The who-when-why triangle of complementary and alternative medicine use among Portuguese IBD patients

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Francisco

Portela

a,∗

,

Camila

C. Dias

b,c

,

Paulo

Caldeira

d

_,

_Marilia

_Cravo

e

_,

_João

_Deus

f

_,

Raquel

Gonc¸

alves

g

_,

_Paula

_Lago

h

_,

_Henrique

_Morna

i

_,

_Paula

_Peixe

j

_,

_Jaime

_Ramos

k

_,

Helena

Sousa

d,l

_,

_Lurdes

_Tavares

m

_,

_Helena

_Vasconcelos

n

_,

_Fernando

_Magro

o,p,q

_,

Paula

Ministro

r

a_Servic¸_o_de_{Gastrenterologia,}_Centro_Hospitalar_{Universitário}_de_Coimbra,_Coimbra,_Portugal

b_CIDES_–_Department_of_Health_Information_and_Decision_Sciences,_Faculty_of_Medicine,_University_of_Porto,_Portugal c_CINTESIS_–_Centre_for_Health_Technology_and_Services_Research,_Porto,_Portugal

d_{Gastroenterology}_Department,_Centro_Hospitalar_do_Algarve,_Portugal e_Serviç_o_de_{Gastrenterologia,}_Hospital_Beatriz_Ângelo,_Loures,_Portugal f_Serviç_o_de_{Gastrenterologia,}_Hospital_Fernandes_da_Fonseca,_Amadora,_Portugal g_Serviç_o_de_{Gastrenterologia,}_Hospital_de_Braga,_Braga,_Portugal

h_{Gastroenterology}_Department,_Centro_Hospitalar_{Porto-Hospital}_Santo_António,_Portugal i_Servic¸_o_de_{Gastrenterologia,}_Hospital_do_Funchal,_Funchal,_Portugal

j_Servic¸_o_de_{Gastrenterologia,}_Centro_Hospitalar_de_Lisboa_Ocidental,_Lisboa,_Portugal k_Servic¸o_de_{Gastrenterologia,}_Hospital_dos_Capuchos,_Lisboa,_Portugal

l_Biomedical_Sciences_and_Medicine_Department,_University_of_Algarve,_Portugal m_Servic¸_o_de_{Gastrenterologia,}_Hospital_de_Santa_Maria,_Lisboa,_Portugal n_Servic¸_o_de_{Gastrenterologia,}_Hospital_de_Santo_André,_Leria,_Portugal o_{Gastroenterology}_Department,_Centro_Hospitalar_São_João,_Porto,_Portugal

p_Department_of_Pharmacology_and_{Therapeutics,}_Faculty_of_Medicine,_University_of_Porto,_Portugal q_MedInUP_–_Centre_for_Drug_Discovery_and_Innovative_Medicines,_University_of_Porto,_Portugal r_Servic¸_o_{Gastrenterologia,}_Centro_Hospitalar_de_Tondela_–_Viseu,_Viseu,_Portugal

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received1December2016 Receivedinrevisedform 29December2016 Accepted30December2016 Availableonline6January2017 Keywords:

Complementaryandalternativemedicine (CAM)

Compliance

Inﬂammatoryboweldiseases(IBD)

a

b

s

t

r

a

c

t

Background:Theuseofcomplementaryandalternativemedicinesisincreasingamongchronicpatients,

particularlythoseafﬂictedwithinﬂammatoryboweldiseases.

Aim:Thisstudyaimedtoaddresstheprevalenceofcomplementaryandalternativemedicinesuseamong

Portugueseinﬂammatoryboweldiseases’patients.

Methods:Patientswereinvitedtoﬁllananonymousquestionnaireconcerningtheuseofcomplementary

andalternativemedicines.

Results: Thirty-oneper cent of the patientsreported having used complementaryand alternative

medicinesin thepast, whereas12%wereusingthembythetimethequestionnairewas

adminis-tered.Fifty-ninepercentoftheusersdidnotsharethisinformationwiththeirphysician,whereas14%

and8%discontinuedtheirmedicationandperiodicalexamination,respectively.Steroidsprescription

(OR=2.880)andahigherinstructionlevel(OR=3.669)werepredictorsofcomplementaryandalternative

medicinesuseinthiscohort.

Conclusions:RoughlyathirdofPortugueseIBDpatientshadusedCAM.Steroidtreatmentandanacademic

degreeareassociatedwithCAMuse.Giventhepotentialsideeffectsandinteractions,patientinformation

aboutthebeneﬁtsandlimitationsofconventionalandcomplementarytreatmentsshouldbereinforced.

∗ Correspondingauthor.

E-mailaddress:[email protected](F.Portela).

1. Introduction

Inﬂammatoryboweldiseases(IBD),whichincludeCrohn’s dis-ease(CD)andulcerativecolitis(UC),arelifelongimmune-mediated disorders characterized by a relapse and remitting course, and http://dx.doi.org/10.1016/j.dld.2016.12.031

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Fig1.RelativefrequencyofconventionaltherapiesusedamongthestudiedIBDpopulation.

particularlycommonindevelopedcountries[1,2].WhereasUCis limitedtotherectumandcolon,CDcanvirtuallyaffectanypart ofthegastrointestinaltract(GI),althoughbeingmorecommonly foundalongtheileumandinthebeginningofthecolon.Despitethis andotherdifferences,CDandUCshareacharacteristicheavy bur-denofsymptomatology:rectalbleeding,abdominalpain,diarrhea andfatiguearesomeofthemoreconspicuoussymptomsaffecting IBDpatients.Sofar,nocurativetherapieshavebeendevelopedfor UCorCD,andthereforethecurrentmanagementofthesediseases aimstocontrolthesymptomsandimprovepatients’health-related quality of life (HRQoL). Thismanagement relies onquite com-plextherapeuticlinesthatcanincludesteroids,anti-inﬂammatory drugs (such as 5-aminosalicylic acid[5-ASA]), immunomodula-tors (suchas azathioprine [AZA] oranti-tumournecrosis factor ␣[anti-TNF␣]),andbowelsurgery.Understandably,bothIBDand themedicationstakentocontroltheburdenofsymptomshavea highimpactonpatients’HRQoLandareassociatedwithahigher prevalenceofpsychologicaldisorders[3].

The awareness and interest in complementary and alterna-tivemedicines (CAM)hasbeenraisingamong IBDpatients.The EuropeanCrohn’sand Colitis Organisation(ECCO) defines com-plementaryand alternativetherapies accordingtotheirpattern ofuse:complementarytherapies arethosethatareused along-side withconventional medicine,whereas alternative therapies are those that are used in the place of conventional medicine [1,2].Theholisticandself-healingnatureofCAMis particularly attractivetochronicpatients,asitisthepopularnotionthatCAM hasno side effects. In thecontext of IBD, differenttechniques andproductsarecommonlyused,someofwhichhavebeenthe subjectof laboratorytestsand/orclinicaltrials:treatmentwith helminths[4],gut-directedhypnotherapy[5–8],herbalmedicines [8–12],acupuncture[8,13],nutritionalstrategies[8,14,15], exer-cise[16],andantioxidanttherapy[17] area fewofthem.Some of the results obtained in these trials are indeed promising – forinstance,theassociationofgut-directedhypnotherapywitha reducedIBD-relatedinflammationandanincreaseofHRQoL[6], orthedemonstrationthatBoswelliaserratagumresinandPlantago ovataseedsareaseffectiveas5-ASAinthetreatmentofUC[11]. However,theseresultsneedtobeinterpretedwithcaution,asthe lackofhigh-qualitydataremainsanissueinmostCAMstudies.The efficacyandsafetyofCAMneedtobeevaluatedbymulticentric anddoubleblindrandomizedcontrolledtrialswithlargesamples beforedefinitiveconclusionsaredrawn.

Theknowledge of CAM utilizationpatternsamong a certain communityis absolutely necessaryin ordertoprevent interac-tions with conventional medicine, potential side effects and a decreaseintherapeuticcompliance.Althoughsuchanissuehas beenapproachedin severalcountriesofNorth America, Europe

andAsia,thepictureinPortugalremainsunknown,andthestrong impactofregionalandculturalfactorsinCAMutilizationprevents theextrapolationoftheresultsfromotherEuropeancountries.As so,thisstudyaimedtoexploretheuseandattitudesofPortuguese IBDpatientstowardCAMbasedontheresultsofananonymous survey.

2. Materialandmethods

2.1. Studypopulation

IBDpatientswererecruitedfromAPDI(PortugueseIBDpatients’ association)andfrom13differentuniversityandcommunity hos-pitalsbetweenOctober2011andMarch2012.Patientsolderthan 18yearsandwithaconﬁrmeddiagnosisofUC,CDorunclassiﬁed colitiswereinvitedtoparticipateinthestudy.Thesepatientswere givenaquestionnairecontaining31yesornoandmultiplechoice questions focused on social-demographic aspects (gender, age, instructionlevelandprofessionalsector),clinicaldata,compliance, andCAMuseandattitudes.Allquestionnaireswereanonymous andself-administered,beingafterwardsreturnedbymail.Thelocal ethiccommitteehasapprovedthisstudy.

2.2. Statisticalanalysis

Categoricalvariables were describedusing absoluteand rel-ativefrequencies, whereas continuousvariables weredescribed using average, median, standard deviation, percentiles, and minimum/maximum values. The Pearson Chi-square test was used to test the independence of categorical variables. T and Mann–Whitneytestswereusedtotestthesimilarityofgroups, dependingonwhethertheirdistributionwasnormalornot nor-mal.Logisticregressionwasemployedtodeterminewhichfactors couldindependentlypredicttheuseofCAM.Alltestswere evalu-atedconsideringasigniﬁcancelevelof5%.Alldatawasarranged, processedandanalysedwithSPSS®v.19.0data(StatisticalPackage forSocialSciences),whereasgraphsweredesignedusingPrism7.

3. Results

3.1. Cohortcharacterization

Atotalof750questionnairesweredistributed,and442were returnedandconsideredvalid,whichcorrespondstoaresponse rateof59%.Ninequestionnaires(1.2%)wereconsideredinvaliddue toalackofanswers.Thesocio-demographicandclinical charac-teristicsofthestudypopulationaresummarizedinTable1.Most respondentswerefemale(57%),wereeducatedtoacollegedegree

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Crohn’sdisease 299 65

Unclassiﬁed 8 2

Diseaseduration(median,P05–P95) 11 3–30

Hospitaladmissions(previous5years)(n,%)

None 253 56

1 90 20

2–5 94 21

>5 13 3

Bowel-relatedsurgeries(previous5years)

(n,%) 96 22

(median,P05–P95) 1 (1–3)

Conventionaltherapyprescription(n,%)

Yes 329 76

Disease-relatedcurrentwell-being(n,%)

Ok 182 40

So-so 213 47

Notok 54 12

Verybad 9 2

HaveyoueverusedalternativemedicinesbecauseofyourIBD?(n,%)

Yes 145 31

DoyoucurrentlyusealternativemedicinesbecauseofyourIBD?(n,%)

Yes 57 12

Howdidyoufeelregardingyourdiseasebythetimeyoudecidedtousealternativemedicines?(n,%)

Ok 14 10

So-so 36 25

Notok 49 34

Verybad 47 32

(39%)andworkedinthetertiarysector(79%).UCafﬂicted33%of

therespondents,whereas65%ofthemhadaCDdiagnosisand2%

hadunclassiﬁedcolitis.Themediantimeofdiseasedurationwas

11years,and22%ofallpatientshadundergoneatleastone

bowel-relatedsurgeryinthepreviousﬁveyears.Duringthesametime

period,20and21%ofallpatientshadoneortwotoﬁvehospital

admissions,respectively.Conventionaltherapieswereprescribed

toatotalof76%ofallrespondents,andthedistributionofthose

therapiesisdepictedonFig.1:salicylateswerethemostcommonly

prescribedmedications(94%of therespondentshad usedthem inthepastand76%wereusingthembythetime the question-naire wasadministered),followed byimmunosuppressors (47% inthepastand34%bythetimethequestionnairewas adminis-tered).Theprescriptionofsteroidswasrelativelycommoninthe ﬁveyearsprecedingthisstudy(41%ofpatientswereonsteroids), butbythetimethequestionnairewasadministeredonly11%ofthe respondersweremedicatedwiththesedrugs.Mostpatients(87%) reportedtheywerefeelingatleastpartiallywellinrelationtotheir IBD(Table1).

Atotalof145patients(31%)ofthiscohorthadusedsomekindof CAMtotreattheirIBDinthepast,and57(12%)werestilldoingsoby thetimethisquestionnairewasdistributed(Table1).Themajority ofthesepatients(66%)statedthattheywereeither“notok”or“very bad”inrelationtotheirIBDbythetimetheydecidedtoresortto CAM.ThetypesofCAMusedaredepictedinFig.2,alongsidewith theirrelativefrequencies.Herbalmedicinesandhomeopathywere theCAMtypesmorefrequentlyusedbythepatientsinthepast(39% and42%,respectively),butonlyherbalmedicinesremainedinthe

toppreferencesofthepatientsbythetimethequestionnairewas addressed(46%),followedbyvitaminsintake(30%).Homeopathy droppeddowntoarateofutilizationof18%.

3.2. AttitudesandreasonsleadingtoandfollowingCAM utilization

Theinabilityofconventionalmedicinetoimprovetheir condi-tionwasthemostcommonlyreportedreasonforpatientstoresort toCAM(33%),and 72%didsoafterreceivingadvicefroma col-league,friendoffamilymember(Fig.3).Atotalof67%ofallCAM usersreportedapositiveoutcomeoftheexperience(i.e.,theyfelt “better”or“muchbetter”afterCAMuse).Thecostsassociatedwith CAMwereconsiderablyhigh,with66%oftheCAMusers spend-ingover50D permonthinthesemedicines,and41%reportinga monthlycostover100D.Indeed,ﬁnancialreasonswerethesecond mostcitedreasonforpatientstoabandonCAMafterexperiencing it(44%),surpassedonlybytheabsenceofpositiveoutcomes(51%). InwhatconcernsthepotentialeffectofCAMuseonconventional medicinecompliance,86% and92%oftherespondentsreported tohavemaintainedtheconventionaltherapy andtheperiodical examinationsandanalyses(respectively)duringthetimeperiod theywereusingCAM.Finally,59%oftheCAMusersconcealedthis informationfromtheirattendingphysician,and71%didsobecause theywereafraidofthephysicianreaction(Fig.3).Still,85%ofall IBDpatientswouldappreciatetheopportunitytodiscussCAMwith theirphysician.

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Fig.2. RelativefrequencyofCAMtherapiesusedamongtheCAMusers.

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Tertiary 102 (86) 194 (76)

IBD(n,%) 0.416

Ulcerativecolitis 41 (29) 109 (35)

Crohn’sdisease 99 (70) 199 (63)

Unclassiﬁed 2 (1) 6 (2)

Diseaseduration(median,P05–P95) 10(4–27) 11(3–30) 0.839***

Disease-relatedcurrentwell-being(n,%) 0.837

Ok 54 (39) 126 (40)

So-so 65 (46) 144 (46)

Notok 17 (12) 37 (12)

Verybad 4 (3) 5 (2)

Hospitaladmissions(previous5years)(n,%) 0.098

None 69 (50) 180 (59)

1 26 (19) 64 (21)

2–5 38 (28) 55 (18)

>5 5 (4) 7 (2)

Bowel-relatedsurgeries(previous5years) 0.601

(n,%) 32 (24) 63 (21)

(median,P05–P95) 2 (1–4) 1 (1–3) 0.318***

Conventionaltherapyprescription(n,%) 0.003

Yes 117 (85) 208 (71)

Conventionaltherapyduringthelast5years(n,%)

Biologics 0.088 Yes 36 (26) 57 (19) Immunossupressors 0.024 Yes 77 (55) 133 (43) Steroids 0.001 Yes 73 (53) 105 (36) Salicilates 0.053 Yes 113 (91) 279 (96)

Currentconventionaltherapy(n,%)

Biologics 0.043 Yes 30 (23) 45 (15) Immunossupressors 0.358 Yes 48 (38) 97 (33) Steroids 0.003 Yes 23 (18) 24 (8) Salicilates 0.078 Yes 90 (70) 231 (78)

Note:Boldmeanssigniﬁcant(p<0,05).

* _Pearson_Chi-square.

** _T_test_for_independent_samples. ***_{Mann–Whitney}_Test.

3.3. ThetypicalproﬁleofaCAMuser-associatedvariablesand predictors

Table2liststhesocio-demographicandclinicalvariables inves-tigatedandtheirassociationwithCAMuse.Neitherdiseasetype nordiseasedurationnornumberofhospitaladmissionsandbowel surgeriesareassociatedtoCAMuseinasigniﬁcantfashion.Onthe otherhand,patientswhoareyounger(anaverageof40yearsold vs.45,p<0.001),females(64%ofallusers,p=0.033),andthathave acollegedegree(53%ofallusers,p<0.001)areparticularlyprone touseCAM.Moreover,CAMuseismorecommonamongpatients towhomconventionaltherapywasprescribed(p=0.003), partic-ularlythosethatwereonimmunosuppressorsorsteroidsinthe ﬁveyears precedingthequestionnaireadministration(p=0.024 andp=0.001,respectively),oronsteroidsor biologicalsbythe

timethequestionnairewasadministered(p=0.003andp=0.043, respectively).

Alogistic regression wasemployedtodiscernwhich factors werepredictiveofCAMuse(Table3).Althoughtherewerea num-berofsignificantvariablesontheunivariatemodel(gender,age, instructionlevel,hospitaladmissionsinthepreviousfiveyearsand prescriptionofconventionaltherapy,namelyimmunosuppressors, steroidsandbiologicals),onlytwoofthemretainedtheir signifi-canceinthemultivariatemodel:instructionlevelandsteroidsuse. IBDpatientseducatedtoacollegedegreeweremorethanthree timesmorelikelytouseCAMwhencomparedtothosewiththe mandatorylevelofinstruction(OR=3.669,95%CI:1.554,8.664), whereasthosethathadusedsteroidsatsometimeinthefiveyears preceding theadministration of thequestionnaire werealmost

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Table3

MultivariateanalysisofvariablesassociatedwithCAMuse.

Univariatemodela _Multivariate_modelb

OR CI95% p OR CI95% p

Gender

Male Ref

Female 1.576 1.037–2.396 0.033

Age,average(stdev) 0.972 0.957–0.988 <0.001 Instructionlevel

Mandatory Ref Ref

High-school 2.332 1.295–4.198 0.005 2.255 0.900–5.650 0.083 College 3.763 2.144–6.608 <0.001 3.669 1.554–8.664 0.003 Professionalsector Primary Ref Secondary 2.717 0.320–23.100 0.360 Tertiary 4.732 0.591–37.871 0.143 IBD

Unclassiﬁedcolitis Ref

Ulcerativecolitis 1.128 0.219–5.818 0.885

Crohn’sdisease 1.492 0.296–7.529 0.628

Diseaseduration 0.996 0.971–1.020 0.721

Disease-relatedcurrentwell-being

Ok Ref

So-so 1.053 0.683–1.624 0.814

Notok 1.072 0.556–2.068 0.835

Verybad 1.867 0.483–7.221 0.336

Hospitaladmissions(previous5years)

None Ref

1 1.060 0.622–1.807 0.831

2–5 1.802 1.095–2.966 0.020

>5 1.863 0.572–6.068 0.302

Bowel-relatedsurgeries(previous5years)

Yes 1.138 0.701–1.847 0.601

No Ref

Howmanysurgeries? 1.219 0.779–1.908 0.386

Conventionaltherapyprescription

Yes 0.450 0.265–0.764 0.003

No Ref

Conventionaltherapyduringthelast5years Biologics Yes 1.510 0.9.9–2.429 0.089 No Ref Immunosuppressors Yes 1.583 1.060–2.364 0.025 No Ref Steroids Yes 2.011 1.333–3.032 0.001 2.880 1.619–5.124 <0.001 No Ref Ref Salicilates Yes 0.442 0.189–1.030 0.059 No Ref

Currentconventionaltherapy Biologics Yes 1.701 1.013–2.854 0.044 No Ref Immunosuppressors Yes 1.225 0.795–1.887 0.358 No Ref Steroids Yes 2.473 1.338–4.574 0.004 No Ref Salicilates Yes 0.656 0.410–1.049 0.079 No Ref

Note:Boldmeanssigniﬁcant(p<0,05).

a_Dependent_variable:_MAC_use.

b_Dependent_variable:_MAC_use;_independent_variables:_all_of_those_that_had_a_p_value_below_0.20_in_the_univariated_model_selected_by_the_Forward_method.

threetimesmorelikelytouseCAMthanthosewhohadnottaken anysteroidsinthattimeperiod(OR=2.880,95%CI:1.619,5.124).

4. Discussion

The utilization of CAM seems to be rising among chronic patients,particularlyamongthosethatsufferfromIBD.Butdespite

thecommonperceptionthatCAM issafe,someoftheproducts employedmayhavekidneyandlivertoxicity,and/ormayinteract withconventionaltherapeutics,decreasingtheireffect.The knowl-edgeonthepatternsofCAMuseisfundamentaltotackletheissues mentionedabove.Suchinformationwas,tothebestofour knowl-edge,unavailableinwhatconcernsPortugueseIBDpatients.This

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theirprevalencevaluesreferto“everused”or“currentuse”ofCAM. Still,theCAMutilizationamong PortugueseIBD patientsseems tobesimilar tothat foundacrossother South European coun-tries(23.6%–28.2%inItaly[18,19]and23.1%inSpain[20]),Korea (29.5%–30%[21,22]),UK(26%[23])andHungary(30.9–31.7%[24]). Ontheotherhand,theprevalenceofCAMuseseemstobehigher amongIBD patientsfrom Germany(51.3%–52%[25,26]), France (65.6%[27]),Norway(30–49%[28,29]),Canada(21%–56%[30,31]), Australia(45.4%[32])andNewZealand(44.1%[33]).Ourresults arebased ona59% response ratewhich isless than whatwas achievedinsomepapers[18,28]butsimilartoothers [25].The factthatpatientswerefreetoanswerthequestionnairesathome andreturnedthembymailmayhavehadanegativeimpacton theresponseratebut,inouropinion,itwasimportanttolimitthe constraintsinherenttohospitalenvironment.

RegardingtheoutcomesofCAMuse,67%oftherespondentsin thisstudyreportedfeeling“better”or“muchbetter”.Thisvalue ishigherthanthatfoundamongotherstudiesthataddressedthis parameter,whichvariedbetween26%and55.6%[20,21,23].D’Inca etal.hasfurtheranalysedthespeciﬁcreasonsthatunderliethe patients’satisfactionwithCAM,andobservedthatwhether45.5%of CAMusersreportedageneralsenseofwell-beingbutwithout clini-caleffect,39.7%and21.8%actuallyexperiencedanimprovementin theirIBDsymptomsandareductioninthenumberofﬂares, respec-tively[18].ItisimportanttonoticethatthepositiveeffectsofCAM inthisandotherstudiesareself-reported,andarethereforethe resultofacomplexinteractionbetweenphysicalandpsychological factors,wheretheplaceboeffectcannotbedismissed.

Thepreferences interms of CAM type unveiledan interest-ingpattern:whereashomeopathy,herbalmedicineandChinese traditional medicine appear to have been popular in the time period that preceded the questionnaire administration, herbal medicine,vitamins,meditationandtraditionalChinesemedicine werethepreferredtherapiesbythetimethepatientsenteredthe study.Theseresultsarenotuncommon:homeopathyand/orherbal medicinestendtorankhighamongthepreferencesofEuropean CAMusers[18–20,23–26,29,34].Ontheotherhand,probioticstend tobethepreferredCAM inNorth America [30,31].Onceagain, thesedifferencesmayresultfromasimplemethodologicalbias: withafewexceptions,probioticsarenotconsideredtobeCAM amongEuropeanstudies(andthereforearenotanoptiononthe questionnaires).

Theabsenceofimprovement followingconventionaltherapy was the most cited reason for CAM users to try these thera-pies(33%),followedbythepossiblesideeffectsofconventional therapies(15%)andbytheinabilityofconventionalmedicineto curetheirdisease(14%).Thismotivational context issimilarto that observed in other studies in what concerns the so-called push-factors(i.e.,factorsthatpushapatientawayfrom conven-tionalmedicine)[19,26,30–32,34].Unfortunately,wehavefailedto includeinourquestionnairethepull-factors(i.e.,factorsthatpulla patienttowardCAM),suchasthepossibilitytohaveagreater

con-self-reported.Andif,ononehand,patientsarenotalwayswilling toadmittheydiscontinuedtheirmedication,ontheotherhand, thelackofadherencemayactuallybeunintended(andunnoticed bypatients).Indeed,Nguyenetal.haveshownthatCAMusewas associatedwithalessfavorableadherencetoconventionaltherapy, but97%ofnon-adherentsreportedthattheirattitudewas uninten-tional[31].Conversely,Weizmanetal.concludedthatCAMusewas notassociatedwithalackofadherencetoconventionaltherapies [30].Morestudiesareneededtoclarifythisissueandtodevelop compliance-enhancingstrategiesforIBDpatients,bothCAMusers andnon-users.

Doctor–patientcommunicationandmutualtrustisan unavoid-ablekeyaspectonehastoconsiderwhenaddressingCAMuse.In thisstudy,59%ofCAMusersdidnot disclosethefactthatthey wereusingCAMtotheirphysician,and71%ofthemclaimedthey didsobecausetheywereafraidoftheMDreaction.However,85% ofallIBD patientsin thiscohort wouldappreciatethe possibil-itytodiscussCAMwiththeirattendingphysician.Thisscenariois transversaltodifferentIBDpopulations:aconsiderableproportion ofCAMuserschoosenottodisclosethatinformationtotheir physi-cian[25,30,32].AqualitativestudybyLindbergetal.suggestedthat IBDpatientswouldliketodiscussCAMusewiththeirphysician, buttheydonotinitiateanyconversationonthissubjectforfear theywouldnotbetakenseriously[35].Incontrast, gastroenterol-ogistswereshowntohaveagenerallypositiveattituderegarding CAM:astudyfromGallingerandNguyenbasedonawebsurvey reportedthat68%ofgastroenterologistsbelievedthatCAMcould beagoodadjuvantinIBDtherapyand72%feltcomfortable dis-cussingit[36];aqualitativestudybyLindbergetal.reportedthat healthprofessionalsbelievedCAMbelongedwithinhealthcareand wasrelevanttoconventionaltherapeutics[37].Notwithstanding,a commoncomplaintamongallgastroenterologistsandotherhealth professionalswasthelackofformalknowledgeinthearea.Given theincreasingimportanceandprevalenceofCAMuse,the intro-ductionofCAM-relatedtopicsinmedicalschoolsandworkshops ofcontinuingmedicaleducationisabsolutelynecessary,andwill undoubtedlybeakeysteptofacilitatedoctor-patient communica-tioninthisparticularsubject.

Thefemalegender,youngerage,collegeeducation,previoususe ofimmunosuppressorsandsteroids,andcurrentuseofbiologicals andsteroidsweresigniﬁcantlyassociatedwithCAMuse.College instructionandprevioususeofsteroidswereactually indepen-dentpredictorfactorsofCAMuse,withORsof3.669and2.880, respectively. These relationships have been noticed before in severalstudiesand, oppositetowhat happens withotherCAM usefeatures,seemtobetransversalacrossdifferentgeographic locationsandIBDpopulations[18,19,22,24,26,28–30,32,33].Other factorsassociatedwithCAMusehavebeendepictedinother stud-ies,butthosewereeithernotexploredorfailedtobeassociated withCAMuseinthepresentstudy:evidenceforahealth-conscious lifestyle, number of hospital admissions and consultations, drug-sideeffectsandothercomplications,relapses,long-term

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evo-lution of the disease,need for psychologicalsupport, presence ofextra-intestinalmanifestations,permanentemployment,higher incomeandpresenceofco-morbidities[18–20,22,26,28,32,33,38]. Conventional therapies have known side effects, the fear of whichmayleadpatientstoresorttoCAMinthesearchofwhat theybelievetobea more naturaland less toxicapproach. The factthat previoususeof steroidswasfoundasanindependent predictorofCAMusecanbe,atleastinpart,explainedbytheside effectsproﬁleofthesedrugs.Steroidscanalsobeconsidereda sur-rogatemarkofamoderateorseveredisease,whichhasbeenlinked toCAMuseinotherstudies[18,19,22,29].Ontheotherhand,the associationofCAMusetoahighlevelofinstructionisquite com-monandmayberelatedtothefactthatcollege-educatedpatients aremoreresourcefulandmorelikelytoexploretheirIBDdisease fromdifferentperspectives.Moreover,theuseofCAMgivesthema senseofcontrolovertheirdisease.Additionally,theyarealsomore likelytobeabletoaffordCAM:infact,andasshownbythisand otherstudies,CAMuseisratherexpensive[18,27].Theassociation ofCAMusewithpermanentemploymentandhigherincomeseen inotherstudiessupportsthishypothesis[22,32,33].Still,the rela-tionshipbetweencollegeeducationandtheuseoftherapiesmostly deprivedofscientiﬁcsupportmeritsfurtherstudies.

Thisstudywasbasedonananonymousquestionnairethatwas distributedacrosstheentirecountry(ruralandurbanareas)and includedpatientsindifferentstagesandwithdifferentseverityof thediseases(patientswererecruitednotonlyfrommedical consul-tationsbutalsofromthePortugueseassociationofIBDpatients).It has,however,afewlimitationsthatshouldbenoticed.Oneofthem isinherenttoallquestionnaire-basedCAMassessments–thelack ofconsistencybetweenthequestionnairesadministeredin differ-entcountriesmakestheircomparisonsdifficultorevenimpossible. Thedevelopmentandnational-validationofaninternationalCAM questionnairewithaprecisedefinitionofwhatshouldbe consid-eredCAM[39],aswellasthethroughoutcharacterizationofthe populationenrolled,arekeystepstosolvetheseissues.Another limitationreferstothefactthatthestudiedpatientswereinpart recruitedfromconventionalmedicinecarecenters:satisfiedusers ofCAMareunlikelytoattendthesecenters,whichintroducesa biasinthesamplingprocess.ThediseasestatusandCAM improve-mentswereself-reportedandnotobjectivelyevaluated–thisis anunavoidableconsequenceofkeepingthequestionnaires anony-mous;however,itdoespreventonetoidentifyplaceboeffectsand inflammatory bowelsyndrome-relatedworsening ofsymptoms. Finally,thequestionnairewasnotpreviouslyvalidated,itdidnot explorepositivemotivationalfactors,andwehadnoinformation onthepatients’psychologicalstateofmindandHRQoL.

Asa globalconclusion, theCAMusepatternsofIBDpatients inPortugalmatchthosepreviouslyfoundamongotherEuropean countries:thetypicaluserisayoungfemalewithacollege educa-tionandanhistoryofsteroidsprescription,whereasthepreferred CAMtypeisherbalism.Theprevalenceisratherhighandis intrin-sically linked with the perceived inability of the conventional medicinetoproducepositiveoutcomes.Patient-doctor communi-cationisanissue:patientswouldliketodiscussCAMwiththeir physicians,but theyfear theirreaction andend upnot disclos-ingCAMuse.Medicinefacultiesandcontinuingmedicaleducation shouldinvestin disseminating formalknowledge onCAM, and physicians should improve their empathy and understand the beneﬁtsofanintegrativehealthcare,includingconventionaland non-conventionaltherapies.Thiswouldlikely enhancepatients’ complianceandsolvepossibleCAM-relatedadherenceissues.

Conﬂictofinterest

F.Portelareceivedapresentingfeefrom:AbbVie,Ferring,MSD, ViforPharma.FMagroreceivedapresentingfeefrom:AbbVie,

Fer-ring,Falk,Hospira,PharmaKern,MSD,Schering,Lab.Vitoria,Vifor, OmPharma.Allothersauthors:nonetodeclare.

Support

GEDII(PortugueseIBDStudyGroup).

Acknowledgments

TheauthorswouldliketoexpresstheirgratitudetoAbbviefor supportingmail-relatedexpenses,toSandraDiasforhersupportas thecoordinatorofthenationalIBDgroup(GEDII–GrupodeEstudo deDoenc¸asInﬂamatóriasIntestinais),andtoCatarinaL.Santosfor medicalwritingassistance.

References

[1]DignassA,EliakimR,MagroF,etal.SecondEuropeanevidence-basedconsensus onthediagnosisandmanagementofulcerativecolitispart1:deﬁnitionsand diagnosis.JournalofCrohn’s&Colitis2012;6:965–90.

[2]VanAsscheG,DignassA,PanesJ,etal.ThesecondEuropeanevidence-based consensusonthediagnosisandmanagementofCrohn’sdisease:deﬁnitions anddiagnosis.JournalofCrohn’s&Colitis2010;4:7–27.

[3]AlarhayemA,AchebeE,LogueAJ.Psychosocialsupportoftheinﬂammatory boweldiseasepatient.TheSurgicalClinicsofNorthAmerica2015;95:1281–93, vii–viii.

[4]SzkudlapskiD,LabuzekK,PokoraZ,etal.Theemeringroleofhelminthsin treatmentoftheinﬂammatoryboweldisorders.JournalofPhysiologyand Pharmacology2014;65:741–51.

[5]MoserG.Theroleofhypnotherapyforthetreatmentofinﬂammatorybowel diseases.ExpertReviewofGastroenterology&Hepatology2014;8:601–6. [6]SzigethyE.Hypnotherapyforinﬂammatoryboweldiseaseacrossthelifespan.

TheAmericanJournalofClinicalHypnosis2015;58:81–99.

[7]PetersSL,MuirJG,GibsonPR.Reviewarticle:gut-directedhypnotherapyinthe managementofirritablebowelsyndromeandinﬂammatoryboweldisease. AlimentaryPharmacology&Therapeutics2015;41:1104–15.

[8]JoosS.Reviewonefﬁcacyandhealthservicesresearchstudiesof complemen-taryandalternativemedicineininﬂammatoryboweldisease.ChineseJournal ofIntegrativeMedicine2011;17:403–9.

[9]SalagaM,ZatorskiH,SobczakM,ChenC,FichnaJ.Chineseherbalmedicines inthetreatmentofIBDandcolorectalcancer:areview.CurrentTreatment OptionsinOncology2014;15:405–20.

[10]AlgieriF,Rodriguez-NogalesA,Rodriguez-CabezasME,RiscoS,OceteMA, GalvezJ.Botanicaldrugsasanemergingstrategyininﬂammatorybowel dis-ease:areview.MediatorsofInﬂammation2015;2015:179616.

[11]TriantafyllidiA,XanthosT,PapaloisA,TriantaﬁllidisJK.Herbalandplant ther-apyinpatientswithinﬂammatoryboweldisease.AnnalsofGastroenterology 2015;28:210–20.

[12]GilardiD,FiorinoG,GenuaM,AlloccaM,DaneseS.Complementaryand alter-nativemedicineininﬂammatoryboweldiseases:whatisthefutureinthe ﬁeldofherbalmedicine?ExpertReviewofGastroenterology&Hepatology 2014;8:835–46.

[13]JiJ,LuY,LiuH,etal.Acupunctureandmoxibustionforinﬂammatorybowel dis-eases:asystematicreviewandmeta-analysisofrandomizedcontrolledtrials. Evidence-BasedComplementaryandAlternativeMedicine2013;2013:158352. [14]ClarkeJO,MullinGE.Areviewofcomplementaryandalternativeapproaches

toimmunomodulation.NutritioninClinicalPractice2008;23:49–62. [15]NguyenDL,LimketkaiB,MediciV,SaireMendozaM,PalmerL,BechtoldM.

Nutritionalstrategiesinthemanagementofadultpatientswithinﬂammatory boweldisease:dietaryconsiderationsfromactivediseasetodiseaseremission. CurrentGastroenterologyReports2016;18:55.

[16]BilskiJ,Mazur-BialyA,BrzozowskiB,etal.Canexerciseaffectthecourseof inﬂammatoryboweldisease?Experimentalandclinicalevidence. Pharmaco-logicalReports2016;68:827–36.

[17]MouraFA,deAndradeKQ,dosSantosJC,AraujoOR,GoulartMO.Antioxidant therapyfortreatmentofinﬂammatoryboweldisease:doesitwork.Redox Biology2015;6:617–39.

[18]D’IncaR,GarribbaAT,VettoratoMG,etal.Useofalternativeand complemen-tarytherapiesbyinﬂammatoryboweldiseasepatientsinanItaliantertiary referralcentre.DigestiveandLiverDisease2007;39:524–9.

[19]BertomoroP,RennaS,CottoneM,etal.Regionalvariationsintheuseof com-plementaryandalternativemedicines(CAM)forinﬂammatoryboweldisease patientsinItaly:anIG-IBDstudy.JournalofCrohn’s&Colitis2010;4:291–300. [20]FernandezA,Barreiro-deAcostaM,VallejoN,etal.Complementaryand alter-nativemedicineininﬂammatoryboweldiseasepatients:frequencyandrisk factors.DigestiveandLiverDisease2012;44:904–8.

[21]KimSB,ParkSJ,ChungSH,etal.Vaccinationandcomplementaryand alterna-tivemedicineinpatientswithinﬂammatoryboweldisease.IntestinalResearch 2014;12:124–30.

(9)

[27]AbitbolV,LahmekP,BuissonA,etal.Impactofcomplementaryandalternative medicineonthequalityoflifeininﬂammatoryboweldisease:resultsfroma Frenchnationalsurvey.EuropeanJournalofGastroenterology&Hepatology 2014;26:288–94.

[28]OpheimR,BernklevT,FagermoenMS,CvancarovaM,MoumB.Useof com-plementaryandalternativemedicineinpatientswithinﬂammatorybowel disease:resultsofacross-sectionalstudyinNorway.ScandinavianJournalof Gastroenterology2012;47:1436–47.

[29]OpheimR,HoivikML,SolbergIC,MoumB,GroupIS.Complementaryand alter-nativemedicineinpatientswithinﬂammatoryboweldisease:theresultsofa population-basedinceptioncohortstudy(IBSEN).JournalofCrohn’s&Colitis 2012;6:345–53.

[30]WeizmanAV,AhnE,ThanabalanR,etal.Characterisationof complemen-taryandalternativemedicineuseanditsimpactonmedicationadherence ininﬂammatorybowel disease.AlimentaryPharmacology &Therapeutics 2012;35:342–9.

[36]GallingerZR,NguyenGC.Practicesandattitudestowardcomplementaryand alternativemedicineininﬂammatoryboweldisease:asurveyof gastroenterol-ogists.JournalofComplementary&IntegrativeMedicine2014;11:297–303. [37]LindbergA,EbbeskogB,KarlenP,OxelmarkL.Inﬂammatoryboweldisease

professionals’attitudestoandexperiencesofcomplementaryandalternative medicine.BMCComplementaryandAlternativeMedicine2013;13:349. [38]Sirois FM. Health-related self-perceptions over time and provider-based

complementaryandalternativemedicine(CAM)useinpeoplewith inﬂam-matory boweldisease orarthritis. ComplementaryTherapiesinMedicine 2014;22:701–9.

[39]QuandtSA,VerhoefMJ,ArcuryTA,etal.Developmentofaninternational questionnairetomeasureuseofcomplementaryandalternativemedicine (I-CAM-Q).JournalofAlternativeandComplementaryMedicine2009;15:331–9.