Optimizing drug therapy in patients with advanced dementia: A patient-centered approach

Pharmacology applied to geriatric medicine

Optimizing drug therapy in patients with advanced dementia:

A patient-centered approach

N. Molist Brunet

*, D. Sevilla-Sa´nchez

, J. Ambla`s Novellas

, C. Codina Jane´

, X. Go´mez-Batiste

, J. McIntosh

, J. Espaulella Panicot

aHospitaldelaSantaCreu,ConsorciHospitalarideVic,Vic,Spain

bHospitaldelaSantaCreu,HospitalGeneraldeVic,consorciHospitalarideVic,Vic,Spain

cHospitalClı´nicdeBarcelona,HospitalGeneraldeVic,Vic,Barcelona,Spain

dPalliativeCareCathedra,UniversidaddeVic,Vic,Barcelona,Spain

eHospitalClı´nicdeBarcelona,Barcelona,Spain

1. Introduction

As the world population continues aging, there will be an increasingnumber of patients withadvanced, complexchronic disease [1]. Many of these patients will deteriorate clinically, functionally,orcognitively,ultimatelyresultinginasituationof limited prognosis [2]. Advanced dementia is one suchchronic condition, and is a problem of serious consequence with a prevalenceashighas80%innursinghomepatients,makingita pressingconcernforbothpatientsandproviders[3,4].

Multi-morbidity is common amongst patients with chronic conditions. This often leads to complex treatment regimens,

evidenced bythepresenceof polypharmacy (definedasfive or more medications)[5] and by theheterogeneityof therapeutic goals,which ofteninclude preventive,therapeutic,and sympto- maticobjectives.Whenapproachingend-of-lifecare,asinthecase ofadvanceddementia,boththenumberofandtheindicationfor themedicationshouldbeevaluated,withthepriorityplacedon symptomaticversuspreventioncare.

Pharmaceuticalcareiswelldefinedinthelastdaysorhoursof life, with the primary focus on symptomatic care and the alleviation of suffering [6–8].In contrast,pharmacological care duringthebroaderend-of-lifetimeframeislesswelldefinedand therearenospecificguidelines,owinginparttolimitedclinical trialdatainthispopulationandtheuncertainprognosisofthese patients [6,9]. Although during this stage a primary goal is symptom management, this is not incompatible with other treatmentobjectives.Thus,a dynamicandsystematic reviewof apatient’s medicationprofileiscalledfor,withtheobjectiveof ARTICLE INFO

Articlehistory:

Received3July2013 Accepted24October2013 Availableonline21November2013

Keywords:

Polypharmacy Advanceddementia End-of-lifecare

ABSTRACT

Background:Advanceddementiais aprevalenthealthproblemingeriatric patients.Thesepatients usuallysufferfromseveralchronicdiseases,frequentlyleadingtoanend-of-lifesituationlastingmonths oryears,generatingcomplexandofteninappropriatemedicationregimens.

Objectives:Describethere-orientationofdrugtherapyinpatientswithadvanceddementiautilizinga systematicmedicationreviewprocess.

Methods: This non-experimental pre-post analysis included all patients with advanced dementia admittedtoacutegeriatricunit(AGU)overoneyear.Medicationswerereviewedbyamultidisciplinary teamandtogetherwiththepatientcaregivers;newtherapeuticobjectivesbasedonend-of-lifecare principleswereestablished.Medicationswereclassifiedaspreventive,therapeutic,orsymptomatic.The averagenumberofmedicationsperpatientpre-andpost-admissionwascompared.

Results:Weincluded73patients(meanage86.1years,meanBarthelIndex:14.5/100).Atadmission, patientshadameanof7.27drugscomparedto4.82atdischarge(66.85%reduction,P<0.05).Themain drugswithdrawnwerecardiovascularandhematological(35.76%).Drugsforpreventiondecreasedby 66.85%(from1.8to0.6,P<0.05)andthoseforsymptomaticcaredecreasedby17,52%(from2.34to1.93, P<0.05).

Conclusion:Medicationtherapyplansinpatientswithadvanceddementiaoftendonot meettheir therapeuticgoals.Theproposedmethodologyisausefultooltoassesstherapeuticappropriateness.

ß2013ElsevierMassonSASandEuropeanUnionGeriatricMedicineSociety.Allrightsreserved.

* Corresponding author. Acute Geriatric Units,Hospital Generalde Vic. C/

FrancescPlaelVigata`,s/n,08500Vic,Barcelona,Spain.Tel.:+34938891111,ext:

1503.

E-mailaddress:[email protected](N.MolistBrunet).

Availableonlineat

ScienceDirect

www.sciencedirect.com

1878-7649/$–seefrontmatterß2013ElsevierMassonSASandEuropeanUnionGeriatricMedicineSociety.Allrightsreserved.

http://dx.doi.org/10.1016/j.eurger.2013.10.011

adjustingtherapytomeetthetrueneedsofthepatient.Thisoften requires a re-orientation in regard to therapies for chronic conditions, includingboth initiatingdiscontinuing, medications chronicmedications.

Raising the withdrawal of chronic therapies constitutes a professionalchallengeforseveralreasons:

itrequirestheidentificationofpatientswhoarewithinthelast monthsoryearoflife;

it requires defining new drug therapy goals, evaluating the potentialrisksofdiscontinuingaspecificmedication[10].

Bothofthesearefeasibleinpatientswithadvanceddementia,a diseasewellestablishedasaterminalillnesswheretheprimary goals focuson symptomatic care[11].Furthermore, removalof unnecessarydrugsmaybebeneficial tothepatient,ascomplex drugtherapyandtheresultingpolypharmacymayincreasetherisk ofadversedrugevents[12–14].

Recently,publishedrecommendationsforend-of-lifepharma- cotherapy provide guidance on individualizing drug therapy regimens [15–17]. This requires re-thinking the prescription process, utilizing criteria specific to this patient population including:

avoidingdrugtherapywheretheprimarygoalisextendinglife;

avoidingtreatmentsforprimaryprevention(thetime-to-benefit islongerthanthepatient’slifeexpectancy);

individualizingtheuseofsecondaryprevention(ensuringtime- to-benefitiswithintheexpectedlifespan);

reducingthenumberofmedicationsperpatient,movingfroma stateofpolypharmacytooligopharmacy(lessthan5medications perpatient);

definingtreatmentgoalsjointlywithpatientsorcaregiver;

acknowledgingthattheprocesswillbedynamicandwillrequire continuousreassessment;

involving multiple health care professionals to create multi- disciplinarycareteams[15].

Theobjectiveofthestudyistodescribethere-orientationof drugtherapyutilizingasystematicapproachfocusingonpatient cantered goals in a groupof patients with advanced dementia admittedtoanacutegeriatricunit(AGU).

2. Methods

Weconductedanon-experimentalpre-postevaluationofthe standardmedicalmanagementofpatientsadmittedtotheAGUin asecondarycareregionalhospitalinCatalonia,SpainbetweenMay 2011 and April 2012. This evaluation includes patients with advanced dementia, defined as either having all three of the following:aninabilitytocompleteactivitiesofdailyliving(Barthel indexless thanorequal to30/100),incontinenceand difficulty recognizingfamilymembers(GlobalDeteriorationScale greater thanorequalto6dincaseofAlzheimertypedementia).Patients whodiedduringhospitalizationwereexcluded.

2.1. Developingmedicationtherapyplan

Inordertocreateanewpatientcantereddrugtherapyregimen, allpatientmedicationprofilesweresystematicallyevaluatedina three-stageprocessbyamultidisciplinaryteamconsistingoftwo geriatriciansandaclinicalpharmacist(Fig.1).

2.1.1. Patientcenteredassessment

Weconductedaninitialmultidimensionalgeriatricassessment ofclinical,functional,cognitive,andsocialindicators.Theobjective

ofthisreviewwastoemployagoal-orientedapproach,takinginto accounttheevolutionarystateofthechronicdisease,toguidecare decisions [18]. If patients were not able to communicate for themselves,thevalues andpreferencesofcaregiversweretaken intoaccountwhenestablishingtherapeuticgoals.Attheendofthis review, newtherapeutic goals were established,guided by the known criteriaforrecognizingkey transitionsattheend-of-life [19].

2.1.2. Diagnosiscentredassessment

Patienthealthproblemswerelistedtogetherwiththemedica- tions prescribed for each diagnosis. Eachmedication was then classified byits objective and placed into oneof the following categories:

preventivetherapies(primaryorsecondary);

therapeuticorcurativetreatments;

orsymptomatictherapy.

Inthisstage,weevaluatedtheapplicabilityofclinicalpractice guidelinesaccordingtoeachpatient’stherapeuticgoals.Although allmedicationswerereviewed,specialattentionwaspaidtothose previouslyidentifiedintheliteratureashavingahighpotentialfor discontinuationattheend-of-life,suchasthoseusedforprimary prevention.(Table1)[15–17].Thisallowedustomakeprescribing decisions based on both the therapeutic objective of the medication and thepreviously established therapeuticgoals of thepatient.

2.1.3. Medicationcentredassessment

We also assessed the medication profile for drug-related problems(Fig.1).

Based on this process, we developed patient-specific thera- peuticplansforeachpatient.

2.2. Datacollectionandanalysis

Basicpatientdemographicinformationwascollected,including age, sex, living arrangements (own home or residence), and discharge destination. The Barthel Index was used to measure functionalityatadmissionandatdischarge.Thechiefcomplaint, length of stay, and presence of delirium duringhospitalization werealsorecorded.Toassessthepresenceofpolypharmacy,the numberofmedicationspre-andpost-admissionwerecollected, along with the number of medication added or discontinued duringthehospitalization.

Finally, we performed a statistical analysis consisting of calculating the differences in the number of medications at admission and discharge using the non-parametric Wilcoxon signed-rank test (SPSS software 15.0) with a significance of P<0.05.Non-normalityofdistributionwasassessedbygoodness- of-fittestofKolmogorov–Smirnov.

3. Results

3.1. Patientdemographics

Duringthestudyyear,atotalof934patientswereadmittedto theAGU,ofwhich73(7.81%)mettheinclusioncriteria.

Ofthoseincludedinthestudy,79.45%werewomenandthe meanagewas86.1years(SD:5.73,range72–100).Themajorityof patients(58.9%)wereinstitutionalized(fromnursinghomes)and theremainderwerelivingathome.ThemeanBarthelIndexofthe studypopulationwas14.5/100.

Themainadmissiondiagnoseswere:trauma35.61%(fractureof thefemur84.52%),infection36.98%(respiratoryinfections44.34%

andurinary tractinfections33.26%), andcardiovasculardisease 20.54%(worseningofheartfailure,acutecoronarysyndromeand cardiacdysrhythmia,etc.).Theaveragestaywas4.89days(global averageduringthesameperiodfortheentireunitwas6.2days).

Almosthalf(43.80)%of thepatients had acute deliriumduring hospitalization.Atdischarge,57.5%ofthepatientswerereferredto their originalplace ofresidenceand theremaining 42.5% were dischargedtoanintermediatecarehospital.

3.2. Medicationprofiles

Patientshadanaverageof7.27medicationspriortohospita- lization,and 82.2% metthecriteria forpolypharmacy. Ofthese medications, 24.80% (average of 1.81 per patient) were for prevention,ofwhich76.2%wereforprimaryprevention(average of 1.38 per patient) and 23.8% were for secondary prevention (averageof0.43perpatient).Medicationsfortherapeuticpurposes represented42.91%ofallmedications(meanof3.12perpatient), andthoseforsymptomaticcarerepresented32.2%(meanof2.34 perpatient)(Table2).

Theaverage number ofmedications perpersonat discharge decreasedby2.45perperson(66.30%)to4.8,excludingtemporary medications initiated to address the chiefcomplaint (Table 2).

Decreases wereseenin all groups (preventive,therapeuticand symptomatic)althoughthemostcommonlydiscontinuedmedica- tionswereforprevention.Two-thirds(66.85%)ofthepreventive medicineswerediscontinuedduetolackofevidenceinanelderly patientpopulation,withthevastmajority(78.50%)indicatedfor primary prevention. More than a quarter (27.24%) of drugs designatedfortreatmentwerediscontinuedduetolackofaclear indication,anddrugsforsymptomaticcontrolwerealsodecreased by17.52%.

Themostcommon systems affectedbymedication disconti- nuationswerethecardiovascularandbloodsystem,accountingfor 35.70%ofalldiscontinuedmedications,followedbydrugsforthe nervous system (19.56%), drugs related to the metabolism or nutrition(16.77%),andmusculoskeletalsystem(14.52%)(Table3).

Duringtheadmission,newmedicationswerestarted,ofwhich 54.30% were to treat the chief complaint and were of limited duration. The most frequently added new medications were:

Fig.1.Methodologyfordevelopmentofpatientcenteredmedicationplan.

antibiotics, (20.43%), low-molecular weight heparin (18.28%), corticosteroids (8.60%)and gastroprotectants (6.99%). Although allpatientswerereceivingend-of-lifecare,somemedicationswere alsoadded for therapeuticpurposes,representing20.43% ofall newmedications.Digoxinforatrialfibrillationandantihyperten- siveswerethemostcommonlyadded.Finally,24.73%ofnewdrugs were to improve symptom control, such as analgesics NSAIDs (26.90%),laxatives(18.40%)andneuroleptics(16.10%).

Althoughthetotalnumberofmedicationsineachthreegroups decreased,becausesignificantlymoremedicationsforprevention werediscontinuedcomparedtotherapeuticorsymptomaticcare, the later two represented a larger proportion of the overall medication profile at discharge (Table 2). For example, at admission, therapeutic medications represented 42.90% of all drugs,butthisproportionroseto47.10%atdischarge.Similarly, symptomatic medications went from 32.20% to 40.20% while preventivemedicationsfellfrom24.80%toonly12.65%.

4. Discussion

Theoptimizationofmedicationtherapyinfrailpatientsatthe end-of-liferemainsachallengetothecurrenthealthcaresystem.

Thisstudydemonstratesthatpatientswithadvanceddementia areoftenmaintainedondrugtherapyforchronicconditionsthat failtotakeintoaccountthepatient’sglobalcondition.Thisis reflected quantitatively by the fact that polypharmacy is common amongst this population and qualitatively, in that thetherapywasnottargetedtotherealneedsofthepatient.We proposeasystematicmethodologythatpersonalizesmedication therapy,whichweappliedtopatientswithadvanceddementia.

In this subgroup of patients, we significantly decreased the number of prescribed medications, from an average of 7.3 chronicmedicationsperpatientatadmissionto4.8atdischarge.

This reduction was primarily seen amongst medications for primaryprevention.

Table2

Preventive,therapeuticandsymptomaticmedicationsaffectedbyproposedchangesintherapeuticgoals.

Averagenumberofmedicationsperpatient Admission Discharge(includingshort-term

andlong-termmedications)

Discharge(excludingshort-term, admission-relatedmedications)

Differencebetween admissionanddischarge

P

Preventivetherapies 1.81(24.8%) 1.44(19.61%) 0.60(12.65%) –1.21(–66.85%) <0.05

Primary 1.38(18.9%) 1.30(17.71%) 0.43(8.92%) –0.95(–68.84%) <0.05

Secondary 0.43(5.9%) 0.14(1.90%) 0.17(3.52%) –0.26(–60.46%) <0.05

Therapeutictreatments 3.12(42.91%) 3.41(46.45%) 2.27(47.1%) –0.85(–27.24%) <0.05

Symptomatictreatment 2.34(32.2%) 2.49(33.92%) 1.93(40.24%) –0.41(–17.52%) <0.05

Total 7.27 7.34 4.8 –2.45(–66.3%) <0.05

Table1

Therapeuticgroups,basedonanatomicaltherapeuticchemical(ATC)classificationsystem,evaluatedinpatientsattheend-of-life.

Anatomicalgroup Therapeuticclass

A:Alimentarytractandmetabolism

Antidiabetics Metformin

Thiazolidinediones

Anti-ulcer(Gastroprotectants) ProtonPumpInhibitors

Antihistamines B:Bloodandbloodformingorgans

Antiplateletandanticoagulant Acetylsalicylicacidandclopidogrel

Anti-anemics Acenocoumarol,warfarina,dabigatran,rivaroxaban

Iron

VitaminB12;folicacid

Lipidmodifyingagents Statins

Fibrates C:Cardiovascular

Antihypertensives Angiotensinconvertingenzymeinhibitorsforpreventionofnephropathy

AngiotensinIIreceptorantagonistsforpreventionofnephropathy H:Hormonal

Drugsforbone-disease CalciumandvitaminDsupplements

Bisphonophonates Teriparatide Estrogen J:Anti-infectives

Bacterialinfections ProphylacticantibioticsAntibio´ticosprofila´cticos

L:Antineoplasticsandimmunomodulatingagents

Cytotoxics Cytotoxicandchemotherapeuticagents

Vaccines Preventivevaccines

M:Musculoskeletal

Anti-inflammatory Non-steroidalanti-inflamatories

Antiarthritics Cytotoxicandbiologictherapy(monoclonalantibodies)

N:Nervoussystem

Anti-dementiadrugs Acetylcholinesteraseinhibitors

Memantine

Anti-Parkinson Anticholinergicstotreatextrapyramidaleffectsofneuroleptics

Antidepressants Tricyclicantidepressants

Anxiolyticsandhypnotics Benzodiazapineswithlonghalf-life

R:Respiratorysystem

Antiasthmatics Theophyline

Theseresultsareconsistentwithotherstudiesinfrailelderly patientsinotherhealthcaresettings[20–22].Aprogramtoaddress polypharmacyinelderlycommunitydwellingpatientsresultedin anaveragedecreaseof4.4medicationperpatient[21]whereasan interventioninageriatricspecialtyhospitaldecreasedmedications by 47% (2.8) per patient [20]. Importantly, these previously publishedstudiesdidnotreportanincreaseinadverseevents,and familiesreportedanincreaseinthequalityoflife,functionality, andcognitivestatus.

Althoughit wasnottheprimaryobjective ofthis study,our resultsconfirmthatpatientswithadvanceddementiapresentwith highlevelsofdependency,asmorethanhalfofthepatientsinthis studywerelivinginaninstitutionalsetting.Wealsoconfirmthat inthis population,infection and traumaarethe mostfrequent reasonsforhospitalization, followed bytheworsening ofother chronicconditions.Furthermore,weobservedfrequenttransitions betweencarelevelswithnearlyhalf ofdischargedpatients not returningtotheoriginallivingsituationandwithmanyofthese goingtoanintermediatecareunit. Thishighlightstheneedfor clearcommunicationbetweenhospitalists,primarycareproviders, patients,andhealthcareprovidersinintermediatecarefacilitiesto preventmedicationerrorsandensurecontinuityofcare[23].

Studies in patients with advanced dementia have typically emphasizedthenaturalhistory ofthediseaseand theresulting problems,but few have resulted in interventionsthat improve pharmacologicaloutcomes[10].Particularlyin theareaof drug therapy, interventions have primarily focused on anticholines- terases and neuroleptics [24], but interventions addressing the overall patient status are lacking. In this study, we describe a methodologytopersonalizemedicationtherapyinpatientswith advanced dementia,resulting in medication therapy plans that take intoaccount theglobal status of thepatient. Thistype of patient-centreddrugtherapyinterventionisthebasisofpatient- centredcare[18],andisapplicabletootherpatientsattheend-of- life,includingthosewithextremelyfrailtyorwithadvancedstage organdiseaseorcancer[25].Forexample,ourproposedsystematic reviewofdrugtherapycanbeusedinparallelwithexistingtools designedtoidentifypotentiallyinappropriatemedicationsinthe elderly,suchtheBeerscriteriaorSTOPP/START[26,27],whichmay notalwaystakeintoaccounttheneedsofanindividualpatient.

This work reflectsthe processdeveloped by our multidisci- plinary team of geriatricians and a clinical pharmacist, and representsa continuous evaluation ofthe drugtherapy profile.

Thebasisofthisprocessis establishingappropriatetherapeutic goalsattheend-of-life,andthenrealigningdrugtherapytomeet thesegoals.

Oneofthelimitationsofthecurrentstudyisthelackofdataon patientoutcomes.Assessingthehealthandqualityoflife,adverse eventsduetomedicationwithdrawal,andtheeconomicimpactof our intervention would have strengthened the results. Future researchshouldaddressthesequestions.

Inconclusion,patientswithadvanceddementiaoftenreceive inadequatedrugtherapy withmany medicationsprescribedfor primary prevention, and the majority of patients meeting the criteria for polypharmacy. Consequently, these patients could benefitfromthepersonalizationoftheirmedicationtherapyfrom a multidisciplinary team,leading to betteragreement between clinical objective that prioritize symptomatic control and the patient’smedicationprofile.

Disclosureofinterest

The authors declare that they have no conflicts of interest concerningthisarticle.

Acknowledgments

We thank to Pere Roura for technical help with statistical analysis.

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Table3

Typeofmedicationschangedordiscontinuedbyorgansystemanddrugclass.

Organsystem Drugclass

Cardiovascularand hematologic(35.76%)

Antiplatlets:13.41%

Antihypertensives:9.50%

Hipolypidemics:5.59%

Anticoagulants:2.23%

Othercardiovascular:5.03%

Nervoussystem(19.56%) Antidepressants:9.50%

Benzodiazapinesandneuroleptics:8.38%

Dementiatherapies:1.68%

Alimentarytractand metabolism(16.77%)

Nutritionalsupplements:8.94%

Gastroprotectants:6.15%

Antidiabetics:1.68%

Musculoskeletal(14.52%) Antiresorptive:7.82%

Analgesics(NSAIDs):6.70%

Respiratory(1.68%) Anti-asthmatics

Genitourinary(0.56%) Antispasmodicsandanticholinergics

Other(11.15%) Eyedrops

Lowvalueintrinsicmedications:brain vasodilatorsandnootropicsdrugs;

chondroprotectors

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