Falls Predict Acute Hospitalization in Parkinson’s Disease

Jou nal o Pa kinson’s Disease 13 (2023) 105–124 DOI 10.3233/JPD-212539 IOS P ess 105 Resea ch Repo Falls P edic Acu e Hospi aliza ion in Pa kinson’s Disease Diego San os Ga c´ ıaa,1,∗, Te esa de Deus Fon icobab, Ca los Co esa, Es e Su´ a ez Cas ob, Jo ge He n´ andez Va ac, Sil ia Jes´ usd,e, Pablo Mi d,e, Ma ina Cosgaya , Ma ia Jos´ e Ma ´ ı , Pau Pas o g, I ia Caboh, Manuel Seijoh,In ´ es Lega dai,B ´ a ba a Vi esi, Nu ia Caballolj, Ja ie R´ uiz Ma ´ ınezk, Ioana C oi o uk, Es he Cubol, Ja ie Mi andal, Ma ia Gema Alonso Losadam, Ca men Labandei am, Nu ia L´ opez A iz eguin, Mabel Mo ales-Casadon, Isabel Gonz´ alez A ambu uo, Jon In an eo, Sonia Escalan ep, Noem´ ı Be na dop, Ma a Bl´ azquez Es adaq, Manuel Men´ endez Gonz´ alezg, Juan Ga c´ ıa Calden ey , Ca men Bo u´ es, Lydia Vela , Ma ia Jos´ e Ca al´ anu, V´ ıc o G´ omez Mayo domou,M ´ onica Ku is , C is ina P ie ow, Ca los O d´ asw,V ´ ıc o Noguei ax, Lydia L´ opez Manzana esy, Ma ia Asunci´ on ´ A ila Ri e az, Vic o Puen eaa, Jose Manuel Ga c´ ıa Mo enobb, Be a Solano Vilacc, Ma ´ ıa ´ Al a ez Saucodd, F ancisco Ca illo Padillaee, Juan Ca los Ma ´ ınez Cas illo , Pila S´ anchez Alonsogg, I zia Gas ´ onhh, Jaime Kulise skye,ii, Ca idad Vale ojj, O iol de F´ ab eguesc, Jessica Gonz´ alez A du akk, Luis Manuel L´ opez D´ ıazll, Pablo Ma inez-Ma ineand COPPADIS S udy G oup aCHUAC, Complejo Hospi ala io Uni e si a io de A Co u˜na, A Co u˜na, Spain bCHUF, Complejo Hospi ala io Uni e si a io de Fe ol, A Co u˜na, Spain cNeu ology Depa men and Neu odegene a i e Diseases Resea ch. Vall D’Heb on Uni e si a y Campus, Ba celona, Spain dUnidad de T as o nos del Mo imien o, Se icio de Neu olog´ıa y Neu ofisiolog´ıa Cl´ınica, Ins i u o de Biomedicina de Se illa, Hospi al Uni e si a io Vi gen del Roc´ıo/CSIC/Uni e sidad de Se illa, Se ille, Spain eCIBERNED (Cen o de In es igaci´on Biom´edica en Red En e medades Neu odegene a i as), Spain Hospi al Cl´ınic de Ba celona, Ba celona, Spain gMo emen diso de s Uni , Uni e si y Hospi al Mu ua de Te assa, Ba celona, Spain hComplejo Hospi ala io Uni e si a io de Pon e ed a (CHOP), Pon e ed a, Spain iHospi al Uni e si a io Son Espases, Palma de Mallo ca, Spain jConso ci Sani a i In eg al, Hospi al Mois´es B oggi, San Joan Desp´ı, Ba celona, Spain kHospi al Uni e si a io Donos ia, San Sebas i´an, Spain lComplejo Asis encial Uni e si a io de Bu gos, Bu gos, Spain mHospi al ´ Al a o Cunquei o, Complejo Hospi ala io Uni e si a io de Vigo (CHUVI), Vigo, Spain nComplejo Hospi ala io de Toledo, Toledo, Spain oHospi al Uni e si a io Ma qu´es de Valdecilla, San ande , Spain pHospi al de To osa Ve ge de la Cin a (HTVC), To osa, Ta agona, Spain qHospi al Uni e si a io Cen al de As u ias, O iedo, Spain Cen o Neu ol´ogico Oms, Palma de Mallo ca, Spain 1ORCID ID: 0000-0002-3126-5111. ∗Co espondence o: D . Diego San os Ga c´ ıa, Depa men o Neu ology, Hospi al Uni e si a io de A Co u˜ na (HUAC), Com- plejo Hospi ala io Uni e si a io de A Co u˜ na (CHUAC), C/ As Xubias 84, 15006, A Co u˜ na, Spain. Tel.: +34 646173341; E-mail: [email p o ec ed]. ISSN 1877-7171 © 2023 – The au ho s. Published by IOS P ess. This is an Open Access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion-NonComme cial License (CC BY-NC 4.0). 106 D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD sHospi al In an a So ´ıa, Mad id, Spain Fundaci´on Hospi al de Alco c´on, Mad id, Spain uHospi al Uni e si a io Cl´ınico San Ca los, Mad id, Spain Hospi al Rube In e nacional, Mad id, Spain wHospi al Rey Juan Ca los, Mad id, Spain xHospi al Da Cos a, Bu ela, Lugo, Spain yHospi al Uni e si a io La P incesa, Mad id, Spain zConso ci Sani a i In eg al, Hospi al Gene al de L’Hospi ale , L’Hospi ale de Llob ega , Ba celona, Spain aaHospi al del Ma , Ba celona, Spain bbHospi al Uni e si a io Vi gen Maca ena, Se illa, Spain ccIns i u d’Assis `encia Sani `a ia (IAS) - Ins i u Ca al`a de la Salu . Gi ona, Spain ddHospi al Gene al Uni e si a io de Elche, Elche, Spain eeHospi al Uni e si a io de Cana ias, San C is ´obal de la Laguna, San a C uz de Tene i e, Spain Hospi al Uni e si a io Ram´on y Cajal, Mad id, Spain ggHospi al Uni e si a io Pue a de Hie o, Mad id, Spain hhComplejo Hospi ala io de Na a a, Pamplona, Spain iiHospi al de San Pau, Ba celona, Spain jjHospi al A nau de Vilano a, Valencia, Spain kkHospi al Uni e si a io Lucus Augus i (HULA), Lugo, Spain llComplejo Hospi ala io Uni e si a io de O ense (CHUO), O ense, Spain Accep ed 14 Ma ch 2021 P e-p ess 7 Ap il 2021 Published 31 Janua y 2023 Abs ac . Backg ound: The e is a need o iden i ying isk ac o s o hospi aliza ion in Pa kinson’s disease (PD) and also in e en ions o educe acu e hospi al admission. Objec i e: To analyze he equency, causes, and p edic o s o acu e hospi aliza ion (AH) in PD pa ien s om a Spanish coho . Me hods: PD pa ien s ec ui ed om 35 cen e s o Spain om he COPPADIS-2015 (COho o Pa ien s wi h PA kinson’s DIsease in Spain, 2015) coho om Janua y 2016 o No embe 2017, we e included in he s udy. In o de o iden i y p edic o s o AH, Kaplan-Meie es ima es o ac o s conside ed as po en ial p edic o s we e ob ained and Cox eg ession pe o med on ime o hospi al encoun e 1-yea a e he baseline isi . Resul s: Thi y- i e ou o 605 (5.8%) PD pa ien s (62.5 ±8.9 yea s old; 59.8% males) p esen ed an AH du ing he 1-yea ollow-up a e he baseline isi . T auma ic alls ep esen ed he mos equen cause o admission, being 23.7% o all acu e hospi aliza ions. To su e om mo o luc ua ions (HR [haza d a io] 2.461; 95% CI, 1.065–5.678; p= 0.035), a e y se e e non-mo o symp oms bu den (HR [haza d a io] 2.828; 95% CI, 1.319–6.063; p= 0.008), alls (HR 3.966; 95% CI 1.757–8.470; p= 0.001), and dysphagia (HR 2.356; 95% CI 1.124–4.941; p= 0.023) was associa ed wi h AH a e adjus men o age, gende , disease du a ion, le odopa equi alen daily dose, o al numbe o non-an ipa kinsonian d ugs, and UPDRS-III- OFF. O he p e ious a iables, only alls (HR 2.998; 95% CI 1.080–8.322; p= 0.035) was an independen p edic o o AH. Conclusion: Falls is an independen p edic o o AH in PD pa ien s. Keywo ds: Falls, hospi aliza ion, non-mo o symp oms, Pa kinson’s disease, p edic o s INTRODUCTION Mo o and non-mo o symp oms (NMS) in Pa kin- son’s disease (PD) p og ess as he disease ad ances, which leads o complica ions such as alls, ac u es, o in ec ions. As a consequence, PD pa ien s a e epo ed o ha e 1.44 imes mo e hospi al admis- sions when compa ed o age and sex-ma ched pee s [1, 2]. These admissions a e associa ed wi h p o- longed leng h-o -s ay and inc eased mo bidi y and mo ali y [3–5]. Once PD pa ien s a e admi ed o hospi al, hey ha e p olonged inpa ien s ays [6], poo mo o ou comes, in ec ions, p esc ip ion e o s, and inc eased pos ope a i e mo ali y [7–10]. Mo eo e , ollowing a i s hospi al encoun e , he a e o a sec- ond encoun e inc eased o app oxima ely 50% when D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD 107 pa ien s we e ollowed in o a second yea [11]. P e- ious s udies epo ed a signi ican economic bu den om PD hospi aliza ion as well [12, 13]. The e is a need o iden i ying isk ac o s o hospi aliza ion in PD and also in e en ions o educe acu e PD hospi al admission [14]. The aim o he p esen s udy was (1) o analyze he equency and causes o acu e hospi aliza ion in PD pa ien s om a Spanish coho ollowed o 1-yea and (2) o iden i y p edic o s o acu e hospi aliza ion. MATERIAL AND METHODS PD pa ien s ec ui ed om 35 cen e s o Spain om he COPPADIS coho [15], om Janua y 2016 o No embe 2017, we e included in he s udy. Me hodology abou COPPADIS-2015 s udy can be consul ed in h ps://bmcneu ol.biomedcen al.com/ a icles/10.1186/s12883-016-0548-9. This is a mul i- cen e , obse a ional, longi udinal-p ospec i e, 5- yea ollow-up s udy designed o analyze disease p og ession in a Spanish popula ion o PD pa ien s. All pa ien s included we e diagnosed acco ding o UK PD B ain Bank c i e ia. Exclusion c i e ia we e: a ypical pa kinsonism, demen ia (Mini-Men al S a e Examina ion [MMSE] < 26), age < 18 o > 75 yea s, inabili y o ead o unde s and he ques ionnai es, o be ecei ing any ad anced he apy (con inuous in usion o le odopa o apomo phine, and/o wi h deep b ain s imula ion a baseline), and he p esence o como bidi y, sequelae, o any diso de ha could in e e e wi h he assessmen . The da a o he p esen s udy was ob ained om he baseline e alua ion [15]. Pa ien baseline e alua ion included s aging o se e i y o disease (modi ied Hoehn &Yah [H&Y] scale), mo o assess- men (Uni ied Pa kinson’s Disease Ra ing Scale [UPDRS] pa III and pa IV, F eezing o Gai Ques ionnai e [FOG-Q]), non-mo o symp oms (Non-Mo o Symp oms Scale [NMSS], Pa kinson’s Disease Sleep Scale [PDSS], Visual Analog Scale- Pain [VAS-Pain], Visual Analog Fa igue Scale [VAFS]), cogni ion (MMSE, Pa kinson’s Disease Cogni i e Ra ing Scale [PD-CRS], comple ing a simple 16-piece puzzle), mood and neu opsy- chia ic symp oms (Beck Dep ession In en o y-II [BDI-II], Neu opsychia ic In en o y [NPI], Ques- ionnai e o Impulsi e-Compulsi e Diso de s in Pa kinson’s Disease-Ra ing Scale [QUIP-RS]), dis- abili y (Schwab &England Ac i i ies o Daily Li ing Scale [S&E]), heal h ela ed quali y o li e (QoL) ( he 39-i em Pa kinson’s disease Ques ionnai e [PDQ- 39SI]), and global QoL (PQ-10, EUROHIS-QOL 8-i em index [EUROHIS-QOL8]) [16]. In e iews we e conduc ed o de e mine he p esence o alls acco ding o he de ini ion o alls p oposed by he Kellogg In e na ional Wo k G oup on he p e en ion o alls by he elde ly [17]: a all is an unin en ional o unexpec ed e en , esul s in he pe son coming o es on he g ound o ano he lowe le el and is no he esul o a majo in insic e en (such as a loss o consciousness) o an o e whelming ex e nal o ce. The e en was conside ed when i was no some hing ha happened o a speci ic eason some ime ago bu was a epea ed abno mal phenomenon. A ime ame was no de ined bu i was speci ically asked abou he p esence and numbe o alls in he las mon h. Mo e- o e , alls dia y, calenda , o pos ca d we e no used. In pa ien s wi h mo o luc ua ions, he mo o assess- men was conduc ed du ing he OFF s a e (wi hou medica ion in he las 12 hou s) and du ing he ON s a e. Howe e , in pa ien s wi hou mo o luc ua- ions, he assessmen was only pe o med wi hou medica ion ( i s hou in he mo ning wi hou aking medica ion in he p e ious 12 hou s). The pa ien s we e ollowed o 1-yea a e he baseline isi and in o ma ion abou hospi al admission was collec ed. Speci ically, he ollowing hospi aliza ion- ela ed da a we e eco ded: numbe o hospi aliza ions, hospi al s ay days, and ea- sons o hospi al admission. Those pa ien s wi h a leas one acu e hospi aliza ion du ing he ollow-up we e de ined as Pa ien s wi h acu e hospi aliza- ion, whe eas hose wi h non-acu e hospi aliza ion du ing he ollow-up was de ined as Pa ien s wi h- ou acu e hospi aliza ion. The e o e, hose pa ien s wi h one o mo e p og ammed admission bu wi h- ou any acu e hospi aliza ion we e conside ed as Pa ien s wi hou acu e hospi aliza ion. Rehospi al- iza ion was no conside ed o he analysis. The easons o hospi al admissions we e di ides in h ee g oups [18]: 1) Di ec PD- ela ed mo bid- i y: mo o complica ions, psychia ic symp oms, au onomic dys unc ion, senso y symp oms, sleep dis- o de s, and side e ec s o an i-pa kinsonian d ugs; 2) Indi ec PD- ela ed mo bidi y: aumas, pneumonia, and in es inal obs uc ion / gas opa esis; 3) Non-PD ela ed causes. Da a analysis Da a we e p ocessed using SPSS 20.0 o Win- dows. Fo compa isons be ween pa ien s wi h and 108 D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD Fig. 1. Flowcha abou PD pa ien s om he COPPADIS coho pa icipa ing in he p esen s udy. O 594 pa ien s, 1 pa ien was excluded due o change in he diagnosis ( om PD o MSA) and 88 o o he easons. O 605 pa ien s included in he analysis, 41 (6.8%) p esen ed a leas one hospi aliza ion (35 acu e and 6 planned hospi aliza ion). MSA, mul iple sys em a ophy; PD, Pa kinson’s disease. wi hou an acu e hospi aliza ion, he S uden ’s - es , Mann-Whi ney-Wilcoxon es , Chi-squa e es , o Fishe es , as app op ia e, we e used (dis ibu ion o a iables was e i ied by one-sample Kolmogo o - Smi no es ). Kaplan-Meie es ima es we e ob ained o de e mine he isk o acu e hospi aliza ion wi h ega ds o he p esence o di e en PD symp oms and/o complica ions: mo o luc ua ions; dyskine- sia; e y se e e NMS (NMSS o al sco e > 70) [19]; majo dep ession [16]; cogni i e impai men [20]; eezing o gai (FOG); alls; dysphagia. Sel - epo ed FOG was de ined ega ding he FOG-Q as p esen ing wi h a FOG-Q i em-3 sco e > 0. Func- ional dependency was de ined as a S&E sco e less han 80% (80% = comple ely independen ; 70% = no comple ely independen ) [21]. Pa ien s wi h a NMSS i em-19 sco e > 0 we e conside ed as su e ing om dysphagia. Cox p opo ional haza ds models we e applied o iden i y independen p edic o s o acu e hospi aliza ion du ing he 1-yea ollow-up. Fac o s included as po en ial p edic o s we e mo o se e - i y, mo o complica ions, axial symp oms and ela ed complica ions (FOG; alls; dysphagia), NMS bu - den, mood, cogni ion, neu opsychia ic symp oms, and disabili y o ac i i ies o daily li ing (Supple- men a y Table 1). Age, gende , disease du a ion, LEDD (le odopa equi alen daily dose [22]), and o al numbe o non-an ipa kinsonian d ugs (as a ma ke o como bidi y [23]) we e included as co a i- a es (Supplemen a y Table 1). Values o p< 0.05 we e conside ed signi ican . S anda d p o ocol app o als, egis a ions, and pa ien consen s Fo his s udy, we ecei ed app o al om he Comi ´ ede ´ E ica de la In es igaci´ onCl ´ ınica de Galicia om Spain (2014/534; 02/DEC/2014). W i - en in o med consen s om all pa icipan s in his s udy we e ob ained be o e he s a o he s udy. COPPADIS-2015 was classi ied by he AEMPS (Agencia Espa˜ nola del Medicamen o y P oduc- os Sani a ios) as a Pos -au ho iza ion P ospec i e Follow-up s udy wi h he code COH-PAK-2014-01. Da a a ailabili y The p o ocol and he s a is ical analysis plan a e a ailable on eques . De-iden i ied pa icipan da a a e no a ailable o legal and e hical easons. RESULTS A o al o 605 (62.5 ±8.9 yea s old; 59.8% males) om he 694 pa ien s diagnosed wi h PD a base- line om he COPPADIS coho we e included in he analysis (87.2%). Figu e 1 shows he easons o he lack o ollow-up o 89 pa ien s. In 64 cases (9.2%) no da a was eco ded. The mean disease du a ion (N = 605) a baseline was 5.5 ±4.4 yea s. Fo y-one ou o 605 PD pa ien s (6.8%) p esen ed a leas one hospi aliza ion du ing he 1-yea ollow-up a e he baseline isi , being 35 o hem (85.4%) wi h a leas D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD 109 one acu e hospi aliza ion. F om he ini ial PD coho (N = 693; 1 case excluded due o change in diagnosis), 5% o he pa ien s p esen ed an acu e hospi aliza ion (Fig. 2A). In 35 ou o 41 pa ien s (85.4%) hospi- al admission was epo ed once, wice in 4 pa ien s (9.8%), and h ee imes in 2 pa ien s (4.8%). The mean hospi al s ay days was 8.4 ±8.3 ( ange 1–39). A o al o 49 admissions we e epo ed, being 38 acu e and 11 p og ammed hospi aliza ions (Table 1). Wi h ega ds o he acu e admissions, 3 pa ien s ou o 35 (8.6%) we e hospi alized due o a di ec PD- ela ed mo bidi y, 15 (42.9%) due o an indi ec PD- ela ed mo bidi y, and 14 (40%) due o non-PD ela ed causes (Fig. 2B). T auma ic alls (9 e en s) ep esen ed he mos equen cause o admission, being 56.3% o all indi ec PD- ela ed mo bidi y causes, 23.7% all acu e hospi iliza ions (38 e en s), and 18.4% o all hospi al- iza ions (49 e en s) (Table 1 and Fig. 2C). No dea hs we e epo ed, nei he in pa ien s who p esen ed a hospi aliza ion no in hose who did no . The e we e no di e ences be ween pa ien s who p esen ed an acu e hospi aliza ion compa ed o hose who did no in e ms o age, gende , disease du a ion, mo o pheno ype, and H&Y mo o s age (Table 2). Howe e , pa ien s who su e ed om an acu e hospi- aliza ion p esen ed a wo se mo o (UPDRS-III-OFF and UPDRS-IV) and non-mo o s a us (PD-CRS, NMSS, BDI-II, NPI, and PDSS) a baseline (Table 2). Mo o luc ua ions, dyskinesia, alls, dysphagia, Table 1 Causes o hospi aliza ion du ing he 1 yea ollow-up a e he baseline isi : 49e en s in 41 PD pa ien s Acu e unplanned hospi aliza ions (38 e en s) Di ec disease ela ed mo bidi y (4 e en s) -DBS PD sys em in ec ion (2 e en s) -Mo o impai men (1 e en ) -O hos a ic hypo ension (1 e en ) Indi ec disease ela ed mo bidi y (16 e en s) -T auma ic alls (9 e en s) -Pneumonia and/o espi a o y in ec ion (4 e en s) -In es inal obs uc ion and/o gas opa esia (3 e en s) Non-PD ela ed causes (16 e en s) -O he in ec ions (6 e en s) -Ca diac ischemic a ack (3 e en s) -U ina y sys em complica ions (3 e en s) -Ca diac insu iciency (1 e en ) -Syncope seconda y o a o ics enosis (1 e en ) -S oke (1 e en ) -Esophagi is (1 e en ) Unclea diagnosis (2 e en s) P og ammed hospi aliza ions (11 e en s) -Lumba canal s enosis su ge y (2 e en s) -Deep b ain s imula ion su ge y (2 e en s) -Ca o id bypass su ge y (1 e en ) -Ao ic al e eplacemen (1 e en ) -knee eplacemen su ge y (1 e en ) -T ansu e h al esec ion o he p os a e (1 e en ) -U ina y incon inence su ge y (1 e en ) -Ca cinoma pulmona y esec ion (1 e en ) -Apomo phine es (1 e en ) Fig. 2. A) Pe cen age o PD pa ien s om he COPPADIS coho (N = 693; 1 excluded due o change in he diagnosis) wi hou ollow-up da a (N = 88; 12.7%), wi hou hospi aliza ion (N = 564; 81.4%), wi h planned hospi aliza ion (N = 6; 1%), and wi h acu e hospi aliza ion (N = 35; 5%) du ing he 1-yea ollow-up a e he baseline isi . B) Pe cen age o pa ien s wi h a leas one acu e hospi aliza ion (N = 35) ega ding he eason o admission: Di ec PD- ela ed mo bidi y (N = 3; 8.6%); Indi ec PD- ela ed mo bidi y (N = 15; 42.9%); Non-PD ela ed causes (N = 40; 40%); Mo e han 1 hospi aliza ion wi h bo h easons (N = 1; 2.8%); Unclea diagnosis (N = 2; 5.7%). C) Reasons o hospi al admissions (38 e en s) in he subg oup o pa ien s wi h acu e hospi aliza ion: 1) Di ec PD- ela ed mo bidi y (4 e en s; 10.5%); 2) Indi ec PD- ela ed mo bidi y: aumas, pneumonia, and in es inal obs uc ion / gas opa esis (16 e en s; 42.1%); 3. Non-PD ela ed causes (16 e en s; 42.1%). PD, Pa kinson’s disease. 110 D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD Table 2 Disease ela ed cha ac e is ics, mo o and non-mo o symp oms, au onomy o ac i i ies o daily li ing and quali y o li e in PD pa ien s wi h and wi hou acu e hospi aliza ion du ing he yea a e he baseline isi (n= 605) All sample Wi hou acu e Wi h acu e p (N = 605) hospi aliza ion hospi aliza ion (N = 570) (N = 35) Age 62.5 ±8.9 62.5 ±8.9 63.5 ±7.9 0.646 Males (%) 59.8 71.4 59.3 0.106 Disease du a ion (yea s) 5.5 ±4.4 5.5 ±4.3 5.8 ±4.4 0.656 Numbe o non an i pa kinsonian d ugs 2.6 ±2.4 2.6 ±2.4 2.6 ±2.5 0.980 L-dopa eq. daily dose (mg) 563.9 ±420.5 555.8 ±416.6 703.7 ±468.4 0.063 Mo o pheno ype (%) 0.621 - T emo icdominan 47.3 48.4 40 - PIGD 38.8 37.8 45.7 - Inde e mina e 13.9 13.8 14.3 Hoehn&Yah 2 [2, 2] 2 [2, 2] 2 [2, 2] 0.720 - S age om 3 o 5(%) 10.3 9.9 13.3 0.373 UPDRS-III 21.6 ±10.4 20.7 ±9.9 27.8 ±11.8 0.001 UPDRS-IV 2 ±2.4 1.8 ±3.3 3.3 ±30.001 - Mo o luc ua ions (%) 32.7 29.3 57.1 0.001 - Dyskinesia (%) 18.1 15.6 36.4 0.006 FOG-Q 3.5 ±4.6 3.4 ±4.5 4.7 ±4.7 0.006 - Pa ien s wi h FOG (%) 33.8 32.5 42.9 0.154 - Pa ien s wi h alls (%) 17.5 15.5 31.4 0.020 PD-CRS 91.6 ±15.3 92.2 ±15.3 86.8 ±13.9 0.049 - Cogni i e impai men (PD-CRS ≤84) (%) 28 26.6 38.2 0.114 NMSS 44.8 ±36.7 41.9 ±35 66.1 ±42.8 < 0.0001 - Se e e and/o NMS bu den (NMSS > 40) (%) 40.7 37 67.6 0.001 - Ve y se e e NMS bu den (NMSS > 70) (%) 21.1 18.3 41.2 0.004 - Dysphagia 21.1 17.5 47.1 < 0.0001 BDI-II 8.9 ±7.7 8.4 ±7.5 12.1 ±8.5 0.007 - Majo dep ession (%) 17.1 15.4 28.6 0.051 NPI 6.7 ±8.4 6.2 ±8.1 10.1 ±9.4 0.005 QUIP-RS 4.3 ±8.1 3.4 ±7.1 4.5 ±8 0.227 PDSS 118.1 ±23.9 119.2 ±23.7 110.9 ±24.3 0.014 VAS-PAIN 2.8 ±3 2.8 ±3.1 3.4 ±2.4 0.133 - Pa ien s wi h pain (%) 61.2 58.9 77.1 0.027 VASF – physical 2.9 ±2.8 2.9 ±2.8 3.3 ±2.8 0.342 VASF – men al 2.1 ±2.6 2.1 ±2.5 2.3 ±2.9 0.668 ADLS 87.5 ±10.9 87.9 ±10.7 84.3 ±11.4 0.048 - Pa ien s wi h unc ional dependency (%) 12.1 11.4 17.1 0.233 PDQ-39SI 17.2 ±14.1 15.9 ±13.3 26.6 ±16 < 0.0001 PQ-10 7.2 ±1.6 7.3 ±1.6 6.8 ±1.7 0.119 EUROHIS-QOL8 3.8 ±0.5 3.8 ±0.5 3.6 ±0.6 0.038 The esul s ep esen pe cen ages, mean ±SD o median [p25, p75].Chi-squa ed and Mann-Whi ney-Wilcoxon es we e applied o compa - isons be ween Non acu e hospi aliza ion (N = 570) and Acu e unplanned hospi aliza ion (N = 35) pa ien s. Da a abou H&Y and UPDRS-III a e du ing he OFF s a e ( i s hing in he mo ning wi hou aking medica ion in he p e ious 12 hou s). ADLS, Schwab and England Ac i i ies o daily li ing Scale); BDI, Beck Dep ession In en o y-II; NMSS, Non-Mo o Symp oms Scale; NPI, Neu opsychia ic In en o y; PD, Pa kinson’s disease; PD-CRS, Pa kinson’s Disease Cogni i e Ra ing Scale; PDSS, Pa kinson’s Disease Sleep Scale; PIGD, Pos u al Ines abili y Gai Di icul y; QUIP-RS, Ques ionnai e o Impulsi e-Compulsi e Diso de s in Pa kinson’s Disease-Ra ing Scale; UPDRS, Uni ied Pa kinson’s Disease Ra ing Scale; VAFS, Visual Analog Fa igue Scale; VAS-Pain, Visual Analog Scale-Pain. a se e e and/o e y se e e NMS bu den, and pain we e mo e equen in pa ien s who p esen ed an acu e hospi aliza ion compa ed o hose who did no (Table 2). Speci ically, he NMSS o al sco e (66.1 ±42.8 s 41.9 ±35; p< 0.0001) and he sco e on domains 2 (sleep/ a igue), 3 (mood/apa hy), 4 (pe cep ual p oblems/hallucina ions), 5 (a en- ion/memo y), 6 (gas oin es inal symp oms), and 7 (u ina y symp oms) o he NMSS indica ing a g ea e se e e bu den we e highe in pa ien s wi h acu e hospi aliza ion (Fig. 3A and Supplemen a y Table 2). Mo eo e , QoL and disabili y we e wo se in his g oup o pa ien s wi h acu e hospi aliza ion, p esen ing a highe sco e a baseline on he PDQ- 39SI (26.6 ±16 s 15.9 ±13.3; p< 0.0001) and a lowe sco e on he EUROHIS-QOL8 (3.6 ±0.6 s 3.8 ±0.5; p= 0.038) and S&E sco e (83.4 ±11.4 s 87.9 ±10.7; p= 0.048) when compa ed wi h pa ien s D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD 111 Fig. 3. A) Compa ison in PD pa ien s wi h s wi hou acu e hospi aliza ion o mean NMSS sco e on each domain o he scale a baseline; NMSS-1, Ca dio ascula (p= 0.892); 2) NMSS-2, Sleep/ a igue (p= 0.003); NMSS-3, Dep ession/apa hy (p= 0.003); NMSS-4, Pe cep ual p oblems/hallucina ions (p= 0.001); NMSS-5, A en ion/memo y (p= 0.001); NMSS-6, Gas oin es inal ac (p= 0.041); NMSS-7, U ina y symp oms (p= 0.040); NMSS-8, Sexual dys unc ion (p= 0.152); NMSS-9, Miscellaneous (p= 0.106). B) Compa ison in PD pa ien s wi h s wi hou acu e hospi aliza ion o mean PDQ-39SI sco e on each domain o he scale: PDQ-39SI-1, Mobili y (p= 0.001); PDQ-39SI-2, Ac i i ies o daily li ing (p= 0.002); PDQ-39SI-3, Emo ional well-being (p= 0.002); PDQ-39SI-4, S igma (p= 0.153); PDQ-39S-5, Social suppo (p= 0.259); PDQ-39SI-6, Cogni ion (p= 0.001); PDQ-39SI-7, Communica ion (p< 0.0001); PDQ-39SI-8, Pain and discom o (p= 0.133). NMS, Non-mo o symp oms; PD, Pa kinson’s disease. wi hou acu e hospi aliza ion (Table 2). Wi h ega ds o he domains o he PDQ-39SI, pa ien s wi h acu e hospi aliza ions p esen ed signi ican ly highe sco es in all domains indica ing a wo se QoL excep on domains 4 (s igma), 5 (social suppo ), and 8 (pain/ discom o ) (Fig. 3B and Supplemen a y Table 2). In Kaplan-Meie analysis, he p esence a base- line o mo o luc ua ions (p= 0.004), dyskinesia (p= 0.003), e y se e e NMS bu den (p= 0.001), majo dep ession (p= 0.037), alls (p= 0.001), and dysphagia (p= 0.001) was ela ed o a highe isk o acu e hospi aliza ion (Fig. 4). Speci ically, o su e om mo o luc ua ions (HR [haza d a io] 2.461; 95% CI, 1.065–5.678; p= 0.035), a e y se e e NMS bu den (HR [haza d a io] 2.828; 95% CI, 1.319–6.063; p= 0.008), alls (HR 3.966; 95% CI 1.757–8.470; p= 0.001), and dysphagia (HR 2.356; 95% CI 1.124–4.941; p= 0.023) was associ- a ed wi h acu e hospi aliza ion a e adjus men o age, gende , disease du a ion, LEDD, o al numbe o non-an ipa kinsonian d ugs, and UPDRS-III-OFF (Table 3). Pa ien s who p esen ed a sco e on he UPDRS-III-OFF > 20 a baseline had a signi ican ly highe isk o acu e hospi aliza ion a e adjus men o he same co a ia es as well (HR 3.644; 95% CI 1.430–9.284; p= 0.007). Al hough unadjus ed HR associa ed wi h dyskinesia (HR 2.792; 95% CI 1.365–5.711; p= 0.005) and majo dep ession (HR 2.159; 95% CI 1.033–4.515; p= 0.041) we e signi i- can (Table 3), he e ec was no a e adjus men o he p e ious commen ed co a ia es. O he p e ious a iables, only alls (HR 2.998; 95% CI 1.080–8.322; p= 0.035) was an independen p edic o o acu e hos- pi aliza ion when di e en co a ia es as po en ial p edic o s o hospi aliza ion we e included in an “a p io i” well-planned model (Table 4). In he model, ha ing alls iples he p obabili y o acu e hospi- al admission ega dless o o he a iables, and he equency o alls a baseline was double in hose pa ien s who we e admi ed du ing he 1-yea ollow- up compa ed o hose who did no (31.4% s 15.5%; p= 0.020). Speci ically, ha ing alls du ing he p e- ious mon h o he baseline isi was associa ed wi h acu e admission du ing he 1-yea ollow-up (Sup- plemen a y Figu e 1). DISCUSSION In he p esen s udy, we obse ed di e en impo - an indings: 1) he p obabili y o p esen ing an acu e hospi aliza ion is no in equen in pa ien s wi h PD; 2) he QoL and au onomy o ac i i ies o daily li ing is wo se and he NMS bu den is g ea e in hose PD pa ien s who will ha e an acu e hospi- aliza ion; 3) he e a e ce ain symp oms associa ed wi h a g ea e isk o acu e hospi aliza ion such as mo o luc ua ions, dyskinesias, se e e NMS bu den, majo dep ession, alls, and dysphagia; 4) alls is an independen p edic o o acu e hospi aliza ion ha inc eases he isk by h ee imes. 112 D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD Fig. 4. P opo ion o pa ien s wi hou acu e hospi aliza ion wi h ega ds o su e ing (in blue) o no (in g een) om mo o luc ua ions (p= 0.004), dyskinesia (p= 0.003), e y se e e NMS bu den (p= 0.001), majo dep ession (p= 0.037), alls (p= 0.001), and dysphagia (p= 0.001). Y, su i al; X, days o ollow-up. NMS, Non-mo o symp oms. Table 3 Analysis abou he isk o acu e hospi aliza ion a e 1 yea o ollow-up wi h ega ds o ha ing o no di e en complica ions (N = 605) Unadjus ed HR (95% CI) pAdjus ed HR(95% CI) p Mo o luc ua ions 2.616 (1.329–5.148) 0.005 2.461 (1.065–5.678) 0.035 Dyskinesia 2.792 (1.365–5.711) 0.005 2.145 (0.905–5.085) 0.083 Se e e o e y se e e NMSB (NMSS > 40) 2.871 (1.400–5.890) 0.004 2.645 (1.154–6.103) 0.022 Ve y se e e NMSB (NMSS > 70) 2.925 (1.477–5.791) 0.002 2.828 (1.319–6.063) 0.008 FOG 1.489 (0.757–2.930) 0.249 1.117 (0.496–2.518) 0.789 Falls 3.262 (1.590–6.696) 0.001 3.966 (1.757–8.470) 0.001 Dysphagia 2.843 (1.450–5.575) 0.002 2.356 (1.124–4.941) 0.023 Majo dep ession 2.159 (1.033–4.515) 0.041 1.934 (0.855–4.377) 0.113 Cogni i e impai men (PD-CRS ≤84) 1.493 (0.743–3.002) 0.260 1.160 (0.514–2.615) 0.721 HY-OFF om 3 o 5 1.331 (0.463–3.826) 0.595 0.703 (0.187–1.719) 0.602 UPDRS-III-OFF > 20 2.800 (1.258–6.233) 0.012 3.644 (1.430–9.284) 0.007∗ Func ional dependency 2.118 (0.877–5.116) 0.095 1.894 (0.675–5.318) 0.225 Age, gende , disease du a ion, LEDD (le odopa equi alen daily dose), o al numbe o non-an i pa kinsonian d ugs (as a ma ke o como bidi y) and UPDRS-III-OFF we e included in he model as co a ia es. ∗Fo his analysis he UPDRS-III-OFF was no included in he model. FOG, eezing o gai ; HR, Haza d a io; NMSB, non-mo o symp oms bu den; NMSS, Non-Mo o Symp oms Scale; PD-CRS, Pa kinson’s Disease Cogni i e Ra ing Scale; UPDRS, Uni ied Pa kinson’s Disease Ra ing Scale. Abou 5% o he pa ien s om he COPPADIS coho [15, 16] p esen ed an acu e hospi aliza ion a e 1-yea o ollow-up. This pe cen age is low com- pa ed o o he s udies, anging om 7 o 28% pe yea [17]. The esul s be ween s udies a y in pa o di e ences in me hodology [1, 2, 24–27]. Mo e- o e , many s udies a e p ospec i e [6, 26, 28] o , mo e equen ly, e ospec i e [29–34] analysis conduc ed only in PD pa ien s admi ed wi h he aim o analyze p oblems du ing hospi aliza ion. Mo eo e , se e al s udies we e conduc ed in small samples and/o wi h- ou con ol g oup: 76 pa ien s [28]; 108 pa ien s [26]; 130 pa ien s [25]; 132 pa ien s [6]; 143 pa ien s [33]; 144 pa ien s [24]; 173 pa ien s [30]; 367 pa ien s [3]. A ecen s udy conduc ed in a la ge popula ion om No h Ame ica, he Ne he lands, and Is ael showed D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD 113 Table 4 Cox- eg ession model abou p edic o s o acu e hospi aliza ion in PD pa ien s a e 1 yea o ollow-up (N = 605) HR (95% CI) p Age 1.002 (0.951–1.056) 0.937 Gende 0.627 (0.267–1.469) 0.282 Disease du a ion 0.838 (0.726–0.968) 0.016 LEDD 1.000 (0.999–1.001) 0.614 To al numbe o non-an i pa kinsonian d ugs 0.839 (0.675–1.042) 0.111 UPDRS-III-OFF 1.032 (0.991–1.074) 0.128 UPDRS-IV 1.071 (0.909–1.260) 0.413 NMSS 0.999 (0.989–1.009) 0.823 BDI-II 1.016 (0.955–1.081) 0.613 PD-CRS 0.986 (0.958–1.015) 0.339 NPI 1.021(0.972–1.072) 0.406 Falls 2.998 (1.080–8.322) 0.035 Dysphagia 1.593 (0.645–3.932) 0.313 ADLS 1.004 (0.962–1.048) 0.865 Haza d a io; LEED, Le odopa equi alen daily dose; NMSS, Non-Mo o Symp oms Scale; NPI, Neu opsychia ic In en o y; PD-CRS, Pa kinson’s Disease Cogni i e Ra ing Scale; UPDRS, Uni ied Pa kinson’s Disease Ra ing Scale. The omnibus es indi- ca ed an o e all signi ican model χ2= 34,149 (p= 0.001). ha o 4,680 PD pa ien s ollowed du ing an a e - age o 2 yea s (median 1.85, maximum 4.85 yea s), 2,264 pa ien s (48.4%) had a hospi al encoun e a e he baseline isi [35]. Compa ed wi h many o he s udies [6, 29, 30, 33, 34, 36, 37], he mean age o he pa ien s om he COPPADIS coho is lowe , and, as p e iously epo ed [23, 38], ou sample is no ully ep esen a i e o he PD popula ion due o inclusion and exclusion c i e ia a baseline (i.e., age limi , no demen ia, no se e e como bidi ies, no sec- ond line he apies, e c.) which subsequen ly en ails a bias owa d ea ly PD. This aspec may explain he lowe equency o admissions in ou analysis a e 1-yea o ollow-up. On he o he hand, wi h ega ds o he causes o hospi aliza ion, ou indings a e in line wi h wo ecen e iew s udies [26, 39], in which in ec ions, wo sening mo o ea u es, alls/ ac u es, ca dio ascula co-mo bidi ies, neu opsychia ic, and gas oin es inal complica ions we e he main easons o hospi aliza ion among people wi h PD. Speci i- cally, in ou s udy, alls was he mos equen cause despi e mo e han 90% o he pa ien s had a s age 2 o he H&Y. By he con a y, admissions ela ed o a di ec PD- ela ed e en we e in equen since ambu- la o y PD symp oms managemen is o en p e e ed. A wo se QoL and a g ea e disabili y and NMS bu den a baseline was obse ed in PD pa ien s who p esen ed an acu e hospi aliza ion in ou s udy. We obse e his inding because, unlike mos o he s udies, he assessmen a baseline was exhaus i e using di e en alida ed scales. Di e ences we e obse ed be ween pa ien s who we e admi ed du - ing he ollow-up and hose who did no as hose who we e admi ed had a wo se mo o and non- mo o s a us and wo se au onomy o ac i i ies o daily li ing and QoL. In o he wo ds, PD pa ien s mo e a ec ed by hei disease may be mo e ulne - able and ha e a highe isk o acu e hospi aliza ion. Symp oms such as pain, dysphagia, alls, mo o luc- ua ions, dyskinesia, a wo se QoL, and a g ea e mo o disabili y we e mo e equen in pa ien s who p esen ed an acu e hospi aliza ion, bu no di e ences we e obse ed in a igue and mo o pheno ype. Falls, ac u es, in ec ions, cogni i e, and mo o decline ha e been iden i ied as isk ac o s o acu e hospi al admissions in pa ien s wi h PD [11, 14]. Mo e speci - ically, longe imed up and go es , highe numbe o como bidi ies, numbe o medica ions, he p esence o mo o luc ua ions, ha ing deep b ain s imula ion, and he deg ee o ca egi e bu den ha e been associ- a ed wi h hospi aliza ion and/o ehospi aliza ion in PD [35]. A highe PDQ-39 o al sco e was obse ed o be associa ed wi h a highe isk o ehospi aliza ion as well [35]. In ou s udy, he ac o s associa ed wi h acu e hospi aliza ion a e no su p ising. Howe e , he only independen p edic o o hospi aliza ion was alls. In his con ex , in a pooled da a o 7 s ud- ies selec ed [27], he main causes o gene al wa d admission we e alls (30%) and PD- ela ed causes (16%), whe eas he main causes o neu ological wa d we e mo o (42.3%) and psychia ic complica ions (21.2%). In any case, ou inding o alls as a p edic o o acu e hospi aliza ion in PD should be in e p e ed wi h cau ion because he a es o admission due o all (N = 9) we e e y low. Ideally, hese indings should be ep oduced o e a longe pe iod o cap u e mo e admission and a guably wi h pa ien s wi h a b oade ange o se e i y. A e y impo an poin is ha some o hese symp oms can be ea ed wi h he aim o educing acu e PD hospi al admission [14]. Fo example, in ou coho , mo o luc ua ions we e associa ed wi h a doubled p obabili y o acu e hospi aliza ion, so educing OFF ime could educe he isk. Many ac- o s a e co ela ed. Falls we e associa ed wi h mo o luc ua ions ( alls we e p esen in 22.4% o pa ien s wi h mo o luc ua ions compa ed o 8.5% o pa ien s wi hou hem; p< 0.0001). One s a egy o educ- ing hem could be o inc ease he ON ime in PD pa ien s. Howe e , alls can ha e di e en e iology. Op imizing mo o symp om con ol and managing medica ion side e ec s may p e en alls and hence 120 D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD Name (Las Name, Fi s Name) Loca ion Role Con ibu ion Aguila , Miquel Hospi al Uni e si a i Mu ua de Te assa, Te assa, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen ´ A ila Ri e a, Ma ia Asunci´ on Conso ci Sani a i In eg al, Hospi al Gene al de L’Hospi ale , L’Hospi ale de Llob ega , Ba celona, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Be na do Lamb ich, Noem´ ı Hospi al de To osa Ve ge de la Cin a (HTVC), To osa, Ta agona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Bej -Kasem, Helena Hospi al de San Pau, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Bl´ azquez Es ada, Ma a Hospi al Uni e si a io Cen al de As u ias, O iedo, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Bo ´ ı Gonz´ alez, Ma ia ´ Angeles Hospi al Uni e si a i Mu ua de Te assa, Te assa, Ba celona, Spain Si e in es iga o Neu opsychologis ; e alua ion o pa icipan s Bo u´ e, Ca men Hospi al In an a So ´ ıa, Mad id, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Buongio no, Ma ia Te esa Hospi al Uni e si a i Mu ua de Te assa, Te assa, Ba celona, Spain Si e in es iga o Nu se s udy coo dina o Cabello Gonz´ alez, Ca olina Complejo Hospi ala io de Na a a, Pamplona, Spain Si e in es iga o Scheduling o e alua ions Cabo L´ opez, I ia Complejo Hospi ala io Uni e si a io de Pon e ed a (CHOP), Pon e ed a, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Caballol, Nu ia Conso ci Sani a i In eg al, Hospi al Mois´ es B oggi, San Joan Desp´ ı, Ba celona, Spain. Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen C´ ama a Lo enzo, Ana Hospi al Cl´ ınic de Ba celona, Ba celona, Spain Si e in es iga o Nu se s udy coo dina o Ca illo, F´ a ima Hospi al Uni e si a io Vi gen del Roc´ ıo, Se illa, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Ca illo Padilla, F ancisco Jos´ e Hospi al Uni e si a io de Cana ias, San C is ´ obal de la Laguna, San a C uz de Tene i e, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Casas, Elena Complejo Asis encial Uni e si a io de Bu gos, Bu gos, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Ca al´ an, Ma ia Jos´ e Hospi al Uni e si a io Cl´ ınico San Ca los, Mad id, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Cla e o, Ped o Complejo Hospi ala io de Na a a, Pamplona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Co ina Fe n´ andez, A Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o Coo dina ion o blood ex ac ions Cosgaya, Ma ina Hospi al Cl´ ınic de Ba celona, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Co s Fo as e , Anna Ins i u d’Assis ` encia Sani ` a ia (IAS) - Ins i u´ ıC ´ a ala de la Salud. Gi ona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen C espo Cue as, Ane Hospi al del Ma , Ba celona, Spain. Si e in es iga o E alua ion o pa icipan s and/o da a managemen Cubo, Es he Complejo Asis encial Uni e si a io de Bu gos, Bu gos, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen De Deus Fon icoba, Te esa Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o Nu se s udy coo dina o E alua ion o pa icipan s and/o da a managemen (Con inued) D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD 121 Name (Las Name, Fi s Name) Loca ion Role Con ibu ion De F´ ab egues, O iol Hospi al Uni e si a io Vall d’Heb on, Ba celona, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen D´ ıez Fai en, M Hospi al Uni e si a i Mu ua de Te assa, Te assa, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen E o, Elena Complejo Hospi ala io de Na a a, Pamplona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Escalan e, Sonia Hospi al de To osa Ve ge de la Cin a (HTVC), To osa, Ta agona, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Es el ich Pey e , Elena Ins i u d’Assis ` encia Sani ` a ia (IAS) - Ins i u´ ıC ´ a ala de la Salud. Gi ona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Fe n´ andez Guill´ an, Noelia Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o Neu oimaging s udies G´ amez, Ped o Complejo Asis encial Uni e si a io de Bu gos, Bu gos, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Gallego, Me cedes Hospi al La P incesa, Mad id, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Ga c´ ıa Calden ey, Juan Cen o Neu ol´ ogico Oms 42, Palma de Mallo ca, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Ga c´ ıa Campos, C is ina Hospi al Uni e si a io Vi gen Maca ena, Se illa, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Ga c´ ıa Mo eno, Jose Manuel Hospi al Uni e si a io Vi gen Maca ena, Se illa, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Gas ´ on, I zia Complejo Hospi ala io de Na a a, Pamplona, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Guill´ en Fopiani, Desi ´ e Complejo Hospi ala io Uni e si a io de Pon e ed a (CHOP), Pon e ed a, Spain Si e in es iga o Neu opsychologis ; e alua ion o pa icipan s G´ omez Ga e, Ma ´ ıa del Pila Hospi al Uni e si a io Vi gen del Roc´ ıo, Se illa, Spain Si e in es iga o Gene ic s udies coo dina ion G´ omez Mayo domo, V´ ıc o Hospi al Cl´ ınico San Ca los, Mad id, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Gonz´ alez Aloy, Ja ie Ins i u d’Assis ` encia Sani ` a ia (IAS) - Ins i u´ ıC ´ a ala de la Salud. Gi ona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Gonz´ alez A ambu u, Isabel Hospi al Uni e si a io Ma qu´ es de Valdecilla, San ande , Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Gonz´ alez A du a, Jessica Hospi al Uni e si a io Lucus Augus i (HULA), Lugo, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Gonz´ alez Ga c´ ıa, Bea iz Hospi al La P incesa, Mad id, Spain Si e in es iga o Nu se s udy coo dina o Gonz´ alez Palm´ as, Ma ia Jose a Complejo Hospi ala io Uni e si a io de Pon e ed a (CHOP), Pon e ed a, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Gonz´ alez Toledo, Gab iel Rica do Hospi al Uni e si a io de Cana ias, San C is ´ obal de la Laguna, San a C uz de Tene i e, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Golpe D´ ıaz, Ana Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o Labo a o y analysis coo dina ion G au Sol´ a, Mi eia Conso ci Sani a i In eg al, Hospi al Mois´ es B oggi, San Joan Desp´ ı, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Gua dia, Gemma Hospi al Uni e si a i Mu ua de Te - assa, Te assa, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen (Con inued) 122 D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD Name (Las Name, Fi s Name) Loca ion Role Con ibu ion He n´ andez Va a, Jo ge Hospi al Uni e si a io Vall d’Heb on, Ba celona, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Ho a Ba ba, And ea Hospi al de San Pau, Ba celona, Spain Si e in es iga o Neu opsychologis ; e alua ion o pa icipan s Idoa e Calde ´ on, Daniel Complejo Hospi ala io Uni e si a io de Pon e ed a (CHOP), Pon e ed a, Spain Si e in es igao neu opsychologis ; e alua ion o pa icipan s In an e, Jon Hospi al Uni e si a io Ma qu´ es de Valdecilla, San ande , Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Jes´ us, Sil ia Hospi al Uni e si a io Vi gen del Roc´ ıo, Se illa, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Kulise sky, Jaime Hospi al de San Pau, Ba celona, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Ku is, M´ onica Hospi al Rube In e nacional, Mad id, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Labandei a, Ca men Hospi al ´ Al a o Cunquei o, Comp- lejo Hospi ala io Uni e si a io de Vigo (CHUVI), Vigo, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Lab ado Espinosa, Miguel ´ Angel Hospi al Uni e si a io Vi gen del Roc´ ıo, Se illa, Spain Si e in es iga o Neu oimaging da a analysis Lac uz, F ancisco Complejo Hospi ala io de Na a a, Pamplona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Lage Cas o, Mel a Complejo Hospi ala io Uni e si a io de Pon e ed a (CHOP), Pon e ed a, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Lega da, In´ es Hospi al Uni e si a io Son Espases, Palma de Mallo ca, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen L´ opez A iz egui, Nu ia Complejo Hospi ala io de Toledo, Toledo, Spain Si e in es iga o / PI E alua ion o pa icipan s and/o da a managemen L´ opez D´ ıaz, Luis Manuel Hospi al Da Cos a de Bu ela, Lugo, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen L´ opez Manzana es, Lydia Hospi al La P incesa, Mad id, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen L´ opez Seoane, Balbino Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o Neu oimaging s udies Lucas del Pozo, Sa a Hospi al Uni e si a io Vall d’Heb on, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Mac´ ıas, Yolanda Fundaci´ on Hospi al de Alco c´ on, Mad id, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Ma a, Ma ina Hospi al In an a So ´ ıa, Mad id, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Ma ´ ı And es, Glo ia Hospi al Uni e si a io Vall d’Heb on, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Ma ´ ı, Ma ia Jos´ e Hospi al Cl´ ınic de Ba celona, Ba celona, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Ma ´ ınez Cas illo, Juan Ca los Hospi al Uni e si a io Ram´ on y Cajal, Mad id, Spain Si e in es iga o /PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Ma inez-Ma in, Pablo Cen o Nacional de Epidemiolog´ ıa y CIBERNED, Ins i u o de Salud Ca los III. Mad id Collabo a o in s a is ical and me hods analysis Me hods and s a is ical e iewe McA ee, Da ian Uni e si y o Pennsyl ania, Philadelphia Collabo a o in english s yle English s yle e iewe (Con inued) D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD 123 Name (Las Name, Fi s Name) Loca ion Role Con ibu ion Mei ´ ın, Ma ia Te esa Hospi al Da Cos a de Bu ela, Lugo, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Men´ endez Gonz´ alez, Manuel Hospi al Uni e si a io Cen al de As u ias, O iedo, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen M´ endez del Ba io, Ca lo a Hospi al Uni e si a io Vi gen del Roc´ ıo, Se illa, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Mi , Pablo Hospi al Uni e si a io Vi gen del Roc´ ıo, Se illa, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Mi anda San iago, Ja ie Complejo Asis encial Uni e si a io de Bu gos, Bu gos, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Mo ales Casado, Ma ia Isabel Complejo Hospi ala io de Toledo, Toledo, Spain. Si e in es iga o E alua ion o pa icipan s and/o da a managemen Mo eno Di´ eguez, An onio Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o Neu oimaging s udies Noguei a, V´ ıc o Hospi al Da Cos a de Bu ela, Lugo, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen No o Amado, Alba Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o Neu oimaging s udies No o Pon e, Sabela Hospi al Uni e si a io Pue a de Hie o, Mad id, Spain. Si e in es iga o E alua ion o pa icipan s and/o da a managemen O d´ as, Ca los Hospi al Rey Juan Ca los, Mad id, Spain, Mad id, Spain. Si e In es iga o E alua ion o pa icipan s and/o da a managemen Pagonaba aga, Ja ie Hospi al de San Pau, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Isabel Pa e´ es Hospi al Rube In e nacional, Mad id, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Pascual-Sedano, Be a Hospi al de San Pau, Ba celona, Spain Si e In es iga o E alua ion o pa icipan s and/o da a managemen Pas o , Pau Hospi al Uni e si a i Mu ua de Te assa, Te assa, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen P´ e ez Fue es, A´ ıda Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o Blood analysis P´ e ez Nogue a, Ra ael Hospi al Uni e si a io Vi gen Maca ena, Se illa, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Planas-Ball ´ e, Ana Conso ci Sani a i In eg al, Hospi al Mois´ es B oggi, San Joan Desp´ ı, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Planellas, Llu´ ıs Hospi al Cl´ ınic de Ba celona, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen P a s, Ma ian ´ Angeles Ins i u d’Assis ` encia Sani ` a ia (IAS) - Ins i u´ ıC ´ a ala de la Salud. Gi ona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen P ie o Ju czynska, C is ina Hospi al Rey Juan Ca los, Mad id, Spain, Mad id, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Puen e, V´ ıc o Hospi al del Ma , Ba celona, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Pueyo Mo lans, Me cedes Hospi al Uni e si a io de Cana ias, San C is ´ obal de la Laguna, San a C uz de Tene i e, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Redondo, Nu ia Hospi al La P incesa, Mad id, Spain Si e In es iga o E alua ion o pa icipan s and/o da a managemen (Con inued) 124 D. San os Ga c´ıa e al. / Acu e Hospi aliza ion in PD Name (Las Name, Fi s Name) Loca ion Role Con ibu ion Rod ´ ıguez M´ endez, Luisa Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o Blood analysis Rod ´ ıguez P´ e ez, Ampa o Bel´ en Hospi al Gene al Uni e si a io de Elche, Elche, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Rold´ an, Flo inda Hospi al Uni e si a io Vi gen del Roc´ ıo, Se illa, Spain Si e in es iga o Neu oimaging s udies Ru´ ız de A cos, Ma ´ ıa Hospi al Uni e si a io Vi gen Maca ena, Se illa, Spain. Si e in es iga o E alua ion o pa icipan s and/o da a managemen Ru´ ız Ma ´ ınez, Ja ie Hospi al Uni e si a io Donos ia, San Sebas i´ an, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen S´ anchez Alonso, Pila Hospi al Uni e si a io Pue a de Hie o, Mad id, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen S´ anchez-Ca pin e o, Maca ena Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o Neu oimaging s udies S´ anchez D´ ıez, Gema Hospi al Uni e si a io Ram´ on y Cajal, Mad id, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen S´ anchez Rod ´ ıguez, An onio Hospi al Uni e si a io Ma qu´ es de Valdecilla, San ande , Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen San ac uz, Pila Hospi al Cl´ ınic de Ba celona, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen San os Ga c´ ıa, Diego CHUAC, Complejo Hospi ala io Uni e si a io de A Co u˜ na Coo dina o o he P ojec Coo dina ion o he COPPADIS-2015 Segundo Rod ´ ıguez, Jos´ e Clemen e Complejo Hospi ala io de Toledo, Toledo, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Seijo, Manuel Complejo Hospi ala io Uni e si a io de Pon e ed a (CHOP), Pon e ed a, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Sie a, Ma ´ ıa Hospi al Uni e si a io Ma qu´ es de Valdecilla, San ande , Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Solano, Be a Ins i u d’Assis ` encia Sani ` a ia (IAS) - Ins i u´ ıC ´ a ala de la Salud. Gi ona, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Su´ a ez Cas o, Es e Complejo Hospi ala io Uni e si a io de Fe ol (CHUF), Fe ol, A Co u˜ na, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Ta a i, Juan Pablo Hospi al Uni e si a i Mu ua de Te assa, Te assa, Ba celona, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Vale o, Ca idad Hospi al A nau de Vilano a, Valencia, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Va gas, Lau a Hospi al Uni e si a io Vi gen del Roc´ ıo, Se illa, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Vela, Lydia Fundaci´ on Hospi al de Alco c´ on, Mad id, Spain Si e in es iga o / PI Coo dina ion a he cen e E alua ion o pa icipan s and/o da a managemen Villanue a, Cla a Hospi al Uni e si a io Cl´ ınico San Ca los, Mad id, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Vi es, B´ a ba a Hospi al Uni e si a io Son Espases, Palma de Mallo ca, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen Villa , Ma ia Dolo es Hospi al Uni e si a io de Cana ias, San C is ´ obal de la Laguna, San a C uz de Tene i e, Spain Si e in es iga o E alua ion o pa icipan s and/o da a managemen