Syndrome: Foodborne Diseases Active Surveillance Network (FoodNet), 2000-2007. PDF

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by  OngKanyin L.
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SUPPLEMENT ARTICLE Strategies for Surveillance of Pediatric Hemolytic Uremic Syndrome: Foodborne Diseases Active Surveillance Network (FoodNet), 2000–2007 KanyinL.Ong,1,2MirasolApostal,3NicoleComstock,4SharonHurd,5TamekaHayesWebb,6StephanieMickelson,7 JoniScheftel,8GlendaSmith,9BeletshachewShiferaw,10EffieBoothe,11andL.HannahGould2 1AtlantaResearchandEducationFoundation;2EntericDiseasesEpidemiologyBranch,NationalCenterforEmergingandZoonoticInfectious Diseases,CentersforDiseaseControlandPrevention,Atlanta,Georgia;3CaliforniaEmergingInfectionsProgram,Oakland;4ColoradoDepartment ofPublicHealthandEnvironment,Denver;5ConnecticutEmergingInfectionsProgram,NewHaven;6GeorgiaEmergingInfectionsProgram,Atlanta; 7MarylandDepartmentofHealthandMentalHygiene,Baltimore;8MinnesotaDepartmentofHealth,StPaul;9NewYorkEmergingInfections Program;10OregonPublicHealthDivision,OfficeofDiseasePreventionandEpidemiology,Portland;11TennesseeDepartmentofHealth,Nashville Background. Postdiarrheal hemolytic uremic syndrome (HUS) is the most common cause of acute kidney failureamongUSchildren.TheFoodborneDiseasesActiveSurveillanceNetwork(FoodNet)conductspopulation- based surveillance of pediatric HUS to measure the incidence of disease and to validate surveillance trends in associatedShigatoxin–producingEscherichiacoli(STEC)O157infection. Methods. We report the incidence of pediatric HUS, which is defined as HUS in children ,18 years. We comparetheresultsfromprovider-basedsurveillanceandhospitaldischargedatareviewandexaminetheimpactof differentcasedefinitionsonthefindingsofthesurveillancesystem. Results. During2000–2007,627pediatricHUScaseswerereported.Fifty-twopercentofcaseswereclassifiedas confirmed (diarrhea, anemia, microangiopathic changes, low platelet count, and acute renal impairment). The averageannualcrudeincidencerateforallreportedcasesofpediatricHUSwas0.78per100000children,18years. Regardless of the case definition used, the year-to-year pattern of incidence appeared similar. More cases were captured by provider-based surveillance (76%) than by hospital discharge data review (68%); only 49% were identifiedbybothmethods. Conclusions. The overall incidence of pediatric HUS was affected by key characteristics of the surveillance system,includingthemethodofascertainmentandthecasedefinitions.However,year-to-yearpatternsweresimilar forallmethodsexamined,suggestingthatseveralapproachestoHUSsurveillancecanbeusedtotracktrends. Hemolyticuremicsyndrome(HUS)isaseveresequela casesfollowadiarrhealillnessandmostareattributable ofShigatoxin–producingEscherichiacoli(STEC)O157 toSTECO157infection[1].HUSisthemostcommon infectioncharacterizedbyhemolyticanemia,thrombo- causeofacuterenalfailureamongUSchildren,5years cytopenia, and kidney failure. Morethan 90% of HUS of age [2, 3]; of the estimated 93 000 domestically ac- quiredSTECO157infectionsintheUnitedStateseach year [4],approximately 6%willdevelop HUS[2].The mortalityrateisapproximately5%[2].HUSmayresult Correspondence: L. Hannah Gould, Enteric Diseases Epidemiology Branch, in major long-term complications, including chronic National Center for Emerging and Zoonotic Infectious Diseases, Centers for renal failure, neurologic dysfunction, and hyperten- DiseaseControlandPrevention,1600CliftonRdNE,MSC09,Atlanta,GA,30333 ([email protected]). sion [5]. Providing appropriate supportive care in ClinicalInfectiousDiseases 2012;54(S5):S424–31 a timely manner improves outcomes [6]. PublishedbyOxford UniversityPressonbehalfofthe InfectiousDiseases Surveillance for HUS provides a way to monitor SocietyofAmerica2012.ThisisanOpenAccessarticledistributedundertheterms oftheCreativeCommonsAttributionNon-CommercialLicense(http://creativecommons. trends in STEC O157 infections, can help to assess org/licenses/by-nc/3.0),whichpermitsunrestrictednon-commercialuse,distribution, which strains of STEC are associated with severe out- andreproductioninanymedium,providedtheoriginalworkisproperlycited. DOI:10.1093/cid/cis208 comes, and can evaluate whether improvements in S424 d CID 2012:54 (Suppl5) d Ongetal medical care are leading to less frequent development of New Mexico. Possible cases were identified from hospital HUSinchildreninfectedwithSTEC.Forexample,trendsin records by International Classification of Diseases, Ninth STEC O157 infections can be influenced by changes in di- Revision, Clinical Modification (ICD-9-CM) codes: 283.1 agnostic practices. By providing a stable marker of STEC (hemolytic uremic syndrome); 584.X, 283.X, and 287.X incidence, HUS surveillance can be used to determine the (acute renal failure with hemolytic anemia and thrombocy- effectiveness of preventive measures. HUS surveillance is topenia);and446.6and008.X,or446.6and009.X(TTPwith complicated by the lack of a single diagnostic test and the diarrhea caused by E. coli or an unknown pathogen) [9]. need for multiple data elements to validate each reported FoodNet personnel obtained lists of patients with the spec- case. The significance of HUS as a public health issue was ified ICD-9-CM codes after annual hospital discharge data reflected in the Healthy People 2010 goal to reduce the in- were available at each hospital within their site. Medical cidence of postdiarrheal HUS among children ,5 years of record reviews were performed for all possible cases that age by 50% (to 0.9 cases per 100 000) [7]. The Foodborne were not previously reported through provider-based Diseases Active Surveillance Network (FoodNet) conducts surveillance. active surveillance for HUS in children ,18 years using 2 A standard case report form was used to collect infor- complementary case ascertainment methods. We compare mation for all persons with HUS, including demographics thefindingofthese2methodsofcaseascertainmentandthe (age,race,sex),datesofhospitalization,monthofspecimen impactofdifferentcasedefinitionsonsurveillancedatafrom collection, antimicrobial use, results of laboratory tests for 2000 to 2007. STECandotherpathogens,outcome,dateofHUSdiagnosis, and date of entry into the FoodNet surveillance system. METHODS CaseDefinitions We classified cases as confirmed, probable, and suspected. FoodNet is a collaborative program among the Centers for Confirmedcasesmetallofthefollowing5criteria:(1)diarrhea DiseaseControlandPrevention,10participatingstatehealth with onset in the 3 weeks before HUS or TTP diagnosis; departments, the US Department of Agriculture’s Food (2) anemia [10, 11]; (3) microangiopathic changes consistent Safety and Inspection Service, and the US Food and Drug with hemolysis on peripheral blood smear (eg, schistocytes or Administration.FoodNetbeganin1996with5sites(California, helmet cells); (4) platelet count ,150 000 platelets/mL; Connecticut,Georgia,Minnesota,andOregon)andby2004 and (5) acute renal impairment (age #12 years: creatinine had grown to 10 sites (with the addition of Colorado, $1mg/dL;age$13:creatinine$1.5mg/dL)[12].Casesthat Maryland, New Mexico, New York, and Tennessee). Food- met all criteria except documented microangiopathic changes Net sites conduct active, population-based surveillance for were considered probable cases. All other illnesses diagnosed by pediatric HUS (HUS in children ,18 years of age) among aphysicianasHUSwereconsideredsuspectedcases. residentsof the FoodNet catchment areas. Until 2007, cases of HUS without a history of diarrhea preceding the illness Analysis were also included in surveillance. Cases of thrombotic We calculated crude incidence rates per 100 000 persons, thrombocytopenic purpura (TTP) were also included be- overall and by site and age, from 2000 to 2007, using pop- cause TTP diagnosed after a diarrheal illness is usually ulation estimates from the US Census Bureau [13]. We caused by infection with STEC O157 or another STEC, and summarized the crude incidence rate by case definition and thus likely representsHUS [8]. methodofascertainment(provider-basedsurveillance,HDD CaseFinding review, or both). Cases were excluded from analyses by Cases of HUS among residents of the FoodNet catchment method of ascertainment in instances where the method of area were ascertained in 2 ways. First, FoodNet personnel ascertainmentwasnotrecorded.Wecalculatedthetimethat routinely contacted an established network of pediatric elapsedbetweenthedateofHUSdiagnosisandthedatethe nephrologistsandhospitalinfectioncontrolpractitionersto case was entered into FoodNet HUS surveillance. We cal- identify patients with a physician diagnosis of HUS (provider- culatedseasonbythemonthofHUSdiagnosis,whereJune– based surveillance). Second, FoodNet sites conducted periodic Augustwasclassifiedassummer,September–Novemberwas reviews of hospital discharge data (HDD) to supplement case classifiedasfall,December–Februarywasclassifiedaswinter, finding. HDD review was implemented in 2004 and was andMarch–Maywasclassifiedasspring.Wesummarizedthe conducted retrospectively to identify HUS cases occurring proportion of patient demographics, illness severity, and since2000thatmayhavebeenmissedbythefirstmethod.All laboratory findings for each case definition and method of FoodNetsitesconductedHDDreviews,withtheexceptionof ascertainment. We used a v2 test to determine if there was FoodNet2000–2007PediatricHUS d CID 2012:54 (Suppl5) d S425 a significant difference of at least P , .05 among the case We compared the crude incidence rates by year for con- definition and the method of ascertainment for each char- firmed cases, confirmed andprobablecases, and confirmed, acteristic. The analysis was conducted using SAS software probable,andsuspectedcases(Figure1A).Regardlessofthe version 9.1.3 (SAS Institute, Cary, North Carolina). case definition used, the year-to-year pattern of incidence appeared similar. When both confirmed and probable cases RESULTS were included, the annual incidence rate was an average of 16% (range, ,1%–32%) higher than the rate when only Atotalof627physician-diagnosedpediatricHUScaseswere confirmed cases were used. However, the annual incidence reported to the FoodNet HUS surveillance system during rate when all cases (confirmed, probable, and suspected) 2000–2007. An average of 78 cases was reported each year were included was an average of 92% (range, 81%–119%) (range, 54–110). Most cases (66%; 416) were in children higher than the rate calculated with only confirmed cases. ,5 years old; of these, 64% were in children ,2 years old. Inclusion of both probable and suspected cases did not Fifty-six percent (350) were female. The overall incidence changetherankorderofincidenceamongsitesorinchildren rate was 0.78 per 100 000 children. Incidence was highest ,5 years. in children ,5 years old (1.9 per 100 000 persons). The TwoFoodNetsites(ConnecticutandMinnesota)hadstate highest incidence rates were in Oregon (1.3), Minnesota restrictionstomedicalrecordaccessthatlimitedtheirability (1.1), and Tennessee (1.0); the lowest rates were in Georgia toconductHDDreview,andtherefore,123(20%)caseswere and Maryland (0.4). excluded from our comparison of ascertainment methods. Of all reported cases, 326 (52%) were classified as con- Among the 504 cases for which a method of ascertainment firmed, 53 (8%) as probable, and 248 (40%) as suspected was verified, 76% were captured by provider-based surveil- (Table 1). Confirmed, probable, and suspected cases were lance and 68% were captured by HDD review (Figure 2). reported every year. The proportion of cases classified as Two hundred forty-nine (49%) were identified independently confirmed in each site ranged from 40% to 67%, the pro- by both provider-based surveillance and HDD review, 136 portion of cases classified as probable ranged from 3% to (27%) were found only by provider-based surveillance, and 96 30%,andtheproportionclassifiedassuspectedrangedfrom (19%) were found only by HDD review (Figure 2). An ad- 29% to 49%. Among the 248 suspected cases, evidence of ditional 23 cases were found by other means (ie, during an microangiopathicchangeswasthecriterionmostcommonly outbreak or during routine STEC surveillance). The propor- notmetormissing(50%notmet,5%missing),followedby tion of cases identified by provider-based surveillance that evidence of renal injury, (37% not met, 9% missing), or were confirmed or probable (55%) was slightly higher than anemia (31% not met, 8% missing). Sixty-nine (28%) sus- the proportion identified by HDD review (49%), but this pected cases did not report diarrhea in the 3 weeks before differencewasnotstatisticallysignificant(Table1).At4sites HUSdiagnosisandanadditional5weremissinginformation (Colorado, Georgia, Maryland, and New York), provider-based on this criterion. Among suspected cases, there were 176 surveillance identified a disproportionately greater number (71%) with 1 criterion not met or missing, 49 (20%) with of confirmed and probable cases, while in one (Oregon), 2criterianotmetormissing,2(8%)with3criterianotmet HDDreviewidentifiedmorecases(Figure3).Thepercentage or missing, and 3 (1%) with 4 criteria notmetor missing. of cases found by both methods ranged from 19% in Table 1. Number and Proportion of Hemolytic Uremic Syndrome Cases by Method of Ascertainment and Case Definition, FoodNet, 2000–2007 MethodofAscertainment Provider-Based HospitalDischargeDataReview OtherorUnknowna AllCases Casedefinition Confirmed 210(55) 168(49) 82(56) 326(52) Probable 36(9) 29(8) 14(10) 53(8) Suspected 139(36) 148(43) 50(34) 248(40) Total 385 345 146 627 Alldataarepresentedasno.(%). a The methodof ascertainmentcould not beconfirmed for 123cases.Twenty-threecasesthatwere identified throughother means(ie, outbreak,routine surveillanceforShigetoxin–producingEscherichiacoli)werealsoreported. S426 d CID 2012:54 (Suppl5) d Ongetal Figure 1. A, Comparison of hemolytic uremic syndrome rates in children ,18 years old, by year and case definition, FoodNet, 2000–2007. B,Comparisonofhemolyticuremicsyndromeratesinchildren,18yearsold,byyearandmethodofascertainment,FoodNet,2000–2007. Coloradoto89%inOregon.Whenthecrudeincidencerates of ascertainment, 79% of those identified by HDD review of cases captured by provider-based surveillance and HDD were entered into the surveillance system within 2 years, review were compared, the year-to-year pattern appeared compared with 95% of those captured by provider-based similar from 2000 to 2006. In 2007, there was a higher rate surveillance. Most (315, 82%) cases captured by provider- among cases captured by HDD review than provider-based based surveillance were entered into the HUS surveillance surveillance (Figure 1B). system within 6 monthsof diagnosis. Ofthe615reportedHUScaseswithcompleteinformation We compared demographics, illness severity, and labora- on dates of illness onset and case ascertainment, the median tory test findings by case definition and method of ascer- durationfromthedateofillnessonsettotheentryofdatainto tainment(Table2).Comparedwithsuspectedcases,ahigher thesurveillancesystemwas2months.Therewere470(76%) proportionofconfirmedcaseswereinchildren,5yearsold cases entered into the system within 1 year of diagnosis and (71% versus 59%, P , .01) and occurred in the summer 535(85%)within2years.Amongcaseswithaverifiedmethod months (48% versus 33%, P , .01). Confirmed cases were FoodNet2000–2007PediatricHUS d CID 2012:54 (Suppl5) d S427 Figure2. Venndiagramillustratingtheproportionofhemolyticuremicsyndromecasesidentifiedthroughprovider-basedsurveillanceandhospital dischargedatareview,FoodNet,2000–2007. also more likely than suspected cases to undergo dialysis FoodNet, a central goal of HUS surveillance is to provide (57% versus 34%, P ,.0001) and to have a stool specimen accurate information on trends over time to monitor prog- obtained (97% versus 79%, P , .0001) or one cultured for ress toward meeting public health goals. Selection of the STEC O157 (93% versus 72%, P 5 .04). Cases identified by optimalsurveillancestrategyforHUSdependsonbalancing provider-based surveillance were more likely than those iden- the best possible sensitivity and positive predictive value tified by HDD review to occur during the summer months withavailableresources.Becausesurveillanceforsyndromes (48% versus 41%, P 5 .04), to have had bloody diarrhea such as HUS is challenging because of the lack of a single (77%versus66%,P,.01),tohaveanystoolspecimenobtained diagnostic test, detailed clinical and laboratory information (94%versus87%,P,.01),andtohaveastoolspecimenthat is needed to validate the reported diagnosis. Additionally, wastestedforShigatoxin(40%versus31%,P,.01). the performance characteristics of the case definition will vary based on the level of clinical and laboratory detail that DISCUSSION are available. Thus, it is important to evaluate the various factors that affect the findings of the system by using dif- The findings of the FoodNet HUS surveillance system were ferentsurveillance methodsto find cases. affected by key characteristics of the surveillance system, The magnitude of the incidence rate reported by the including the methods for case ascertainment and classifi- FoodNetHUSsurveillancesystemvariedbyasmuchas92% cation. However, year-to-year patterns were similar for all dependingonhowcaseswereclassified.Althoughallpersons methods examined, suggesting that although the sensitivity with HUS were identified through a provider network or and specificity of the various approaches for HUS surveillance were found using hospital discharge codes for HUS and re- vary, several methods can be used to track trends. For lated conditions, almost half were classified as suspected S428 d CID 2012:54 (Suppl5) d Ongetal Figure 3. Proportion of confirmed and probable hemolytic uremic syndrome cases ascertained by provider-based surveillance and hospital discharge data review, bysite, FoodNet, 2000–2007 (N 5481). Categories are not mutually exclusive—cases could beidentified by eitherorboth methods.Percentageofcasesidentifedbybothmethods:California,80%;Colorado,19%;Georgia,25%;Maryland,19%;NewYork,82%;Oregon,89%; Tennessee,64%.ThreeFoodNetsites(Connecticut,Minnesota,NewMexico)hadstaterestrictionstomedicalrecordaccessthatlimitedtheirability toconducthospitaldischargedatareview.Abbreviation:HUS,hemolyticuremicsyndrome. using our definitions. However, regardless of the case defi- identify potential HUS cases for surveillance purposes. Be- nition, the interpretation of trends remained the same, sug- cause the FoodNet form did not collect information on the gesting that the system would yield similar incidence patterns specificcodesthatwereusedtoidentifyeachcase,itwasnot independentofascertainmentmethodsorcase definition. The possibletolookatthesensitivityofeachcodebythelevelof use of a more sensitive, less specific case definition for HUS case classification. However, most of the other case charac- that did not require laboratory evidence of HUS likelyledto teristics were similar, regardless of the mode of ascertain- the inclusion of some persons without HUS, as well as many ment, suggesting that either method will capture a similar withlesssevereHUS,asevidencedbytheconsiderablylower cross-sectionofcases.Differencesintheproportionofcases dialysis requirements of children meeting only the suspected wherestoolwastestedforShigatoxinindicatethatproviders case definition. Conversely, the use of a less sensitive, more shouldbeinformedabouttheimportanceoftestingforShiga specific case definition (confirmed cases only) would likely toxin. result in a failure to include some true HUS cases. All case Several factors determine the optimal strategy for HUS definitions showed similar changes in HUS rates at FoodNet surveillance. While provider-based surveillance is timelier sitesovertime. than HDD review, extensive resources are necessary to es- Provider-based surveillance was the more sensitive tablishandmaintainrelationshipswithhealthcareproviders. methodofcaseascertainment,contributing28%morecases Although less timely, HDD review can be a valuable sur- than HDD review alone. However, using HDD review to veillance tool for illnesses that frequently result in hospi- supplementactivesurveillanceincreasedthetotalnumberof talization, are rare, or have severe outcomes [14–16]. HDD casesby 19%. Ina perfectworld, all casesof HUS would be review can be done only once annually, although issues of identified by both methods. However, we observed consid- restrictedaccesstomedicalrecordscandelaytheprocess.In erablesite-to-sitevariationintheproportionofcasesfound the case of some FoodNet sites, this resulted in delays of by each method, illustrating potential gaps in surveillance .2 years until a case was reported, or not having access to that require improvement. Using multiple methods of case the patient-level clinical data needed to confirm the HUS ascertainment periodically can also help to validate the ef- diagnosis because some sites were only allowed access to fectiveness of surveillance. aggregate data on HUS cases that were identified through CasesfoundbyHDDreviewwerelesslikelytobeconfirmed HDD review. These issues might make HDD review pro- than those found by provider-based surveillance. This was hibitiveforotherstatesthatareconsideringstrengtheningor likely due, in part, to the use of broad discharge codes to expandingHUS surveillance. FoodNet2000–2007PediatricHUS d CID 2012:54 (Suppl5) d S429 Table2. ComparisonofCharacteristicsofCasesofHemolyticUremicSyndromebyCaseDefinitionandMethodofCaseAscertainment, FoodNet,2000–2007 CaseDefinition MethodofAscertainment Hospital Discharge Confirmed Probable Suspected Provider-Based DataReview (n5326) (n553) (n5248) (n5385) (n5345) Characteristic No.(%) No.(%) No.(%) PValue No.(%) No.(%) PValue Medianage,years 3 3 4 . 3 3 . Age,5years 230(71) 39(74) 147(59) ,.01 276(72) 237(69) .42 Female 175(54) 33(62) 142(57) .40 223(58) 195(57) .71 June–August(summer) 157(48) 22(42) 82(33) ,.01 185(48) 140(41) .04 Illnessseverity Death 9(3) 0(0) 10(4) .c 10(3) 8(2) .82 Mediandayshospitalized 12 13 10 . 12 11 . Bloodydiarrhea 253(78) 48(91) 137(55) .18 297(77) 229(66) ,.01 Dialysis 186(57) 31(58) 85(34) ,.01 202(52) 159(46) .09 Laboratorytesting Stoolspecimenobtained 315(97) 51(96) 197(79) ,.01 360(94) 300(87) ,.01 StooltestedforShigatoxina 160(49) 29(55) 88(53) .16 155(40) 106(31) ,.01 StoolpositiveforShigatoxinb 100(63) 25(86) 63(72) .11 114(74) 75(71) .67 StoolculturedforSTECO157a 303(93) 49(92) 179(72) .04 346(90) 279(81) .08 STECO157isolatedfromstoolb 162(53) 32(65) 110(61) .07 212(61) 155(56) .16 StoolculturedforSTECnon-O157a 40(12) 2(4) 12(5) .c 28(7) 15(4) .16 STECnon-O157isolatedfromstoolb 9(23) 2(100) 2(17) .c 6(21) 5(33) .47 Serumcollected 47(14) 7(13) 28(11) .05 73(19) 55(16) .33 SerumpositiveforSTECLPSb 42(89) 7(100) 23(82) .20 50(68) 39(71) .56 Abbreviations:LPS,lipopolysaccharide;STEC,Shigatoxin–producingEscherichiacoli. a Ofstoolsobtained. b Ofstoolstested/cultured. c Cellstoosmalltoconductavalidstatisticaltest. Because we limited our analysis only to the surveillance Supplement sponsorship. This article was published as part of a supplement entitled ‘‘Studies From the Foodborne Diseases Active techniques used by the FoodNet surveillance system, our Surveillance Network,’’ sponsored by the Division of Foodborne, findings might not be comparable to other studies that Waterborne, and Environmental Diseases of the National Center for found cases of HUS using other case definitions [17–21]. Emerging and Zoonotic Infectious Diseases from the Centers for Dis- Despite the use of 2 surveillance techniques, it is likely that ease Control and Prevention, and the Association of Public Health Laboratories. we missed cases and that other surveillance mechanisms Potentialconflictsofinterest. Allauthors:Noreportedconflicts. could further enhance case finding. At some sites, the ma- AllauthorshavesubmittedtheICMJEFormforDisclosureofPotential jority of cases were identified by only one method, sug- Conflicts of Interest. Conflicts that the editors consider relevant to the contentofthemanuscripthavebeendisclosed. gesting that there may have been other cases that were missed. Surveillance for HUS is challenging, ideally re- References quiring the use of multiple methods to detect trends over time and ascertain all cases. Health departments should 1. Mahon BE, Griffin PM, Mead PS, Tauxe RV. Hemolytic uremic consider available resources and data needs when choosing syndromesurveillancetomonitortrendsininfectionwithEscherichia coliO157:H7andotherShigatoxin-producingE.coli.EmergInfect the optimal surveillance strategy. Dis1997;3:409–12. 2. GouldLH,DemmaL,JonesTF,etal.Hemolyticuremicsyndrome and death in persons with Escherichia coli O157:H7 infection, Notes FoodborneDiseasesActiveSurveillanceNetworksites,2000–2006. ClinInfectDis2009;49:1480–5. 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