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1. GBA-Related Parkinson’s Disease:Dissection of Genotype–Phenotype Correlates in a LargeItalian Cohort

Author

Petrucci, S., Ginevrino, M., Trezzi, I., Monfrini, E., Ricciardi, L., Albanese, A., Avenali, M., Barone, P., Bentivoglio, A. R., Bonifati, V., Bove, F., Bonanni, L., Brusa, L., Cereda, C., Cossu, G., Criscuolo, C., Dati, G., De Rosa, A., Eleopra, R., Fabbrini, G., Fadda, L., Garbellini, M., Minafra, B., Onofrj, M., Pacchetti, C., Palmieri, I., Pellecchia, M. T., Petracca, M., Picillo, M., Pisani, A., Vallelunga, A., Zangaglia, R., Di Fonzo, A., Morgante, F., Valente, E. M., Altavista, M. C., Amboni, M., Ardolino, G., Berardelli, A., Cogiamanian, F., Colosimo, C., Costanti, D., De Michele, G., Bonaventura, C. D., Di Lazzaro, G., Di Lazzaro, V., Emanuele Elia, A., Erro, R., Ferrazzano, G., Guerra, A., Ialongo, T., Malaguti, M. C., Melis, M., Moro, E., Oppo, V., Ottaviani, D., Peluso, S., Quadri, M. L., Romito, L. M., Sarchioto, M., Schirinzi, T., Sorbera, C., Stefani, A., Thomas, A., Valente, M. L., Volpe, G, ITA-GENE-PD Study, Group., Petrucci, S, Ginevrino, M, Trezzi, I, Monfrini, E, Ricciardi, L, Albanese, A, Avenali, M, Barone, P, Bentivoglio, Ar, Bonifati, V, Bove, F, Bonanni, L, Brusa, L, Cereda, C, Cossu, G, Criscuolo, C, Dati, G, De Rosa, A, Eleopra, R, Fabbrini, G, Fadda, L, Garbellini, M, Minafra, B, Onofrj, M, Pacchetti, C, Palmieri, I, Pellecchia, Mt, Petracca, M, Picillo, M, Pisani, A, Vallelunga, A, Zangaglia, R, Di Fonzo, A, Morgante, F, Valente, Em, Clinical Genetics, Erasmus MC other, and Radiology & Nuclear Medicine

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Parkinson's disease, Genotype, genotype–phenotype correlates, Disease, Settore MED/05, Genotype phenotype, dementia, GBA, impulsive–compulsive behavior, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Internal medicine, medicine, Dementia, Humans, Sanger sequencing, business.industry, Dissection, Parkinson Disease, medicine.disease, Phenotype, Settore MED/26 - NEUROLOGIA, 030104 developmental biology, Glucosylceramidase, Italy, Mutation, Neurology, Cohort, symbols, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

BACKGROUND Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. OBJECTIVES We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. METHODS Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. β-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed. RESULTS Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest β-glucocerebrosidase activity. CONCLUSIONS GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society.

Published
2020

2. The Prevalence of Diarrhea and Its Association With Drug Use in Elderly Outpatients: A Multicenter Study

Author

Pilotto, A, Franceschi, M, Vitale, D, Zaninelli, A, Di Mario, F, Seripa, D, Rengo, F, FIRI e. SOFIA Project Investigators, Barbagallo, M, Bavazzano, A, Bernabei, R, Biagini, C, Cucinotta, D, Guizzardi, G, Granchi, F, Laguzzi, E, Masotti, G, Maugeri, D, Mazzei, B, Nicìta, MV, Nieddu, A, Noro, G, Olivari, G, Palummeri, E, Policicchio, D, Postacchini, D, Putzu, P, Tardi, S, Abbiati, C, Alpa, A, Antiga, I, Antonina, MR, Arnaboldi, L, Ballotti, E, Bargellini, N, Barisone, G, Battelli, M, Beccari, G, Bitetti, E, Bologni, A, Bongera, P, Bortot, M, Bracalenti, L, Buonono, G, Busolo, M, Campanini, MC, Caputo, L, Cartei, A, Cascavilla, P, Casciaro, L, Casula, E, Cesarone, L, Chiesa, D, Chiumeo, F, Ciciarello, A, Cincotta, G, Corò, G, Corona, S, Corsini, M, Cosola, C, Dainese, A, Danza, M, De Bastiani, R, De Cesare, P, De Facci, G, De Lorenzo, R, De Vuono, AD, Della Piccola, P, D'Errico, G, Di Benedetto, G, Dodaro, M, Ercolino, M, Fatarella, P, Fazzari, F, Fiorese, G, Foco, G, Formicola, G, Franchi, F, Fronges, D, Gaetano, MA, Giordano, G, Guarino, M, Guasti, D, Kuel, AM, Kusanovic, M, Lanzavecchia, D, Lofiego, MC, Lorenzano, E, Losi, C, Magrini, F, Mancini, NM, Mander, A, Manneschi, M, Marchi, R, Maronato, G, Marsala, V, Mascia, R, Matuonto, V, Mauceri, ML, Mazzi, PA, Mezzapica, A, Mochi, F, Molenda, G, Morelli, F, Morsia, D, Mosna, MC, Muglia, A, Murgia, P, Muscetta, M, Muscetta, S, Nucci, P, Olimpi, G, Orro, W, Poletto, C, Palmieri, IP, Pastacaldi, G, Pastori, C, Pieresca, G, Pietragalla, M, Pilo, S, Poggesi, S, Poli, L, Ricciardi, A, Riggi, V, Romano, V, Rossi, T, Saccarello, A, Salatino, A, Salvati, R, Sannino, A, Santelli, M, Santucci, A, Saponaro, GM, Schergna, A, Schiavone, C, Sammarco, R, Scornavacca, G, Serena, D, Silvino, G, Sistilli, L, Soldan, S, Soro, A, Tatti, R, Tempestini, L, Testini, D, Tibeloli Carnevali, A, Toniolo, B, Torselli, R, Tremul, L, Trevisan, F, Trifilò, P, Cimenti, T, Valente, S, Vannucchi, CE, Vencato, PG, Vigotti, G, Virdis, G, Zaccaro, F, Zanzot, S, Zingone, FM, Zirillo, AM, ANNONI, GIORGIO, Pilotto, A, Franceschi, M, Vitale, D, Zaninelli, A, Di Mario, F, Seripa, D, Rengo, F, FIRI e., S, Annoni, G, Barbagallo, M, Bavazzano, A, Bernabei, R, Biagini, C, Cucinotta, D, Guizzardi, G, Granchi, F, Laguzzi, E, Masotti, G, Maugeri, D, Mazzei, B, Nicìta, M, Nieddu, A, Noro, G, Olivari, G, Palummeri, E, Policicchio, D, Postacchini, D, Putzu, P, Tardi, S, Abbiati, C, Alpa, A, Antiga, I, Antonina, M, Arnaboldi, L, Ballotti, E, Bargellini, N, Barisone, G, Battelli, M, Beccari, G, Bitetti, E, Bologni, A, Bongera, P, Bortot, M, Bracalenti, L, Buonono, G, Busolo, M, Campanini, M, Caputo, L, Cartei, A, Cascavilla, P, Casciaro, L, Casula, E, Cesarone, L, Chiesa, D, Chiumeo, F, Ciciarello, A, Cincotta, G, Corò, G, Corona, S, Corsini, M, Cosola, C, Dainese, A, Danza, M, De Bastiani, R, De Cesare, P, De Facci, G, De Lorenzo, R, De Vuono, A, Della Piccola, P, D'Errico, G, Di Benedetto, G, Dodaro, M, Ercolino, M, Fatarella, P, Fazzari, F, Fiorese, G, Foco, G, Formicola, G, Franchi, F, Fronges, D, Gaetano, M, Giordano, G, Guarino, M, Guasti, D, Kuel, A, Kusanovic, M, Lanzavecchia, D, Lofiego, M, Lorenzano, E, Losi, C, Magrini, F, Mancini, N, Mander, A, Manneschi, M, Marchi, R, Maronato, G, Marsala, V, Mascia, R, Matuonto, V, Mauceri, M, Mazzi, P, Mezzapica, A, Mochi, F, Molenda, G, Morelli, F, Morsia, D, Mosna, M, Muglia, A, Murgia, P, Muscetta, M, Muscetta, S, Nucci, P, Olimpi, G, Orro, W, Poletto, C, Palmieri, I, Pastacaldi, G, Pastori, C, Pieresca, G, Pietragalla, M, Pilo, S, Poggesi, S, Poli, L, Ricciardi, A, Riggi, V, Romano, V, Rossi, T, Saccarello, A, Salatino, A, Salvati, R, Sannino, A, Santelli, M, Santucci, A, Saponaro, G, Schergna, A, Schiavone, C, Sammarco, R, Scornavacca, G, Serena, D, Silvino, G, Sistilli, L, Soldan, S, Soro, A, Tatti, R, Tempestini, L, Testini, D, Tibeloli Carnevali, A, Toniolo, B, Torselli, R, Tremul, L, Trevisan, F, Trifilò, P, Cimenti, T, Valente, S, Vannucchi, C, Vencato, P, Vigotti, G, Virdis, G, Zaccaro, F, Zanzot, S, Zingone, F, and Zirillo, A

Subjects
Diarrhea, Drug, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, health care facilities, manpower, and services, media_common.quotation_subject, MEDLINE, Internal medicine, Outpatients, Prevalence, medicine, Humans, Psychiatry, Aged, media_common, Polypharmacy, Hepatology, business.industry, Gastroenterology, social sciences, humanities, Multicenter study, elderly outpatients, drug use, Diarrhea, MED/09 - MEDICINA INTERNA, medicine.symptom, business
Abstract

OBJECTIVES: To evaluate the prevalence of diarrhea and its association with drug use in elderly outpatients. METHODS: The study was carried out by 133 general practitioners (GPs) who referred to 24 geriatric units in Italy. The demographic data, disability, gastrointestinal symptoms, and current medications were evaluated using a structured interview, including the evaluation of the activities of daily living (ADL), the instrumental activities of daily living (IADL), and the gastrointestinal symptoms rating scale (GSRS). RESULTS: The study included 5,387 elderly subjects who regularly completed the structured interview. In total, 488 patients (9.1% of the whole population, 210 men and 278 women, mean age 75.6 6.2 yr, range 65–100 yr) reported diarrhea, that is, items 11 and 12 of the GSRS, during the 7-day period before the interview. The prevalence of diarrhea significantly increased with older age (P= 0.025), the severity of ADL (P < 0.0001) and IADL disability (P < 0.0001), and the number of drugs taken (P= 0.0002). A multivariate analysis demonstrated that the presence of diarrhea was significantly associated with the use of antibiotics (odds ratio [OR] 4.58, 95% confidence interval [CI] 1.95–10.73), proton pump inhibitors (OR 2.97, 95% CI 2.03–4.35), allopurinol (OR 2.19, 95% CI 1.26–3.81), psycholeptics (OR 1.82, 95% CI 1.26–2.61), selective serotonin reuptake inhibitors (OR 1.71, 95% CI 1.01–2.89), and angiotensin II receptor blockers (OR 1.46, 95% CI 1.08–1.99), also accounting for sex, age, and the use of antidiarrheal agents and drugs for functional gastrointestinal disorders. CONCLUSION: Diarrhea is a common problem in elderly outpatients. Its prevalence increases with old age, the severity of disability, and the number of drugs. Monitoring the presence of diarrhea and its complications in elderly patients who need treatments with drugs significantly associated with diarrhea may be clinically useful.

Published
2008

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