REVISTA
BRASILEIRA
DE
REUMATOLOGIA
www . r e u m a t o l o g i a . c o m . b r
Review
article
Monitoring
the
functional
capacity
of
patients
with
rheumatoid
arthritis
for
three
years
Leda
M.
de
Oliveira,
Jamil
Natour
∗,
Suely
Roizenblatt,
Pola
M.
Poli
de
Araujo,
Marcos
B.
Ferraz
DisciplineofRheumatology,EscolaPaulistadeMedicina,UniversidadeFederaldeSãoPaulo(UNIFESP),SãoPaulo,SP,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received17October2013 Accepted12June2014
Availableonline3December2014
Keywords:
Rheumatoidarthritis Functionalcapacity HAQ
EPM-ROM
a
b
s
t
r
a
c
t
Objective:Toquantifymodificationoffunctionalcapacityinathree-yearperiodinagroup ofpatientswithrheumatoidarthritis(RA)usingHAQandEPM-ROMinventories.
Methods:FortypatientswithRAonmethotrexate(MTX)asdisease-modifyingantirheumatic drug(DMARD)werefollowedforuptothreeyears.Thefunctionalstatuswasassessedat thebeginningandendoftheperiodbyHAQandEPM-ROM.
Results:Thirty-twopatientswereretrieved,withinitialHAQscoreof1.14±0.49(mean±SD) andEPM-ROMscoreof5.8±2.75.Afteranaverageperiodofthreeyears,theHAQscorewas 1.13±0.49andEPM-ROMscore,6.81±3.66.Inthesubgroupofsevenpatientssubmittedto orthopedicsurgery,HAQscoredecreasedfrom0.84±0.72to1.64±0.56andtheEPM-ROM score,from5.8±1.80to8.3±0.74.Inthesubgroupofnon-operatedpatients,HAQscore variedfrom1.2±0.45to1.07±0.70andEPM-ROMscore,from5.7±3.06to6.4±3.90.
Conclusion:InagroupofRApatientsinuseofonlyMTXasDMARD,therewaslittlechangeon HAQscoreandEPM-ROMscoresovertheaverageperiodofthreeyears.Worseningfunctional capacitywasobservedinthegroupofoperatedpatientsincomparisontothenotoperated ones.Thisfactalertsustotheneedforuseofbroadertherapeuticregimensavailabilityof musculoskeletalsurgeriesinatimelymannerinpatientswithRA.
©2014ElsevierEditoraLtda.Allrightsreserved.
Acompanhamento
da
capacidade
funcional
de
pacientes
com
artrite
reumatoide
por
três
anos
Palavras-chave:
Artritereumatoide Capacidadefuncional HAQ
EPM-ROM
r
e
s
u
m
o
Objetivo:Quantificaramodificac¸ãodacapacidadefuncionalemumperíododetrêsanos emumgrupodepacientescomartritereumatoide(AR),utilizandoosinventáriosHAQe EPM-ROM.
Métodos:QuarentapacientescomARemtratamentocommetotrexato(MTX)comofármaco antirreumáticomodificadordadoenc¸a(DMARD)foramacompanhadosporatétrêsanos.O estadofuncionalfoiavaliadonoinícioenofinaldoperíodoporHAQeEPM-ROM.
∗ Correspondingauthor.
E-mail:jnatour@unifesp.br(J.Natour). http://dx.doi.org/10.1016/j.rbre.2014.06.007
Resultados: Trintaedoispacientesforamrecuperados,comescoreHAQinicialde1,14±0,49 (média±DP)eEPM-ROMde5,8±2,75.Apósumperíodomédiodetrêsanos,oHAQfoide 1,13±0,49eEPM-ROMem6,81±3,66.Nosubgrupodesetepacientessubmetidosa cirur-giaortopédica,oHAQdiminuiude0,84±0,72para1,64±0,56;eoEPM-ROM,de5,8±1,80 para8,3±0,74.Nosubgrupodepacientesnãooperados,oHAQvarioude1,2±0,45para 1,07±0,70;eoEPM-ROM,de5,7±3,06para6,4±3,90.
Conclusão: EmumgrupodepacientescomARmedicadosapenascomMTXcomoDMARD, houvepoucamudanc¸anaspontuac¸õesHAQeEPM-ROMduranteoperíodomédiodetrês anos.Observou-seagravamentodacapacidadefuncionalnogrupodepacientesoperados, emcomparac¸ãocomosnãooperados.Estefatonosalertaparaanecessidadedousode esquemasterapêuticosmaisabrangentesedemaiordisponibilidadedecirurgias muscu-loesqueléticas,emtempohábil,empacientescomAR.
©2014ElsevierEditoraLtda.Todososdireitosreservados.
Introduction
Rheumatoidarthritis(RA)isachronicinflammatorydisease inwhichthe jointinflammationpresentsas synovitis.The inflammationcauses joint pain, swelling, and stiffness, as wellassystemicsymptomssuchasfatigue,weightlossand anemia.Thesynovitisisthemainfactorthatleadstojoint destructionand,ifuntreated,mayprogresstoseriousjoint damage,withlossoffunctionalcapacity.1
RAisaconditionthataffectsapproximately0.5–1%ofthe adultpopulationworldwide,anditsoccurrenceisobservedin allethnicgroups.Thereisapredominanceoffemales(twoto threetimes,comparedtomales),occurringmainlyinpatients betweenthefourthandsixthdecadesoflife,althoughthere areoccurrencesofRAinallagegroups.2
ThenegativeconsequencesforphysicalfunctioninginRA patientsaremultidimensional,withlossofmusclestrength and endurance,besidesthe loss ofrange ofmotion(ROM) ofjoints,duetochangescausedbythedisease.Foraproper understandingofthesituationofthepatient,amultifaceted viewisrequired,becausetheonlyuseoflaboratorytestswill notallowacomprehensiveassessmentofhis/herfunctional capacity.3
Functionalcapacityisakeyfactorofmorbidityanda pre-dictorofmortality4 inRApatients. TheHealthAssessment
Questionnaire(HAQ)isacommonlyusedtooltoassessthe functionalstatusinRApatients,butsomestudieshaveshown aninverserelationshipbetweensensitivitytochangeinHAQ anddiseaseduration,sothatthedurationofthedisease influ-encesthedegreeoffunctionalimprovement.5
HAQwasdevelopedbyFriesetal.(1980)6toassess
func-tionalcapacityinRA;andthedysfunctionoccursearlyinthe disease,duetofactorsthatarenotentirelyclear.
Thepain persecanleadtofunctional loss,eveninthe absenceofradiologicalchanges,whichonlybecomeevident withthepersistenceofsynovitis.7HAQhasbeentranslated
andvalidatedintomanylanguages,includingBrazilian Por-tuguesebyFerrazetal.in1990.8
FunctionalcapacityinRAcanalsobeassessedby EPM-ROM,whichisastandardizedmeasureofthepotentialrange of motion of joints in upper and lower limbs.9 The scale
assessesROMof10large-and-small,right-and-leftjointsby usingagoniometer.10
Theprogressionofjointdysfunctionoccursinasubclinical, slowandprogressivewayinthedifferentstagesofthedisease, which complicatesthe acceptanceofsurgical indicationby RApatients.However,theindicationofsurgerymustbedone early,inordertoavoidtheonsetofjointdeformities.11
Inourenvironment,therearenostudiesonthelong-term outcomeoffunctionalcapacityinRApatientswhowerenot treatedwithbiologicals.Thisstudyportraysthesituationof availabilityofmusculoskeletalsurgeriesperformedinatimely fashioninpatientsseeninthePublicHealthService.
“Inourcountrytherearenostudiesonthelong-term out-come of functional capacity of patients withRA taking biologic medication.Thisstudy portraysthesituationof availabilityofmusculoskeletalsurgeriesinatimelyfashion in patients seen inthe Public Health Service. Consider-ing that HAQand EPM-ROM may reflect thechanges in functional capacity over time,12 this study assessed the
modificationoftheindicesinquestionasaresult param-eter ofindicationof orthopedicsurgerywithin a3-year periodinRApatients.”
Objectives
This study aims to quantify the change in the functional capacity of RApatients treated routinely atour Service of Rheumatology,UniversidadeFederaldeSãoPaulo.
Methods
Thisprospectivestudyinvolved40RApatientsaccordingto AmericanCollegeofRheumatologycriteria,13allagedover18
yearsatdiseaseonset.Allpatientswereinformedonthe con-tent ofthe researchand agreed toparticipateinthestudy bysigningaconsentform.RApatientsinfunctionalclasses 2 and 314 treated with corticosteroids, nonsteroidal
userswerealsoexcluded.Ourpatientswereselected sequen-tially,beinginquiredaboutdurationofthedisease,presence ofmorningstiffness(inminutes)andmedicationsusedatthe timeofenrollment.Theoverallclinicalassessmentandthe countingofinflamedjointswereperformedbya rheumatol-ogist,and HAQandEPM-ROM toolswere appliedbyoneof theauthorsofthisstudy(OliveiraLM).Afteranaverage3-year period,32ofthosepatientsstillbeingmonitoredatthe out-patientserviceofRheumatology,UniversidadeFederaldeSão Paulo,werereassessed.
Considering the occurrence of a 10% loss of functional capacityeveninhealthyindividualsaftertheageof50,15we
settherateoflossoffunctionalcapacityexpectedbyHAQin RAin20%.Thus,wecomparedbaselineandfinalassessment datawithrespecttothelossoffunction,usingHAQ(greateror lesserthan20%)andwithrespecttowhetherornotperform asurgery.
Continuousdatawerepresentedasmean(standard devi-ation–SD)andminimumandmaximumvalues.Categorical datawereexpressedasabsolutenumberandpercentage.For thecomparisonbetweenbaselineand finalassessmentsof variables(e.g.,medicationsinuseandfunctionlossgreateror lesserthan20%measuredbyHAQ),thechi-squareorFisher’s exacttestwasused.
Comparisonsbetweencontinuousvariables,suchasHAQ andEPM-ROMscoresandHAQandEPM-ROMscorechanges, wereonlydescriptive,duetothelimitationimposedbythe samplesize.Thecorrelationbetweenvariableswasperformed usingtheSpearmantest.
ThestatisticalpackageSPSS,version15.0,wasused,and significancewassetat5%.
Results
Aftera3-yearperiod,ofthose40patientsincludedinthestudy wecouldreassess32subjects.Thus,eightpatientswerenot reassessed:threehaddiedandfivefailedtovisittheservice ofRheumatology.Thecharacteristicsofthegroupareshown inTable1.
Sevenpatientsunderwentorthopedicsurgeryduringthe time period of this study and their data are described in Table2.Table3showsthevaluesforHAQandEPM-ROMfor patientssubmittedor nottosurgery. Ofthe sevenpatients surgicallytreated,fourunderwentmorethanoneprocedure. Theoperationsperformedintheupperlimbs(n=5)were: syn-ovectomyinthreepatients,wristfixationinonepatient,and metacarpophalangealprosthesisapplicationinonepatient. Thesurgeriesperformedinthelowerlimbs(n=9)were: syn-ovectomyinthefootofapatient,atalocalcanealfixationon another and knee prosthesis application inthree patients. Table 4 shows the comparison of patients stratified with respecttolossoffunctionbyHAQandwhetherornotasurgery wasperformed.
Withrespecttosurgeryprocedures,althoughthefrequency ofpatientswhohadgreaterthan20%lossoffunctional capac-itywas notsignificant (Fisher,P=0.16), those patientswho underwentsurgeryhadathreetimesgreater riskof suffer-inglossoffunctional capacitygreaterthan 20%duringthe
Table1–Clinicalanddemographiccharacteristics.
Gender(women/men) 29:3
Averageage(years) 53.8(13)
Min/Max 28–75years
Race,n(%)
White 15(46.9)
Mixedrace(“pardos”) 12(37.5)
Black 3(9.4)
Oriental 2(6.3)
Durationofillness 12.2(7.4)
Min/Max 4–33years
Numberofinflamedjoints 5(7.1)
HAQ,baseline 1.14(0.49)
HAQ,final 1.13(0.49)
EPM-ROM(DP),baseline 5.8(2.75)
EPM-ROM(DP),final 6.81(3.66)
Methotrexate(%) 23(73.6)
Continuousdataexpressedasmean(SD),minimumandmaximum values.
Categoricaldatainabsolutenumbers,n(percentage).
studyperiod(hazardratio=3.42)comparedwithpatientsnot operated.
Acorrelationwasnotedbetweennumberofinflamedjoints
and baselineEPM-ROM score(0.46);betweenbaseline
EPM-ROMandbaselineHAQ(0.46);betweenfinalEPM-ROMscore
and disease duration (0.45); and between disease duration
andEPM-ROMchange(differencebetweenbaselineandfinal
scores). Astrong correlation was notedbetweenfinal HAQ
scoreandHAQchange(0.74),influencedbythesubgroupof patientswhounderwentsurgery(Table5).
Discussion
This prospective study involved 32 RA patients aged over 18 years at disease onset and with moderate functional impairment according to HAQ and EPM-ROM scores. After a meanfollow-up ofthreeyears,thefrequencyofpatients who had greater than 20% loss offunctional capacity was
Table2–CharacteristicsofRApatientswhounderwent surgeryduringthestudyperiod.
Conservative treatment
Surgery
Gender(women/men) 22:3 7:0
Age(years) 50.0 49.7
Min/Max 28–75 31–69
Diseaseduration(years) 11.3 14.2
Min/Max 4–33 8–23
Morningstiffness(minutes) 29.2 23.5
Min/Max 0–360 0–120
Numberofinflamedjoints 5.2 7
Min/Max 0–26 0–30
Table3–HAQandEPM-ROMscoresforpatientswhowereornotsubmittedtoorthopedicsurgery.
Baseline Final Methotrexateuse
Surgery HAQ0.84(0.72) HAQ1.64(0.56) 4(57%)
n=7 EPM-ROM5.8(1.80) EPM-ROM8.3(0.74)
Withoutsurgery HAQ1.20(0.45) HAQ1.07(0.70) 21(84%)
n=25 EPM-ROM5.7(3.06) EPM-ROM6.4(3.90)
Dataexpressedasmean(SD).
Table4–LossoffunctionasmeasuredbyHAQafter threeyearsofprogression.
Lossoffunction >20% <20%
Surgery 4(57%) 3(43%)
Withoutsurgery 7(28%) 18(72%)
Datainabsolutenumbersandpercentages.
notsignificant.Patientswhounderwentsurgeryhadathree timesgreaterriskoffunctionalcapacitylossgreaterthan20% duringthestudyperiodcomparedwithnotsurgicallytreated patients.
Ourdata indicate a relative score stability, notonly for HAQ,16butalsoforEPM-ROMovertime.Althoughextensively
used,theexclusiveuseofHAQhasprovenmoresuitableto evaluateRAactivity,17whileEPM-ROMisamoresensitivetool
tochangesinfunctionalcapacity.10 TheuseofEPM-ROMin
thisstudyhasprovidedobjectivedataabouttheROMneeded toperformingactivitiesofdailyliving.Infact,theEPM-ROM score is sensitive to the modification of functional status, translatingthegoniometryrequiredtoperformthebasic activ-itiesoflife.17
Even in healthy individuals, there is loss of functional capacitythroughoutlife;18andinRApatients,suchalossis
moresignificant.19InoursampleofRApatientswithamean
ageof58years,anHAQscoreof1.1isequivalenttothescore forpeopleaged85years.18Sokkaetal.,assessingfunctional
capacityinRApatients,establishedthatHAQvaluessmaller than1would meanamilderdisease,whilevaluesabove2 wouldsuggestasevereillness.12TheannualincreaseinHAQ
scorefoundbytheseauthorswas confirmedbyScottetal. Theseauthorsfoundanannualincreaseof1%inHAQscore.20
Althoughtheliteratureconsidersa0.24-changeinHAQas clin-icallyrelevant,21reductionsof0.19canalreadyconsideredas
minimalimprovementinfunction.20
ThefunctionalcapacitymeasuredbyHAQisinfluencednot onlybyageordurationofdisease,butalsobylevelsofpain
andmedicationsused.InBrazilianpatients,therewasafaster progressioninHAQscorescomparedtoSpanishpatients.This findingwasattributedtothedifferenceinthepainassessment andmedicationsused.21Atthattime,therewasscarceaccess
tobiologicdrugsinseveralcentersinBrazil,whileinSpain thesemedicationswerealreadywidelyavailable.
HAQcanpredicttheseverityand dysfunctioncausedby RAduringtheprogressionofthedisease–whichisnot evi-dentwiththeuseofotherclinicalmeasures.Thefunctional lossafterfiveyearsisrelatedtofemalegender,olderageat diseaseonset,HAQ>1inthefirstassessment,comorbidities anddepression.16Inadditiontoapositivecorrelationwith
dis-easeduration,HAQpresentsalsoanegativecorrelationwith socioeconomicstatus.20
Inthe presentstudy,weobservedaslightimprovement in functional capacity measured by HAQ in the group of patientswhodidnotundergosurgeryandasignificant wors-eningintheoperatedgroup.Onecaninterpretthis finding asadifferenceindiseaseseveritybetweengroups.Allegedly, the group notoperated would suffer aless aggressive dis-ease,althoughwithadiseasedurationsimilartothatofthe operatedgroup.Thus,themorefavorableprogressionofthe non-operatedgroupmay reflectaconditionmore suscepti-bletocontrolbymedication.AworseningofbothHAQand EPM-ROMscoreswasobservedintheRAgroupwho under-went orthopedic surgery, denoting that their surgery may have occurred late, whenthe anatomical deformities(e.g., musculoskeletalimpairment)alreadyinstalledwouldprevent functionalimprovementofthejoint.
Backwhenthepatientsinthisstudyshowedthefirst symp-tomsofRA,biologicalswerenotavailableinthePublicHealth Service.CurrentlytheimportanceoftheearlyuseofDMARDs and biologicals in controlling the course ofthe disease in itsfirst yearshasalreadybeenestablished.Thiswindowof opportunitymayhavebeenlostbythepatientsinthisstudy, whohadonlymethotrexateavailableasDMARD.Ourfindings agreewithSokkaetal.’s,whichemphasizethepositiveimpact ofanearlyuseofDMARDsinfunctionalcapacitymeasured
Table5–Correlationsfoundamongclinicaldata.
BaselineEPM-ROMscoring FinalEPM-ROMscoring EPM-ROMchange HAQchange
Inflamedjoints(n) 0.46 NS NS NS
Durationofdisease NS 0.45 0.48 NS
HAQ,baseline 0.46 NS NS NS
FinalHAQscoring NS NS NS 0.74
EPM-ROM,baseline NS 0.53 NS NS
byHAQ.Wecanaddtothisthefindingthatfunctional dis-abilitywasapredictorfactorofmortalityinRA.12Painand
joint mobility are considered as importantfactors limiting thefunctionalcapacityofRApatients.3,22,23Thelossof
func-tionalcapacityoccursearlyinthedisease,withthepresenceof acuteinflammation.24WiththeearlyuseofDMARDsandafter
controllingthediseaseactivity,afunctionalrecoveryoccurs, followedbystructurallesionsthatsettle slowly and cumu-latively.Thus, the functional deteriorationmay occur even beforetheradiographicchanges,whichbecomerelevantafter alapseoffiveyearsfromtheonsetofthedisease.7,20
An inverse correlation between HAQ score and ROM of somejoints,e.g.wrists,shouldersandknees,wasobserved.24
EPM-ROM takes into account the ROM ranges needed to performwide-ranging functions,and notjusta percentage ofamplitude loss caused bythe disease,which can differ dependingonthejoint.8Ourdatashowtheexpected
corre-lationbetweenthebaselineevaluationbyEPM-ROMandthe numberofinflamedjoints.WealsonotedanEPM-ROM varia-tionwiththedurationofdisease,showingworseninginjoint mobilizationcapacityaftera3-yearperiod.
Insubjectswithjointimpairmentconsolidatedbyadisease durationlongerthan12years,EPM-ROMremainsstable,while HAQ varies depending on the degree ofdisease activity.22
Thesequestionnairesarecomplementary,totheextentthat HAQisinfluencedbythesubject’sadaptationtodysfunction overtime,whileEPM-ROMreflectsthecapacityofthe move-mentitself.
Althoughthedysfunctionduetopainandinflammation canbemodifiedbyclinicalandrehabilitativeapproaches,this strategymaynotbesufficientinthecontext ofthesumof structuraljointinjuries,regardlessofthesurgicalapproach.25
The best time for surgery indicationin RA remains to be defined,being hamperedbythe availabilityofsurgical ser-vicesandthepatient’smotivation.7,11,25Wemustaddtothis
thefactthat,evenwhenindicatedearly,thesurgeryactsin anindirect mannerinfunction improvement, i.e.,through improvementof pain, rather than through regaining func-tionalcapacity.19 Fewstudieshaveevaluatedthelong-term
effectofsurgicalinterventions. Benoniet al.demonstrated improvementinpaininRApatientswhounderwentsurgery oflowerlimbjointsafteroneyearoffollow-up.The improve-mentinHAQscoreofatleast0.2occurredonlyincasesof kneeandhipsurgery,butnotinankleandfeetsurgery.26On
theotherhand,Marchetal.observedareductioninHAQonly inpatientsundergoingkneearthroplasty,andstabilityinHAQ inthoseundergoinghiparthroplasty.19Therefore,totalHAQ
doesnotreflectthepotentiallyexpectedfunctional improve-mentafteranorthopedicsurgeryinRApatients;andclinical practiceshows that the modification of HAQhas value as a measureof the effect ofother therapeutic modalities in RA.27
Inourstudy,weobservedapositivecorrelationbetween thefinal scoreoftheHAQ andits changes overthe 3-year period, influenced bythe subgroupof patients undergoing surgery.Thisfindinghighlightsthedeteriorationoffunctional capacityinthegroupofoperatedpatients,whichisin agree-ment withother authors that the effectof arthroplasty in RAismoreprominentinrelievingpainthanintherecovery offunction.19,26,27 Consideringthatdiseaseactivity isakey
determinantfactor toexplainthe lossoffunctional capac-ity,patientstreatedbyrheumatologistshaveamorefavorable progression ofARversus those treatedbyphysicians from otherspecialties.12
Furthermore,weobservedlower baselineHAQscoresin the surgery group compared to the conservatively treated group.Nostatisticalanalysiscouldbeperformedbetweenthe twogroups,inviewofthediversityinthegroupofpatients operatedand thesmall samplesize.Infour patients,more thanonetypeofsurgerywasperformed,andthreepatients underwentsurgerybothintheirupperandlowerlimb.Two patientsunderwentanklesurgerywhich,accordingtoBenoni et al., evolvesunfavorably,withreductionofHAQ.27 Asfor
metacarpophalangealarthroplasty,itisknownthat,although the patientdemonstrates satisfactionwithimproved pinch and grip strength, the functional capacity shows modest gains.28
Someofthelimitationsofthisstudyreflectthe deficien-ciesintertiary careofPublicHealth Services inourmidst. Amongthem,wecanmentionthedifficulty inestablishing the diagnosisofRAwithinthewindowofopportunitythat wouldallowthepreservationofjointfunction,aswellasto gettingthesurgeryneededinatimelymanner.Inourcountry, therearelongwaitinglinesfortreatmentinthePublicHealth Service,andthiscancontributetothedeteriorationof func-tionalcapacitytothepointthat,whenfinallythesurgeryis performed,thepreservationoffunctionisnolongerpossible. Inthiscontext,theheterogeneitywithrespecttodisease dura-tionandthesmallnumberofpatientsundergoingsurgeryare included.
This study was limited to abaseline evaluation and to another,afterapproximatelythreeyearsofprogression.The fulfillment ofinterim evaluations, and in particulara pre-operativeassessmentforthesurgicalgroup,couldshedlight ontheworstcourseofoperatedpatients.Thesepatientsmay present amoreaggressivedisease,andperhapstheir func-tionalcapacitywasverypooratthetimeofsurgery,justifying theirunfavorableoutcome.
Finally, patients taking biologic medications were not includedinthisstudy.Itisnotyetclearwhetherthe biolog-icalsare responsible forareductioninsurgicalindications inRApatients.24,25,29 Ingeneral,it isknown thatthe early
use of DMARDs in RA tends to decrease the disease pro-gression,improvequalityoflifeandalsoreducethecostsof hospitalization,surgicalprocedures,andthelongperiodsof rehabilitation.11,30
OurdatademonstratethatHAQandEPM-ROMscoresina groupofRApatientsseeninthePublicHealthServicehave not changed over an average 3-year period. The group of patientsundergoingorthopedicsurgeryexperienced worsen-ing offunctionalcapacityversusthegroupofpatientswho werenotoperated.Thisfactservesasawarningoftheneedto usebroadertherapeuticregimensandalsooftheneedforthe availabilityofmusculoskeletalsurgeriesinatimelymanner forRApatients.
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