Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study

107noNonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) Conclusions: NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment. (Hepatology 2016;63:827-838)openopenPiscaglia F.; Svegliati-Baroni G.; Barchetti A.; Pecorelli A.; Marinelli S.; Tiribelli C.; Bellentani S.; Bernardi M.; Biselli M.; Caraceni P.; Domenicali M.; Garuti F.; Gramenzi A.; Lenzi B.; Magalotti D.; Cescon M.; Ravaioli M.; Del Poggio P.; Olmi S.; Rapaccini G.L.; Balsamo C.; Di Nolfo M.A.; Vavassori E.; Alberti A.; Benvegnau L.; Gatta A.; Giacomin A.; Vanin V.; Pozzan C.; Maddalo G.; Giampalma E.; Cappelli A.; Golfieri R.; Mosconi C.; Renzulli M.; Roselli P.; Dell'isola S.; Ialungo A.M.; Risso D.; Marenco S.; Sammito G.; Bruzzone L.; Bosco G.; Grieco A.; Pompili M.; Rinninella E.; Siciliano M.; Chiaramonte M.; Guarino M.; Camma C.; Maida M.; Costantino A.; Barcellona M.R.; Schiada L.; Gemini S.; Lanzi A.; Stefanini G.F.; Dall'aglio A.C.; Cappa F.M.; Suzzi A.; Mussetto A.; Treossi O.; Missale G.; Porro E.; Mismas V.; Vivaldi C.; Bolondi L.; Zoli M.; Granito A.; Malagotti D.; Tovoli F.; Trevisani F.; Venerandi L.; Brandi G.; Cucchetti A.; Bugianesi E.; Vanni E.; Mezzabotta L.; Cabibbo G.; Petta S.; Fracanzani A.; Fargion S.; Marra F.; Fani B.; Biasini E.; Sacco R.; Morisco F.; Caporaso N.; Colombo M.; D'ambrosio R.; Croce L.S.; Patti R.; Giannini E.G.; Loria P.; Lonardo A.; Baldelli E.; Miele L.; Farinati F.; Borzio M.; Dionigi E.; Soardo G.; Caturelli E.; Ciccarese F.; Virdone R.; Affronti A.; Foschi F.G.; Borzio F.Piscaglia, F.; Svegliati-Baroni, G.; Barchetti, A.; Pecorelli, A.; Marinelli, S.; Tiribelli, C.; Bellentani, S.; Bernardi, M.; Biselli, M.; Caraceni, P.; Domenicali, M.; Garuti, F.; Gramenzi, A.; Lenzi, B.; Magalotti, D.; Cescon, M.; Ravaioli, M.; Del Poggio, P.; Olmi, S.; Rapaccini, G. L.; Balsamo, C.; Di Nolfo, M. A.; Vavassori, E.; Alberti, A.; Benvegnau, L.; Gatta, A.; Giacomin, A.; Vanin, V.; Pozzan, C.; Maddalo, G.; Giampalma, E.; Cappelli, A.; Golfieri, R.; Mosconi, C.; Renzulli, M.; Roselli, P.; Dell'Isola, S.; Ialungo, A. M.; Risso, D.; Marenco, S.; Sammito, G.; Bruzzone, L.; Bosco, G.; Grieco, A.; Pompili, M.; Rinninella, E.; Siciliano, M.; Chiaramonte, M.; Guarino, M.; Camma, C.; Maida, M.; Costantino, A.; Barcellona, M. R.; Schiada, L.; Gemini, S.; Lanzi, A.; Stefanini, G. F.; Dall'Aglio, A. C.; Cappa, F. M.; Suzzi, A.; Mussetto, A.; Treossi, O.; Missale, G.; Porro, E.; Mismas, V.; Vivaldi, C.; Bolondi, L.; Zoli, M.; Granito, A.; Malagotti, D.; Tovoli, F.; Trevisani, F.; Venerandi, L.; Brandi, G.; Cucchetti, A.; Bugianesi, E.; Vanni, E.; Mezzabotta, L.; Cabibbo, G.; Petta, S.; Fracanzani, A.; Fargion, S.; Marra, F.; Fani, B.; Biasini, E.; Sacco, R.; Morisco, F.; Caporaso, N.; Colombo, M.; D'Ambrosio, R.; Croce, L. S.; Patti, R.; Giannini, E. G.; Loria, P.; Lonardo, A.; Baldelli, E.; Miele, L.; Farinati, F.; Borzio, M.; Dionigi, E.; Soardo, G.; Caturelli, E.; Ciccarese, F.; Virdone, R.; Affronti, A.; Foschi, F. G.; Borzio, F

Mortality rate and risk factors for gastrointestinal bleeding in elderly patients

Background: Gastrointestinal bleeding (GIB) is burdened by high mortality rate that increases with aging. Elderly patients may be exposed to multiple risk factors for GIB. We aimed at defining the impact of GIB in elderly patients. Methods: Since 2008, samples of elderly patients (age 65 65 years) with multimorbidity admitted to 101 internal medicine wards across Italy have been prospectively enrolled and followed-up (REPOSI registry). Diagnoses of GIB, length of stay (LOS), mortality rate, and possible risk factors, including drugs, index of comorbidity (Cumulative Illness Rating Scale [CIRS]), polypharmacy, and chronic diseases were assessed. Adjusted multivariate logistic regression models were computed. Results: 3872 patients were included (mean age 79 \ub1 7.5 years, F:M ratio 1.1:1). GIB was reported in 120 patients (mean age 79.6 \ub1 7.3 years, F:M 0.9:1), with a crude prevalence of 3.1%. Upper GIB occurred in 72 patients (mean age 79.3 \ub1 7.6 years, F:M 0.8:1), lower GIB in 51 patients (mean age 79.4 \ub1 7.1 years, F:M 0.9:1), and both upper/lower GIB in 3 patients. Hemorrhagic gastritis/duodenitis and colonic diverticular disease were the most common causes. The LOS of patients with GIB was 11.7 \ub1 8.1 days, with a 3.3% in-hospital and a 9.4% 3-month mortality rates. Liver cirrhosis (OR 5.64; CI 2.51\u201312.65), non-ASA antiplatelet agents (OR 2.70; CI 1.23\u20135.90), and CIRS index of comorbidity >3 (OR 2.41; CI 1.16\u20134.98) were associated with GIB (p < 0.05). Conclusions: A high index of comorbidity is associated with high odds of GIB in elderly patients. The use of non-ASA antiplatelet agents should be discussed in patients with multimorbidity

Drug\u2013drug interactions involving CYP3A4 and p-glycoprotein in hospitalized elderly patients

Polypharmacy is very common in older patients and may be associated with drug-drug interactions. Hepatic cytochrome P450 (notably 3A4 subtype, CYP3A4) is a key enzyme which metabolizes most drugs; P-glycoprotein (P-gp) is a transporter which significantly influences distribution and bioavailability of many drugs. In this study, we assess the prevalence and patterns of potential interactions observed in an hospitalized older cohort (Registro Politerapia Societ\ue0 Italiana di Medicina Interna) exposed to at least two interacting drugs involving CYP3A4 and P-gp at admission, during hospitalization and at discharge. Individuals aged 65 and older (N-4039; mean age 79.2; male 48.1%), hospitalized between 2010 and 2016, were selected. The most common combinations of interacting drugs (relative frequency > 5%) and socio-demographic and clinical factors associated with the interactions were reported. The prevalence of interactions for CYP3A4 was 7.9% on admission, 10.3% during the stay and 10.7% at discharge; the corresponding figures for P-gp interactions were 2.2%, 3.8% and 3.8%. The most frequent interactions were amiodarone-statin for CYP3A4 and atorvastatin-verapamil-diltiazem for P-gp. The prevalence of some interactions, mainly those involving cardiovascular drugs, decreased at discharge, whereas that of others, e.g. those involving neuropsychiatric drugs, increased. The strongest factor associated with interactions was polypharmacy (OR 6.7, 95% CI 5.0\u20139.2). In conclusion, hospital admission is associated with an increased prevalence, but also a changing pattern of interactions concerning CYP3A4 and P-gp in elderly. Educational strategies and appropriate use of dedicated software seem desirable to limit drug interactions and the inherent risk of adverse events in older patients

Polypharmacy in older people: lessons from 10 years of experience with the REPOSI register

reserved361siAs a consequence of population aging, we have witnessed in internal medicine hospital wards a progressive shift from a population of in-patients relatively young and mainly affected by a single ailment to one of ever older and more and more complex patients with multiple chronic diseases, followed as out-patients by many different specialists with poor integration and inevitably treated with multiple medications. Polypharmacy (defined as the chronic intake of five or more drugs) is associated with increased risks of drug-drug interactions and related adverse effects, prescription and intake errors, poor compliance, re-hospitalization and mortality. With this background, the Italian Society of Internal Medicine chose to start in 2008 a prospective register called REPOSI (REgistro POliterapie SIMI, Società Italiana di Medicina Interna) in internal medicine and geriatric hospital wards. The country wide register is an ongoing observatory on multimorbidity and polypharmacy in the oldest old, with the goal to improve prescription appropriateness and, thus to avoid potentially inappropriate medications. The main findings of the register, that has accrued so far, 7005 older patients throughout a 10 year period, are summarized herewith, with special emphasis on the main patterns of poor prescription appropriateness and related risks of adverse events.mixedMannucci PM, Nobili A, Pasina L; Tettamanti M, Franchi C, Corrao S, Marengoni A, Salerno F, Cesari M, Perticone F, Licata G, Violi F, Corazza GR, Franchi C, Cortesi L, Tettamanti M, Cortesi L, Ardoino I, Prisco D, Silvestri E, Cenci C, Emmi G, Biolo G, Zanetti M, Guadagni M, Zaccari M, Vanoli M, Grignani G, Pulixi EA, Bernardi M, Bassi SL, Santi L, Zaccherini G, Mannarino E, Lupattelli G, Bianconi V, Paciullo F, Nuti R, Valenti R, Ruvio M, Cappelli S, Palazzuoli A, Olivieri O, Girelli D, Matteazzi T, Barbagallo M, Dominguez L, Cocita F, Beneduce V, Plances L, Zoli M, Lazzari I, Brunori M, Pasini FL, Capecchi PL, Palasciano G, Modeo ME, Di Gennaro C, Cappellini MD, Maira D, Di Stefano V, Fabio G, Seghezzi S, Mancarella M, Cesari M, Rossi PD, Damanti S, Clerici M, Conti F, Corazza GR, Miceli E, Lenti MV, Pisati M, Dominioni CC, Murialdo G, Marra A, Cattaneo F, Secchi MB, Ghelfi D, Anastasio L, Sofia L, Carbone M, Cipollone F, Guagnano MT, Angelucci E, Valeriani E, Mancuso G, Calipari D, Bartone M, Delitala G, Berria M, Muscaritoli M, Molfino A, Petrillo E, Zuccalà G, D'Aurizio G, Romanelli G, Marengoni A, Zucchelli A, Picardi A, Gentilucci UV, Gallo P, Dell'Unto C, Annoni G, Corsi M, Bellelli G, Zazzetta S, Mazzola P, Szabo H, Bonfanti A, Arturi F, Succurro E, Rubino M, Serra MG, Bleve MA, Gasbarrone L, Sajeva MR, Brucato A, Ghidoni S, Fabris F, Bertozzi I, Bogoni G, Rabuini MV, Cosi E, Manfredini R, Fabbian F, Boari B, De Giorgi A, Tiseo R, Paolisso G, Rizzo MR, Borghi C, Strocchi E, De Sando V, Pareo I, Sabbà C, Vella FS, Suppressa P, Agosti P, Schilardi A, Loparco F, Fenoglio L, Bracco C, Giraudo AV, Fargion S, Periti G, Porzio M, Tiraboschi S, Peyvandi F, Rossio R, Ferrari B, Colombo G, Monzani V, Savojardo V, Folli C, Ceriani G, Salerno F, Pallini G, Dallegri F, Ottonello L, Liberale L, Caserza L, Salam K, Liberato NL, Tognin T, Bianchi GB, Giaquinto S, Purrello F, Di Pino A, Piro S, Rozzini R, Falanga L, Spazzini E, Ferrandina C, Montrucchio G, Petitti P, Salmi R, Gaudenzi P, Violi F, Perri L, Landolfi R, Montalto M, Mirijello A, Guasti L, Castiglioni L, Maresca A, Squizzato A, Molaro M, Grossi A, Bertolotti M, Mussi C, Libbra MV, Dondi G, Pellegrini E, Carulli L, Perticone F, Colangelo L, Falbo T, Stanghellini V, De Giorgio R, Ruggeri E, Del Vecchio S, Salvi A, Leonardi R, Damiani G, Gabrielli A, Capeci W, Mattioli M, Martino GP, Biondi L, Pettinari P, Ghio R, Col AD, Minisola S, Colangelo L, Afeltra A, Marigliano B, Pipita ME, Castellino P, Blanco J, Zanoli L, Pignataro S, Saracco V, Fogliati M, Bussolino C, Mete F, Gino M, Cittadini A, Vigorito C, Arcopinto M, Salzano A, Bobbio E, Marra AM, Sirico D, Moreo G, Gasparini F, Prolo S, Pina G, Ballestrero A, Ferrando F, Berra S, Dassi S, Nava MC, Graziella B, Baldassarre S, Fragapani S, Gruden G, Galanti G, Mascherini G, Petri C, Stefani L, Girino M, Piccinelli V, Nasso F, Gioffrè V, Pasquale M, Scattolin G, Martinelli S, Turrin M, Sechi L, Catena C, Colussi G, Passariello N, Rinaldi L, Berti F, Famularo G, Patrizia T, Castello R, Pasino M, Ceda GP, Maggio MG, Morganti S, Artoni A, Del Giacco S, Firinu D, Losa F, Paoletti G, Montalto G, Licata A, Malerba V, Antonino L, Basile G, Antonino C, Malatino L, Stancanelli B, Terranova V, Di Marca S, Mecocci P, Ruggiero C, Boccardi V, Meschi T, Lauretani F, Ticinesi A, Minuz P, Fondrieschi L, Pirisi M, Fra GP, Sola D, Porta M, Riva P, Quadri R, Scanzi G, Mengoli C, Provini S, Ricevuti L, Simeone E, Scurti R, Tolloso F, Tarquini R, Valoriani A, Dolenti S, Vannini G, Tedeschi A, Trotta L, Volpi R, Bocchi P, Vignali A, Harari S, Lonati C, Cattaneo M, Nieves RD, Alberto MM, Pedro AR, Vanessa LP, Lara T, Xavier CV, Francesc F, Jesus DM, Esperanza BT, Esther DCB, Maria SP, Romero M, Blanca PL, Cristina LG, Victoria VGM, Saez L, Bosco J, Susana SB, Marta AG, Concepcion GB, Antonio FM, Hernandez MG, Borrego MP, Raquel PC, Florencia PR, Beatriz GO, Sara CG, Alfonso GC, Marta PM, Garcia SC, Alberto RC, Antonio AA, Montserrat GG, Ángel BRM, Manuel MJ, Ignacio NV, Lucía AS, Alfonso L, David RB, Iria IV, Monica RP.Mannucci, Pm; Nobili, A; Pasina, L; Tettamanti, M; Franchi, C; Corrao, S; Marengoni, A; Salerno, F; Cesari, M; Perticone, F; Licata, G; Violi, F; Corazza, Gr; Franchi, C; Cortesi, L; Tettamanti, M; Cortesi, L; Ardoino, I; Prisco, D; Silvestri, E; Cenci, C; Emmi, G; Biolo, G; Zanetti, M; Guadagni, M; Zaccari, M; Vanoli, M; Grignani, G; Pulixi, Ea; Bernardi, M; Bassi, Sl; Santi, L; Zaccherini, G; Mannarino, E; Lupattelli, G; Bianconi, V; Paciullo, F; Nuti, R; Valenti, R; Ruvio, M; Cappelli, S; Palazzuoli, A; Olivieri, O; Girelli, D; Matteazzi, T; Barbagallo, M; Dominguez, L; Cocita, F; Beneduce, V; Plances, L; Zoli, M; Lazzari, I; Brunori, M; Pasini, Fl; Capecchi, Pl; Palasciano, G; Modeo, Me; Di Gennaro, C; Cappellini, Md; Maira, D; Di Stefano, V; Fabio, G; Seghezzi, S; Mancarella, M; Cesari, M; Rossi, Pd; Damanti, S; Clerici, M; Conti, F; Corazza, Gr; Miceli, E; Lenti, Mv; Pisati, M; Dominioni, Cc; Murialdo, G; Marra, A; Cattaneo, F; Secchi, Mb; Ghelfi, D; Anastasio, L; Sofia, L; Carbone, M; Cipollone, F; Guagnano, Mt; Angelucci, E; Valeriani, E; Mancuso, G; Calipari, D; Bartone, M; Delitala, G; Berria, M; Muscaritoli, M; Molfino, A; Petrillo, E; Zuccalà, G; D'Aurizio, G; Romanelli, G; Marengoni, A; Zucchelli, A; Picardi, A; Gentilucci, Uv; Gallo, P; Dell'Unto, C; Annoni, G; Corsi, M; Bellelli, G; Zazzetta, S; Mazzola, P; Szabo, H; Bonfanti, A; Arturi, F; Succurro, E; Rubino, M; Serra, Mg; Bleve, Ma; Gasbarrone, L; Sajeva, Mr; Brucato, A; Ghidoni, S; Fabris, F; Bertozzi, I; Bogoni, G; Rabuini, Mv; Cosi, E; Manfredini, R; Fabbian, F; Boari, B; De Giorgi, A; Tiseo, R; Paolisso, G; Rizzo, Mr; Borghi, C; Strocchi, E; De Sando, V; Pareo, I; Sabbà, C; Vella, Fs; Suppressa, P; Agosti, P; Schilardi, A; Loparco, F; Fenoglio, L; Bracco, C; Giraudo, Av; Fargion, S; Periti, G; Porzio, M; Tiraboschi, S; Peyvandi, F; Rossio, R; Ferrari, B; Colombo, G; Monzani, V; Savojardo, V; Folli, C; Ceriani, G; Salerno, F; Pallini, G; Dallegri, F; Ottonello, L; Liberale, L; Caserza, L; Salam, K; Liberato, Nl; Tognin, T; Bianchi, Gb; Giaquinto, S; Purrello, F; Di Pino, A; Piro, S; Rozzini, R; Falanga, L; Spazzini, E; Ferrandina, C; Montrucchio, G; Petitti, P; Salmi, R; Gaudenzi, P; Violi, F; Perri, L; Landolfi, R; Montalto, M; Mirijello, A; Guasti, L; Castiglioni, L; Maresca, A; Squizzato, A; Molaro, M; Grossi, A; Bertolotti, M; Mussi, C; Libbra, Mv; Dondi, G; Pellegrini, E; Carulli, L; Perticone, F; Colangelo, L; Falbo, T; Stanghellini, V; De Giorgio, R; Ruggeri, E; Del Vecchio, S; Salvi, A; Leonardi, R; Damiani, G; Gabrielli, A; Capeci, W; Mattioli, M; Martino, Gp; Biondi, L; Pettinari, P; Ghio, R; Col, Ad; Minisola, S; Colangelo, L; Afeltra, A; Marigliano, B; Pipita, Me; Castellino, P; Blanco, J; Zanoli, L; Pignataro, S; Saracco, V; Fogliati, M; Bussolino, C; Mete, F; Gino, M; Cittadini, A; Vigorito, C; Arcopinto, M; Salzano, A; Bobbio, E; Marra, Am; Sirico, D; Moreo, G; Gasparini, F; Prolo, S; Pina, G; Ballestrero, A; Ferrando, F; Berra, S; Dassi, S; Nava, Mc; Graziella, B; Baldassarre, S; Fragapani, S; Gruden, G; Galanti, G; Mascherini, G; Petri, C; Stefani, L; Girino, M; Piccinelli, V; Nasso, F; Gioffrè, V; Pasquale, M; Scattolin, G; Martinelli, S; Turrin, M; Sechi, L; Catena, C; Colussi, G; Passariello, N; Rinaldi, L; Berti, F; Famularo, G; Patrizia, T; Castello, R; Pasino, M; Ceda, Gp; Maggio, Mg; Morganti, S; Artoni, A; Del Giacco, S; Firinu, D; Losa, F; Paoletti, G; Montalto, G; Licata, A; Malerba, V; Antonino, L; Basile, G; Antonino, C; Malatino, L; Stancanelli, B; Terranova, V; Di Marca, S; Mecocci, P; Ruggiero, C; Boccardi, V; Meschi, T; Lauretani, F; Ticinesi, A; Minuz, P; Fondrieschi, L; Pirisi, M; Fra, Gp; Sola, D; Porta, M; Riva, P; Quadri, R; Scanzi, G; Mengoli, C; Provini, S; Ricevuti, L; Simeone, E; Scurti, R; Tolloso, F; Tarquini, R; Valoriani, A; Dolenti, S; Vannini, G; Tedeschi, A; Trotta, L; Volpi, R; Bocchi, P; Vignali, A; Harari, S; Lonati, C; Cattaneo, M; Nieves, Rd; Alberto, Mm; Pedro, Ar; Vanessa, Lp; Lara, T; Xavier, Cv; Francesc, F; Jesus, Dm; Esperanza, Bt; Esther, Dcb; Maria, Sp; Romero, M; Blanca, Pl; Cristina, Lg; Victoria, Vgm; Saez, L; Bosco, J; Susana, Sb; Marta, Ag; Concepcion, Gb; Antonio, Fm; Hernandez, Mg; Borrego, Mp; Raquel, Pc; Florencia, Pr; Beatriz, Go; Sara, Cg; Alfonso, Gc; Marta, Pm; Garcia, Sc; Alberto, Rc; Antonio, Aa; Montserrat, Gg; Ángel, Brm; Manuel, Mj; Ignacio, Nv; Lucía, As; Alfonso, L; David, Rb; Iria, Iv; Monica, Rp

Gender-differences in disease distribution and outcome in hospitalized elderly: data from the REPOSI study.

Women live longer and outnumber men. On the other hand, older women develop more chronic diseases and conditions such as arthritis, osteoporosis and depression, leading to a greater number of years of living with disabilities. The aim of this study was to describe whether or not there are gender differences in the demographic profile, disease distribution and outcome in a population of hospitalized elderly people.Retrospective observational study including all patients recruited for the REPOSI study in the year 2010. Analyses are referred to the whole group and gender categorization was applied.A total of 1380 hospitalized elderly subjects, 50.5% women and 49.5% men, were considered. Women were older than men, more often widow and living alone or in nursing homes. Disease distribution showed that malignancy, diabetes, coronary artery disease, chronic kidney disease and chronic obstructive pulmonary disease were more frequent in men, but hypertension, osteoarthritis, anemia and depression were more frequent in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment evaluated by the Short Blessed Test (SBT), mood disorders by the Geriatric Depression Scale (GDS) and disability in daily life measured by Barthel Index (BI) were worse in women. In-hospital and 3-month mortality rates were higher in men.Our study showed a gender dimorphism in the demographic and morbidity profiles of hospitalized elderly people, emphasizing once more the need for a personalized process of healthcare