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1. Comparing Long-Acting Antipsychotic Discontinuation Rates Under Ordinary Clinical Circumstances: A Survival Analysis from an Observational, Pragmatic Study

Author

Bertolini, F., Ostuzzi, G., Pievani, M., Aguglia, A., Bartoli, F., Bortolaso, P., Callegari, C., Caroleo, M., Carra, G., Corbo, M., D'Agostino, A., De Fazio, P., Magliocco, F., Martinotti, G., Ostinelli, E. G., Piccinelli, M. P., Tedeschi, F., Barbui, C., Boschello, F., Gastaldon, C., Mazzi, M. A., Nose, M., Papola, D., Perini, G., Piccoli, A., Purgato, M., Ruggeri, M., Terlizzi, S., Turrini, G., Raffaele, G., Cavallotti, S., Chirico, M., Ferrato, F., Limosani, I., Mastromo, D., Monzani, E., Porcellana, M., Restaino, F., Annese, P. M., Bolognesi, S., Cerretini, M., De Capua, A., Debolini, S., Del Zanna, M., Fargnoli, F., Giannini, A., Luccarelli, L., Lucii, C., Pierantozzi, E., Tozzi, F., Bardicchia, F., Cardamone, G., Facchi, E., Magnani, N., Soscia, F., Biancosino, B., Zotos, S., Giacomin, M., Pompei, F., Spano, M., Zonta, F., Buzzi, A., Callegred, C., Calzolari, R., Caselli, I., Diurni, M., Giana, E., Ielmini, M., Milano, A., Poloni, N., Sani, E., Zizolfi, D., Alberini, G., Cazzamalli, S., Costantini, C., Di Caro, A., Paronelli, C., Piantanida, S., Piccinelli, M., Alessandro, P., Barbanti, S. V., D'Ippolito, C., Gozzi, M., Moretti, V., Campese, O., Di Capro, L., di Giannantonio, M., Fiori, F., Lorusso, M., Mancini, V., Viceconte, D., Calandra, C., Luca, M., Signorelli, M. S., Suraniti, F., Balzarro, B., Boncompagni, G., Caretto, V., Emiliani, R., Lupoli, P., Menchetti, M., Rossi, E., Storbini, V., Tarricone, I., Terzi, L., Boso, M., Catania, C., De Paoli, G., Risaro, P., Aspesi, F., Bava, M., Bono, A., Brambilla, G., Castagna, G., Lucchi, S., Nava, R., Provenzi, M., Tabacchi, T., Tremolada, M., Verrengia, E., Barchiesi, M., Oriani, M. G., Pacetti, M., Ferro, M., Ghio, L., Beneduce, R., Laffranchini, L., Magni, L. R., Rossi, G., Tura, G. B., Addeo, L., Balletta, G., De Vivo, E., Di Benedetto, R., Parise, V. F., Carpiniello, B., Pinna, F., Pecile, D., Mattei, C., Bonavigo, T., Fabrici, E. P., Panarello, S., Peresson, G., Vitucci, C., Gardellin, F., Strizzolo, S., Cossetta, E., Fizzotti, C., Moretti, D., Di Gregorio, L., Sozzi, F., Colli, G., La Barbera, D., Laurenzi, S., Bertolini, F, Ostuzzi, G, Pievani, M, Aguglia, A, Bartoli, F, Bortolaso, P, Callegari, C, Caroleo, M, Carra, G, Corbo, M, D'Agostino, A, De Fazio, P, Magliocco, F, Martinotti, G, Ostinelli, E, Piccinelli, M, Tedeschi, F, Barbui, C, Boschello, F, Gastaldon, C, Mazzi, M, Nose, M, Papola, D, Perini, G, Piccoli, A, Purgato, M, Ruggeri, M, Terlizzi, S, Turrini, G, Raffaele, G, Cavallotti, S, Chirico, M, Ferrato, F, Limosani, I, Mastromo, D, Monzani, E, Porcellana, M, Restaino, F, Annese, P, Bolognesi, S, Cerretini, M, De Capua, A, Debolini, S, Del Zanna, M, Fargnoli, F, Giannini, A, Luccarelli, L, Lucii, C, Pierantozzi, E, Tozzi, F, Bardicchia, F, Cardamone, G, Facchi, E, Magnani, N, Soscia, F, Biancosino, B, Zotos, S, Giacomin, M, Pompei, F, Spano, M, Zonta, F, Buzzi, A, Calzolari, R, Caselli, I, Diurni, M, Giana, E, Ielmini, M, Milano, A, Poloni, N, Sani, E, Zizolfi, D, Alberini, G, Cazzamalli, S, Costantini, C, Di Caro, A, Paronelli, C, Piantanida, S, Alessandro, P, Barbanti, S, D'Ippolito, C, Gozzi, M, Moretti, V, Campese, O, Di Capro, L, di Giannantonio, M, Fiori, F, Lorusso, M, Mancini, V, Viceconte, D, Calandra, C, Luca, M, Signorelli, M, Suraniti, F, Balzarro, B, Boncompagni, G, Caretto, V, Emiliani, R, Lupoli, P, Menchetti, M, Rossi, E, Storbini, V, Tarricone, I, Terzi, L, Boso, M, Catania, C, De Paoli, G, Risaro, P, Aspesi, F, Bava, M, Bono, A, Brambilla, G, Castagna, G, Lucchi, S, Nava, R, Provenzi, M, Tabacchi, T, Tremolada, M, Verrengia, E, Barchiesi, M, Oriani, M, Pacetti, M, Ferro, M, Ghio, L, Beneduce, R, Laffranchini, L, Magni, L, Rossi, G, Tura, G, Addeo, L, Balletta, G, De Vivo, E, Di Benedetto, R, Parise, V, Carpiniello, B, Pinna, F, Pecile, D, Mattei, C, Bonavigo, T, Fabrici, E, Panarello, S, Peresson, G, Vitucci, C, Gardellin, F, Strizzolo, S, Cossetta, E, Fizzotti, C, Moretti, D, Di Gregorio, L, Sozzi, F, Colli, G, La Barbera, D, Laurenzi, S, Bertolini F., Ostuzzi G., Pievani M., Aguglia A., Bartoli F., Bortolaso P., Callegari C., Caroleo M., Carra G., Corbo M., D'Agostino A., De Fazio P., Magliocco F., Martinotti G., Ostinelli E.G., Piccinelli M.P., Tedeschi F., Barbui C., Boschello F., Gastaldon C., Mazzi M.A., Nose M., Papola D., Perini G., Piccoli A., Purgato M., Ruggeri M., Terlizzi S., Turrini G., Raffaele G., Cavallotti S., Chirico M., Ferrato F., Limosani I., Mastromo D., Monzani E., Porcellana M., Restaino F., Annese P.M., Bolognesi S., Cerretini M., De Capua A., Debolini S., Del Zanna M., Fargnoli F., Giannini A., Luccarelli L., Lucii C., Pierantozzi E., Tozzi F., Bardicchia F., Cardamone G., Facchi E., Magnani N., Soscia F., Biancosino B., Zotos S., Giacomin M., Pompei F., Spano M., Zonta F., Buzzi A., Callegred C., Calzolari R., Caselli I., Diurni M., Giana E., Ielmini M., Milano A., Poloni N., Sani E., Zizolfi D., Alberini G., Cazzamalli S., Costantini C., Di Caro A., Paronelli C., Piantanida S., Piccinelli M., Alessandro P., Barbanti S.V., D'Ippolito C., Gozzi M., Moretti V., Campese O., Di Capro L., di Giannantonio M., Fiori F., Lorusso M., Mancini V., Viceconte D., Calandra C., Luca M., Signorelli M.S., Suraniti F., Balzarro B., Boncompagni G., Caretto V., Emiliani R., Lupoli P., Menchetti M., Rossi E., Storbini V., Tarricone I., Terzi L., Boso M., Catania C., De Paoli G., Risaro P., Aspesi F., Bava M., Bono A., Brambilla G., Castagna G., Lucchi S., Nava R., Provenzi M., Tabacchi T., Tremolada M., Verrengia E., Barchiesi M., Oriani M.G., Pacetti M., Ferro M., Ghio L., Beneduce R., Laffranchini L., Magni L.R., Rossi G., Tura G.B., Addeo L., Balletta G., De Vivo E., Di Benedetto R., Parise V.F., Carpiniello B., Pinna F., Pecile D., Mattei C., Bonavigo T., Fabrici E.P., Panarello S., Peresson G., Vitucci C., Gardellin F., Strizzolo S., Cossetta E., Fizzotti C., Moretti D., Di Gregorio L., Sozzi F., Colli G., La Barbera D., and Laurenzi S.

Subjects
Male, Pediatrics, respectively), 0302 clinical medicine, Delayed-Action Preparation, Brief Psychiatric Rating Scale, Pharmacology (medical), he STAR Network ‘Depot Study’ prospectively followed 394 subjects initiating treatment with long-acting injections (LAIs) of antipsychotics under naturalistic conditions for 12 months. LAI discontinuation was frequent in everyday clinical practice in Italy, Original Research Article, Prospective Studies, Prospective cohort study, treatment, Mental Disorders, Hazard ratio, whereas more than half of participants initiating risperidone LAI and olanzapine LAI discontinued during the 12 months of follow-up (51.4 and 62.5%, Psychiatric Status Rating Scale, Middle Aged, side efects, Psychiatry and Mental health, Italy, Mental Disorder, Female, he STAR Network ‘Depot Study’ prospectively followed 394 subjects initiating treatment with long-acting injections (LAIs) of antipsychotics under naturalistic conditions for 12 months. LAI discontinuation was frequent in everyday clinical practice in Italy, occurring in almost 40% of the entire sample, side efects, participant refusal to continue LAIs and LAIs no longer being required were the most frequently reported reasons for discontinuation. Paliperidone LAI and aripiprazole LAI were the least discontinued medications (33.9 and 35.4%, respectively), whereas more than half of participants initiating risperidone LAI and olanzapine LAI discontinued during the 12 months of follow-up (51.4 and 62.5%, respectively). In multivariate analysis, being prescribed olanzapine LAI and poor medication adherence at baseline were signifcantly associated with higher discontinuation risk, Human, Antipsychotic Agents, medicine.drug, Psychopathology, Adult, medicine.medical_specialty, Discontinuation, Follow-Up Studie, Medication Adherence, 03 medical and health sciences, medicine, Humans, Paliperidone, Adverse effect, Settore MED/25 - Psichiatria, discontinuation rates, Psychiatric Status Rating Scales, respectively). In multivariate analysis, business.industry, Long-Acting Antipsychotic, long-acting injectable antipsychotics, Survival Analysis, Confidence interval, participant refusal to continue LAIs and LAIs no longer being required were the most frequently reported reasons for discontinuation. Paliperidone LAI and aripiprazole LAI were the least discontinued medications (33.9 and 35.4%, 030227 psychiatry, Prospective Studie, Antipsychotic Agent, occurring in almost 40% of the entire sample, Delayed-Action Preparations, Neurology (clinical), business, 030217 neurology & neurosurgery, being prescribed olanzapine LAI and poor medication adherence at baseline were signifcantly associated with higher discontinuation risk, Follow-Up Studies
Abstract

Background Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses. Objective Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors. Methods The STAR Network ‘Depot Study’ was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively. Results The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4–44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3–43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4–84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6–40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6–27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742–0.981; p = 0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003–4.634; p = 0.049). Conclusions Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation. Supplementary Information The online version contains supplementary material available at 10.1007/s40263-021-00809-w.

Published
2021

2. Clinical correlates of paliperidone palmitate and aripiprazole monohydrate prescription for subjects with schizophreniaspectrum disorders: Findings from the STAR Network Depot Study

Author

Barbui C, Nosè M, Purgato M, Turrini G, Ostuzzi G, Mazzi MA, Papola D, Gastaldon C, Terlizzi S, Bertolini F, Piccoli A, Ruggeri M, De Fazio P, Magliocco F, Caroleo M, Raffaele G, D'Agostino A, Ostinelli EG, Chirico M, Cavallotti S, Lucii C, Bolognesi S, Debolini S, Pierantozzi E, Fargnoli F, Del Zanna M, Giannini A, Luccarelli L, De Capua A, Annese PM, Cerretini M, Tozzi F, Magnani N, Cardamone G, Bardicchia F, Facchi E, Soscia F, Zotos S, Biancosino B, Zonta F, Pompei F, Callegari C, Zizolfi D, Poloni N, Ielmini M, Caselli I, Giana E, Buzzi A, Diurni M, Milano A, Sani E, Calzolari R, Bortolaso P, Piccinelli M, Cazzamalli S, Alberini G, Piantanida S, Costantini C, Paronelli C, Di Caro A, Moretti V, Gozzi M, D'Ippolito C, Barbanti SV, Papalini A, Corbo M, Martinotti G, Campese O, Fiori F, Lorusso M, Di Capro L, Viceconte D, Mancini V, Suraniti F, Signorelli MSI, Rossi E, Lupoli P, Menchetti M, Terzi L, Boso M, Risaro P, De Paoli G, Catania C, Tarricone I, Caretto V, Storbini V, Emiliani R, Balzarro B, Carrà G, Bartoli F, Tabacchi T, Nava R, Bono A, Provenzi M, Brambilla G, Aspesi F, Trotta G, Tremolada M, Castagna G, Bava M, Verrengia E, Lucchi S, Oriani MG, Barchiesi M, Pacetti M, Aguglia A, Magni LR, Rossi G, Beneduce R, Tura GB, Laffranchini L, Mastromo D, Ferrato F, Restaino F, Monzani E, Porcellana M, Limosani I, Ghio L, Ferro M, Parise VF, Balletta G, Addeo L, De Vivo E, Di Benedetto R, Pinna F, Carpiniello B, Spano M, Giacomin M, Pecile D, Mattei C, Fabrici EP, Panarello S, Peresson G, Vitucci C, Bonavigo T, Perini G, Boschello F, Strizzolo S, Gardellin F, Di Giannantonio M, Moretti D, Fizzotti C, Cossetta E, Di Gregorio L, Sozzi F, Boncompagni G, La Barbera D, Colli G, Laurenzi S, Calandra C, Luca M, Crocamo C, STAR Network Depot Investigators, Bartoli F., Ostuzzi G., Crocamo C., Corbo M., D'Agostino A., Martinotti G., Ostinelli E.G., Tabacchi T., Barbui C., Carr G., Nose M., Purgato M., Turrini G., Mazzi M.A., Papola D., Gastaldon C., Terlizzi S., Bertolini F., Piccoli A., Ruggeri M., De Fazio P., Magliocco F., Caroleo M., Raffaele G., Chirico M., Cavallotti S., Lucii C., Bolognesi S., Debolini S., Pierantozzi E., Fargnoli F., Del Zanna M., Giannini A., Luccarelli L., De Capua A., Annese P.M., Cerretini M., Tozzi F., Magnani N., Cardamone G., Bardicchia F., Facchi E., Soscia F., Zotos S., Biancosino B., Zonta F., Pompei F., Callegari C., Zizolfi D., Poloni N., Ielmini M., Caselli I., Giana E., Buzzi A., Diurni M., Milano A., Sani E., Calzolari R., Bortolaso P., Piccinelli M., Cazzamalli S., Alberini G., Piantanida S., Costantini C., Paronelli C., Di Caro A., Moretti V., Gozzi M., D'Ippolito C., Barbanti S.V., Papalini A., Campese O., Fiori F., Lorusso M., Di Capro L., Viceconte D., Mancini V., Suraniti F., Signorelli M.S., Rossi E., Lupoli P., Menchetti M., Terzi L., Boso M., Risaro P., De Paoli G., Catania C., Tarricone I., Caretto V., Storbini V., Emiliani R., Balzarro B., Carra G., Nava R., Bono A., Provenzi M., Brambilla G., Aspesi F., Trotta G., Tremolada M., Castagna G., Bava M., Verrengia E., Lucchi S., Oriani M.G., Barchiesi M., Pacetti M., Aguglia A., Magni L.R., Rossi G., Beneduce R., Tura G.B., Laffranchini L., Mastromo D., Ferrato F., Restaino F., Monzani E., Porcellana M., Limosani I., Ghio L., Ferro M., Parise V.F., Balletta G., Addeo L., De Vivo E., Di Benedetto R., Pinna F., Carpiniello B., Spano M., Giacomin M., Pecile D., Mattei C., Fabrici E.P., Panarello S., Peresson G., Vitucci C., Bonavigo T., Perini G., Boschello F., Strizzolo S., Gardellin F., Di Giannantonio M., Moretti D., Fizzotti C., Cossetta E., Di Gregorio L., Sozzi F., Boncompagni G., La Barbera D., Colli G., Laurenzi S., Calandra C., Luca M., Barbui C, Nosè M, Purgato M, Turrini G, Ostuzzi G, Mazzi MA, Papola D, Gastaldon C, Terlizzi S, Bertolini F, Piccoli A, Ruggeri M, De Fazio P, Magliocco F, Caroleo M, Raffaele G, D'Agostino A, Ostinelli EG, Chirico M, Cavallotti S, Lucii C, Bolognesi S, Debolini S, Pierantozzi E, Fargnoli F, Del Zanna M, Giannini A, Luccarelli L, De Capua A, Annese PM, Cerretini M, Tozzi F, Magnani N, Cardamone G, Bardicchia F, Facchi E, Soscia F, Zotos S, Biancosino B, Zonta F, Pompei F, Callegari C, Zizolfi D, Poloni N, Ielmini M, Caselli I, Giana E, Buzzi A, Diurni M, Milano A, Sani E, Calzolari R, Bortolaso P, Piccinelli M, Cazzamalli S, Alberini G, Piantanida S, Costantini C, Paronelli C, Di Caro A, Moretti V, Gozzi M, D'Ippolito C, Barbanti SV, Papalini A, Corbo M, Martinotti G, Campese O, Fiori F, Lorusso M, Di Capro L, Viceconte D, Mancini V, Suraniti F, Signorelli MSI, Rossi E, Lupoli P, Menchetti M, Terzi L, Boso M, Risaro P, De Paoli G, Catania C, Tarricone I, Caretto V, Storbini V, Emiliani R, Balzarro B, Carrà G, Bartoli F, Tabacchi T, Nava R, Bono A, Provenzi M, Brambilla G, Aspesi F, Trotta G, Tremolada M, Castagna G, Bava M, Verrengia E, Lucchi S, Oriani MG, Barchiesi M, Pacetti M, Aguglia A, Magni LR, Rossi G, Beneduce R, Tura GB, Laffranchini L, Mastromo D, Ferrato F, Restaino F, Monzani E, Porcellana M, Limosani I, Ghio L, Ferro M, Parise VF, Balletta G, Addeo L, De Vivo E, Di Benedetto R, Pinna F, Carpiniello B, Spano M, Giacomin M, Pecile D, Mattei C, Fabrici EP, Panarello S, Peresson G, Vitucci C, Bonavigo T, Perini G, Boschello F, Strizzolo S, Gardellin F, Di Giannantonio M, Moretti D, Fizzotti C, Cossetta E, Di Gregorio L, Sozzi F, Boncompagni G, La Barbera D, Colli G, Laurenzi S, Calandra C, Luca M, Crocamo C, STAR Network Depot Investigators, Bartoli, F, Ostuzzi, G, Crocamo, C, Corbo, M, D'Agostino, A, Martinotti, G, Ostinelli, E, Tabacchi, T, Barbui, C, and Carra, G

Subjects
Aripiprazole monohydrate, Long-acting injectable antipsychotics, Paliperidone palmitate, Schizophrenia, Adult, Antipsychotic Agents, Aripiprazole, Female, Health Knowledge, Attitudes, Practice, Humans, Male, Medication Adherence, Paliperidone Palmitate, Practice Patterns, Physicians', Schizophrenic Psychology, Young Adult, Long-acting injectable antipsychotic, medicine.medical_specialty, medicine.medical_treatment, Aripiprazole monohydrate, Long-acting injectable antipsychotics, Paliperidone palmitate, Schizophrenia, Practice Patterns, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Brief Psychiatric Rating Scale, medicine, Pharmacology (medical), Antipsychotic, Settore MED/25 - Psichiatria, Practice, Physicians', business.industry, Health Knowledge, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Attitudes, Propensity score matching, Observational study, business, 030217 neurology & neurosurgery, medicine.drug, Psychopathology
Abstract

This study, based on the 'Servizi Territoriali Associati per la Ricerca' (STAR) Network Depot Study nationwide baseline data, explored whether individual symptoms severity and clusters might influence the prescription of paliperidone palmitate 1-month (PP1M) vs. aripiprazole monohydrate. The Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology and relevant symptoms clusters. Drug Attitude Inventory, 10 items, was used to test attitude towards medications. Adherence to treatments was rated according to the Kemp seven-point scale. We assessed for eligibility 451 individuals and, among them, we included 195 subjects (n = 117 who started PPM1 and n = 78 aripiprazole monohydrate). Individuals were comparable in terms of age, gender, treatment years, recent hospitalizations, previous long-acting injectable antipsychotic treatments, additional oral treatments, attitude toward drugs, medication adherence, and alcohol/substance-related comorbidities. Subjects starting PP1M presented higher BPRS overall (P = 0.009), positive (P = 0.015), and negative (P = 0.010) symptom scores compared to subjects starting aripiprazole monohydrate. Results were confirmed by appropriate regression models and propensity score matching analysis. No differences were found comparing the other BPRS subscale scores: affect, resistance, and activation. Clinicians may be more prone to prescribe PPM1, rather than aripiprazole monohydrate, to subjects showing higher overall symptom severity, including positive and negative symptoms. No additional clinical factors influenced prescribing attitudes in our sample.

Published
2020

3. Factors associated with first- versus second-generation long-acting antipsychotics prescribed under ordinary clinical practice in Italy

Author

Ostuzzi, G., Mazzi, M. A., Terlizzi, S., Bertolini, F., Aguglia, A., Bartoli, F., Bortolaso, P., Callegari, C., Caroleo, M., Carrà, G., Corbo, M., D'Agostino, A., Gastaldon, C., Lucii, C., Magliocco, F., Martinotti, G., Nosé, M., Ostinelli, E. G., Papola, D., Piccinelli, M. P., Piccoli, A., Purgato, M., Tabacchi, T., Turrini, G., Ruggeri, M., Barbui, C., De Fazio, P., Raffaele, G., Chirico, M., Cavallotti, S., Bolognesi, S., Debolini, S., Pierantozzi, E., Fargnoli, F., Del Zanna, M., Giannini, A., Luccarelli, L., De Capua, A., Annese, P. M., Cerretini, M., Tozzi, F. E., Magnani, N., Cardamone, G., Bardicchia, F., Facchi, E., Soscia, F., Zotos, S., Biancosino, B., Zonta, F., Pompei, F., Zizolfi, D., Poloni, N., Ielmini, M., Caselli, I., Giana, E., Buzzi, A., Diurni, M., Milano, A., Sani, E., Calzolari, Roberta, Cazzamalli, S., Alberini, Gabrio, Piantanida, Silvia, Costantini, C., Paronelli, Chiara, Di Caro, A., Moretti, V., Gozzi, M., D'Ippolito, C., Barbanti, S. V., Alessandro, P., Campese, O., Fiori, F., Lorusso, M., Di Capro, L., Viceconte, D., Mancini, V., Suraniti, F., Signorelli, M. S., Rossi, E., Lupoli, P., Menchetti, M., Terzi, L., Boso, M., Risaro, P., De Paoli, G., Catania, C., Tarricone, I., Caretto, V., Storbini, V., Emiliani, R., Balzarro, B., Nava, R., Bono, A., Provenzi, M., Brambilla, G., Aspesi, F., Tremolada, M., Castagna, G., Bava, M., Verrengia, E., Lucchi, S., Oriani, M. G., Barchiesi, M., Pacetti, M., Magni, L. R., Rossi, G., Beneduce, R., Tura, G. B., Laffranchini, L., Mastromo, D., Ferrato, F., Restaino, F., Monzani, E., Porcellana, M., Limosani, I., Ghio, L., Ferro, M., Parise, V. F., Balletta, G., Addeo, L., De Vivo, E., Benedetto, R. D., Pinna, F., Carpiniello, B., Spano, M., Giacomin, M., Pecile, D., Mattei, C., Fabrici, E. P., Panarello, S., Peresson, G., Vitucci, C., Bonavigo, T., Perini, G., Boschello, F., Strizzolo, S., Gardellin, F., Di Giannantonio, M., Moretti, D., Fizzotti, C., Cossetta, E., Gregorio, L. D., Sozzi, F., Boncompagni, G., Barbera, D. L., Colli, G., Laurenzi, S., Calandra, C., Luca, M., Ostuzzi, Giovanni, Mazzi, Maria Angela, Terlizzi, Samira, Bertolini, Federico, Aguglia, Andrea, Bartoli, Francesco, Bortolaso, Paola, Callegari, Camilla, Caroleo, Mariarita, Carrà, Giuseppe, Corbo, Mariangela, D'Agostino, Armando, Gastaldon, Chiara, Lucii, Claudio, Magliocco, Fabio, Martinotti, Giovanni, Nosé, Michela, Ostinelli, Edoardo Giuseppe, Papola, Davide, Piccinelli, Marco Piero, Piccoli, Alberto, Purgato, Marianna, Tabacchi, Tommaso, Turrini, Giulia, Ruggeri, Mirella, Barbui, Corrado, De Fazio, Pasquale, Raffaele, Gaetano, Chirico, Margherita, Cavallotti, Simone, Bolognesi, Simone, Debolini, Sara, Pierantozzi, Elisa, Fargnoli, Francesco, Del Zanna, Maria, Giannini, Alessandra, Luccarelli, Livia, De Capua, Alberto, Annese, Pasqua Maria, Cerretini, Massimiliano, Tozzi, Fior-Ella, Magnani, Nadia, Cardamone, Giuseppe, Bardicchia, Francesco, Facchi, Edvige, Soscia, Federica, Zotos, Spyridon, Biancosino, Bruno, Zonta, Filippo, Pompei, Francesco, Zizolfi, Daniele, Poloni, Nicola, Ielmini, Marta, Caselli, Ivano, Giana, Edoardo, Buzzi, Aldo, Diurni, Marcello, Milano, Anna, Sani, Emanuele, Calzolari, Roberta, Piccinelli, Marco, Cazzamalli, Sara, Alberini, Gabrio, Piantanida, Silvia, Costantini, Chiara, Paronelli, Chiara, Di Caro, Angela, Moretti, Valentina, Gozzi, Mauro, D'Ippolito, Chiara, Barbanti, Silva Veronica, Alessandro, Papalini, Campese, Ornella, Fiori, Federica, Lorusso, Marco, Di Capro, Lucia, Viceconte, Daniela, Mancini, Valerio, Suraniti, Francesco, Signorelli, Maria Salvina, Rossi, Eugenio, Lupoli, Pasqualino, Menchetti, Marco, Terzi, Laura, Boso, Marianna, Risaro, Paolo, De Paoli, Giuseppe, Catania, Cristina, Tarricone, Ilaria, Caretto, Valentina, Storbini, Viviana, Emiliani, Roberta, Balzarro, Beatrice, Nava, Roberto, Bono, Adele, Provenzi, Milena, Brambilla, Giulia, Aspesi, Flora, Tremolada, Martina, Castagna, Gloria, Bava, Mattia, Verrengia, Enrica, Lucchi, Sara, Oriani, Maria Ginevra, Barchiesi, Michela, Pacetti, Monica, Magni, Laura Rosa, Rossi, Giuseppe, Beneduce, Rossella, Tura, Giovanni Battista, Laffranchini, Laura, Mastromo, Daniele, Ferrato, Farida, Restaino, Francesco, Monzani, Emiliano, Porcellana, Matteo, Limosani, Ivan, Ghio, Lucio, Ferro, Maurizio, Parise, Vincenzo Fricchione, Balletta, Giovanni, Addeo, Lelio, De Vivo, Elisa, Benedetto, Rossella Di, Pinna, Federica, Carpiniello, Bernardo, Spano, Mariangela, Giacomin, Marzio, Pecile, Damiano, Mattei, Chiara, Fabrici, Elisabetta Pascolo, Panarello, Sofia, Peresson, Giulia, Vitucci, Claudio, Bonavigo, Tommaso, Perini, Giovanni, Boschello, Filippo, Strizzolo, Stefania, Gardellin, Francesco, Di Giannantonio, Massimo, Moretti, Daniele, Fizzotti, Carlo, Cossetta, Edoardo, Gregorio, Luana Di, Sozzi, Francesca, Boncompagni, Giancarlo, Barbera, Daniele La, Colli, Giuseppe, Laurenzi, Sabrina, Calandra, Carmela, Luca, Maria, Ostuzzi, G, Mazzi, M, Terlizzi, S, Bertolini, F, Aguglia, A, Bartoli, F, Bortolaso, P, Callegari, C, Caroleo, M, Carrà, G, Corbo, M, D'Agostino, A, Gastaldon, C, Lucii, C, Magliocco, F, Martinotti, G, Nosé, M, Ostinelli, E, Papola, D, Piccinelli, M, Piccoli, A, Purgato, M, Tabacchi, T, Turrini, G, Ruggeri, M, Barbui, C, De Fazio, P, Raffaele, G, Chirico, M, Cavallotti, S, Bolognesi, S, Debolini, S, Pierantozzi, E, Fargnoli, F, Del Zanna, M, Giannini, A, Luccarelli, L, De Capua, A, Annese, P, Cerretini, M, Tozzi, F, Magnani, N, Cardamone, G, Bardicchia, F, Facchi, E, Soscia, F, Zotos, S, Biancosino, B, Zonta, F, Pompei, F, Zizolfi, D, Poloni, N, Ielmini, M, Caselli, I, Giana, E, Buzzi, A, Diurni, M, Milano, A, Sani, E, Calzolari, R, Cazzamalli, S, Alberini, G, Piantanida, S, Costantini, C, Paronelli, C, Di Caro, A, Moretti, V, Gozzi, M, D'Ippolito, C, Barbanti, S, Alessandro, P, Campese, O, Fiori, F, Lorusso, M, Di Capro, L, Viceconte, D, Mancini, V, Suraniti, F, Signorelli, M, Rossi, E, Lupoli, P, Menchetti, M, Terzi, L, Boso, M, Risaro, P, De Paoli, G, Catania, C, Tarricone, I, Caretto, V, Storbini, V, Emiliani, R, Balzarro, B, Nava, R, Bono, A, Provenzi, M, Brambilla, G, Aspesi, F, Tremolada, M, Castagna, G, Bava, M, Verrengia, E, Lucchi, S, Oriani, M, Barchiesi, M, Pacetti, M, Magni, L, Rossi, G, Beneduce, R, Tura, G, Laffranchini, L, Mastromo, D, Ferrato, F, Restaino, F, Monzani, E, Porcellana, M, Limosani, I, Ghio, L, Ferro, M, Parise, V, Balletta, G, Addeo, L, De Vivo, E, Benedetto, R, Pinna, F, Carpiniello, B, Spano, M, Giacomin, M, Pecile, D, Mattei, C, Fabrici, E, Panarello, S, Peresson, G, Vitucci, C, Bonavigo, T, Perini, G, Boschello, F, Strizzolo, S, Gardellin, F, Di Giannantonio, M, Moretti, D, Fizzotti, C, Cossetta, E, Gregorio, L, Sozzi, F, Boncompagni, G, Barbera, D, Colli, G, Laurenzi, S, Calandra, C, and Luca, M

Subjects
Genetics and Molecular Biology (all), Male, Pediatrics, European People, Bipolar Disorder, Cross-sectional study, Economics, Epidemiology, medicine.medical_treatment, assessment, viruses, lcsh:Medicine, Social Sciences, Longitudinal Studie, Biochemistry, Prescription, Geographical locations, 0302 clinical medicine, Mathematical and Statistical Techniques, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), immune system diseases, Medicine and Health Sciences, long-acting intramuscular (LAI) antipsychotics, clinical practice, second-generation antipsychotic (SGA) LAIs, Antipsychotics, Ethnicities, Longitudinal Studies, lcsh:Science, Multidisciplinary, virus diseases, Drugs, Middle Aged, Italian People, Europe, Prescriptions, Italy, Physical Sciences, Aripiprazole, Female, Bivariate Analysis, Statistics (Mathematics), medicine.drug, Human, Research Article, Antipsychotic Agents, Employment, Adult, medicine.medical_specialty, Adolescent, Research and Analysis Methods, 03 medical and health sciences, Mental Health and Psychiatry, medicine, Humans, Paliperidone, Bipolar disorder, European Union, Statistical Methods, Antipsychotic, Cross-Sectional Studie, Pharmacology, Risperidone, business.industry, Mood Disorders, lcsh:R, medicine.disease, 030227 psychiatry, Antipsychotic Agent, Cross-Sectional Studies, Labor Economics, Multivariate Analysis, Schizophrenia, Observational study, lcsh:Q, Population Groupings, People and places, business, 030217 neurology & neurosurgery, Mathematics
Abstract

Background For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. Methods The STAR Network "Depot" Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed. Results Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past. Discussion LAIs' prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAIs.

Published
2018

4. Contemporary antithrombotic strategies in patients with acute coronary syndromes managed without revascularization: insights from the EYESHOT study

Author

De Luca, Leonardo, Leonardi, Sergio, Smecca, Ignazio Maria, Formigli, Dario, Lucci, Donata, Gonzini, Lucio, Tuccillo, Bernardino, Olivari, Zoran, Gulizia, Michele Massimo, Bovenzi, Francesco Maria, De Servi, Stefano, Caporale, R., Cavallini, C., Ceravolo, R., Lupi, A., Musumeci, G., Rakar, S., Maggioni, A. P., Lorimer, A., Orsini, G., Fabbri, Giorgio, Bianchini, E., Abrignani, M. G., Bonura, F., Trimarco, B., Galasso, Giorgia, Misuraca, G., Manes, M. T., Irace, Lorenzo, Totis, O., Ledda, A., Mauro, C., Boccalatte, M., Iliceto, S., Cacciavillani, L., Savonitto, S., Tortorella, G., Esposito, L., DE ROSA, Paolo, Calabrò, P., Bianchi, R., Napoletano, C., Lalla Piccioni, L., Pavesi, P. C., Boni, Allegra, Merenda, R., Wolff, S., De Ferrari, G. M., Camporotondo, R., Gambino, Paolo, Cutaia, A., Picariello, C., Cemin, R., Chiarella, F., Grazioli Gauthier, L., Mircoli, L., Del Pinto, M., Finocchiaro, M. L., Scioli, R., Farina, R., Naddeo, C., Scherillo, M., Santopietro, S., Metra, M., Costa, F., Calculli, G., Troito, G., Pennisi, V., Adornato, E. M. F., Pirelli, S., Fadin, B. M., Di Biase, M., Ieva, R., Zuin, G., Sanfilippo, N., Mancuso, LAURA CATERINA, Pani, Luisa Anna, Serra, Eleonora, Marenzi, G., Assanelli, E. M., Ansalone, G., Cacciotti, L., Morocutti, G., Fresco, C., Berti, S., Paradossi, U., Bozzano, A., Mauro, A., Noussan, P., Zanini, P., Bolognese, L., Falsini, G., Costa, P., Manca, G., Caldarola, P., Locuratolo, N., Cipolla, T., Becchina, M., Cocco, Gabriele, Scalera, G., Stefanelli, S., Giunta, N., Sinagra, G., Meloni, L., Lai, O., Chiaranda, G., Luca, G., Sleiman Helou, J., Biscottini, E., Magliari, F., Callerame, M., Uguccioni, M., Pugliese, M., Sanchez, F., Tartaglione, S., Ignone, G., Mavilio, G., Mantovan, R., Bini, R., Caico, S. I., Demolli, V., Proietti, F., Michisanti, M., Musmeci, G., Cantamessa, P., Sicuso, G., Micalef, S. S., Accogli, M., Zaccaria, MICHELA MARIA, Caputo, M., Di Paolo, G., Piatti, L., Farina, A., Vicinelli, P., Paloscia, L., Di Clemente, D., Felis, S., Castini, D., Rota, C., Casu, Gabriella, Bonano, S., Margheri, M., Ricci Lucchi, G., Serdoz, R., Proietti, P., Autore, C., Conti, E., Russo, V., Orlando, P., Ramondo, A. B., Bontorin, M., Marcolongo, M., Marrara, F., Maestroni, A., Vitti, P., Rodella, P., Bonetti, P., Elia, M., Lumare, R., Politi, A., Gritti, S., Poletti, F., Mafrici, A., Fusco, R., Bongo, A. S., Bacchini, S., Gasparetto, V., Ferraiuolo, G., Campana, C., Bonatti, R., Gaita, F., Bergerone, S., Bonmassari, R., Zeni, P., Langialonga, T., Scarcia, A., Caravita, L., Musacchio, E., Augello, G., Usmiani, T., Stomaci, B., Cirino, D., Pierini, S., Bottiglieri, G., Liso, A., Mussardo, M., Tosi, P., Sala, R., Belloni, A., Blengino, S., Lisi, E., Delfino, P., Auguadro, C., Brunazzi, M. C., Pacchioni, E., Fattore, L., Bosco, B., Blandizzi, S., Pajes, G., Patruno, N., Perna, G. P., Francioni, M., Favale, S., Vestito, D., Lombardi, A., Capecchi, A., Ferrero, P., De Vincenzo, C., Magri, G., Indolfi, C., De Rosa, S., Rossi, M., Collarini, L., Agnelli, D., Conti, G., Tonelli, C., Spadaro, C., Negroni, S., Di Noto, G., Lanari, A., Casolo, G., Del Meglio, J., Negrini, M., Celentano, A., Sifola, C., Rellini, G., Della Mattia, A., Molero, U., Piovaccari, G., Grosseto, D., Callegarin, L., Fiasconaro, G., Crivello, R., Thiebat, B., Leone, G., Tamburino, C., Caruso, G., Cassadonte, F., Sassone, B., Fuca, G., Sormani, L., Percoco, G. F., Mazzucco, R., Cazzani, E., Gianni, M., Limido, A., Luvini, M., Guglielmi, R., Mannarini, A., Moruzzi, P., Pastori, P., Golia, B., Marzano, A., Orazi, S., Marchese, I., Anselmi, M., Girardi, P., Nassiacos, D., Meloni, S., Busacca, P., Generali, C. A., Corda, S., Costanza, G., Montalto, S., Argenziano, L., Tommasini, P., Emdin, M., Pasanisi, E. M., Colivicchi, F., Tubaro, M., Azzolini, P., Luciani, C., Doronzo, B., Coppolino, A., Dellavesa, P., Zenone, F., Di Marco, A., De Conti, F., Piccinni, G. C., Gualtieri, M. R., Bisignani, G., Leone, A., Arcuri, G. M., Marinacci, L., Rossi, P., Perotti, S., Cotti Cometti, V., Arcidiacono, S., Tramontana, M., Bazzucchi, M., Mezzetti, P., Romano, M., Villani, R., Di Giovambattista, R., Volpe, B., Tedesco, L., Carini, M., Vinci, S., Paolini, E. A., Busoni, F., Piergentili, C., Navazio, A., Manca, F., Cocco, F., Pennetta, C. A., Maggiolini, S., Galbiati, R., Bruna, C., Ferrero, L., Brigido, S., Barducci, E., Musacchio, D., Manduca, B., Marchese, D., Patrassi, L. A., Pattarino, F. A., Rocchi, M., Briglia, S., Fanelli, R., Villella, M., Gronda, E., Massa, D., Lenti, V., Di Gregorio, L., Bottero, M., Bazzanini, F., Braggion, G., Antoniceli, R., Caraceni, D., Guzzo, V., Di Giovanni, P., Scarpini, S., Severgnini, B., Musolino, M. F., Della Casa, S., Gobbi, M., Arena, G., Bonizzato, S., Agnoletto, V., Sansoni, S., Pes, R. A. M., Denti, S., Polizzi, G. M., Pino, R., Commisso, B., Merlino, A., Di Lorenzo, L., Porchetta, I., Del Furia, F., Colombi, E., Covini, D., Cavalieri, F., Antonaci, S., Rubino, G., Ciulla, A., Bui, F., Casorelli, E., Caliendo, L., Laezza, A., Americo, L., Schillaci, A. M., Cordoni, M., Barsotti, L., Gaudio, C., Barilla, F., Cannone, M., Memeo, R., Truncellito, L., Andriani, A., Salituri, S., Verrina, F., Pafi, M., Sebastiani, M. L., Amico, A. F., Scolozzi, D., D'Alea, A., Catanzariti, D., Angheben, C., Ottaviano, A., and Levantesi, G.

Subjects
Male, Ticagrelor, medicine.medical_specialty, Acute coronary syndrome, medicine.medical_treatment, Conservative strategy, Population, Acute coronary syndromes, Revascularization, acute coronary syndromes, anticoagulant, antithrombotic therapy, conservative strategy, prasugrel, ticagrelor, aged, coronary care units, female, fibrinolytic agents, follow-up studies, hospital mortality, humans, iItaly, length of stay, male, myocardial revascularization, retrospective studies, survival rate, thrombolytic therapy, practice guidelines as topic, Fibrinolytic Agents, Anticoagulant, Antithrombotic therapy, Prasugrel, Acute Coronary Syndrome, Aged, Coronary Care Units, Female, Follow-Up Studies, Hospital Mortality, Humans, Italy, Length of Stay, Myocardial Revascularization, Retrospective Studies, Survival Rate, Thrombolytic Therapy, Practice Guidelines as Topic, Cardiology and Cardiovascular Medicine, Pharmacology (medical), Internal medicine, Antithrombotic, medicine, education, Survival rate, education.field_of_study, business.industry, Clopidogrel, medicine.disease, Cardiology, business, Fibrinolytic agent, medicine.drug
Abstract

Aims Patients with acute coronary syndromes (ACSs) who are managed without coronary revascularization represent a mixed and understudied population that seems to receive suboptimal pharmacological treatment. Methods and results We assessed patterns of antithrombotic therapies employed during the hospitalization and in-hospital clinical events of medically managed patients with ACS enrolled in the prospective, multicentre, nationwide EYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units) registry. Among the 2585 consecutive ACS patients enrolled in EYESHOT, 783 (30.3%) did not receive any revascularization during hospital admission. Of these, 478 (61.0%) underwent coronary angiography (CA), whereas 305 (39.0%) did not. The median GRACE and CRUSADE risk scores were significantly higher among patients who did not undergo CA compared with those who did (180 vs. 145, P < 0.0001 and 50 vs. 33, P < 0.0001, respectively). Antithrombotic therapies employed during hospitalization significantly differ between patients who received CA and those who did not with unfractioned heparin and novel P2Y12 inhibitors more frequently used in the first group, and low-molecular-weight heparins and clopidogrel in the latter group. During the index hospitalization, patients who did not receive CA presented a higher incidence of ischaemic cerebrovascular events and of mortality compared with those who underwent CA (1.6 vs. 0.2%, P = 0.04 and 7.9 vs. 2.7%, P = 0.0009, respectively). Conclusion Almost one-third of ACS patients are managed without revascularization during the index hospitalization. In this population, a lower use of recommended antiplatelet therapy and worse clinical outcome were observed in those who did not undergo CA when compared with those who did. Clinical Trial Registration Unique identifier: [NCT02015624][1], . [10.1093/ehjcvp/pvv017][2] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02015624&atom=%2Fehjcardpharm%2F1%2F3%2F168.atom [2]: /lookup/doi/10.1093/ehjcvp/pvv017

Published
2015
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5. Antithrombotic strategies in the catheterization laboratory for patients with acute coronary syndromes undergoing percutaneous coronary interventions: insights from the EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units Registry

Author

De Luca, L., Musumeci, G., Leonardi, S., Gonzini, L., Cavallini, C., Calabro, P., Mauro, C., Cacciavillani, L., Savonitto, S., De Servi, S., Caporale, R., Ceravolo, R., Formigli, D., Lupi, A., Rakar, S., Smecca, I. M., Maggioni, A. P., Lucci, D., Lorimer, A., Orsini, G., Fabbri, G., Bianchini, E., Abrignani, M. G., Bonura, F., Trimarco, B., Galasso, G., Misuraca, G., Manes, M. T., Tuccillo, B., Irace, L., Olivari, Z., Totis, O., Ledda, A., Boccalatte, M., Iliceto, S., Tortorella, G., Esposito, L., De Rosa, P., Bianchi, R., Napoletano, C., Piccioni, L. L., Pavesi, P. C., Bovenzi, F. M., Boni, A., Merenda, R., Wolff, S., De Ferrari, G. M., Camporotondo, R., Gambino, P., Cutaia, A., Picariello, C., Cemin, R., Chiarella, F., Gauthier, L. G., Mircoli, L., Del Pinto, M., Finocchiaro, M. L., Scioli, R., Farina, R., Naddeo, C., Scherillo, M., Santopietro, S., Metra, M., Costa, F., Calculli, G., Troito, G., Pennisi, V., Adornato, E. M. F., Pirelli, S., Fadin, B. M., DI Biase, M., Ieva, R., Zuin, G., Sanfilippo, N., Mancuso, L., Pani, A., Serra, E., Marenzi, G., Assanelli, E. M., Ansalone, G., Cacciotti, L., Morocutti, G., Fresco, C., Berti, S., Paradossi, U., Bozzano, A., Mauro, A., Noussan, P., Zanini, P., Bolognese, L., Falsini, G., Costa, P., Manca, G., Caldarola, P., Locuratolo, N., Cipolla, T., Becchina, M., Cocco, G., Scalera, G., Stefanelli, S., Giunta, N., Sinagra, G., Meloni, L., Lai, O., Chiaranda, G., Luca, G., Helou, J. S., Biscottini, E., Magliari, F., Callerame, M., Uguccioni, M., Pugliese, M., Sanchez, F., Tartaglione, S., Ignone, G., Mavilio, G., Mantovan, R., Bini, R., Caico, S. I., Demolli, V., Proietti, F., Michisanti, M., Musmeci, G., Cantamessa, P., Sicuso, G., Micalef, S. S., Accogli, M., Zaccaria, M., Caputo, M., DI Paolo, G., Piatti, L., Farina, A., Vicinelli, P., Paloscia, L., DI Clemente, D., Felis, S., Castini, D., Rota, C., Casu, G., Bonano, S., Margheri, M., Lucchi, G. R., Serdoz, R., Proietti, P., Autore, C., Conti, E., Russo, V., Orlando, P., Ramondo, A. B., Bontorin, M., Marcolongo, M., Santagostino, M., Maestroni, A., Vitti, P., Rodella, P., Bonetti, P., Elia, M., Lumare, R., Politi, A., Gritti, S., Poletti, F., Mafrici, A., Fusco, R., Bongo, A. S., Bacchini, S., Gasparetto, V., Ferraiuolo, G., De Luca, M., Campana, C., Bonatti, R., Gaita, F., Bergerone, S., Bonmassari, R., Zeni, P., Langialonga, T., Scarcia, A., Caravita, L., Musacchio, E., Augello, G., Usmiani, T., Stomaci, B., Cirino, D., Pierini, S., Bottiglieri, G., Liso, A., Mussardo, M., Tosi, P., Sala, R., Belloni, A., Blengino, S., Lisi, E., Delfino, P., Auguadro, C., Brunazzi, M. C., Pacchioni, E., Fattore, L., Bosco, B., Blandizzi, S., Pajes, G., Patruno, N., Perna, G. P., Francioni, M., Favale, S., Vestito, D., Lombardi, A., Capecchi, A., Ferrero, P., De Vincenzo, C., Magri, G., Indolfi, C., De Rosa, S., Rossi, M., Collarini, L., Agnelli, D., Conti, G., Tonelli, C., Spadaro, C., Negroni, S., DI Noto, G., Lanari, A., Casolo, G., Del Meglio, J., Negrini, M., Celentano, A., Sifola, C., Rellini, G., Mattia, A. D., Molero, U., Piovaccari, G., Grosseto, D., Callegarin, L., Fiasconaro, G., Crivello, R., Thiebat, B., Leone, G., Tamburino, C., Caruso, G., Cassadonte, F., Sassone, B., Fuca, G., Sormani, L., Percoco, G. F., Mazzucco, R., Cazzani, E., Gianni, M., Limido, A., Luvini, M., Guglielmi, R., Mannarini, A., Moruzzi, P., Pastori, P., Golia, B., Marzano, A., Orazi, S., Marchese, I., Anselmi, M., Girardi, P., Nassiacos, D., Meloni, S., Busacca, P., Generali, C. A., Corda, S., Costanza, G., Montalto, S., Argenziano, L., Tommasini, P., Emdin, M., Pasanisi, E. M., Colivicchi, F., Tubaro, M., Azzolini, P., Luciani, C., Doronzo, B., Coppolino, A., Dellavesa, P., Zenone, F., DI Marco, A., De Conti, F., Piccinni, G. C., Gualtieri, M. R., Bisignani, G., Leone, A., Arcuri, G. M., Marinacci, L., Rossi, P., Perotti, S., Cometti, V. C., Arcidiacono, S., Tramontana, M., Bazzucchi, M., Mezzetti, P., Romano, M., Villani, R., DI Giovambattista, R., Volpe, B., Tedesco, L., Carini, M., Vinci, S., Paolini, E. A., Busoni, F., Piergentili, C., Navazio, A., Manca, F., Cocco, F., Pennetta, C. A., Maggiolini, S., Galbiati, R., Bruna, C., Ferrero, L., Brigido, S., Barducci, E., Musacchio, D., Manduca, B., Marchese, D., Patrassi, L. A., Pattarino, F. A., Rocchi, M., Briglia, S., Fanelli, R., Villella, M., Gronda, E., Massa, D., Lenti, V., DI Gregorio, L., Bottero, M., Bazzanini, F., Braggion, G., Antoniceli, R., Caraceni, D., Guzzo, V., DI Giovanni, P., Scarpini, S., Severgnini, B., Musolino, M. F., Casa, S. D., Gobbi, M., Arena, G., Bonizzato, S., Agnoletto, V., Sansoni, S., Pes, R. A. M., Denti, S., Polizzi, G. M., Pino, R., Commisso, B., Merlino, A., DI Lorenzo, L., Porchetta, I., Del Furia, F., Colombi, E., Covini, D., Cavalieri, F., Antonaci, S., Rubino, G., Ciulla, A., Bui, F., Casorelli, E., Caliendo, L., Laezza, A., Americo, L., Schillaci, A. M., Cordoni, M., Barsotti, L., Gaudio, C., Barilla, F., Cannone, M., Memeo, R., Truncellito, L., Andriani, A., Salituri, S., Verrina, F., Pafi, M., Sebastiani, M. L., Amico, A. F., Scolozzi, D., Lupi, G., D'Alea, A., Catanzariti, D., Angheben, C., Ottaviano, A., Levantesi, G., de Luca, Leonardo, Musumeci, Giuseppe, Leonardi, Sergio, Gonzini, Lucio, Cavallini, Claudio, Calabrò, Paolo, Mauro, Ciro, Cacciavillani, Luisa, Savonitto, Stefano, de Servi, Stefano, Caporale, Roberto, Ceravolo, Roberto, Formigli, Dario, Lupi, Alessandro, Rakar, Sadir, Smecca, Ivan, Maggioni, Aldo Pietro, Lucci, Donata, Lorimer, Andrea, Orsini, Giampietro, Fabbri, Gianna, Bianchini, Elisa, Abrignani, Maurizio Giuseppe, Bonura, Francesc, Trimarco, Bruno, Galasso, Gennaro, Misuraca, Gianfranco, Manes, Maria Teresa, Tuccillo, Bernardino, and Irace, Luigi.

Subjects
Male, Prasugrel, medicine.medical_treatment, Myocardial Infarction, antithrombotic therapy, 030204 cardiovascular system & hematology, acute coronary syndromes, bivalirudin, heparins, percutaneous coronary intervention, prasugrel, ticagrelor, 0302 clinical medicine, Antithrombotic, 80 and over, Bivalirudin, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, Registries, Aged, 80 and over, General Medicine, Hirudins, Middle Aged, Recombinant Proteins, Italy, Female, Cardiology and Cardiovascular Medicine, Ticagrelor, medicine.drug, medicine.medical_specialty, Platelet Glycoprotein GPIIb-IIIa Complex, NO, 03 medical and health sciences, Percutaneous Coronary Intervention, Internal medicine, medicine, Humans, Acute Coronary Syndrome, Aged, Aspirin, business.industry, Heparin, Percutaneous coronary intervention, Anticoagulants, medicine.disease, Peptide Fragments, Clinical trial, Cross-Sectional Studies, Logistic Models, Conventional PCI, Multivariate Analysis, business
Abstract

Aims In the last decades, several new therapies have emerged for the treatment of acute coronary syndromes (ACS). We sought to describe real-world patterns of use of antithrombotic treatments in the catheterization laboratory for ACS patients undergoing percutaneous coronary interventions (PCI). Methods EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in ACS patients in Italy. Results Over a 3-week period, a total of 2585 consecutive ACS patients have been enrolled in 203 cardiac care units across Italy. Among these patients, 1755 underwent PCI (923 with ST-elevation myocardial infarction and 832 with non-ST-elevation ACS). In the catheterization laboratory, unfractioned heparin was the most used antithrombotic drug in both ST-elevation myocardial infarction (64.7%) and non-ST-elevation ACS (77.5%) undergoing PCI and, as aspirin, bivalirudin and glycoprotein IIb/IIIa inhibitors (GPIs) more frequently employed before or during PCI compared with the postprocedural period. Any crossover of heparin therapy occurred in 36.0% of cases, whereas switching from one P2Y12 inhibitor to another occurred in 3.7% of patients. Multivariable analysis yielded several independent predictors of GPIs and of bivalirudin use in the catheterization laboratory, mainly related to clinical presentation, PCI complexity and presence of complications during the procedure. Conclusion In our contemporary, nationwide, all-comers cohort of ACS patients undergoing PCI, antithrombotic therapies were commonly initiated before the catheterization laboratory. In the periprocedural period, the most frequently employed drugs were unfractioned heparin, leading to a high rate of crossover, followed by GPIs and bivalirudin, mainly used during complex PCI. Clinical trial registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02015624.

Published
2017

6. Properties of the corticostriatal long term depression induced by medial prefrontal cortex high frequency stimulation in vivo

Author

M. Gustavo Murer, Gregorio L. Galiñanes, Barbara Y. Braz, and Juan E. Belforte

Subjects
0301 basic medicine, Hippocampus, PREFRONTAL CORTEX, Striatum, DOPAMINE, Mice, 0302 clinical medicine, Piperidines, Receptor, Cannabinoid, CB1, Neural Pathways, Prefrontal cortex, Long-term depression, Neurons, purl.org/becyt/ford/3.1 [https], Medicina Básica, medicine.anatomical_structure, purl.org/becyt/ford/3 [https], Psychology, Motor cortex, medicine.drug, Heparin-binding EGF-like Growth Factor, CIENCIAS MÉDICAS Y DE LA SALUD, Interneuron, Tyrosine 3-Monooxygenase, Inmunología, Prefrontal Cortex, Mice, Transgenic, Choline O-Acetyltransferase, 03 medical and health sciences, Cellular and Molecular Neuroscience, Adrenergic Agents, Dopamine, medicine, Animals, Oxidopamine, Pharmacology, Long-Term Synaptic Depression, CORTICOSTRIATAL PLASTICITY, Benzazepines, Corpus Striatum, Mice, Inbred C57BL, 030104 developmental biology, NMDA, nervous system, Animals, Newborn, Forebrain, Dopamine Antagonists, Pyrazoles, Dizocilpine Maleate, Neuroscience, Excitatory Amino Acid Antagonists, 030217 neurology & neurosurgery
Abstract

Repetitive stimulation of cognitive forebrain circuits at frequencies capable of inducing corticostriatal long term plasticity is increasingly being used with therapeutic purposes in patients with neuropsychiatric disorders. However, corticostriatal plasticity is rarely studied in the intact brain. Our aim was to study the mechanisms of corticostriatal long term depression (LTD) induced by high frequency stimulation (HFS) of the medial prefrontal cortex in vivo. Our main finding is that the LTD induced in the dorsomedial striatum by medial prefrontal cortex HFS in vivo (prefrontostriatal LTD) is not affected by manipulations that block or reduce the LTD induced in the dorsolateral striatum by motor cortex HFS in brain slices, including pharmacological dopamine receptor and CB1 receptor blockade, chronic nigrostriatal dopamine depletion, CB1 receptor genetic deletion and selective striatal cholinergic interneuron (SCIN) ablation. Conversely, like in the hippocampus and other brain areas, prefrontostriatal LTD is NMDA receptor dependent. Thus, we describe a novel form of corticostriatal LTD that operates in brain circuits involved in reward and cognition and could be relevant for understanding the therapeutic effects of deep brain stimulation. Fil: Braz, Bárbara Yael. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Belforte, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Galiñanes, Gregorio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina

Published
2017

7. Inducible ablation of dopamine D2 receptors in adult mice impairs locomotion, motor skill learning and leads to severe parkinsonism

Author

E P Bello, R Casas-Cordero, Mariano A. Belluscio, Vanina Rodriguez, Gregorio L. Galiñanes, Eric Casey, M Rubinstein, Daniela Noain, and Mario Gustavo Murer

Subjects
Ablation Techniques, Male, 0301 basic medicine, CIENCIAS MÉDICAS Y DE LA SALUD, Dopamine, Neurociencias, Stimulation, Motor Activity, Basal Ganglia, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Parkinsonian Disorders, Basal ganglia, medicine, Animals, Humans, Learning, Molecular Biology, Motor skill, Mice, Knockout, Receptors, Dopamine D2, Receptors, Dopamine D1, Parkinsonism, medicine.disease, Corpus Striatum, Motor coordination, Parkinson'S Disease, Psychiatry and Mental health, Medicina Básica, 030104 developmental biology, Motor Skills, Schizophrenia, Dopamine Antagonists, Motor learning, Psychology, Neuroscience, Locomotion, 030217 neurology & neurosurgery, medicine.drug
Abstract

Motor execution and planning are tightly regulated by dopamine D1 and D2 receptors present in basal ganglia circuits. Although stimulation of D1 receptors is known to enhance motor function, the global effect of D2 receptor (D2R) stimulation or blockade remains highly controversial, with studies showing increasing, decreasing or no changes in motor activity. Moreover, pharmacological and genetic attempts to block or eliminate D2R have led to controversial results that questioned the importance of D2R in motor function. In this study, we generated an inducible Drd2 null-allele mouse strain that circumvented developmental compensations found in constitutive Drd2−/− mice and allowed us to directly evaluate the participation of D2R in spontaneous locomotor activity and motor learning. We have found that loss of D2R during adulthood causes severe motor impairments, including hypolocomotion, deficits in motor coordination, impaired learning of new motor routines and spontaneous catatonia. Moreover, severe motor impairment, resting tremor and abnormal gait and posture, phenotypes reminiscent of Parkinson’s disease, were evident when the mutation was induced in aged mice. Altogether, the conditional Drd2 knockout model studied here revealed the overall fundamental contribution of D2R in motor functions and explains some of the side effects elicited by D2R blockers when used in neurological and psychiatric conditions, including schizophrenia, bipolar disorder, Tourette’s syndrome, dementia, alcohol-induced delusions and obsessive-compulsive disorder. Fil: Bello Gay, Estefania Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina Fil: Casas Cordero, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina Fil: Galiñanes, Gregorio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Casey, Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina Fil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Rodríguez, V. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina Fil: Noain, Daniela Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina

Published
2016

8. Relationship between total hip (TH) BMD T-score and incidence of nonvertebral fracture (NVFX) with up to 10 years of Denosumab (Dmab) treatment

Author

A. Wang, Felicia Cosman, Serge Ferrari, E. M. Lewiecki, Edward Czerwiński, Jacques P. Brown, Jorge Malouf, S. Adami, J-Y Reginster, Nadia Daizadeh, Gregorio L H de, and Rachel B. Wagman

Subjects
medicine.medical_specialty, Denosumab, business.industry, Incidence (epidemiology), medicine, Total hip replacement, Fracture (geology), Urology, General Medicine, Standard score, business, medicine.drug
Published
2016
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9. Striatal gating through up states and oscillations in the basal ganglia: Implications for Parkinson’s disease

Author

Mariela Veronica Escande, Mario Gustavo Murer, Fernando Kasanetz, Pablo E. Pomata, Luis A. Riquelme, Camila Lidia Zold, Mariano A. Belluscio, and Gregorio L. Galiñanes

Subjects
Parkinson's disease, Striatum, Biology, Medium spiny neuron, Indirect pathway of movement, Receptors, N-Methyl-D-Aspartate, Basal Ganglia, Biological Clocks, Dopamine, Physiology (medical), Dopamine receptor D2, Basal ganglia, medicine, Animals, Humans, Excitatory Amino Acid Agents, Neurons, Receptors, Dopamine D2, musculoskeletal, neural, and ocular physiology, General Neuroscience, Parkinson Disease, medicine.disease, Corpus Striatum, nervous system diseases, Globus pallidus, nervous system, Ion Channel Gating, Neuroscience, medicine.drug
Abstract

Up states are a hallmark of striatal physiology. Spontaneous activity in the thalamo-cortical network drives robust plateau depolarizations in the medium spiny projection neurons of the striatum. Medium spiny neuron firing is only possible during up states and is very tightly regulated by dopamine and NMDA receptors. In a rat model of Parkinson's disease the medium spiny neurons projecting to the globus pallidus (indirect pathway) show more depolarized up states and increased firing. This is translated into abnormal patterns of synchronization between the globus pallidus and frontal cortex, which are believed to underlie the symptoms of Parkinson's disease. Here we review our work in the field and propose a mechanism through which the lack of D2 receptor stimulation in the striatum allows the establishment of fixed routes of information flow in the cortico-striato-pallidal network.

Published
2012
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10. Dopamine-Dependent Periadolescent Maturation of Corticostriatal Functional Connectivity in Mouse

Author

Gregorio L. Galiñanes, M. Gustavo Murer, and Irene R. E. Taravini

Subjects
Serotonin, Dopamine, Action Potentials, Stimulation, Striatum, Hyperkinesis, Medium spiny neuron, Article, Mice, chemistry.chemical_compound, Neural Pathways, medicine, Animals, Oxidopamine, Amphetamine, Cerebral Cortex, Neurons, General Neuroscience, Age Factors, Corpus Striatum, Electric Stimulation, Disease Models, Animal, Electrophysiology, medicine.anatomical_structure, Animals, Newborn, chemistry, Cerebral cortex, Psychology, Neuroscience, Locomotion, medicine.drug
Abstract

Altered corticostriatal information processing associated with early dopamine systems dysfunction may contribute to attention deficit/hyperactivity disorder (ADHD). Mice with neonatal dopamine-depleting lesions exhibit hyperactivity that wanes after puberty and is reduced by psychostimulants, reminiscent of some aspects of ADHD. To assess whether the maturation of corticostriatal functional connectivity is altered by early dopamine depletion, we examined preadolescent and postadolescent urethane-anesthetized mice with or without dopamine-depleting lesions. Specifically, we assessed (1) synchronization between striatal neuron discharges and oscillations in frontal cortex field potentials and (2) striatal neuron responses to frontal cortex stimulation. In adult control mice striatal neurons were less spontaneously active, less responsive to cortical stimulation, and more temporally tuned to cortical rhythms than in infants. Striatal neurons from hyperlocomotor mice required more current to respond to cortical input and were less phase locked to ongoing oscillations, resulting in fewer neurons responding to refined cortical commands. By adulthood some electrophysiological deficits waned together with hyperlocomotion, but striatal spontaneous activity remained substantially elevated. Moreover, dopamine-depleted animals showing normal locomotor scores exhibited normal corticostriatal synchronization, suggesting that the lesion allows, but is not sufficient, for the emergence of corticostriatal changes and hyperactivity. Although amphetamine normalized corticostriatal tuning in hyperlocomotor mice, it reduced horizontal activity in dopamine-depleted animals regardless of their locomotor phenotype, suggesting that amphetamine modified locomotion through a parallel mechanism, rather than that modified by dopamine depletion. In summary, functional maturation of striatal activity continues after infancy, and early dopamine depletion delays the maturation of core functional capacities of the corticostriatal system.

Published
2009
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11. Effectiveness and safety of olanzapine in the treatment of schizophrenia among Asian patients switching from conventional antipsychotics

Author

Jian Hu, Tsuo Hung Lan, Byoung Yong Lee, Qiuqing Ang, Zheng Lu, Gavan Harrison, Heather McElroy, C K Chen, and Gregorio L. Diokno

Subjects
Adult, Male, Olanzapine, Dyskinesia, Drug-Induced, Pediatrics, medicine.medical_specialty, Psychosis, medicine.medical_treatment, Benzodiazepines, Asian People, Quality of life, medicine, Asian country, Humans, Prospective Studies, Antipsychotic, Psychiatry, Biological Psychiatry, Psychiatric Status Rating Scales, Pharmacology, business.industry, Dopamine antagonist, medicine.disease, Treatment Outcome, Schizophrenia, Sample Size, Quality of Life, Female, Schizophrenic Psychology, Observational study, business, Antipsychotic Agents, medicine.drug
Abstract

The objectives of this study were: (1) to investigate, in a clinical practice setting, the effectiveness of olanzapine in the treatment of schizophrenia among partially-responding, symptomatic Asian patients who switch from conventional antipsychotic treatment, (2) to assess the safety of olanzapine and (3) to assess the change in quality of life in Asian patients with schizophrenia who switch to olanzapine.Effectiveness, safety and quality of life were assessed in outpatients with schizophrenia (n=1267) who lacked symptomatic control with conventional antipsychotics and were switched to olanzapine therapy. Data for this prospective, observational study were collected for 12 months from Asian patients in China, Hong Kong, the Philippines, South Korea and Taiwan.Significant clinical improvements (P0.05) were observed following 12 months of olanzapine treatment and 87.3% of the subjects responded to treatment at endpoint (i.e. Brief Psychiatric Rating Scale Total score reduced byor =30% relative to baseline; last observation carried forward). Abnormal involuntary movements (mean change in Abnormal Involuntary Movement Scale: -3.20, P0.001) and quality of life were significantly improved in patients treated with olanzapine. However, some patients experienced significant weight gain (3.60+/-4.50 kg, P0.001) with olanzapine treatment, relative to baseline.This study shows that switching to olanzapine may be effective in improving symptoms, may be well-tolerated and may improve the quality of life in Asian patients who are only partially responsive to treatment with conventional antipsychotics. The pragmatic design and naturalistic setting of this large study make the findings relevant for treating patients from some Asian countries in routine clinical practice.

Published
2007
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12. Altered Corticostriatal Connectivity and Exploration/Exploitation Imbalance Emerge as Intermediate Phenotypes for a Neonatal Dopamine Dysfunction

Author

Mario Gustavo Murer, Barbara Y. Braz, Irene Rita Eloisa Taravini, Gregorio L. Galiñanes, and Juan E. Belforte

Subjects
CIENCIAS MÉDICAS Y DE LA SALUD, Dopamine, Neurociencias, Spatial Behavior, Motor Activity, Medium spiny neuron, chemistry.chemical_compound, Mice, Neural Pathways, medicine, Attention deficit hyperactivity disorder, Animals, Foraging, Oxidopamine, Social Behavior, Pharmacology, Cerebral Cortex, Dopaminergic, Cognition, Dendrites, medicine.disease, Immunohistochemistry, Corpus Striatum, Electrodes, Implanted, Psychiatry and Mental health, Medicina Básica, Disease Models, Animal, medicine.anatomical_structure, Phenotype, chemistry, Animals, Newborn, Cerebral cortex, Forebrain, Exploratory Behavior, Original Article, Psychology, Neuroscience, medicine.drug, Juvenile Locomotor Hyperactivity
Abstract

Findings showing that neonatal lesions of the forebrain dopaminergic system in rodents lead to juvenile locomotor hyperactivity and learning deficits have been taken as evidence of face validity for the attention deficit hyperactivity disorder. However, the core cognitive and physiological intermediate phenotypes underlying this rodent syndrome remain unknown. Here we show that early postnatal dopaminergic lesions cause long-lasting deficits in exploitation of shelter, social and nutritional resources, and an imbalanced exploratory behavior, where nondirected local exploration is exacerbated, whereas sophisticated search behaviors involving sequences of goal directed actions are degraded. Importantly, some behavioral deficits do not diminish after adolescence but instead worsen or mutate, particularly those related to the exploration of wide and spatially complex environments. The in vivo electrophysiological recordings and morphological reconstructions of striatal medium spiny neurons reveal corticostriatal alterations associated to the behavioral phenotype. More specifically, an attenuation of corticostriatal functional connectivity, affecting medial prefrontal inputs more markedly than cingulate and motor inputs, is accompanied by a contraction of the dendritic arbor of striatal projection neurons in this animal model. Thus, dopaminergic neurons are essential during postnatal development for the functional and structural maturation of corticostriatal connections. From a bottom-up viewpoint, our findings suggest that neuropsychiatric conditions presumably linked to developmental alterations of the dopaminergic system should be evaluated for deficits in foraging decision making, alterations in the recruitment of corticostriatal circuits during foraging tasks, and structural disorganization of the frontostriatal connections. Fil: Braz, Bárbara Yael. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Galiñanes, Gregorio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Ginebra; Suiza Fil: Taravini, Irene Rita Eloisa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Belforte, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina

Published
2015

13. Denosumab treatment in postmenopausal women with osteoporosis does not interfere with fracture-healing: results from the FREEDOM trial

Author

Joseph M. Lane, Mohit Bhandari, S. Adami, Daniel Uebelhart, G. P. Lyritis, Cummings, C Roux, Heinrich R, N. Gilchrist, Karel Pavelka, Cesar Libanati, Andrea Wang, Steven Boonen, Jonathan D. Adachi, de Gregorio L, Ethel S. Siris, G. Möller, Santiago Palacios, and P.R. Ho

Subjects
Bone density, Osteoporosis, Fracture Fixation, Internal, Absorptiometry, Photon, Bone Density, Fracture Fixation, Reference Values, Fracture fixation, Monoclonal, 80 and over, Orthopedics and Sports Medicine, Prospective Studies, Prospective cohort study, Humanized, Osteoporosis, Postmenopausal, Aged, 80 and over, Fracture Healing, Aged, Antibodies, Monoclonal, Humanized, Bone Density Conservation Agents, Chi-Square Distribution, Denosumab, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Fractures, Spontaneous, Humans, Injections, Subcutaneous, Middle Aged, Risk Assessment, Spinal Fractures, Treatment Outcome, Subcutaneous, General Medicine, Photon, Postmenopausal, Drug, medicine.drug, medicine.medical_specialty, Nonunion, Bone healing, Placebo, Antibodies, Injections, Dose-Response Relationship, medicine, Absorptiometry, business.industry, Spontaneous, medicine.disease, Internal, Surgery, business, Fractures
Abstract

Background: Fracture is the major complication of osteoporosis, and it allows the identification of individuals needing medical intervention for osteoporosis. After nonvertebral fracture, patients often do not receive osteoporosis medical treatment despite evidence that this treatment reduces the risk of subsequent fracture. In this preplanned analysis of the results of the three-year, placebo-controlled FREEDOM trial, we evaluated the effect of denosumab administration on fracture-healing to address theoretical concerns related to initiating or continuing denosumab therapy in patients presenting with a nonvertebral fracture. Methods: Postmenopausal women aged sixty to ninety years with osteoporosis were randomized to receive 60 mg of denosumab (n = 3902) or a placebo (n = 3906) subcutaneously every six months for three years. Investigators reported complications associated with a fracture or its management and with fracture-healing for all nonvertebral fractures that occurred during the study. Delayed healing was defined as incomplete fracture-healing six months after the fracture. Results: Six hundred and sixty-seven subjects (303 treated with denosumab and 364 who received a placebo) had a total of 851 nonvertebral fractures (386 in the denosumab group and 465 in the placebo group), including 199 fractures (seventy-nine in the denosumab group and 120 in the placebo group) that were treated surgically. Delayed healing was reported in seven subjects (two in the denosumab group and five in the placebo group), including one with subsequent nonunion (in the placebo group). Neither delayed healing nor nonunion was observed in any subject who had received denosumab within six weeks preceding or following the fracture. A complication associated with the fracture or intervention occurred in five subjects (2%) and twenty subjects (5%) in the denosumab and placebo groups, respectively (p = 0.009). Conclusions: Denosumab in a dose of 60 mg every six months does not seem to delay fracture-healing or contribute to other complications, even when it is administered at or near the time of the fracture. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Published
2012

14. Origin and properties of striatal local field potential responses to cortical stimulation: temporal regulation by fast inhibitory connections

Author

Barbara Y. Braz, Gregorio L. Galiñanes, and Mario Gustavo Murer

Subjects
Male, Central Nervous System, Silicon, Anatomy and Physiology, Mouse, Neural Networks, Neural facilitation, lcsh:Medicine, Action Potentials, Neurophysiology, Evoked field, Local field potential, Inhibitory postsynaptic potential, Medium spiny neuron, Synaptic Transmission, Neurological System, chemistry.chemical_compound, Mice, Model Organisms, Receptors, GABA, medicine, Animals, lcsh:Science, Electrodes, Evoked Potentials, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Biology, Cerebral Cortex, Neurons, Motor Systems, Multidisciplinary, GABAA receptor, lcsh:R, Neural Inhibition, Animal Models, Neurotransmitters, Bicuculline, Corpus Striatum, Electrophysiology, chemistry, nervous system, CNQX, lcsh:Q, Neuroscience, medicine.drug, Research Article, Nervous System Physiology
Abstract

Evoked striatal field potentials are seldom used to study corticostriatal communication in vivo because little is known about their origin and significance. Here we show that striatal field responses evoked by stimulating the prelimbic cortex in mice are reduced by more than 90% after infusing the AMPA receptor antagonist CNQX close to the recording electrode. Moreover, the amplitude of local field responses and dPSPs recorded in striatal medium spiny neurons increase in parallel with increasing stimulating current intensity. Finally, the evoked striatal fields show several of the basic known properties of corticostriatal transmission, including paired pulse facilitation and topographical organization. As a case study, we characterized the effect of local GABA(A) receptor blockade on striatal field and multiunitary action potential responses to prelimbic cortex stimulation. Striatal activity was recorded through a 24 channel silicon probe at about 600 µm from a microdialysis probe. Intrastriatal administration of the GABA(A) receptor antagonist bicuculline increased by 65±7% the duration of the evoked field responses. Moreover, the associated action potential responses were markedly enhanced during bicuculline infusion. Bicuculline enhancement took place at all the striatal sites that showed a response to cortical stimulation before drug infusion, but sites showing no field response before bicuculline remained unresponsive during GABA(A) receptor blockade. Thus, the data demonstrate that fast inhibitory connections exert a marked temporal regulation of input-output transformations within spatially delimited striatal networks responding to a cortical input. Overall, we propose that evoked striatal fields may be a useful tool to study corticostriatal synaptic connectivity in relation to behavior.

Published
2011

15. Predictors of opioid prescribing for non-malignant low back pain in an italian primary care setting

Author

Valeria Conti, Marianna Fogliasecca, Alfredo Valente, Pasquale Dolce, Anna Citarella, Teresa Iannaccone, Luigi Di Gregorio, Valentina Manzo, Bernardo Toraldo, Vincenzo Passaro, Simona Cammarota, Graziamaria Corbi, Cammarota, S., Conti, V., Corbi, G., Di Gregorio, L., Dolce, P., Fogliasecca, M., Iannaccone, T., Manzo, V., Passaro, V., Toraldo, B., Valente, A., and Citarella, A.

Subjects
medicine.medical_specialty, Lower back pain, Non-steroidal anti-inflammatory drugs, Opioid, Primary care, Article, Internal medicine, Statistical significance, medicine, Non-steroidal anti-inflammatory drug, Medical prescription, Asthma, business.industry, Medical record, General Medicine, Odds ratio, medicine.disease, Low back pain, Confidence interval, Medicine, medicine.symptom, business, medicine.drug
Abstract

This study explores which patient characteristics could affect the likelihood of starting low back pain (LBP) treatment with opioid analgesics vs. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in an Italian primary care setting. Through the computerized medical records of 65 General Practitioners, non-malignant LBP subjects who received the first pain intensity measurement and an NSAID or opioid prescription, during 2015–2016, were identified. Patients with an opioid prescription 1-year before the first pain intensity measurement were excluded. A multivariable logistic regression model was used to determine predictive factors of opioid prescribing. Results were reported as Odds Ratios (ORs) with a 95% confidence interval (CI), with p &lt, 0.05 indicating statistical significance. A total of 505 individuals with LBP were included: of those, 72.7% received an NSAID prescription and 27.3% an opioid one (64% of subjects started with strong opioid). Compared to patients receiving an NSAID, those with opioid prescriptions were younger, reported the highest pain intensity (moderate pain OR = 2.42, 95% CI 1.48–3.96 and severe pain OR = 2.01, 95% CI 1.04–3.88) and were more likely to have asthma (OR 3.95, 95% CI 1.99–7.84). Despite clinical guidelines, a large proportion of LBP patients started with strong opioid therapy. Asthma, younger age and pain intensity were predictors of opioid prescribing when compared to NSAIDs for LBP treatment.

Published
2021

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