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153 results on '"Pani L"'

1. Scaling up health knowledge at European level requires sharing integrated data: an approach for collection of database specification

Author

Menditto E, Bolufer de Gea A, Cahir C, Marengoni A, Riegler S, Fico G, Costa E, Monaco A, Pecorelli S, Pani L, and Prados-Torres A

Subjects
healthcare-databases, adherence, electronic health records, outcome research, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Enrica Menditto,1 Angela Bolufer De Gea,2 Caitriona Cahir,3,4 Alessandra Marengoni,5 Salvatore Riegler,1 Giuseppe Fico,6 Elisio Costa,7 Alessandro Monaco,8 Sergio Pecorelli,5 Luca Pani,8 Alexandra Prados-Torres9 1School of Pharmacy, CIRFF/Center of Pharmacoeconomics, University of Naples Federico II, Naples, Italy; 2Directorate-General for Health and Food Safety, European Commission, Brussels, Belgium; 3Division of Population Health Sciences, Royal College of Surgeons in Ireland, 4Department of Pharmacology and Therapeutics, St James’s Hospital, Dublin, Ireland; 5Department of Clinical and Experimental Science, University of Brescia, Brescia; 6Life Supporting Technologies, Photonics Technology and Bioengineering Department, School of Telecomunications Engineering, Polytechnic University of Madrid, Madrid, Spain; 7Faculty of Pharmacy, University of Porto, Porto, Portugal; 8Italian Medicines Agency – AIFA, Rome, Italy; 9EpiChron Research Group on Chronic Diseases, Aragón Health Sciences Institute (IACS), IIS Aragón REDISSEC ISCIII, Miguel Servet University Hospital, University of Zaragoza, Zaragoza, Spain Abstract: Computerized health care databases have been widely described as an excellent opportunity for research. The availability of “big data” has brought about a wave of innovation in projects when conducting health services research. Most of the available secondary data sources are restricted to the geographical scope of a given country and present heterogeneous structure and content. Under the umbrella of the European Innovation Partnership on Active and Healthy Ageing, collaborative work conducted by the partners of the group on “adherence to prescription and medical plans” identified the use of observational and large-population databases to monitor medication-taking behavior in the elderly. This article describes the methodology used to gather the information from available databases among the Adherence Action Group partners with the aim of improving data sharing on a European level. A total of six databases belonging to three different European countries (Spain, Republic of Ireland, and Italy) were included in the analysis. Preliminary results suggest that there are some similarities. However, these results should be applied in different contexts and European countries, supporting the idea that large European studies should be designed in order to get the most of already available databases. Keywords: health care databases, adherence, electronic health records, outcome research

Published
2016

3. HTA307 Evolving Principles for Defining and Assessing the Economic and Societal Value of Cancer Therapies

Author

Lee, M., primary, Abrams, K., additional, Baird, A.M., additional, Brown, S., additional, Bruns, J., additional, Clark, R., additional, Cortes, J., additional, Curigliano, G., additional, Ferris, A., additional, Garrison, L., additional, Lyman, G., additional, Pani, L., additional, Kanesvaran, R., additional, Pemberton-Whiteley, Z., additional, Salmonson, T., additional, Sawicki, P., additional, Stein, B., additional, Suh, D., additional, Velikova, G., additional, and Grueger, J., additional

Published
2023
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4. The future is now: Model‐based clinical trial design for Alzheimer's disease

Author

Romero, K, Ito, K, Rogers, JA, Polhamus, D, Qiu, R, Stephenson, D, Mohs, R, Lalonde, R, Sinha, V, Wang, Y, Brown, D, Isaac, M, Vamvakas, S, Hemmings, R, Pani, L, Bain, LJ, Corrigan, B, and Diseases**, Alzheimer's Disease Neuroimaging Initiative for the Coalition Against Major

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Neurosciences, Dementia, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Brain Disorders, Neurodegenerative, Alzheimer's Disease, Clinical Trials and Supportive Activities, Aging, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Neurological, Alzheimer Disease, Clinical Trials as Topic, Computer Simulation, Drug Approval, Europe, Humans, United States, United States Food and Drug Administration, Alzheimer's Disease Neuroimaging Initiative, Coalition Against Major Diseases, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

Failures in trials for Alzheimer's disease (AD) may be attributable to inadequate dosing, population selection, drug inefficacy, or insufficient design optimization. The Coalition Against Major Diseases (CAMD) was formed in 2008 to develop drug development tools (DDT) to expedite drug development for AD and Parkinson's disease. CAMD led a process that successfully advanced a clinical trial simulation (CTS) tool for AD through the formal regulatory review process at the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).

Published
2015

7. Efficacy of esmethadone in patients with major depressive disorder and antidepressant tolerance (antidepressant tachyphylaxis)

Author

Fava, M., primary, Stahl, S.M., additional, Pani, L., additional, De Martin, S., additional, Guidetti, C., additional, Alimonti, A., additional, Comai, S., additional, Mattarei, A., additional, Folli, F., additional, Bushnell, D., additional, O'Gorman, C., additional, Traversa, S., additional, Inturrisi, C.E., additional, Manfredi, P.L., additional, and Pappagallo, M., additional

Published
2023
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8. A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Author

Sforzini, L, Worrell, C, Kose, M, Anderson, IM, Aouizerate, B, Arolt, V, Bauer, M, Baune, BT, Blier, P, Cleare, AJ, Cowen, PJ, Dinan, TG, Fagiolini, A, Ferrier, IN, Hegerl, U, Krystal, AD, Leboyer, M, McAllister-Williams, RH, McIntyre, RS, Meyer-Lindenberg, A, Miller, AH, Nemeroff, CB, Normann, C, Nutt, D, Pallanti, S, Pani, L, Penninx, BWJH, Schatzberg, AF, Shelton, RC, Yatham, LN, Young, AH, Zahn, R, Aislaitner, G, Butlen-Ducuing, F, Fletcher, C, Haberkamp, M, Laughren, T, Mantyla, F-L, Schruers, K, Thomson, A, Arteaga-Henriquez, G, Benedetti, F, Cash-Gibson, L, Chae, WR, De Smedt, H, Gold, SM, Hoogendijk, WJG, Mondragon, VJ, Maron, E, Martynowicz, J, Melloni, E, Otte, C, Perez-Fuentes, G, Poletti, S, Schmidt, ME, van de Ketterij, E, Woo, K, Flossbach, Y, Ramos-Quiroga, JA, Savitz, AJ, Pariante, CM, Sforzini, L, Worrell, C, Kose, M, Anderson, IM, Aouizerate, B, Arolt, V, Bauer, M, Baune, BT, Blier, P, Cleare, AJ, Cowen, PJ, Dinan, TG, Fagiolini, A, Ferrier, IN, Hegerl, U, Krystal, AD, Leboyer, M, McAllister-Williams, RH, McIntyre, RS, Meyer-Lindenberg, A, Miller, AH, Nemeroff, CB, Normann, C, Nutt, D, Pallanti, S, Pani, L, Penninx, BWJH, Schatzberg, AF, Shelton, RC, Yatham, LN, Young, AH, Zahn, R, Aislaitner, G, Butlen-Ducuing, F, Fletcher, C, Haberkamp, M, Laughren, T, Mantyla, F-L, Schruers, K, Thomson, A, Arteaga-Henriquez, G, Benedetti, F, Cash-Gibson, L, Chae, WR, De Smedt, H, Gold, SM, Hoogendijk, WJG, Mondragon, VJ, Maron, E, Martynowicz, J, Melloni, E, Otte, C, Perez-Fuentes, G, Poletti, S, Schmidt, ME, van de Ketterij, E, Woo, K, Flossbach, Y, Ramos-Quiroga, JA, Savitz, AJ, and Pariante, CM

Abstract

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Published
2022

14. Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

Author

Ascione, A, De Luca, M, Melazzini, M, Montilla, S, Trotta, M, Petta, S, Puoti, M, Sangiovanni, V, Messina, V, Bruno, S, Izzi, A, Villa, E, Aghemo, A, Zignego, A, Orlandini, A, Fontanella, L, Gasbarrini, A, Marzioni, M, Giannini, E, Craxi, A, Abbati, G, Alberti, A, Andreone, P, Andreoni, M, Angeli, P, Angelico, M, Angarano, G, Angrisani, D, Antinori, A, Antonini, C, Avancini, I, Barone, M, Bruno, R, Benedetti, A, Bernabucci, V, Blanc, P, Boarini, C, Boffa, N, Boglione, L, Borghi, V, Borgia, G, Brancaccio, G, Brunetto, M, Cacciola, I, Calabrese, P, Calvaruso, V, Campagnolo, D, Canovari, B, Caporaso, N, Capra, F, Carolo, G, Cassola, G, Castelli, F, Cauda, R, Silberstein, F, Cecere, R, Chessa, L, Chiodera, A, Chirianni, A, Ciancio, A, Cima, S, Coco, B, Colombo, M, Coppola, N, Corti, G, Cosco, L, Corradori, S, Cozzolongo, R, Cristaudo, A, Danieli, E, Monforte, A, Monache, M, Del Poggio, P, de Luca, A, Dentone, C, Di Biagio, A, Di Leo, A, Di Perri, G, Di Stefano, M, D'Offizi, G, Donato, F, Durante, E, Erne, E, Fagiuoli, S, Falasca, K, Federico, A, Felder, M, Ferrari, C, Gaeta, G, Ganga, R, Gatti, P, Giacomet, V, Giacometti, A, Gianstefani, A, Giordani, M, Giorgini, A, Grieco, A, Guerra, M, Gulminetti, R, Ieluzzi, D, Imparato, M, Iodice, V, La Monica, S, Lazzarin, A, Lenzi, M, Levrero, M, Lichtner, M, Lionetti, R, Guercio, C, Madonna, S, Magnani, S, Maida, I, Marignani, M, Marrone, A, Marsetti, F, Martini, S, Masarone, M, Maserati, R, Mastroianni, C, Memoli, M, Menzaghi, B, Merli, M, Miele, L, Milella, M, Mondelli, M, Montalbano, M, Monti, M, Morelli, O, Morisco, F, Nardone, G, Novara, S, Onnelli, G, Onofrio, M, Paganin, S, Pani, L, Parisi, M, Parruti, G, Pasquazzi, C, Pasulo, L, Perno, C, Persico, M, Piai, G, Picciotto, A, Pigozzi, G, Piovesan, S, Piras, M, Pirisi, M, Piscaglia, A, Ponti, L, Potenza, D, Pravadelli, C, Quartini, M, Quirino, T, Raimondo, G, Rapaccini, G, Rendina, M, Rizzardini, G, Rizzetto, M, Rizzo, S, Romagnoli, D, Romano, A, Rossi, C, Rumi, M, Russello, M, Russo, F, Russo, M, Sansonno, D, Santantonio, T, Saracco, G, Schimizzi, A, Serviddio, G, Simeone, F, Solinas, A, Soria, A, Tabone, M, Taliani, G, Tarantino, G, Tarquini, P, Tavio, M, Termite, A, Teti, E, Toniutto, P, Torti, C, Tundi, P, Vecchiet, G, Verucchi, G, Gentilucci, U, Vinci, M, Vullo, V, Zolfino, T, Zuin, M, Ascione A., De Luca M., Melazzini M., Montilla S., Trotta M. P., Petta S., Puoti M., Sangiovanni V., Messina V., Bruno S., Izzi A., Villa E., Aghemo A., Zignego A. L., Orlandini A., Fontanella L., Gasbarrini A., Marzioni M., Giannini E. G., Craxi A., Abbati G., Alberti A., Andreone P., Andreoni M., Angeli P., Angelico M., Angarano G., Angrisani D., Antinori A., Antonini C., Avancini I., Barone M., Bruno R., Benedetti A., Bernabucci V., Blanc P., Boarini C., Boffa N., Boglione L., Borghi V., Borgia G., Brancaccio G., Brunetto M., Cacciola I., Calabrese P., Calvaruso V., Campagnolo D., Canovari B., Caporaso N., Capra F., Carolo G., Cassola G., Castelli F., Cauda R., Silberstein F. C., Cecere R., Chessa L., Chiodera A., Chirianni A., Ciancio A., Cima S., Coco B., Colombo M., Coppola N., Corti G., Cosco L., Corradori S., Cozzolongo R., Cristaudo A., Danieli E., Monforte A. D. A., Monache M., Del Poggio P., de Luca A., Dentone C., Di Biagio A., Di Leo A., Di Perri G., Di Stefano M., D'Offizi G., Donato F., Durante E., Erne E., Fagiuoli S., Falasca K., Federico A., Felder M., Ferrari C., Gaeta G. B., Ganga R., Gatti P., Giacomet V., Giacometti A., Gianstefani A., Giordani M., Giorgini A., Grieco A., Guerra M., Gulminetti R., Ieluzzi D., Imparato M., Iodice V., La Monica S., Lazzarin A., Lenzi M., Levrero M., Lichtner M., Lionetti R., Guercio C. L., Madonna S., Magnani S., Maida I., Marignani M., Marrone A., Marsetti F., Martini S., Masarone M., Maserati R., Mastroianni C. M., Memoli M., Menzaghi B., Merli M., Miele L., Milella M., Mondelli M., Montalbano M., Monti M., Morelli O., Morisco F., Nardone G., Novara S., Onnelli G., Onofrio M., Paganin S., Pani L., Parisi M. R., Parruti G., Pasquazzi C., Pasulo L., Perno C. F., Persico M., Piai G., Picciotto A., Pigozzi G. M., Piovesan S., Piras M. C., Pirisi M., Piscaglia A. M., Ponti L., Potenza D., Pravadelli C., Quartini M., Quirino T., Raimondo G., Rapaccini G. L., Rendina M., Rizzardini G., Rizzetto M., Rizzo S., Romagnoli D., Romano A., Rossi C., Rumi M. G., Russello M., Russo F. P., Russo M. L., Sansonno D. E., Santantonio T. A., Saracco G., Schimizzi A. M., Serviddio G., Simeone F., Solinas A., Soria A., Tabone M., Taliani G., Tarantino G., Tarquini P., Tavio M., Termite A., Teti E., Toniutto P., Torti C., Tundi P., Vecchiet G., Verucchi G., Gentilucci U. V., Vinci M., Vullo V., Zolfino T., Zuin M., Ascione, A, De Luca, M, Melazzini, M, Montilla, S, Trotta, M, Petta, S, Puoti, M, Sangiovanni, V, Messina, V, Bruno, S, Izzi, A, Villa, E, Aghemo, A, Zignego, A, Orlandini, A, Fontanella, L, Gasbarrini, A, Marzioni, M, Giannini, E, Craxi, A, Abbati, G, Alberti, A, Andreone, P, Andreoni, M, Angeli, P, Angelico, M, Angarano, G, Angrisani, D, Antinori, A, Antonini, C, Avancini, I, Barone, M, Bruno, R, Benedetti, A, Bernabucci, V, Blanc, P, Boarini, C, Boffa, N, Boglione, L, Borghi, V, Borgia, G, Brancaccio, G, Brunetto, M, Cacciola, I, Calabrese, P, Calvaruso, V, Campagnolo, D, Canovari, B, Caporaso, N, Capra, F, Carolo, G, Cassola, G, Castelli, F, Cauda, R, Silberstein, F, Cecere, R, Chessa, L, Chiodera, A, Chirianni, A, Ciancio, A, Cima, S, Coco, B, Colombo, M, Coppola, N, Corti, G, Cosco, L, Corradori, S, Cozzolongo, R, Cristaudo, A, Danieli, E, Monforte, A, Monache, M, Del Poggio, P, de Luca, A, Dentone, C, Di Biagio, A, Di Leo, A, Di Perri, G, Di Stefano, M, D'Offizi, G, Donato, F, Durante, E, Erne, E, Fagiuoli, S, Falasca, K, Federico, A, Felder, M, Ferrari, C, Gaeta, G, Ganga, R, Gatti, P, Giacomet, V, Giacometti, A, Gianstefani, A, Giordani, M, Giorgini, A, Grieco, A, Guerra, M, Gulminetti, R, Ieluzzi, D, Imparato, M, Iodice, V, La Monica, S, Lazzarin, A, Lenzi, M, Levrero, M, Lichtner, M, Lionetti, R, Guercio, C, Madonna, S, Magnani, S, Maida, I, Marignani, M, Marrone, A, Marsetti, F, Martini, S, Masarone, M, Maserati, R, Mastroianni, C, Memoli, M, Menzaghi, B, Merli, M, Miele, L, Milella, M, Mondelli, M, Montalbano, M, Monti, M, Morelli, O, Morisco, F, Nardone, G, Novara, S, Onnelli, G, Onofrio, M, Paganin, S, Pani, L, Parisi, M, Parruti, G, Pasquazzi, C, Pasulo, L, Perno, C, Persico, M, Piai, G, Picciotto, A, Pigozzi, G, Piovesan, S, Piras, M, Pirisi, M, Piscaglia, A, Ponti, L, Potenza, D, Pravadelli, C, Quartini, M, Quirino, T, Raimondo, G, Rapaccini, G, Rendina, M, Rizzardini, G, Rizzetto, M, Rizzo, S, Romagnoli, D, Romano, A, Rossi, C, Rumi, M, Russello, M, Russo, F, Russo, M, Sansonno, D, Santantonio, T, Saracco, G, Schimizzi, A, Serviddio, G, Simeone, F, Solinas, A, Soria, A, Tabone, M, Taliani, G, Tarantino, G, Tarquini, P, Tavio, M, Termite, A, Teti, E, Toniutto, P, Torti, C, Tundi, P, Vecchiet, G, Verucchi, G, Gentilucci, U, Vinci, M, Vullo, V, Zolfino, T, Zuin, M, Ascione A., De Luca M., Melazzini M., Montilla S., Trotta M. P., Petta S., Puoti M., Sangiovanni V., Messina V., Bruno S., Izzi A., Villa E., Aghemo A., Zignego A. L., Orlandini A., Fontanella L., Gasbarrini A., Marzioni M., Giannini E. G., Craxi A., Abbati G., Alberti A., Andreone P., Andreoni M., Angeli P., Angelico M., Angarano G., Angrisani D., Antinori A., Antonini C., Avancini I., Barone M., Bruno R., Benedetti A., Bernabucci V., Blanc P., Boarini C., Boffa N., Boglione L., Borghi V., Borgia G., Brancaccio G., Brunetto M., Cacciola I., Calabrese P., Calvaruso V., Campagnolo D., Canovari B., Caporaso N., Capra F., Carolo G., Cassola G., Castelli F., Cauda R., Silberstein F. C., Cecere R., Chessa L., Chiodera A., Chirianni A., Ciancio A., Cima S., Coco B., Colombo M., Coppola N., Corti G., Cosco L., Corradori S., Cozzolongo R., Cristaudo A., Danieli E., Monforte A. D. A., Monache M., Del Poggio P., de Luca A., Dentone C., Di Biagio A., Di Leo A., Di Perri G., Di Stefano M., D'Offizi G., Donato F., Durante E., Erne E., Fagiuoli S., Falasca K., Federico A., Felder M., Ferrari C., Gaeta G. B., Ganga R., Gatti P., Giacomet V., Giacometti A., Gianstefani A., Giordani M., Giorgini A., Grieco A., Guerra M., Gulminetti R., Ieluzzi D., Imparato M., Iodice V., La Monica S., Lazzarin A., Lenzi M., Levrero M., Lichtner M., Lionetti R., Guercio C. L., Madonna S., Magnani S., Maida I., Marignani M., Marrone A., Marsetti F., Martini S., Masarone M., Maserati R., Mastroianni C. M., Memoli M., Menzaghi B., Merli M., Miele L., Milella M., Mondelli M., Montalbano M., Monti M., Morelli O., Morisco F., Nardone G., Novara S., Onnelli G., Onofrio M., Paganin S., Pani L., Parisi M. R., Parruti G., Pasquazzi C., Pasulo L., Perno C. F., Persico M., Piai G., Picciotto A., Pigozzi G. M., Piovesan S., Piras M. C., Pirisi M., Piscaglia A. M., Ponti L., Potenza D., Pravadelli C., Quartini M., Quirino T., Raimondo G., Rapaccini G. L., Rendina M., Rizzardini G., Rizzetto M., Rizzo S., Romagnoli D., Romano A., Rossi C., Rumi M. G., Russello M., Russo F. P., Russo M. L., Sansonno D. E., Santantonio T. A., Saracco G., Schimizzi A. M., Serviddio G., Simeone F., Solinas A., Soria A., Tabone M., Taliani G., Tarantino G., Tarquini P., Tavio M., Termite A., Teti E., Toniutto P., Torti C., Tundi P., Vecchiet G., Verucchi G., Gentilucci U. V., Vinci M., Vullo V., Zolfino T., and Zuin M.

Abstract

Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12 weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5 g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2 mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.

Published
2018

15. The Italian compassionate use of sofosbuvir in HCV patients waitlisted for liver transplantation: A national real-life experience

Author

Martini, S, Donato, M, Mazzarelli, C, Rendina, M, Visco-Comandini, U, Fili, D, Gianstefani, A, Fagiuoli, S, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Carrai, P, Caraceni, P, Angeli, P, Ballardini, G, Bernabucci, V, Bhoori, S, Burra, P, Civolani, A, D'Offizi, G, Felder, M, Gaeta, G, Ganga, R, Ginanni Corradini, S, Iemmolo, R, Lenci, I, Lionetti, R, Montalbano, M, Morelli, M, Picciotto, A, Sapere, C, Serviddio, G, Tame, M, Verucchi, G, Zignego, A, Martini S., Donato M. F., Mazzarelli C., Rendina M., Visco-Comandini U., Fili D., Gianstefani A., Fagiuoli S., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Carrai P., Caraceni P., Angeli P., Ballardini G., Bernabucci V., Bhoori S., Burra P., Civolani A., D'Offizi G., Felder M., Gaeta G. B., Ganga R., Ginanni Corradini S., Iemmolo R. M., Lenci I., Lionetti R., Montalbano M., Morelli M. C., Picciotto A., Sapere C., Serviddio G., Tame M., Verucchi G., Zignego A. L., Martini, S, Donato, M, Mazzarelli, C, Rendina, M, Visco-Comandini, U, Fili, D, Gianstefani, A, Fagiuoli, S, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Carrai, P, Caraceni, P, Angeli, P, Ballardini, G, Bernabucci, V, Bhoori, S, Burra, P, Civolani, A, D'Offizi, G, Felder, M, Gaeta, G, Ganga, R, Ginanni Corradini, S, Iemmolo, R, Lenci, I, Lionetti, R, Montalbano, M, Morelli, M, Picciotto, A, Sapere, C, Serviddio, G, Tame, M, Verucchi, G, Zignego, A, Martini S., Donato M. F., Mazzarelli C., Rendina M., Visco-Comandini U., Fili D., Gianstefani A., Fagiuoli S., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Carrai P., Caraceni P., Angeli P., Ballardini G., Bernabucci V., Bhoori S., Burra P., Civolani A., D'Offizi G., Felder M., Gaeta G. B., Ganga R., Ginanni Corradini S., Iemmolo R. M., Lenci I., Lionetti R., Montalbano M., Morelli M. C., Picciotto A., Sapere C., Serviddio G., Tame M., Verucchi G., and Zignego A. L.

Abstract

Background & Aims: This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. Methods: Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. Results: Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for <4 weeks or still viraemic at transplant: 34 patients continued treatment after LT (bridging therapy) (SVR12: 88%), while 15 stopped treatment (SVR12: 53%). 98 patients completed SOF/R without LT (SVR12: 73%). In patients with advanced decompensated cirrhosis (basal MELD ≥15 and/or C-P ≥B8), a marked improvement of the scores occurred in about 50% of cases and almost 20% of decompensated patients without HCC reached a condition suitable for inactivation and delisting. Conclusions: These real-life data indicate that in waitlisted patients: (i) bridging antiviral therapy can be an option for patients still viraemic or negative <4 weeks at LT; and (ii) clinical improvement to a condition suitable for delisting can occur even in patients with advanced decompensated cirrhosis.

Published
2018

18. Nutraceuticals: opening the debate for a regulatory framework

Author

Santini A., Cammarata S. M., Capone G., Ianaro A., Tenore G. C., Pani L., Novellino E., Santini, A., Cammarata, S. M., Capone, G., Ianaro, A., Tenore, G. C., Pani, L., and Novellino, E.

Subjects
claim, Functional Food, label, health, regulation, nutraceutical, regulatory, Legislation, Food, Dietary Supplement, Human, Diet
Abstract

Currently, nutraceuticals do not have a specific definition distinct from those of other food-derived categories, such as food supplements, herbal products, pre- and probiotics, functional foods, and fortified foods. Many studies have led to an understanding of the potential mechanisms of action of pharmaceutically active components contained in food that may improve health and reduce the risk of pathological conditions while enhancing overall well-being. Nevertheless, there is a lack of clear information and, often, the claimed health benefits may not be properly substantiated by safety and efficacy information or in vitro and in vivo data, which can induce false expectations and miss the target for a product to be effective, as claimed. An officially shared and accepted definition of nutraceuticals is still missing, as nutraceuticals are mostly referred to as pharma-foods, a powerful toolbox to be used beyond the diet but before the drugs to prevent and treat pathological conditions, such as in subjects who may not yet be eligible for conventional pharmaceutical therapy. Hence, it is of utmost importance to have a proper and unequivocal definition of nutraceuticals and shared regulations. It also seems wise to assess the safety, mechanism of action and efficacy of nutraceuticals with clinical data. A growing demand exists for nutraceuticals, which seem to reside in the grey area between pharmaceuticals and food. Nonetheless, given specific legislation from different countries, nutraceuticals are experiencing challenges with safety and health claim substantiation.

Published
2018

19. The Italian compassionate use of sofosbuvir observational cohort study for the treatment of recurrent hepatitis C: clinical and virological outcomes

Author

Carrai, P, Morelli, C, Cordone, G, Romano, A, Tame, M, Lionetti, R, Pietrosi, G, Lenci, I, Piai, G, Russo, F, Coppola, C, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Martini, S, Toniutto, P, Bandiera, F, Bhoori, S, Brillanti, S, Burra, P, Corsale, S, De Luca, A, Fagiuoli, S, Fattovich, G, Fava, G, Felder, M, Forte, P, Galeota-Lanza, A, Gitto, S, Grieco, A, Grossi, P, Ialungo, A, Iemmolo, R, Loiacono, L, Mangia, A, Merli, M, Piacentini, A, Pellicelli, A, Rigamonti, C, Gabriella, V, Zignego, A, Carrai P., Morelli C., Cordone G., Romano A., Tame M., Lionetti R., Pietrosi G., Lenci I., Piai G., Russo F. P., Coppola C., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Martini S., Toniutto P., Bandiera F., Bhoori S., Brillanti S., Burra P., Corsale S., De Luca A., Fagiuoli S., Fattovich G., Fava G., Felder M., Forte P., Galeota-Lanza A., Gitto S., Grieco A., Grossi P., Ialungo A. M., Iemmolo R. M., Loiacono L., Mangia A., Merli M., Piacentini A., Pellicelli A., Rigamonti C., Gabriella V., Zignego A. L., Carrai, P, Morelli, C, Cordone, G, Romano, A, Tame, M, Lionetti, R, Pietrosi, G, Lenci, I, Piai, G, Russo, F, Coppola, C, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Martini, S, Toniutto, P, Bandiera, F, Bhoori, S, Brillanti, S, Burra, P, Corsale, S, De Luca, A, Fagiuoli, S, Fattovich, G, Fava, G, Felder, M, Forte, P, Galeota-Lanza, A, Gitto, S, Grieco, A, Grossi, P, Ialungo, A, Iemmolo, R, Loiacono, L, Mangia, A, Merli, M, Piacentini, A, Pellicelli, A, Rigamonti, C, Gabriella, V, Zignego, A, Carrai P., Morelli C., Cordone G., Romano A., Tame M., Lionetti R., Pietrosi G., Lenci I., Piai G., Russo F. P., Coppola C., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Martini S., Toniutto P., Bandiera F., Bhoori S., Brillanti S., Burra P., Corsale S., De Luca A., Fagiuoli S., Fattovich G., Fava G., Felder M., Forte P., Galeota-Lanza A., Gitto S., Grieco A., Grossi P., Ialungo A. M., Iemmolo R. M., Loiacono L., Mangia A., Merli M., Piacentini A., Pellicelli A., Rigamonti C., Gabriella V., and Zignego A. L.

Abstract

Direct antivirals are available for treating recurrent hepatitis C (RHC). This study reported outcomes of 424 patients with METAVIR F3–F4 RHC who were treated for 24 weeks with sofosbuvir/ribavirin and followed for 12 weeks within the Italian sofosbuvir compassionate use program. In 55 patients, daclatasvir or simeprevir were added. Child–Pugh class and model of end stage liver disease (MELD) scores were evaluated at baseline and 36 weeks after the start of therapy. The sustained viral response (SVR) was 86.7% (316/365) in patients who received sofosbuvir/ribavirin and 98.3% (58/59) in patients who received a second antiviral (P < 0.01). In patients treated with sofosbuvir/ribavirin, a significant difference in SVR was observed between patients diagnosed with METAVIR F4 (211/250; 84.4%), METAVIR F3 (95/105; 90.5%) and fibrosing cholestatic hepatitis (10/10; 100%) (P = 0.049). A significant association was found between patients who worsened from Child–Pugh class A and who experienced viral relapse (4/26 vs. 8/189, P = 0.02). In patients with a baseline MELD score <15, a significant association was found between maintaining a final MELD score <15 and the achievement of SVR (187/219 vs. 6/10, P = 0.031). This real-world study indicates that sofosbuvir/ribavirin treatment for 24 weeks was effective, and the achievement of SVR was associated with a reduced probability of developing worsening liver function.

Published
2017

23. La valutazione Economica dei Farmaci

Author

Bonaretti, P, Cerreta, F, Curto, A, Scroccaro, G, Scaccabarozzi, M, Spandonaro, F, Xaxi, E, and Pani, L

Subjects
Settore SECS-P/06 - Economia Applicata
Published
2017

24. Impact of reimbursement limits on patient access to direct-acting antivirals in Italy: analysis of data from national registries.

Author

RUSSO, P., PANI, L., STANISCIA, T., ROMANO, F., and MARZIONI, M.

Abstract

OBJECTIVE: Hepatitis C virus (HCV) infection is a global epidemic, still highly prevalent in Europe. Given efficacy and safety of HCV therapy by Direct Antiviral Agents (DAA), World Health Organization called for actions to eliminate HCV infection. A limit is represented by access to care, mostly due to the high costs of medicines. In Italy, in 2015, the access to DAA therapy was reimbursed for patients with advanced disease, whereas in 2017 universal access was granted. The aim of this study was to analyse changes in patient recruitment trends treated with DAA with or without limitations to access to therapy. PATIENTS AND METHODS: 165,105 patients treated with DAA in Italy from 2015 to December 2018 were analysed. Daily patient treatment rate was obtained by segmented regression of interrupted time series analysis. RESULTS: 74,199 patients with advanced disease (62% with cirrhosis) had access to the therapy during the time period from 2015 to 2017. Following the extension of reimbursement criteria, 90,906 additional patients were treated (43.2% with F0-F1 and 22.9% with F2), with an absolute reduction of 59.9% of patients with advanced disease (cirrhosis decreased to 18.5%). Segmented regression of interrupted time series analysis of daily patient treatment rate showed a progressive reduction of patients with advanced disease, offset by those with initial disease. Notably, elimination of restrictions to therapy did not change the overall treatment rate. CONCLUSIONS: This study showed that a no-limit reimbursement policy for DAAs prescriptions to HCV infected individuals in Italy widened the types of treated patients, but the process towards elimination of HCV infection was not significantly changed. [ABSTRACT FROM AUTHOR]

Published
2020

25. Identification and characterization of the kynurenine pathway in the pond snail Lymnaea stagnalis

Author

Benatti Cristina, Rivi Veronica, Alboni Silvia, Grilli Andrea, Castellano Sara, Pani Luca, Brunello Nicoletta, Blom Johanna M.C., Bicciato Silvio, and Tascedda Fabio

Subjects
Medicine, Science
Abstract

Abstract Dysregulation of the kynurenine pathway (KP) is implicated in many human diseases and disorders, from immunological, metabolic, neurodegenerative, and neuropsychiatric conditions to cancer, and represents an appealing target for new therapeutic approaches. In this intricate scenario, invertebrates, like Lymnaea stagnalis (LS), provide a flexible tool to unravel the complexity of the KP. Starting from the available LS genome and transcriptome, we identified putative transcripts of all KP enzymes containing an ORF; each predicted protein possessed a high degree of sequence conservation to known orthologues of other invertebrate and vertebrate model organisms. Sequences were confirmed by qualitative PCR and sequencing. At the same time, the qRT-PCR analysis revealed that Lym IDO-like, Lym TDO-like, Lym AFMID-like, Lym KMO-like, Lym AADAT-like, Lym KYAT I/III-like, Lym KYNU-like, Lym HAAO-like, and Lym ACMSD-like showed widespread tissue expression. Then, tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxy-kynurenine, xanthurenic acid, picolinic acid, and quinolinic acid were identified in the hemolymph of LS by UHPLC-Q exactive mass spectrometer. Our study provides the most thorough characterization to date of the KP in an invertebrate model, supporting the value of LS for future functional studies of this pathway at the cellular, synaptic, and behavioral levels.

Published
2022
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26. Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study

Author

Petta, S, Marzioni, M, Russo, P, Aghemo, A, Alberti, A, Ascione, A, Antinori, A, Bruno, R, Bruno, S, Chirianni, A, Gaeta, G, Giannini, E, Merli, M, Messina, V, Montilla, S, Perno, C, Puoti, M, Raimondo, G, Rendina, M, Silberstein, F, Villa, E, Zignego, A, Pani, L, Craxì, A, Fagiuoli, S, Gaeta, GB, Giannini, EG, Perno, CF, Silberstein, FC, Zignego, AL, FAGIUOLI, STEFANO, Petta, S, Marzioni, M, Russo, P, Aghemo, A, Alberti, A, Ascione, A, Antinori, A, Bruno, R, Bruno, S, Chirianni, A, Gaeta, G, Giannini, E, Merli, M, Messina, V, Montilla, S, Perno, C, Puoti, M, Raimondo, G, Rendina, M, Silberstein, F, Villa, E, Zignego, A, Pani, L, Craxì, A, Fagiuoli, S, Gaeta, GB, Giannini, EG, Perno, CF, Silberstein, FC, Zignego, AL, and FAGIUOLI, STEFANO

Abstract

Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. Findings 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4·76 [95% CI 1·83–12·3]; p=0·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring in 36 (5%) p

Published
2017

27. Pricing and reimbursement experiences and insights in the EU and US: Lessons learned to approach adaptive payer pathways

Author

Faulkner, S, Lee, M, Qin, D, Morrell, L, Xoxi, E, Sammarco, A, Cammarata, S, Russo, P, Pani, L, and Barker, R

Subjects
health care economics and organizations
Abstract

Earlier patient access to beneficial therapeutics that address unmet need is one of the main requirements of innovation in global healthcare systems– already burdened by unsustainable budgets. ‘Adaptive pathways’ (1), encompass earlier cross-stakeholder engagement, regulatory tools, and iterative evidence generation through the life cycle of the medicinal product. A key enabler of earlier patient access is through more flexible and adaptive payer approaches to pricing and reimbursement that reflect the emerging evidence generated.

Published
2016

28. Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: A retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database

Author

Fadini, G. P., Avogaro, A., Degli Esposti, L., Russo, P., Saragoni, S., Buda, S., Rosano, G., Pecorelli, S., Pani, L., Martinetti, S., Mero, P., Raeli, L., Migliazza, S., Dellagiovanna, M., Cerra, C., Gambera, M., Piccinelli, R., Zambetti, M., Atzeni, F., Valsecchi, V., Deluca, P., Scopinaro, E., Moltoni, D., Pini, E., Leoni, O., Oria, C., Papagni, M., Nosetti, G., Caldiroli, E., Moser, V., Roni, R., Polverino, A., Bovo, C., Mezzalira, L., Andretta, M., Trentin, L., Palcic, S., Pettinelli, A., Arbo, A., Bertola, A., Capparoni, G., Cattaruzzi, C., Marcuzzo, L., Rosa, F. V., Basso, B., Saglietto, M., Delucis, S., Prioli, M., Filippi, R., Coccini, A., Ghia, M., Sanfelici, F., Radici, S., Scanavacca, P., Campi, A., Bianchi, S., Verzola, A., Morini, M., Borsari, M., Danielli, A., Dal Maso, M., Marsiglia, B., Vujovic, B., Pisani, M., Bonini, P., Lena, F., Aletti, P., Marcobelli, A., Sagratella, S., Fratini, S., Bartolini, F., Riccioni, G., Meneghini, A., Di Turi, R., Fano, V., Blasi, A., Pagnozzi, E., Quintavalle, G., D'Avenia, P., De Matthaeis, M. C., Ferrante, F., Crescenzi, S., Marziale, L., Venditti, P., Bianchi, C., Senesi, I., Baci, R., De Carlo, I., Lavalle, A., Trofa, G., Marcello, G., Pagliaro, C., Troncone, C., Farina, G., Tari, M. G., Motola, G., De Luca, F., Saltarelli, M. L., Granieri, C., Vulnera, M., Palumbo, L., La Viola, F., Florio, L., De Francesco, A. E., Costantino, D., Rapisarda, F., Lazzaro, P. L., Pastorello, M., Parlli, M., Visconti, M., Uomo, I., Sanna, P., and Lombardo, F.

Subjects
Adult, Male, medicine.medical_specialty, Epidemiology, Population, Administration, Oral, Medications, Heart failure, Type 2 diabetes, Lower risk, Diabetes, Incretin, Cardiology and Cardiovascular Medicine, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, education, Aged, Retrospective Studies, education.field_of_study, Analysis of Variance, Dipeptidyl-Peptidase IV Inhibitors, business.industry, Hazard ratio, Absolute risk reduction, Retrospective cohort study, Middle Aged, medicine.disease, Hospitalization, Endocrinology, Sulfonylurea Compounds, Diabetes Mellitus, Type 2, Italy, Propensity score matching, Female, business, Diabetic Angiopathies
Abstract

Aims Oral glucose-lowering medications are associated with excess risk of heart failure (HF). Given the absence of comparative data among drug classes, we performed a retrospective study in 32 Health Services of 16 Italian regions accounting for a population of 18 million individuals, to assess the association between HF risk and use of sulphonylureas, DPP-4i, and glitazones. Methods and results We extracted data on patients with type 2 diabetes who initiated treatment with DPP-4i, thiazolidinediones, or sulphonylureas alone or in combination with metformin during an accrual time of 2 years. The endpoint was hospitalization for HF (HHF) occurring after the first 6 months of therapy, and the observation was extended for up to 4 years. A total of 127 555 patients were included, of whom 14.3% were on DPP-4i, 72.5% on sulphonylurea, 13.2% on thiazolidinediones, with average 70.7% being on metformin as combination therapy. Patients in the three groups differed significantly for baseline characteristics: age, sex, Charlson index, concurrent medications, and previous cardiovascular events. During an average 2.6-year follow-up, after adjusting for measured confounders, use of DPP-4i was associated with a reduced risk of HHF compared with sulphonylureas [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.62–0.97; P = 0.026]. After propensity matching, the analysis was restricted to 39 465 patients, and the use of DPP-4i was still associated with a lower risk of HHF (HR 0.70; 95% CI 0.52–0.94; P = 0.018). Conclusion In a very large observational study, the use of DPP-4i was associated with a reduced risk of HHF when compared with sulphonylureas.

Published
2015

30. Identification and validation of biomarkers for autism spectrum disorders

Author

Loth, E., Spooren, W., Ham, L.M., Isaac, M.B., Auriche-Benichou, C., Banaschewski, T., Baron-Cohen, S., Broich, K., Bolte, S., Bourgeron, T., Charman, T., Collier, D., Andres-Trelles, F. de, Durston, S., Ecker, C., Elferink, A., Haberkamp, M., Hemmings, R., Johnson, M.H., Jones, E.J.H., Khwaja, O.S., Lenton, S., Mason, L., Mantua, V., Meyer-Lindenberg, A., Lombardo, M.V., O'Dwyer, L., Okamoto, K., Pandina, G.J., Pani, L., Persico, A.M., Simonoff, E., Tauscher-Wisniewski, S., Llinares-Garcia, J., Vamvakas, S., Williams, S., Buitelaar, J.K., Murphy, D.G.M., Loth, E., Spooren, W., Ham, L.M., Isaac, M.B., Auriche-Benichou, C., Banaschewski, T., Baron-Cohen, S., Broich, K., Bolte, S., Bourgeron, T., Charman, T., Collier, D., Andres-Trelles, F. de, Durston, S., Ecker, C., Elferink, A., Haberkamp, M., Hemmings, R., Johnson, M.H., Jones, E.J.H., Khwaja, O.S., Lenton, S., Mason, L., Mantua, V., Meyer-Lindenberg, A., Lombardo, M.V., O'Dwyer, L., Okamoto, K., Pandina, G.J., Pani, L., Persico, A.M., Simonoff, E., Tauscher-Wisniewski, S., Llinares-Garcia, J., Vamvakas, S., Williams, S., Buitelaar, J.K., and Murphy, D.G.M.

Abstract

Item does not contain fulltext

Published
2015

31. Advanced Age and Medication Prescription: More Years, Less Medications? A Nationwide Report From the Italian Medicines Agency

Author

Onder, Graziano, Marengoni, A, Russo, P, Degli Esposti, L, Fini, M, Monaco, A, Bonassi, S, Palmer, K, Marrocco, W, Pozzi, G, Sangiorgi, D, Buda, S, Marchionni, N, Mammarella, F, Bernabei, Roberto, Pani, L, Pecorelli, S., Onder, Graziano (ORCID:0000-0003-3400-4491), Bernabei, R (ORCID:0000-0002-9197-004X), Onder, Graziano, Marengoni, A, Russo, P, Degli Esposti, L, Fini, M, Monaco, A, Bonassi, S, Palmer, K, Marrocco, W, Pozzi, G, Sangiorgi, D, Buda, S, Marchionni, N, Mammarella, F, Bernabei, Roberto, Pani, L, Pecorelli, S., Onder, Graziano (ORCID:0000-0003-3400-4491), and Bernabei, R (ORCID:0000-0002-9197-004X)

Abstract

In older adults co-occurrence of multiple diseases often leads to use of multiple medications (polypharmacy). The aim of the present study is to describe how prescription of medications varies across age groups, with specific focus on the oldest old.

Published
2015

32. Development of Screening Tools to Predict Medication-Related Problems Across the Continuum of Emergency Department Care: A Prospective, Multicenter Study

Author

Simone E. Taylor, Elise A. Mitri, Andrew M. Harding, David McD Taylor, Adrian Weeks, Leonie Abbott, Pani Lambros, Dona Lawrence, Dana Strumpman, Reyhan Senturk-Raif, Stephen Louey, Hamish Crisp, Emily Tomlinson, and Elizabeth Manias

Subjects
emergency department, medication management, risk factors, patient transfer, workforce, Therapeutics. Pharmacology, RM1-950
Abstract

Background: Medication-related problems (MRPs) occur across the continuum of emergency department (ED) care: they may contribute to ED presentation, occur in the ED/short-stay unit (SSU), at hospital admission, or shortly after discharge to the community. This project aimed to determine predictors for MRPs across the continuum of ED care and incorporate these into screening tools (one for use at ED presentation and one at ED/SSU discharge), to identify patients at greatest risk, who could be targeted by ED pharmacists.Methods: A prospective, observational, multicenter study was undertaken in nine EDs, between July 2016 and August 2017. Blocks of ten consecutive adult patients presenting at pre-specified times were identified. Within 1 week of ED discharge, a pharmacist interviewed patients and undertook a medical record review to determine a medication history, patient understanding of treatment, risk factors for MRPs and to manage the MRPs. Logistic regression was undertaken to determine predictor variables. Multivariable regression beta coefficients were used to develop a scoring system for the two screening tools.Results: Of 1,238 patients meeting all inclusion criteria, 904 were recruited. Characteristics predicting MRPs related to ED presentation were: patient self-administers regular medications (OR = 7.95, 95%CI = 3.79–16.65), carer assists with medication administration (OR = 15.46, 95%CI = 6.52–36.67), or health-professional administers (OR = 5.01, 95%CI = 1.77–14.19); medication-related ED presentation (OR = 9.95, 95%CI = 4.92–20.10); age ≥80 years (OR = 3.63, 95%CI = 1.96–6.71), or age 65–79 years (OR = 2.01, 95%CI = 1.17–3.46); potential medication adherence issue (OR = 2.27, 95%CI = 1.38–3.73); medical specialist seen in past 6-months (OR = 2.02, 95%CI = 1.42–2.85); pharmaceutical benefit/pension/concession cardholder (OR = 1.89, 95%CI = 1.28–2.78); inpatient in previous 4-weeks (OR = 1.60, 95%CI = 1.02–2.52); being male (OR = 1.48, 95%CI = 1.05–2.10); and difficulties reading labels (OR = 0.63, 95%CI = 0.40–0.99). Characteristics predicting MRPs related to ED discharge were: potential medication adherence issue (OR = 6.80, 95%CI = 3.97–11.64); stay in ED > 8 h (OR = 3.23, 95%CI = 1.47–7.78); difficulties reading labels (OR = 2.33, 95%CI = 1.30–4.16); and medication regimen changed in ED (OR = 3.91, 95%CI = 2.43–6.30). For ED presentation, the model had a C-statistic of 0.84 (95% CI 0.81–0.86) (sensitivity = 80%, specificity = 70%). For ED discharge, the model had a C-statistic of 0.78 (95% CI 0.73–0.83) (sensitivity = 82%, specificity = 57%).Conclusion: Predictors of MRPs are readily available at the bedside and may be used to screen for patients at greatest risk upon ED presentation and upon ED/SSU discharge to the community. These screening tools now require external validation and implementation studies to evaluate the impact of using such tools on patient care outcomes.

Published
2022
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35. Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study

Author

Petta, Salvatore, Marzioni, Marco, Russo, Pierluigi, Aghemo, Alessio, Alberti, Alfredo, ASCIONE, ANTONIO, Antinori, Andrea, Bruno, Raffaele, Bruno, Savino, Chirianni, Antonio, Gaeta, Giovanni Battista, Giannini, Edoardo G, Merli, Manuela, Messina, Vincenzo, Montilla, Simona, Perno, Carlo Federico, Puoti, Massimo, Raimondo, Giovanni, Rendina, Maria, Silberstein, Francesca Ceccherini, Villa, Erica, Zignego, Anna Linda, Pani, Luca, Craxì, Antonio, Tabone, Marco, Andreoni, Massimo, Teti, Elisabetta, Angelico, Mario, Persico, Marcello, Masarone, Mario, Chiodera, Aledssandro, Solinas, Attilio, delle Monache, Marco, Cecere, Roberto, Maria Schimizzi, Anna, Piovesan, Sara, Campagnolo, Davide, Chiara Piras, Maria, Zolfino, Teresa, Paolo Russo, Francesca, Morelli, Olivia, Sangiovanni, Vincenzo, Onofrio, Mirella, Iodice, Valentina, Izzi, Antonio, Pirisi, Massimo, Danieli, Elena, Vinci, Maria, Rizzardini, Giuliano, Fagiuoli, Stefano, Pasulo, Luisa, D'Arminio Monforte, Antonella, Zuin, Massimo, Giorgini, Alessia, Simeone, Filomena, Piali, Guido, Lo Guercio, Carmela, Federico, Alessandro, Brancaccio, Giuseppina, Marrone, Aldo, Abbati, Giuseppe, Boarini, Chiara, Borghi, Vanni, Bernabucci, Veronica, Corti, Giampaolo, Monti, Monica, Rizzetto, Mario, Martini, Silvia, Andreone, Pietro, Gianstefani, Alice, Lenzi, Marco, Verucchi, Gabriella, Toniutto, Pierluigi, Borgia, Guglielmo, Caporaso, Nicola, Morisco, Filomena, Nardone, Gaetano, Angrisani, Debora, Giacometti, Andrea, Benedetti, Antonio, Tarantino, Giuseppe, Marsetti, Fabio, Tavio, Marcello, Novara, Sergio, Antonia Santantonio, Teresa, Serviddio, Gaetano, Brunetto, Maurizia, Coco, Barbara, Angarano, Gioacchino, Milella, Michele, BARONE, MICHELE, Di Leo, Alfredo, Ettore Sansonno, Domenico, Cacciola, Irene, Boffa, Nicola, Saracco, Giorgio, Di Biagio, Antonio, Picciotto, Antonino, de Luca, Andrea, Calvaruso, Vincenza, Corradori, Silvia, Ferrari, Carlo, Orlandini, Alessandra, Maida, Ivana, Torti, Carlo, Chessa, Luchino, Felder, Martina, Vespasiani Gentilucci, Umberto, Angeli, Paolo, Romano, Antonietta, Ludovico Rapaccini, Gian, Miele, Luca, Cima, Serena, Luisa Russo, Maria, Cozzolongo, Raffaele, Onnelli, Giovanna, D'Offizi, Giampiero, Lionetti, Raffaella, Montalbano, Marzia, Guerra, Michele, Di Perri, Giovanni, Boglione, Lucio, Capra, Franco, Carolo, Giada, Ieluzzi, Donatella, Antonini, Cinzia, Termite, Antonio, Madonia, Salvatore, Tarquini, Pierluigi, Parruti, Giustino, Vecchiet, Giacomo, Falasca, Katia, Menzaghi, Barbara, Quirino, Tiziana, Dentone, Chiara, Maria Piscaglia, Anna, Rossi, Cristina, Giordani, Maria, Fontanella, Luca, Cassola, Giovanni, Russello, Maurizio, Cristaudo, Antonio, Giacomet, Vania, Colombo, Massimo, Donato, Francesca, Durante, Emanuele, Cosco, Lucio, Marignani, Massimo, Quartini, Mariano, Memoli, Massimo, Ganga, Roberto, Ponti, Laura, Soria, Alessandro, Grazia Rumi, Maria, Gulminetti, Roberto, Maserati, Renato, Mondelli, Mario, Lazzarin, Adriano, Rita Parisi, Maria, Canovari, Benedetta, Avancini, Ivo, Pravadelli, Cecilia, Blanc, Pier, Pasquazzi, Caterina, Maria Mastroianni, Claudio, Lichtner, Myriam, Distefano, Marco, Magnani, Silvia, Paganin, Simona, Erne, Elke, Gatti, Pietro, Tundi, Paolo, Calabrese, Paolo, Gasbarrini, Antonio, Grieco, Antonio, Coppola, Nicola, Del Poggio, Paolo, Levrero, Massimo, Talliani, Gloria, Vullo, Vincenzo, Cauda, Roberto, La Monica, Silvia, Potenza, Domenico, Rizzo, Salvatore, Castelli, Francesco, Marie Pigozzi, Grazielle, Ciancio, Alessia, Romagnoli, Dante, Barchetti, Federica, Ivanovic, Jelena, Longo, Olimpia, Petraglia, Sandra, Paola Trotta, Maria, NARDONE, GERARDO ANTONIO PIO, Petta, Salvatore, Marzioni, Marco, Russo, Pierluigi, Aghemo, Alessio, Alberti, Alfredo, Ascione, Antonio, Antinori, Andrea, Bruno, Raffaele, Bruno, Savino, Chirianni, Antonio, Gaeta, Giovanni Battista, Giannini, Edoardo G, Merli, Manuela, Messina, Vincenzo, Montilla, Simona, Perno, Carlo Federico, Puoti, Massimo, Raimondo, Giovanni, Rendina, Maria, Silberstein, Francesca Ceccherini, Villa, Erica, Zignego, Anna Linda, Pani, Luca, Craxì, Antonio, Tabone, Marco, Andreoni, Massimo, Teti, Elisabetta, Angelico, Mario, Persico, Marcello, Masarone, Mario, Chiodera, Aledssandro, Solinas, Attilio, delle Monache, Marco, Cecere, Roberto, Maria Schimizzi, Anna, Piovesan, Sara, Campagnolo, Davide, Chiara Piras, Maria, Zolfino, Teresa, Paolo Russo, Francesca, Morelli, Olivia, Sangiovanni, Vincenzo, Onofrio, Mirella, Iodice, Valentina, Izzi, Antonio, Pirisi, Massimo, Danieli, Elena, Vinci, Maria, Rizzardini, Giuliano, Fagiuoli, Stefano, Pasulo, Luisa, D'Arminio Monforte, Antonella, Zuin, Massimo, Giorgini, Alessia, Simeone, Filomena, Piali, Guido, Lo Guercio, Carmela, Federico, Alessandro, Brancaccio, Giuseppina, Marrone, Aldo, Abbati, Giuseppe, Boarini, Chiara, Borghi, Vanni, Bernabucci, Veronica, Corti, Giampaolo, Monti, Monica, Rizzetto, Mario, Martini, Silvia, Andreone, Pietro, Gianstefani, Alice, Lenzi, Marco, Verucchi, Gabriella, Toniutto, Pierluigi, Borgia, Guglielmo, Caporaso, Nicola, Morisco, Filomena, Nardone, Gaetano, Angrisani, Debora, Giacometti, Andrea, Benedetti, Antonio, Tarantino, Giuseppe, Marsetti, Fabio, Tavio, Marcello, Novara, Sergio, Antonia Santantonio, Teresa, Serviddio, Gaetano, Brunetto, Maurizia, Coco, Barbara, Angarano, Gioacchino, Milella, Michele, Barone, Michele, Di Leo, Alfredo, Ettore Sansonno, Domenico, Cacciola, Irene, Boffa, Nicola, Saracco, Giorgio, Di Biagio, Antonio, Picciotto, Antonino, de Luca, Andrea, Calvaruso, Vincenza, Corradori, Silvia, Ferrari, Carlo, Orlandini, Alessandra, Maida, Ivana, Torti, Carlo, Chessa, Luchino, Felder, Martina, Vespasiani Gentilucci, Umberto, Angeli, Paolo, Romano, Antonietta, Ludovico Rapaccini, Gian, Miele, Luca, Cima, Serena, Luisa Russo, Maria, Cozzolongo, Raffaele, Onnelli, Giovanna, D'Offizi, Giampiero, Lionetti, Raffaella, Montalbano, Marzia, Guerra, Michele, Di Perri, Giovanni, Boglione, Lucio, Capra, Franco, Carolo, Giada, Ieluzzi, Donatella, Antonini, Cinzia, Termite, Antonio, Madonia, Salvatore, Tarquini, Pierluigi, Parruti, Giustino, Vecchiet, Giacomo, Falasca, Katia, Menzaghi, Barbara, Quirino, Tiziana, Dentone, Chiara, Maria Piscaglia, Anna, Rossi, Cristina, Giordani, Maria, Fontanella, Luca, Cassola, Giovanni, Russello, Maurizio, Cristaudo, Antonio, Giacomet, Vania, Colombo, Massimo, Donato, Francesca, Durante, Emanuele, Cosco, Lucio, Marignani, Massimo, Quartini, Mariano, Memoli, Massimo, Ganga, Roberto, Ponti, Laura, Soria, Alessandro, Grazia Rumi, Maria, Gulminetti, Roberto, Maserati, Renato, Mondelli, Mario, Lazzarin, Adriano, Rita Parisi, Maria, Canovari, Benedetta, Avancini, Ivo, Pravadelli, Cecilia, Blanc, Pier, Pasquazzi, Caterina, Maria Mastroianni, Claudio, Lichtner, Myriam, Distefano, Marco, Magnani, Silvia, Paganin, Simona, Erne, Elke, Gatti, Pietro, Tundi, Paolo, Calabrese, Paolo, Gasbarrini, Antonio, Grieco, Antonio, Coppola, Nicola, Del Poggio, Paolo, Levrero, Massimo, Talliani, Gloria, Vullo, Vincenzo, Cauda, Roberto, La Monica, Silvia, Potenza, Domenico, Rizzo, Salvatore, Castelli, Francesco, Marie Pigozzi, Grazielle, Ciancio, Alessia, Romagnoli, Dante, Barchetti, Federica, Ivanovic, Jelena, Longo, Olimpia, Petraglia, Sandra, Paola Trotta, Maria, Petta, S., Marzioni, M., Russo, P., Aghemo, A., Alberti, A., Ascione, A., Antinori, A., Bruno, R., Bruno, S., Chirianni, A., Gaeta, G., Giannini, E., Merli, M., Messina, V., Montilla, S., Perno, C., Puoti, M., Raimondo, G., Rendina, M., Silberstein, F., Villa, E., Zignego, A., Pani, L., Craxi, A., Tabone, M., Andreoni, M., Teti, E., Angelico, M., Persico, M., Masarone, M., Chiodera, A., Solinas, A., delle Monache, M., Cecere, R., Maria Schimizzi, A., Piovesan, S., Campagnolo, D., Chiara Piras, M., Zolfino, T., Paolo Russo, F., Morelli, O., Sangiovanni, V., Onofrio, M., Iodice, V., Izzi, A., Pirisi, M., Danieli, E., Vinci, M., Rizzardini, G., Fagiuoli, S., Pasulo, L., D'Arminio Monforte, A., Zuin, M., Giorgini, A., Simeone, F., Piali, G., Lo Guercio, C., Federico, A., Brancaccio, G., Marrone, A., Abbati, G., Boarini, C., Borghi, V., Bernabucci, V., Corti, G., Monti, M., Rizzetto, M., Martini, S., Andreone, P., Gianstefani, A., Lenzi, M., Verucchi, G., Toniutto, P., Borgia, G., Caporaso, N., Morisco, F., Nardone, G., Angrisani, D., Giacometti, A., Benedetti, A., Tarantino, G., Marsetti, F., Tavio, M., Novara, S., Antonia Santantonio, T., Serviddio, G., Brunetto, M., Coco, B., Angarano, G., Milella, M., Barone, M., Di Leo, A., Ettore Sansonno, D., Cacciola, I., Boffa, N., Saracco, G., Di Biagio, A., Picciotto, A., de Luca, A., Calvaruso, V., Corradori, S., Ferrari, C., Orlandini, A., Maida, I., Torti, C., Chessa, L., Felder, M., Vespasiani Gentilucci, U., Angeli, P., Romano, A., Ludovico Rapaccini, G., Miele, L., Cima, S., Luisa Russo, M., Cozzolongo, R., Onnelli, G., D'Offizi, G., Lionetti, R., Montalbano, M., Guerra, M., Di Perri, G., Boglione, L., Capra, F., Carolo, G., Ieluzzi, D., Antonini, C., Termite, A., Madonia, S., Tarquini, P., Parruti, G., Vecchiet, G., Falasca, K., Menzaghi, B., Quirino, T., Dentone, C., Maria Piscaglia, A., Rossi, C., Giordani, M., Fontanella, L., Cassola, G., Russello, M., Cristaudo, A., Giacomet, V., Colombo, M., Donato, F., Durante, E., Cosco, L., Marignani, M., Quartini, M., Memoli, M., Ganga, R., Ponti, L., Soria, A., Grazia Rumi, M., Gulminetti, R., Maserati, R., Mondelli, M., Lazzarin, A., Rita Parisi, M., Canovari, B., Avancini, I., Pravadelli, C., Blanc, P., Pasquazzi, C., Maria Mastroianni, C., Lichtner, M., Distefano, M., Magnani, S., Paganin, S., Erne, E., Gatti, P., Tundi, P., Calabrese, P., Gasbarrini, A., Grieco, A., Coppola, N., Del Poggio, P., Levrero, M., Talliani, G., Vullo, V., Cauda, R., La Monica, S., Potenza, D., Rizzo, S., Castelli, F., Marie Pigozzi, G., Ciancio, A., Romagnoli, D., Barchetti, F., Ivanovic, J., Longo, O., Petraglia, S., Paola Trotta, M., Savino, Bruno, Nardone, GERARDO ANTONIO PIO, Petta, S, Marzioni, M, Russo, P, Aghemo, A, Alberti, A, Ascione, A, Antinori, A, Bruno, R, Bruno, S, Chirianni, A, Gaeta, G, Giannini, E, Merli, M, Messina, V, Montilla, S, Perno, C, Puoti, M, Raimondo, G, Rendina, M, Silberstein, F, Villa, E, Zignego, A, Pani, L, Craxì, A, and Fagiuoli, S

Subjects
Cyclopropanes, Compassionate Use Trials, Liver Cirrhosis, Male, chemistry.chemical_compound, 0302 clinical medicine, 2-Naphthylamine, HCV, direct-acting antiviral, mixed cryoglobulinemia, RBV, Anilides, 030212 general & internal medicine, Longitudinal Studies, Prospective Studies, Chronic, Adult, Aged, Antiviral Agents, Carbamates, Drug Therapy, Combination, Female, Genotype, Hepatitis C, Chronic, Humans, Macrocyclic Compounds, Middle Aged, Ribavirin, Ritonavir, Sulfonamides, Treatment Outcome, Uracil, Settore MED/12 - Gastroenterologia, Dasabuvir, HCV DAA, Gastroenterology, virus diseases, Valine, Settore MED/07 - Microbiologia e Microbiologia Clinica, Hepatitis C, Hepatology, Combination, 030211 gastroenterology & hepatology, medicine.drug, medicine.medical_specialty, Proline, Lactams, Macrocyclic, Hepatitis C virus genotype 1, Hepatitis C virus genotype 4, decompensated liver cirrhosis, antiviral therapy, dasabuvir, ombitasvir, paritaprevir, 03 medical and health sciences, Drug Therapy, Internal medicine, medicine, Decompensation, Adverse effect, business.industry, Virology, Ombitasvir, Clinical trial, chemistry, Paritaprevir, business
Abstract

Summary Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. Findings 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4·76 [95% CI 1·83–12·3]; p=0·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring in 36 (5%) patients. Interpretation Our findings suggest that the safety and effectiveness of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin in patients with HCV genotype 1 or 4 infection and cirrhosis at high risk of decompensation in a real-life setting are similar to those reported in clinical trials. The concordance with clinical trials provides reassurance that the reported efficacy of this treatment in clinical trials will translate to its use in routine clinical practice. Funding Dipartimento Biomedico di Medicina Interna e Specialistica dell'Universita di Palermo.

Published
2017

36. A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Author

Luca Sforzini, Courtney Worrell, Melisa Kose, Ian M. Anderson, Bruno Aouizerate, Volker Arolt, Michael Bauer, Bernhard T. Baune, Pierre Blier, Anthony J. Cleare, Philip J. Cowen, Timothy G. Dinan, Andrea Fagiolini, I. Nicol Ferrier, Ulrich Hegerl, Andrew D. Krystal, Marion Leboyer, R. Hamish McAllister-Williams, Roger S. McIntyre, Andreas Meyer-Lindenberg, Andrew H. Miller, Charles B. Nemeroff, Claus Normann, David Nutt, Stefano Pallanti, Luca Pani, Brenda W. J. H. Penninx, Alan F. Schatzberg, Richard C. Shelton, Lakshmi N. Yatham, Allan H. Young, Roland Zahn, Georgios Aislaitner, Florence Butlen-Ducuing, Christine Fletcher, Marion Haberkamp, Thomas Laughren, Fanni-Laura Mäntylä, Koen Schruers, Andrew Thomson, Gara Arteaga-Henríquez, Francesco Benedetti, Lucinda Cash-Gibson, Woo Ri Chae, Heidi De Smedt, Stefan M. Gold, Witte J. G. Hoogendijk, Valeria Jordán Mondragón, Eduard Maron, Jadwiga Martynowicz, Elisa Melloni, Christian Otte, Gabriela Perez-Fuentes, Sara Poletti, Mark E. Schmidt, Edwin van de Ketterij, Katherine Woo, Yanina Flossbach, J. Antoni Ramos-Quiroga, Adam J. Savitz, Carmine M. Pariante, Sforzini, L., Worrell, C., Kose, M., Anderson, I. M., Aouizerate, B., Arolt, V., Bauer, M., Baune, B. T., Blier, P., Cleare, A. J., Cowen, P. J., Dinan, T. G., Fagiolini, A., Ferrier, I. N., Hegerl, U., Krystal, A. D., Leboyer, M., McAllister-Williams, R. H., Mcintyre, R. S., Meyer-Lindenberg, A., Miller, A. H., Nemeroff, C. B., Normann, C., Nutt, D., Pallanti, S., Pani, L., Penninx, B. W. J. H., Schatzberg, A. F., Shelton, R. C., Yatham, L. N., Young, A. H., Zahn, R., Aislaitner, G., Butlen-Ducuing, F., Fletcher, C., Haberkamp, M., Laughren, T., Mantyla, F. -L., Schruers, K., Thomson, A., Arteaga-Henriquez, G., Benedetti, F., Cash-Gibson, L., Chae, W. R., De Smedt, H., Gold, S. M., Hoogendijk, W. J. G., Mondragon, V. J., Maron, E., Martynowicz, J., Melloni, E., Otte, C., Perez-Fuentes, G., Poletti, S., Schmidt, M. E., van de Ketterij, E., Woo, K., Flossbach, Y., Ramos-Quiroga, J. A., Savitz, A. J., Pariante, C. M., Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden = Dresden University of Technology (TU Dresden), The Florey Institute of Neuroscience and Mental Health, University of Melbourne, IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and European Project: (grant No 116060),IMPRiND

Subjects
Depression, Diagnostic markers, DISORDER, STIMULATION, STAR-ASTERISK-D, SEROTONIN REUPTAKE INHIBITORS, Major Depressive Disorder, Clinical Trials and Supportive Activities, Medical and Health Sciences, Depressive Disorder, Treatment-Resistant, Cellular and Molecular Neuroscience, REPORT QIDS-SR, SDG 3 - Good Health and Well-being, Clinical Research, Humans, RATING-SCALE, Molecular Biology, METAANALYSIS, Psychiatry, Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Psychology and Cognitive Sciences, Major, REMISSION, Biological Sciences, Serious Mental Illness, Brain Disorders, Psychiatry and Mental health, QUICK INVENTORY, Mental Health, Good Health and Well Being, SYMPTOMATOLOGY, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Published
2022
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37. Should Patients Receiving ACE Inhibitors or Angiotensin Receptor Blockers be Switched to Other Antihypertensive Drugs to Prevent or Improve Prognosis of Novel Coronavirus Disease 2019 (COVID-19)?

Author

Filippo Drago, Patrizia Hrelia, Gianluca Trifirò, Marco Pistis, Annalisa Capuano, Giambattista Bonanno, Cristiano Chiamulera, Renato Bernardini, Luca Pani, Giuseppe Cirino, Nicoletta Brunello, Romano Danesi, Liberato Berrino, Antonio D'Avolio, Emilio Clementi, Giorgio Racagni, Maurizio Taglialatela, Alessandro Mugelli, Annamaria Luca, Carla Ghelardini, Francesco Scaglione, Salvatore Crisafulli, Marzia Del Re, Giuseppe Andò, Trifiro, G., Crisafulli, S., Ando, G., Racagni, G., Drago, F., Berrino, L., Re, M., Bernardini, R., Chiamulera, C., D'Avolio, A., Pani, L., Clementi, E., Capuano, A., Scaglione, F., Danesi, R., Cirino, G., Mugelli, A., Bonanno, G., Brunello, N., Luca, A., Hrelia, P., Pistis, M., Ghelardini, C., and Taglialatela, M.

Subjects
Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Pharmacology toxicology, Angiotensin-Converting Enzyme Inhibitors, Pharmacology, Toxicology, medicine.disease_cause, Article, Angiotensin Receptor Antagonists, Antihypertensive Agents, Betacoronavirus, Coronavirus Infections, Humans, Pandemics, Prognosis, Coronavirus, Diabetes Mellitus, Hypertension, Diabetes mellitus, Pandemic, Medicine, Pharmacology (medical), Viral, biology, SARS-CoV-2, business.industry, COVID-19, Pneumonia, biology.organism_classification, medicine.disease, Angiotensin Receptor Blockers, business
Published
2020

38. Association of neovascular age-related macular degeneration with month and season of birth in Italy

Author

Gilda Cennamo, Salvatore Cillino, Andrea Russo, Michele Reibaldi, Luca Pani, Vincenza Bonfiglio, Maurizio G. Uva, Alessandra Casuccio, Claudio Furino, Mariacristina Parravano, Entela Xoxi, Antonio Longo, Teresio Avitabile, Guglielmo Parisi, Longo, A., Casuccio, A., Pani, L., Avitabile, T., Cillino, S., Uva, M., Bonfiglio, V., Russo, A., Parisi, G., Cennamo, G., Furino, C., Parravano, M., Xoxi, E., Reibaldi, M., Longo, Antonio, Casuccio, Alessandra, Pani, Luca, Avitabile, Teresio, Cillino, Salvatore, Uva, Maurizio G, Bonfiglio, Vincenza, Russo, Andrea, Parisi, Guglielmo, Cennamo, Gilda, Furino, Claudio, Parravano, Mariacristina, Xoxi, Entela, and Reibaldi, Michele

Subjects
Male, Vascular Endothelial Growth Factor A, Aging, genetic structures, Month of birth, VEGF receptors, neovascular AMD, Angiogenesis Inhibitors, Aptamers, Macular Degeneration, 0302 clinical medicine, Season of birth, Receptors, 80 and over, Medicine, Registries, Aged, 80 and over, Neovascularization, Pathologic, biology, Vascular Endothelial Growth Factor, Incidence, Incidence (epidemiology), Aptamers, Nucleotide, Bevacizumab, Treatment Outcome, Italy, anti-VEGF, Female, Seasons, Nucleotide, Neovascular age-related macular degeneration, Research Paper, medicine.drug, Anti-VEGF, Neovascular AMD, Aged, Humans, Ranibizumab, Receptors, Vascular Endothelial Growth Factor, Recombinant Fusion Proteins, Cell Biology, neovascular age-related macular degeneration, 03 medical and health sciences, Age related, Neovascularization, Pathologic, season of birth, business.industry, month of birth, Macular degeneration, medicine.disease, eye diseases, 030221 ophthalmology & optometry, biology.protein, sense organs, business, 030217 neurology & neurosurgery, Demography
Abstract

In order to investigate the influence of season and month of birth on the risk of neovascular age-related macular degeneration (n-AMD) in Italy, we evaluated the month birth and sex of all patients, recorded in the anti-vascular endothelial growth factor (VEGF) monitoring registry of the Italian Medicines Agency, born between 1925-1944, who received intravitreal anti-VEGF injections for n-AMD between January 1, 2013 and July 29, 2015. The numbers of all births in Italy in the same years, extracted from the Italian National Institute of Statistics, were used to calculate the expected number of n-AMD cases. Overall, 45,845 patients (19,207 men, 26,638 women) received intravitreal anti-VEGF for n-AMD; in the same years, 20,140,426 people (10,334,262 male, 9,806,164 female) were born in Italy. Comparing the observed number of n-AMD cases with the expected number of n-AMD cases in each season, we found that the season-specific risk for n-AMD was 2.5% higher for those born in summer (OR= 1.03, Bonferroni-corrected P= 0.008) and 3% lower for those born in winter (OR= 0.96, Bonferroni-corrected P= 0.0004). When considering the month of birth, the risk of n-AMD was 5.9% lower for people born in January (OR= 0.93, Bonferroni-corrected P= 0.0012). The factors causing such differences should be determined.

Published
2016
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39. Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

Author

Giada Carolo, Veronica Bernabucci, Luchino Chessa, Maria Luisa Russo, Giorgio Maria Saracco, Marzia Montalbano, Barbara Menzaghi, Giovanni Di Perri, Adriano Lazzarin, Silvia La Monica, Raffaele Bruno, Gian Ludovico Rapaccini, Mario U. Mondelli, Anna Maria Schimizzi, Caterina Pasquazzi, Maurizia Rossana Brunetto, Antonio Craxì, Filomena Morisco, Carmela Lo Guercio, Vania Giacomet, Alessia Giorgini, Mario Masarone, Francesca Paolo Russo, T. Zolfino, Vincenzo Sangiovanni, Alessia Ciancio, Antonella d'Arminio Monforte, Savino Bruno, E.M. Erne, Antonio Gasbarrini, Francesco Castelli, Sergio Novara, G. Nardone, Andrea De Luca, Claudio Maria Mastroianni, Gioacchino Angarano, Chiara Dentone, Renato Maserati, Anna Maria Piscaglia, Tiziana Quirino, Giuseppe Tarantino, M. Lichtner, Antonio Chirianni, Giuseppina Brancaccio, S. Paganin, Alfredo Alberti, Silvia Corradori, Edoardo G. Giannini, Carlo Torti, Chiara Boarini, Raffaele Cozzolongo, Marco Di Stefano, Alessandro Soria, Paolo Tundi, Giovanni Cassola, Debora Angrisani, Antonio Grieco, Cecilia Pravadelli, Giuliano Rizzardini, Roberto Gulminetti, Vincenzo Messina, Maria Rendina, Massimo Pirisi, Irene Cacciola, Roberto Ganga, Raffaella Lionetti, Paolo Calabrese, Laura Ponti, Filomena Simeone, Maurizio Russello, Monica Monti, Nicola Boffa, Pierluigi Tarquini, Franco Capra, Ivo Avancini, Domenico Sansonno, Stefano Fagiuoli, Michele Barone, Giacomo Vecchiet, Salvatore Rizzo, Carlo Federico Perno, Teresa Santantonio, Pierluigi Toniutto, Massimo Zuin, Nicola Caporaso, Alessandra Orlandini, Grazielle Marie Pigozzi, Martina Felder, Antonio Cristaudo, Roberto Cecere, Massimo Marignani, Vincenza Calvaruso, G. Abbati, Domenico Potenza, Maria Chiara Piras, Mario Rizzetto, Serena Cima, Marco delle Monache, Alessio Aghemo, D. Ieluzzi, Guglielmo Borgia, Giampaolo Corti, Paolo Poggio, Manuela Merli, Elena Danieli, Andrea Giacometti, Massimo Andreoni, Antonino Picciotto, Mario Angelico, Benedetta Canovari, Sara Piovesan, Anna Linda Zignego, Antonio Benedetti, Emanuele Durante, Erica Villa, Marcello Persico, Antonio Patrizio Termite, Barbara Coco, Maria Vinci, Lucio Boglione, Cristina Rossi, Paolo Angeli, Massimo Memoli, Maria Teresa Giordani, Massimo De Luca, Luisa Pasulo, Vincenzo Vullo, Mario Melazzini, Attilio Solinas, Pietro Gatti, Michele Guerra, Silvia Martini, Antonio Ascione, Massimo Puoti, Roberto Cauda, Giovanna Onnelli, Silvia Magnani, Salvatore Madonna, Giovanni Raimondo, Marco Tabone, Gloria Taliani, Dante Romagnoli, Aldo Marrone, Umberto Vespasiani Gentilucci, Luca Miele, Marcello Tavio, Andrea Antinori, Giampiero D'Offizi, Mirella Onofrio, Valentina Iodice, Lucio Cosco, Guido Piai, Luca Pani, Francesca Ceccherini Silberstein, Simona Montilla, Marco Lenzi, Luca Fontanella, Alessandro Federico, Carlo Ferrari, Giustino Parruti, Antonio Di Biagio, Gabriella Verucchi, Fabio Marsetti, Michele Milella, Maria Grazia Rumi, Antonio Izzi, Marco Marzioni, Francesca Donato, Vanni Borghi, Mariano Quartini, Massimo Colombo, Michele Imparato, Giovanni Battista Gaeta, P.L. Blanc, Alfredo Di Leo, Nicola Coppola, Alessandro Chiodera, Ivana Maida, Davide Campagnolo, Cinzia Antonini, Antonietta Romano, A. Gianstefani, Katia Falasca, Massimo Levrero, Gaetano Serviddio, Maria Paola Trotta, Olivia Morelli, Salvatore Petta, Elisabetta Teti, Maria Rita Parisi, Pietro Andreone, Ascione, Antonio, De Luca, Massimo, Melazzini, Mario, Montilla, Simona, Trotta, Maria Paola, Petta, Salvatore, Puoti, Massimo, Sangiovanni, Vincenzo, Messina, Vincenzo, Bruno, Savino, Izzi, Antonio, Villa, Erica, Aghemo, Alessio, Zignego, Anna Linda, Orlandini, Alessandra, Fontanella, Luca, Gasbarrini, Antonio, Marzioni, Marco, Giannini, Edoardo G., Craxì, Antonio, Abbati, Giuseppe, Alberti, Alfredo, Andreone, Pietro, Andreoni, Massimo, Angeli, Paolo, Angelico, Mario, Angarano, Gioacchino, Angrisani, Debora, Antinori, Andrea, Antonini, Cinzia, Avancini, Ivo, Barone, Michele, Bruno, Raffaele, Benedetti, Antonio, Bernabucci, Veronica, Blanc, Pier, Boarini, Chiara, Boffa, Nicola, Boglione, Lucio, Borghi, Vanni, Borgia, Guglielmo, Brancaccio, Giuseppina, Brunetto, Maurizia, Cacciola, Irene, Calabrese, Paolo, Calvaruso, Vincenza, Campagnolo, Davide, Canovari, Benedetta, Caporaso, Nicola, Capra, Franco, Carolo, Giada, Cassola, Giovanni, Castelli, Francesco, Cauda, Roberto, Silberstein, Francesca Ceccherini, Cecere, Roberto, Chessa, Luchino, Chiodera, Alessandro, Chirianni, Antonio, Ciancio, Alessia, Cima, Serena, Coco, Barbara, Colombo, Massimo, Coppola, Nicola, Corti, Giampaolo, Cosco, Lucio, Corradori, Silvia, Cozzolongo, Raffaele, Cristaudo, Antonio, Danieli, Elena, Monforte, Antonella D’Arminio, Monache, Marco delle, Del Poggio, Paolo, de Luca, Andrea, Dentone, Chiara, Di Biagio, Antonio, Di Leo, Alfredo, Di Perri, Giovanni, Di Stefano, Marco, D’Offizi, Giampiero, Donato, Francesca, Durante, Emanuele, Erne, Elke, Fagiuoli, Stefano, Falasca, Katia, Federico, Alessandro, Felder, Martina, Ferrari, Carlo, Gaeta, Giovanni Battista, Ganga, Roberto, Gatti, Pietro, Giacomet, Vania, Giacometti, Andrea, Gianstefani, Alice, Giordani, Maria, Giorgini, Alessia, Grieco, Antonio, Guerra, Michele, Gulminetti, Roberto, Ieluzzi, Donatella, Imparato, Michele, Iodice, Valentina, La Monica, Silvia, Lazzarin, Adriano, Lenzi, Marco, Levrero, Massimo, Lichtner, Myriam, Lionetti, Raffaella, Guercio, Carmela Lo, Madonna, Salvatore, Magnani, Silvia, Maida, Ivana, Marignani, Massimo, Marrone, Aldo, Marsetti, Fabio, Martini, Silvia, Masarone, Mario, Maserati, Renato, Mastroianni, Claudio Maria, Memoli, Massimo, Menzaghi, Barbara, Merli, Manuela, Miele, Luca, Milella, Michele, Mondelli, Mario, Montalbano, Marzia, Monti, Monica, Morelli, Olivia, Morisco, Filomena, Nardone, Gaetano, Novara, Sergio, Onnelli, Giovanna, Onofrio, Mirella, Paganin, Simona, Pani, Luca, Parisi, Maria Rita, Parruti, Giustino, Pasquazzi, Caterina, Pasulo, Luisa, Perno, Carlo Federico, Persico, Marcello, Piai, Guido, Picciotto, Antonino, Pigozzi, Grazielle Marie, Piovesan, Sara, Piras, Maria Chiara, Pirisi, Massimo, Piscaglia, Anna Maria, Ponti, Laura, Potenza, Domenico, Pravadelli, Cecilia, Quartini, Mariano, Quirino, Tiziana, Raimondo, Giovanni, Rapaccini, Gian Ludovico, Rendina, Maria, Rizzardini, Giuliano, Rizzetto, Mario, Rizzo, Salvatore, Romagnoli, Dante, Romano, Antonietta, Rossi, Cristina, Rumi, Maria Grazia, Russello, Maurizio, Russo, Francesca Paolo, Russo, Maria Luisa, Sansonno, Domenico Ettore, Santantonio, Teresa Antonia, Saracco, Giorgio, Schimizzi, Anna Maria, Serviddio, Gaetano, Simeone, Filomena, Solinas, Attilio, Soria, Alessandro, Tabone, Marco, Taliani, Gloria, Tarantino, Giuseppe, Tarquini, Pierluigi, Tavio, Marcello, Termite, Antonio, Teti, Elisabetta, Toniutto, Pierluigi, Torti, Carlo, Tundi, Paolo, Vecchiet, Giacomo, Verucchi, Gabriella, Gentilucci, Umberto Vespasiani, Vinci, Maria, Vullo, Vincenzo, Zolfino, Teresa, Zuin, Massimo, Ascione, A, De Luca, M, Melazzini, M, Montilla, S, Trotta, M, Petta, S, Puoti, M, Sangiovanni, V, Messina, V, Bruno, S, Izzi, A, Villa, E, Aghemo, A, Zignego, A, Orlandini, A, Fontanella, L, Gasbarrini, A, Marzioni, M, Giannini, E, Craxi, A, Abbati, G, Alberti, A, Andreone, P, Andreoni, M, Angeli, P, Angelico, M, Angarano, G, Angrisani, D, Antinori, A, Antonini, C, Avancini, I, Barone, M, Bruno, R, Benedetti, A, Bernabucci, V, Blanc, P, Boarini, C, Boffa, N, Boglione, L, Borghi, V, Borgia, G, Brancaccio, G, Brunetto, M, Cacciola, I, Calabrese, P, Calvaruso, V, Campagnolo, D, Canovari, B, Caporaso, N, Capra, F, Carolo, G, Cassola, G, Castelli, F, Cauda, R, Silberstein, F, Cecere, R, Chessa, L, Chiodera, A, Chirianni, A, Ciancio, A, Cima, S, Coco, B, Colombo, M, Coppola, N, Corti, G, Cosco, L, Corradori, S, Cozzolongo, R, Cristaudo, A, Danieli, E, Monforte, A, Monache, M, Del Poggio, P, de Luca, A, Dentone, C, Di Biagio, A, Di Leo, A, Di Perri, G, Di Stefano, M, D'Offizi, G, Donato, F, Durante, E, Erne, E, Fagiuoli, S, Falasca, K, Federico, A, Felder, M, Ferrari, C, Gaeta, G, Ganga, R, Gatti, P, Giacomet, V, Giacometti, A, Gianstefani, A, Giordani, M, Giorgini, A, Grieco, A, Guerra, M, Gulminetti, R, Ieluzzi, D, Imparato, M, Iodice, V, La Monica, S, Lazzarin, A, Lenzi, M, Levrero, M, Lichtner, M, Lionetti, R, Guercio, C, Madonna, S, Magnani, S, Maida, I, Marignani, M, Marrone, A, Marsetti, F, Martini, S, Masarone, M, Maserati, R, Mastroianni, C, Memoli, M, Menzaghi, B, Merli, M, Miele, L, Milella, M, Mondelli, M, Montalbano, M, Monti, M, Morelli, O, Morisco, F, Nardone, G, Novara, S, Onnelli, G, Onofrio, M, Paganin, S, Pani, L, Parisi, M, Parruti, G, Pasquazzi, C, Pasulo, L, Perno, C, Persico, M, Piai, G, Picciotto, A, Pigozzi, G, Piovesan, S, Piras, M, Pirisi, M, Piscaglia, A, Ponti, L, Potenza, D, Pravadelli, C, Quartini, M, Quirino, T, Raimondo, G, Rapaccini, G, Rendina, M, Rizzardini, G, Rizzetto, M, Rizzo, S, Romagnoli, D, Romano, A, Rossi, C, Rumi, M, Russello, M, Russo, F, Russo, M, Sansonno, D, Santantonio, T, Saracco, G, Schimizzi, A, Serviddio, G, Simeone, F, Solinas, A, Soria, A, Tabone, M, Taliani, G, Tarantino, G, Tarquini, P, Tavio, M, Termite, A, Teti, E, Toniutto, P, Torti, C, Tundi, P, Vecchiet, G, Verucchi, G, Gentilucci, U, Vinci, M, Vullo, V, Zolfino, T, and Zuin, M

Subjects
Cyclopropanes, Liver Cirrhosis, Male, Cirrhosis, Dasabuvir, Elderly, Ombitasvir, Paritaprevir, Aged, 80 and over, Anilides, Antiviral Agents, Biomarkers, Carbamates, Female, Hepacivirus, Hepatitis C, Chronic, Humans, Macrocyclic Compounds, Ribavirin, Ritonavir, Sulfonamides, Treatment Outcome, Uracil, Drug Therapy, Combination, Genotype, Cirrhosis, Dasabuvir, Elderly, Ombitasvir, Paritaprevir, Microbiology (medical), Infectious Diseases, Aged, 80 and over, Hepatitis C, Chronic, Drug Therapy, Combination, Microbiology (medical), Infectious Diseases, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, 2-Naphthylamine, Medicine, 030212 general & internal medicine, Valine, General Medicine, 030211 gastroenterology & hepatology, Macrocyclic Compound, medicine.drug, Human, medicine.medical_specialty, Proline, Lactams, Macrocyclic, Settore MED/12 - GASTROENTEROLOGIA, Liver Cirrhosi, Sulfonamide, 03 medical and health sciences, Internal medicine, Decompensation, Hepatitis, Antiviral Agent, Cirrhosi, Hepaciviru, business.industry, Settore MED/09 - MEDICINA INTERNA, Anilide, Biomarker, medicine.disease, chemistry, Carbamate, business
Abstract

Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100mg) and twice-daily dasabuvir (250mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.

Published
2018

40. The Italian compassionate use of sofosbuvir in HCV patients waitlisted for liver transplantation: A national real-life experience

Author

Martini, Silvia, Donato, Maria Francesca, Mazzarelli, Chiara, Rendina, Maria, Visco-Comandini, Ubaldo, Filì, Daniela, Gianstefani, Alice, Fagiuoli, Stefano, Melazzini, Mario, Montilla, Simona, Pani, Luca, Petraglia, Sandra, Russo, Pierluigi, Trotta, Maria Paola, Carrai, Paola, Caraceni, Paolo, ITACOPS study group, Angeli, P, Ballardini, G, Bernabucci, V, Bhoori, S, Burra, P, Civolani, A, D'Offizi, G, Felder, M, Gaeta, Gb, Ganga, R, Ginanni Corradini, S, Iemmolo, Rm, Lenci, I, Lionetti, R, Montalbano, M, Morelli, Mc, Picciotto, A, Sapere, C, Serviddio, G, Tamè, M, Verucchi, G, Zignego, A. L., Martini, Silvia, Donato, Maria Francesca, Mazzarelli, Chiara, Rendina, Maria, Visco-Comandini, Ubaldo, Filì, Daniela, Gianstefani, Alice, Fagiuoli, Stefano, Melazzini, Mario, Montilla, Simona, Pani, Luca, Petraglia, Sandra, Russo, Pierluigi, Trotta, Maria Paola, Carrai, Paola, Caraceni, Paolo, Martini, S, Donato, M, Mazzarelli, C, Rendina, M, Visco-Comandini, U, Fili, D, Gianstefani, A, Fagiuoli, S, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Carrai, P, Caraceni, P, Angeli, P, Ballardini, G, Bernabucci, V, Bhoori, S, Burra, P, Civolani, A, D'Offizi, G, Felder, M, Gaeta, G, Ganga, R, Ginanni Corradini, S, Iemmolo, R, Lenci, I, Lionetti, R, Montalbano, M, Morelli, M, Picciotto, A, Sapere, C, Serviddio, G, Tame, M, Verucchi, G, and Zignego, A

Subjects
Compassionate Use Trials, Liver Cirrhosis, Male, Cirrhosis, Sofosbuvir, bridging therapy, decompensated cirrhosis, delisting, direct-acting antivirals, hepatitis C, liver transplantation, Adult, Aged, Antiviral Agents, Carcinoma, Hepatocellular, Drug Therapy, Combination, Female, Hepacivirus, Hepatitis C, Chronic, Humans, Italy, Kaplan-Meier Estimate, Liver Neoplasms, Middle Aged, Prospective Studies, Ribavirin, Liver Transplantation, Waiting Lists, Hepatology, medicine.medical_treatment, Liver transplantation, chemistry.chemical_compound, 0302 clinical medicine, Chronic, Hepatitis C, 030220 oncology & carcinogenesis, Combination, 030211 gastroenterology & hepatology, medicine.drug, medicine.medical_specialty, 03 medical and health sciences, Drug Therapy, Internal medicine, medicine, direct-acting antiviral, business.industry, decompensated cirrhosi, Carcinoma, Hepatocellular, medicine.disease, Surgery, Transplantation, chemistry, business
Abstract

Background & aims This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. Methods Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. Results Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for

Published
2018

41. Kounis syndrome due to antibiotics: A global overview from pharmacovigilance databases

Author

Virginia Cuconato, Giovanni Landoni, Francesca Renda, Luca Pani, Alessandro Belletti, Elena Marotta, Renda, F, Marotta, E, Landoni, Giovanni, Belletti, A, Cuconato, V, and Pani, L.

Subjects
Male, Acute coronary syndrome, Databases, Factual, medicine.drug_class, Antibiotics, Histamine Antagonists, Coronary Vasospasm, Kounis syndrome, 030204 cardiovascular system & hematology, computer.software_genre, Amoxicillin-Potassium Clavulanate Combination, 03 medical and health sciences, Pharmacovigilance, 0302 clinical medicine, Rare Diseases, Clavulanic acid, Medicine, Humans, 030212 general & internal medicine, Acute Coronary Syndrome, Adverse effect, Anaphylaxis, Glucocorticoids, Database, business.industry, Syndrome, Amoxicillin, Middle Aged, medicine.disease, Anti-Bacterial Agents, Female, Cardiology and Cardiovascular Medicine, business, computer, Coronary vasospasm, Drug hypersensitivity, Myocardial infarction, Rare diseases, medicine.drug
Abstract

Background Kounis syndrome (KS) is characterized by concurrent presence of anaphylactic and cardiac components. Available evidence suggests that antibiotics are frequently associated to KS. We therefore analyzed KS cases associated with antibiotics use from the two largest pharmacovigilance databases. Methods Two pharmacovigilance databases, EudraVigilance and VigiLyze, were searched for cases reporting the adverse reaction "Kounis Syndrome" with antibiotics as suspected active substance. We analyzed the period from December 1st, 2001 to February 16th, 2016. For the most reported active substance, proportional reporting ratio (PRR) was calculated. Results A total of 10 cases of KS associated with antibiotic use were retrieved from EudraVigilance database. Mean patients' age was 58.2years and 70% were male. The most frequently reported suspected antibiotic was the combination amoxicillin/clavulanic acid (four cases). VigiLyze database reported 13 KS cases associated to antibiotics. Mean age was 56years and 61% of patients were male. The most frequently reported antibiotic was again the combination amoxicillin/clavulanic acid (five cases). Seven duplicate cases were identified, leaving a total of 16 cases of KS, with six of them associated to amoxicillin/clavulanic acid use. The PRR value for amoxicillin/clavulanic acid against other kinds of antibiotics was 2.62 considering EudraVigilance data and 1.61 considering VigiLyze data. Conclusions This analysis provided a complete picture of the cases of KS associated with antibiotic use and identified a possible association between amoxicillin/clavulanic acid and KS. Since the number of cases is low, especially considering its wide use, further analyses are needed to confirm the association.

Published
2016

42. Kounis Syndrome: An analysis of spontaneous reports from international pharmacovigilance database

Author

Francesca Renda, Francesco Trotta, Luca Pani, Patrizia Felicetti, Gabriele Finco, Giuseppe Pimpinella, Desiderio Piras, Giovanni Landoni, Renda, F, Landoni, Giovanni, Trotta, F, Piras, D, Finco, G, Felicetti, P, Pimpinella, G, and Pani, L.

Subjects
Adult, Male, Acute coronary syndrome, Databases, Factual, Coronary vasospasm, Drug hypersensivity, Miocardial infarction, Rare diseases, Acute Coronary Syndrome, Anaphylaxis, Female, Global Health, Humans, Middle Aged, Myocardial Infarction, Pharmacovigilance, Syndrome, Kounis syndrome, 030204 cardiovascular system & hematology, computer.software_genre, World health, Databases, 03 medical and health sciences, 0302 clinical medicine, medicine, Global health, 030212 general & internal medicine, Myocardial infarction, Factual, Database, business.industry, medicine.disease, Cardiology and Cardiovascular Medicine, business, computer
Abstract

Introduction The coincidental occurrence of a cardiac symptomatology (e.g. an acute coronary syndrome or a myocardial infarction), during an anaphylactic or anaphylactoid episode is known as Kounis Syndrome. A variety of drugs, substances, food and environmental exposures are associated with this reaction. There is an exponential increase in the number of published scientific articles reports on this syndrome, but since it is rare, the largest case series published so far included only 10 and 6 patients. Methods We searched the global World Health Organization database called VigiBase™ to detect all cases of Kounis Syndrome ever reported (last update December 31st 2014). Results We identified 51 cases of Kounis Syndrome reported to International Pharmacovigilance Agency (VigiBase™). All these cases were reported in the period 2010–2014 and almost half cases (22 reports) belonged to the year 2014. Most cases occurred in the USA and non-steroidal anti-inflammatory drugs were the most frequent trigger drugs. Discussion We collected pharmacovigilance international data representing the largest case series ever published on the recently identified Kounis Syndrome.

Published
2015

43. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A National Analysis of Data from 10-Year Post-marketing Surveillance

Author

Luca Pani, Giuseppe Pimpinella, Marta Mucchetti, Renato Bertini Malgarini, Francesca Renda, Giovanni Landoni, Maria Luisa Azzolini, Alessandro Assisi, Renda, F, Landoni, Giovanni, Bertini Malgarini, R, Assisi, A, Azzolini, Ml, Mucchetti, M, Pimpinella, G, and Pani, L.

Subjects
Adult, Male, Drug, medicine.medical_specialty, media_common.quotation_subject, Postmarketing surveillance, Toxicology, Marketing authorization, Risk Factors, Pharmacovigilance, Product Surveillance, Postmarketing, Aged, Drug Hypersensitivity Syndrome, Female, Humans, Italy, Middle Aged, Pharmaceutical Preparations, Medicine, Pharmacology (medical), media_common, Pharmacology, business.industry, Mortality rate, medicine.disease, Dermatology, Immunology, Etiology, business, Adverse drug reaction
Abstract

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, severe and potentially fatal cutaneous adverse drug reaction (the mortality rate is up to 10 %) associated with numerous and apparently heterogeneous drugs. The aetiology is unknown. OBJECTIVE: To report Italian cases of DRESS over a 10-year period. METHODS: We searched the National Pharmacovigilance Network (NPN) for the term 'drug reaction with eosinophilia and systemic symptoms' from 1 January 2004 to 1 January 2014, to identify all reports of DRESS. Each case was checked to avoid duplication. RESULTS: In the NPN, we identified 91 serious cases of DRESS: 68 were spontaneous, still-unpublished reports, while 23 additional cases were derived from screening of the scientific literature, performed by marketing authorization holders. Notably, the single common element linking all cases of DRESS was intake of a drug containing an aromatic ring. CONCLUSION: Thanks to the largest national DRESS case series ever reported, we were able to hypothesize, for the first time, that there is an association between use of drugs containing an aromatic ring in their chemical structure and DRESS. This might aid understanding of the aetiology of DRESS and facilitate diagnosis.

Published
2015

44. Red Yeast Rice or Lovastatin? A Comparative Evaluation of Safety and Efficacy Through a Multifaceted Approach.

Author

Rigillo G, Baini G, Bruni R, Puja G, Miraldi E, Pani L, Tascedda F, and Biagi M

Abstract

The increasing use of red yeast rice (RYR) as a natural supplement to manage blood cholesterol levels is driven by its active compound, monacolin K (MK), which is chemically identical to the statin drug lovastatin (LOV). Despite its growing popularity, concerns persists regarding the safety and efficacy of RYR compared to pure statins. This study aimed to evaluate the phytochemical composition, pharmacological effects, and safety profile of various RYR samples in comparison with LOV. RYR samples with different MK content were analyzed using HPLC-DAD to quantify monacolins and other bioactive compounds. The inhibitory activity on HMG-CoA reductase was assessed through an enzymatic assay, while pharmacokinetic properties were predicted using in vitro simulated digestion and in silico models. In vitro cytotoxicity was evaluated in intestinal, hepatic, renal, and skeletal muscle cell models. Additionally, the transcriptional levels of muscle damage-related target genes were evaluated by qRT-PCR in skeletal muscle cells treated with a selection of RYR samples. Significant variability in the phytochemical composition of RYR samples was observed, particularly in the content of secondary monacolins, triterpenes, and polyphenols. The RYR phytocomplex exhibited superior inhibition of HMG-CoA reductase activity compared to isolated LOV, suggesting synergistic effects between secondary monacolins and other compounds. Molecular insights revealed that RYR samples had a lower impact on muscle cells than LOV, as reflected also by cell viability. These findings suggest that RYR could serve as a safe alternative to purified statins. However, further research is needed to fully elucidate the mechanisms behind the synergistic activity of the phytocomplex and to firmly establish the clinical efficacy of this natural product., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Published
2024
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45. Comprehensive Analysis of Berberis aristata DC. Bark Extracts: In Vitro and In Silico Evaluation of Bioaccessibility and Safety.

Author

Rigillo G, Cappellucci G, Baini G, Vaccaro F, Miraldi E, Pani L, Tascedda F, Bruni R, and Biagi M

Subjects
Humans, Biological Availability, Cell Movement drug effects, Phytochemicals pharmacology, Phytochemicals pharmacokinetics, Cell Line, Tumor, Berberis chemistry, Plant Extracts pharmacology, Plant Extracts pharmacokinetics, Plant Bark chemistry, Berberine pharmacokinetics, Berberine analogs & derivatives, Berberine pharmacology, Computer Simulation
Abstract

Berberine (BER) is an alkaloid found, together with other protoberberinoids (PROTBERs), in several species used in medicines and food supplements. While some herbal preparations containing BER and PROTBERs, such as Berberis aristata DC. bark extracts, have shown promising potential for human health, their safety has not been fully assessed. Recently, the EFSA issued a call for data to deepen the pharmacokinetic and pharmacodynamic understanding of products containing BER and PROTBERs and to comprehensively assess their safety, especially when used in food supplements. In this context, new data were collected in this work by assessing: (i) the phytochemical profile of 16 different commercial B. aristata dry extracts, which are among the most widely used preparations containing BER and PROTBERs in Europe; (ii) the In Vitro and In Silico investigation of the pharmacokinetic properties of BER and PROTBERs; (iii) the In Vitro cytotoxicity of selected extracts in different human cell lines, including tests on hepatic cells in the presence of CYP450 substrates; (iv) the effects of the extracts on cancer cell migration; and (v) the In Vitro molecular effects of extracts in non-cancer human cells. Results showed that commercial B. aristata extracts contain BER as the main constituent, with jatrorrhizine as main secondary PROTBER. BER and jatrorrhizine were found to have a good bioaccessibility rate, but they interact with P-gp. B. aristata extracts showed limited cytotoxicity and minimal interaction with CYP450 substrates. Furthermore, tested extracts demonstrated inhibition of cancer cell migration and were devoid of any pro-tumoral effects in normal cells. Overall, our work provides a valuable overview to better elucidate important concerns regarding botanicals containing BER and PROTBERs.

Published
2024
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46. Different stressors uniquely affect the expression of endocannabinoid-metabolizing enzymes in the central ring ganglia of Lymnaea stagnalis.

Author

Rivi V, Rigillo G, Batabyal A, Lukowiak K, Pani L, Tascedda F, Benatti C, and Blom JMC

Subjects
Animals, Ganglia, Invertebrate metabolism, Ganglia, Invertebrate enzymology, Stress, Physiological physiology, Lipopolysaccharides pharmacology, Lymnaea metabolism, Endocannabinoids metabolism
Abstract

The endocannabinoid system (ECS) plays an important role in neuroprotection, neuroplasticity, energy balance, modulation of stress, and inflammatory responses, acting as a critical link between the brain and the body's peripheral regions, while also offering promising potential for novel therapeutic strategies. Unfortunately, in humans, pharmacological inhibitors of different ECS enzymes have led to mixed results in both preclinical and clinical studies. As the ECS has been highly conserved throughout the eukaryotic lineage, the use of invertebrate model organisms like the pond snail Lymnaea stagnalis may provide a flexible tool to unravel unexplored functions of the ECS at the cellular, synaptic, and behavioral levels. In this study, starting from the available genome and transcriptome of L. stagnalis, we first identified putative transcripts of all ECS enzymes containing an open reading frame. Each predicted protein possessed a high degree of sequence conservation to known orthologues of other invertebrate and vertebrate organisms. Sequences were confirmed by qualitative PCR and sequencing. Then, we investigated the transcriptional effects induced by different stress conditions (i.e., bacterial LPS injection, predator scent, food deprivation, and acute heat shock) on the expression levels of the enzymes of the ECS in Lymnaea's central ring ganglia. Our results suggest that in Lymnaea as in rodents, the ECS is involved in mediating inflammatory and anxiety-like responses, promoting energy balance, and responding to acute stressors. To our knowledge, this study offers the most comprehensive analysis so far of the ECS in an invertebrate model organism., (© 2024 International Society for Neurochemistry.)

Published
2024
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47. Behavioral and transcriptional effects of carnosine in the central ring ganglia of the pond snail Lymnaea stagnalis.

Author

Rivi V, Caruso G, Caraci F, Alboni S, Pani L, Tascedda F, Lukowiak K, Blom JMC, and Benatti C

Subjects
Animals, Ganglia, Invertebrate drug effects, Ganglia, Invertebrate metabolism, Neuronal Plasticity drug effects, Neuronal Plasticity physiology, Conditioning, Operant drug effects, Behavior, Animal drug effects, Lymnaea drug effects, Carnosine pharmacology, Memory, Long-Term drug effects, Memory, Long-Term physiology, Lipopolysaccharides pharmacology
Abstract

Carnosine is a naturally occurring endogenous dipeptide with well-recognized anti-inflammatory, antioxidant, and neuroprotective effects at the central nervous system level. To date, very few studies have been focused on the ability of carnosine to rescue and/or enhance memory. Here, we used a well-known invertebrate model system, the pond snail Lymnaea stagnalis, and a well-studied associative learning procedure, operant conditioning of aerial respiration, to investigate the ability of carnosine to enhance long-term memory (LTM) formation and reverse memory obstruction caused by an immune challenge (i.e., lipopolysaccharide [LPS] injection). Exposing snails to 1 mM carnosine for 1 h before training in addition to enhancing memory formation resulted in a significant upregulation of the expression levels of key neuroplasticity genes (i.e., glutamate ionotropic receptor N-methyl-d-aspartate [NMDA]-type subunit 1-LymGRIN1, and the transcription factor cAMP-response element-binding protein 1-LymCREB1) in snails' central ring ganglia. Moreover, pre-exposure to 1 mM carnosine before an LPS injection reversed the memory deficit brought about by inflammation, by preventing the upregulation of key targets for immune and stress response (i.e., Toll-like receptor 4-LymTLR4, molluscan defense molecule-LymMDM, heat shock protein 70-LymHSP70). Our data are thus consistent with the hypothesis that carnosine can have positive benefits on cognitive ability and be able to reverse memory aversive states induced by neuroinflammation., (© 2024 The Author(s). Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Published
2024
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48. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup.

Author

Jack CR Jr, Andrews JS, Beach TG, Buracchio T, Dunn B, Graf A, Hansson O, Ho C, Jagust W, McDade E, Molinuevo JL, Okonkwo OC, Pani L, Rafii MS, Scheltens P, Siemers E, Snyder HM, Sperling R, Teunissen CE, and Carrillo MC

Subjects
Humans, United States, Disease Progression, Brain pathology, Brain diagnostic imaging, National Institute on Aging (U.S.), tau Proteins cerebrospinal fluid, Alzheimer Disease diagnosis, Alzheimer Disease pathology, Biomarkers cerebrospinal fluid
Abstract

The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 and single work groups in 2012 and 2018 to create recommendations for the diagnosis and characterization of Alzheimer's disease (AD). The present document updates the 2018 research framework in response to several recent developments. Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine (e.g., oncology), and is becoming a unifying concept common to all neurodegenerative diseases, not just AD. The present document is consistent with this principle. Our intent is to present objective criteria for diagnosis and staging AD, incorporating recent advances in biomarkers, to serve as a bridge between research and clinical care. These criteria are not intended to provide step-by-step clinical practice guidelines for clinical workflow or specific treatment protocols, but rather serve as general principles to inform diagnosis and staging of AD that reflect current science. HIGHLIGHTS: We define Alzheimer's disease (AD) to be a biological process that begins with the appearance of AD neuropathologic change (ADNPC) while people are asymptomatic. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms. Early-changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers [especially phosphorylated tau 217]) map onto either the amyloid beta or AD tauopathy pathway; however, these reflect the presence of ADNPC more generally (i.e., both neuritic plaques and tangles). An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum. Later-changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms. An integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Published
2024
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50. Time- and Region-specific Effect of Vortioxetine on Central LPS-induced Transcriptional Regulation of NLRP3 Inflammasome.

Author

Ciani M, Rigillo G, Benatti C, Pani L, Blom JMC, Brunello N, Tascedda F, and Alboni S

Abstract

Background: Inflammasome overactivation, multiprotein complexes that trigger inflammatory responses, plays a critical role in Major Depressive Disorder (MDD) pathogenesis and treatment responses. Indeed, different antidepressants alleviate depression-related behaviours by specifically counteracting the NLRP3 inflammasome signalling pathway. The immunomodulatory effects of vortioxetine (VTX), a multimodal antidepressant with cognitive benefits, were recently revealed to counter memory impairment induced by a peripheral lipopolysaccharide (LPS) injection 24 hours (h) postchallenge., Methods: The potential link between VTX and NLRP3, along with other inflammasomes, remains unexplored. Hence, adult C57BL/6J male mice (n = 73) were fed with a standard or VTX-enriched diet (600 mg/kg of food, 28 days), injected with LPS (830 μg/kg) or saline, and sacrificed 6/24 h post-LPS. At these time-points, transcriptional effects of LPS and VTX's on NLRP3, NLRP1, NLRC4, AIM2 (inflammasomes), ASC and CASP1 (related subunits) and NEK7 mediator (NLRP3 regulator) were assessed in dorsal and ventral hippocampal subregions, frontal-prefrontal cortex and hypothalamus, brain regions serving behavioural-cognitive functions impaired in MDD., Results: Varied expression patterns of inflammasomes were revealed, with long-term NLRP3 and ASC transcriptional changes observed in response to LPS. It was discovered that VTX counteracted the LPS-mediated NLRP3 and ASC upregulation in memory-related brain areas like the dorsal hippocampus at 24 h time-point, potentially via regulating NEK7 expression. No VTX-mediated transcriptional effects were observed on other inflammasomes, reinforcing a potentially specific modulation on the NLRP3 inflammasome signalling pathway., Conclusion: Thus, a novel VTX's molecular mechanism in modulating the NLRP3 inflammasome in a time- and area-specific manner in the brain was highlighted, with significant clinical implications in treating depression and cognitive impairments.

., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Published
2024
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