AdequacyoftheComprehensiveClinicalEvaluationProgramAFocusedAssessment

CommitteeontheEvaluationoftheDepartmentofDefenseComprehensiveClinicalEvaluationProgram

DivisionofHealthPromotionandDiseasePrevention

INSTITUTEOFMEDICINE

NATIONALACADEMYPRESSWashington,D.C.1997

title:AdequacyoftheComprehensiveClinicalEvaluationProgram:AFocusedAssessment

author:publisher: NationalAcademiesPress

isbn10|asin: 0309059496printisbn13: 9780309059497ebookisbn13: 9780585002521

language: English

subject

PersianGulfWar,1991--Veterans--Diseases--UnitedStates,PersianGulfWar,1991--Veterans--Medicalcare--UnitedStates,PersianGulfWar,1991--Healthaspects--UnitedStates,UnitedStates.--Dept.ofDefense.--PersianGulfComprehensiveClinicalEvaluat

publicationdate: 1997lcc: DS79.744.H42A341997ebddc: 956.70442

PersianGulfWar,1991--Veterans--

subject:

Diseases--UnitedStates,PersianGulfWar,1991--Veterans--Medicalcare--UnitedStates,PersianGulfWar,1991--Healthaspects--UnitedStates,UnitedStates.--Dept.ofDefense.--PersianGulfComprehensiveClinicalEvaluat

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NOTICE:TheprojectthatisthesubjectofthisreportwasapprovedbytheGoverningBoardoftheNationalResearchCouncil,whosemembersaredrawnfromthecouncilsoftheNationalAcademyofSciences,theNationalAcademyofEngineering,andtheInstituteofMedicine.Themembersofthecommitteeresponsibleforthereportwerechosenfortheirspecialcompetencesandwithregardforappropriatebalance.

ThisreporthasbeenreviewedbyagroupotherthantheauthorsaccordingtoproceduresapprovedbytheReportReviewCommitteeconsistingofmembersoftheNationalAcademyofSciences,theNationalAcademyofEngineering,andtheInstituteofMedicine.

TheInstituteofMedicinewascharteredin1970bytheNationalAcademyofSciencestoenlistdistinguishedmembersofappropriateprofessionsintheexaminationofpolicymatterspertainingtothehealthofthepublic.Inthis,theInstituteactsunderboththeAcademy's1863congressionalcharterresponsibilitytobeanadvisertothefederalgovernmentanditsowninitiativeinidentifyingissuesofmedicalcare,research,andeducation.Dr.KennethI.ShineisthepresidentoftheInstituteofMedicine.

ThisstudywassupportedbytheUSDepartmentofDefenseunderContractNumberDASW01-96-K-007.TheviewspresentedarethoseoftheInstituteofMedicineCommitteeontheEvalutionoftheDepartmentofDefenseComprehensiveClinicalEvaluationProgramandarenotnecessarilythoseofthefundingorganization.

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COMMITTEEONTHEEVALUATIONOFTHEDoDCOMPREHENSIVECLINICALEVALUATIONPROGRAM

DanG.Blazer,*Chair,DeanofMedicalEducationandJ.P.GibbonsProfessorofPsychiatry,DukeUniversityMedicalCenter,Durham,NorthCarolina

RebeccaBascom,Director,EnvironmentalResearchFacility,UniversityofMaryland,Baltimore

MargitL.Bleecker,DirectoroftheCenterforOccupationalandEnvironmentalNeurology,Baltimore,Maryland

EvelynJ.Bromet,Professor,DepartmentofPsychiatry,StateUniversityofNewYorkatStonyBrook,StonyBrook,NewYork

GerardN.Burrow,*SpecialAdvisortothePresidentforHealthAffairs,YaleUniversitySchoolofMedicine,NewHaven,Connecticut

HowardKipen,AssociateProfessorandChief,OccupationalHealthDivision,UMDNJ,RobertWoodJohnsonMedicalSchool,Piscataway,NewJersey

AdelA.Mahmoud,*Chairman,DepartmentofMedicine,CaseWesternReserveUniversityandUniversityHospitalsofCleveland,Cleveland,Ohio

RobertS.Pynoos,ProfessorofPsychiatryandDirectoroftheTraumaPsychiatryService,UniversityofCalifornia,LosAngeles,California

GuthrieL.Turner,Jr.,ChiefMedicalConsultant,OfficeofDisabilityDeterminationServices,StateofWashington,Tummwater,Washington

MarkJ.Utell,ProfessorofMedicineandEnvironmentalMedicineandDirector,Pulmonary/CriticalCareandOccupationalMedicine

Divisions,UniversityofRochesterMedicalCenter,Rochester,NewYork

MichaelH.Weisman,Professor,DivisionofRheumatology,DepartmentofMedicine,UniversityofCaliforniaatSanDiego

BoardonHealthPromotionandDiseasePreventionLiaison

ElenaO.Nightingale,*Scholar-in-Residence,InstituteofMedicineandBoardonChildren,YouthandFamilies,Washington,DC

BoardonNeuroscienceandBehavioralHealthLiaison

WilliamE.Bunney,Jr.,*DistinguishedProfessorandDellaMartinChairofPsychiatry,UniversityofCalifornia,Irvine,California

*Member,InstituteofMedicine.

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Staff

LylaM.Hernandez,StudyDirector

SanjayS.Baliga,ResearchAssociate

DonnaM.Livingston,ProjectAssistant

KathleenR.Stratton,Director,DivisionofHealthPromotionandDiseasePrevention

ConstanceM.Pechura,Director,DivisionofNeuroscienceandBehavioralHealth

DonnaD.Thompson,DivisionAssistant

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ContentsEXECUTIVESUMMARY

1INTRODUCTION 11

2OVERVIEWOFTHEINSTITUTEOFMEDICINE'SPERSIANGULFACTIVITIES

15

3THECOMPREHENSIVECLINICALEVALUATIONPROGRAM17

Overview, 17

Signs,Symptoms,andIll-DefinedConditions(SSID), 18

ChronicFatigueSyndrome(CFS)andFibromyalgiaintheCCEPPopulation,

20

StressandPsychiatricDisorders, 21

4IOMREVIEW:DIFFICULT-TO-DIAGNOSEANDILL-DEFINEDCONDITIONS

25

ChronicFatigueSyndrome, 26

Fibromyalgia, 29

MultipleChemicalSensitivity, 31

ControversiesandOverlap, 34

5IOMREVIEW:STRESS,PSYCHIATRICDISORDERS,ANDTHEIRRELATIONSHIPTOPHYSICALSIGNSANDSYMPTOMS

37

StressorsandStress, 37

ConsequencesofStress, 39

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6 CONCLUSIONSANDRECOMMENDATIONS 45

MedicallyUnexplainedSymptomSyndromes, 46

Stress, 47

Screening, 48

ProgramEvaluation, 50

CoordinationwiththeVA, 51

REFERENCESANDSELECTEDBIBLIOGRAPHY 53

APPENDIXES

APresidentialAdvisoryCommitteeonGulfWarVeterans'Illnesses:FinalReportRecommendations

61

BHealthConsequencesofServiceDuringthePersianGulfWar:InitialFindingsandRecommendationsforImmediateAction

67

CHealthConsequencesofServiceDuringthePersianGulfWar:RecommendationsforResearchandInformationSystems

79

DEvaluationoftheU.S.DepartmentofDefensePersianGulfComprehensiveClinicalEvaluationProgram:OverallAssessmentandRecommendations

91

EWorkshopontheAdequacyoftheCCEPforEvaluatingIndividualsPotentiallyExposedtoNerveAgents:AgendaandSpeakersList

109

FAdequacyoftheComprehensiveClinicalEvaluationProgram:NerveAgents

113

GWorkshopAgendasandSpeakersLists 121

WorkshoponDifficult-to-DiagnoseandIll-Defined 121

Conditions,

WorkshoponStressandPsychiatricDisorders, 123

HOutlineoftheCCEPMedicalProtocol 127

I ScreeningInstrumentsforSubstanceAbuse 131

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AdequacyoftheComprehensiveClinicalEvaluationProgramAFocusedAssessment

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ExecutiveSummaryOnAugust2,1990,IraqinvadedKuwait.Within5daystheUnitedStateshadbeguntodeploytroopstothePersianGulfinOperationDesertShield.InJanuary1991,UNcoalitionforcesbeganintenseairattacksagainsttheIraqiforces(OperationDesertStorm),onFebruary24,agroundattackwaslaunchedandwithin4days,Iraqiresistancecrumbled.Almost700,000UStroopsparticipatedinthePersianGulfWar.Followingthefighting,thenumberofUSpersonnelbegantodeclinerapidly.

Mosttroopsreturnedhomeandresumedtheirnormalactivities.Withinarelativelyshorttime,anumberofthosewhohadbeendeployedtothePersianGulfbegantoreporthealthproblemstheybelievedtobeconnectedtotheirdeployment.Theseproblemsincludedthesymptomsoffatigue,memoryloss,severeheadaches,muscleandjointpain,andrashes.

In1992theDepartmentofVeteransAffairs(VA)developedaPersianGulfRegistrytoassistinaddressingquestionsabouthealthconcernsofPersianGulfveterans.Exposures,particularlythoseassociatedwithoilwellfires,wereincludedaspartofthehistorytaking.By1994,withcontinuingconcernaboutpotentialhealthconsequencesofserviceinthePersianGulf,theDepartmentofDefense(DoD)implementedaclinicalevaluationprogramsimilartotheVA'sandnamedittheComprehensiveClinicalEvaluationProgram(CCEP).

Alsoin1994,DoDaskedtheInstituteofMedicine(IOM)toassembleagroupofmedicalandpublichealthexpertstoevaluatetheadequacyoftheCCEP.Thiscommitteeconcludedthatalthoughoverall"theCCEPisacomprehensiveefforttoaddresstheclinicalneedsofthethousandsofactivedutypersonnelwhoservedintheGulfWar,"

specificrecommendedchangesin

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theprotocolwouldhelptoincreaseitsdiagnosticyield.(SeeAppendixDforacompletesetofrecommendations.)

Latein1995,DoDaskedtheIOMtocontinueitsevaluationoftheCCEPwithspecialattentiontotheadequacyoftheprotocolasitrelatedto(1)difficult-to-diagnoseindividualsandthosewithill-definedconditions;(2)thediagnosisandtreatmentofpatientswithstressandpsychiatricconditions;and(3)assessmentofthehealthproblemsofthosewhomayhavebeenexposedtolowlevelsofnerveagents.Itisimportanttonotewhatwasnotincludedinthecommitteecharge.Itwasnotthecommittee'schargetodeterminewhetherornotthereissuchanentity(orentities)as"PersianGulfIllness"norwasitthiscommittee'schargetodeterminewhetherornottherearelong-termhealtheffectsfromlow-levelexposuretonerveagents.Thesequestionsaremoreproperlythesubjectforextensivescientificresearch.

Giventheurgencysurroundingthelastquestionthehealthproblemsofindividualswithpossibleexposuretolowlevelsofnerveagentsthecommitteeaddressedthisissuefirstandseparately,releasingitsreport,AdequacyoftheComprehensiveClinicalEvaluationProgram:NerveAgents,inApril1997.ThecommitteeconcludedthatalthoughtheCCEPcontinuestoprovideanappropriatescreeningapproachtothediagnosisofdisease,certainrefinementswouldenhanceitsvalue.AcompletesetofrecommendationsisfoundinAppendixF.

Tocompletetheremainingportionsofitscharge,thecommitteeconvenedtwoworkshopsontherelevanttopics,heardpresentations,reviewedwrittenmaterial,andreceivedcommentsfromleadingscientificandclinicalexperts,representativesofDoDandtheVA,thePresidentialAdvisoryCommittee,theGeneralAccountingOffice,andrepresentativesofveteransgroups.

AgreatdealoftimeandefforthasbeenexpendedevaluatingDoD's

ComprehensiveClinicalEvaluationProgram.IthasbeenreviewedbythePresident'sAdvisoryCommittee,theGeneralAccountingOffice,theOfficeofTechnologyAssessment,theInstituteofMedicine,andmanyotherorganizations.Asmoreislearned,itbecomeseasiertofocusonthekindsofquestionstheCCEPshouldbeasking.AsDr.PenelopeKeylsaidinherworkshoppresentationonthedevelopmentofgoodscreeninginstruments,progressmadeovertimewillnecessitatenewgenerationsofscreeninginstruments.Thisdoesnotimplythatthefirstinstrumentdevelopedisbad,butratherthattimeleadstonewknowledge,whichleadstotheabilitytoimprovetheinstrument.

SuchisthecasewiththeCCEP.Overtime,theCCEPandotherprogramshavegeneratedinformationthathasincreasedourunderstandingandledustofocusonareasofimportanceforthoseconcernedaboutthehealthconsequencesofPersianGulfdeployment.Thisinformationhasenabledustotakeacloserlook,tomakeamorethoroughexaminationofthesystem,andtoidentifyareasinwhichchangewillbeofbenefit.Thecommitteebelievesthatsuchchangeis

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healthy,thatitreflectsgrowth,andthatitshouldbeanaturalpartofanysystemhavingasoneofitsgoalsthedeliveryofhigh-qualityhealthcareservices.

Changealsooccurswithindividuals.Itmaybethatastimepassesornewinformationisreleased,someofthosewhohavealreadyparticipatedintheCCEPwilldevelopnewconcernsorproblems.ThecommitteehopesthatDoDwillencouragetheseindividualstoreturntotheCCEPforfurtherevaluationanddiagnosisiftheysodesire.

CONCLUSIONSANDRECOMMENDATIONS

MedicallyUnexplainedSymptomSyndromes

Thecommitteespenttimedeliberatingontheprecisemeaningof"difficulttodiagnose"or"illdefined"asadescriptionofacategoryofconditions.Difficulttodiagnoseisgenerallyusedtodescribeaconditionforwhichspecialexpertiseisrequiredtoarriveatadiagnosis,butsomeoftheconditionsunderconsiderationdonotrequiresuchexpertise.Chronicfatiguesyndrome(CFS),fibromyalgia,andmultiplechemicalsensitivityaresymptomcomplexesthathaveagreatdealofoverlapinthesymptomspresentineachcondition.Theyaresymptom-based,withoutobjectivefindings.However,theyareactuallyfairlywelldefinedbyoperationalcriteria,eveniftheyaremedicallyunexplained.Despitethefactthattheyaremedicallyunexplained,theymaycausesignificantimpairment,andtheyareconditionsthatarebetterunderstoodthroughtime(i.e.,adequateevaluationofthesedisordersrequiresalongitudinalperspectivethatincludesknowledgeofpreviousservicesandresponsestotreatment).Thecommitteedecided,therefore,torefertothisspectrumofillnessesasmedicallyunexplainedsymptomsyndromes.Thisspectrumofillnessesmayincludethosewhichareetiologicallyunexplained,lackcurrentlydetectable

pathophysiologicalchanges,and/orcannotcurrentlybediagnosticallylabeled.

Medicallyunexplainedsymptomsyndromesareoftenassociatedwithdepressionandanxiety,yetthisdoesnotimplythatthesyndromesarepsychiatricdisorders.Thereremainsadebateabouthowtodistinguishthesesyndromesfrompsychiatricdiagnoses.However,sincemostoftherecommendedtreatmentsformedicallyunexplainedsymptomsyndromesoverlapwiththepharmacologicalandbehavioraltreatmentsforpsychiatricdiagnoses,thecommitteebelievesthatitisimportanttoidentifyandevaluatethesymptomsassociatedwiththeseconditionsandthentreatthosesymptoms.

Thecommitteerecommendsthatwhenpatientspresentingwithmedicallyunexplainedsymptomsyndromesareevaluated,theprovider

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musthaveaccesstothefullandcompletemedicalrecord,includingprevioususeofservices.

Intheareaofmedicallyunexplainedsymptomsyndromes,itissometimesnotpossibletoarriveatadefinitivediagnosis.Itmaybepossible,however,totreatthepresentingcomplaintsorsymptoms.

Thecommitteerecommendsthatincaseswhereadiagnosiscannotbeidentified,treatmentshouldbetargetedtospecificsymptomsorsyndromes(e.g.,fatigue,pain,depression).

ThecommitteerecommendsthattheCCEPbeencouragedtoidentifypatientsinthisspectrumofillnessesearlyintheprocessoftheirdisease.Inaddition,primarycareprovidersshouldidentifythepatients'functionalimpairmentssoastobeabletosuggesttreatmentsthatwillassistinimprovingthesedisabilities.

Stress

Stressisamajorissueinthelivesofpatientswithinthisspectrumofillness.Stressneednotbelookedatsomuchasacausativeagent,butratherasapartoftheconditionofthepatientthatcannotbeignored.Withmedicallyunexplainedsymptomsyndromes,thepotentialforstressproliferationisgreatamongboththepersondeployedtothePersianGulfandthefamilymembers.

Researchhasshownthatstressorshavebeenassociatedwithmajordepression,substanceabuse,andvariousphysicalhealthproblems.ThosedeployedtotheGulfwereexposedtoavastarrayofdifferentstressorsthatcarrywiththemtheirownpotentialhealthconsequences.Thecurrentcollectionofexposureinformationdoesnotadequatelyaddressaninvestigationoftraumaticeventstowhichthedeployedsoldiermayhavebeenexposed.Inaddition,mediaattentionandreportsbythemilitarytoGulfWarveteransthattoxicexposurecouldhaveoccurredareverystressfulevents.Thestressassociatedwith

thesereportsneedstoberecognizedandaddressed.

ThecommitteerecommendsthattheCCEPcontainquestionsontraumaticeventexposuresinadditiontotheexposureinformationcurrentlybeingcollected.Thiswouldincludetheadditionofopen-endedquestionsthataskthepatienttolisttheeventsthatweremostupsettingtohimorherwhiledeployed.Positiveresponsestoquestionsregardingsuchevents,aswellastootherexposurequestions,shouldbepursuedwithanarrativeinquiry,whichwouldaddresssuchitemsasthespecificnatureoftheexposure;theduration;thefrequencyofrepetition;thedoseor

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intensity(ifappropriate);whetherthepatientwastakingprotectivemeasuresand,ifso,whatthesemeasureswere;andthesymptomsmanifested.

ThecommitteerecommendsthatDoDprovidersacknowledgestressorsasalegitimatebutnotnecessarilysolecauseofphysicalsymptomsandconditions.

Everysoldierwhogoestowarwillbesubjectedtomajordisturbingeventssincewarinvolvesdeathanddestruction.Therearecertainjobsundertakeninthemidstofwarthat,bytheirverynature,resultinhighstress(e.g.,graveregistrationduty).Theeffectofstressassociatedwiththesejobscanbemitigatedifapproachedproperly.Suchefforts,however,requiretimefortheproviderandthepatienttointeract.Itisnotpossibletohandthepatientapamphletoraquestionnaireandexpectthatallnecessaryinformationwillberevealedorunderstood.

ThecommitteerecommendsthatDoDprovidespecialtraininganddebriefingforthosewhoareengagedinhigh-riskjobssuchasjobsassociatedwiththePersianGulfexperience.

ThecommitteerecommendsthatDoDprovidetoeachabout-to-bedeployedsoldier,riskorhazardcommunicationthatiswelldevelopedanddesignedtoprovideinformationregardingwhattheindividualcanexpectandthepotentiallytraumaticeventstowhichheorshemightbeexposed.

ThecommitteerecommendsthatadequatetimemustbeprovidedduringinitialinteractionswithpatientsintheCCEPinordertoinsurethatallpertinentinformationisforthcoming.

Screening

Depressionisaconditionthatiscommoninprimarycare.Mostindividualswhoexperiencedepressioncontinuetofunction,butif

theyareleftuntreated,theirconditionmaydeteriorate.Unlikemanyofthemedicallyunexplainedsymptomsyndromes,thereareacceptedandeffectivetreatmentsfordepression.

Thecommitteerecommendsthattherebeincreasedscreeningattheprimarycarelevelfordepression.

Everyprimarycarephysicianshouldhaveasimplestandardizedscreenfordepression.Ifapatientscoresinthesignificantrange,thispersonshouldbereferredtoaqualifiedmentalhealthprofessionalforfurtherevaluationandtreatment.

Ifdepressionisidentified,therehastobemorequestioningonexposuretotraumaticsituations.

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Thecommitteerecommendsthatanyindividualwhoreportsanysignificantsymptomsofposttraumaticstressdisorder(PTSD)and/orasignificanttraumaticstressorshouldbereferredtoaqualifiedmentalhealthprofessionalforfurtherevaluationandtreatment.

Substanceabuseormisuseproblemsareprevalentinprimarycare.Inaddition,individualsunderstressand/orwithuntreateddepressionormedicallyunexplainedsymptomsyndromesmaybeatincreasedriskforsubstanceabuse.

Thecommitteerecommendsthateveryprimarycarephysicianhaveasimple,standardizedscreenforsubstanceabuse.Everyindividualwhoscreenspositiveshouldbereferredforfurtherevaluationandtreatment.

Therearecertainareasinwhichbaselineassessmentsareofimmensevalueintheclinicalevaluationofanindividualpatient'sstatus(e.g.,pulmonaryfunctionandneurobehavioraltesting).Changesinneurocognitiveandperipheralnervefunctionaremeasuredbycomparingtheindividual'scurrentstatustoabaselinemeasure.Individualbaselineinformationisnecessarybecausethevariabilityacrossindividualsistoogreattoidentifyageneralized''normal"screeninglevel.

ThecommitteerecommendsthatDoDexplorethepossibilityofusingneurobehavioraltestingatentryintothemilitarytodeterminewhetheritisfeasibletousesuchteststopredictchangeinfunctioningortrackchangeinfunctionduringasoldier'smilitarycareer.

ProgramEvaluation

MostpatientsintheCCEPreceiveadiagnosisaftercompletingaPhaseIexamination;somearereferredtoPhaseIIforevaluation;andafewhavegoneontoparticipateintheprogramattheSpecializedCareCenter(SCC).Informationpresentedtothecommitteeindicates

thatthereisgreatvariationacrossregionsinthepercentageofpatientswhoarediagnosedwithprimarypsychiatricdiagnosesandmedicallyunexplainedsymptomsyndromes.Adeterminationshouldbemadeastowhythisvariationexists.Althoughtheremaybemanyreasons,oneexplanationcouldrelatetotheconsistencywithwhichproceduresfordiagnosisandreferralareimplementedfromfacilitytofacility.

Thecommitteerecommendsthatanevaluationbeconductedtoexamine(1)theconsistencywithwhichPhaseIexaminationsareconductedacrossfacilities;(2)thepatternsofreferralfromPhaseItoPhaseII;and

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(3)theadequacyoftreatmentprovidedtocertaincategoriesofpatientswherethereisthepotentialforgreatimpactonpatientoutcomeswheneffectivetreatmentisrendered(e.g.,depression).

TheSCChasprovidedevaluationandtreatmentto78patientssinceitwasbegun.Agreatdealofeffortandthoughthasgoneintothedevelopmentofaprogramdesignedtohelpthepatientunderstandhisorherconditionsandengageinbehaviorsmostlikelytoresultinimprovement.Thecommitteewasaskedtoassesstheeffectivenessofthiscenter,butrealizedthatsuchanassessmentdependedonanumberoffactorsthathavenotbeenwelldefined.Whatisthegoalofthecenterisittreatment,research,oreducation?Shouldamajorconsiderationinthecenter'sevaluationbecost-effectiveness?Shouldthenumbersofthosereceivingcarebetakenintoconsiderationand,ifso,whatarethebarrierstopatientsaccessingthislevelofcare?WhatisthetriageprocessbywhichindividualsgetreferredtotheSCC?

Thecommitteerecommendsthatashort-term(perhaps5-year)planbedevelopedfortheSpecializedCareCenterthatwouldspecifygoalsandexpectedoutcomes.

CoordinationwiththeVA

GiventhatmanynowreceivingservicesintheDoDhealthcaresystemwilleventuallymovetotheVAhealthcaresystem,itisimportantfortheretobegoodcommunicationbetweenDoDandtheVA.Thismaybeparticularlytrueintheareasofmedicallyunexplainedsymptomsyndromesandpsychiatricdisorders,whereaccuratediagnosisand/orassessmentofresponsetotreatmentisimportantforpositivepatientoutcomes.

ThecommitteerecommendsthatDoDexplorewaystoincreasecommunicationwiththeVA,particularlyasitrelatestotheongoingtreatmentofpatients.

BothprovidersandpatientswouldbenefitfromincreasededucationalactivityregardingPersianGulfhealthissues.ProviderturnoverwithinDoDisafactorthatmustbetakenintoconsiderationwhenexaminingthespecialhealthneedsandconcernsofactive-dutypersonnelwhoweredeployedtothePersianGulf.AlthougheffortstoeducateproviderswereextensiveatthetimetheCCEPwasimplemented,3yearshavepassedandmanynewprovidershaveenteredthesystem.Theseindividualsshouldbeorientedtothespecialneeds,concerns,andproceduresinvolved,andallprovidersshouldbeupdatedregularly.

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TheVAhasdevelopedanumberofapproachestoprovidereducationwhichcouldserveasusefulmodels.Interactivesatelliteteleconferencesareavailableformedicalcenterstafftodiscussparticularissuesofconcern.TheVAconductsquarterlynationaltelephoneconferencecalls,directsperiodiceducationalmailingstoPersianGulfRegistryprovidersineachhealthfacility,andconductsanannualconferenceonthehealthconsequencesofPersianGulfservice.

Inadditiontoproviders,thereisagreatneedforeducationofandcommunicationwithindividuals(andtheirfamilies)whoweredeployedtotheGulf.TheseindividualsareconcernedaboutthepotentialimpactofPersianGulfdeploymentontheirhealth,whetherornottheirhealthconcernswillaffecttheirmilitarycareers,theirabilitytoobtainhealthinsuranceoncetheyleavetheservice,andanumberofotherissuesthatneedtobeaddressed.

ThecommitteerecommendsthatDoDexaminetheactivitiesandmaterialsforprovidereducationdevelopedbytheVAtodetermineifsomeoftheitemsmightbeusedaseducationalapproachesforDoDproviders.

ThecommitteerecommendsthatDoDmountaneffortdesignedtoeducateproviderstothefactthatconditionsrelatedtostressarenotnecessarilypsychiatricconditions.Thecommitteerecommendsthatdepressionbeatopicofeducationforallprimarycareproviders,withemphasisonthefactsthatdepressioniscommon,itistreatable,andindividualswhoexperiencedepressioncancontinuetofunction.

ThecommitteerecommendsthatCCEPinformationbeusedtodevelopcasestudiesthatwillhelpeducateprovidersaboutPersianGulfhealthproblems.

ThecommitteerecommendsthatDoDdevelopapproachesto

communicationandeducationthataddresstheconcernsofindividualsdeployedtothePersianGulfandtheirfamilies.

Determiningtheetiology(ies)ofhealthproblemsexperiencedbythosedeployedtothePersianGulfWarmaynotalwaysbepossible.However,itispossiblethattreatmentcanbeprovidedformanyofthesymptomsorconditionsassociatedwithsomeoftheseproblems.Thecommitteewishes,therefore,toemphasizetheimportanceofadequateassessmentofmedicallyunexplainedsymptomsyndromesandoftraumaticeventexposure,aswellasscreeningfordepressionandforsubstanceabuse.SuchadditionstotheCCEPwillenhanceitsabilitytoidentifyand,ultimately,treatthehealthproblemsbeingexperiencedbythosewhoservedinthePersianGulfWar.

Table1providesasummaryofthecommittee'srecommendations.

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TABLE1SummaryofCommitteeRecommendationsTopic RecommendationMedicallyunexplainedsymptomsyndromes

Theproviderevaluatingthesepatientsmusthaveaccesstothecompletemedicalrecordincludingpriortreatment.

Ratherthanattemptingtofitatreatmenttoadiagnosis,treatmentshouldtargetspecificsymptomsorsyndromes(e.g.,pain,fatigue,depression).Apatient'sfunctionalimpairmentsshouldbeidentifiedearlytofacilitatetreatment.

Stress TheinitialCCEPexaminationshouldincludequestionsregardingtraumaticeventexposure.Anypositiveresponseshouldbefollowedupwithanarrativeinquiry.Stressorsmustbeacknowledgedasalegitimatebutnotnecessarilysolecauseofphysicalsymptomsandconditions.DoDshouldprovidespecialtraininganddebriefingforthoseengagedinhigh-riskjobsduringdeployment,e.g.,gravesregistration.DoDshouldprovideriskorhazardcommunicationtoeachabout-to-bedeployedsoldier.Adequatetimemustbeprovidedforprovider/patientinteractionduringCCEPexaminations.

Screening Thereshouldbeincreasedscreeningfordepressionattheprimarycarelevel.Everyphysicianshouldemployasimple,standardizedscreenfordepression(e.g.,BDI,ZungScale,CES-D,IDD).Patientswhoscreenpositivefordepressionshouldbereferredforscreening,furtherevaluation,andtreatment.Patientsdiagnosedwithdepressionshouldbeinterviewedregardingtraumaticexposure.PatientsidentifiedwithanysignificantPTSDsymptomsand/orasignificanttraumaticstressorshouldbereferredtoaqualifiedmentalhealthprofessionalforfurtherevaluationandtreatment.Everyphysicianshouldemployasimplestandardizedscreenforsubstanceabuse(e.g.,CAGE,briefMAST,TACE,TWEAK,

substanceabuse(e.g.,CAGE,briefMAST,TACE,TWEAK,AUDIT).Everypatientwhoscreenspositiveforsubstanceabuseshouldbereferredforfurtherevaluationandtreatment.DoDshouldexplorefeasibilityofneurobehavioraltestingatentryintomilitaryforusefulnessinmeasuringchangeinfunction.

Continued

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TABLE1ContinuedTopic RecommendationProgramevaluation

Anevaluationshouldbeconductedtoexamine:(1)theconsistencyofPhaseIexaminationsacrossfacilities;(2)thepatternsofreferralprogramfromPhaseItoPhaseII;and(3)theadequacyoftreatmentprovidedtocertaincategoriesofpatientswherethepotentialforpositiveimpactisgreat(e.g.,depression).DoDshoulddevelopashort-termplanfortheSpecializedCareCenterthatspecifiesgoalsandexpectedoutcomes.

EducationDoDshouldexplorewaystoincreasecommunicationwiththeVA,particularlyasitrelatestotheongoingtreatmentofpatients.DoDshouldexaminetheprovidereducationmaterialsandprogramsdevelopedbytheVAtodetermineiftheymightserveasmodelsforDoDapproaches.Educationisneededtoemphasizethatconditionsrelatedtostressarenotnecessarilypsychiatricconditions.Educationshouldemphasizethatdepressioniscommonandtreatable,andthatpatientswithdepressioncancontinuetofunction.CCEPinformationshouldbeusedtodevelopcasestudieswhichwillhelpeducateprovidersaboutPersianGulfhealthproblems.DoDeducationaleffortsshouldalsoaddresstheconcernsofPersianGulf-deployedindividualsandtheirfamilies.

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1IntroductionAlargeIraqiforceinvadedtheindependentnationofKuwaitonAugust2,1990.Within5days,inresponsetoUnitedNationsResolution678,theUnitedStatesbegandeployingtroopstothePersianGulfinOperationDesertShield.OnJanuary16,1991,UNcoalitionforcesbeganintenseairattacksagainsttheIraqiforces(OperationDesertStorm).ByFebruary1991,morethan500,000UStroopswerepresentandreadytoengagetheIraqiarmy.AgroundattackwaslaunchedonFebruary24,andwithin4daysIraqiresistancecrumbled.Afterthefighting,thenumberofUStroopsintheareabegantodeclinerapidly.ByJune1991,fewerthan50,000UStroopsremained.

Almost700,000UStroopsparticipatedinOperationsDesertShieldandDesertStorm.ThecompositionofthesetroopsdifferedfromanypreviousUSarmedforce.Overall,theywereolder;alargeproportion(about17%)werefromNationalGuardandReserveunits;andalmost7%ofthetotalforceswerewomen.

TheUScasualtieswerelowduringthePersianGulfWar.Therewere148combatdeaths,withanadditional145deathsduetodiseaseoraccident.Despitethelownumberoffatalitiesandinjuries,servicepersonnelinthePersianGulfwereexposedtoanumberofstressors.Theseincludedenvironmentalfactorssuchasoilsmoke,dieselandjetfuel,solventsandotherpetrochemicals,CARC(chemicalagentresistantcoating)paint,depleteduranium,chemicalwarfareagents,sand,andendemicinfectionssuchasleishmaniasis.Inaddition,somesoldiersweregivenanthraxandbotulinumvaccinesandingestedpyridostigminebromidepillstoprotectagainstchemicalwarfare

agents.

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Otherstressorsincludedtherapidmobilizationformilitaryservice,withanaccompanyingdisruptionofnormalpatterns;theunfamiliarcharacteroftheregionandtherequirementthatUSmilitarypersonnelhavevirtuallynointeractionwiththeindigenouspopulations;theprimitivelivingconditionsofUStroops;andtheimmensedestructionvisitedonthewholenationofIraq.

Afterthewar,mosttroopsreturnedhomeandresumedtheirnormalactivities.Withinarelativelyshorttime,anumberofactive-dutymilitarypersonnelandveteransreportedvarioushealthproblemsthattheybelievedwereconnectedtotheirPersianGulfdeployment.Symptomscommonlydescribedincludefatigue,memoryloss,severeheadaches,muscleandjointpain,andrashes(Schwartsetal.,1997).Asreportsofapurported"PersianGulfillness"circulated,publicconcerngrew.

In1992,theDepartmentofVeteransAffairs(VA)developedandimplementedthePersianGulfRegistrytocreateamechanismfortrackingmedicalandotherdataonPersianGulfveterans.ItwasthoughtthatinformationintheRegistrywouldassistinaddressingquestionsaboutpossiblefutureeffectsofexposuretoairpollutantsandotherenvironmentalagents.Inaddition,thisRegistrywastoserveasthebasisforfuturemedicalsurveillanceofPersianGulfveterans.Exposures,particularlythoseassociatedwiththeoilwellfires,wereincludedaspartofthehistorytaking.

Asconcerncontinuedtoescalate,theDepartmentofDefense(DoD)alsodecidedtodevelopandimplementaPersianGulfclinicalprogram.DoDandtheVAmet,usedexpertstodevelopclinicalprotocols,andby1994,hadimplementedsimilarclinicalevaluationprograms.DoDnameditsprogramtheComprehensiveClinicalEvaluationProgram(CCEP).ThestatedpurposeoftheCCEPistodiagnoseandtreatactive-dutymilitarypersonnelwhohavemedical

complaintsthattheyattributetoserviceintheGulf.

Inadditiontotheclinicalprograms,researchinvestigationswerelaunchedtodiscoverwhetherornotthereissuchanentity(orentities)asPersianGulfillness.OtherexaminationsofPersianGulfissuesandthegovernment'sresponsewereundertakenbytheGeneralAccountingOfficeandtheOfficeofTechnologyAssessment.InMay1995,PresidentClintonannouncedtheestablishmentofaPresidentialAdvisoryCommitteeonGulfWarVeterans'Illnesses.ThisAdvisoryCommitteewaschargedwithanalyzingthegovernment'scoordinationandactivitiesregardingoutreach,medicalcare,research,andchemicalandbiologicalweapons,pertinenttoGulfWarveterans'illnesses.Italsoinvestigatedtheshort-andlong-termhealtheffectsofGulfWarriskfactors.

ThePresidentialAdvisoryCommitteereport,releasedonDecember31,1996,concludedthatitisvitaltocontinuetoprovideclinicalcaretoevaluateandtreattheillnessesthatmanyveteransareclearlyexperiencinginconnectionwiththeirserviceintheGulfWar.TheAdvisoryCommitteedidnot,however,discoveranyresearchorevidencedocumentingacausallinkbetweenanysingle

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factorandthesymptomsreportedbyGulfWarveterans.Althoughseveralrecommendationsweremadeto"fine-tune"thegovernment'sprogramsonGulfWarhealthmatters,theAdvisoryCommitteeconcludedthatonlyintheareaofDoD'seffortsrelatedtochemicalweaponswerethereseriousquestions.ForacompletesetofPresidentialAdvisoryCommitteerecommendations,seeAppendixA.

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2OverviewoftheInstituteofMedicine'sPersianGulfActivitiesTheInstituteofMedicine(IOM)hasundertakenseveralactivitiesfocusingonthepotentialhealthimplicationsofdeploymentinthePersianGulfWarandtheeffortsofDoDandtheVAtorespondtohealthconcerns.TheIOMMedicalFollow-upAgencyconductedaprojectfocusedonthehealthconsequencesofserviceintheGulfanddevelopedrecommendationsforresearchandinformationsystems.Thefirstreportofthisgroup(IOM,1995b)concludedthattherehadbeenafragmentedattempttosolvethehealthproblemsofPersianGulfveteransandthat"sustained,coordinated,andseriouseffortsmustbemadeintheneartermtofocusboththemedical,social,andresearchresponseoftheGovernmentandofindividualsandresearchers."(SeeAppendixBforacompletesetofrecommendations.)ThesecondreportoftheMedicalFollow-upAgency(IOM,1996b)detailed16recommendationswithaccompanyingfindingsconcerningresearchandinformationsystemsneededregardingthehealthconsequencesofserviceduringthePersianGulfWar(AppendixC).

In1994,DoDaskedtheIOMtoassembleagroupofmedicalandpublichealthexpertstoevaluatetheadequacyoftheCCEP.ThefirstcommitteemetfourtimesandpreparedthreereportsbetweenOctober1994andJanuary1996(IOM,1994,1995a,1996a).Thecommitteeconcludedthatalthoughoverall"theCCEPisacomprehensiveefforttoaddresstheclinicalneedsofthethousandsofactive-dutypersonnelwhoservedintheGulfWar,"specificrecommendedchangesintheprotocolwouldhelptoincreaseitsdiagnosticyield.ThecommitteealsoconcludedthattheCCEPisnotappropriateasaresearchtoolbut

thattheresultscouldandshouldbeusedtoeducatePersianGulfveteransandthephysicianscaringforthem,toimprovethemedical

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protocolitself,andtoevaluatepatientoutcomes.AcompletelistofthefirstCCEPcommittee'srecommendationsappearsinAppendixD.

Latein1995,DoDaskedtheIOMtocontinueitsevaluationoftheCCEPwithspecialattentiontothreeissues:(1)difficult-to-diagnoseindividualsandthosewithill-definedconditions;(2)thediagnosisandtreatmentofpatientswithstressandpsychiatricconditions;and(3)assessmentofthehealthproblemsofthosewhomayhavebeenexposedtolowlevelsofnerveagents.ThecommitteewasalsotoconsiderwhethertherearemedicaltestsorconsultationsthatshouldbeaddedsystematicallytotheCCEPtoincreaseitsdiagnosticyield.Anewcommitteewasconvenedtoaddresstheseissues.MostmembersofthenewlyformedcommitteewerealsomembersofthefirstIOMCCEPcommittee.

Indefiningthetasksincludedinthisreview,thecommitteenotedwhatwasnotincludedinitscharge.Itwasnotthiscommittee'schargetodeterminewhetherthereissuchanentity(orentities)asPersianGulfIllness,norwasitthiscommittee'schargetodeterminewhethertherearelong-termhealtheffectsfromlow-levelexposuretonerveagents.Thesequestionsaremoreproperlythesubjectofextensivescientificresearch.

Aseriesofworkshopswasplannedtoobtaininformationonthesetopics.Giventheurgencysurroundingthequestionofhealthproblemsofthosewhomayhavebeenexposedtolowlevelsofnerveagents,DoDaskedthecommitteetoaddressthistopicfirst,separatelyandasrapidlyaspossible.A1-dayworkshopwasheldonDecember3,1996,duringwhichinformationwasgatheredfromleadingresearchersandcliniciansabouttheeffectsofexposuretonerveagentsandchemicallyrelatedcompounds,aswellasabouttestsavailabletomeasurethepotentialhealtheffectsofsuchexposures.(SeeAppendixEfortheworkshopagendaandlistofparticipants.)

Thecommitteereviewedextensiveclinicalandresearchresultsregardingtheeffectsofnerveagents,includingthosepresentedattheworkshopaswellasintheliterature.InitsreportAdequacyoftheComprehensiveClinicalEvaluationProgram:NerveAgents(1997),thecommitteeconcludedthatalthoughtheCCEPcontinuestoprovideanappropriatescreeningapproachtothediagnosisofdisease,certainrefinementswouldenhanceitsvalue.Foracompletesetofrecommendations,seeAppendixF.

Overthecourseoftheproject,thecommitteeheardpresentations,reviewedwrittenmaterial,andreceivedcommentsfromleadingscientificandclinicalexperts;representativesoftheDepartmentofDefenseandtheDepartmentofVeteransAffairs;thePresidentialAdvisoryCommittee;theGeneralAccountingOffice;andrepresentativesofveterans'groups.Thecommitteealsoheldtwopublicworkshops(seeAppendixGforworkshopagendasandparticipantlists).

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3TheComprehensiveClinicalEvaluationProgram*

OVERVIEW

InJune1994,DoDinstitutedtheCCEPtoprovideathorough,systematicclinicalevaluationprogramforthediagnosisandtreatmentofPersianGulfveteransatmilitaryfacilitiesintheUSandoverseas.

TheCCEPwasdesignedto(1)strengthenthecoordinationbetweenDoDandtheVA;(2)streamlinepatientaccesstomedicalcare;(3)makeclinicaldiagnosesinordertotreatpatients;(4)provideastandardized,stagedevaluationandtreatmentprogram;and(5)assesspossibleGulfWar-relatedconditions.(VeteranswhohaveleftmilitaryserviceentirelyareeligibleforevaluationsfromtheVA;personnelstillonactiveduty,intheReserves,orintheNationalGuardmayrequestmedicalevaluationsfromDoD.)PhaseIoftheCCEPconsistsofamedicalhistory,physicalexaminations,andlaboratorytests.Thesearecomparableinscopeandthoroughnesstoanevaluationconductedduringaninpatientinternalmedicinehospitaladmission(seeAppendixH).AllCCEPparticipantsareevaluatedbyaprimarycarephysicianattheirlocalmedicaltreatmentfacilityandreceivespecialtyconsultationsifthesearedeemedappropriatebytheirprimarycarephysician.Evaluationatthisphaseincludesasurveyfornonspecificpatientsymptoms,includingfatigue,jointpain,diarrhea,difficultyconcentrating,memoryandsleepdisturbances,andrashes.

*Thematerialinthissectionisbased,inpart,onpresentationsanddiscussionbyLt.Col.TimCooper,M.D.,MAJCharlesEngel,M.D.,COLKurtKroenke,M.D.,MAJCharlesMagruder,M.D.,andMAJMichaelRoy,M.D.

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TheprimarycarephysicianmayreferpatientstoPhaseIIforfurtherspecialtyconsultationsifheorshedeterminesthatitisclinicallyindicated.ThesePhaseIIevaluationsareconductedataregionalmedicalcenterandconsistoftargeted,symptom-specificexaminations,labtests,andconsultations.Duringthisphase,thepotentialcausesofunexplainedillnessesareassessed,includinginfectiousagents,environmentalexposures,socialandpsychologicalfactors,andvaccinesorotherprotectiveagents.BothPhaseIandPhaseIIareintendedtobethoroughforeachindividualpatientandtobeconsistentamongpatients.

EverymedicaltreatmentfacilityhasadesignatedCCEPphysiciancoordinatorwhoisaboard-certifiedfamilypractitionerorinternalmedicinespecialist.ThecoordinatorisresponsibleforoverseeingboththecomprehensivenessandthequalityofPhaseIexams.Atregionalmedicalcenters,CCEPactivitiesarecoordinatedbyboard-certifiedinternalmedicinespecialistswhoalsooverseeprogramoperationsofthemedicaltreatmentfacilitiesintheirregion.

InMarch1995,DoDestablishedtheSpecializedCareCenteratWalterReedArmyMedicalCentertoprovideadditionalevaluation,treatment,andrehabilitationforpatientswhoaresufferingfromchronicdebilitatingsymptoms.Seventy-eightpatientshavegonethroughtheSpecializedCareProgram,whichconsistsofanintensive3-weekevaluationandtreatmentprotocoldesignedtoimprovetheirhealthstatus.

TheSpecializedCareCenterhasthreeteamsthatoverlap:(1)thephysicalteam(physiatrist,physicaltherapist,occupationaltherapist,fitnesstrainer);(2)themedicalteam(internist,physiatrist,specialists,nutritionist);and(3)thepsychosocialteam(psychologist,socialworker,wellnesscoordinator).Physicaltraining,individualizedtothepatient,isanimportantpartoftheprogram,asiseducation.The

programworkswiththepatientonissuesthatresultindysfunctionorimpairment.Thefocusisnotonthecauseoftheproblems,butratheronhowthepatientcangetbetter.

SIGNS,SYMPTOMS,ANDILL-DEFINEDCONDITIONS(SSID)

TheDepartmentofDefensereportedtothecommitteethatapproximately17%ofthe21,579patientsintheCCEPhadaprimarydiagnosisofSSID,whileabout42%had''anydiagnosis"ofSSID.ThesubcategoriesofSSIDaresymptoms,nonspecificabnormalfindings,andill-definedandunknowncausesofmorbidityandmortality.OfthepatientswithSSID,96.6%(3,591patients)ofthediagnoseswereinthesymptomsubcategory,3%(112)inthenonspecificabnormalfindingsubcategory,and0.4%(16)intheremainingsubcategory(Table3.1).

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TABLE3.1DiagnosesWithintheSymptomGroup(percentage)

SymptomPrimaryDiagnosis

AnyDiagnosis

Fatigue 27 30

Sleepdisturbance 18 24

Headache 14 21

Memoryloss 10 16

Chestpain 5 7

Rash 4 5

DoDreportedthatacomparisonofpatientsinthediagnosticcategoriesofprimarySSID,anySSID,non-SSID,andhealthyfoundessentiallynodifferencesinpercentagesofmalesandfemales,nosignificantagedifferences,andnosignificantethnicdifferences.Forbranchofservice,theMarinesareslightlymorerepresentedinthenon-SSIDpopulation.Inacomparisonofactive-dutyversusreservestatus,theactivedutyareslightlymorelikelytobeinthenon-SSIDdiagnosticcategory,whereasthereservesareslightlymorelikelytobeinanSSIDcategory(Table3.2).

TABLE3.2MostCommonPrimarySSIDDiagnosisbyPhaseofCCEP(percentage)

Symptom PhaseI PhaseII

Fatigue 28 18.0

Sleepdisturbance 17 37.5

Headache 14 17.0

Memoryloss 10 6.5

Chestpain 5 2.5

Chestpain 5 2.5

Rash 4 1.5

Ofthe21,579patientsseeninPhaseI,4,012(18.6%)initiallyreceivedanSSIDdiagnosis.Ofthese,703(17.5%)werereferredtoPhaseII;only239(34%)ofthisgroupcontinuedtobediagnosedwithSSID,whereas464(66%)receivedanalternativediagnosisthatdidnotincludeSSID.About40%ofthesechangedtoaprimarydiagnosiswithinthepsychologicalcategory.However,3,309patientswhoreceivedanSSIDdiagnosisatPhaseIwerenotreferredtoPhaseII.

Ofthe17,567patientswhodidnotreceiveadiagnosisofSSID,1,603werereferredforaPhaseIIexam.Ofthese,171receivedanSSIDdiagnosis,whereas1,432hadnoSSIDdiagnosisassigned.Insummary,DoDreportednodemographicdifferencesbetweenSSIDandnon-SSIDpatients;fatigueisthe

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mostcommonchiefcomplaintinSSIDpatients;jointpainisthemostcommonchiefcomplaintinnon-SSIDpatients;themostcommonprimarySSIDdiagnosisdiffersbyphase;andadiagnosisofprimarySSIDmadeinPhaseIiscommonlychangedinPhaseII.

CHRONICFATIGUESYNDROME(CFS)ANDFIBROMYALGIAINTHECCEPPOPULATION

TheCentersforDiseaseControlandPrevention(CDC)consensusdefinitionforCFSandtheAmericanCollegeofRheumatology(ACR)definitionoffibromyalgiawerecommunicatedtoallmedicaltreatmentfacilitiesinMarch1995.ThoseperformingPhaseIandPhaseIIexaminationswereencouragedtousethesedefinitions.

OfthetotalpopulationseenintheCCEP,12.4%,or3,078,individualsreceivedanydiagnosisoffatigue(ICD-9780.7).Aprimarydiagnosisoffatiguewasgivento4.5%,or1,120individuals.Ofthe1,120individualsreceivingaprimarydiagnosisoffatigue,48(4%)werediagnosedwithCFS,8(1%)withidiopathicchronicfatigue,242(22%)withchronicfatigue,and822(73%)withfatigue.Ifsecondarydiagnosesareincluded,atotalof74individualsreceivedadiagnosisofCFS.Thus,CFSwasdiagnosiedin2.4%ofthepopulationwhoreceivedanydiagnosisoffatiguebutonlyin0.3%ofthetotal24,8231CCEPparticipants.

TheprevalenceofCFSinthegeneralpopulationrangesfrom0.007%to0.037%;inmedicalclinics,from0.13%to0.3%,andinfatigueclinicsitis5.0%.Forfibromyalgia,accordingtotheACRdefinition,ofthe24,823CCEPparticipants,141(0.57%)hadaprimarydiagnosisoffibromyalgiaandanadditional177(0.71%)hadanysecondarydiagnosisoffibromyalgia.Forthetotalnumber(318)ofpatientswitheitheraprimaryorasecondarydiagnosisoffibromyalgia,thenumberofpatientswiththecomorbiddiagnosesareshowninTable3.3.

1IndividualswithinDoDconductedanalysesofCCEPdatabasedoncommitteerequestsforinformation;therefore,theseanalyseswereperformedatdifferenttimes.Asaresult,thetotalnumberofCCEPparticipantsvaried.AnalysisofSSIDwasconductedonatotalCCEPpopulationof21,579patients,whereasanalysisofCFSandfibromyalgiaincluded24,823CCEPparticipants.Sincethecommitteefocusednotonnumbersofcasesbutratherongeneralpatterns,membersdidnotfeelitwasnecessarytoaskforupdatedfigures.

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TABLE3.3NumberofComorbidDiagnosesinPatientswithPrimaryorSecondaryDiagnosisofFibromyalgiaIrritablebowelsyndrome 57(17.9%)Tensionheadaches 44(13.8%)Sleepdisturbances 65(20.4%)Depression 77(24.2%)Posttraumaticstressdisorder 54(17.0%)

Table3.4showsthesymptomsassociatedwithCFSandfibromyalgia.Thefirstcolumnliststhesymptom;theCCEPcolumnreferstothepercentageofCCEPpatientscomplainingofthatsymptom;thefibromyalgiaandCFScolumnsrepresentpercentagesofpatientsdiagnosedwiththeseconditionswhocomplainofthatsymptom.

TABLE3.4PercentageofPatientsDiagnosedwiththeConditionTheyComplainAbout

Sympton CCEP(%) Fibro(%) CFS(%)Difficultyconcentrating 26.8 53.8 59.5Headache 39.6 60.4 55.4Jointpain 51.2 76.4 68.9Memorydeficit 34.6 59.7 62.2Musclepain 21.8 62.3 44.6Sleepdisturbance 33.6 60.7 52.7Abdominalpain 16.4 36.2 28.4Bleedinggums 8.5 18.6 12.2Depression 22.1 46.9 45.9Diarrhea 22.1 46.9 45.9Hairloss 12.5 17.9 14.9Rash 29.9 40.6 50.0Dyspnea 19.2 29.9 32.4

STRESSANDPSYCHIATRICDISORDERS

PatientswhoarereferredtoPhaseIIaremuchmorelikelytoreceivea

PatientswhoarereferredtoPhaseIIaremuchmorelikelytoreceiveapsychologicaldiagnosisthanthosewhoarediagnosedinPhase1.Itisalsothecasethatpsychologicaldiagnosesseemtobemorecommonintheenlistedpopulation.Inlookingattheprevalenceofpsychologicaldiagnoses,whetherprimaryorsecondary,somatoformdisordersaccountfor14.3%andmooddisordersfor12.8%.Theprevalenceofposttraumaticstressdisorder(PTSD)is5.5%;anxietydisorders,3.2%;substanceabuse,4.2%;andotherpsychologicaldiagnoses,8.5%.

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MooddisordersandPTSDarealmostequallylikelytobeprimaryorsecondary,whereassomatoformdisorders,substanceabuse,andotheranxietydisordersaremuchmorelikelytobesecondarydiagnoses.Inexaminingthedistributionofprimarypsychologicaldiagnosesovertime,ithasbeenfoundthatdepressionincreasedfromaboutone-thirdofthediagnosesinthelasthalfof1994toalmost50%oftheprimarypsychologicaldiagnosesinthelasthalfof1996,withthegreatestportionofthisincreaseoccurringinthelast6months.Depressionisalsomorecommonamongolderpatients.

Womenaremorelikelytobediagnosedwithsomatoformandmooddisorders,whereasPTSDandsubstanceabusearemorecommonamongmen.Intermsofdutystatus,mooddisordersandPTSDtendtobemorecommonamongguardsorreservistsandretiredparticipantsthanamongthoseonactiveduty,whereassomatoformdisordersaremorecommonamongtheactive-dutypopulation(Table3.5).

Iftensionheadacheisincludedasasomatoformdisorder,itisbyfarthemostcommonat19.4%ofthe24.6%withaprimarydiagnosisofsomatoformdisorder.Forthosewithaprimarydiagnosisofsubstanceabuse,themostcommondisorderisgenerallyalcoholmisusefollowedbymisuseoftobacco.Anyothersubstanceabuseproblemsweredistinctlyrare,withonly4individuals(0.1%)inthiscategory.

Forthoseinthecategoryofprimaryotherpsychiatricdiagnosis,7.9%areadjustmentdisordersand3.7%organicmentaldisorders(Note:someofthesearereportedasactuallybeingpsychosisduetoalcoholorsubstanceabuse);sleepdisordersrepresent3.2%;schizophreniaorunspecifiedpsychosisamountto0.2%,andotherdisordersconstitute2.5%.

Forthe7,564individualswhoreceivedasecondarypsychiatricdiagnosis,themostcommondiagnosiswassomatoformdisorders(39.2%)followedbymooddisorders(26.9%),substanceabuse

(14.1%),PTSD(11%),anxietydisorders(8.9%),andotherpsychiatricdisorders(22.1%).

Sinceitisimportanttoexaminecomorbidity,patientsintheCCEPhaveacodedprimarydiagnosisanduptosixadditionaldiagnoses.ForCCEPpatientswithaprimarypsychiatricdiagnosis,thecomorbidityofotherdiagnoses(secondtoseventh)arefoundinTable3.6.

Anexaminationofonlytheseconddiagnosisforcomorbiditywithaprimarypsychiatricdiagnosisrevealsthatpsychologicaldisordersarethemostcommonat18.0%,followedbymusculoskeletaldisordersat11.1%,ill-definedconditionsat8.2%,digestivediseasesat6.0%,neurologicaldisordersat4.3%,skindiseasesat3.7%,respiratorydiseasesat2.9%,infectiousdiseasesat1.9%,andneoplasmsat0.6%.

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TABLE3.5DistributionofDiagnosesforthe4,304PatientsReceivingaPrimaryPsychiatricDiagnosisDiagnosis Percentage No.ofPatientsMooddisorders 34.0 1,461Somatoformdisorders 24.4 1,059PTSD 14.9 640Anxietydisorders 5.5 237Substanceabuse 3.5 152Otherdiagnoses 17.5 755

Mooddisorderscanbebrokenintothefollowingcategories:Otherdepressivesyndromes 16.0 715Majordepression 8.9 838Dysthymia 7.4 319Bipolardisorder 0.7 30Othermooddisorders 0.3 14

TABLE3.6ComorbidityofOtherDiagnosesforPatientswithPrimaryPsychiatricDiagnosis

Diagnosis Percentage No.ofPatientsPsychologicaldisorders 40.1 1,735Neurologicaldisorders 17.1 740Musculoskeletaldisorders 48.4 2,091Ill-definedconditions 32.9 1,422Digestivediseases 23.0 995Skindiseases 17.6 762Respiratorydiseases 13.8 596Infectiousdiseases 8.2 356Neoplasms 2.4 104

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4IOMReview:Difficult-to-DiagnoseandIll-DefinedConditions*ThecommitteereviewedinformationonthedevelopmentofscreeninginstrumentsinordertocontributetotheunderstandingandassessmentoftheadequacyoftheCCEPprotocol.Theroleofscreeningintheareaofill-definedconditionsistobeabletoidentifyasubsetofindividualsfromalargergroupwhoclearlyfitadescriptionofinterest.Screeningisnotsynonymouswithdiagnosis.Therefore,thecriteriaforagoodscreeninginstrumentarenotthesameasthecriteriafordiagnosis.

Screeningincludesthesystematiccollectionofinformation.Itdiffersfromasurveyinthatthegoalofasurveyistomakeinferences,whereasthegoalofascreeninginstrumentistoidentifyaparticulargroupofpeople.Itisalsoimportanttonotethatscreeningdoesnottakeplaceunderstaticconditions.Overtime,progressmadeintheunderstandingoftheseconditionswillnecessitatedifferentgenerationsofthescreeninginstrument.Thisdoesnotimplythatthefirstinstrumentdevelopedisbad,butratherthattimeleadstonewknowledge,whichleadstotheabilitytoimprovetheinstrument.

Ascreeninginstrumentshouldbesystematic,quantitative,standardized,andcontaintestsandprocedureswhichthepopulationtobescreenediswillingtoundergo.Theproceduresshouldbespecifiedinadvance,oneshouldbeabletoassignnumericalvaluestononnumericalcharacteristics(e.g.,theseverityof

*Thematerialinthissectionisbased,inpart,uponpresentationsanddiscussionbyDedraS.Buchwald,M.D.,DanielClauw,M.D.,Lt.Col.TimCooper,M.D.,NelsonGantz,M.D.,PenelopeKeyl,M.D.,Howard

Kipen,M.D.,RobertSimms,M.D.,andFrederickWolfe,M.D.

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symptoms),andtheremustbestandardizedquestionsandresponses.Inaddition,agoodscreeninginstrumentdoesnotjustaskaboutthepresenceorabsenceofsymptoms,italsoasksaboutthepresentationofthesymptoms;underwhatcircumstancestheyoccur;andtheirintensity,severity,frequency,andduration(howlongbeforeasymptomresolvesaswellashowlongthepatienthasbeenexperiencingit).

Withthedevelopmentofagoodscreeninginstrument,onecanelicitimportantinformationthatwillhelpidentifyagroupofpatientsaboutwhomonewishestoanswerfurtherquestionsregardingdiagnosisandtreatment.

CHRONICFATIGUESYNDROME

Chronicfatiguesyndromeisaclinicallydefinedconditioncharacterizedbysevere,disablingfatiguethatpersistsforatleast6monthsandhasadefiniteonset.Thesymptomsincludeself-reportedproblemsinconcentration,shorttermmemory,sleepdisturbances,andmusculoskeletalpain.Adiagnosisismadeonlyafteralternativemedicalandpsychiatriccausesoffatiguingillnessareexcluded.Therearenodiagnosticteststhatcanvalidateitsdiagnosis,nopathognomicmedicalcharacteristicthatiscommontoallpatients,andnodefinedtreatmentthatalleviatesthesymptomsforallpatients.AmajorquestionsurroundingdiagnosisofCFSconcernswhetherCFSoranyofitssubsetisapathologicallydiscreteentityasopposedtoadebilitatingbutnonspecificconditionsharedbymanydifferententities.

In1994,theCDCconvenedtheInternationalChronicFatigueSyndromeStudyGrouptodevelopaconceptualframeworkandasetofresearchguidelinesforuseinstudiesofCFS.Thisgroupdevelopedthefollowingcriteriafordefiningchronicfatiguesyndrome(Fukuda

etal.,1994).

Apersoncanbeclassifiedashavingchronicfatiguesyndromeifbothofthefollowingcriteriaaremet:

1.clinicallyevaluated,unexplained,persistent,orrelapsingfatigueofnewordefiniteonsetthatisnotduetoongoingexertion,isnotsubstantiallyrelievedbyrest,andresultsinasubstantialreductioninpreviouslevelsofoccupational,educational,social,orpersonalactivities;and

2.theconcurrentoccurrenceoffourormoreofthefollowingsymptoms,allofwhichmusthavepersistedorrecurredforatleastsixmonths:

impairedshorttermmemoryorconcentrationsevereenoughtocausesubstantialreductioninpreviouslevelsofactivity;

sorethroat;

tendercervicaloraxillarylymphnodes;

musclepain,multijointpainwithoutjointswellingorredness;

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headachesofanewtypeorseverity;

unrefreshingsleep;

postexertionalmalaiselastingmorethan24hours.

TheminimumlaboratoryevaluationofpatientswithsuspectedCFSincludescompletebloodcountwithdifferential;electrolytes,BUN(bloodureanitrogen),creatinine,calcium,glucose,andthyroidfunctiontests;erythrocytesedimentationrate;antinuclearantibodies;andurinalysis.Althoughmanypatientshavesignificantabnormalitiesonroutinelabtests,uniformityofabnormalitiesislacking,andthereforeroutinelaboratorytestscannotbeusedtodeterminewhetherapatienthasCFS.

NosinglecauseofCFShasbeenidentified.OfthepatientsdiagnosedwithCFS,80%ormorereportedthatitstartedwithaviralillness.ManysuspectedagentswerereviewedincludingtheEpstein-Barrvirus,butnonehavebeenfoundtobecausativeforCFS.From60%to70%ofCFSpatientsreportedallergies,comparedto20%ofthegeneralpopulation.Avarietyoftestsindicatedthattheredoesseemtobeheightenedreactivitytoallergensandahigherprevalenceofallergiesinpatientswithchronicfatiguesyndrome.

Sinceallergiesareimmunologicphenomena,scientistsstartedinvestigatingotherpotentialimmunologicalproblems.Findingsincludeddecreasednaturalkillercellnumberandactivity,alteredlymphocytesubsetnumbersandpercentage;andincreasedexpressionofactivationmarkersonlymphocytesubsets.However,noneofthesefindingswasultimatelyfoundtobeadequatelyconsistenttobeusedasadiagnosticmeasure.Otherareasinvestigatedincludedneuroendocrineandmetabolicabnormalities.AlthoughabnormalitiesdoexistinsomepatientswithCFS,thereisdisagreementovertheirrelevance.

Arecenttheoryisoneofdysfunctionoftheautonomicnervoussystem.Someofthesymptomsofchronicfatiguesyndromecanmimicconditionsassociatedwithautonomicdysfunction,forexample,neurallymediatedhypotension.Thisisaconditioninwhichthegeneralsymptomsincludelightheadedness,sweating,abdominaldiscomfort,blurredvision,andthenpresyncopeandfainting.TheTiltTabletestisusedtodiagnoseneurallymediatedhypotension.WhenTiltTabletestingwasappliedinastudybyBouHolaigahetal.(1995),anabnormalresponsetouprighttilt(i.e.,developmentofsyncopeorseverepresyncopewithatleasta25mmHgdecreaseinsystolicbloodpressureandnoassociatedincreaseinheartrate)wasobservedin22of23patientswithCFSversus4of14controls.TheauthorsofthestudyconcludedthatCFSisassociatedwithneurallymediatedhypotensionandthatitssymptomsmaybeimprovedinasubsetofpatientsbytherapydirectedatthisabnormalcardiovascularreflex.

Thereareconditionsthatexplainthepresenceofseverefatigueand,therefore,precludethediagnosisofCFS.Theseincludepastorcurrentpsychiatricconditionsofmajordepressionwithmelancholicorpsychotic

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features;delusionaldisordersofanysubtype;bipolaraffectivedisorder;schizophreniaofanysubtype;dementiasofanytype;anorexianervosa;andbulimia.

ThefollowingcomorbidconditionsdonotexcludeCFS:

Anyconditiondefinedprimarilybysymptomsthatcannotbeconfirmedbydiagnosticlaboratorytests(e.g.,fibromyalgia,anxietydisorders,somatoformdisorders,nonpsychoticornonmelancholicdepression,neurasthenia,panicdisorder,andmultiplechemicalsensitivitydisorder).

Anyconditionunderspecifictreatmentsufficienttoalleviateallsymptomsrelatedtotheconditionforwhichtheadequacyoftreatmenthasbeenwelldocumented(e.g.,hypothyroidisminwhichtheadequacyofreplacementhormonehasbeenverifiedbynormalthyroid-stimulatinghormonelevelsandasthmainwhichtheadequacyoftreatmenthasbeendeterminedbypulmonaryfunctionandothertesting).

Anyconditionthatwaspreviouslytreatedwithdefinitivetherapybeforethedevelopmentofchronicsymptomaticsequelae(e.g.,Lymediseaseorsyphilis).

Anyisolatedandunexplainedphysicalexaminationfindingorlaboratoryorimagingtestabnormalitythatisinsufficienttostronglysuggesttheexistenceofanexclusionaryconditions(e.g.,anelevatedantinuclearantibodytiterthatisinadequatetostronglysupportthediagnosisofadiscreteconnectivetissuedisorderwithoutotherlaboratoryorclinicalevidence,Fukudaetal.,1994).

TheobjectivesoftherapyforCFSaretohelpthepatientdeveloprealisticgoalsandexpectationsthrougheducation,toprovidesymptomaticrelief,andtopreserveandimprovethepatient'sabilitytofunction(FukudaandGantz,1995).Anecessarycomponentofthis

therapyisfortheprovidertoacknowledgethatthepatient'ssufferingisreal.

TherapyforCFSpatientsincludesprovisionofsymptomatictreatmentsuchasmedicationsfordepression,anxiety,pain,sleepproblems,andallergies.Topreventfurtherdisabilityitisimportantforthepatienttoengageingradedexerciseandphysicaltherapy.Cognitivebehavioraltherapy(CBT)isalsousedinanattempttoalterattitudes,perceptions,andbeliefsthatcancontributetomaladaptivebehavior.Patientsneedtoestablishrealisticgoalsformanagingtheirlives,toapplystressreductiontechniques,andtorestructuretheiractivitiestobetteraccommodatetheirneedsandcondition.ThelongerapatienthasbeenillwithCFS,thelesslikelyheorsheistogetbetter.Therefore,earlydiagnosisandtreatmentareextremelyimportant.

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FIBROMYALGIA

Fibromyalgia(FM)isadisorderofwidespreadpain,tenderness,fatigue,sleepdisturbance,andpsychologicaldistress(Wolfeetal.,1995).Additionalclinicalfeaturesmayincludeirritablebowelsyndrome,paresthesias,headache,irritablebladder,somatization,andsocialdysfunction.

ProblemswiththeclassificationanddiagnosisoffibromyalgialedtodevelopmentofthefollowingcriteriabytheAmericanCollegeofRheumatology.

Theremustbeahistoryofwidespreadpain.Painisconsideredwidespreadwhenallofthefollowingarepresent:

painintheleftsideofthebody,painintherightsideofthebody,painabovethewaist,andpainbelowthewaist.

Inaddition,axialskeletonpain(cervicalspineoranteriorchestorthoracicspineorlowback)mustbepresent.Shoulderandbuttockpainisconsideredpainforeachinvolvedside.''Lowback"painisconsideredlowersegmentpain.

Thereispainondigitalpalpationin11ofthe18followingsitesoftenderpoints:

1.Occiput:bilateral,atthesuboccipitalmuscleinsertions.

2.Lowcervical:bilateral,attheanterioraspectsoftheintertransversespacesatC5-C7.

3.Trapezius:bilateral,atthemidpointoftheupperborder.

4.Supraspinatus:bilateral,atorigins,abovethescapularspinenearthemedialborder.

5.Secondrib:bilateral,atthesecondcostochondraljunctions,justlateraltothejunctionsonuppersurfaces.

6.Lateralepicondyle:bilateral,2cmdistaltotheepicondyles.

7.Gluteal:bilateral,inupperouterquadrantsofbuttocksinanteriorfoldofmuscle.

8.Greatertrochanter:bilateral,posteriortothetrochantericprominence.

9.Knee:bilateral,atthemedialfatpadproximaltothejointline.

Fibromyalgiapatientscanbedifferentiatedfromcontrolsbytestingtheirpainthresholdortoleranceanywhereonthebody,notjustontenderpoints(Clauw,1995).Fibromyalgiapatientshaveallodynia,areductioninpainthreshold,aswellashyperalgesia,whichmeansthatthingsthathurtaremore

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hurtful.Patientswithfibromyalgiamayreportpainonlyincertainareas,however,becausethoseareasarethemosttroublesome.Partofthediagnosticprocessmust,therefore,carefullyelicitinformationaboutallpainfulareas.Thismaybeaccomplishedbyusingapaindiagramorbyaskingrepeatedlyaboutvariousbodyregions.

Themajorfeaturedistinguishingfibromyalgiafromotherdisordersistenderness(orsensitivity).Thetwomethodsformeasuringtendernessaredigitalpalpationanddolorimetry.Theamountofforceusedinpalpationisimportantbecausetoolargeaforcewillelicitpaininsomeonewithoutfibromyalgia,whereastoolittleforcemaymisspaininsomeonewithfibromyalgia.Ithasbeensuggestedthatthebestmethodfordeterminingtheamountofpressurerequiredistopalpate"normal"individualsofthesamebuildandstatureasthesuspectedfibromyalgiapatient.Althoughquestionsaboutthevalidityofpalpationcanberaised,studieshaveshownthattrainedexaminerscanreachhighlevelsofagreementintheidentificationofpatientswithandwithoutfibromyalgia(Wolfeetal.,1992).

Dolorimetryisatechniquethatusesarubberendplatewithaspring-loadedforcegauge.Thisgaugeispressedonthetenderpointsite.Asthepressureischanged,patientsareaskedtonotewhentheyfeelachangefrompressuretopain.Althoughdolorimetrywouldappeartobeamorereliableapproachthandigitalpalpationtomeasuringthepainthresholdbecauseiteliminatesexaminervariabilityinboththeamountofpressureusedandtheinterpretationofpatientresponse,dataanalysesindicatethatbothdigitalpalpationandmanualpalpationaremoreaccuratediagnosticapproaches.Thismaybebecausethegaugeispressedononesiteatatime,whereasduringpalpation,theexaminercanfeelaroundfortheexactplacetoexertpressure.Inaddition,therollingmotioninvolvedinfeelingforthecorrectsitemayfindatendernessnotnotedbydirectpressurealone(Wolfe,1994).

Inadditiontopain,thereareothersignsandsymptomscommontopatientswithfibromyalgia.Ina1990ACRstudyofcriteriafortheclassificationoffibromyalgia,81%ofthepatientscomplainedoffatigueand74%complainedofsleepdisturbance.Psychologicalfactorsarealsoimportant.Ofpatientswithfibromyalgia,30%reportthesymptomofdepression(Wolfe,1994).Itisimportanttopointoutthatfibromyalgiacannotbeexplainedsolelyasapsychiatricillnesslikedepression,however.

Familymembersoffibromyalgiapatientshaveahigher-than-expectedrateoffibromyalgia.Inaddition,trauma,eitherphysicaloremotional,mayprecipitateone-thirdofthecasesoffibromyalgia.InfectionssuchasLymediseaseandHIVandconnectivetissuedisorderssuchassystemiclupuserythematosusandrheumatoidarthritisfrequentlycoexistwithfibromyalgia.Aerobicfitnessmaybeapositivemodulatingfactor,thatis,itmaylessenthenegativeeffectsofthecondition(Clauw,1995).

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Manyinvestigatorsnowagreethataberrantcentralnervoussystemmechanismsarelikelytoberesponsibleforthemajorityofclinicalfindingsinfibromyalgia.Acentralnervoussystemgenesisexplainsnotonlythehighincidenceofnonmusculoskeletalsymptomsinawidevarietyoforgansandtissues,butalsotheaffectivedisordersandneurologicalfeatureswhichoccurinthiscondition(Clauw,1995).

Availabletreatmentsforfibromyalgiarangefromconventionalmedicationtherapywithtricyclicantidepressantstononconventionalinterventionssuchasbiofeedback.Itappearsthatthereisshort-termbenefitinthetreatmentoffibromyalgiasyndromewithtricyclicagents,butthishasnotprovedlonglastinginplacebo-controlledtrials.Arelativelysmallproportionofpatients(about25%to30%)havesignificantimprovement.Themajorityhavelittleornoimprovement.

Inadditiontocommonlyusedpharmacologictherapies,patienteducation,reassurance,andanexerciseprogramcaneachplayanimportantroleinrelievingthesymptomsassociatedwiththismusculoskeletalsyndrome.Patienteducationisimportantinassuringpatientsthattheyhaveacommon,nonthreateningcondition.Sucheducationshouldincludeadescriptionofhowthediagnosiswasmade,whattheconditionrepresents,andtheentiretherapeuticplan.Inadditiontoeducation,exercisehasbeenshowntocontributetoimprovementinpainthresholdscores.

Electromyography(EMG)biofeedbackhasbeentestedincontrolledtrialsettings.Ferracciolietal.(1987)conductedacontrolledstudyofbiofeedbackin12patientsandreporteda50%clinicalimprovementin9ofthosepatients,sustainedforsixmonths.Astudyofelectroacupunctureshowedimprovementintheactivetreatmentgroup,butlimitationstothestudyincludenomeasureoffunctionalorpsychologicalstatus,lackofspecificationoftimeoffollow-upassessment,thefactthatpatientsmaynothavebeenoptimally

blinded,andnodeterminationofwhetherelectroacupunctureisequivalenttoacupuncture.

Itappearsthatwhereasthemosteffectiveshort-termtreatmentforfibromyalgiaisantidepressanttherapy,thelong-termefficacyoftreatmentremainselusive.

MULTIPLECHEMICALSENSITIVITY

Multiplechemicalsensitivity(MCS)isadiagnosisgiventopatientswho,inresponsetoachemicalexposurethatistoleratedbymostindividuals,exhibitavarietyofsymptomsthathavenoapparentorganic(orphysiologic)basis.MCSisreportedtoresultfromasingleepisodeorrecurringepisodesofachemicalexposure,suchassolventorpesticidepoisoning,butitalsoariseswithoutreportsofuntowardinitialexposure.Thereisverylittleagreementonwhatthesymptomsrepresent,andnodefinitionhasyetbeenendorsedforclinicaluseby

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abodyofphysicians.TheAmericanMedicalAssociation(AMA)andtheAmericanCollegeofPhysicianshavebothconsideredthegeneraltopicbuthavenotyetrecognizedaspecificdiseaseentityordefinition.

Cullen'sdefinitionofMCS,primarilyforresearchpurposes,appearstobethemostwidelyaccepted.ThedefinitionallowsphysicianstodistinguishMCSfromotherclustersofcommonlyexperiencedsymptoms(Sparksetal.,1994a.Thisdefinitionhasfourcharacteristics:

1.MCSisacquiredinrelationtosomedocumentableenvironmentalexposurethatmayinitiallyhaveproducedademonstrabletoxiceffect.Thisaspectexcludespatientswithlong-standinghealthproblemswholaterattributecertainsymptomstochemicalexposure.

2.Symptomsinvolvemorethanoneorgansystem,andtheyrecurandabateinresponsetopredictableenvironmentalstimuli.

3.Symptomsareelicitedbyexposurestochemicalsthataredemonstrablebutverylow(perhapsseveralstandarddeviationsbelowtheaverageexposuresknowntocausetoxicorirritanthealtheffectsinhumans).

4.ThemanifestationsofMCSaresubjective.Nowidelyavailabletestoforgansystemfunctioncanexplainthesymptoms,andthereisnoobjectiveevidenceoforgansystemdamageordysfunction.Thesyndromemaybeseverelydistressingandfunctionallydisabling,however,becausepatientsincreasinglyattempttoavoidchemicalexposures.

Thechemicalsmostcloselyassociatedwiththemajorityofinitiatingepisodesareorganicsolvents,pesticides,andrespiratoryirritants.Thiscouldbebecauseofthewidespreaduseofthesematerials.Theothercommonsettinginwhichmanycasesarereportedisinbuildingswith

indoorairproblems(Cullen,1997).

Therearemanytheoriesoftheetiologyofmultiplechemicalsensitivity.Oneperspectivehasfocusedontherelationshipbetweenthemucosaeoftheupperrespiratorytractandthelimbicsystem,especiallythelinkageinthenose.MCSpatientstypicallyreportheightenedodorsensitivity.FindingssuggestthatMCSpatientsdonotdetectodorsatlowerthresholdsthanothers,buttheymayrespondmoremarkedlyonceodorsaredetected.Therelationshipofthisfindingtoreportsofinflammatorynasalpathologyandincreasednasalresistanceisunexplored,butthepathologicfindingsrequireconfirmationwithcontrolledstudies.

OthershavesuggestedthatMCSmightberelatedtoadisturbanceoftheimmunesystem.NocontrolledandblindedstudieshavebeenpublisheddemonstratingaconsistentpatternofalterationinimmuneparametersinMCSpatientsafterchemicalexposure(Sparksetal.,1994a).Anotherhypothesisisthatchemicalexposuresproducetoxicfreeradicalsthatcausecellmembranesto

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releaseinflammatorymediators.Noscientificdatahavebeenputforthtosupportthistheory,however(Sparksetal.,1994a).

AnothertheoryisthatpsychologicalmechanismsexplainMCS.IthasbeenproposedthatMCSmaybeamanifestationofthehumanresponsetostressoraconditionedresponsetoaninitialtoxicexperience(Jewett,1992).SomehavehypothesizedthatMCSisalate-liferesponsetoearlychildhoodtraumassuchassexualabuse.SomeinvestigatorsarguethatMCSisamisdiagnosedpsychiatricdiseasesuchasdepression,anxietydisorders,somatizationdisorders,orothercommonpsychiatricdisorders(Sparksetal.,1994a).

Manyscientists,physicians,andothershavepostulatedthatMCSis,inmanyways,abeliefsystempromotedbyclinicalecologistsandthosesympathetictotheirviewsandfollowedbymedicallyunsophisticatedpersons.Aspartofthisscenario,MCSpatientsviewthemselvesasvictimsofexternalanduncontrollablefactors,andtheyrejecttheconceptthatsymptomsarenotindicativeofseverediseaseandmayhavepsychologicalcomponents.Afactorthatmaycontributetothisbeliefsystemistheincreasingconcernofthepublicregardingenvironmentalpollutionandthehealtheffectsofexposuretomanmadechemicals(Sparksetal.,1994a).

AlthoughagreatdealofliteraturecanbefoundonthepathogenesisofMCS,thereislittleclinicalorexperimentalevidencethatsupportsstronglyanyoftheviewsputforth.TheavailableevidenceshowsthatpatientsdiagnosedwithMCSareveryheterogeneousandthatparticularhealthbeliefmodels,concurrentpsychiatricillness,andpsychologicstresscharacterizeavulnerablegroupofpeoplewhothendevelopasensitivitytoodorsorlow-levelchemicalirritants(Sparksetal.,1994b).Despitethelackofagreementonetiology,clinicianscanstillhelpaffectedpatientswiththeirsymptoms.

TherearenolaboratoryfindingsthatarecharacteristicofMCS.To

considerthisdiagnosis,onemusttakeahistoryandelicitboththesymptomsandthefactthattheywaxandwanewithexposuretorealagentsthataretoleratedbymostpeople.Diagnostictestingisdoneprimarilytoruleoutotherillnessinthedifferentialdiagnosis.DiagnosticevaluationofthesuspectedMCSpatientincludesthefollowing:

A.History

Detailedexposurehistory(workplaceandotherenvironmentalexposures)

Industrialhygienedata(MaterialSafetyDataSheets,resultsofexposuremonitoring,etc.)

Currentandpastmedicalillnessesandresultsofpreviousdiagnosticwork-upsandtreatments

Reviewofpriormedicalrecords

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B.Physicalexaminationtoruleoutotherillnessesinthedifferentialdiagnosis

C.Consultation

Occupationalandenvironmentalmedicinespecialist

Psychiatrist

Otherspecialistsasappropriatetoruleoutothermedicalconditionsinthedifferentialdiagnosis

D.Other

Symptomdiary(thiscancausepeopletobeoverlyfocusedonthingstheymightotherwiseignore)

Short-termremovalfromexposure

Thefocusoftreatmentistoacknowledgethatthesymptomsarerealanddistressingevenifthereisnoevidenceofobservableorganicpathology.Thegoaloftherapyisthecontrolofsymptoms.Successdependsonthepatient'simprovedunderstandingoftherolestressplaysinexacerbatingsymptomsandontheacquisitionofskillsforcopingwiththeimpactoftheillnessondailylife(Sparksetal.,1994b).Treatmentshouldbeindividualizedbutshouldincludeenhancingthepatient'ssenseofcontroloverworkplaceorhomestressors.Approachestoreducingstresshaveincludedmassage,physicaltherapy,meditation,orregularexercise.ThepatientshouldbereassuredthatMCSisnotfatalandisnotassociatedwithsignsofprogressivedisease.

Arecommendationforcompleteavoidanceofchemicalexposuresisnotindicatedbecausethereisnoevidenceforacumulativetoxicinjuryanditisimpossibletoaccomplish.Treatmentcouldalsoincludemedicationtocontrolsymptoms,anincreaseinphysicaland

socialactivity,andtreatmentofothercoexistingmedicalillnesses.Itisveryimportanttotreatcoexistingpsychiatricmanifestationssuchasdepressionandpanicattacks.Suchtreatmentsmaybehelpfulincontrollingsymptomsnomatterwhattheetiology.

CONTROVERSIESANDOVERLAP

PatientswithCFS,fibromyalgia,andMCShavemanysymptomsincommon.Accordingtosomeinvestigations,theseconditionsmayrepresentoverlappingclinicalsyndromes.InastudybyBuchwaldandGarrity(1994),itwasfoundthat70%ofpatientswithfibromyalgiaand30%ofthosewithMCSmetthecriteriaforCFS.AstudybyHudsonetal.foundthat42%offibromyalgiapatientshavemetthecriteriaforCFS(1992),andresearchconductedbyWysenbeeketal.(1991)foundthat21%ofFMpatientsmetCFS

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criteria.Goldenbergetal.(1990)foundthat70%ofpatientsdiagnosedashavingCFSmettheACRcriteriaforfibromyalgia.

ThereareotherdisordersthatoverlapwithCFS.ForpatientswithTMD,ortemporomandibulardisorder(alsoknownasTMJarthritis),almost60%havetheCFSsymptomoffatigueformorethansixmonths(BuchwaldandGarrity,etal.,1994)and30%meetthesecondpartofthedefinition,whichisreducedactivity.AnotheroverlappingsyndromeonwhichlittlehasbeenpublishedisSjögren'ssyndrome,anautoimmunedisorder.Onestudy(Calabreseetal.,1994)producedresultsthatseemedtoindicatetherewasasubsetofCFSpatientswhohaveaSjögren's-likesyndrome,withdryeyes,drymouth,andatleastsomeofthelaboratoryabnormalitiesseeninSjögren'ssyndrome.

Thecardinalfeaturesoftheseillnessesarechronicregionalorchronicwidespreadpainintheabsenceofnociceptiveinput,fatigue,anddysfunctionofvisceralorgansorsensoryamplification.Individualswhohavemultiplechemicalsensitivity,forexample,sometimesfindthattheyaresensitivetomanykindsofsensoryinputsuchasbrightlightsandloudnoises.Therefore,ifonedefinesagroupofindividualsinthepopulationthathasahighdegreeofpainorthathasahighdegreeoffatigueoranyofthesesymptoms,manyoftheindividualswillalsohaveanumberofothersymptoms.However,itisdifficulttodefinethedegreeofpainortoratethepainastointensity.

Fatigueislikewiseaproblem.Accuratetoolstoquantifyfatiguehaveyettobedevelopedandaccepted.Thereforeitisdifficulttodefineapathologicaldegreeoffatigue.Anywhereonedecidestodrawthelineresultsinanarbitrarydistinction.Theminorsymptoms(headaches,constipation,etc.)arealsoproblematic.Anumberofpopulation-basedstudieshaveshownthatthemoreofthesesymptomsindividualshave,themorelikelytheyaretohavepsychologicalorpsychiatriccomorbidities.

Whateverdiagnosticlabelisarrivedat,patientsinthisspectrumofillnesswillhaveahigherthannormalincidenceofthingssuchastensionandmigraineheadaches,affectivedisorders,TMD,irritablebowelsyndrome,andsoon.Fibromyalgiaisadiagnosiswhichdefinesanextremeofpainandtendernessexperiencedby3%to4%ofthegeneralpopulation.CFSdefinesasmallerpercentageofthepopulationthatismostfatigued.Inreality,fatigueandpainortendernessinthepopulationoccuronacontinuum.Whatisseenforallofthesedifferentsymptomsisthattheyoccuroverawidecontinuuminthepopulationandthatcurrentdefinitionsattempttodrawalinesomewhereandsaythatonesideofthelinerepresentsillnessandtheother,wellness.

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5IOMReview:Stress,PsychiatricDisorders,andTheirRelationshiptoPhysicalSignsandSymptoms*InMay1997,thecommitteeconvenedaworkshopofresearchandclinicalexpertsintheareasofstress(includingmilitarystress),theeffectsofstressontheendocrineandimmunesystems,substanceabuse,posttraumaticstressdisorder(PTSD),depression,andsubthresholddepression.PresentationswerefocusedonprovidingthelatestinformationintheseareasthatcouldassistthecommitteeinitsreviewoftheadequacyoftheComprehensiveClinicalEvaluationProgramindiagnosingstressandpsychiatricdisordersandindeterminingwhetherornoteffectivetreatmentsexistedfortheseconditions.

STRESSORSANDSTRESS

Asdiscussedearlier,individualsdeployedtothePersianGulfwereexposedtoanumberofstressors.Thetermstressorsgenerallyreferstotheexternalcircumstancesthatchallengeorobstructanindividual.Stress,ontheotherhand,isthestateofarousalresultingfromthepresenceofsocioenvironmentaldemandsthattaxtheordinaryadaptivecapacityoftheindividual.Productionofstressisanenvironmentpersoninteractionandisinfluencedbysuchcharacteristicsasneeds,values,perceivedabilitytorespond,andcopingskills.

*Thematerialinthissectionisbased,inpart,onpresentationsbyHagopAkiskal,M.D.,CarolAneshensel,Ph.D.,FirdausDhabhar,Ph.D.,MAJCharlesEngel,M.D.,DavidFoy,Ph.D.,WalterLing,M.D.,MAJMichaelRoy,M.D.,andJohnD.Wynn,M.D.

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Therearetwobroadtypesofstressors:(1)eventfulchangesthathaveadiscreteonsetandadiscretecessationand(2)chronicstressorsthatemergefromongoingsituationsuntilitbecomesapparentthatthereisaproblem.Mostchronicstressorsarerelatedtotheongoingnatureofsocialorganizationandsocialroles.Otherchronicstressorsincludedailyhassles(e.g.,aslowdownonthefreeway)andambientstressors(e.g.,deterioratingaspectsofaneighborhood).

Lifeeventstressorsrefertoobjectivechangesinlifecircumstancesthatareofsufficientmagnitudetochangeaperson'susualactivities(e.g.,acutephysicalillness).Thesecanbeexpectedtooccurthroughoutthelifecourse,anditistheundesirableeventsthatarestressfulforpeople.

Stressproliferationreferstothenotionthataparticularstressfulcircumstanceisusuallynotconfinedinaperson'slifebuttendstospreadoutandcreateadditionalproblemsinotherareasoflife(i.e.,aprimarystressormayproduceasecondarystressor).Primarystressorsareprimaryinthesensethattheyaretherootoriginofaseriesofotherproblematiclifecircumstancescalledsecondarystressors.Thesesecondarystressorsarenotnecessarilysecondaryintheirpotencyandrefertothespilloveroftheprimarystressorintootheraspectsofaperson'slife(e.g.,interferencewithjob,disruptionofrelationshipswithfamilyandfriends,constrictionofsocialactivities).

Fortraumaticevents,ifsecondaryadversitiesorotherstressorsarise,theeffectsmaybeadditive,thatis,theymayproliferate.

Oncetheseadditionalorsecondarystressorshavebeencreated,theythenserveasanindependentsourceofstress.Stressmayproliferatefortheindividualwhoistheprimarytargetofinterestandalsoforthefamilyandfriendsofthatindividual.

Ingeneral,thedurationofanexposureisrelatedtotheeffectsof

stress.Themorelongtermtheexposure,themorelongtermaretheeffects.Inaddition,justbecauseapersonisremovedfromastressfullifecircumstance,theeffectsofhavingbeeninthatconditionorcircumstancepersist,eventhoughthestressorisabsent.

TheGulfWarhadmanyverystressfulexperiences,despitethefactthatitwasamilitarysuccess.ThereweremanymonthsleadinguptothewarinwhichtheUStroopswereuncertainaboutthestrengthofIraqitroops,whetherchemicalorbiologicalweaponswouldbeused,andwhethertheywouldbeinjuredorkilledintheengagement.Inaddition,troopswererapidlyandunexpectedlydeployed,separatedfromfamilyandfriends,facedwithaharshdesertenvironmentandenvironmentalhazards,andexposedtoadirectlifethreat;theyalsowitnesseddeathanddestruction.

WhenindividualsdeployedtotheGulfreturnedhome,itwasassumedthatsincethewaritselfwasbriefandtheleveloflossofUSliveswaslow,problemsassociatedwiththewarwouldbefew.TheDepartmentofVeteransAffairsdiddevelopaPersianGulfRegistryasameansofaddressingquestionsabout

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possiblefutureeffectsofairpollutantexposureandotherenvironmentalagents,particularlythoseassociatedwiththeoilwellfires.However,astimepassed,itbecameapparentthattherewereconcernsaboutanumberofexposureissues.

Informationonexposuresandtheirhealthconsequenceswascontradictoryand,assuch,potentiallyworsenedthealreadystressfulsituationbymakingitambiguous.Becausetheperceptionthatonehassomethingwrongwithone'sbodyisitselfasourceofstress,theveryvaguenesssurroundingtheinformationthatwasforthcomingaboutagentstowhichonewasexposedandthelackofknowledgeofhealthconsequencesofsuchexposureshaveexacerbatedtheimpactofthestressassociatedwithhealthcomplaints.

Indeterminingthenegativeeffectscreatedbyexposuretostress,itisnecessarytolookbeyondtheoneprimarystressortothecreationofproblemsinotherareasofaperson'slifeand,additionally,inthelivesofpeoplewithwhomheorsheisincloseassociation.

CONSEQUENCESOFSTRESS

Researchhasshownthatstressorshavebeenassociatedwithmajordepression,symptomsofdepressionandanxiety,alcoholabuseanddependence,andsubstanceabuseanddependence.Manyoftheseconditionsareundiagnosedinprimarycarepopulationsforanumberofreasonsincludingthetrainingandexperienceoftheexaminer,thetimepressureforcompletingexaminations,stigmatizationandsocialattitudes,andthemisperceptionthattreatmentdoesnotwork.

Depression

Thediagnosisofdepressionintheprimarycaresettingisfrequentlymissed,andwhenproperlydiagnosed,depressionisofteninadequatelytreated.A4yearlongitudinalstudyofmedicaloutcomes

wasbeguninthelate1980sandinvolvedmorethan20,000patientsinthreecenters(Boston,LosAngeles,andChicago)anddifferentfinancingsystems.Generalmedicalclinicianssaw364patientsandwereawarethatthefocusofthestudywasdepression.Despitethisfact,theseprimarycarephysiciansmissedthediagnosisofdepression50%ofthetime(WellsandBurnham,1991).

Ofthepatientsfoundbyscreeningduringtheprimarycarevisittohaveamajorongoingdepression,59%receivednomedicationandwerenotinpsychotherapy.Ofthosewhoreceivedmedication,19%receivedonlyaminortranquilizer,and12%onlyanantidepressant,andoftheonesreceivingantidepressants,39%receivedhomeopathicdoses.Theunderdiagnosis,then,wascompoundedbyundertreatment.

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Tofacilitatethetaskofdiagnosingmentaldisorders,primarycareprovidersmustbecomefamiliarwithdiagnosticcategories,historicalfeatures,andinterviewtechniques.

Therearethreediagnosticcategoriesofmajormentaldisorders:(1)mooddisorders,(2)anxietydisorders,and(3)psychoticdisorders.Amooddisorderisadiagnosisestablishedonthebasisofarecurrentpatternofmoodepisodes.Moodepisodesareagroupofsignsandsymptomsthatco-occurforaminimaldurationoftime.Theycanbepartofamooddisorder,apsychoticdisorder,orageneralmedicaldisorder.Kindsofmoodepisodesincludemajordepressive,manic,mixed,andhypomanic.

Toidentifyamajordepressiveepisode,onelooksforeitherapersistentdepressedmoodthatoccurseverydayormostofthedayandlastsatleasttwoweeks,ordiminishedinterestorpleasureinalloralmostallactivitiesandfiveofthefollowing:significantweightlossorchangeinappetite;insomniaorhypersomnianearlyeveryday;psychomotorretardationoragitation(observable);fatigueorlossofenergy;feelingsofworthlessnessorexcessive(orinappropriate)guilt;diminishedabilitytothink,concentrate,ormakedecisions;recurrentthoughtsofdeathorsuicide,orasuicideattempt.

Amanicepisodeincludesadistinctperiodofabnormallyandpersistentlyelevated,expansive,orirritablemoodnecessitatinghospitalizationorlastingatleastoneweekandthreeormoreofthefollowing:inflatedself-esteemorgrandiosity;decreasedneedforsleep;greatertalkativenessthanusualorpressuretokeeptalking;flightofideasorracingthoughts;distractibility;orriskymeasurableactivitiesorendangerment.

Therearedifferentkindsofmania.Thedysphoricormixedepisodeisacombinationofmaniaanddepression,characterizedbymarkedimpairment.Thehypomanicepisodeisnotsevereenoughtoshow

impairmentinsocialoroccupationalfunctioningortonecessitatehospitalization,andtherearenopsychoticfeatures.

Thelanguageofepisodescanbetranslatedintothelanguageoftheprimarycareclinician.Anepisodeisasyndrome(i.e.,acollectionofsignsandsymptoms).Syndromesleadtoclinicalevaluation;todifferentialdiagnosis,andultimately,toclinicaldiagnosis,prognosis,andtreatment.Disordersarediagnoses.

Mooddisordersaredividedintodepressivedisordersandbipolardisorders.Thedepressivedisordersincludemajordepression(oneormoremajordepressiveepisodes),minordepression(sadnessand/oranhedonia,atleastonemoresymptomofmajordepression,andtwoweeksimpairmentand/ordistress),anddysthymia(2yearsormoreofadepressedmoodfor''moredaysthannot,"twoormoreneurovegetativesymptoms,andhasnevermetcriteriaformajordepressiveepisode).

Depressionisfurtherdividedintomelancholic,chronic,andothertypes.Melancholicdepressionsoftendonotrespondwelltotreatment,andresultin

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decreasingactivityandmarkedsleepdisturbanceswithaworseprognosis.Thechronictypeofdepressionlastsatleast2yearsinarowwithoutanyremissionofmorethan2months,andlaterinterventionresultsinslowerrecovery.Thisisnotdysthmia.

Misdiagnosisisoftentoduetothefactthatthereisanoverlapinthesignsandsymptomsofdepressionwithmanymedicalconditions.Acommonerrorbeginswiththeidea,"Wellwouldn'tyoubedepressedifyouweresosick?"Inaddition,theclinicalpresentationofdepressionincludesconfusingorambiguous(non-mood)complaintssuchaspervasiveboredom,decreasedenergy,insomnia,andfatigue.Anotherpresentationisirritability.Patientsmaysaytheyfeelsadallthetime-ordepressed,hopeless,pessimistic,orblue.Therearesomepatientswhoseekcarebecausetheyhavevagueornonspecificphysicalcomplaintssuchasfatigue,lossofenergy,sleepdifficulties,orunexplainedsomaticsymptoms.

Anumberofinstrumentscanbeusedtoscreenfordepression.TheseincludetheBeckDepressionInventory,theZungSelf-ratingDepressionScale(SDS),theCenterforEpidemiologicalStudies-DepressionScale(CES-D),andtheInventorytoDiagnoseDepression(IDD).Whenindoubtaboutadiagnosisofanymentaldisorder,aphysicianshouldscheduleearlyfollow-uptoconfirmordenythediagnosisandtoletthepatientknowthatthephysicianisconcerned.Ithasbeenshownthatasmanyas15%ofpatientswithinadequatelytreateddepressionkillthemselves.

Indiagnosingdepressioninprimarycare,itisimportanttoscreenpopulationsatelevatedrisk,toincreasetheclinicalsensitivityofprimarycareproviders,toensurethatthereisadequatetimetoperformtheevaluation,toremovebarrierstospecialtycare,toencouragemultidisciplinarymanagement,toassesscomorbidity,andtoovercomestereotypes.

PosttraumaticStressDisorder

Posttraumaticstressdisorder(PTSD)appearedasanofficialdiagnosisintheAmericanPsychiatricAssociation's1980publicationoftheDiagnosticandStatisticalManualofMentalDisorders(DSM-III).PTSDwasrecognizedasanewdisorder,linkedtoexternalstressorsthatareoverwhelmingandextreme.PTSDhasbeenfoundtobefrequentinveteransofmilitarycombatandrepresentsanimportantconcerninprovidingcaretotheveteranpopulation.IntheNationalVietnamVeteransReadjustmentStudy,investigatorsfoundthatanestimated15.2%ofallmaleVietnamWartheaterveterans(about479,000Americanmen)metthecriteriaforcurrentPTSDatthetimethedatawerecompiled(RundellandUrsano,1996).AstudybySouthwicketal.(1995)foundthatina2-yearfollow-uptoastudyofPersianGulfveteransconducted6monthsafterthewar'send,"althoughsymptomswererelativelymild,therewas

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anoverallincreaseinPTSDsymptomsat2years,andnotbefore."Theygoontosuggestthatitmaytaketimefortheconsequencesoftraumaticexposuretobecomeapparent.

TherequiredfeaturesofPTSDareatraumaticeventthatprecipitatessymptomsofacrisisreactionintheindividual(i.e.,theindividualwasoverwhelmedphysiologicallyandshowedsignsofextremehorror,helplessness,orgrief,inthecaseofatragicloss).ThisisfrequentlyreferredtoasCriterionA.Otherrequiredfeaturesarethatthetraumabereexperiencedindreamsorthoughtsorthatitbereenacted,thattherebeanumbingofresponsiveness,andthatatleasttwoofthefollowingsymptomsoccur:hyperalertness(exaggeratedstartleresponse),sleepdisturbance,guilt,troubleconcentrating,avoidanceofactivitiespromptingrecalloftheoriginalevent,andworseningofsymptomsbyexposuretoeventsresemblingtheoriginalevent(Helzeretal.,1987).

ForprovidersnotexperiencedinthediagnosisofPTSD,themostcommonerroristomaketheassumptionthattheonlyrequirementforsatisfyingCriterionAistodeterminewhethertheindividualpersonallyexperiencedatraumaticevent(e.g.,servedinahostilefirezone).However,theprovidermustgobeyondthistoelicittheindividual'sresponsetothetrauma(i.e.,theextenttowhichheorsheexperiencedreactionssuchasintensefear,helplessness,andhorror).

Althoughdirectexposureisprobablythemostpotent,observationalexperiences(e.g.,observinghorrificthingshappeningtoothers)cannotbedisregardedastraumaticevents.Vicariousexposure,especiallyinthecaseofclosesocialdistancetothevictim,isalsocapableofproducingPTSDsymptoms.

Ithasbeenwelldocumentedfrombothclinicalandepidemiologicaldatathatcombat-relatedPTSDisfrequentlyassociatedwithotherpsychiatricmorbidity,andithasbeensuggestedthatalcoholand

substanceusehavearoleinprecipitatinganxietyandmood-relatedsymptoms(Mellmanetal.,1992).Inaddition,individualswithPTSDareatriskfordevelopingsecondaryaffective,alcoholandsubstanceabuse,aswellaspanicandphobicdisorders.TreatmentofthesecomorbidconditionsisessentialtothemanagementofPTSD(Marmaretal.,1993).AccordingtoMarmaretal.,theseverityandcourseofPTSDareinfluencedbytheinteractionofthetraumaticstressexposurewithabackgroundofindividualpsychologicalandbiologicalvulnerability.

SubstanceAbuse

Substanceabuseproblemsarefairlyprevalentinprimarycare.About20%to30%ofpatientswhovisitprimarycarephysiciansdosoforproblemsthatrelateinsomewaytosubstanceabuseormisuse.Substanceabuseresultsfromaddiction,whichisadiseaseprocesscharacterizedbythecompulsiveuseofa

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specificpsychoactivesubstance.Anindividualengagesinasetofbehaviorsregardingthesubstancethatcanleadtoadependencedisorderoranabusedisorder.

Intermsofsubstanceabuse,theroleoftheprimarycarephysicianistwofold.First,theprimarycarephysicianmustassessandtreatthemedicalproblemsrelatedtosubstanceabuse.Thereare,forexample,anumberofmedicaldiseasesrelatedtoparenteraldrugusesuchasendocarditis,acutehepatitis,cirrhosis,bleedingulcers,pancreatitis,stroke,seizures,amnesia,dementia,andcertaincardiovascularandpulmonarydiseases,aswellasoverdose,trauma,andhormonalabnormalities.Medicalproblemsthatresultfromalcoholabuseincludeneurologicalproblems,liverdisease,pancreaticdisease,andhematologicdiseases.Thereisalsoagreatdealofcomorbiditybetweensubstanceabuseandpsychiatricdisorderssuchasschizophrenia,affectivedisorders,anxietydisorders,andantisocialpersonalitydisorders.

Thesecondmajorresponsibilityoftheprimarycarephysicianistoconductsubstanceabusescreening.Ifapatientpresentswithamedicalproblemrelatedtosubstanceabuse,theprimarycarephysicianshouldscreenforabuseasacauseoftheproblem.Averyimportantcomponentofthisscreeningistodeterminetheseverityoftheproblemandtheriskofcomplications.Toconducteffectivescreening,thephysicianmustinterviewthepatientconcerninghisorhergeneralhealthhabits,dietandexercise,useofprescriptions,useofover-thecounterandhomeremedies,smoking,drinking,anduseofmarijuanaandotherdrugs.Inaddition,theprimarycarephysicianshoulduseoneofthesubstanceabusescreeninginstruments(e.g.,CAGE,MAST/DAST,AUDIT,HSS,andtheT-ACE/TWEAK;seeAppendixIforcopiesoftheinstruments).

OtherConsequences

Stresshasalsobeenassociatedwithvariousphysicalhealthproblems,particularlyimmunesystemfunctioning.AstudybyCohenetal.(1991)showedthatforindividualsinoculatedwithacoldvirus(rhinovirustype2,9,or14,respiratorysyncytialviruses,orcoronavirustype229E),therewasanincreasedinfectionrateinthosewhoreportedahighlevelofrecentstress.AccordingtoworkconductedrecentlyatRockefellerUniversity,itappearsthatmoderatestress(i.e.,stressthatiscircumscribedbothinitsphysicaldurationanditsperception),maintainedinahealthyindividual,seemstoenhancecellmediatedimmunity.Thereisalsoevidencethatitmightenhancehumoralorantibody-dependentimmunity.However,chronicstressdisruptsequilibriumanddecreasescellmediatedimmunity(Dhabharpresentation,1997).

Thereareotherpotentialconsequencesofstressforhealthoutcomes,forexample,theeffectsofstressonhealthbehavior.Somebehaviorsmayproducepositiveeffects(e.g.,runningasacopingmechanism),whereasmanyare

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unhealthy(e.g.,smoking,drinking,overeating).Stressexertsanindirecteffectonhealthviathesekindsofbehaviors.

Therearealsostresseffectsonillnessbehavior,thatis,whatapersondoeswhoperceiveshimorherselfashavingsomesortofsickness.Ithasbeenacceptedformanyyearsthatpersonswhoengageincertaintypesofstressfulbehaviorareathigherriskofdevelopingcoronaryheartdisease(Williams,1995).Lesswellknownisthefactthatthosewhosufferfromclinicaldepressionexperiencea5-foldhighermortalityfollowingmyocardialinfarctionthannondepressedpatients.

AccordingtoChrousosandGold(1992),astresssystemwithinthebodyproducespathophysiologicstatesthatcanmakeapersonvulnerabletoarangeofdisorders,includingendocrine,inflammatory,andpsychiatricdisorders.Ithasalsobeenshownthatjobsthatplacehighdemandsonaworkerwhileallowinglittlelatitudeindecidinghowthedemandsaremetcreatehighjobstrain.Employmentinhigh-strainjobshasbeenassociatedwithincreasedambulatorybloodpressurelevels(Schnalletal.,1992).

FriedmanandSchnurr(1995)conductedareviewoftheliteratureonphysicalhealthoutcomesassociatedwithtraumaticeventsincludingexposuretoawarzone,sexualorothercriminalvictimization,naturalorhuman-madedisasters,andseriousaccidents.Theyconcludedthat"thetraumaandhealthliteratureisimpressivefortheconsistencyofresultsshowingthatexposuretocatastrophicstressisassociatedwithadversehealthreports,medicalutilization,morbidity,andmortalityamongsurvivors."Althoughthereissomeconcernthatthisliteratureincludesworkwithmethodologicalflaws,FriedmanandSchnurr(1995)emphasizedthattherewas"generalconsistencyoffindingsacrossdiversetraumapopulationsandoutcomes...,"includingmorbidityandmortalitydatathatsupportedself-reportandutilizationdata.

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6ConclusionsandRecommendationsAgreatdealoftimeandefforthasbeenexpendedevaluatingDoD'sComprehensiveClinicalEvaluationProgram.IthasbeenreviewedbythePresident'sAdvisoryCommittee,theGeneralAccountingOffice,theOfficeofTechnologyAssessment,theInstituteofMedicine,andmanyotherorganizations.Asmoreislearned,itbecomeseasiertofocusonthekindsofquestionstheCCEPshouldbeasking.AsDr.PenelopeKeylsaidinherworkshoppresentationonthedevelopmentofgoodscreeninginstruments,progressmadeovertimewillnecessitatenewgenerationsofscreeninginstruments.Thisdoesnotimplythatthefirstinstrumentdevelopedisbad,butratherthattimeleadstonewknowledge,whichleadstotheabilitytoimprovetheinstrument.

SuchisthecasewiththeCCEP.Overtime,theCCEPandotherprogramshavegeneratedinformationthathasledustofocusonareasofimportanceforthoseconcernedaboutthehealthconsequencesofPersianGulfdeployment.Thisinformationhasenabledustotakeacloserlook,tomakeamorethoroughexaminationofthesystem,andtoidentifyareasinwhichchangewillbeofbenefit.Thecommitteebelievesthatsuchchangeishealthy,thatitreflectsgrowth,andthatitshouldbeanaturalpartofanysystemhavingasoneofitsgoalsthedeliveryofhigh-qualityhealthcareservices.

Changealsooccurswithindividuals.Itmaybethatastimepassesornewinformationisreleased,someofthosewhohavealreadyparticipatedintheCCEPwilldevelopnewconcernsorproblems.ThecommitteehopesthatDoDwillencouragetheseindividualstoreturntotheCCEPforfurtherevaluationanddiagnosis.

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ThecommitteewishestoemphasizethatitisimpressedwiththededicationandconcernexhibitedbyDoDpersonnelwithwhomcommitteemembersmet.TheseindividualsareknowledgeableregardingPersianGulfissuesandwillingtolearnmoreaboutidentifyingandresolvingareasofconcernforimprovingthehealthofactive-dutypersonneldeployedtotheGulf.

MEDICALLYUNEXPLAINEDSYMPTOMSYNDROMES

Thecommitteespentsometimedeliberatingontheprecisemeaningof"difficulttodiagnose"or"illdefined"asadescriptionofacategoryofconditions.Whenlabelingsomethingasdifficulttodiagnose,oneusuallymeansthatspecialexpertiseisrequiredtoarriveatadiagnosis,butmanyoftheseconditionsdonotrequiresuchexpertise.Chronicfatiguesyndrome,fibromyalgia,andmultiplechemicalsensitivityaresymptomcomplexesthathaveagreatdealofoverlapinthesymptomspresentineachconditionbutarewelldefinedclinically,eveniftheyaremedicallyunexplained.Despitethefactthattheyaremedicallyunexplained,theymaycausesignificantimpairmentandtheyareillnessesthatareonlyunderstoodthroughtime,thatis,itrequiresthepassageoftimeandtheevaluationofresponsestotreatmenttoarriveatthesediagnoses.Thecommitteedecided,therefore,torefertothisspectrumofillnessesasmedicallyunexplainedsymptomsyndromes.Thisspectrumofillnessesmayincludethosewhichareetiologicallyunexplained,lackcurrentlydetectablepathophysiologicalchanges,and/orcannotcurrentlybediagnosticallylabeled.

Thesemedicallyunexplainedsymptomsyndromesareoftenassociatedwithdepressionandanxiety.Thereremainsadebateabouthowtodistinguishthesesyndromesfrompsychiatricdiagnoses,butitisclearthattheyarenotsimplypsychiatricdiagnoses.However,sincemostoftherecommendedtreatmentsformedicallyunexplained

symptomsyndromesoverlapwiththepharmacologicalandbehavioraltreatmentsforpsychologicalconditionsorpsychiatricdiagnoses,thecommitteebelievesthatitisimportanttoidentifyandevaluatethesymptomsassociatedwiththeseconditionsandthentreatthosesymptoms.

Thecommitteerecommendsthatwhenpatientspresentingwithmedicallyunexplainedsymptomsyndromesareevaluated,theprovidermusthaveaccesstothefullandcompletemedicalrecord,includingprevioususeofservices.Thepresenceofsuchinformationisimportantbecauseadequateevaluationofthesedisordersinvolvesalongitudinalperspectivethatincludesresponsetotreatment.

Intheareaofmedicallyunexplainedsymptomsyndromes,itissometimesnotpossibletoarriveatadefinitivediagnosis.Itmaybepossible,however,totreatthepresentingcomplaintsorsymptoms.Thecommitteerecommendsthatincaseswhereadiagnosiscannotbeidentified,treatmentshouldbe

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targetedtospecificsymptomsorsyndromes(e.g.,fatigue,pain,depression).Ifthesesymptomsandconditionsareleftuntreated,theycanbecomechronicandpotentiallydisabling.ThecommitteerecommendsthattheCCEPbeencouragedtoidentifypatientsinthisspectrumofillnessesearlyintheprocessoftheirdisease.Inaddition,primarycareprovidersshouldidentifythepatients'functionalimpairmentssoastobeabletosuggesttreatmentsthatwillhelpimprovethesedisabilities.

STRESS

Inthisgroupofmedicallyunexplainedsymptomsyndromesitisimportanttorecognizeandacknowledgethattheproblemsandstressfacingthepatientwillcontinuetobedifficult.Stressisamajorissueinthelivesofpatientswithinthisspectrumofillness.Stressneednotbelookedatsomuchasacausativeagent,butratherasapartoftheconditionofthepatientthatcannotbeignored.Withthesemedicallyunexplainedsymptomsyndromes,thepotentialforstressproliferationisgreatamongboththepersondeployedtothePersianGulfandthefamilymembers.

MediaattentionandreportsbythemilitarytoGulfWarveteransthattoxicexposurecouldhaveoccurredareverystressfulevents,regardlessofanyone'seffortstoexplainwhathappened.Suchannouncementscarrywiththemstressfulburdensfortheveteran.Thestressassociatedwiththesereportsofandworryovertoxicexposuresneedstoberecognizedandaddressed.

Researchhasshownthatstressorshavebeenassociatedwithmajordepression,substanceabuse,andvariousphysicalhealthproblems.ThosedeployedtotheGulfwereexposedtoavastarrayofdifferentstressorsthatcarrywiththemtheirownpotentialhealthconsequences.Currentcollectionofexposureinformationdoesnotadequately

addressaninvestigationoftraumaticeventstowhichthedeployedsoldiermayhavebeenexposed.ThecommitteerecommendsthattheCCEPcontainquestionsontraumaticeventexposuresinadditiontotheexposureinformationcurrentlybeingcollected.Thiswouldincludetheadditionofopen-endedquestionsthataskthepatienttolisttheeventsthatweremostupsettingtohimorherwhiledeployed.Positiveresponsestoquestionsregardingsuchevents,aswellastootherexposurequestions,shouldbepursuedwithanarrativeinquiry,whichwouldaddresssuchitemsasthespecificnatureoftheexposure;theduration;thefrequencyofrepetition;thedoseorintensity(ifappropriate);whetherthepatientwastakingprotectivemeasuresand,ifso,whatthesemeasureswere;andthesymptomsmanifested.

OthersuggestionsforquestionsthatcouldbeaddedtotheCCEPincludethefollowing:Whendidyoufirsthavequestionsorworriesaboutbeingexposed?Whendidyoufirsthearotherinformationonpossibleexposures?

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Whatwereyourresponsestothatinformation?ProvidersintheCCEPneedtotakeahistorythatincludessomenarrativetoallowtheveterantoexpresshowheorshefeels.

Itisalwaysimportanttounderstandandacknowledgethatthepatients'complaintsarereal.ItiscertainlyimportantforprovidersintheCCEPtodosowhenattemptingtoidentifyandaddressthehealthconcernsofPersianGulfveterans.Furthermore,nomatterwhatadditionalinformationmaybeforthcomingaboutpotentialexposurestotoxinsandtheireffects,thecommitteerecommendsthatDoDprovidersacknowledgestressorsasalegitimatebutnotnecessarilysolecauseofphysicalsymptomsandconditions.

Thecommitteebelievesthattherearecertainjobsundertakeninthemidstofwarthat,bytheirverynature,resultinhighstress(e.g.graveregistrationduty).Theeffectofstressassociatedwiththesejobscanbemitigatedifapproachedproperly.ThecommitteerecommendsthattheDoDprovidespecialtraininganddebriefingforthosewhoareengagedinhigh-riskjobssuchasthoseassociatedwiththePersianGulfexperience.Everysoldierwhogoestowarwillbesubjectedtomajordisturbingeventssincewarbyitsverynatureinvolvesdeathanddestruction.ThecommitteerecommendsthatDoDprovidetoeachabout-to-bedeployedsoldierriskorhazardcommunicationwhichiswelldevelopedanddesignedtoprovideinformationregardingwhattheindividualcanexpectandthepotentiallytraumaticeventstowhichheorshemightbeexposed.

Thecommitteewishestoemphasizethattheaccuratediagnosisofpatientswithmedicallyunexplainedsymptomsyndromesand/orconditionsinducedorexacerbatedbyupsettingeventsrequirestheexpenditureoftime,timeinwhichtheproviderandthepatientinteract.Itisnotpossibletohandthepatientaquestionnaireandexpectthatallnecessaryinformationwillberevealed.Inaworldof

timeconstraintsandtightlyscheduledappointments,thecommitteerecommendsthatadequatetimemustbeprovidedduringinitialinteractionswithpatientsintheCCEPinordertoensurethatallpertinentinformationisforthcoming.Thecommitteebelievesthatthepatient-physicianinteractionshouldbefostered,andtheperceptionthatevaluationisdirectedbytheclockshouldbeavoided.

SCREENING

Depressionisaconditionthatiscommoninprimarycare.Mostindividualswhoexperiencedepressioncontinuetofunction,butiftheyareleftuntreated,theirconditiondeteriorates.Unlikemanyofthemedicallyunexplainedsymptomsyndromes,thereareeffectivetreatmentsfordepression.ThedatapresentedindicaterisingratesofdepressionamongthoseexaminedintheCCEP

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butnoevidencethatindividualsarebeingproperlydiagnosedortreatedaccordingtocurrentlyacceptedclinicalpracticeguidelines.Therearemanyself-ratedscreeningtests(e.g.,theBeckDepressionInventory[BDI],theZungScale,theCenterforEpidemiologicalStudies-DepressionScale[CES-D],theInventorytoDiagnoseDepression[IDD])thatcouldbeusedasafirst-levelscreenattheprimarycarelevel.

Thecommitteerecommendsthattherebeincreasedscreeningattheprimarycarelevelfordepression.Everyprimarycarephysicianshouldhaveasimplestandardizedscreenfordepression.Ifapatientscoresinthesignificantrange,thispersonshouldbereferredtoaqualifiedmentalhealthprofessionalforfurtherevaluationandtreatment.Ifdepressionisidentified,therehastobemorequestioningonexposuretotraumaticproblems.

TherehasbeenagreatdealofconcernevincedaboutthepossibilityofwidespreadPSTDinthosedeployedtothePersianGulf.MostoftheindividualsidentifiedashavingPTSDarediagnosedfollowingastructuredinterviewatPhaseII.However,thecommitteebelievesthattherearethosewhohavesomeofthesymptomsofPTSDorofdepressionbutarenottruePTSDcasesyetmightbehelpedwithtreatmentoftheirsymptoms.

ThecommitteerecommendsthatanyindividualwhoreportsanysignificantPTSDsymptomsand/orasignificanttraumaticstressorshouldbereferredtoaqualifiedmentalhealthprofessionalforfurtherevaluationandtreatment.

Substanceabuseormisuseproblemsareprevalentinprimarycare.Inaddition,individualswithuntreateddepressionorwithmedicallyunexplainedsymptomsyndromesmayhaveanenhancedriskofsubstanceabuse.(SeeAppendixIforexamplesofscreeninginstruments.)Thecommitteerecommends,therefore,thatevery

primarycarephysicianshouldhaveasimple,standardizedscreenforsubstanceabuse.Everyindividualwhoscreenspositiveshouldbereferredforfurthertreatmentandevaluation.

Therearecertainareasinwhichbaselineassessmentsareofimmensevalueintheclinicalevaluationofanindividualpatient'sstatus(e.g.,pulmonaryfunctionandneurobehavioraltesting).Changesinneurocognitiveandperipheralnervefunctionaremeasuredbycomparingtheindividual'scurrentstatustoabaselinemeasure.Thisisalsotrueformeasuringcomplaintsofmemoryimpairment.Individualbaselineinformationisnecessarybecausethevariabilityacrossindividualsistoogreattoidentifyageneralized"normal"screeninglevel.

ThecommitteerecommendsthatDoDexplorethepossibilityofusingneurobehavioraltestingatentryintothemilitarytodeterminewhetheritisfeasibletousesuchteststopredictchangeinfunctioningortrackchangeinfunctionduringasoldier'smilitarycareer.

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PROGRAMEVALUATION

MostpatientsintheCCEPreceiveadiagnosisaftercompletingaPhaseIexamination;somearereferredtoPhaseIIforevaluation;andafewhavegoneontoparticipateintheprogramattheSpecializedCareCenter.Informationpresentedtothecommitteeindicatesthatthereisgreatvariationacrossregionsinthepercentageofpatientswhoarediagnosedashavingprimarypsychiatricdiagnoses.Adeterminationofthereasonsforthisvariationshouldbemade.Althoughtheremaybemanyreasons,oneexplanationcouldrelatetotheconsistencywithwhichproceduresfordiagnosisandreferralareimplementedfromfacilitytofacility.Thecommitteerecommendsthatanevaluationbeconductedtoexamine(1)theconsistencywithwhichPhaseIexaminationsareconductedacrossfacilities;(2)thepatternsofreferralfromPhaseItoPhaseII;and(3)theadequacyoftreatmentprovidedtocertaincategoriesofpatientswherethereisthepotentialforgreatimpactonpatientoutcomeswheneffectivetreatmentisrendered(e.g.,depression).

ThiseffortcouldbefacilitatedbythedevelopmentanduseofclinicalpracticeguidelinessuchasthosecurrentlybeingdevelopedbytheDepartmentofVeteransAffairsandmanymedicalspecialties.Clinicalpracticeguidelinesaresystematicallydevelopedstatementsthatassistpractitionersandpatientsindecisionmakingaboutappropriatehealthcareforspecificclinicalcircumstances(IOM,1992).Theprocessofdevelopingtheseguidelinescouldalsoserveasanopportunityforincreasedlearningforproviderssincetheirparticipationiscrucialtosuccessfulimplementation.

TheSpecializedCareCenteratWalterReedArmyMedicalCenterhasprovidedevaluationandtreatmentto78patients.Agreatdealofeffortandthoughthasgoneintothedevelopmentofaprogramdesignedtohelpthepatientunderstandhisorherconditionsandengagein

behaviorsmostlikelytoresultinimprovement.Thecommitteewasaskedtoassesstheeffectivenessofthiscenterwithinthecontextofmedicallyunexplainedsymptomsyndromes,stress,andpsychiatricdisorders.AsthecommitteebeganitsdiscussionoftheeffectivenessoftheSpecializedCareCenteritbecameapparentthatsuchanassessmentwasdependentonanumberoffactorsthathavenotbeenwelldefined.Whatisthegoalofthecenter-isittreatment,research,oreducation?Shouldamajorconsiderationinthecenter'sevaluationbethecostofservices?Shouldthenumbersofthosereceivingcarebetakenintoconsideration,andifso,whatarethebarrierstopatientsaccessingthislevelofcare?

Thecommitteeconcludedthatatthistime,itisnotpossibletoconductafairoradequateevaluationoftheSpecializedCareCenter.Thecommitteerecommendsthatashort-termplan(perhaps5years)bedevelopedfortheSpecializedCareCenterthatwouldspecifygoalsandexpectedoutcomes.Basedonsuchaplan,anevaluationcouldthenbeundertakentoassesstheeffectivenessofthecenter.

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COORDINATIONWITHTHEVA

GiventhatmanynowreceivingservicesintheDoDhealthcaresystemwilleventuallymovetotheVAhealthcaresystem,itisimportanttohavegoodcommunicationbetweenDoDandtheVA.Thismaybeparticularlytrueintheareasofmedicallyunexplainedsymptomsyndromesandpsychiatricdisorders,whereaccuratediagnosisandassessmentofresponsetotreatmentareimportantforpositivepatientoutcomes.ThecommitteerecommendsthatDoDexplorewaystoincreasecommunicationwiththeVA,particularlyasitrelatestotheongoingtreatmentofpatients.

BothpatientsandproviderswouldbenefitfromincreasededucationalactivityregardingPersianGulfhealthissues.ProviderturnoverwithinDoDisafactorthatmustbetakenintoconsiderationwhenexaminingthespecialhealthneedsandconcernsofactive-dutypersonnelwhoweredeployedtothePersianGulf.AlthougheffortsatprovidereducationwereextensiveatthetimetheCCEPwasimplemented,threeyearshavepassedandmanynewprovidershaveenteredthesystem.Theseindividualsshouldbeorientedtothespecialneeds,concerns,andproceduresinvolved,andallprovidersshouldbeupdatedregularly.

TheVAhasdevelopedanumberofapproachestoprovidereducation.Interactivesatelliteteleconferencesareavailableperiodicallyformedicalcenterstafftodiscussparticularissuesofconcern.TheVAconductsquarterlynationaltelephoneconferencecalls,directsperiodiceducationalmailingstoPersianGulfRegistryprovidersineachhealthfacility,andconductsanannualconferenceonthehealthconsequencesofPersianGulfservice.ThecommitteerecommendsthatDoDexaminetheactivitiesandmaterialsforprovidereducationdevelopedbytheVAtodetermineifsomeoftheitemsmightbeusedaseducationalapproachesforDoDproviders.

AlthoughthetopicsofongoingeducationaleffortsarebestdeterminedbyDoDonaperiodicbasis,thecommitteerecommendsthatDoDmountaneffortdesignedtoeducateproviderstothefactthatconditionsrelatedtostressarenecessarilypsychiatricconditions.Thecommitteerecommendsthatdepressionbeatopicofeducationforallprimarycareproviders,withemphasisonthefactsthatdepressioniscommon,itistreatable,andindividualswhoexperiencedepressioncancontinuetofunction.

ThecommitteewishestoreemphasizethefactthattheCCEPisnotaresearchprotocolbutratheraprogramdesignedtodiagnosethehealthproblemsofthosewhoservedinthePersianGulf.Assuch,informationobtainedthroughtheCCEPshouldnotbeusedtoanswerresearchquestions.Itisappropriate,however,tousethedataandnarrativeinformationobtainedfromtheCCEPtoinformtheclinicaltreatmentprocess.Indoingso,thecommitteebelievesthatitisimportanttounbundlediagnosticcategories.Forexample,tensionheadache

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isclassifiedasasomatoformdisorderwithinthecategoryofpsychiatricdiagnosis.

Inaddition,atremendousamountofqualitativeinformationcouldbeusedindevelopingcasestudiestohelpprovidersbetterunderstanddiagnosticandtreatmentapproachesthatappeareffectiveatimprovingindividualpatients'conditions.

ThecommitteerecommendsthatCCEPinformationbeusedtodevelopcasestudiesthatwillhelpeducateprovidersaboutPersianGulfhealthproblems.Thereareanumberofwaysinwhichthesecasestudiescouldbesharedincludingpresentationduringprofessionalmeetings.

ThereisalsoaneedforeducationandcommunicationwithindividualswhoweredeployedtotheGulfandwiththeirfamilies.TheseindividualsareconcernedaboutthepotentialimpactofPersianGulfdeploymentontheirhealth,whetherornottheirhealthconcernswillaffecttheirmilitarycareers,theirabilitytoobtainhealthinsuranceoncetheyleavetheservice,andanumberofotherissuesthatneedtobeaddressed.

Avarietyofmechanismsareavailableforprovidingsuchinformationincludingindividualpostnewsletters,theInternet,mailingstothoseintheRegistry,andpublicforums.Itisespeciallyimportanttoprovideaforumfordiscussioneachtimenewinformationisreleasedonpossibleexposures.ThecommitteerecommendsthatDoDdevelopapproachestocommunicationandeducationthataddresstheconcernsofindividualsdeployedtothePersianGulfandtheirfamilies.

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AppendixAPresidentialAdvisoryCommitteeonGulfWarVeterans'Illnesses:FinalReportRecommendations*

RECOMMENDATIONS

TheCommittee'sevaluationofthegovernment'sresponsetoconcernsaboutGulfWarveterans'illnessesledustofindingsinoutreach,medicalandclinicalissues,research,chemicalandbiologicalweapons,andcoordination.Basedonouranalysesandthesefindings,theCommitteemakesthefollowingrecommendations:

Outreach

DODandVAshouldfollowthemodeloffield-basedoutreachdemonstratedintheVetCentersandthePersianGulfFamilySupportProgramwhendevelopinghealtheducationandriskcommunicationcampaignsforactivedutyservicemembers,ReserveandNationalGuardpersonnel,andotherveterans.General,lessspecificoutreachmethods-e.g.,hotlinesandpublicserviceannouncements-shouldbeviewedasimportantsupplements,butnotasreplacements.

VAshoulddirectitsTransitionAssistanceProgramworkshopbenefitscounselorstospecificallymentionDODandVAprogramsrelatedtoGulfWarveterans'illnesses.

*ThisappendixhasbeenexcerptedfromthePresidentialAdvisoryCommitteeonGulfWarVeterans'Illnessesreport,PresidentialAdvisoryCommitteeonGulfWarVeterans'Illnesses:FinalReport,Washington,D.C.:U.S.GovernmentPrintingOffice,1996.

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VAshouldensurethatitsinitiativesundertheWomenVeteransHealthProgramsspecificallyprovideinformationaboutGulfWar-relatedprograms.

VAshouldensurethatitsoutreachtoLatinopopulationsspecificallyprovidesinformationaboutGulfWar-relatedprograms.AstheCommitteestatedinitsInterimReport,DODandVAshoulddevelopandutilizemorerefinedperformancemeasurestodeterminehowwelloutreachservicesarereachingconcernedparties.DODandVAofficials(specificallythoseintheAmericanForcesInformationServiceanditsbroadcastingarm,theArmedForcesRadioandTelevisionService)usingmediaproductsforoutreachinitiativesshouldbeawareofthedifficultyinenumeratingtheactualreadershipandviewershipfiguresandbeconcernedabouthoweffectivelytheirmessagesaturatesthetargetedpopulation.

DODshouldreissueitsInternalInformationPlanonGulfWar-relatedillnesses.ItshouldmakeaspecialefforttonotetherevisionprovidesthetollfreenumberandthatindividualsareencouragedtoregisterforitsComprehensiveClinicalEvaluationProgram.Italsoshouldtakethisopportunitytoprovideupdatedinformation.

Inanattempttoincreaseveterans'andthepublic'sawarenessandunderstandingofthefullrangeofthegovernment'scommitmenttoaddressingthenatureofGulfWarveterans'illnesses,DODandVAshouldreevaluatethegoalsandobjectivesoftheirriskcommunicationefforts.DODandVAshoulddevelopeffectivemethodsthatprovidetheaffectedcommunitywithcomprehensiveinformationconcerningpossibleexposurestoenvironmentalhazards,potentialhealtheffectsfromriskfactors,andexplanationsofongoingandcompletedclinicalandepidemiologicstudies.

DODandVAshouldimmediatelydevelopandimplementacomprehensiveriskcommunicationplan.Thiseffortshouldmove

forwardinclosecooperationwithagenciesthathaveahighdegreeofpublictrustandexperiencewithriskcommunication,suchastheAgencyforToxicSubstancesandDiseaseRegistryandtheNationalInstituteforOccupationalSafetyandHealth.

Becausehealthriskinformationandeducationappliestoservicememberswhoremainonactiveduty,membersoftheReservesandNationalGuard,andveteransnolongerinmilitaryservice,DODandVAshouldcloselycoordinatethefederalgovernment'sriskcommunicationeffortforGulfWarveteransandothermembersoftheaffectedcommunity.Departmentalcommitmentstoanyplanshouldbeviewedascontinuousandlong-term;asustainedeffortisparticularlycriticalinlightofveterans'andpublicskepticismarisingfromtherecentrevelationsrelatedtochemicalweapons.

Initscoordinatedriskcommunicationplan,DODandVAshouldengageveteransserviceorganizationsasintermediaries-andincludepersonnelinleadershippositions,suchasseniorenlistedpersonnel(foractivedutymilitary)

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andstateveterans'serviceofficials-intheefforttoestablishanefficientinformationexchangeprocesswhereveteransreceiveaccurateinformationandthedepartmentsreceivevaluablefeedbackonclinicalprograms,healthconcerns,andcommunicationefforts.

MedicalandClinicalIssues

GiventhattheFoodandDrugAdministration's(FDA)InterimFinalRulepermittingawaiverofinformedconsentforuseofunapprovedproductsinamilitaryexigencyisstillineffect,DODshoulddevelopenhancedorientationandtrainingprocedurestoalertservicepersonneltheymayberequiredtotakedrugsorvaccinesnotfullyapprovedbyFDAifaconflictpresentsaseriousthreatofchemicalandbiologicalwarfare.

FDAshouldsolicittimelypublicandexpertcommentonanyrulethatpermitswaiverofinformedconsentforuseofinvestigationalproductsinmilitaryexigencies.Amongtheareasthatspecificallyshouldberevisitedare:adequacyofdisclosuretoservicepersonnel;adequacyofrecordkeeping;longtermfollowupofindividualswhoreceiveinvestigationalproducts;reviewbyaninstitutionalreviewboardoutsideofDOD;andadditionalprocedurestoenhanceunderstanding,oversight,andaccountability.

DODofficialsatthehighestechelons,includingtheJointChiefsofStaffandtheCommanderinChief,shouldassignahighprioritytodealingwiththeproblemoflostormissingmedicalrecords.Acomputerizedcentraldatabaseisimportant.Specializeddatabasesmustbecompatiblewiththecentraldatabase.Attentionshouldbedirectedtowarddevelopingamechanismforcomputerizingmedicaldata(includingclassifiedinformation,ifandwhenitisneeded)inthefield.DODandVAshouldadoptstandardizedrecordkeepingtoensurecontinuity.

ThePersianGulfVeteransCoordinatingBoardandotherappropriatedepartmentsandagenciesshouldbechargedtodevelopaprotocoltoimplementthefollowingrecommendation,whichwasmadeintheCommittee'sInterimReport:Priortoanydeployment,DODshouldundertakeathoroughhealthevaluationofalargesampleoftroopstoenablebetterpostdeploymentmedicalepidemiology.Medicalsurveillanceshouldbestandardizedforacoresetoftestsacrossallservices,includingtimelypostdeploymentfollowup.

VAandDODshould,intheireducationaloutreachprograms,specificallytargetstaffmembersnotdirectlyinvolvedinthecareofGulfWarveterans.

DODandVAshouldincludetimelyupdatesontheComprehensiveClinicalEvaluationProgramorPersianGulfHealthRegistry,respectively,intheirContinuingMedicalEducationprograms.

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VAandDODshouldregularlybrieftheirstaffsontheGulfWarresearchportfolioandontheresultsofresearchstudiesastheybecomeavailable.

VAandDODshouldregularlyreviewstaffingneeds,particularlyinmentalhealth,andincreaserecruitmentandretentionofadequatenumbersofmedicalprofessionalstosatisfypatientneeds.Staffingreviewsshouldconsiderthat,despiteincreasedmedicalsurveillanceandbetterpreventivemeasures,futuredeploymentsalsowillgenerateasignificantnumberofveteranswhowillneedcareforillnessesthataredifficulttodiagnose.

Since1986,U.S.servicememberswithcertainchronicillnesses,e.g.,asthmaanddiabetes,havebeenallowedtoremainonactivedutywhenregularmedicalmonitoringisnecessary.VeteransoftheGulfWarwithchronicillnessesarenodifferent.Troopcommandersshouldberemindedthatadequatetimeoffforfollow-upmedicalappointmentsisanecessityandapriority.

Thegovernmentshouldconductathoroughreviewofitspoliciesconcerningreproductivehealthandseekstatutoryauthoritytotreatveteransandtheirfamiliesforservice-connectedproblems.Whenindicated,geneticcounselingshouldbeprovided-eitherviaVAtreatmentfacilitiesorreferraltoassistveteransandtheirfamilieswhohavereproductiveconcernsstemmingfrommilitaryservice.

Thegovernmentshouldcontinueandintensifyitseffortstodevelopstressreductionprogramsforalltroops,withspecialemphasisondeployedtroops.

Sinceleadershipandunitcohesionaresoimportantinmanagingstress,DODshouldspecificallyinvolveseniorcommandersandseniornoncommissionedofficersinstressmanagementprograms.

Research

TheResearchWorkingGroupofthePersianGulfVeteransCoordinatingBoardshouldrequirethatanyproposalsfornew,large-scaleGulfWarveterans'epidemiologichealthresearchdescribeaplantoincorporateapublicadvisorycommitteeintothestudydesign,disseminationofresults,orboth.TheResearchWorkingGroupshouldconsiderjustifyingawaiverofsuchacommitteeonlyunderrarecircumstances.

Thegovernmentshoulddevelopmoreaccurateandreliablemethodsofrecordingtrooplocationstofacilitatepost-conflicthealthresearchinthefuture.DODshouldmakefulluseofglobalpositioningtechnologies.

Thegovernmentshouldplanforfurtherresearchonpossiblelong-termhealtheffectsoflow-levelexposuretoorganophosphorusnerveagentssuchassarin,soman,orvariouspesticides,basedonstudiesofgroupswithwellcharacterizedexposures,including:(a)casesofU.S.workersexposedto

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organophosphoruspesticides;and(b)civiliansexposedtothechemicalwarfareagentsarinduringthe1994and1995terroristattacksinJapan.AdditionalworkshouldincludefollowupandevaluationofanappropriatesubsetofanyU.S.servicepersonnelwhoarepresumedtobeexposedduringtheGulfWar.Thegovernmentshouldbeginbyconsultingwithappropriateexperts,bothgovernmentalandnongovernmental,onorganophosphorusnerveagenteffects.Studiesofhumanpopulationswithwell-characterizedexposureswillbemuchmorerevealingthanstudiesbasedonanimalmodels,whichshouldbegivenlowerpriority.

SinceanumberofGulfWarriskfactorsarepotentialhumancarcinogensthatcouldresultinincreasedratesofcancerbeginningdecadesafterexposure,VAshouldcontinuetomonitorGulfWarveteransthroughitsongoingmortalitystudyforincreasedratesoflung,liver,andothercancers.

DepleteduraniummunitionsarelikelytobeusedinfutureconflictsinvolvingU.S.servicepersonnel.Tofullyelucidatethehealtheffectsofdepleteduraniummunitions,VAshouldconductresearchthatcomparesthehealthstatusofindividualswithembeddedfragmentsofDUshrapnelwithappropriatecontrolgroups.

ThegovernmentshouldcontinuetocollectandarchiveserumsamplesfromU.S.servicepersonnelwhenfeasible.

TheResearchWorkingGroupshouldmorethoroughlyconsultwithotherfederalagencieswithrelevantexpertise-suchastheNationalInstitutesofHealth(particularlytheNationalInstituteofEnvironmentalHealthSciences)andtheAgencyforToxicSubstancesandDiseaseRegistry-onbasic,clinical,andepidemiologicresearchandonriskcommunication.

ChemicalandBiologicalWeapons

AllU.S.servicepersonnelassignedtounitsneartheKhamisiyahdemolitionactivityshouldbenotifiedandencouragedtoenrollinVA'sPersianGulfHealthRegistryorDOD'sComprehensiveClinicalEvaluationProgram.IndeterminingtheextentofpossiblechemicalwarfareagentexposureatKhamisiyahandanyothersitesthatfutureinvestigationsuncover,thegovernmentshouldusethebesttheoreticalandpracticalassessmenttoolsavailable.TheCommitteerecognizesthelargenumberofvariablesthatcanaffecttheoutcomeofanydetermination,butidentifiesthefollowingasessentialprinciples:

Whereobjective,unrebuttedevidencesuggeststhereleaseofchemicalwarfareagentsinthevicinityofU.S.troops,everyeffortshouldbemadetoidentifythesourceoftheagentandtomodel

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thedownwindfootprintofthepotentialdistributionofagentatthegeneralpopulationexposurelevel(orlowerthreshold,ifappropriate);

Whenadownwindfootprintisestablished,aconservative,presumptive-exposureareashouldbedefinedthatreflectstheuncertaintiesofthemodelingeffort.Thepresumptive-exposureareashould,ataminimum,includeallsiteswithinacirclethathasaradiusequaltothelengthofthedownwindfootprint;and

Troopswithinthepresumptive-exposureareashouldbenotifiedandencouragedtoenrollintheCCEPorRegistry.

AllreportsofpositiveM256kitsandFoxdetectionsmustbethoroughlyinvestigated.Whereunitlogsrecordpositivedetectionsbyeithertypeofequipment,membersofthatunitshouldbenotifiedandencouragedtoenrollinVA'sPersianGulfHealthRegistryorDOD'sComprehensiveClinicalEvaluationProgram.

Toensurecredibilityandthoroughness,furtherinvestigationofpossiblechemicalorbiologicalwarfareagentexposuresduringtheGulfWarshouldbeconductedbyagroupindependentofDOD.Opennessinoversightactivitiesincludingpublicaccesstoinformationandveteranparticipation-publicnoticeofmeetings,opportunityforpubliccomment,andregularreportingareessential.Fullpublicaccountabilityiscritical.

Coordination

APresidentialReviewDirective(PRD)shouldbeissuedtoinstructtheNationalScienceandTechnologyCounciltodevelopaninteragencyplantoaddresshealthpreparednessforandreadjustmentofveteransandfamiliesafterfutureconflictsandpeacekeepingmissions.ThePresident'sCommitteeofAdvisorsonScienceandTechnologyandothernongovernmentalexperts,asappropriate,shouldbeaskedtoreviewtheplan12monthsafterthePRDisissued

andagainat18monthstoensurenationalexpertiseisbroughttobearontheseissues.

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AppendixBHealthConsequencesofServiceDuringthePersianGulfWar:InitialFindingsandRecommendationsforImmediateAction*

FINDINGSANDRECOMMENDATIONS

Inthisreport,theIOMCommitteehasattemptedtohighlightissueswebelievewouldbenefitfromimmediateaction.Inreviewingthelargevolumeofdocumentsandtheprogressofresearchcurrentlyunderway,wehaveidentifiedareasthatneedpromptattention.AsthescopeandextentofhealthproblemsofPersianGulfveteranshaveappearedtoexpand,thesocialresponsealsohasgrown.Thecommitteebelievesthatthishasresultedinafragmentedattempttosolvetheseproblems.Thuswebelievethatsustained,coordinated,andseriouseffortsmustbemadeintheneartermtofocusboththemedical,social,andresearchresponseoftheGovernmentandofindividualsandresearchers.Hence,thefindingsandrecommendationsthatfollowareofferedwiththeintenttofocusandsharpenthedebate,andtoimprovethequalityofthedata,andthereby,scientificinference.Finally,wehopetoimpactinapositivewaythehealthinpersonswhoservedinthePersianGulfWar,aswellasinthosewhomayfollowinothermilitaryencounters.

Recommendationsforimmediateactionfollowbasedonthefindingspresentedhereandthebackgroundinformationpresentedinthenextchapter.Therecommendationsaretobeviewedasindependent,andarenotpresentedinanypriorityorderwithincategories.Therecommendationsaredividedinto

*ThisappendixwasexcerptedfromtheInstituteofMedicinereport

HealthConsequencesofServiceDuringthePersianGulfWar:InitialFindingsandRecommendationsforImmediateAction,Washington,D.C.:NationalAcademyPress,1995.

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threecategories:dataanddatabases,coordination/process,andconsiderationsofstudydesignneeds.

DATAANDDATABASES

FindingI

TheVAPersianGulfHealthRegistryisnotapopulationdatabaseandisnotadministereduniformly,therefore,itcannotservethepurposesofresearchintotheetiologyortreatmentofpossiblehealthproblems.TheCommitteerecognizesthatcertaintabulateddescriptionsofaffectedpersonsmaylegitimatelybecarriedoutforreasonsotherthanthegenerationofscientificdata.Specifically,theremaybemedicalreasonsforcollectinginformationaboutpatientswithcertainkindsofproblems,especiallydiagnosticproblems,particularlyinmedicalsettingswheretheinformationmaybesubjectedtomoreintensescrutiny.AnexampleistheestablishmentoftheVAreferralcentersforGulfWarveterans.Sincealimitednumberofveteranshavebeenreferredtothesecenters,andbecausethesampleisself-selected,theCommitteeconcludesthatitisunlikelythatproductivescientificresearch(especiallyofanepidemiologicalnature)caneverbebasedonthedatageneratedbythereferralcentersorthehealthregistryascurrentlyorganized.

Recommendations

TheVAPersianGulfHealthRegistryshouldbelimitedandspecifictogatheringinformationtodeterminethetypesofconditionsreported.TheroleofthisregistryshouldbeclearlydefinedasameansforidentifyingandreportingillnessesamongGulfWarveteranswithconcernsabouttheirhealth.ThereshouldbeeffortstoimplementqualitycontrolandstandardizationofdatacollectedbytheregistryfromotherVAfacilities.TheVAregistrydatashouldnotbepromotedordescribedasameanstodetermineprevalenceestimatesoridentify

theetiologyofadisease,butshouldbereviewedpromptlyforenrollmenttrendsandpotentialsentinelevents.

TheVAshouldimprovepublicityregardingtheexistenceofthePersianGulfHealthRegistry,andencourageallconcernedPGWveteranstoberegistered.

Wherepossiblethereferralcenters,standardizedprotocolshouldbeusedineachVAfacility.

ThetimelinessofdatareceivedfromtheVAMedicalCenters(VAMC)tobeenteredintothePGHealthRegistrydatabaseneedstobeimproved.

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Finding2

NosinglecomprehensivedatasystemexiststhatenablesresearcherstotrackthehealthofPersianGulfWarveteransbothwhileonactivedutyandafterseparation.Asaresult,itisnotpossibletoconductresearchanddeterminethemorbidityandmortalityexperienceofthispopulation.AlthoughboththeVAandtheDoDhavemedicalrecordssystemsinplace,theyareinadequateandunlinked.Thislackofasingledatasystemisahindrancetoresearchconcerningdelayedhealtheffects,bothforPersianGulfveteransandforthoseservinginfutureencounters.

Recommendation

TheVicePresidentoftheUnitedStatesshouldchairacommitteecomposedofrepresentativesfromHHS,DoD,andVAtodeviseaplantolinkdatasystemsonhealthoutcomeswiththedevelopmentofstandardizedhealthforms,theabilitytoaccessinformationrapidly,andanorganizedsystemofrecordsforrapidentryintothedatasystem.

Finding3

ThecharacteristicsofthepopulationatriskarecriticaltoanydefinitivestudiesofGulfWarhealtheffects.TheDoDhastakentheproperstepstoenumerateanddescribethispopulationthatwillbepartoftheplanned,butyetincomplete,ArmyGeographicalInformationSystemmodel.

Recommendations

TheDoDregistryneedstobecompletedasquicklyandaccuratelyaspossible.

TheSecretariesofDoDandVAshoulddevelopasingleserviceconnectedhealthrecord,foreachpresentactivedutyand

formerservicemember.Allhealthdataentriesshouldberecordedinthissinglerecordfortheindividual.

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COORDINATION/PROCESS

Finding4

Thecommitteehasnotedwithinterestandsomeconcernthewidevarietyofdisciplinesandexpertiseamongpersonswhohaveconsideredpossiblecausesofamysteryillness.Ithasappearedtothecommitteethatsomeofthesepersonsandorganizationsaresimplynotqualifiedtodrawreasonedscientificconclusions,ortoimplementthoseconclusionsbymeansofspecificmedicalintervention.Theremaybesubstantialriskfrominappropriateinterventionsbecauseofadversereactionstodrugs,developmentofresistantstrainsofmicroorganisms,orespeciallythediversionofattentionawayfrommoreorthodoxdiagnosesandtreatmentsthatholdsomepromiseofrelieffromsymptomsofa''mysteryillness."

Recommendation

Decisionstoprovidefunding,toreferpatients,ortochangeusualoperatingproceduresforprovidingfinancialsupportshouldbebasedonmoresolidscientificbasesthanhassometimesbeenevidentinpriorresourceallocation.Fundingshouldbesubjecttoexternalpeerreviewandapproval.

Finding5

TherearedozensofstudiesofPGWhealtheffectsunderwaynow,andmanyothersarebeinginitiated.Severaleffortsappeartoberedundant,yetthereareclearlygapswhereresearcheffortsarenecessary.Initsfinalreport,theIOMCommitteewillrecommendsomeadditionalspecificresearchprojects.

Presently,thetotalnumberofundiagnosedconditionsisunknownbecausethedataeitherareinsufficientlyunderstoodorunavailable.Datathatareavailablearefragmented,managedbydifferentmethods

indifferentagencies,andbasedonawidevarietyofunconnectedrationales,frombothmilitaryandcivilianinstitutions.Manyresearcheffortsshould,butdonot,relyonacommonsetofdataresources.Becausesomanyunansweredquestionsremainconcerningmulti-systemetiologiesthathavebeenproposedtoexplainundiagnosedsignsandsymptoms,allfutureaswellascurrentevaluationsmustensurethatfindingscanbereconciledacrossstudies.

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Recommendations

ThePersianGulfVeteransCoordinatingBoard(chairedbytheSecretariesofVA,DoD,HHS)shouldactivelycoordinateallstudiesdevelopedfromanynewinitiativesthatreceivefederalfunding,topreventunnecessaryduplicationandtoassurethathighpriorityrecommendedstudiesbeconducted.Thesestudiesshouldundergoappropriateexternalpeerreviewbefore,during,andafterdatacollectionandanalysis.

MorestaffshouldbeassignedbythePersianGulfVeteransCoordinatingBoardinordertomonitor,collect,assemble,andmakeaccessiblewhenappropriateallrelevantrequestedemergingdatafromstudiesnowunderway,andmakeperiodicreportstotheappropriatefederaloversightauthority.

Eachnewinitiativeshouldbeevaluatedinthecontextofwhatitcancontribute.Thatis,eachnewstudyshouldaddsomethingofvaluetotheinformationalreadybeingobtainedoraccumulated.

CONSIDERATIONSOFSTUDYDESIGNNEEDS

Finding6

Todate,moststudiesofPGWveteranshavebeenpiecemeal-onemilitaryunithere,onecollectionofvolunteerswithsomeproblemthere,etc.But,someofthesestudieshaveseveralfundamentalproblems.Theyarenecessarilyincomplete,theyusuallylackpropercontrols,theyarehardtogeneralize,theyaresubjecttogravestatisticalproblemsbecauseofpost-hochypothesesandmultiplecomparisons,andwhereaneffecttrulyexiststheytendtohavelowstatisticalpowertodetectadifference.Thus,bitsandpiecesarenotlikelytoansweranycriticalquestions.Thecommitteerecognizesthataninitialefforttosurveyasampleofveteransisunderway,butmore

isneeded.

Overall,therehasbeenabroadandseriouslackofadequateattentiontothedesignofindividualstudies,andevenmoreseriously,thescopeandorganizationofanappropriatecollectionofstudies,eachfocusedontheresolutionofaspecificquestion.Thecommitteeregardsthisasagrave,thoughunderstandablefailure.Expertsinresearchdesigncanandshouldworkshouldertoshoulderwithexpertsinthesubjectmatterofeachindividualstudy;thisisparticularlytrueforworkinepidemiology.Abroaderviewofthewholecollectionofstudies,includinginputfromexpertsinsubjectmatterandinresearchmethods,personsknowledgeableaboutdatasourcesandmedicalcaresystems,andthosewithgeneralappreciationofpublicconcernsandpublicpolicy,hasbeenconspicuouslylacking.Webelievethatgoodstudiescouldbedone,butthattheywillrequiresubstantialinputfromexpertsinepidemiologicalmethods.

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Recommendations

TheVAandDoDshoulddeterminethespecificresearchquestionsthatneedtobeanswered.Epidemiologicstudiesshouldbedesignedwiththeobjectiveofansweringthesequestionsgiventheinputofexpertsinepidemiologicresearchmethodsanddataanalysis,alongwiththeinputofexpertsinthesubjectmatterareastobeinvestigated.

Toobtaindataonsymptomprevalence,healthstatus,anddiagnoseddisease,theSecretariesofDoDandVAshouldcollaboratetoconductapopulation-basedsurveyofpersonswhoservedinthePG,andofPG-eraservicepersonnel.Thestudyshouldbedesignedtoallowforadequatecomparisonsofoutcomebysex,servicebranch,andrank,withoversamplingamongcertainsubgroupstoallowforanalysis.TheIOMcommitteeiswillingtocommentonandassistinthestudydesign.Anevaluationofthefeasibilityandneedforalongitudinalstudyshouldtakeplacecoincidentwiththisnationalsurvey.

Finding7

Initialcharacterizationsofsmokeandunburnedcontaminantsfromtheoilwellfiresandothersourcesarenotadequate,norhavethedataavailablebeenreducedtoaformatusablefordrawingconclusionsorconductinghealthstudies.Considerabledataexistfromawidenumberofsources,buttheyhavenotbeencompiledoranalyzedinanyorganizedorefficientway.Forexample,leadlevelsthatwouldcauseacutetoxicityhavebeenreported;however,questionsaboutthevalidityofthesereportshavenotbeenadequatelyaddressed.

Recommendations

DoDshouldassembleandorganizethesedatafromallsourcesforevaluationbytheIOMcommittee.

DoDshouldconductastudythatsimulatesexposureintentsheated

bydieselfuel,withcompositionsimilartothatusedinthePG.FuelsandconditionsshouldsimulateascloselyaspossibletheconditionsthatexistedinthePG.Exposuretoleadanditspossibleeffectsshouldbeexploredfurther.ThecommitteereviewedworkdoneindicatingthatsomepersonnelintheGulfhadleadlevelsconsistentwithacuteintoxication.Thusininvestigatingleadexposure,specialattentionshouldbegiventoanyhistoryofabdominalpainormentaldisorders.

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Finding8

Asacknowledgedbytheinvestigator,theVAstudyofmortalityinthePGveteranpopulationisofinsufficientdurationtoobserveahigherrateofdeaththanwouldbeexpectedfromchronicdiseaseoutcomes.

Recommendation

TheVAshouldplanandprovidesupportforitsmortalitystudytocontinueinthefutureinordertopermitthedetectionandinvestigationoflong-termmortalityfromchronicdisease.

Finding9

Althoughinfertility,unrecognizedandrecognizedpregnancyloss,prematuredelivery,fetalgrowthretardation,birthdefects,andabnormaldevelopmentareallcomponentsofreproductivehealth,studiesandsurveillanceeffortstodatehavefocusedprimarilyonbirthdefects,fetalandneonataldeaths,andlowbirthweight.Adversereproductiveeffectscanbemediatedthroughmalesaswellasfemales,soitisimportanttostudyexposuresofbothparents.InformationoninfertilityandmiscarriagehasnotbeenincludedintheVAHealthRegistryefforts.Moreover,dataonoutcomesareavailableonlyfromasingleclusterstudyinMississippiandtheArmySurgeonGeneral'spreliminarydataevaluation.DoDlaunchedrecentlyastudyofreproductivehealth,andtheVAandDoDclinicalevaluationprotocolsprovidesomesurveillanceofinfertility,miscarriage,birthdefects,andinfantdeaths.

Thedesignofscientificstudiestoaddressreproductiveriskassociatedwithenvironmentalexposuresiscomplex.Avarietyofendpointsmayoccurthroughoutthecontinuumbeginningwithfertility,throughintrauterine,peripartum,andneonataldevelopment,andcontinuingwitheffectsmanifestedonlylaterinchildhood.Additionally,sophisticatedexpertiseisrequiredtodocumentenvironmental

exposuresastheetiologyforadversepregnancyexperience.Thereareresearchgroupsinsomeacademicandfederalsettingsthatcould,ifdeemedappropriate,conductsuchcomplexresearch.

Recommendations

VAandDoDshouldincludereproductiveoutcomesamongthearrayofhealthendpointsinsurveillanceprogramsbasedonmedicalrecordsandindividualquestionnaires.Medicalrecords,suchasthosetobeincludedintheSeabees

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reproductivestudyandtheDoDreproductivehealthstudy,wouldbesuitabletoascertainstillbirth,lowbirthweight,pretermdelivery,andmajorbirthdefects.QuestionnairessuchasthoseadministeredfortheVAhealthregistryexamcould,inaddition,addressquestionsofinfertilityandclinicallyrecognizedmiscarriage.

ThePersianGulfVeteransCoordinatingBoardshouldconsiderspecificexposuresthataremostlikelytoadverselyaffectreproductivehealthofwomen,menorboth,distinguishingbetweenagentsthatwouldaffectreproductivehealthonlyifexposureoccurredatoraroundthetimeofcriticalperiodsduringpregnancyversusthosethatmighthaveeffectsthatwouldpersistafterthecessationofexposure.Asspecifichypotheseslinkingexposureandreproductiveoutcomesareidentified,studiesthataresuitabletoprovidingmoreconclusiveresultsforthoseassociationsshouldbedesigned.

ThePersianGulfVeteransCoordinatingBoardshouldremainalertbutskepticalaboutclusterstudiessuchasthoseunderwayinMississippi.Studiesofthiskindmaybevaluableinsuggestingetiologichypotheses;however,theyhavelittlepromiseforresolvingquestionsaboutlinksbetweenexperiencesinthePersianGulfandreproductivehealth.Population-basedstudiesofreproductivehealthoutcomesareessentialtoresolvequestionsofeffectsofPersianGulfWarservice.

Finding10

WomenwhodidnotrealizethattheywerepregnantatthetimeweredeployedtotheGulf;othersbecamepregnantduringtheirserviceintheGulf.Thesegroupsofwomenmayhavebeenexposedtosubstancespotentiallyhazardoustothemselvesandtotheirunbornbabies.Astudywouldpermitcomparisonsofbirthoutcomesandpotentialadversehealtheffectsonwomenexposedatdifferenttimesintheirpregnancies.

Recommendation

ThePersianGulfVeteransCoordinatingBoardshouldconductastudytocomparewomendeployedtothePGwhowereorwhobecamepregnantatanytimeduringthePersianGulfWarwithanappropriategroupofotherwomenwhowerepregnant,butdidnotserveinthePGW,toevaluatepotentialadversehealthoutcomestothemotherorchild.Thisstudyshouldonlybedoneifasufficientnumberofwomencanbeidentified.Effortsshouldbemadetogatherexposureinformationrelevanttoserviceatpotentiallyhigh-risktimesduringgestation.

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Finding11

Thecommitteehasbecomeawarethatrostersexistthatcontainthenamesofpersonsvaccinatedwithanthraxandbotulinumtoxoid.

Recommendation

DoDshouldmaintainitslistsofthosereceivinganthraxandbotulinumvaccinesforthepurposeofconductingfollow-upstudiesonthesecohorts.

Finding12

Troopsweregivenpacketsofpyridostigminebromide(PB)pillstobetakenasaprophylactictothethreatofnerveagentexposure,atthedirectionoftheircommandingofficer.PBbyitself,inrecommendeddoses,isasafedrug.Additionally,DEET(N,N-diethyl-m-toluamide)andpermethrinwereusedbythetroopstopreventinsectbites.Thereissomeinformationaboutthepossiblelong-termtoxicitytohumansofDEETabsorbedthroughtheskin;howeverthereappearstobelittleornoinformationaboutdermalabsorptionofpermethrinfromresiduesleftonclothing,bedding,orelsewhere.Althoughpermethrinisgenerallynotappliedtoskin,animalstudieshaveshownthatpermethrinistransferredfromclothtoskin,andsubsequentlyabsorbed(NRC,1994).ThereislittleinformationabouthowPB,DEET,andpermethrinmightinteract;interactionsamongthesecompoundsarepossibleandareinadequatelystudied.

Recommendation

StudiesareneededtoresolveuncertaintiesaboutwhetherPB,DEET,andpermethrinhaveadditiveorsynergisticeffects.Unsubstantiatedsuggestionsthattheymayhavechronicneurotoxiceffectsneedtobetestedincarefullycontrolledstudiesinappropriateanimalmodels.AppropriatelaboratoryanimalstudiesofinteractionsbetweenDEET,

PB,andpermethrinshouldbeconducted.

Finding13

Reportedsymptomssuggestiveofvisceralleishmanialinfectionsincludefever,chronicfatigue,malaise,cough,intermittentdiarrhea,abdominalpain,weightloss,anemia,lymphadenopathy,andsplenomegaly.Thecommitteehas

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consideredtwoaspectsofexposuretoL.tropicaandresultinginfectionwithleishmania:theoccurrenceofeithercutaneousorvisceralleishmaniasis;andthepossibilitythatsomecomponentofthepoorlydefinedillnessreferredtoas"GulfWarSyndrome"mayresultfromleishmaniainfection.

Leishmaniasis(L.tropica)inPGWveteranshasbeenevaluatedinsomeverylimitedclinicalstudies,butnotinepidemiologicalstudies.TheclinicalstudiessuggestthatthecomplexofsymptomsinthePGWveteransdiagnosedwithleishmaniasisdiffersfromwhathasbeendescribedintheliteratureforotherformsofleishmaniasis.Amajorlimitationtofurtherinvestigationanddiagnosisofleishmaniasisisthelackofaninformativeserologictestorothereasytousescreeningtests.

Recommendations

TheDoDJointTechnologyCoordinationGroupIIhasresearchresponsibilitiesforinfectiousdiseasesofmilitaryimportanceandshouldgivehighprioritytothedevelopmentofascreeningapproachtobeusedunderfieldconditionsexpectedindeployment,andausefuldiagnostictestforL.tropica.Theboardalsoshouldreviewthestatusofleishmaniaresearch,withaviewtowardeitherdraftingarequestforproposalsfortestdevelopment,orthestructuredcoordinationofexistingactivities.

Allphysiciansshouldbenotifiedtolookforsymptomsthatareconsistentwithbothleishmaniainfectionandthosereportedas"GulfWarSyndrome"Clearinstructionsforfollow-upactionsshouldbewidelycommunicatedthroughthephysiciancommunity.VeteransofDesertStormshouldbenotifiedthatiftheyhavesymptomsthatmaysuggestviscerotropicleishmaniasistheyshouldbringthispossibilitytotheattentionofthestaffatanyfacilitywheretheyobtainanyhealthcare,whetheritisintheVAsystemornot.Thelattermaybe

particularlyimportantduetothepotentialforlong-termsurvivalofleishmaniainthehost.

Whenitbecomesfeasible,VA,DoD,orbothshouldconductanepidemiologicandseroepidemiologicstudyofleishmaniasisinPGWveteranspresentingsymptomsorconditionsandappropriatecontrols.Specialattentionshouldcenteronapossiblerelationbetweenleishmaniasisandthe"GulfWarSyndrome."

Finding14

TheecologyandepidemiologyofL.tropicaareinsufficientlystudied.Manyimportantquestionsremainunansweredconcerninghostspecies,vectors,andmeansoftransmissiontomilitarypersonnel.Thepossibleroleofdogsas

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reservoirsofdiseaseandtheexistenceofvectorsotherthansandfliesarequestionsthathavebeenraised.

Recommendations

DoDshouldcloselymonitorallinformationregardingecologicalandclinicalstudiesofL.tropicabeingconductedintheU.S.andabroad.

InternationalandU.S.researchersshouldbequeriedconcerninganyadvancesindiagnostictechniquesforidentifyingL.tropica.

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AppendixCHealthConsequencesofServiceDuringthePersianGulfWar:RecommendationsforResearchandInformationSystems*

CHARGETOTHECOMMITTEE:ITSFINDINGSANDRECOMMENDATIONS

Overview

InthischapterwesummarizethefindingsandprincipalrecommendationsoftheCommitteetoReviewtheHealthConsequencesofServiceDuringthePersianGulfWar(PGW).Mostofthefindingsarediscussedatgreaterlengthinthechaptersthatfollow.

Ourtaskwastorespondtothreespecificcharges.Eachfindingislinkedtoatleastoneofthecharges,andforeachwenotetheprincipalconnection.Recommendationsfolloweachofthefindings.Thecommitteewaschargedasfollows:

*ThesefindingsandrecommendationsweretakenfromtheInstituteofMedicinereport,HealthConsequencesofServiceDuringthePersianGulfWar:RecommendationsforResearchandInformationSystems,Washington,D.C.:NationalAcademyPress,1996.

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THECOMMITTEE'SCHARGE

Charge1

AssesstheeffectivenessofactionstakenbytheSecretaryofVeteransAffairsandtheSecretaryofDefensetocollectandmaintaininformationthatispotentiallyusefulforassessingthehealthconsequencesofmilitaryservicereferredtosubsection(a)[ofPL102-585,PersianGulf(PG)theaterofoperationsduringthePGW].

Thecommitteemakesfourrecommendations(recommendations13-16)inthisreportregardingthecollectionandmaintenanceofinformationthatispotentiallyusefulforassessingthehealthconsequencesofmilitaryserviceinthePGW.Theserecommendationssupportcompletionofcertaindatasets,promptreportingofresearchfindingsandsubmissionforpublicationinpeerreviewedjournals,strengthenedmedicalandepidemiologicresearchcapabilitiesofthearmedforces,andstrengtheningthedecision-makingprocessesforstudyselection.

Charge2

Makerecommendationsonmeansofimprovingthecollectionandmaintenanceofsuchinformation.

Thecommitteemakesfiverecommendations(recommendations1,4,and8-10)onthecollectionandmaintenanceofinformationonthehealthconsequencesofserviceinthePG.Wealsogiveconsiderableattentiontoinformationsystemsthatwouldbeusefulinfutureconflicts.TheserecommendationsarebasedlargelyonexperiencewithsystemsinplaceforthePGWthathaveshownsomegapsanddefectsthatcanberemedied.

Charge3

Makerecommendationsastowhetherthereis[a]soundscientificbasisfor

anepidemiologicstudyorstudiesofthehealthconsequencesofsuchservice,andiftherecommendationisthatthereis[a]soundscientificbasisforsuchastudyorstudies,thenatureofthestudyorstudies.

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Thecommitteebelievesthatthereisindeedasoundbasisforepidemiologicstudies,andeightrecommendationsfollow(recommendations2,3,5-7,and11-13).1However,thecommitteedoesnotrecommendanadditionalnationwideepidemiologicstudyofPGveterans,becausesuchastudyislikelytobeoflimitedscientificvalueatthistime.Thoselargestudiesthatarecurrentlyunderwayshouldbecompletedasquicklyaspossible,whilemeetinghighscientificstandards,includingahighresponserateandathoroughinvestigationofpotentialbiases,asrecommendedbelow.

FINDINGSANDRECOMMENDATIONS

Finding

Recentmilitarydeployments,especiallyinVietnamandinthePersianGulf,havedemonstratedthatconcernsaboutthehealthconsequencesofparticipationinmilitaryactionmayariselongafterdeploymenthasendedandthattheevaluationofthoseconcernsandtheprovisionofhealthcaretoaffectedpersonnelmaypresentformidablechallengesbothtoepidemiologistsandtomedicalcaregivers.Althoughsomeofthesechallengescanbeattributedtotheintrinsicdifficultyofevaluatingpoorlyunderstoodclustersofeventsthatwerenotamongtheexpectedconsequencesofcombatorofenvironmentalconditions,theyalsomaybeattributedinparttolimitationsofthesystemsusedtocollectandmanagedataregardingthehealthandservice-relatedexposuresofmilitarypersonnel.Nosystemofrecordkeepingcanbeexpectedtoprovidetheinformationneededtoaddresseveryunanticipatedresearchissue,includingthoseregardingthehealthconsequencesofmilitaryservice.Nevertheless,thecommitteehasidentifiedseveralpossibleimprovementsinthesystemsandpracticesforcollectinginformationonthehealthandservice-relatedexposuresofmilitarypersonnel.Suchchangeswouldincreasetheabilityofthemilitaryservicestopursueappropriateinvestigationsinthefuture.

Suchchangesalsowouldincreasethecapacityoftheservicestoevaluatetheefficacyofmobilization-supportinghealthservices(includingapproachesandmethodologiesfordiseasepreventionemployedbefore,during,andaftermobilization)andwouldaidinprovidingthebestpossiblemedicalcaretomilitaryservicepersonnelandveterans(Charge2).

Recommendation1.TheDepartmentofDefense(DoD),thebranchesofthearmedservices,andtheDepartmentofVeteransAffairs(DVA)

1Recommendation13hasbeencountedasapplicabletobothCharge1andCharge3,andthereforeappearswithboth.

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shouldcontinuetoworktogethertodevelop,fund,andstaffmedicalinformationsystemsthatincludeasingle,uniform,continuous,andretrievableelectronicmedicalrecordforeachserviceperson.Theuniformrecordshouldincludeeachrelevanthealthitem(includingbaselinepersonalriskfactors,everyinpatientandoutpatientmedicalcontact,andallhealth-relatedinterventions),allowlinkagetoexposureandotherdatasets,andhavethecapabilitytoincorporaterelevantmedicaldatafrombeyondDoDandDVAinstitutions(e.g.,U.S.PublicHealthServicefacilities,civilianmedicalproviders,andotherhealthcareinstitutions).Appropriateconsentandprotectionofindividualprivacymustbeconsideredforinformationobtainedandincluded.

Finding

ThenumberandvarietyofstudiesregardingconsequencesofthePGWarealreadyconsiderable.Todate,mosthealth-relatedstudiesspecificallyinvolvingPGWveteranshavefocusedonshort-termmentalhealthconsequencesofdeployment,theroleofcombatexposure,andotherstressorsexperiencedinthetheaterofoperationsand,toalesserextent,onproblemsrelatingtodemobilizationandreadjustmenttocivilianlifeamongreservistandNationalGuardpersonnel.Afewreportshaveincludedlimitedlongitudinalfollow-updataconcerningmenandwomenwhoservedinthePG.Importantinformationmaybegainedthroughlongerfollow-upofsomeofthesegroups,particularlysinceatleastoneofthesegroupswasfirsttoarriveinthetheater,andprecombatdataareavailable.Alsoneededarestudiesofriskfactorsinmoderndeploymentspredictiveofcombatstressreactions,posttraumaticstressdisorder(PTSD),andotherpsychiatricdisordersofmilitarypersonnelandveterans.Studiesrelevanttothetraumaofwarandtheensuingmentalhealthconsequencesshouldconcentratespecialattentiononimprovingeffortsinprevention,intervention,andfollow-up(Charge3).

Recommendation2.TheDoDandDVAshouldconductfurtherstudies,withappropriatestatisticalandepidemiologicalsupport,toidentifyriskfactorsforstress-relatedpsychiatricdisordersamongmilitarypersonnel(activeandreserve)andtodevelopbettermethodstobufferandamelioratethepsychiatricconsequencesofmoderntraining,deployment,combat,demobilization,andreturntodailyliving.

Recommendation3.StudiesbeingconductedbyDoDandDVAthathaveincludedlongitudinalfollow-upofthementalhealthofveterans

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whoservedinthePGshouldbesupportedwithcontinuedfollow-upafterappropriatepeerreviewofstudymethods.Follow-upinthesestudiesshouldbesufficienttoprovideatleastadecadeofinformationcomparingthementalhealthstatusofthosedeployedwiththosenotdeployed.

Finding

ThemilitarydominanceofU.S.forcesinthePGWincreasedtherelativesignificanceofphysicalandnaturalenvironmentalexposuresasimportantsourcesofpotentialmorbidityandmortality,comparedwithcombatinjuries.Thisislikelytorecurinfuturedeployments(Charge2).

Recommendation4.TheDoDshouldensurethatmilitarymedicalpreparednessfordeploymentsincludesdetailedattemptstomonitornaturalandman-madeenvironmentalexposuresandtoprepareforrapidresponse,earlyinvestigation,andaccuratedatacollection,whenpossible,onphysicalandnaturalenvironmentalexposuresthatareknownorpossibleinthespecifictheaterofoperations.

Finding

NationalGuardandreservecomponentpersonnelmaydiffersubstantiallyfromactivedutypersonnelinaverageage,leveloftraining,occupationalspecialties,familystatus,andreadinessfordeployment.Further,itisunclearwhethereitherpoliciesandproceduresorthemannerinwhichtheyareimplementeddiffersbetweenactivatedreserveorNationalGuardunitsandactivedutytroopsformobilization,deployment,demobilization,andreturn.Allofthesefactorsmayaffectthehealthconsequencesofdeployment(Charge3).

Recommendation5.Researchisneededtodeterminewhetherdifferencesinpersonalcharacteristicsordifferencesinpoliciesand

proceduresformobilization,deployment,demobilization,andreturnofreserves,NationalGuard,andregulartroopsareassociatedwithdifferentoradversehealthconsequences.Ifthereareassociations,strategiesnecessarytopreventorreducetheseadversehealtheffectsshouldbedeveloped.

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Finding

CompletedstudieshavedescribedthemortalityexperienceoftroopsdeployedtothePGduringtheperiodofdeploymentandinthe2-yearperiodafterdeployment.ThesestudieshavedocumentedaconsistentpatternofincreasedriskofdeathfromunintentionalinjuryforthecohortofdeployedtroopscomparedwiththosenotdeployedtothePG.However,deathratesfromdiseasewerenotsignificantlyincreased.ContinuedmonitoringandfurtherstudyofmortalityratesamongveteransofthePGWwillbeofvalueinassessingthelong-termhealthconsequencesofdeployment(Charge3).

Recommendation6.ThemortalityexperienceofPGveteransshouldcontinuetobemonitoredforaslongas30years,onaregularbasis,includingcomparisonswiththatofPG-eraveterans.(PG-eraveteranshavebeendefinedasthoseinmilitaryserviceatthetimeofthePGW,butassignedordeployedelsewhere.)Researchinvestigatorsshouldfocusonthereportedexcessmortalityfromunintentionalinjury,onmortalityfromspecificillnesses,andonevidenceofelevation(orreduction)intheriskofdeathfromothercauses.

Recommendation7.TheDVAshouldexertgreaterefforttoimproveunderstandingofthereasonsforexcessmortalityfromunintentionalinjury.Detailedevaluationisneededbeyonddeathcertificatedataconcerningthecircumstancessurroundingfatalinjurythroughmorefocusedcase-controlstudiestoidentifybothindividualriskfactorsandremediablecauses.

Finding

ThearmedservicesandtheDVAtogetheraredevelopingasharedbasicepidemiologicaldatasystem,theDefenseMedicalEpidemiologicalDatabase(DMED)(Charge2).

Recommendation8.TheDMEDsystemshouldbecontinued,

expandedasplanned,expeditedtodeveloptheproposedintegratedinformationmanagementsystem,linkedtootherkeysystems,andevaluatedregularly.

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Finding

ConsiderableefforthasbeendevotedbyDoDtothedevelopmentofaTroopExposureAssessmentModel(TEAM)fordescribingthePGWexperienceofveterans.ThishasincludedthecompletionofaninformationsystemdesignedtoestablishthegeographiclocationofeachunitfromJanuary15,1991,untiltheunitdepartedfromtheGulftheater.Thissystemhasthepotentialtobelinkedtodataonregionalenvironmentalconditionsbutwillnecessarilybedevoidofmostindividualdata(suchaspesticideexposureorindividualhealthriskfactors)(Charge2).

Recommendation9.TheDoDshouldcompletedevelopmentofinformationsystemstoexpeditiouslyanddirectlypinpointunitlocationsatahighlevelofdisaggregationinspaceandtime(thatis,finedetail)andtodocumentlocalenvironmentalconditions,includingappropriatedataqualitychecks,withdirectdataentryintothesystem.Thereislikelytobeaneedforasimilarinformationsystemduringandafteranyfutureconflict,andDoDshouldprepareandcontinuallyupdateplansforsuchanonpapersystem.Amanualforuseoftheinformationsystemsbyresearchinvestigatorsshouldbecompiled,withthestrengthsandlimitationsidentified.

Finding

Thepowerandcomplexityofanalysesbasedonspace-timegeographicalinformationsystem(GIS)datarequirecarefulattentiontodataqualityandthelimitsimposedbyvariousdataitems.Qualityimprovementandassessmentoflimitsarecontinuousprocessesanddependondetailedevaluationofdataneedsforspecificanalyticquestions(Charge2).

Recommendation10.ForeveryspecificquestionposedtothecurrentTEAM,DoDshouldassessthestrengthsandlimitationsoftheTEAM

asaresourceforevaluatingthehealthsignificanceofgeographicallydefinedexposuresoftroops,includingthoseinthePGWandthoseinconflictsthatmaydevelopinthefuture.EvaluationsandrecommendationsforpossiblemodificationoftheTEAMshouldbereportedtothePGCoordinatingBoard,ResearchWorkingGroup.

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Finding

GiventheunprecedentednumbersofwomenservinginthePG,especiallythoseinlargelynewroles,includingcombatsupport,itisimportanttospeciallyevaluatethehealthconsequencesandneedsforhealthservicesofwomenwhoservedinthePG.PreliminaryfindingsfromstudiesbeingconductedattheBostonVAMedicalCenter(VAMC)indicatethatadditionalresearchinthisareaisneeded.Additionalresearchisalsoneededonthehealtheffectsofhavingmaleandfemalepersonnelservetogetherincombatorunderthreatofcombat(Charge3).

Recommendation11.TheDoDandDVAshouldensurethatstudiesofthehealtheffectsofdeployment,includingeffectsonPGWveterans,includeevaluationofexposures,experiences,andsituationsofbothwomenandmen,withattentiontotheirage,priormilitaryservice,maritalandparentalstatus,andothergender-specificparameters.

Recommendation12.TheDoDandDVAshouldconductstudiesofthehealthconsequencesofassigningmenandwomentoservetogetherincombatorunderthethreatofenemyaction.Suchworkshouldbeundertakenwithafocusonpreventionandameliorationofanyaddedstresses.

Finding

Severalimportantstudiesarecurrentlyunderway.Worthwhiledataarebeingcollectedandprepared,andthestudiesshouldbecompletedpromptly,withthenecessarypersonnelandfundingtocollecttheadditionaldataneeded,toconductappropriateanalyses,andtoevaluatepotentialbiases.Findingsfromthesestudiesarelikelytoprovideleadsastowhetherornotadditionalresearchalongtheselinesisrequiredtoproducemorespecificfindings(Charges1and3).

TheNavalHealthResearchCenteratSanDiegohasundertakena

seriesofstudiesunderthegeneraltitleof''EpidemiologicStudiesofMorbidityAmongGulfWarVeterans:ASearchforEtiologicAgentsandRiskFactors."ThesestudiesholdpromiseforansweringsomeimportantquestionsaboutthehealthofPGWveteransafterdemobilizationandaboutthepossibilitythatveteransandtheirspousesmayexperienceanexcessriskofadversepregnancyoutcomesasaresultofserviceinthePGW.Thestudiesarebeingcarriedoutwithcare,excellentplanning,andproperpiloteffortstodeterminefeasibility.

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Uponcompletion,thesestudiesshouldprovideimportantguidanceconcerningwhetherveteranshaveexperiencedhospitalizationatratesinexcessoftheirnondeployedpeers,havedevelopedspecificsymptomsorillnessesrelatedtotheirPGWexperience,orhaveexperiencedrisksthathaveresultedinadversereproductiveoutcomesrelatedtotheirserviceintheGulf.

Recommendation13a.TheNavalHealthResearchstudiesinSanDiegoshouldbecompletedandresultspublishedasdesignedandscheduled.

AlthoughtherearesignificantproblemswiththeDVANationalHealthSurvey,theinvestigatorshavedesignedadditionalphasesofthestudythatwillbeimportanttocomplete.Thephysicalexaminationsandfollow-upofnonrespondentstothemailsurveywillbeanimportantsteptowarddescribingpotentialbiasesandevaluatingsignsandsymptomsofbothPGandPG-erastudyparticipants.

Recommendation13b.TheDVANationalHealthSurveyshouldbecompletedandresultspublishedasdesignedandscheduled.

TheDVA-DoDstudythatwasdesignedtoexaminepredictorsofenrollmentintheDVAPGHealthRegistry(PGHR)mayprovideusefulinformationastowhatobjectivelymeasurablefactorscontributetoselfselectionintotheregistry.Inadditiontotheproposedanalysisofassociationsamongdemographics,pasthealthexperiences,andhealthbehaviorsaspossiblepredictorsofenrollment,informationontheeligibilityofindividualsforhealthcare,aswellasthetypeofhealthcare,couldgenerateadditionalhypothesestobeinvestigated.

Recommendation13c.EvaluationofpredictorsofenrollmentintheDVAPGHRshouldbepromptlycompletedandresultspublished.Included,ifpossible,shouldbeinformationontypeofcarerequested,required,andreceived.

Finding

Thearmedforceshavehadsmallbuthigh-qualityandeffectivecapabilitiesinepidemiology.Recentcutbackshavereducedthesecapabilities,withpotentiallyseriouseffectsonbothmilitarypreparednessandthehealthcareofveterans.TheTheaterAreaMedicalLaboratory(TAML)isanexampleofhowspecialistscanrespondrapidlytopotentialhealthproblemsoftroopsdeployedinvariousareasof

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theworldandprovideimmediateandusefulinformationnecessarytomaintainthemilitaryreadinessofthearmedforces.Inaddition,well-trainedepidemiologistsandpreventivemedicinespecialistsarenecessaryforconductingtherelevantpopulation-basedepidemiologicstudies,withcomprehensiveexposureassessment,thathavethegreatestlikelihoodofbeinginformativeaboutthehealthconsequencesofanyfuturedeployment.Suchcapabilityshouldpermitstudiesthatextendbeyondthetimeofanindividual'sactivedutyserviceandthatarecapableofrespondingtoquestionsofdelayedeffectsthatmayemergeonlyyears,orevendecades,afteramilitaryoperation(Charge1).

Recommendation14.Theepidemiologiccapabilitiesofthearmedforcesshouldbestrengthenedratherthanreduced.Thecommandstructureshouldbekeptinformedaboutthereasonsforandtheresultsofthisrecommendationanditsrelevancetomilitarypreparednessandeffectiveness,andshouldbeencouragedtosupportappropriateepidemiologicworkinthetheaterofoperationsandinthepostdeploymentperiod.

Finding

MuchgoodworkonsymptomcomplexesandothermattersdiscussedinthisreporthasbeendonebyDoD,DVA,andtheircontractors.However,itisevidentfromthereferencescitedinthisreportthatmanyareinthe"grayliterature"-availabletothosewhoknowtheyexistandhowtoaskforthem,butnotpublishedintheopen,peer-reviewedscientificliteraturewheretheywillbefullyindexedandreadilyavailable,withsomeassurancethattheymeetatleastminimalscientificstandards.Eventhiscommittee,withthecontactsandexpertiseitdevelopedovertime,haddifficultyinidentifyingandobtainingsomeofthesereports.Thecommitteealsoisconcernedaboutthehighcostofmuchrecentresearchandthenecessityfor

maximizingthenation'soverallreturnonthatinvestment.Insummary,thecommitteebelievesthathealthrelatedresearchisnotfinalizeduntilitispublishedandreadilyaccessibleinpeer-reviewedjournals(Charge1).

Recommendation15.TheDoDandDVAshouldadoptapolicythatinternalandcontract-supportedreportsonhealthresearchwillbesubmittedforpublicationinthepeer-reviewedscientificliteratureinatimelymanner.

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Finding

SomeresearchdirectedtowardreportsofunexplainedillnessesafterthePGWwasflawedinthequestionsposed,populationsstudied,orresearchdesign.Webelievethatthesedefectscouldhavebeenidentifiedbeforeresearchprojectswerefundedifrequestsforproposalshadbeenannouncedgenerallyandhadbeenopentothescientificcommunityatlargeandiffullydevelopedresearchproposalshadbeenreviewedbypanelsofqualifiedexpertpeers.Someresearchwasannouncedandreviewedinthismanner,butmuchmorecouldbesotreated,tothebenefitofbothveteransandthepublic(Charge1).

Recommendation16.TheCongress,DVA,andDoDshouldadoptapolicythatunlesstherearewell-specified,openlystatedreasonstothecontrary,requestsforproposalsforresearchrelatedtounexplainedillnessesorotherneededhealth-relatedresearchwillbepubliclyannouncedandopentothescientificcommunityatlarge,thatproposalswillbereviewedbypanelsofappropriatelyqualifiedexperts,andthatfundingwillfollowtherecommendationsofthoseexperts.

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AppendixDEvaluationoftheU.S.DepartmentofDefensePersianGulfComprehensiveClinicalEvaluationProgram:OverallAssessmentandRecommendations*

1.)OVERALLASSESSMENTOFTHECCEPGOALSPROCEDURES:

TheComprehensiveClinicalEvaluationProgram(CCEP)clinicalprotocolisathorough,systematicapproachtothediagnosisofawidespectrumofdiseases.AspecificmedicaldiagnosisordiagnosescanbereachedformostpatientsbyusingtheCCEPprotocol.TheDepartmentofDefense(DoD)hasmadeconscientiouseffortstobuildconsistencyandqualityassuranceintothisprogramatthemanymedicaltreatmentfacilities(MTFs)andregionalmedicalcenters(RMCs)acrossthecountry.

Thecommitteeisimpressedwiththequalityofthedesignandtheefficiencyoftheimplementationoftheclinicalprotocol,theconsiderabledevotionofresourcestothisprogram,andtheremarkableamountofworkthathasbeenaccomplishedinayear.Thehighprofessionalstandards,commitment,anddiligenceofthephysiciansinvolvedintheCCEPattheRMCswerereadilyapparentatthethreecommitteemeetings.ThecommitteecommendstheDoDforitseffortstoprovidehigh-qualitymedicalcareintheCCEPandthesuccessthatithasachievedtodateindevelopingtheinfrastructurenecessarytoefficientlycontact,schedule,refer,andtrackthousandsofpatientsthroughthesystem.

Overall,thesystematic,comprehensivesetofclinicalpracticeguidelinessetforthintheCCEPareappropriate,andtheyhave

assistedphysiciansinthedeterminationofspecificdiagnosesforthousandsofpatientsacrossthecountry.

*ThisappendixisexcerptedfromtheInstituteofMedicinereport,EvaluationoftheU.S.DepartmentofDefensePersianGulfComprehensiveClinicalEvaluation,Washington,D.C.:NationalAcademyPress,1996.

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2.)GENERALRECOMMENDATIONSFORTHEIMPLEMENTATIONOFTHECCEP:

2.1.)ReferralsofPatientsfromPhaseItoPhaseIIoftheCCEP:

2.1.1.)StructureandrevisetheCCEPprotocolandlogisticstoallowthemajorityofpatientstoreceiveafinaldiagnosisbyPhaseI:

Currently,themajorityofpatientsdonotreceiveafinaldiagnosisuntilPhaseII,yetsomeofthesepatientshavestraightforwardmedicalproblems.TheCommitteerecommendsthatfinaldiagnosescouldbereachedinPhaseIifmorediagnosticresourcesaremadeavailable.ThismajorchangewouldrequiretheavailabilityofsubstantialnumbersofinternistsorfamilypractitionersatMTFstoperformcomprehensiveevaluations.Itwouldalsorequirebetter,moreconsistentexplanationstoMTFphysiciansaboutthepurposesandproceduresoftheCCEP.ItwouldrequireregionalmedicalcenterphysicianstoprovideadequatequalityassuranceofMTFwork-upsandtimelyfeedbacktoMTFproviders.

OnJanuary17,1995,theDoDadoptedthesesuggestionsbysettinggoalsthatabout80%ofpatientswouldreceiveadefinitivediagnosisatanMTFlevel.Forsomepatients,thischangehasrequiredspecialtyconsultationsattheMTF,aswellasadvicefromanRMCphysician.ThesechangesnecessitatedanenhancedqualitycontrolrolebytheRMCphysicianandprompt,appropriatefeedbacktotheMTFphysician.

2.1.2.)Curtaildiagnosticwork-upsinpatientsnotseriouslydisabledwithminorcomplaints:

Initially,patientswhodonotaccepttheirinitialdiagnosiscouldrequestacontinuedevaluationallthewaythroughPhaseII.The

Committeerecommendsthatdiagnosticwork-upsinpatientsnotseriouslydisabledbutwithminorcomplaintsshouldbecurtailed.Alternatively,ifaphysicianhasmadeadefinitivediagnosisandappropriatetreatmenthasbeengiven,theevaluationwouldbeconcluded.

OnJanuary17,1995,theDoDimplementedthesuggestionsthatreferraltoPhaseIIbemadeonthebasisoftheclinicaljudgmentoftheprimarycarephysician,andpatientswerenolongerpermittedtoselfrefertoanRMC.

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2.1.3.)Requireadditionaleffortstoprovidemorecareattheprimarycarelevel:

TheCommitteeencourageseffortstoprovidemorecareattheprimarycarelevel,becausetheywillenhancethecontinuityofcareandwillfostertheestablishmentofanongoingtherapeuticrelationship.

2.1.4.)Continuereferralofsubgroupsofpatientswhoseillnessesaredifficulttodiagnose:

PatientswhoseillnessesaredifficulttodiagnoseshouldcontinuetobereferredtoPhaseIIatanRMC.ThedecisiontorefertoPhaseIIshouldbebasedontheclinicaljudgmentoftheprimarycarephysician,which,inturn,wouldbedependentontheclarityofthepatient'sdiagnosesandthefeasibilityoftheproposedtreatmentprogramattheMTFlevel.TheDoDshouldcontinueitsgoalofenhancedaccessibilityofRMCphysicianstoallowregularconsultationswithMTFprimarycarephysiciansonpatientswithmorecomplexdiagnoses.

2.2.)SystematicGuidelinesforPsychiatricReferralsandAdequacyofPsychiatricResources:

2.2.1.)DevelopexplicitguidelinesfortheidentificationofPhaseIpatientswhowouldbenefitfromapsychiatricevaluation:

CCEPphysicianshavenotedtheneedforstandardizedguidelinesforscreening,assessing,evaluating,andtreatingpatients.SuchPhaseIguidelinesshouldbedevelopedtohelpensureadequatepsychiatricresourcesforboththeinitialevaluationandlong-termfollow-upcare.

2.2.2.)Alertprimarycarephysiciansaboutthehighprevalenceofpsychiatricdisorders:

TwomethodsthathavebeenproposedbyRMCphysicianstoexpeditetheschedulingofpsychiatricevaluationswouldbe(1)themore

frequentuseofcivilianpsychiatristsand(2)considerationofusingPh.D.levelpsychologists,aswellaspsychiatrists,whennecessary.

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3.)SPECIFICOBSERVATIONSOFANDRECOMMENDATIONSFORTHEIMPLEMENTATIONOFTHECCEP:

3.1.)AnalysisandInterpretationoftheCCEPResults:

3.1.1.)SymptomsanddiagnosesintheCCEPpopulation:

3.1.1.1.)NoevidencehasbeenfoundthattheDoDhasbeentryingtoavoidreachingasingleunifyingdiagnosis:

ThecommitteefoundnoevidencethattheDoDhasbeentryingtoavoidreachingasingle"unifying"diagnosiswhenaplausibleonewasavailable.A"unifying"diagnosisisdefinedhereasasinglediagnosisthatcouldexplainmostorallofapatient'ssymptoms.

3.1.1.2.)Signsandsymptomsinmanypatientscanbeexplainedbywell-recognizedconditions:

OneinterpretationoftheCCEPresultsisthatthesignsandsymptomsinmanypatientscanbeexplainedbywell-recognizedconditionsthatarereadilydiagnosableandtreatable.ThecommitteeconcludesthatthisisamorelikelyinterpretationthantheinterpretationthatahighproportionoftheCCEPpatientsaresufferingfromaunique,previouslyunknown"mysterydisease."

3.1.1.3.)Providemoredetailedinformationonspecificdiagnosesinfuturereports:

Byprovidingmoredetailedinformationonspecificdiagnosesinitsfuturereports,theDoDmighthelpcorrecttheimpressionsamongthegeneralpublicthatexistaboutthehighdegreeofprevalenceofa"mysterydisease"oranew,unique"PersianGulfSyndrome."

3.1.1.4.)Investigatethediagnosisinpatientswithdisabilityprocessingactions:

DisabilityprocessingactionsintheServices'PhysicalDisability

ProcessingSystemshavebeencompletedfor246ofthe10,020CCEPpatients.TheDoDhasnotprovidedanydataabouttheirdiagnosesortheirreasonsformedicalseparationfromthemilitary.ThecommitteerecommendsthattheDoDinvestigatethediagnosesinthisgroupofpatientsinfuturereports,aswellaswhetherornotthedisorderscouldhavebeencausedorexacerbatedbyserviceinthePersianGulf.

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3.1.1.5.)Don'tviewCCEPresultsasestimatesoftheprevalenceofdisabilityrelatedtoPersianGulfservice:

ManyotherindividualswhoservedinthePersianGulfhaveleftactiveserviceand,hence,arenoteligiblefortheDoD'sCCEP.SomeoftheseveteransmayhavedisabilitiesrelatedorunrelatedtotheirserviceinthePersianGulf,andthosewithdisabilitiesmightbemorelikelytohaveleftactiveservice.Forthesereasons,theCCEPresultsshouldnotbeviewedasestimatesoftheprevalenceofdisabilityrelatedtoPersianGulfservice.

3.1.2.)EvidenceofaNew,UniquePersianGulfSyndrome:

3.1.2.1.)ThereisalackofclinicalevidenceofauniquePersianGulfSyndrome:

ThecommitteeagreeswithDoDthatthereiscurrentlynoclinicalevidenceintheCCEPofapreviouslyunknown,seriousillnessamongPersianGulfveterans.IftherewereaneworuniqueillnessorsyndromeamongPersianGulfveteransthatcouldcauseseriousimpairmentinahighproportionofveteransatrisk,itwouldprobablybedetectableinthepopulationof10,020CCEPpatients.Ontheotherhand,ifanunknownillnessweremildoraffectedonlyasmallproportionofveteransatrisk,itmightnotbedetectableinacaseseries,nomatterhowlarge.

3.1.2.2.)SharetheentireCCEPdatasetwithqualifiedresearchersoutsideoftheDoD:

ThecommitteeencouragestheDoD'splantosharetheentireCCEPdatasetwithqualifiedresearchersoutsideoftheDoDwhomightbeabletoundertakethekindofresearchwiththemethodologicalsophisticationthattheidentificationofanewsyndromewouldrequire.

3.1.3.)PotentialRelationshipofIllnessesinCCEPPatientstoServiceinthePersianGulf:

3.1.3.1.)Discusstheissueofcausalityexplicitlyandunambiguouslyinitsfuturereports:

PhysiciansinvolvedwiththedevelopmentandtheadministrationoftheCCEPhave,invariouspublicpresentations,acknowledgedthatsomeCCEPpatientshavedevelopedillnessesthataredirectlyrelatedtotheirserviceinthePersianGulf.TherecentDoDreporton10,020CCEPparticipants,however,only

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touchesonthisissueindirectly.ThecommitteeencouragestheDoDtodiscusstheissueofcausalityexplicitlyandunambiguouslyinitsfuturereports.SuchadiscussionmighthelptoalleviatethecurrentclimateofconfusionandmistrustthatexistsamongsomePersianGulfveteransandthegeneralpublic.

3.1.3.2.)Determinethetimingoftheonsetofdisease:

ThecommitteerecommendsthattheDoDattempttodeterminethetimingoftheonsetofdisease,especiallyforpatientswhohavesignificantimpairments.ReviewofmilitaryorcivilianmedicalrecordsthatpredateenrollmentintheCCEPmayprovidecontemporaneousdocumentationoftheonsetofsymptomsinsomepatients,especiallyifthesymptomsareserious.Inaddition,itisimportanttodeterminewhetherserviceinthePersianGulfhascontributedtotheexacerbationofpreexistingdiseasesinsomeCCEPpatients.

3.1.4.)ComparisonoftheCCEPPopulationwithOtherPopulations:

3.1.4.1.)Becautiousaboutcomparisonwithotherpopulations:

Initsmostrecentreport,theDoDcomparesthesymptomsanddiagnosesintheCCEPpopulationwiththesymptomsanddiagnosesinseveralcommunity-basedandclinicallybasedpopulations.Inthecommittee'sview,interpretationsbasedoncomparisonswithotherpopulationsshouldbemadewithgreatcautionandonlywiththeexplicitrecognitionofthelimitationsoftheCCEPasaself-selectedcaseseries.TheCCEPwasnotdesignedtoanswerepidemiologicalquestions,suchashowthefrequenciesofcertaindiagnosescomparebetweentheCCEPpopulationandacontrolpopulation.Instead,itwasdesignedasamedicalevaluationandtreatmentprogram.Indeed,theresearchaimsoftheCCEPdonotappeartobestatedexplicitly,nordoesthereappeartobeaconcreteepidemiologicalstudyplan.

Withoutresearchhypotheses,itisnotpossibletojudgewhetheranyparticularcomparisongroupisappropriate.Eachindividualpopulationshouldbedescribedtopreventconfusion.

3.1.4.2.)It'sdifficulttoestablishcausalrelationshipsbyrelyingonCCEPdataalone:

Itwouldbeextremelydifficulttoestablishcausalrelationshipsortoidentifyandcharacterizeanew"PersianGulfSyndrome"definitivelybyrelyingondatafromtheCCEPalone.Thelatitude

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permittedintheclinicalexaminationprogramconflictswiththerigornecessarytoansweranepidemiologicalquestion.

3.1.4.3.)ConsidertheCCEPdatatohavehighclinicalutility:

TheCCEPdatadohaveconsiderableclinicalutility,andtheycouldbeusedtoaddressmanyimportantquestionsfromadescriptiveperspective.Manycaseseriescouldbederivedfromthesedata.Inaddition,theresultsoftheclinicalexamscouldprovideguidanceintheselectionofresearchquestionsandinthedesignoffutureepidemiologicalresearch.TheCCEPfindingscouldbeusedtogenerateepidemiologicalquestionsonothertypesofdiseasesthataremuchmorefrequentintheCCEPpopulation,suchasmusculoskeletaldiseases.

3.2.)SpecificMedicalDiagnosis:

3.2.1.)PsychiatricConditions:

3.2.1.1.)Makepatientsawareofpsychiatricconditionsandtheirprevalenceandmorbidity:

Patientsneedtounderstandthatpsychiatricconditionsanddisordersarerealdiseasesthatcauserealsymptomsandthatdiagnosesaremadewithobjectivecriteriaandarenotmerely''labels"appliedbecausephysicalabnormalitieswerenotfound.TheCCEPpatients,aswellastheirprimarycarephysicians,alsoneedtounderstandtheprevalenceofandtheconcomitantmorbiditythatresultfrompsychiatricdisordersinthegeneralpopulation(majordepression,forexample).Finally,theCCEPpatientsneedtobeawarethateffectivetreatmentsthatactuallyamelioratesymptomsexistformanyofthesedisorders.

3.2.1.2.)Emphasizeeffectsanddiagnosisofpsychosocialstressors:

Initsfuturereports,theDoDisencouragedtoemphasizethat

psychosocialstressorscanproducephysicalandpsychologicaleffectsthatareasrealandpotentiallydevastatingasphysical,chemical,orbiologicalstressors.TheDoDshouldalsoemphasizethatthorougheffortstodiagnosepsychiatricconditionsintheCCEPpopulationmayleadtoappropriate,successfultreatments.

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3.2.1.3.)IdentifypeoplewithriskofdevelopingdepressionorPost-TraumaticStressDisorder(PTSD):

ThecommitteeisparticularlyconcernedabouttheCCEPpatientswhohavedevelopedorwhoareatriskofdevelopingmajordepressionorPTSD.Thesepeopleneedtobeidentifiedandprovidedwithsomeformofpreventiveintervention.

3.2.1.4.)Improvestandardizationofpsychiatricevaluations:

ThecommitteerecommendsthattheDoDconsidermethodsofimprovingthestandardizationofthepsychiatricevaluationsintheCCEP.TheDoDshouldconsiderestablishingdetailedguidelinesforthepsychiatricevaluationsandshouldattempttoobtaingreaterstandardizationoftheseevaluationsamongthevarioushospitalsacrossthecountry.Theseguidelinescouldprovidesuggestedproceduresfortheuseofselectedself-reportinstrumentsfortheassessmentofthemostcommonlydiagnoseddisorders,aswellasproceduresformorein-depthstructuredclinicalinterviewswhenindicated.

3.2.1.5.)Documentandinvestigatetheonsetandcourseofsymptomsandpsychosocialstressors:

Itwouldbeespeciallyimportanttodocumenttheonsetandcourseofsymptomsandtoinvestigatetheirpossiblelinkwithpsychosocialstressorsassociatedwithmobilizationandreturnhome,aswellaswithservice-relatedexposuresinthePersianGulfregion.ThisassessmentwouldrequireanadditionalsetofquestionstosupplementthequestionnairecurrentlyusedinPhaseIoftheCCEP.Thethoroughassessmentofpsychosocialstressorsisessentialinformationfortreatmentplanningforpatientswithcomplex,chronicsymptoms.

3.2.1.6.)Standardizeneuropsychologicalevaluations:

Standardizationoftheneuropsychologicalevaluationsisarelatedconcern.Theneuropsychologicalmethodsvaryfrompencilandpapertestingatsomesitestocomputer-administeredtestingatothersites.Onemethodofachievingabetterconsensusistoconveneameetingattendedbyonepsychiatristandoneneuropsychologistfromeachcentertoattempttostandardizetheirmethods.

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3.2.1.7.)Standardizeclassificationandcodingofdiseases:

InadditiontothestandardizationofpsychiatricevaluationsintheCCEP,theclassificationandcodingofthesediseasesshouldalsobestandardized.

3.2.1.8.)Documentheadachecategoriesdifferently:

TheclassificationofdifferenttypesofheadachesintothreeseparatecategoriesmaybeconsistentwithICD-9codingrules,buttheDoDshouldalsoreportaspecialtabulationthatcombinesallheadachesintoonegroup.

3.2.1.9.)Addexplicitwritteninstructiononmedicalrecordkeepingandcoding:

MoreexplicitwritteninstructionscouldbeaddedtotheCCEPguidelinestohelppreventthemostfrequentproblemsfoundinthemedicalrecordkeepingandcoding.Committeecommentsaboutinconsistenciesaremainlyaimedatthequalitycontrolnecessaryforaccuratereportingofsummarydataratherthanatthequalityofthemedicalcareitself.

3.2.1.10.)Expanddiscussionofpsychologicalstressors:

DoDshouldconsiderexpandingdiscussionofthepsychologicalstressorsthatwerepresentduringthePersianGulfWar.

3.2.1.11.)UtilizeresultsofongoingstudiestoreviseCCEP:

ItispossiblethattheDoDwillbeabletousetheresultsofongoingepidemiologicstudiesonpsychiatricconditionstorevisetheCCEP,thatis,torevisethestandardizedquestionnairesortoaddordeletetargetedlabtestsorspecialtyconsultations.Inaddition,theCCEPcliniciansmaybeabletoutilizetheseresultsinthecounselingandtreatmentoftheirpatients.Theseresultsmayalsobeusefulforthe

DoDinitsplanningtominimizetheeffectsofpsychosocialstressorsinfuturedeploymentsthroughtheuseofpreventivemedicineinterventions.

3.2.2.)MusculoskeletalConditions:

3.2.2.1.)Providemoredetailsofdiagnosticcategorizationofmusculoskeletalconditions:

ThedraftandfinalDoDreportson10,020CCEPpatientsdonotprovideadequatedetailsfortheIOMcommitteetomakeathoroughevaluationofthediagnosticcategorizationofmusculoskeletal

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conditions.Moreexplanationaboutthediagnosticaspectsofthesemusculoskeletalconditionswouldbeuseful,forexample,informationonsingle-jointinvolvementversusmultijointconditionsorarticularversusnon-articularconditions.Inaddition,detailsondiseaseseverityanddiseaseactivitywouldbeuseful.

3.2.2.2.)Placemoreemphasisonmusculoskeletalconditions:

TheDoDandtheDVAshouldconsiderplacingmoreemphasisonresearchonmusculoskeletalconditions,sincethesearethemostprevalentdisordersamongtheCCEPpopulations.

3.2.3.)Signs,Symptoms,andIll-DefinedConditions:

3.2.3.1.)ClarifytypesofdisordersincludedintheICD-9category:

ThecommitteerecommendsthatinfuturereportstheDoDattempttoclarifythetypesofdisordersthatareincludedintheICD9categoryofsigns,symptoms,andill-definedconditions(SSIDC).Individualswiththesesigns,symptoms,andill-definedconditionsshouldbeevaluatedinarigorousmanner,justasindividualswithanyothersymptomsareevaluated.

3.2.4.)InfectiousDiseases:

3.2.4.1.)Infectiousdiseaseisnotafrequentcauseofseriousillness:

TheIOMcommitteeconcludesthatinfectiousdiseasesarenotafrequentcauseofseriousillnessintheCCEPpopulation.

3.2.4.2.)Veteransarenotlikelyafflictedwithsomepreviouslyunknownpathogen:

Onthebasisofthecurrentevidence,itisunlikelythatasignificantproportionofPersianGulfveteransareafflictedwithsomepreviouslyunknownpathogenthatisevadingthecurrentdiagnosticefforts.

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3.2.5.)ChronicFatigueSyndrome,Fibromyalgia,andMultipleChemicalSensitivity:

3.2.5.1.)Estimatingprevalenceofchronicfatiguesyndrome,fibromyalgia,andmultiplechemicalsensitivityisdifficult:

TheIOMcommittee'sreviewoftheCCEPprotocolsuggeststhatdataonchronicfatiguesyndrome(CFS),fibromyalgia(FM),andmultiplechemicalsensitivity(MCS)mayhavebeencollectedbyvariousdiagnosticmethods.Forthisreason,itisnotpossibletoestimatetheprevalenceoftheseconditionsfromtheCCEPdata.

3.2.5.2.)CollectdatausingestablisheddiagnosticcriteriaforCFSandFM:

Intheclinicalevaluations,datashouldbecollectedbyusingestablisheddiagnosticcriteriaforCFSandFM.

3.2.5.3.)EstablisheddiagnosticcriteriadonotexistforMCS:

AwidelyacceptedsetofdiagnosticcriteriadoesnotexistforMCS.Consequently,themedicalevaluationinCCEPcannotbeexpectedtodiagnosetheclinicalsyndromeofMCS.

3.2.5.4.)IncludeCFS,FM,andMCSinongoingandfutureepidemiologicalresearchstudies:

Ifmoreistobelearnedabouttherelationshipbetweenthesedisorders(CFS,FM,andMCS)andPersianGulfservice,theyshouldbeincludedamongtheepidemiologicalresearchstudiesthatareongoingorplannedforthefuture.

3.2.5.5.)Continuethoroughworkuptodiagnosesleepdisturbancesandfatigue:

Becauseofthethorough,systematicworkupmandatedintheCCEP,manydisordersthatcouldcontributetosleepdisturbanceandfatigue

havebeendiagnosed.Thesediligenteffortstounmaskoccultmedicalproblemsthatcouldsubstantiallycontributetofatiguehavebeenproductiveandshouldcontinue.

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3.3.)UseoftheCCEPResultsforEducationImprovementsintheMedicalProtocolandOutcomeEvaluations:

3.3.1.)UseoftheCCEPResultsforEducation:

3.3.1.1.)ContinuepublicreleaseofanalysisresultsoftheCCEPonanongoing,periodicbasis:

TheIOMcommitteeencouragestheDoDtocontinuetoreleaseitsanalysisoftheresultsoftheCCEPonanongoing,periodicbasis.Severalaudiencesthatwouldbeinterestedintheseresultsincludeactive-dutymembersoftheservice,veterans,membersoftheU.S.Congress,thelaymedia,aswellasmilitary,DVA,andcivilianmedicalandpublichealthprofessionals.TheCCEPmedicalfindingswouldalsobeofinteresttophysiciansintheDVAsystemandinthegeneralcommunity.

3.3.1.2.)DistributeCCEPfindingstoallprimarycarephysiciansatMTFsandRMCs:

ThemedicalfindingsoftheCCEPshouldbedistributedpromptlytoallprimarycarephysiciansattheMTFsandRMCs.Thiswouldprovidefeedbackontheirdiagnosticdecision-making.InformationonthefrequenciesofparticularsymptomsandtheirspecificdiagnosesmadeintheCCEPpopulationcouldbeuseful,forinstance,indevelopingadifferentialdiagnosisforindividualpatients.

3.3.1.3.)DevelopamoreconciseversionoftheDoDreportforactive-dutyservicepersonnelandveterans:

AmoreconciseversionoftheDoDreporton10,020patients,writteninnontechnicallanguageandwithclearlystatedconclusions,shouldbedevelopedforatargetaudienceofactive-dutyservicepersonnelandveterans.IftheDoDdevelopedanddistributedafactsheetornewsletteraimedatPersianGulfveterans,theinformationonthe

CCEPwouldbemoreaccurateandmorecomprehensivethanmostreportsinthegeneralnewsmedia.ThiswouldalsoprovideanadditionalopportunitytonotifythereadersabouttheavailabilityofthemedicalexamintheCCEP,thehotlinenumber,andtheeligibilitycriteria.

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3.3.1.4.)Developamorecomprehensivedocumentdescribingpotentialexposuresinmoredetail:

TheDoDshouldalsoconsiderdevelopingforclinicaluseintheCCEPamorecomprehensivedocumentthatdescribesthemanypotentialexposuresinmoredetail.Anydocumentthatisprepared,however,mustmakeclearwhatisknownandwhatisunknownabouttherelationshipbetweenthesestressorsandthephysicalorpsychologicalconsequences.

3.3.2.)UseoftheCCEPResultstoImprovetheMedicalProtocol:

3.3.2.1.)UseCCEPexaminationresultstoimprovestandardizationpractices:

TheDoDnowhasresultsontheexaminationsofmorethan10,000CCEPpatients,whichcouldbeusedtoimprovethestandardizedquestionnaires,labtests,andspecialtyconsultations.

3.3.2.2.)Refinequestionsrelatedtopotentialpsychologicalstressors:

MorerefinedquestionsrelatedtopotentialpsychologicalstressorscouldbeaddedsystematicallytothePhaseImedicalhistory.TheCCEPphysiciansmightfindthisinformationusefulindiagnosingandcounselingtheirpatients.Inaddition,itmaybepossibletoidentifypatientswhoareatincreasedriskofpsychologicalproblemsonthebasisoftheirexperiencesinthewar.PerhapsexplicitquestionsondeathexposureandotherknownriskfactorscouldbeaddedtothePhaseIquestionnaire.

3.3.2.3.)DetermineiflabtestsorspecialtyconsultationsshouldbeaddedtoPhaseI:

TheCCEPresultsshouldbeanalyzedtodeterminewhethertherearelabtestsorspecialtyconsultationsthatshouldbeaddedsystematicallytoPhaseItoincreaseitsdiagnosticyield.Diseasesthatarediagnosed

relativelyfrequentlyinPhaseIImayoftenbeoverlookedinPhaseI.Ifsuchdiseasescouldbeidentified,perhapsappropriatescreeninginstrumentscouldbeaddedtoPhaseI.

3.3.2.4.)CompareandcoordinatemethodsandclinicalresultsoftheCCEPandUCAP:

TheDVAusesaprotocolsimilartothatusedintheCCEPcalledtheUniformCaseAssessmentProtocol(UCAP).Themethods

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andclinicalresultsoftheCCEPandUCAPshouldbecomparedtocoordinateandimprovethetwoprograms.

3.3.3.)UseoftheCCEPResultsforPatientOutcome:

3.3.3.1.)Performtargetedpatientevaluations:

Onthebasisofmorethan10,000patientevaluationstodate,RMCphysicianscouldbegintoperformaseriesoftargetedpatientevaluations.ThemostcommondiseasesintheCCEPcouldbeidentified,andsuggestedapproachestopatienttreatmentcouldbedeveloped.ConsensusguidelinesforthetreatmentandcounselingofCCEPpatientswhohavethemostcommondisorderscouldbeusefulforprimarycarephysicians.

3.3.3.2.)CommunicatesuccessfultreatmentmethodsbetweenRMCs:

IfoneRMChashadalotofexperiencewithaparticulardiseasecategoryandsomemeasureofsuccessinitstreatment,theDoDcouldensurethatadescriptionoftheirsuccessfulmethodsiscommunicatedtotheotherMTFsandRMCsacrossthecountry.

3.3.3.3.)ReviewdisordersamongCCEPpatientswhohaveappliedfordisabilitypaymentsorformedicaldischargefromtheservice:

TheDoDcouldperformareviewofthetypesandseveritiesofthedisordersamongCCEPpatientswhohaveappliedfordisabilitypaymentsorformedicaldischargefromtheservice.Inaddition,thefinaldispositionofthesecasescouldbeevaluated,includingthepotentialrelationshipbetweenparticulardiseasesandPersianGulfservice.TheDoDcouldusetheresultsofthesedisabilitydeterminationstopredictwhichdiseasesarelikelytobeassociatedwiththemostimpairmentamongCCEPpatientsinthefuture.TheDoDcouldalsousetheseresultstodeveloprehabilitationandearlyinterventionmethodsforimpairedPersianGulfveterans,suchasthe

SpecializedCareCenters(SCC).Anotherreasontoanalyzethesedisabilityclaimswouldbetoinvestigatepossiblepreexistingriskfactorsforthedevelopmentoftheimpairment.Ifsuchriskfactorsareidentifiable,thentargetedpreventivemedicineinterventionscouldbeplannedforindividualsparticipatinginfutureoverseasdeployments.

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3.3.4.)SpecializedCareCenter(SCC):

3.3.4.1.)TheDoDhasmadeseriouseffortstodevelopanSCCprogramthathasambitiousgoals:

TheIOMcommitteeconcludesthattheDoDhasmadeseriouseffortstodevelopanSCCprogramwithambitiousgoalsforaselectgroupofseriouslyimpairedmilitarypersonnel.Thecommittee'sreviewshouldbeconsideredpreliminary,however,becauseitisbasedononevisitanditisstillearlyinthedevelopmentoftheprogram.

3.3.4.2.)Providemultidisciplinarytreatmentmodalities:

TheSCCcurrentlyperformsathoroughreevaluationofeachpatient'smedicalproblems.SCCphysiciansshouldconsiderlimitingthediagnosticrolethattheyplaytofocusingontheincomingpatientswhohavebeenverydifficulttodiagnoseattheRMClevel.Instead,theSCCshouldfocusonprovidingmultidisciplinarytreatmentmodalitiesthatarenotreadilyavailableattheRMClevel.

3.3.4.3.)Needforindividualizedfollow-upandtherapeuticregimens:

Theneedforindividualizedfollow-upiscrucialforthetypesofdifficultpatientswhoarelikelytobetreatedattheSCC.MedicalstaffattheSCCwillneedtoknowwhetheraparticulartherapeuticplanisfeasibleatthepatient'snearestMTFandwhetherlong-termfollow-upcarecanbeperformed.TheprimarycarephysicianattheMTFneedstoencouragecontinuouspatientcompliancewiththecarefullydesigned,individualizedtherapeuticregimens.

3.3.4.4.)Developobjectivemeasureoffunctionalstatusforfollow-upevaluation:

TheSCCphysiciansshoulddevelopasetofrelativelyobjectivemeasuresoffunctionalstatusforthefollow-upevaluation.Thesecouldinclude(1)appropriateutilizationofmedicalcare,(2)

appropriateuseofmedicationsorothermethodstocopewithsymptoms,(3)generallevelofactivitiesofdailyliving,(4)employmentstatus,and(5)statusofinterpersonalrelationships.

3.3.4.5.)EvaluatetheSCCprogramitself:

TheSCCprogramitselfneedsanevaluationcomponentafterseveralofitsgraduateshavereturnedfortheir6-monthreevaluations.Severalissueswillneedtobeevaluatedinlightofthe

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successesandbarriersthattheprogramhasexperienced,includingeligibilitycriteriaforpatients;rolesoftheSCCinadiagnosticreevaluationofpatients;successfulcontinuityofcareofpatients,withsharedresponsibilitybytheSCCandMTFs;andtheuniqueneedfortheSCC,beyondtheusualstandardofatertiarycaremedicalcenter.

3.3.4.6.)DoDhastakenaseriousapproachtothetreatmentandrehabilitationofthesepatientsintheSCC:

ThecommitteebelievesthattheDoDhastakenaseriousapproachtothetreatmentandrehabilitationoftheseimpairedpatientswhohavetreatable,chronicdiseases.

3.3.4.7.)InvestigatecostsandbenefitsoftheSCCprogram:

Becausethisprogramisverylabor-intensive,itisprobablyveryexpensiveonaper-patientbasis.Atthesametime,thepotentialbenefitsforeachpatientcouldbehigh,ifsuccessfulrehabilitationofserious,long-termimpairmentcanbeachieved.SubsequentevaluationsoftheSCCprogramshouldinvestigateitscostsandbenefits,ifpossible.

3.3.4.8.)IdentifythemosteffectiveelementsoftheSCCprogram:

IftheSCCprogramissuccessfulinimprovingthehealthandfunctionalstatusofitspatients,perhapstheelementsthataremosteffectiveinenablingthepatientstocopewiththeirsymptomscouldbeidentified.PerhapssomeoftheseelementscouldbedisseminatedandintegratedintoexistingMTFprogramsthatareclosetowhereCCEPpatientsliveandwork.

3.4.)ResearchRelevanttotheCCEP:

3.4.1.)EpidemiologicalResearchRelevanttotheCCEP:

3.4.1.1.)Utilizeon-goingepidemiologicalstudiesforrevisingor

improvingtheCCEP:

Theresultsofon-goingepidemiologicalstudiesmaybeusefulformakingrevisionsorimprovementsintheCCEPmedicalprotocolitself,forexample,torevisethestandardizedquestionnairesortoaddordeletetargetedlabtests.ThestudyresultsmayalsobeusefulinthecounselingandtreatmentofCCEPpatients.

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3.4.1.2.)AcknowledgetheseriouslimitationsoftheCCEPdataforepidemiologicalpurposes:

DatafromindividualsintheCCEParealsobeingusedinsomeoftheseepidemiologicalstudies.Inthesestudies,theseriouslimitationsoftheCCEPdataforepidemiologicalpurposesthatwerepreviouslyidentifiedmustbekeptinmind.

3.4.2.)ExposureAssessmentResearchRelevanttotheCCEP:

3.4.2.1.)InvestigateexperiencesofindividualsinUICswithhigherratesofCCEPparticipation:

TheIOMcommitteeencouragesDoDtoperformfurtherinvestigationsonthewarandpostwarexperiencesofindividualsintheUnitIdentificationCodes(UICs)withhigherratesofCCEPparticipation.

3.4.2.2.)Investigateexposuresrestrictedtoparticularlocationsorspecialoccupationalgroups:

ThecommitteeencouragestheDoDtoinvestigateexposuresthatwererestrictedtoparticularlocationsorspecialoccupationalgroups,suchastroopswhohaddirectcombatexposure.ThetypesofsymptomsanddiseasesinCCEPparticipantsinthesespecialgroupsandUICscouldbeanalyzedandcontrastedwiththesymptomsanddiagnosesofCCEPparticipantsinotherunits.

COMMITTEEONTHEDODPERSIANGULFSYNDROMECOMPREHENSIVECLINICALEVALUATIONPROGRAM

GerardBurrow*,Chair,Dean,YaleUniversitySchoolofMedicine,NewHaven,Connecticut

DanBlazer,DeanofMedicalEducationandProfessorofPsychiatry,DukeUniversityMedicalCenter,Durham,NorthCarolina

MargitBleecker,Director,CenterforOccupationalandEnvironmentalNeurology,Baltimore,Maryland

RalphHorwitz,Chairman,DepartmentofInternalMedicine,YaleUniversitySchoolofMedicine,NewHaven,Connecticut

*Member,InstituteofMedicine.

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HowardKipen,AssociateProfessorandDirector,OccupationalHealthDivision,RobertWoodJohnsonMedicalSchool,Piscataway,NewJersey

AdelMahmoud,*Chairman,DepartmentofMedicine,CaseWesternReserveUniversityandUniversityHospitalsofCleveland,Cleveland,Ohio

MichaelOsterholm,StateEpidemiologist,MinnesotaDepartmentofHealth,Minneapolis,Minnesota

RobertPynoos,ProfessorofPsychiatry,UniversityofCaliforniaatLosAngeles,LosAngeles,California

AnthonyScialli,AssociateProfessor,DepartmentofObstetricsandGynecology,GeorgetownUniversityMedicalCenter,Washington,D.C.

RosemarySokas,AssociateProfessorofMedicine,DivisionofOccupationalandEnvironmentalMedicine,GeorgeWashingtonUniversitySchoolofMedicine,Washington,D.C.

GuthrieTurner,ChiefMedicalConsultant,DivisionofDisabilityDeterminationServices,StateofWashington,Tummwater,Washington

MichaelWeisman,Professor,DivisionofRheumatology,UniversityofCaliforniaatSanDiegoMedicalCenter,SanDiego,California

Staff

MichaelA.Stoto,Director,DivisionofHealthPromotionandDiseasePrevention

KelleyA.Brix,StudyDirector

DeborahKatz,ResearchAssistant

AmyNoelO'Hara,ProjectAssistant

DonnaD.Thompson,DivisionAssistant

MonaBrinegar,FinancialAssociate

AppendixEWorkshopontheAdequacyoftheCCEPforEvaluatingIndividualsPotentiallyExposedtoNerveAgents:AgendaandSpeakersList

NATIONALACADEMYOFSCIENCESINSTITUTEOFMEDICINE

December3,1996FoundryBuildingFO-2004,Georgetown

AGENDA

10:00-10:15 Welcome/PurposeandConductoftheWorkshop

Dr.DanBlazer,Chair,CommitteeontheEvaluationoftheDoDComprehensiveClinicalEvaluationProgramforPersianGulfVeterans

10:15-12:00 WorkshopSessionIIssuesregardingtheCCEPDr.RaymondChung,Origins/BackgroundDr.CharlesEngel,MentalHealthDr.AndrewDutka,NeurologicConditionsDr.TimothyCooper,PainDr.AnthonyAmato,NeuromuscularSymptomsDr.KurtKroenke,DiagnosticApproach/GeneralizedSymptoms

12:00-1:00 Lunchinmeetingroom

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1:00-2:45 WorkshopSessionIIIssuesregardingorganophosphates,anticholinesterases,andnerveagentsDr.PeterSpencer,NeurotoxicologyoforganophosphatesDr.RobertMacPhail,Behavioraltoxicologyoforgano-phosphatesandpyridostigmineDr.RobertGum,Possiblehealtheffectsinhumansfromlow-levelexposuretonerveagentsDr.BhupendraP.Doctor,Endogenousdetoxificationofsarin

2:45-3:00 Break3:00-4:45 WorkshopSessionIIIIssuesregardingneurological

testingprotocolsNeurophysiologicaltestingDr.EvaFeldmanDr.DavidCornblathNeurobehavioralandneurocognitivetestingDr.KentAngerDr.RobertaWhite

4:45-5:00 Break5:00-6:30 WorkshopSessionIVModeratedDiscussion

Dr.DanBlazer,ModeratorDr.RichardJohnsonDr.ArthurAsburyDr.DavidJanowsky

6:30 Workshopadjourns

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SPEAKERS

AnthonyA.Amato,M.D.UniversityofTexasSanAntonioDepartmentofNeurologyandMedicine

Capt.AndrewJ.Dutka,M.D.NeurologyServiceNationalNavalMedicalCenterBethesda,MD

W.KentAnger,Ph.D.AssociateDirectorforOccupa-tionalResearchandHealthPromotionOregonHealthSciencesUniversityPortland

Maj.CharlesC.Engel,Jr.,M.D.Chief,GulfWarHealthCenterWalterReedArmyMedicalCenterWashington,DC

ArthurAsbury,M.D.VanMeterProfessorofNeurologyHospitaloftheUniversityofPennsylvaniaPhiladelphia

EvaFeldman,M.D.,Ph.D.AssociateProfessorDepartmentofNeurologyUniversityofMichiganAnnArbor

Col.RaymondChungGulfWarHealthCenterWalterReedArmyMedicalCenterWashington,DC

Lt.Col.RobertGum,M.D.Chief,ChemicalCasualtyCareOfficeU.S.ArmyMedicalResearchInstituteofChemicalDefenseAberdeenProvingGround,MD

Lt.Col.TimothyW.Cooper,M.D.InfectiousDiseaseService74thMedicalGroupHospitalWrightPattersonAFB,OH

DavidJanowsky,M.D.DepartmentofPsychiatryUniversityofNorthCarolinaNeurosciencesHospitalChapelHill

DavidCornblath,M.D.PathologyDepartment

RichardJohnson,M.D.Director,DepartmentofNeurology

JohnsHopkinsHospitalBaltimore,MD

JohnsHopkinsUniversitySchoolofMedicineBaltimore,MD

BhupendraDoctor,M.D.Director,DivisionofBiochemistryWalterReedInstituteofResearchWashington,DC

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Col.KurtKroenke,M.D.GeneralInternistUniformedServicesUniversityofHealthSciencesBethesda,MD

PeterS.Spencer,Ph.D.DirectorCenterforResearchonOccupa-tionalandEnvironmentalToxicologyOregonHealthSciencesUniversityPortland

RobertC.MacPhail,Ph.D.NeurotoxicologyDivisionEnvironmentalProtectionAgencyResearchTrianglePark,NC

RobertaWhite,Ph.D.EnvironmentalHazardsCenterDepartmentofVeteransAffairsMedicalCenterBoston

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AppendixFAdequacyoftheComprehensiveClinicalEvaluationProgram:NerveAgents*

RECOMMENDATIONS

ThechargetothecommitteewastodeterminewhethertheComprehensiveClinicalEvaluationProgramcouldadequatelydiagnoseandtreatpossiblehealthproblemsamongservicepersonnelwhomayhavebeenexposedtolowlevelsofnerveagents.Thecommitteereviewedextensiveclinicalandresearchresultsregardingtheeffectsofnerveagents.Noevidenceavailabletothecommitteeconclusivelyindicatedtheexistenceoflong-termhealtheffectsoflow-levelexposuretonerveagents.Becausefirmconclusionsabouttheseeffectsremainelusive,thecommitteereviewedinformationaboutthetypesofhealtheffectsthatmightexistasaresultofexposure.Leadingscientistspresentedinformationsuggestingthatthepossibleeffectsmightincludeneurologicalproblemssuchasperipheralsensoryneuropathiesandpsychiatricproblemssuchasalterationsinmood,cognition,orbehavior.

Recentreportssuggestingapossibletoxicsynergisticeffectfollowingexposuretomultipleagentsknowntoinfluencecholinesteraseactivitywillrequireextensiveresearchtodeterminetheirsignificance(HaleyandKurt,1997;Haleyetal.,1997a,b;Lottieetal.,1993).Theresultsoftheresearchtodate,however,didnotappeartoindicateanyadditionalpossiblehealtheffectsshouldbeconsideredbythecommitteeotherthanthosealreadyidentified.

*ThisappendixisexcerptedfromtheInstituteofMedicinereport,AdequacyoftheComprehensiveClinicalEvaluationProgram:NerveAgents,Washington,D.C.:NationalAcademyPress,1997.

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ThecommitteeconcludedthattheCCEPcontinuestoprovideanappropriatescreeningapproachtothediagnosisofdisease.MostCCEPpatientsreceiveadiagnosisand80%ofparticipantsreceivemorethanonediagnosis.AlthoughthetypesofprimarydiagnosescommonlyseenintheCCEPinvolveavarietyofconditions,65%ofallprimarydiagnosesfallintothreediagnosticgroups(1)psychologicalconditions;(2)musculoskeletaldiseases;and(3)symptoms,signs,ill-definedconditionsorafourthgroupdesignatedas''healthy."However,inviewofpotentialexposuretolowlevelsofnerveagents,certainrefinementsintheCCEPwouldincreaseitsvalue.Theserefinementsareviewedaspartofanaturalevolutionandimprovementprocessand,therefore,neednotbeappliedretrospectively.Thecommitteedoesencouragerapidimplementationinordertoprovidethebenefitsofanimprovedsystemtonewenrollees.

ThecommitteerecommendsimproveddocumentationofthescreeningusedduringPhaseIforpatientswithpsychologicalconditionssuchasdepressionandposttraumaticstressdisorder(PTSD).TheDoD(DoD,1996)reportedthatdepressionandPTSDaccountforasubstantialpercentageofthosereceivingadiagnosisofapsychologicalcondition.Inaddition,iftherearelongtermhealtheffectsofnerveagentexposure,itispossiblethattheseeffectscouldbemanifestedaschangesinmoodorbehavior.Thecommitteewillbeconductinganin-depthexaminationoftheadequacyoftheCCEPasitrelatestostressandpsychiatricdisordersatalatertime;however,becauseoftheincreasedimportanceofensuringthatallpossibilitiesarethoroughlychecked,betterdocumentationinthisareaisencouraged.Primaryphysicianscoulduseanyofanumberofself-reportscreeningscales,butconsistentuseofthesamescaleacrossfacilitieswouldensureconsistentresults.

Thecommitteerecommendsimproveddocumentationofneurological

screeningdoneduringbothPhaseIandPhaseIIoftheCCEP.Concernaboutnerveagentexposureaswellasthenumberofnonspecific,undiagnosedillnessesamongCCEPpatientsmakesdocumentationofneurologicalscreeningextremelyimportant.CCEPpatientsarereferredtoneuromuscularspecialistsiftheyhavecomplaintsofseveremuscleweakness,fatigue,ormyalgiaslastingforatleast6monthsthatsignificantlyinterferewithactivitiesofdailyliving.Thesepatientsareevaluatedbyboard-certifiedneurologistswhohavesubspecialtytraininginneuromusculardisease.Basedonthedescriptionofthetestsadministeredandexaminationsconducted,thecommitteefindsthattheCCEPissufficienttoensurethatnochronic,well-establishedneurologicalproblemisbeingoverlooked.Thedocumentationoftheuseofthesetestsandprocedures,however,couldandshouldbeimproved.Suchimprovementswouldengenderconfidencethatneurologicalexaminationsandtreatmentsacrossfacilitiesarecomparable.

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Giventheimportanceofthoroughneurologicalandpsychiatricscreening,thecommitteerecommendsthatPhaseIprimaryphysicianshavereadyaccesstoareferralneurologistandareferralpsychiatrist.Asmentionedearlier,patientsarereferredtoneuromuscularspecialistsiftheyhavecomplaintsofseveremuscleweakness,fatigue,ormyalgiaslastingforatleast6monthsthatsignificantlyinterferewithactivitiesofdailyliving.Appropriatepsychiatricreferralscouldincludethosewithchronicdepressionthatistreatment-resistant,anunexplained,persistentcomplaintofmemoryproblems,orsignificantimpairmentsecondarytobehavioraldifficulties,suchasnotbeingabletomaintainproductiveworkduetobehavioralabnormalities.WhilepatientsreferredforPhaseIIconsultationswithaneurologistorpsychiatristarecaredforadequately,itissometimesdifficultfortheprimaryphysiciantodeterminewhetherornotareferralisappropriate.Insuchinstances,thephysiciantendstorefermorefrequentlythannot.Itmaybethat,iftheprimarycarephysicianhadneurologicalandpsychiatricconsultationsreadilyavailable,referraldecisionscouldbemademoreeasilyandappropriately.

Thecommitteerecommendsthatphysicianstakemorecompletepatienthistories,particularlyregardingpersonalandfamilyhistories,theonsetofhealthproblems,andoccupationalandenvironmentalexposures.WhiletherecurrentlyisgraveconcernaboutexposuretonerveagentsduringdeploymentinthePersianGulf,otherfactorshaveanaffectonpsychologicalandneurologicaldisorders.Patientscanperformbelowexpectationsonneuropsychologicaltestsforanumberofreasons.Inclinicalassessments,therefore,itisimportanttoruleoutalternativecausesofimpairment.Inaddition,currentandpastexposurestooccupationalandenvironmentaltoxicantsareimportant.Detailedhistoriesareavaluabletoolinidentifyingtheetiologyofapatient'sproblems.

Thecommitteerecommendsthat,totheextentpossible,

predeploymentphysicalexaminationsgiventomembersofthearmedforcesshouldbestandardizedamongtheservices.Thelackofuniformbaselineinformationaboutservicemembersmakesdiagnosisandtreatmentofpostdeploymentproblemsmoredifficult.Totheextentthatadequatebaselineinformationisunavailable,physiciansmustrelyonself-reporting.Adequatepredeploymentphysicalexaminations,standardizedacrossservices,couldproveanimportanttoolforbothclinicalassessmentandstructuredresearch.

ThecommitteerecommendsthatDoDincreasetheuniformityofCCEPformsandreportingproceduresacrosssites.TheCCEPsystemwouldbenefitfromincreasedconsistencyandtheknowledgethateachserviceiscollectingandusingthesameinformation.Currently,eachbranchofserviceandeachfacilityusedifferentformstocompleteexaminations,tests,andreferrals.IncreasingtheconsistencyofsuchformsandprocedureswouldprovideamorereliablepictureofthecaregiventopatientsintheCCEP.Aswasstatedinthe

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1996reportontheHealthConsequencesofServiceDuringthePersianGulfWar,itisextremelyimportanttocreateauniform,continuous,andretrievablemedicalrecord.Inaddition,the1996reportstatedthattheinformationshouldbecollectedaccordingtostandardizedproceduresandmaintainedinacomputer-accessibleformat(IOM,1996b).Thecommitteeconcurswiththosefindings.

Foreachpatient,thephysicianshouldprovidewrittenevidencethatallorgansystemswereevaluated.TheCCEPprimarycarephysiciansexaminepatients,and,ifthereareproblemsrequiringadditionalexpertise,thepatientsarereferredtospecialists.ThisisstandardmedicalpracticeusedacrosstheUnitedStates.Itwouldbeappropriate,however,fortheCCEPprimarycarephysicianstodocumentthattheirevaluationscoveredallorgansystems.Thecommitteeisnotrecommendingtheuseofneworsophisticatedtestingmechanisms.Itisreinforcingtheimportanceofthecomponentsofthebasicmedicalexamination.Thisincreaseddocumentationcouldbecompletedbynotingtheorgansystemsevaluatedandwhethereachwasnormalorabnormal.Forthoselistedasabnormal,additionalinformationcouldbeprovided.

ThecommitteestronglyurgestheDoDtooffergroupeducationandcounselingtosoldiersandtheirfamiliesconcernedaboutexposuretotoxicagents.FollowingtherevelationbytheDoDofpossibleexposuretonerveagentsduetothedestructionofthemunitionsdumpatKhamisiyah,approximately20,000servicepersonnelreceivedaletterfromtheDoDstatingthattheirunitswereinthevicinityduringthedemolition.Eachrecipientwasencouragedtocontactan800numberifheorshewasexperiencinghealthproblemsbelievedtobearesultofserviceinthePersianGulf.Giventhisrevelation,theremaybeaheightenedsenseofinsecurityandconcernamongPersianGulfveteransandtheirfamiliesaboutpossibleexposuretonerveagents.Riskcommunicationisanimportantclinicalactivity.Familyand

groupcounselingcanaddressheightenedconcernsaboutexposureaswellasotherissues.SuchanapproachprovidesanappropriatepublichealthmechanismforimpartinginformationandaddressingconcernsandshouldbemadeavailabletoallPersianGulfveterans.

Althoughitisbeyondthescopeofthechargetothiscommitteetodeterminewhetherlow-levelexposuretonerveagentscauseslong-termhealtheffects,thecommitteebelievesstronglythatthisisanimportantresearchareathatoughttobepursued.Mostoftheliteratureregardinghealtheffectsofexposuretonerveagents(i.e.,sarinandcyclosarin)addressesexposureshighenoughtocauseclinicallyobservableeffects.Theseclinicaleffectsarewelldocumentedandincludemiosis,blurredvision,nausea,vomiting,musculartwitching,weakness,convulsions,anddeath.Littleknownresearchhasbeenconductedregardingthelong-termhealtheffectsoflowlevelsofexposuretothesenerveagents.Theapplicationoffindingsfromresearchon

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organophosphatepesticideexposuretotheareaofnerveagentexposurehaslimitations.However,eveninsuchpesticidestudies,long-termhealtheffectshavebeendocumentedonlyforacutelypoisonedindividuals-thatis,personswithimmediateclinicalsymptoms.

ThecommitteeemphasizesthattheCCEPisnotanappropriatevehicleforscientificallyassessingquestionsaboutlong-termhealtheffectsoflowlevelsofexposuretonerveagents.TheCCEPisaclinicaltreatmentprogram,notaresearchprotocol.Itisimportant,therefore,nottoattempttousethefindingsoftheCCEPtoanswerresearchquestions.Thosequestionsmustbeaddressedthroughrigorousscientificresearch.

ThecommitteenotesthattheCCEPcouldbeusefulinidentifyingpromisingdirectionsforseparateresearchstudies.Examinationsofthehealtheffects-ifany-ofvariouswartimeexposureshavebeenhamperedbypoorinformationaboutthelevelofexposureandaninabilitytoidentifytheindividualswhomayhavebeenexposed.Itisoftendifficulttoretrospectivelyestimateexposurelevels.However,informationaboutwhereindividualswereandwhentheyweretherecouldbecombinedwithdataregardingthepresenceofanexposuretodevelopsurrogatemeasures.Thesesurrogatemeasurescouldthenbelinkedtohealthinformationandusedtoexaminepotentialassociationsbetweenexposuresandhealtheffects.

AlthoughdatafromtheCCEPcannotbeusedtotestforassociations,itcanbecombinedwithotherinformationtohelpidentifyareasforfutureresearch.Forexample,theDoDidentifiedapproximately20,000servicepeoplebelongingtounitsthatwerewithina50-kilometerradiusofKhamisiyahatthetimeofthemunitionsdemolition.ExaminingthehealthrecordsofthesepeoplemayyieldinsightsintowhetherthosewhoparticipatedintheCCEP(orasimilar

programadministeredbytheVA)havedifferentillnessesorpatternsofillnessesthandoCCEPparticipantsoutsidethe50-kilometerradius.MoredetaileddiscriminationofproximitytoKhamisiyah(e.g.,within20kilometersorwithintheunitsdirectlyresponsibleforthemunitionsdestruction)mayprovideadditionalinformation.

Itisimportant,however,tounderstandthelimitationsofsuchcomparisons.TheresultscannotbetakenasresearchfindingsandgeneralizedtotheentirepopulationofthosedeployedtothePersianGulf.Active-dutymilitarypersonnelparticipatingintheDoDhealthregistrymaybeeithermoreorlesshealthythanothernonparticipantsonactiveduty.CCEPcomparisonsonthisself-selectedgroupofpatientsshouldnotbeusedtodrawconclusionsabouttheentirepopulationofPersianGulfveterans.

Morebroadly,thecommitteenotesthatinformationthathelpstoidentifywhereindividualswereinthePersianGulfandwhentheyweretherewillalsofacilitateresearchintopotentialservice-relatedhealthproblems.Thisinformationiscurrentlyneededtoaddressthequestionofwhomighthavebeen

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exposedtonerveagentsandwhocouldbepartofthe(unexposed)comparisongroupsnecessaryforepidemiologicalstudies.Suchinformationcouldalsobeusedtomorequicklyandeasilyidentifytheexposedandunexposedgroupsthatwouldberequiredtoassessanyfutureconcernsregardingthisorotherexposures.

Generatinggeographicalandtemporalinformationforall700,000peoplewhoservedinthePersianGulfwouldbeanimmenseendeavor.Itwouldnotbeprudenttoundertakesuchataskwithoutfirstthoroughlyunderstandingtheeffortrequiredtocompleteit.Itwould,however,beappropriatetotakestepsnowtoidentifyandpreserverecordsthatcouldassistinthegenerationofsuchadatabaseinthefuture.Records-basedinformationisintrinsicallysuperiortopersonalrecollections,especiallyseveralyearsafterthefact.

COMMITTEEONTHEEVALUATIONOFTHEDoDCOMPREHENSIVECLINICALEVALUATIONPROGRAM

DanG.Blazer,*Chair,DeanofMedicalEducationandProfessorofPsychiatry,DukeUniversityMedicalCenter,Durham,NorthCarolina

MargitL.Bleecker,DirectoroftheCenterforOccupationalandEnvironmentalNeurology,Baltimore,Maryland

EvelynJ.Bromet,Professor,DepartmentofPsychiatry,StateUniversityofNewYorkatStonyBrook,StonyBrook,NewYork

GerardBurrow,*Dean,YaleUniversitySchoolofMedicine,NewHaven,Connecticut

HowardKipen,AssociateProfessorandDirector,OccupationalHealthDivision,RobertWoodJohnsonMedicalSchool,Piscataway,NewJersey

AdelA.Mahmoud,*Chairman,DepartmentofMedicine,Case

WesternReserveUniversityandUniversityHospitalsofCleveland,Cleveland,Ohio

RobertS.Pynoos,AssociateProfessorofPsychiatryandDeanoftheTraumaPsychiatryService,UniversityofCaliforniaatLosAngeles,LosAngeles,California

GuthrieL.Turner,ChiefMedicalConsultant,OfficeofDisabilityDeterminationServices,StateofWashington,Tummwater,Washington

MichaelWeisman,Professor,DivisionofRheumatology,UniversityofCaliforniaatSanDiegoMedicalCenter,SanDiego,California

Staff

LylaM.Hernandez,StudyDirector

SanjayS.Baliga,ResearchAssociate

*Member,InstituteofMedicine.

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DavidA.Butler,SeniorProgramOfficer

DonnaM.Livingston,ProjectAssistant

JamesA.Bowers,ProjectAssistant

KathleenR.Stratton,Director,DivisionofHealthPromotionandDiseasePrevention

ConstanceM.Pechura,Director,DivisionofNeuroscienceandBehavioralHealth

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AppendixGWorkshopAgendasandSpeakersLists

WORKSHOPONDIFFICULT-TO-DIAGNOSEANDILL-DEFINEDCONDITIONS

GreenBuilding,Washington,D.C.March3,1997

AGENDA

8:30-8:45 WelcomeandIntroductionDanG.Blazer,M.D.,Chair,CommitteeontheAssessmentoftheDoDComprehensiveClinicalEvaluationProgram

8:45-10:00 ChronicFatigueSyndromeDescription/DiagnosisandTreatmentDescription/DiagnosisDedraS.Buchwald,M.D.TreatmentNelsonGantz,M.D.Q&A

10:00-10:15

BREAK

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10:15-11:30FibromyalgiaDefinition/DiagnosisFrederickWolfe,M.D.TreatmentRobertSimms,M.D.Q&A

11:30-12:30MultipleChemicalSensitivityDescription,Diagnosis,andTreatmentHowardKipen,M.D.,M.P.H.Q&A

12:30-1:30 LunchinMeetingRoom1:30-2:00 DifficulttoDiagnoseandIll-DefinedConditionsA

DiscussionoftheIssuesDanielJ.Clauw,M.D.

2:00-2:30 WhataretheCriteriaforaGoodScreeningInstrumentPenelopeM.Keyl,Ph.D.

2:30-3:30 DepartmentofDefensePresentationSigns,symptoms,andill-definedconditionsMajCharlesMagruderFibromyalgiaandChronicFatigueSyndromeintheCCEPLtColTimCooperInterpretationofCCEPData:DiagnosticandTreatmentApproachestoDateCOLKurtKroenke

3:30 ADJOURNWORKSHOP

SPEAKERS

DedraStefanieBuchwald,M.D.UniversityofWashingtonSeattle,WA

LtColTimCooper74thMedicalGroupHospitalWright-PattersonAFB,OH

DanielJ.Clauw,M.D.GeorgetownUniversity

NelsonM.Gantz,M.D.,F.A.A.C.P.

GeorgetownUniversityWashington,DC

F.A.A.C.P.PolyclinicHospitalHarrisburg,PA

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PenelopeM.Keyl,Ph.D.JohnsHopkinsUniversityBaltimore,MD

MajEdwinC.Matthews59thMedicalWingHospitalLacklandAFB,TX

HowardKipen,M.D.,M.P.H.EnvironmentalandOccupationalHealthSciencesInstitutePiscataway,NJ

RobertSimms,M.D.BostonUniversitySchoolofMedicineBoston,MA

COLKurtKroenkeUniformedServicesUniversityofHealthSciencesBethesda,MD

FrederickWolfe,M.D.TheArthritisCenterWichita,KS

MAJCharlieMagruderDeploymentSurveillanceTeamFallsChurch,VA

WORKSHOPONSTRESSANDPSYCHIATRICDISORDERS

ArnoldandMabelBeckmanCenterIrvine,CAMay22,1997

AGENDA

8:00 WelcomeandIntroductionDanG.Blazer,M.D.,ChairCommitteeontheEvaluationoftheCCEP

8:15-10:15StressorsGeneralStressorsCarolAneshensel,Ph.D.MilitaryStress(includingcombatandGulfWarspecific)CharlesEngel,M.D.

StressanditsEffectsontheEndocrineandtheImmuneSystemsFirdausDhabhar,Ph.D.Discussion

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10:15-10:30BREAK

10:30-11:00 SubstanceAbuseWalterLing,M.D.

11:00-12:00 DepartmentofDefenseDescriptionofDiagnosticProcess/ProtocolDataPresentationMichaelRoy,M.D.

12:00-1:00 LUNCH1:00-1:30 DepartmentofDefense

SpecializedCareCenterCharlesEngel,M.D.

1:30-3:30 PosttraumaticStressDisorder(PTSD)DavidFoy,Ph.D.DiagnosingDepressioninaPrimaryCareSettingJohnD.Wynn,M.D.SubthresholdDepressions:Clinical,Familial,andSleepEEGValidationHagopAkiskal,M.D.Discussion

3:30 WORKSHOPENDS

SPEAKERS

HagopAkiskal,M.D.UniversityofCaliforniaSanDiego,CA

MAJCharlesEngel,M.D.,MCWalterReedArmyMedicalCenterWashington,DC

CarolAneshensel,Ph.D.UniversityofCaliforniaLosAngeles,CA

DavidFoy,Ph.D.PepperdineUniversityMalibu,CA

FirdausDhabhar,Ph.D.TheRockefellerUniversityNewYork,NY

WalterLing,M.D.UniversityofCaliforniaLosAngeles,CA

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MAJMichaelRoy,M.D.,MCWalterReedArmyMedicalCenterWashington,DC

JohnD.Wynn,M.D.UniversityofWashingtonSeattle,WA

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AppendixHOutlineoftheCCEPMedicalProtocol

FORMREQUIREMENTS

AttheMTFlevel,theCCEPrecordshouldincludeallCCEPformsandrelevantmedicaldatatotheprogram.

BlankformsincludedwiththisguidesupersedepreviouseditionsoftheseformsandareintendedtobeusedwiththenewCCEP.

Allindividualformswillbecompleteandlegible.

FormsforwardedtoNMIMCandmaintainedintheparticipantrecordshallbeinthefollowingorder:

PhaseIcompleted:

MTFPhaseIDiagnosisFormPatientQuestionnaireProvider-AdministeredSymptomQuestionnaireInformationReleaseFormDeclination/CompletionForm

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PhaseIIcompleted:

RMCPhaseIIDiagnosisFormDeclination/CompletionForm

MEDICALPROTOCOLS

TheCCEPisbaseduponathoroughclinicalevaluationwhichemphasizescomprehensiveandcontinuousprimarycare.ThelocalMTFprimarycareprovidermaintainsresponsibilityforpatientevaluationandcarethroughouttheCCEPprocess.

MedicalTreatmentFacility(PhaseI)

PhaseIwillconsistofacomprehensivehistoryandmedicalevaluationwithcompletionofPhaseIquestionnairesandrelatedforms.Theexamination,bothincontentandquality,shouldparallelaninpatientadmissionwork-up.ThePhaseIexaminationwillincludeacompletemedicalhistoryincluding:family,occupation,social(includingtobacco,alcohol,anddruguse),exposuretopossibletoxicagents,psychosocialconditionandreviewofsymptoms.TheproviderwillspecificallyinquireaboutthesymptomslistedontheCCEPProvider-AdministeredPatientQuestionnaire.Acomprehensivemedicalevaluation,withfocusedattentiontothepatients'symptomsandhealthconcerns,shouldbeconducted.

Individualswho,aftercompletingMTFPhaseIevaluations,donothaveaclearlydefineddiagnosiswhichexplainstheirsymptomsshouldbereviewedbytheCCEP-designatedphysicianforfurtherevaluationandconsultationsneededand/orforreferraltotheRMC.

PhaseIIlevelevaluationsareperformedonlyaftercompleteclinicallyindicatedevaluations(includingappropriatespecialtyconsultations)areconductedattheMTFandtheRMC.

PhaseILaboratoryTests

CBCU/ASMA-12

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RegionalMedicalCenter(PhaseII)

PhaseIIevaluationsconsistofthefollowinglaboratorytests,consultations,andasnecessary,symptom-specificexaminations.ElementsofthePhaseIIevaluationmaybeaccomplishedbythelocalMTFasneededinthecomprehensiveevaluationofthePhaseIpatientinordertoobtainadefinitivediagnosis.

PhaseIILaboratoryTests

CBCSedimentationrate(ESR)C-ReactiveproteinRheumatoidfactor B12andfolateANA ThyroidfunctiontestsLiverfunctionCPKUrinalysisTBskintest(PPD)withcontrolsChestX-ray

HepatitisserologyHIVtestingVDRLB12andfolateThyroidfunctiontests

PhaseIIConsults

(ifnotaccomplishedatMTFlevel)Dental:Dentalonlyifparticipant'sannualscreeningnotdoneInfectiousdiseasePsychiatry:Withphysician-administeredinstruments:StructuredClinicalInterviewforDSMIII-R(SCID)(deletemodulesformaniaandpsychosis)Clinician-AdministeredPTSDScale(CAPS)

NeuropsychologicalTesting:Onlyasindicatedbypsychiatryconsult

SYMPTOM-SPECIFICEXAMINATIONS

TheRMCCCEPphysicianensuresthatPhaseIIpatientswiththefollowingundiagnosedsymptomsreceivethetestsandconsultationslistedbelow.

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DiarrheaGIconsultStoolforOandPStoolleukocytesStoolcultureStoolcultureStoolvolumeColonscopywithbiopsiesEGDwithbiopsiesandaspiration

MuscleAches/NumbnessEMG/NCV

ChronicFatigue

PolysomnographyandMSLT

ChronicCough/SOBPulmonaryconsultPulmonaryfunctionTestswithexerciseandABGMethacholinechallengeIfPFTsarenormal,considerbroncho-scopywithbiopsy/lavage

AbdominalGIconsultEGDwithbiopsy/aspirationColonscopywithbiopsyAbdominalultrasoundUGIserieswithsmallbowelFTAbdominalCTscan

MemoryLoss(Onlyifverifiedbypsychevaluation)MRI-headLumbarpunctureNeuroconsultNeuropsychtesting

ChestPain/PalpitationsECGExercisestresstestHoltermonitor

HeadacheMRI-headLP(glucoseprotein,cellcount,VDRL,oligo-clonalmyelin,basicprotein,pressure)Neuroconsult

Vertigo/TinnitusAudiogramENGBAER

SkinRashDermatologyconsultConsiderbiopsy

ReproductiveConcernsUrologyconsultGYNconsult

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AppendixIScreeningInstrumentsforSubstanceAbuse

CAGE

1.Haveyoutriedtocutdownonyourdrinkingoruse?

2. Doyougetannoyedbyothers'commentsaboutyourdrinkingoruse?3. Doyoueverfeelguiltyaboutyourdrinkingoruse?4. Doyouevertakeaneyeopenerinthemorningtogetgoing?

BriefMAST

1.Doyoufeelyouareanormaldrinker?

2.Dofriendsorrelativesthinkyouareanormaldrinker?3.HaveyoueverattendedameetingofAlcoholicsAnonymous(AA)?4.Haveyoueverlostfriendsorgirlfriends/boyfriendsbecauseofdrinking?

5.Haveyoueverneglectedyourobligations,yourfamily,orworkfor2ormoredaysinarowbecauseyouweredrinking?

6.Haveyoueverhaddeliriumtremens(DTs),severeshaking,orseenthingsthatweren'tthereafterheavydrinking?

7.Haveyouevergonetoanyoneforhelpaboutyourdrinking?8.Haveyoueverbeeninahospitalbecauseofdrinking?9.Haveyoueverbeenarrestedfordrunkdrivingordrivingafterdrinking?(Pokotnyetal.,1972)

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T-ACE

TTOLERANCE:Howmanydrinksdoesittaketomakeyoufeelhigh?

AHavepeopleANNOYEDyoubycriticizingyourdrinking?CHaveyoueverfeltyououghttoCUTdownonyourdrinking?EEYEOPENER:Haveyoueverhadadrinkfirstthinginthemorning?

Twoormorepositiveresponsesindicatethatthewomanislikelytohaveanalcoholproblem(Sokoletal.,1989).

TWEAK

T TOLERANCE:Howmanydrinkscanyouhold?

W HaveclosefriendsorrelativesWORRIEDorcomplainedaboutyourdrinkinginthepastyear?

E EYEOPENER:Doyousometimestakeadrinkinthemorningwhenyoufirstgetup?

A AMNESIA:Hasafriendorfamilymemberevertoldyouaboutthingsyousaidordidwhileyouweredrinkingthatyoucouldnotremember?

K(C)

DoyousometimesfeeltheneedtoCUTdownonyourdrinking?

A7-pointscaleisusedtoscorethetest.Thetolerancequestionscores2pointsifthewomanreportsshecanholdmorethanfivedrinkswithoutfallingasleeporpassingout.ApositiveresponsetotheWORRIEDquestionscores2points,andapositiveresponsetothelastthreequestionsscores1pointeach.Atotalscoreof2ormorepointsindicatesthatthewomanislikelytohaveanalcoholproblem(Russeletal.,1993).

AUDIT

1.Howoftendoyouhaveadrinkcontainingalcohol?

1.Howoftendoyouhaveadrinkcontainingalcohol?

2.Howmanydrinkscontainingalcoholdoyouhaveonatypicaldaywhenyouaredrinking?