End-of-Life Decisions: A Cross-National Study of Treatment Preference Discussions and Surrogate Decision-Maker Appointments

Transcription

1 En-of-Life Deisions: A Cross-National Stuy of Treatment Preferene Disussions an Surrogate Deision-Maker Appointments Natalie Evans *, H. Roeline Pasman, Tomás Vega Alonso 2, Lieve Van en Blok 3, Guio Miinesi 4, Viviane Van Casteren 5,GéDonker 6, Stefano Bertolissi 7, Osar Zurriaga 8,9,0, Lu Deliens,3, Bregje Onwuteaka-Philipsen, on behalf of EUROIMPACT " Department of Publi an Oupational Health, EMGO + Institute, VU University Meial Center, Amsteram, The Netherlans, 2 Publi Health Diretorate, Ministry of Health (Direión General e Salu Públia, Consejería e Sania), Vallaoli, Castille an León, Spain, 3 En-of-Life Care Researh Group, Vrije Universiteit Brussel, Brussels, Belgium, 4 Clinial an Desriptive Epiemiology Unit, Caner Prevention an Researh Institute, (ISPO L Istituto per lo Stuio e la Prevenzione Onologia), Florene, Italy, 5 Sientifi Institute of Publi Health (WIV-ISP - Wetenshappelijk Instituut Volksgezonhei, Institut Sientifique e Santé Publique), Brussels, Belgium, 6 Netherlans Institute of Health Servies Researh (NIVEL - Neerlans instituut voor onerzoek van e gezonheiszorg), Utreht, The Netherlans, 7 Italian Soiety of General Pratie (SIMG Soietà Italiana i Meiina Generale), Florene, Italy, 8 Publi Health an Researh General Diretorate, Valenian Regional Health Aministration, Valenia, Spain, 9 Higher Publi Health Researh Centre (CSISP - Centro Superior e Investigaion en Salu Públia), Valenia, Spain, 0 Spanish Consortium for Researh on Epiemiology an Publi Health (CIBERESP - El Consorio e Investigaión Bioméia e Epiemiología y Salu Públia), Mari, Spain Abstrat Bakgroun: Making treatment eisions in antiipation of possible future inapaity is an important part of patient partiipation in en-of-life eision-making. This stuy estimates an ompares the prevalene of GP-patient en-of-life treatment isussions an patients appointment of surrogate eision-makers in Italy, Spain, Belgium an the Netherlans an examines assoiate fators. Methos: A ross-setional, retrospetive survey was onute with representative GP networks in four ountries. GPs reore the health an are harateristis in the last three months of life of 4,396 patients who ie non-suenly. Prevalenes were estimate an logisti regressions were use to examine between ountry ifferenes an ountryspeifi assoiate patient an are fators. Results: GP-patient isussion of treatment preferenes ourre for 0%, 7%, 25% an 47% of Italian, Spanish, Belgian an of Duth patients respetively. Furthermore, 6%, 5%, 6% an 29% of Italian, Spanish, Belgian an Duth patients ha a surrogate eision-maker. Despite some ountry-speifi ifferenes, previous GP-patient isussion of primary iagnosis, more frequent GP ontat, GP provision of palliative are, the importane of palliative are as a treatment aim an plae of eath were positively assoiate with preferene isussions or surrogate appointments. A iagnosis of ementia was negatively assoiate with preferene isussions an surrogate appointments. Conlusions: The stuy reveale a higher prevalene of treatment preferene isussions an surrogate appointments in the two northern ompare to the two southern European ountries. Fators assoiate with preferene isussions an surrogate appointments suggest that elaying iagnosis isussions impees antiipatory planning, whereas early preferene isussions, partiularly for ementia patients, an the provision of palliative are enourage partiipation. Citation: Evans N, Pasman HR, Vega Alonso T, Van en Blok L, Miinesi G, et al. (203) En-of-Life Deisions: A Cross-National Stuy of Treatment Preferene Disussions an Surrogate Deision-Maker Appointments. PLoS ONE 8(3): e oi:0.37/journal.pone Eitor: Thomas A. Smith, Swiss Tropial & Publi Health Institute, Switzerlan Reeive Otober 25, 202; Aepte January 29, 203; Publishe Marh 5, 203 Copyright: ß 203 Evans et al. This is an open-aess artile istribute uner the terms of the Creative Commons Attribution Liense, whih permits unrestrite use, istribution, an reproution in any meium, provie the original author an soure are reite. Funing: Funing for the stuy ame from the Institute for the Promotion of Innovation by Siene an Tehnology in Flaners as a Strategi Basi Researh projet (SBO) (ontrat SBO IWT 05058) ( ), as part of the Monitoring Quality of En-of-Life Care (MELC) Stuy, a ollaboration between the Vrije Universiteit Brussel, Ghent University, Antwerp University, the Sientifi Institute for Publi Health, Belgium, an VU University Meial Centre Amsteram, the Netherlans. Funing also ame from the Italian Ministry of Health through the Evaluation, testing an implementation of supportive are, are interventions, integrate programs an improving the quality of are for aner patients program Integrate Onology Projet nu6, years le by Massimo Costantini (IRCCS AOU San Martino-IST, Genoa), from the annual bugets of the Autonomous Community of Castilla y León an Comunitat Valeniana an from EUROIMPACT: European Intersetorial an Multiisiplinary Palliative Care Researh Training, fune by the European Union Seventh Framework Programme (FP7/ , uner grant agreement nu [264697]). The funers ha no role in stuy esign, ata olletion an analysis, eision to publish, or preparation of the manusript. Competing Interests: The authors have elare that no ompeting interests exist. * n.evans@vum.nl " Membership of EUROIMPACT is provie in the Aknowlegments. PLOS ONE Marh 203 Volume 8 Issue 3 e57965

2 En-of-Life: Preferene Disussions an Surrogates Introution The nature of the patient-physiian relationship has hange onsierably over the last forty years with patient autonomy an partiipation in eision-making inreasingly reognise []. For patients reeiving en-of-life (EoL) are, partiipation inlues preparation for possible future inapaity. The most well known form of antiipatory eision-making is an avane iretive. Avane iretives are ouments that outline treatments that a patient onsiers aeptable in the event that he or she an no longer ommuniate or that esignate a surrogate eision-maker to make treatment hoies on the patient s behalf [2]. Researh iniates that, even in the US, where avane iretives are atively promote an legally bining, uptake amongst the general publi remains low, at aroun 20% [3,4]. International stuies an omparisons suggest even lower uptake [5,6]. Avane iretives however are just one aspet of antiipatory eision-making. The ornerstone of this is rather the proess of patient-physiian isussion regaring EoL treatment eisions [7]. Therefore, measures of patient-physiian isussions about treatment preferenes or the informal an formal appointment of surrogate eision-makers may be more appropriate iniators of patients involvement in treatment eisions than avane iretive uptake [8,9]. Moreover, ue to ross-ountry ifferenes in legal status an use of avane iretives, suh measures are partiularly appropriate for international omparisons [5,0]. Few stuies have examine patient-physiian EoL treatment preferene isussions or patients appointment of surrogate eision-makers (written an verbal). Furthermore, results of these stuies are iffiult to ompare ue to ifferenes in stuy population an question formulation. Previous stuies have fouse on the isussion of speifi treatments [ 3], formal surrogate appointments (legal guarians or power of attorney) [4,5] or on speifi patient populations [,4 6]. This stuy examines GP-patient isussions of meial EoL treatment preferenes an patients appointment of surrogate eision-makers in Italy, Spain, Belgium an the Netherlans. The stuy raws on information from representative GP sentinel networks about patient are in the last three months of life. In the four ountries, almost all patients are registere with a GP [7] an GPs are instrumental in the elivery an oorination of EoL are [8 22]. Speifi objetives inlue: to estimate an ompare the prevalene of GP-patient meial EoL treatment preferene isussions an patients appointment of surrogate eisionmakers in four European ountries; an to examine ountry speifi fators assoiate with treatment preferene isussions an surrogate appointments. Methos Stuy Design, Setting an Population The stuy follows a ross-setional, retrospetive esign. Partiipants from representative GP networks registere every patient eath an esribe the patient an are harateristis using a stanarise registration form. In Spain, Belgium an the Netherlans, existing GP sentinel networks, use for epiemiologial surveillane, took part in the stuy [8,20,23]. In Italy a network was reate speifially for the stuy [24]. To avoi seleting GPs with a partiular interest in EoL are, reruite GPs were not informe about the subjet of the surveillane prior to partiipation [24]. In Belgium an the Netherlans the networks were nationwie an overe.75% an 0.8% of the population respetively. The Spanish network operate in two autonomous ommunities (Castile an León, an Valenia), overing 3.8% an 2.2% of the respetive regional populations. The Italian network operate in nine loal health istrits an overe 4% of the population per health istrit. GPs registere eaths (age 8 or oler) from 0/ 0/2009 to 3/2/200, apart from Spanish GPs who registere eaths from 0/0/200 to 3/2/200. A total of 6,858 eaths were reore. To inlue only patients who oul have reeive EoL are, eaths registere as suen an totally unexpete (n = 2243), or for whih this information was missing (n = 97), were exlue. As the stuy onerns patient- GP isussions, only patients uner their GP s are were inlue (patients resient in their own or a family member s home, or a are/resiential home). Duth nursing home patients, are for by the nursing home physiian, were exlue (n = 22). Patients whose main plae of resiene was unknown (n = 28) or other (often institutions outsie the GP s are) (n = 72) were also exlue. The final sample onsiste of 4,396 eaths (Italy n =,808, Spain n = 379, Belgium n =,556, the Netherlans n = 653). Comparing the ata with national ata on non-suen eaths (exluing Duth nursing home eaths in the Netherlans) verifie representativeness of all eaths (exept for a slight unerrepresentation of non-suen hospital eaths an people uner the age of 65 in Belgium, an women in the Netherlans) [24]. Informe Consent, Patient Anonymity an Ethis Approval After being informe of the objetives an proeures of the stuy, partiipating GPs gave written informe onsent at the beginning of eah registration year. Strit proeures regaring patient anonymity were employe uring ata olletion an entry; every patient reeive an anonymous referene oe from their GP an any ientifying patient an GP ata (suh as ate of birth, postoe an GP ientifiation number) were replae with aggregate ategories or anonymous oes. In Belgium the protool of the stuy was approve by the Ethial Review Boar of Brussels University Hospital of the Vrije Universiteit Brussel (2004). In Italy, ethis approval for ata olletion was obtaine from the Loal Ethial Committee Comitato Etio ella Aziena U.S.L. n. 9 i Grosseto, Tusany (2008). Ethial approval was not require for posthumous olletion of anonymous patient ata in the Netherlans [25,26] or Spain [27 29]. Measurement Instrument The 2009/200 EURO SENTI-MELC (European Sentinel Network Monitoring En-of-Life Care) form onsiste of 2 struture questions about the patient s emographi, health, an are harateristis in the last three months of life. Partiipants were requeste to inlue information from hospital physiians an patient reors. Disussion of treatment preferenes was etermine from the two-part question, Di the patient ever express speifi wishes about a meial treatment that he/she woul or woul not want in the final phase of life? An, if yes, Di you ever speak to the patient about these wishes? The urrent artile fouses on the seon part of this question. With regar to surrogate eisionmaker appointments, the registration form inlue the item, Di the patient ever express a wish about who was to make eisions regaring meial treatments or ativities in his/her plae in the event he/she woul no longer be able to speak for him/herself? PLOS ONE 2 Marh 203 Volume 8 Issue 3 e57965

3 En-of-Life: Preferene Disussions an Surrogates The following inepenent variables, assoiate with antiipatory eision making in previous stuies [20,30,3], were also ollete: age; sex; ause of eath; ementia iagnosis; resiene in the last year of life; plae of eath; GP ontats; GP provision of palliative are (as efine by the GP); the importane of urative, life-prolonging an palliative are (on a 5-point Likert Sale); an whether the GP ha isusse the primary iagnosis with the patient. Most questions inlue in the registration form ha been use in previous Duth an Belgian stuies [20,30,32] an ha been subjete to extensive piloting [30,33]. New questions were evelope in ollaboration with all partners. The final registration form unerwent forwar an bakwar translations from Duth into English, from English into Italian an Spanish, an from Duth into Frenh an was pilote in eah ountry (with 0 to 5 GPs) [24]. Data Analysis For eah ountry, stuy population harateristis were assesse using esriptive statistis an ifferenes between ountries were assesse using Pearson s hi-sq tests. Prevalene of patient-gp treatment preferene isussions an appointment of surrogate eision-makers were estimate per ountry using esriptive statistis. Differenes between ountries were examine using logisti regressions (ontrolling for stuy populations harateristis whih iffere signifiantly between ountries). Country speifi fators assoiate with treatment preferene isussions an surrogate appointments were examine through univariate an multivariable logisti regressions. Assoiations signifiant in univariate analyses were inlue in multivariable moels. Stepwise bakwars proeures were use (riteria for entry p,0.05 an for removal p.0.) an resiuals examine. Continuous variables were transforme to be ategorial (age, number of GP ontats). Cause of eath was re-ategorise as aner or non-aner. Furthermore, the treatment aims were ihotomise by ombining important an very important in one ategory an other responses in another. All ata analysis was arrie out in SPSS version 8. Results Charateristis of the Stuy Population Patient an are harateristis are shown in Table. The mean age of eath was 80, 8, 79 an 77 for Italian, Spanish, Belgian an Duth patients respetively. Although harateristis varie between ountries, the most ommon ause of eath was aner (37 52%). Just uner a thir of patients in Italy, Spain an Belgium suffere from ementia (29 3%), ompare with 3% of Duth patients. Approximately half of the Italian, Spanish an Duth patients ie at home (44 50%), ompare with uner a quarter of Belgian patients (24%) % of patients in the last week of life, an 8 20% of patients in the seon an thir months before eath ha no ontat with their GP. GPs however provie palliative are to 5 65% of patients. Curative treatment was important in the are of 8 3% of patients, prolonging life in 24 49% of ases an palliative are in 42 65% of ases. GPs ha isusse the primary iagnosis with 49% of Italian, 50% of Spanish, 60% of Belgian an 78% of Duth patients. Patient-GP Disussion of Meial EoL Treatment Preferenes an Patient Appointment of a Surrogate Deision-maker Table 2 shows the prevalene of treatment preferene isussions an surrogate eision-maker appointments in the four ountries. A minority of patients from all ountries (0 3%), exept the Netherlans (52%), ha either isusse treatment preferenes or appointe a surrogate eision-maker. GP-patient isussion of treatment preferenes ha taken plae with 0% of Italian, 7% of Spanish, 25% of Belgian an 47% of Duth patients. Furthermore, 6% of Italian, 5% of Spanish, 6% of Belgian an 29% of Duth patients ha appointe (either verbally or in writing) a surrogate eision-maker. Multivariable logisti regressions reveale a strong assoiation between ountry an both treatment preferene isussions an surrogate appointments. The os of isussing treatment preferenes with a GP were over six times higher for a Duth patient, an almost four times higher for a Belgian patient, ompare with an Italian patient. Similarly, the os of appointing a surrogate eision-maker were over four times higher for a Duth patient, an almost three times higher for a Belgian patient, than for an Italian patient. There were no signifiant ifferenes in the os of GP-patient isussion of treatment preferenes or appointment of surrogate eision-makers between Italy an Spain. Surrogate appointment was entirely verbal in Italy an Spain an most frequently verbal in the Netherlans an Belgium. Fators Assoiate with Disussion of a Meial EoL Treatment Preferene Table 3 shows the fators assoiate with GP-patient isussion of EoL treatment preferenes in univariate an multivariable analyses. The multivariable moels reveale ountry speifi assoiations. Diagnosis of ementia was negatively assoiate with treatment preferene isussions in Belgium an the Netherlans. Palliative are unit (PCU) eaths were positively assoiate with preferene isussions ompare with hospital eaths in Belgium. Furthermore, in Belgium, more frequent GP ontat in the last week of life was positively assoiate with preferene isussions, an in both Belgium an the Netherlans more frequent ontat in the seon an thir months before eath was positively assoiate with preferene isussions. GP provision of palliative are was positively assoiate with preferene isussions in all ountries an the reognition of palliative are as an important/ very important treatment aim was positively assoiate with preferene isussions in Belgium. Previous GP-patient isussion of the primary iagnosis was positively assoiate with preferene isussions in all ountries. Fators Assoiate with Patient Appointment of a Surrogate Deision-maker The fators assoiate with surrogate eision-maker appointments in univariate an multivariable analyses are presente in Table 4. Country speifi assoiations were reveale in the multivariable moels. Surrogate appointments were negatively assoiate with male patients in the Netherlans. In Spain PCU/ hospie eaths were positively assoiate with surrogate appointments ompare with hospital eaths. More frequent patient-gp ontat in the last week before eath was positively assoiate with surrogate appointments for Belgium an the Netherlans. Furthermore, the importane of palliative are was positively assoiate with surrogate appointments in Belgium, the Netherlans an Spain. PLOS ONE 3 Marh 203 Volume 8 Issue 3 e57965

4 En-of-Life: Preferene Disussions an Surrogates Table. Patients personal an are harateristis (n = 4,396) a. IT ES BE NL p value b n = 808 n = 379 n = 556 n = 653 n(%) n(%) n(%) n(%) Age, = (3) 43 () 24 (4) 9 (8), (6) 47 (2) 22 (4) 25 (9) (3) 24 (33) 56 (33) 98 (30) (40) 65 (44) 602 (39) 2 (32) Mean Sex Male 844 (47) 202 (53) 72 (46) 304 (47) Female 964 (53) 77 (47) 840 (54) 342 (53) Cause of eath Caner 820 (46) 47 (39) 58 (37) 339 (52),0.00 Cariovasular isease 37 (2) 63 (7) 226 (5) 0 (6) Respiratory isease 29 (7) 53 (4) 68 () 50 (8) Diseases of the nervous 04 (6) 7 (5) 3 (7) 20 (3) system Stroke 77(0) 40 () 03 (7) 28 (4) Other 63 (9) 56 (5) 363 (23) 2 (7) Patient iagnose with ementia 520 (29) 2 (3) 478 (3) 84 (3),0.00 Plae of eath Hospital 697 (39) 24 (33) 556 (36) 7 (28),0.00 Resiential or are home 63 (9) 46 (2) 479 (3) 2 (8) Home (inlu. servie flat) or 842 (47) 86 (50) 365 (24) 273 (44) with family Palliative are unit/hospie 00 (6) 6 (4) 47 (0) 65 (0) (Other n = 4) Number of GP-patient ontats (26) 23 (32) 366 (24) 62 (25),0.00 in the week before eath or (43) 49 (39) 768 (49) 73 (26) (30) 07 (28) 422 (27) 38 (49) Number of GP-patient ontats in the seon an thir month before eath 0 45 (8) 73 (9) 27 (8) 30 (20),0.00 or (54) 222 (59) 227 (79) 369 (57) (38) 84 (22) 202 (3) 54 (24) GP provie palliative are 995 (55) 232 (65) 787 (5) 374 (60),0.00 Treatment aim important or Curative treatment 322 (8) 9 (24) 468 (3) 4 (24),0.00 very important Life prolongation 747 (42) 9 (24) 573 (39) 65 (28),0.00 Palliative are 749 (42) 82 (48) 733 (5) 390 (65),0.00 GP an patient ha isusse the primary iagnosis 880 (49) 72 (50) 932 (60) 498 (78),0.00 a % of missing observations range from %. b test of assoiation: Pearson s hi-sq. not inlue in statistial analyses - Patients for whom the main plae of are in the last year of life was reporte as other an Duth patients in nursing homes were exlue from the analysis for reasons esribe in the methos setion. oi:0.37/journal.pone t00 Previous isussion of the primary iagnosis between the patient an the GP was positively assoiate with surrogate appointments in all four ountries. Disussion These ata reveal that a minority of patients from all ountries, with the exeption of the Netherlans, ha either isusse treatment preferenes or appointe a surrogate eision-maker. Furthermore, there are important ross-ountry ifferenes in prevalene of isussions an surrogate appointments, whih were highest in the Netherlans, followe by Belgium, with no signifiant ifferenes between Spain an Italy. The single most important patient or are fator assoiate with treatment preferenes isussions in all ountries, an with surrogate appointments in the Netherlans an Italy, was prior GP-patient isussion of the primary iagnosis. PLOS ONE 4 Marh 203 Volume 8 Issue 3 e57965

5 En-of-Life: Preferene Disussions an Surrogates Table 2. The prevalene of patient-gp ommuniation about meial EoL treatment preferenes an patient appointment of a surrogate eision-maker (n = 4,396) a. IT ES BE NL n = 808 n = 379 n = 556 n = 653 n(%) Multivariable n(%) Multivariable n(%) Multivariable n(%) Multivariable OR (CI) b OR (CI) b OR (CI) b OR (CI) b Patient either isusse a treatment preferene or appointe a surrogate 234 (3) 37 (0) 0.80 (0.54,.20) 487 (3) 3.53 (2.84, 4.39) 339 (52) 6.02 (4.64, 7.8) Patient isusse a meial EoL treatment preferene with their GP 73 (0) 26 (7) 0.83 (0.52,.33) 394 (25) 3.80 (2.99, 4.83) 304 (47) 6.44 (4.88, 8.50) Patient appointe a surrogate eision-maker 0 (6) 20 (5) 0.93 (0.55,.57) 244 (6) 2.78 (2.2, 3.64) 87 (29) 4.48 (3.32, 6.05) Manner of surrogate appointment Only verbally 05 (6) 9 (5) 0.97 (0.57,.65) 9 (2) 2.5 (.62,2.86) 28 (20) 2.87 (2.08, 3.97) In writing 4 (0) (0) 53 (3) 53 (8) a % of missing observations range from 0.3.2%. b multivariable logisti regressions (fore enter). Depenent variables were Patient i not isuss a meial EoL preferene with GP or appoint a surrogate eision-maker ; Patient isusse a meial EoL preferene ; Patient appointe a surrogate eision-maker ; Patient appointe a surrogate eision-maker in writing ; an Patient only appointe a surrogate eision-maker verbally. Inepenent variables inlue ountry (OR an p-value shown), age, ause of eath, ementia iagnosis; plae of eath; the number of ontats with the GP in the last week an in the seon an thir months before eath; GP palliative are provision; the importane of urative, lifeprolonging an palliative are as treatment aims an if the GP ha isusse the primary iagnosis. The results of the multivariate logisti regressions were ompare with equivalent univariate analyses (not shown) to hek for any major ifferenes in the magnitue or iretion of assoiations. Too few patients in this ategory to onut a logisti regression. oi:0.37/journal.pone t002 PLOS ONE 5 Marh 203 Volume 8 Issue 3 e57965

6 En-of-Life: Preferene Disussions an Surrogates Table 3. Charateristis assoiate with a patient having isusse a meial EoL treatment preferene with their physiian in univariate an multivariable analyses (n = 4,396) a. Preferene isusse IT (n = 808) ES (n = 379 ) BE (n = 556) NL (n = 653) Logisti regression b Logisti regression b Logisti regression b Logisti regression b Univariate Multivariable Univariate Multivariable Univariate Multivariable Univariate Multivariable OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) Age, = (.48, 3.79) 4.32 (.9, 5.7).7 (.22, 2.42).4 (0.72,.79) (.46, 3.52) 4.68 (.36, 6.).44 (.0, 2.04).34 (0.86, 2.09) (0.92, 2.08) 2.8 (0.93, 8.43).06 (0.80,.40).03 (0.70,.53) 85. Sex Male.24 (0.90,.69).03 (0.46, 2.29).0 (0.88,.39) 0.73 (0.54,.00) Cause of eath Respiratory isease Cariovasular isease.05 (0.50, 2.2) 0.83 (0.6, 4.3) 2.04 (.23, 3.4).3 (0.64, 2.68) Caner.7 (0.87, 3.37).9 (0.53, 6.88) 3.4 (2.00, 4.93) 2.42 (.29, 4.53) Diseases of the nervous system 0.73 (0.26, 2.08).04 (0.0, 0.73) 0.97 (0.50,.88) 0.98 (0.33, 2.93) Stroke 0.56 (0.22,.47) 0.43 (0.04, 4.27) 0.79 (0.39,.62) 0.32 (0.09,.07) Other.2 (0.48, 2.6) 0.94 (0.8, 4.89).9 (0.73,.96).4 (0.56, 2.32) No ementia iagnosis 3.64 (2.23, 5.93) 3.62 (.06, 2.3) 4.8 (3.03, 5.78) 2.30 (.52, 3.50) 3.04 (.80, 5.3) 2.28 (.8, 4.44) Plae of eath Hospital Resiential or are home 0.82 (0.44,.52) e 0.84 (0.6,.5) 0.96 (0.62,.49) 3.32 (.98, 5.56) Home (inlu. servie flat) or with family.03 (0.73,.45) 2.69 (0.98, 7.39) 3.09 (2.30, 4.6).7 (.5, 2.53) 5.83 (3.77, 9.00) Palliative are unit/hospie0.93 (0.45,.93).57 (0.7, 4.39) 2.39 (.6, 3.56).93 (.22, 3.04) 2.42 (.32, 4.44) Number of GP-patient ontats Last week before eath 0 or (0.55,.33) 0.80 (0.50,.26) 2.6 (0.66, 7.05).67 (.20, 2.32).7 (.4, 2.55) 2.28 (.38, 3.77) 0.93 (0.47,.86) (.4, 3.9).53 (0.97, 2.39) 3.76 (.7, 2.03) 3.37 (2.38, 4.76) 2.93 (.8, 4.75) 8.47 (5.36, 3.39).88 (0.94, 3.75) Seon an thir months before eath 0 or 2.79 (0.8, 3.96) 0.47 (0.6,.37).89 (.3, 3.7).78 (0.90, 3.5) 2.25 (.46, 3.47) 2.09 (.3, 3.84) (.25, 6.).7 (0.60, 4.87) 4.0 (2.3, 7.27) 2.36 (.3, 4.95) 3.38 (2.06, 5.56) 2.04 (.04, 3.99) PLOS ONE 6 Marh 203 Volume 8 Issue 3 e57965

7 En-of-Life: Preferene Disussions an Surrogates Table 3. Cont. Preferene isusse IT (n = 808) ES (n = 379 ) BE (n = 556) NL (n = 653) Logisti regression b Logisti regression b Logisti regression b Logisti regression b Univariate Multivariable Univariate Multivariable Univariate Multivariable Univariate Multivariable OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) GP provie palliative are 2.59 (.8, 3.69) 2.07 (.40, 3.07) 4.53 (.33, 5.4) 4.96 (.43, 7.25) 2.27 (.79, 2.88).54 (., 2.4) 8.8 (6.00, 2.93) 4.40 (2.57, 7.54) Care aim important or very important Curative treatment 0.84 (0.55,.30).8 (0.48, 2.89) 0.64 (0.49, 0.83) 0.84 (0.57,.23) Life prolongation 0.80 (0.58,.0) 0.75 (0.27, 2.04) 0.88 (0.69,.2) 0.88 (0.6,.25) Palliative are.65 (.20, 2.26) 2.7 (0.94, 4.99).68 (.32, 2.4).45 (.09,.93) 2.42 (.7, 3.43) Primary iagnosis isusse 8.40 (5.3, 3.28) 7.47 (4.7,.87) (3.94, 220.0) (3.8, 24.63) 7.22 (5.22, 0.00) 4.66 (3.3, 6.94).5 (6.33, 9.63) 5.66 (2.5, 2.75) Values for whih p,0.05 are highlighte in bol. a % of values for eah harateristi were not provie by the GP (missing values). b Bakwars stepwise logisti regression - epenent variable Patient isusse a meial EoL preferene with their GP. Not entere into logisti regression. Remove uring logisti regression. e No patients in the ategory ha isusse a meial EoL preferene with their GP (os ratio of 0). oi:0.37/journal.pone t003 PLOS ONE 7 Marh 203 Volume 8 Issue 3 e57965

8 En-of-Life: Preferene Disussions an Surrogates Table 4. Charateristis assoiate with patients appointment of a surrogate eision-maker by ountry in iunivariate an multivariable analyses (n = 4,396) a. Surrogate appointe IT (n = 808) ES (n = 379 ) BE (n = 556) NL (n = 653) Logisti regression b Logisti regression b Logisti regression b Logisti regression b Univariate Multivariable Univariate Multivariable Univariate Multivariable Univariate Multivariable OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) Age, = (0.64, 2.25).25 (0.24, 6.44).2 (0.74,.68).3 (0.69,.85) (0.9, 2.65) 3.3 (0.9, 0.77) 0.73 (0.46,.6). (0.68,.80) (0.76,.96).56 (0.5, 4.77) 0.86 (0.62,.9) 0.97 (0.63,.50) 85. Sex Male.25 (0.85,.83).30 (0.52, 3.26) 0.96 (0.73,.26) 0.54 (0.38, 0.77) 0.43 (0.28, 0.65) Cause of eath Respiratory isease Cariovasular isease0.93 (0.35, 2.42).37 (0.22, 8.5).22 (0.7, 2.).9 (0.54, 2.62) Caner.65 (0.70, 3.89).89 (0.40, 8.92).33 (0.83, 2.3).6 (0.8, 3.2) Diseases of the nervous system 0.82 (0.23, 3.00) e 0.87 (0.44,.73) 0.88 (0.24, 3.9) Stroke.34 (0.48, 3.74) e 0.48 (0.2,.) 0.56 (0.6,.95) Other.46 (0.53, 4.06) 2.55 (0.47, 3.76) 0.83 (0.49,.40) 0.89 (0.40,.97) No ementia iagnosis.60 (.00, 2.56).32 (0.47, 3.73).30 (0.96,.77).85 (.04, 3.29) Plae of eath Hospital Resiential or are home 0.5 (0.20,.30) e e.9 (0.83,.70) 2.20 (.23, 3.94) Home (inlu. servie flat) or with family. (0.73,.69).52 (0.5, 4.48) 2.20 (0.67, 7.9).76 (.23, 2.52) 3.34 (2.07, 5.40) Palliative are unit/ hospie.4 (0.64, 3.) 9.44 (2.8, 40.84) 2.49 (2.54, 6.49).96 (.23, 3.2).99 (.00, 3.93) Number of GP-patient ontats Last week before eath 0 or 2.03 (0.62,.73).2 (0.42, 3.49).90 (.26, 2.87).86 (.20, 2.89).22 (0.64, 2.36) 0.57 (0.26,.23) (.0, 2.82) 0.9 (0.27, 3.06) 2.99 (.95, 4.59) 3.4 (.99, 4.95) 6.43 (3.75,.02) 3.27 (.74, 6.5) Seon an thir months before eath PLOS ONE 8 Marh 203 Volume 8 Issue 3 e57965

9 En-of-Life: Preferene Disussions an Surrogates Table 4. Cont. Surrogate appointe IT (n = 808) ES (n = 379 ) BE (n = 556) NL (n = 653) 0 or 2.59 (0.63, 4.05).06 (0.28, 3.96).72 (0.93, 3.7) 2.77 (.58, 4.84) (0.88, 5.70) 2.00 (0.50, 8.05) 2.83 (.43, 5.58) 4.28 (2.34, 7.84) GP provie palliative are.53 (.02, 2.28) 2. (0.69, 6.50).66 (.25, 2.9) 3.93 (2.60, 5.95) Care aim important or very important Curative treatment 0.89 (0.53,.49).03 (0.36, 2.9) 0.87 (0.64,.8) 0.75 (0.49,.5) Life prolongation.07 (0.72,.58).7 (0.66, 4.43).09 (0.82,.45) 0.72 (0.48,.08) Palliative are.78 (.2, 2.63).67 (.2, 2.48).60 (0.64, 4.00).54 (.5, 2.04).49 (., 2.0) 2.38 (.60, 3.55).62 (.02, 2.57) Primary iagnosis isusse 2.5 (.43, 3.23).92 (.27, 2.89) 5.74 (.64, 20.09) 5.68 (.58, 20.37) 2.69 (.95, 3.7) 2.56 (.83, 3.58) 5.98 (3.4,.38) 5.37 (2.3, 2.49) Values for whih p,0.05 are highlighte in bol. a % of values for eah harateristi were not provie by the GP (missing values). b Bakwars stepwise logisti regression - epenent variable Patient ha appointe a surrogate eision-maker. Not entere into logisti regression. Remove uring logisti regression. e No patients in the ategory ha appointe a surrogate eision-maker (os ratio of 0). oi:0.37/journal.pone t004 PLOS ONE 9 Marh 203 Volume 8 Issue 3 e57965

10 En-of-Life: Preferene Disussions an Surrogates Differenes between Countries There are notable ifferenes between northern an southern European ountries with a lower prevalene of treatment preferene isussions an surrogate appointments in Italy an Spain. Consiering the strong assoiation between isussion of the primary iagnosis an both preferene isussions an surrogate appointments, these ross-ountry ifferenes are linke to lower levels of primary iagnosis isussion in Italy an Spain ompare with the Netherlans an Belgium. Previous stuies have also reporte limite islosure [9,3,34,35] an isussion of EoL treatment preferenes [,36] in the two southern European ountries. Meñaa et al [9], in a review of EoL are an ulture in Italy, Spain an Portugal, highlighte the influene of Catholiism on islosure of iagnoses an prognoses. Catholi teahing permits the graual islosure of truth to terminal patients in a way that oes not estroy hope [37]. Meñaa [9] also foun that although avane iretives have a strong legal status in Spain (in ontrast to Italy) in pratie physiians are more guie by the priniple of benefiene [9]. In Italy, it has been suggeste that physiians onern about istress ause by EoL treatment isussions leas them to elay or avoi suh isussions [37]. Belgium, in ontrast, although nominally Catholi, has more in ommon with the Netherlans. The proess of legalization of euthanasia in both ountries engenere open publi ebate on EoL issues [5,38]. A higher frequeny of antiipatory eisionmaking in the Netherlans an Belgium may therefore be expete onsiering the importane of self-etermination an the open isussion of eath an ying. This is espeially true in the Netherlans, where patients prioritize autonomy an ontrol in the ying proess [39,40]. Cross-ountry stuies have repeately foun that Duth physiians more frequently isuss EoL issues than their European ounterparts [3,4,42]. Family members opposition to full-islosure of primary iagnosis, the so alle onspiray of silene, has also been sai to ontribute to low levels of islosure in both Italy an Spain [9]. A lak of islosure an subsequent EoL isussions may also impat patients appointment of surrogate eision-makers. Equally, suh appointments may be eeme unneessary if family members are onsiere e fato proxies. This may ontribute to the lower prevalene of surrogate appointments ompare with preferene isussions in all ountries, partiularly in Spain an Italy, whih are often seen as more family orientate. An aitional onsieration onerns patients wishes for information. A systemati review of EoL ommuniation reporte that stuies from northern European ountries report higher levels of esire information amongst patients than stuies from the south of Europe [43]. Although the esire for iagnosis an prognosis information may not be as ommon amongst patients an the general publi in Italy an Spain ompare to northern European ountries; in general, the proportion reporte to prefer full islosure is still greater than the proportion that reeives full islosure in linial pratie [9,44]. A GP s responsibility for EoL are also varies between the four ountries. In the Netherlans there is a strong fous on GP EoL are provision: GPs are primarily responsible for generalist EoL are provision an have easy aess to palliative are guielines an onsultation [45,46]. In Belgium, Spain an Italy however provision is more often share with palliative are home teams [2,47,48]. Furthermore GPs have a gatekeeper role (oorinating all referrals to speialist servies) in the Netherlans an Spain, but not in Belgium an Italy. A further explanation for the strong ross-ountry ifferenes lies in the amount of palliative are training physiians reeive. A survey of physiians from Belgium, Denmark, Italy, the Netherlans, Sween an Switzerlan reveale that the perentage of physiians who ha unertaken formal palliative are training was lowest in Italy an highest in the Netherlans [49]. Palliative are training may improve EoL ommuniation skills an may ontain speifi EoL ommuniation training. Country Speifi Fators Assoiate with Treatment Preferene Disussions an Surrogate Appointments A number of patient an are harateristis were assoiate with treatment preferenes isussions. As mentione previously GP-patient isussion of the primary iagnosis was strongly assoiate with both treatment preferenes an surrogate appointments. In aition, ementia iagnosis was assoiate with less frequent isussion of treatment preferenes in Belgium an the Netherlans. Timely isussions are a priority for patients with ementia. A relate issue is the early iagnosis of ementia. Researh shows that 50 66% of patients with ementia are not iagnose with the onition by primary are physiians [50]. GPs are reommene to begin preferene isussions as soon as mental apaity eline is etete. Frequeny of ontat with GPs, GP provision of palliative are an the importane of palliative are as a treatment aim were also assoiate with preferene isussions an surrogate appointments. Palliative are unit an home eaths were assoiate with treatment preferene isussions in Belgium. This may reflet an emphasis on palliative home are in Belgium [5] an isussion of preferenes in the palliative are setor. In Spain, surrogate appointment was assoiate with PCU an hospie eaths. Inee, for Spain, plae of eath was the fator most strongly assoiate with surrogate appointments in the multivariable moel; suggesting that, for Spanish patients, surrogate appointment is speifially relate to speialist inpatient palliative are. Interestingly, in the Netherlans patient surrogate appointment was more frequent amongst female patients. This may iniate a greater relutane amongst GPs to isuss surrogate appointments with male patients or of male patients to assign eision-making responsibilities. Men are also more likely to have a living partner, so may feel less nee to appoint a surrogate eision-maker [5]. Why this shoul only be signifiant in the Netherlans an not the other ountries is, however, unlear. Strengths an Limitations This is the first population-base stuy to estimate the prevalene of meial EoL treatment isussions an patients appointment of surrogates in the Netherlans, Belgium, Italy an Spain. The use of the same stuy esign amongst representative GP sentinel networks in eah ountry provie robust an omparable ata. Bias was avoie by seleting GPs with no speifi interest in EoL are. As most people in eah ountry are registere with a GP, representative samples of non-suen eaths were obtaine. A strength of the retrospetive esign is that a representative sample of the palliative are population oul be ientifie. The stuy was, however, subjet to a number of limitations. Although GPs omplete registration forms on a weekly basis, there may have been some reall bias. In aition, GPs may have provie soially esirable answers espeially onerning items that reflet on their own are ompetenies; partiularly high levels of GP provision of palliative are for example were reporte in all four ountries. Furthermore, the stuy reports the isussion of treatment preferenes aoring to the GP. Patients an physiians may iffer in their pereption of what onstitutes the PLOS ONE 0 Marh 203 Volume 8 Issue 3 e57965

11 En-of-Life: Preferene Disussions an Surrogates isussion of treatment preferenes an patients may have isusse preferenes with other health professionals. The Spanish an Italian sentinel networks were not nationwie, although they were representative of the areas they overe (Italy was representative for the largest statistial regions). Duth nursing home resients were exlue from analyses an there was a slight unerrepresentation of non-suen hospital eaths an people uner the age of 65 in Belgium an a slight unerrepresentation of females in the Netherlans. Some suen eaths in hospitals may also have been misse by GPs in Spain an Italy. However, ue to a lak of national ata on plae of eath, this oul not be teste. The survey also relie on GPs to report are in other settings, although GPs were aske to maximize information from other soures. In aition, GPs harateristis were unavailable; preventing examination of assoiations with GP harateristis. Finally, the stuy only examines the prevalene of treatment preferene isussions an surrogate appointments an some assoiate fators. Further qualitative researh on the patientphysiian ommuniation proess may help in unerstaning the omplex reasons for between ountry ifferenes. Conlusions Disussion of both meial EoL treatment preferenes an surrogate appointments were highest in the Netherlans, followe by Belgium, with no signifiant ifferenes between Spain an Italy. A number of fators relate to the isussion of the primary iagnosis, patient s mental apaity an speialist or generalist palliative are were assoiate with treatment isussions an surrogate appointments. These finings suggest that the proess of planning for the EoL often starts with the isussion of the primary iagnosis: if avoie or elaye, opportunities for patient partiipation in eisionmaking may be misse. Communiation training for physiians an help hange attitues towars iagnosis islosure [52,53]. Ieally training woul also highlight the right of a patient not to reeive suh information if he or she so wishes; suh a preferene however must be state by the patient an not assume a priori by the physiian. Referenes. Hoving C, Visser A, Mullen PD, van en Borne B (200) A history of patient euation by health professionals in Europe an North Ameria: From authority to share eision making euation. Patient Eu Couns 78: Bravo G, Dubois MF, Paquet M (2003) Avane iretives for health are an researh: Prevalene an orrelates. Alzheimer Dis Asso Disor 7: DeLua Havens G (2000) Differenes in the exeution/nonexeution of avane iretives by ommunity welling aults. Res Nurs Health 23: Ott BB (999) Avane iretives: the emerging boy of researh. Am J Crit Care 8: Gysels M, Evans N, Meñaa A, Anrew EVW, Tosani F, et al. (202) Culture an En of Life Care: A Soping Exerise in Seven European Countries. PLoS ONE 7 e3488. oi: /journal.pone Voltz R, Akabayashi A, Reese C, Ohi G, Sass HM (998) En-of-life eisions an avane iretives in palliative are: A ross-ultural survey of patients an health-are professionals. J Pain Symptom Manage 6: Conroy S, Fae P, Fraser A, Shiff R (2009) Avane are planning: onise eviene-base guielines. Clin Me 9: Simon-Lora P, Tamayo-Velazquez MI, Barrio-Cantalejo IM (2008) Avane iretives in Spain. Perspetives from a meial bioethiist approah. Bioethis 22: Meñaa A, Evans N, Anrew EVW, Tosani F, Finetti S, et al. (20) En-of-life are aross Southern Europe: A ritial review of ultural similarities an ifferenes between Italy, Spain an Portugal. Crit Rev Onol Hematol 82: Anorno R, Biller-Anorno N, Brauer S (2009) Avane health are iretives: towars a oorinate European poliy? Eur J Health Law 6: Formiga F, Chivite D, Ortega C, Casas S, Ramón JM, et al. (2004) En-of-life preferenes in elerly patients amitte for heart failure. QJM: An International Journal of Meiine 97: Furthermore, early preferene isussions for all patients, partiularly those with ementia or ognitive eline, an the provision of palliative are support patients partiipation in EoL eision-making. Aknowlegments EURO IMPACT, European Intersetorial an Multiisiplinary Palliative Care Researh Training, aims to evelop a multiisiplinary, multiprofessional an inter-setorial euational an researh training framework for palliative are researh in Europe. EURO IMPACT is oorinate by Prof Lu Deliens an Prof Lieve Van en Blok of the En-of-Life Care Researh Group, Ghent University & Vrije Universiteit Brussel, Brussels, Belgium. Collaborators an their affiliations are as follows: Van en Blok Lieve a, Meeussen Koen a, Brearley Sarah e, Caraeni Augusto g, Cohen Joahim a, Costantini Massimo h, Franke Anneke b, Haring Rihar,, Higginson Irene J,, Kaasa Stein f, Linen Karen k, Miinesi Guio i, Onwuteaka-Philipsen Bregje b, Paron Koen a, Pasman Roeline b, Pautex Sophie j, Payne Sheila e, Deliens Lu a,b. Affiliations: Ghent University & Vrije Universiteit Brussel, Brussels a ;VU University Meial Center, EMGO Institute for health an are researh, Amsteram, the Netherlans b ; King s College Lonon, Ciely Sauners Institute, Lonon, Ciely Sauners International, Lonon, an International Observatory on En-of-Life Care, Lanaster University, Lanaster, Unite Kingom e ; Norwegian University of Siene an Tehnology f, an EAPC Researh Network g, Tronheim, Norway; Regional Palliative Care Network, IRCCS AOU San Martino-IST, Genoa h, an Caner Researh an Prevention Institute, Florene, Italy i ; EUGMS European Union Geriatri Meiine Soiety, Geneva, Switzerlan j ; Springer Siene an Business Meia, Houten, the Netherlans k. Author Contributions Drafte the paper: NE. Critially appraise an amene the paper: NE BOP HRP LVDB TVA GM VVC GD SB OZ LD. Supervision: BOP HRP. Coneive an esigne the experiments: BOP LVDB TVA OZ GM LD. Performe the experiments: TVA GM VVC GD SB OZ LD. 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