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a Department of Gerontology, Catholic University of Rome, Italy
b Department of Preventive Medicine, University of Tennessee, Memphis.
c The GIFA Investigators are listed in the Appendix
Giuseppe Zuccalà, Chair of Gerontology, Catholic University of the Sacred Heart, L.go F. Vito, 1-00168 Rome, Italy E-mail: Cepsag{at}mclink.it.
Decision Editor: William B. Ershler, MD
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Abstract |
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 Top Abstract MethodsResultsDiscussionAppendix ENDIXReferences |
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Methods. The association between age and incident hypokalemia was examined in 18,872 patients with normal baseline serum potassium enrolled during three yearly multicenter surveys; 4,035 patients started receiving loop diuretics during their hospital stay. Demographic variables, comorbid conditions, medications, and objective tests that were associated with incident hypokalemia in separate age- and sex-adjusted logistic regression models were examined as potential confounders.
Results. Among patients with normal baseline serum potassium, the factors of age, presence of coronary disease or diabetes, comorbidity, the use of ACE inhibitors, loop diuretics, digitalis, corticosteroids, or insulin, and baseline serum potassium were associated with incident hypokalemia in initial models. After these variables were adjusted for, age (for each decade, 
; 
; p < .0001) was associated with incident hypokalemia. The use of parenteral (2.30; 1.53–3.46; p < .0001) but not oral (1.16; 0.79–1.69; p = .44) loop diuretics was associated with hypokalemia. Eventually, age was associated with hypokalemia when the summary regression model was analyzed in patients taking loop diuretics (1.33; 1.03–1.71; 
), as well as in those taking intravenous loop diuretics only (1.84; 1.25–2.70; 
).
Conclusions. Older age is independently associated with the in-hospital development of hypokalemia, particularly among patients taking loop diuretics. Monitoring of serum potassium levels is therefore advisable when older patients are treated with these agents.
THE prevalent use of diuretics increases with advancing age; in particular, among older patients the consumption of loop diuretics has been growing over the most recent years (1)(2). This trend is probably linked to an increase in the incidence and prevalence of cardiovascular disorders, chiefly hypertension and heart failure, which has been reported among older populations (3)(4). Treatment with thiazide diuretics has been associated in general populations with an increased risk of hypokalemia, ventricular arrhythmias, and sudden death (5)(6)(7); noticeably, hypokalemia is a common finding among older patients taking diuretic medications (8)(9). It has been suggested that the use of loop diuretics, as a result of their shorter duration of action and greater natriuresis/kaliuresis ratio, may offer advantages over thiazides in the treatment of older patients (10). In a more general sense, it has been observed that older subjects, because of a decreased glomerular filtration rate and blunted renin-aldosterone axis, should be protected from the development of hyperkalemia (11). However, definite data regarding the association between age and incident hypokalemia, as well as the specific impact of older age on the risk of hypokalemia from loop diuretics, are currently lacking (8).
We assessed the determinants of the in-hospital development of hypokalemia in a series of patients who were enrolled in three yearly surveys of a multicenter Italian pharmacoepidemiologic study group (GIFA) in order to assess both the association between age and risk of hypokalemia and the impact of advanced age on the risk of hypokalemia from treatment with loop diuretics.
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Methods |
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TopAbstractMethodsResultsDiscussionAppendix ENDIXReferences |
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Diagnoses were coded according to the International Classification of Diseases, Ninth Edition, Clinical Modification codes (14). Comorbidity was quantified by using the Charlson comorbidity index score by adding scores assigned to specific discharge diagnoses (15)(16). A score of 1 was attributed to myocardial infarction (codes 410–410.9, 412), congestive heart failure (codes 428–428.9), peripheral vascular disease (443.9, 441–441.9, 785.4, V43.4), cerebrovascular disease (430–438), dementia (290–290.9), chronic pulmonary disease (490–496, 500–505, 506.4), rheumatologic disease (710.0, 710.1, 710.4, 714.0–714.2, 714.8, 725), peptic ulcer disease (531–534.9, 531.4–531.7, 532.4–532.7, 533.4–533.7, 534.4–534.7), mild liver disease (571.2, 571.4–571.6), and diabetes (250–250.3, 250.7). The following conditions scored 2: diabetes with chronic complications (codes 250.4–250.6), hemiplegia or paraplegia (344.1, 342–342.9), renal disease (582–582.9, 583–583.7, 585, 586, 588–588.9), and any malignancy, including leukemia and lymphoma (140–172.9, 174–195.8, 200–208.9). Moderate-to-severe liver disease (codes 572.2–572.8, 456.0–456.2) scored 3. Finally, a score of 6 was assigned to metastatic solid tumor (codes 196–199.1) and AIDS (042–044.9). In addition, coronary disease (codes 410–414.9), hypertension (401–405.9), heart failure (428–428.9), chronic pulmonary disease (491–496), and diabetes (250–250.7) were analyzed as separate variables.
Statistical Methods
Data of continuous variables are presented as mean values ±SE. Statistical analyses were performed by using SPSS for Windows 7.5.2 statistical software; differences were considered significant at the p < .05 level. Variations in use of loop diuretics over the study years were analyzed by the Mantel-Haenszel chi-square test. Variations in serum potassium levels during the hospital stay were evaluated by using the Wilcoxon matched-pairs rank test. Analysis of variance (ANOVA) for normally distributed variables in relation to the in-hospital use of loop diuretics was performed by ANOVA comparisons; otherwise, the nonparametric Kruskal-Wallis H test was adopted. A chi-square analysis was used for dichotomous variables. A logistic regression analysis was used to estimate the association of variables of interest with the in-hospital development of hypokalemia (i.e., serum potassium levels below 3.4 mmol/L) in patients with normal serum potassium on admission. As a way to assess independent risk factors for incident hypokalemia that might have confounded the association of the use of loop diuretics with the development of hypokalemia, groups of variables (demographic variables, comorbid conditions, medications, and objective tests) were examined in separate age- and sex-adjusted regression models, as depicted in Table 1 . Those variables, significant at the p < .01 level in these initial models, were simultaneously entered into a summary age- and sex-adjusted regression model. This summary model was also analyzed both in patients on loop diuretics and in those taking parenteral loop diuretics only. As overall potassium supplementation (probably as a result of confounding by indication) was associated with an increased risk of hypokalemia (odds ratio or 
; 95% confidence interval or 
), in the multivariate model that included medication use we considered only potassium administration that started contemporaneously with diuretic treatment.
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Results |
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3.4 and <5.5 mmol/L (17). Among these, 3,979 patients were given furosemide (median dosage, 25 mg), 65 ethacrynic acid (50 mg), 19 torasemide (10 mg), 17 etozoline (200 mg), and 3 piretamide (3.7 mg); 983 subjects were given parenteral furosemide or torasemide. The main characteristics of the study sample according to the use of loop diuretics are depicted in Table 1 . Overall, the in-hospital prevalent use of loop diuretics increased from 12% in 1988 to 19% in 1993 and 22% in 1995 (p for trend is <.0001). Among patients on loop diuretics, serum potassium levels decreased from 4.36 ± 0.02 to 4.29 ± 0.02 mmol/L during the hospital stay (). However, this variation was statistically significant among subjects aged above the median (75+), from 4.39 ± 0.03 to 4.28 ± 0.02 mmol/L, p < .0001, but not among younger patients, from 4.30 ± 0.03 to 4.29 ± 0.03 mmol/L. After exclusion of patients with abnormal serum potassium levels on admission, and of those who were receiving ACE inhibitors, potassium supplementation, or potassium-sparing diuretics, hypokalemia was found at discharge in 180 (2.7%) of 6,630 participants: 44 (4%) among the 1,110 receiving loop diuretics, and 136 (2.5%) among the remaining 5,520 subjects (Fisher exact 
). Among these patients, treatment with loop diuretics was associated with marked hypokalemia (i.e., 
3.0 mmol/L) in 24 (2%) of 1,110 patients; overall, an in-hospital reduction in serum potassium levels during treatment with loop diuretics could be observed among older patients, but not in younger participants (Fig. 1). Patients who took diuretic weight-adjusted dosages above the median values were older than other participants (78 ± 0.7 vs 75 ± 0.7 years, respectively; 
). However, patients who received higher dosages did not show an increased incidence of hypokalemia as compared with remaining subjects (3.9% vs 3.4%, respectively). Eventually, parenteral diuretics were given to 8% of patients aged 75+, and to 4% of younger participants (Fisher exact 
).
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; 95% 
; p < .0001), use of loop diuretics (
) and corticosteroids (
; p < .0001), and the Charlson comorbidity index (15) (
; p < .0001) were again associated with development of hypokalemia (Fig. 2). In this model, the use of ACE inhibitors was associated with a decreased probability of hypokalemia (
). No differences were found in the hypokalemic effect of loop diuretics after stratification of dosages; however, when the administration route was analyzed in the summary regression model, subjects receiving parenteral (for each decade, 
; p < .0001), but not oral (
) loop diuretics showed an increased probability of developing hypokalemia as compared to nonusers.
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), and to those receiving parenteral loop diuretics only (
2; see Fig. 2). |
Discussion |
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The overall incidence of hypokalemia in the present study (4% among older patients) is in agreement with previous findings (4–14%) in younger patients treated with loop diuretics because of hypertension or heart failure (10)(17). However, it should be considered that the average daily dosages in our patients were lower than those utilized in other studies: for instance, the mean dosage of administered furosemide in the RALES study ranged between 63 and 85 mg across the study subgroups (17). Indeed, we did not find any dose-related gradient in the hypokalemic effect of loop diuretics; rather, an increased probability of developing hypokalemia was found for parenteral but not oral administration. Older patients received higher weight-adjusted dosages; this finding is in keeping with previous findings on overtreatment of low-weight elderly (18). Anyway, use of higher dosages was not associated with an increased incidence of hypokalemia. In addition, parenteral treatment was more frequently adopted in older participants. However, the association between age and incident hypokalemia persisted among patients treated with loop diuretics, as well as in those receiving parenteral treatment (Fig. 2). It has been repeatedly suggested that a decreased tubular mass and glomerular filtration rate, and blunted renin-aldosterone axis, might reduce potassium loss in older subjects (11). Despite this theoretical background, hypokalemia is a common finding among older patients treated with diuretics (8)(9)(10). It has been found that atrial natriuretic peptide serum levels are predictive of diuretic-induced hypokalemia (19). Noticeably, older age has been associated with increased levels of this peptide (20), which may therefore increase the diuretic-induced potassium loss. In the present study, age was associated with incident hypokalemia, after several potential confounders (comorbidity, presence of coronary disease and diabetes, baseline serum potassium, and use of ACE inhibitors, corticosteroids, digitalis, insulin, and loop diuretics) were adjusted for. Also, as evidenced by repeated analyses in patients on loop diuretics (Fig. 2), the hypokalemic effect of these agents was heavily dependent upon advancing age; indeed, diuretic treatment was associated with potassium loss only in patients aged 75 and older (Fig. 1). Reduced dietary potassium intake in older patients might also contribute to the observed age-related differences in the probability of developing hypokalemia from diuretic treatment. All participants in the present study received hospital meals; however, older persons frequently consume less than 40% of the prescribed food during a hospital stay (21).
In agreement with previous reports, the prevalent use (22%) of loop diuretics among patients aged 75+ was remarkable (1)(22). Thus, despite its relatively low incidence, hypokalemia from loop diuretics represents a clinically relevant issue among geriatric patients. The extent of reduction in serum potassium levels observed in this study is modest, even though statistically significant. However, these variations developed within a short period of exposure to drugs; also, it should be considered that a larger variation in potassium levels had been probably identified and corrected by the hospital physicians. Preventive potassium administration was not associated with a reduced probability of developing hypokalemia. Other studies reported little or no effect of potassium substitution on the risk of hypokalemia in patients treated with potassium-losing diuretics (23)(24). Furthermore, in the present study treatment with potassium-sparing diuretics was not associated with a reduced probability of hypokalemia (Table 1 ). In contrast, the use of ACE inhibitors was associated with a 48% reduction in the probability of developing hypokalemia. ACE inhibitors seem therefore to be the most effective agents in preventing in-hospital hypokalemia. Our analyses of the association between age and incident hypokalemia allowed us to control for many potential confounders (Table 1 ). However, it should be observed that some unexplored variables might account for the observed association among age and risk of hypokalemia. Indeed, the complex relationships between age, comorbidity, polypharmacy, and adverse drug reactions are difficult to disentangle (25), even with well controlled statistical evaluation. However, whether because age per se or because of multiple drug treatment, clinicians should be aware of the increased risk of hypokalemia when treating older subjects.
Recently, withdrawal of diuretic treatment in older patients without manifest heart failure or hypertension has been found to lead to symptoms of heart failure or increased blood pressure levels in most cases (26). Thus, suspension of treatment with diuretics does not seem to be warranted by the risk of diuretic-induced hypokalemia; however, serum potassium levels should be monitored in older subjects who are being treated with loop diuretics.
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Acknowledgments |
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Received March 3, 1999
Accepted August 26, 1999
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Appendix ENDIX |
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Investigators: Marco Pahor, Luciana Carosella, Antonio Sgadari, Giuseppe Zuccalà, Claudio Pedone, and Roberto Bernabei.
Participating Centers.-- Acquaviva delle Fonti—Ospedale Regionale "Miulli"—V. Aloia, G. Baldassarre, and L. Venezia.
Agnone—P. Occhionero, I. Masciotra, and P. Pescetelli.
Ancona—Centro di Patologia Cardiovascolare, INRCA—E. Paciaroni, A. Andreoni, P. Angelini, L. Gigli, C. Ferroni, and P. F. Tomassini.
Ancona—Divisione di Medicina II, INRCA—G. De Tommaso, M. Badiali, and F. Guidi.
Ancona—Divisione di Geriatria, INRCA—Remo G., G. Cadeddu, and F. Giovagnoli.
Appignano—Divisione di Geriatria, INRCA—S. Bonaiuto, L. Panichetti, P. F. Tomassini, and E. Giannandrea.
Avellino—Dipartimento di Geriatria, Ospedale Maffucci—M. Lingetti, F. Di Grezia, A. Marro, E. Piermatteo, and P. Sorrentino.
Bari—Cattedra di Gerontologia, Università di Bari—A. Capurso, C. Capurso, D. Ciancia, N. Marella, G. A. Nardo', G. Nicoletti, F. Resta, S. Giovanni, V. Solfrizzi, G. Triggiani, A. Venezia, and E. Vespertino.
Bari—Clinica Malattie Nervose e Mentali, Università di Bari—E. Ferrari and coworkers.
Bologna—Centro Aterosclerosi, Policlinico S. Orsola-Malpighi—A. Gaddi, B. Benassi, S. D'Addato, G. De Simone, A. Dormi, C. Galetti, G. Magri, L. Marri, D. Pomata, and G. Volta.
Brindisi—Divisione di Neurologia, Ospedale A. Di Summa—G. Masi, C. Nozzoli, B. Passarella, and C. Monetti.
Bologna—Terza Divisione Geriatrica, Ospedale Malpighi di Bologna—D. Cucinotta, F. Cavazzuti, M. Corneli, R. Del Buono, P. Kalfus, and R. Manopulo.
Bologna—Patologia Medica I, Policlinico S. Orsola—G. Ravaglia, F. Boschi, M. Buttazzo, A. Cicognani, P. Forti, and F. Maioli.
Cagliari—Divisione di Geriatria, Ospedale SS. Trinità—M. Jovine, P. F. Putzu, and M. R. Frau.
Campobasso—Divisione di Medicina Interna, Ospedale Cardarelli—L. Carile, O. Grassi, and T. Sanzò.
Campoli del Monte—Divisione Cardiologica, Centro Medico di Riabilitazione—F. Rengo, N. Ferrara, and A. Nicolino.
Castelfranco Veneto—Divisione di Neurologia, Ospedale Civile—V. Toso, and L. Bartolomei.
Chieti—Istituto Clinica Geriatrica, Università "G. D'Annunzio"—G. Abate, M. D'Aviero, M. A. Cavoni, S. Capasso, C. Cervone, L. D'Andrea, F. Di Giangiacomo, A. Di Iorio, P. Lamanna, T. Palmerio, F. Pennese, G. Maria Puddu, L. Savini, and M. Zito.
Chieti—Istituto di Clinica Medica, Università di Chieti—S. Sensi and A. Blasioli.
Cortona—Unità Operativa di Medicina Generale, Ospedale Civile—M. Ricca, F. Cosmi, and M. Margioni.
Cosenza—Divisione Medicina Geriatrica, INRCA—F. Corsonello, E. Cundari, G. Gaudio, B. Mazzei, L. Pranno, and C. Zottola.
Cosenza—Servizio di Neuroriabilitazione, USL 9—L. Pugliese and coworkers.
Eboli—Divisione di Geriatria, Presidio Ospedaliero Eboli—L. D'Alessandro, V. Butrico, M. R. Coccaro, D. Di Biase, R. Esposito, and M. Mandia.
Fano—Divisione di Geriatria, Ospedale S. Croce—M. Cuzzupoli and P. Candelora.
Ferrara—Istituto di Medicina Interna II, Università di Ferrara—R. Fellin, A. Passaro, F. Romagnoni, and G. Zuliani.
Firenze—Dipartimento di Farmacologia, Universita' di Firenze—A. Mugelli and E. Cecchi.
Firenze—Istituto di Geriatria, Università di Firenze—G. Masotti, E. Biondi, S. Fumagalli, L. Magherini, N. Marchionni, M. Marini, and L. Matteucci.
Firenze—Istituto di Clinica Medica — Universita' di Firenze—G. Gensini, E. Cangioli, S. Del Pace, S. Gioni, I. Simone, and A. Crucitti.
Foiano—Divisione di Medicina, Ospedale di Foiano della Chiana—C. Pedace, P. Corsi, and S. Simonetti.
Genova—Gerontologia e Geriatria, Dipartimento di Medicina Interna—R. Balestreri, V. Aimale, M. G. Carli, P. Cavagnaro, U. Compagnoni, R. Pizzorno, and P. Mosca.
Isernia—Divisione di Medicina Interna, Ospedale F. Veneziale—E. Melaragno, E. Calabrese, I. Masciotra, G. Angelone, and C. Disernia.
Larino—Divisione di Medicina Generale, Ospedale Civile—F. Porfilio, N. Frate, and A. Potena.
Loiano—Divisione di Medicina Interna, Ospedale "Simiani"—A. Bernardini, R. Nardi, D. Panuccio, and M. R. Trabatti.
Messina—Dipartimento di Medicina Interna, Scuola Specializzazione in Geriatria—D. Ceruso, A. Allegra, S. Bonanzinga, C. Bontempo, L. Castagna, F. Corica, A. Corsonello, G. Cucinotta, T. De Gregorio, I. Granà, M. Pensabene, F. Rubino, M. S. Giacobbe, S. Chiarenza, and A. Artuso.
Messina—I Clinica Neurologica, Policlinico Gazzi—R. Di Perri, P. La Spina, and R. Mussolino.
Milano—Cattedra Medicina Interna II, Università di Milano—P. M. Mannucci, P. Ferrazzi, D. Mari, and M. Venturati.
Milano—Istituto Pio Albergo Trivulzio—A. E. Tammaro, A. Borghese, G. Campiglio, L. Laghi, C. Negri Chinaglia, L. Palvarini, and C. Albanese.
Modena—Cattedra di Geriatria e Gerontologia, Universita' di Modena—G. Salvioli, S. Ascari, and C. Mussi.
Napoli—Dipartimento di Geriatria, Università di Napoli—M. Varricchio, L. Amato, S. Ammendola, V. Balbi, A. Gambardella, L. Pesce, M. R. Rizzo, M. R. Tagliamonte, R. Tortoriello, and G. Cennamo.
Napoli—IV Divisione Medicina Interna, Università di Napoli—L. Saccà and V. Coto.
Napoli—Istituto di Medicina Interna, Cattedra di Geriatria—F. Rengo, P. Abete, P. Caccese, and P. Landino.
Napoli—Divisione di Neurologia, Ospedale Cardarelli—L. Stella, A. M. Fasanaro, and V. Pizza.
Napoli—Istituto di Scienze Neurologiche, I Policlinico Universitario—B. Bonavita and G. Tedeschi.
Novara—III Divisione di Medicina, Ospedale Maggiore—C. Franzini, M. Sartori, M. Ruzza, and S. Andorno.
Padova—Chirurgia Geriatrica, Università di Padova—O. Terranova, M. Baldan, and D. Celi.
Padova—Terza Divisione Geriatria, Ospedale Geriatrico—O. De Candia, V. Bernini, and M. Fabbris.
Palermo—Divisione Medicina Geriatrica, Ospedale Villa Sofia—A. Pardo, M. C. Fuschi, M. Pagano, M. Russotto, M. Sapienza, and A. Spagnuolo.
Palermo—Istituto di Medicina Interna e Geriatria, Università di Palermo—G. Barbagallo, M. Barbagallo, G. Castiglione, G. Catania, G. Di Lorenzo, A. Di Sciacca, A. Geraci, M. Lo Bue, G. Lucania, and F. Raspanti.
Parma—Cattedra di Geriatria, Università di Parma—G. Valenti and D. Magnani.
Parma—Istituto Clinica Medica, Università di Parma—M. Passeri, M. C. Baroni, E. Courlios, A. De Blasio, R. Delsignore, R. Fiorini, and S. Vourna.
Perugia—Cattedra di Gerontologia e Geriatria, Università di Perugia—U. Senin, S. Cesarini, A. Cherubini, M. Freddio, A. Longo, P. Mecocci, and B. Salatino.
Pontremoli—Divisione di Medicina, Ospedale S. Antonio Abate—A. Leone, P. Fabiano, and A. Martelli.
Prato—Divisione di Geriatria, Ospedale di Prato—A. Bavazzano, F. Boni, D. Calvani, R. Guarducci, M. P. Lunardelli, and A. Mitidieri Costanza.
Roma—Cattedra di Geriatria, Università "La Sapienza"—V. Marigliano, L. Capponi, P. Cicconetti, M. G. Di Bernardo, C. F. Di Gioacchino, L. Persechino, and F. Thau.
Roma—Dipartimento di Medicina Clinica, Università la Sapienza—P. Serra, P. Carfagna, M. Gaglie', V. Paravati, and A. Paris.
Roma—Divisione di Medicina, Ospedale Fatebenefratelli—E. Bologna, A. M. Sidoti, D. Terracina, and M. Di Girolamo.
Roma—Divisione Geriatria e Sezione Cerebrovascolare Ospedale Israelitico—S. M. Zuccaro, M. Manor, and C. Pitigliani.
Roma—Medicina Degenze Speciali, Ospedale Militare Principale—M. Anaclerio, A. Graco, and P. Pisanti.
Roma—Divisione di Geriatria, Ospedale Addolorata—V. Lumia, G. Marangi, and C. Carletta.
Roma—Clinica Neurologica, II Università Tor Vergata—G. Bernardi, C. Caltagirone, and G. A. Carlesimo.
Roma—Clinica Neurologica, Ospedale Fatebenefratelli—P. Rossini and M. T. De Lisio.
Roma—Divisione di Geriatria, Università Cattolica—A. Cocchi, V. Cardone, L. Manigrasso, A. Manto, F. Ardito, A. Russo, E. Gaetani, G. Di Niro, V. Venturiero, A. Baldaccini, G. Onder, G. Orsitto, and S. Urgese.
Roma—Istituto di Medicina Interna e Geriatria, Università Cattolica—G. Ciappi, S. a Cardo, A. Carlucci, G. M. Corbo, G. Fumagalli, and L. Fuso.
Roma—Istituto di Medicina Interna e Geriatria, Univerità Cattolica—C. Barone and coworkers.
Roma—Istituto di Medicina Interna e Geriatria, Università Cattolica—Nicola Gentiloni and coworkers.
Roma—Ospedale S. Camillo, II Divisione "Bassi"—G. Di Lascio, C. Bizzarri, S. De Maria, G. C. Nicotra, and S. Pedace.
Rovigo—Divisione di Geriatria, Ospedale Civile—P. L. Forte, A. Andriolli, C. Boscolo, E. Carbonin, and S. Sparesato.
S. Giovanni Rotondo—Divisione di Geriatria, Ospedale Casa Sollievo della Sofferenza—M. Giuliani, C. Ritrovato, P. D'Ambrosio, A. M. Colusso, and G. Maruzzi.
S. Giovanni Rotondo—Divisione di Medicina, Ospedale Casa Sollievo della Sofferenza—R. Lucentini and A. Greco.
Sezze—Divisione di Geriatria, Ospedale di Sezze Romano—L. Bartorelli and G. Mazzella.
Siena—Cattedra di Geriatria—M. Guerrini, S. Gori, C. Iaccarino, P. Sani, M. Bicchi, and C. De Matteis.
Siena—Cattedra di Geriatria—S. Forconi, C. De Matteis, and F. Leoncini.
Taranto—Medicina Generale, Ospedale S. S. Annunziata—A. Marinosci, M. C. Bonanno, A. Di Gena, and G. Lantone.
Termoli—Reparto di Medicina, Ospedale Civile—M. Cariello, F. Baccari, and V. Di Marco.
Torino—I Clinica Neurologica, Università di Torino—L. Bergamini and coworkers.
Trento—Divisione di Geriatria, Centro S. Chiara—G. Bertoluzza, B. Bagozzi, E. Battisti, R. Garuti, G. Mansoldo, and G. Tava.
Trieste—Istituto di Clinica Medica, Universita' di Trieste—L. Cattin, F. Feruglio, C. Adamo, E. Grande, R. La Verde, M. Fonda, A. Petrucco, D. Nadalut, and D. Trento.
Venafro—Reparto di Medicina, Ospedale SS. Rosario—A. Bucci, G. Farrocco, and D. Santilli.
Venafro—Sanitrix, INRCA—P. Simonelli, R. Marconi, and A. Ricci.
Verona—I Divisione Medico Geriatrica, Ospedale Civile Borgo Trento—G. Zavateri, C. Bellamoli, G. Beltrami, L. Bettili, M. P. Conti, C. Di Battisti, P. Garzotti, P. Peroli, G. Raschella', C. Ruggiano, and F. Pedrazzi.
Vicenza—Divisione di Geriatria, Ospedale Civile—G. Valerio, F. Azzini, E. Bianchi, and F. Gioia.
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