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1. Testing for equivalence: an intersection-union permutation solution

Author

Arboretti, R., Carrozzo, E., Pesarin, F., and Salmaso, L.

Subjects
Statistics - Applications
Abstract

The notion of testing for equivalence of two treatments is widely used in clinical trials, pharmaceutical experiments,bioequivalence and quality control. It is essentially approached within the intersection-union (IU) principle. According to this principle the null hypothesis is stated as the set of effects lying outside a suitably established interval and the alternative as the set of effects lying inside that interval. The solutions provided in the literature are mostly based on likelihood techniques, which in turn are rather difficult to handle, except for cases lying within the regular exponential family and the invariance principle. The main goal of present paper is to go beyond most of the limitations of likelihood based methods, i.e. to work in a nonparametric setting within the permutation frame. To obtain practical solutions, a new IU permutation test is presented and discussed. A simple simulation study for evaluating its main properties, and three application examples are also presented., Comment: 21 pages, 2 figures

Published
2018

3. Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering

Author

Di Castelnuovo, A, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Costanzo, S, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Castiglione, G, Cicullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gaudiosi, C, Gentile, I, Gianfagna1, F, Giuliano, G, Graziani, E, Guarnieri, G, Langella, V, Larizza, G, Leone, A, Maccagni, G, Magni, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Meschiari, M, Milic, J, Minutolo, F, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pivato, C, Poletti, V, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Schiano Moriello, N, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Tamburrini, E, Torti, C, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virdis, A, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Gialluisi, Alessandro, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Costanzo, Simona, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio, Vergori, Alessandra, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Cannata, Francesco, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cicullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gaudiosi, Carlo, Gentile, Ivan, Gianfagna1, Francesco, Giuliano, Gabriele, Graziani, Emauele, Guarnieri, Gabriella, Langella, Valerio, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Magni, Federica, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mengozzi, Alessandro, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Mussinelli, Roberta, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Righetti, Giulia, Rognoni, Andrea, Rossato, Marco, Rossi, Ilaria, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Schiano Moriello, Nicola, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Tamburrini, Enrica, Torti, Carlo, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virdis, Agostino, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Costanzo, S, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Castiglione, G, Cicullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gaudiosi, C, Gentile, I, Gianfagna1, F, Giuliano, G, Graziani, E, Guarnieri, G, Langella, V, Larizza, G, Leone, A, Maccagni, G, Magni, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Meschiari, M, Milic, J, Minutolo, F, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pivato, C, Poletti, V, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Schiano Moriello, N, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Tamburrini, E, Torti, C, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virdis, A, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Gialluisi, Alessandro, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Costanzo, Simona, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio, Vergori, Alessandra, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Cannata, Francesco, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cicullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gaudiosi, Carlo, Gentile, Ivan, Gianfagna1, Francesco, Giuliano, Gabriele, Graziani, Emauele, Guarnieri, Gabriella, Langella, Valerio, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Magni, Federica, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mengozzi, Alessandro, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Mussinelli, Roberta, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Righetti, Giulia, Rognoni, Andrea, Rossato, Marco, Rossi, Ilaria, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Schiano Moriello, Nicola, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Tamburrini, Enrica, Torti, Carlo, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virdis, Agostino, De Caterina, Raffaele, and Iacoviello, Licia

Abstract

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Published
2021

4. Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Author

Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Aiello, L, Agostoni, P, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bologna, C, Bonfanti, P, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Chiarito, M, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Dalena, G, Dal Pra, C, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Filippini, T, Maria Fusco, F, Gaudiosi, C, Gentile, I, Gini, G, Grandone, E, Guarnieri, G, Lamanna, G, Larizza, G, Leone, A, Lio, V, Losito, A, Maccagni, G, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Milic, J, Minutolo, F, Molena, B, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Perroni, A, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Visconti, E, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Agostino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Ageno, Walter, Aiello, Luca, Agostoni, Piergiuseppe, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Chiarito, Mauro, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesco, Dalena, Giovanni, Dal Pra, Chiara, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Filippini, Tommaso, Maria Fusco, Francesco, Gaudiosi, Carlo, Gentile, Ivan, Gini, Giancarlo, Grandone, Elvira, Guarnieri, Gabriella, Lamanna, Gennaro L F, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Losito, Angela Raffaella, Maccagni, Gloria, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marra, Lorenzo, Maresca, Giulio, Marotta, Claudia, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Perroni, Annalisa, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Trecarichi, Enrico Maria, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Visconti, Elena, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Aiello, L, Agostoni, P, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bologna, C, Bonfanti, P, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Chiarito, M, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Dalena, G, Dal Pra, C, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Filippini, T, Maria Fusco, F, Gaudiosi, C, Gentile, I, Gini, G, Grandone, E, Guarnieri, G, Lamanna, G, Larizza, G, Leone, A, Lio, V, Losito, A, Maccagni, G, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Milic, J, Minutolo, F, Molena, B, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Perroni, A, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Visconti, E, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Agostino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Ageno, Walter, Aiello, Luca, Agostoni, Piergiuseppe, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Chiarito, Mauro, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesco, Dalena, Giovanni, Dal Pra, Chiara, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Filippini, Tommaso, Maria Fusco, Francesco, Gaudiosi, Carlo, Gentile, Ivan, Gini, Giancarlo, Grandone, Elvira, Guarnieri, Gabriella, Lamanna, Gennaro L F, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Losito, Angela Raffaella, Maccagni, Gloria, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marra, Lorenzo, Maresca, Giulio, Marotta, Claudia, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Perroni, Annalisa, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Trecarichi, Enrico Maria, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Visconti, Elena, Vocciante, Laura, De Caterina, Raffaele, and Iacoviello, Licia

Abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Published
2021

5. Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: the Multicenter Italian CORIST Study

Author

Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Guaraldi, G, Menicanti, L, Mennuni, M, Parruti, G, Patti, G, Santilli, F, Signorelli, C, Vergori, A, Abete, P, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fantoni, M, Fusco, F, Gentile, I, Gianfagna, F, Grandone, E, Graziani, E, Grisafi, L, Guarnieri, G, Larizza, G, Leone, A, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Montineri, A, Mussini, C, Musso, M, Niola, D, Odone, A, Olivieri, M, Palimodde, A, Parisi, R, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Poletti, V, Ravaglia, C, Rognoni, A, Rossato, M, Rossi, M, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Taddei, E, Torti, C, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Parruti, Giustino, Patti, Giuseppe, Santilli, Francesca, Signorelli, Carlo, Vergori, Alessandra, Abete, Pasquale, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Astuto, Marinella, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fantoni, Massimo, Fusco, Francesco Maria, Gentile, Ivan, Gianfagna, Francesco, Grandone, Elvira, Graziani, Emauele, Grisafi, Leonardo, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Montineri, Arturo, Mussini, Cristina, Musso, Maria, Niola, Daniela, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Parisi, Roberta, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Poletti, Venerino, Ravaglia, Claudia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Taddei, Eleonora, Torti, Carlo, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Guaraldi, G, Menicanti, L, Mennuni, M, Parruti, G, Patti, G, Santilli, F, Signorelli, C, Vergori, A, Abete, P, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fantoni, M, Fusco, F, Gentile, I, Gianfagna, F, Grandone, E, Graziani, E, Grisafi, L, Guarnieri, G, Larizza, G, Leone, A, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Montineri, A, Mussini, C, Musso, M, Niola, D, Odone, A, Olivieri, M, Palimodde, A, Parisi, R, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Poletti, V, Ravaglia, C, Rognoni, A, Rossato, M, Rossi, M, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Taddei, E, Torti, C, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Parruti, Giustino, Patti, Giuseppe, Santilli, Francesca, Signorelli, Carlo, Vergori, Alessandra, Abete, Pasquale, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Astuto, Marinella, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fantoni, Massimo, Fusco, Francesco Maria, Gentile, Ivan, Gianfagna, Francesco, Grandone, Elvira, Graziani, Emauele, Grisafi, Leonardo, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Montineri, Arturo, Mussini, Cristina, Musso, Maria, Niola, Daniela, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Parisi, Roberta, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Poletti, Venerino, Ravaglia, Claudia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Taddei, Eleonora, Torti, Carlo, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, De Caterina, Raffaele, and Iacoviello, Licia

Abstract

INTRODUCTION: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality.AIM: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients.METHODS: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores.RESULTS: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio=0.60; 95% confidence interval: 0.49-0.74; E-value=2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation.CONCLUSION: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Published
2021

6. RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

Author

Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, Mussinelli, R, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abete, P, Ageno, W, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Cianfrone, S, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Cozzi, O, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gentile, I, Graziani, E, Guarnieri, G, Larizza, G, Leone, A, Lio, V, Lucia, M, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scoppettuolo, G, Scorzolini, L, Sgariglia, R, Simeone, P, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, Iacoviello, L, De Caterina, R, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Mussinelli, Roberta, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Abete, Paolo, Ageno, Walter, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cianfrone, Stefania, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Cozzi, Ottavia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gentile, Ivan, Graziani, Emauele, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Lucia, Mothanje Barbara, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scoppettuolo, Giancarlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, Iacoviello, Licia, De Caterina, Raffaele, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, Mussinelli, R, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abete, P, Ageno, W, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Cianfrone, S, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Cozzi, O, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gentile, I, Graziani, E, Guarnieri, G, Larizza, G, Leone, A, Lio, V, Lucia, M, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scoppettuolo, G, Scorzolini, L, Sgariglia, R, Simeone, P, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, Iacoviello, L, De Caterina, R, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Mussinelli, Roberta, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Abete, Paolo, Ageno, Walter, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cianfrone, Stefania, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Cozzi, Ottavia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gentile, Ivan, Graziani, Emauele, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Lucia, Mothanje Barbara, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scoppettuolo, Giancarlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, Iacoviello, Licia, and De Caterina, Raffaele

Abstract

Objective: The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID-19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID-19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods: We analyzed 4,069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results: Out of 4,069 COVID-19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID-19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR=0.89, 0.67-1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N=2,057) patients (HR=1.00, 0.78-1.26 and HR=0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID-19 adult patients, 9,700 with hypertension) confirmed the absence of association. Conclusions: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID-19 patients.

Published
2020

14. The Clinical Use of Statistical Permutation Test Methodology: A Tool for Identifying Predictive Variables of Outcome

Author

Racioppi, M., primary, Salmaso, L., additional, Brombin, C., additional, Arboretti, R., additional, D''Agostino, D., additional, Colombo, R., additional, Serretta, V., additional, Brausi, M., additional, Casetta, G., additional, Gontero, P., additional, Hurle, R., additional, Tenaglia, R., additional, Altieri, V., additional, Bartoletti, R., additional, Maffezzini, M., additional, Siracusano, S., additional, Morgia, G., additional, and Bassi, P.F., additional

Published
2014
Full Text
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16. Epidemiological survey on severe infectious diseases

Author

Di Sabatino, G, Romero, M, Arboretti, R, Sasso, E, Spoltore, C, Tognoni, G, Orsini, A, Spolaor, A, Fantone, G, D'Antonio, D, Castellaneta, E, Parruti, G, Maretti, S, Di Biase, E, Ciarrocchi, M, Gatti, G, Evangelista, P, Altamura, G, Di Giammartino, D, Zaccagna, A, Forestieri, M, De Trana, L, Berardi, S, Scaramozzino, A, Megna, As, Maio, G, D'Alessio, G, Apperti, M, Iannuzzi, E, Langella, S, De Matteis, Va, Perillo, G, Pasi, E, Martuzzi, F, Fasulo, G, Pizzardi, Ca, Bersani, G, Bonsi, P, Sangiorgi, G, Potena, A, Ballerin, L, Petocchi, B, Vaccari, C, Pellegrino, F, Damonti, E, Civardi, G, Montagni, F, Bellvardo, C, Alberici, F, Ratti, G, Viani, N, Dallasta, A, Gabbi, E, Plescia, A, Corvetta, A, Imola, M, Pivi, P, Martelli, Lt, D'Orlando, L, Mercante, W, Silvestri, L, Poldini, F, Gullo, A, Cattaruzzi, C, Salmaso, F, Bertone, A, Vergine, C, Chierichini, A, Nardelli, S, Spiezia, R, Zanini, R, Vetica, A, Iaiani, G, Tirimbelli, L, Cudillo, L, Cannata, D, De Nardo, D, Buonomo, O, Curatola, D, Testore, G, Pavan, R, Rinaldi, P, Pagani, R, Mennini, Ms, Ciacco, E, Miano, C, Bianchi, R, Cinquini, S, Guarany, G, Parenzi, A, Sbordoni, L, Valentini, Gb, Artioli, S, Cassano, V, Goglio, A, De Gonda, F, Lorenzi, N, Gnecchi, F, Acquarolo, A, and Parati, G

Subjects
Settore MED/18 - Chirurgia Generale
Published
1997

17. The Clinical Use of Statistical Permutation Test Methodology: A Tool for Identifying Predictive Variables of Outcome.

Author

Racioppi, M., Salmaso, L., Brombin, C., arboretti, R., D''agostino, D., Colombo, R., Serretta, V., Brausi, M., Casetta, G., Gontero, P., Hurle, R., Tenaglia, R., altieri, V., Bartoletti, R., Maffezzini, M., Siracusano, S., Morgia, G., and Bassi, P.F.

Subjects
BLADDER cancer treatment, CYSTECTOMY, HEALTH outcome assessment, ONCOLOGY, HISTORY of medicine, MEDICAL databases
Abstract

Objectives: To identify the predictive variables affecting the outcome after radical surgery for bladder cancer by a newer statistical methodology, i.e. nonparametric combination (NPC). Methods: A multicenter study enrolled 1,312 patients who had undergone radical cystectomy for bladder cancer in 11 Italian oncological centers from January 1982 to December 2002. A statistical analysisof their medical history and diagnostic, pathological and postoperative variables was performed using a NPC test. Thepatients were included in a comprehensive database with medical history and clinical and pathological data. Five-year survival was used as the dependent variable, and p values were corrected for multiplicity using a closed testing procedure. The newer nonparametric approach was used to evaluate the prognostic importance of the variables. All of the analyses were performed using routines developed in MATLAB© and the significance level was set at α = 0.05. Results: A significant prognostic predictive value (p < 0.01) for tumor clinical staging, hydronephrosis, tumor pathological staging, grading, presence of concomitant carcinoma in situ, regional lymph node involvement, corpora cavernosa invasion, microvascular invasion, lymphatic invasion and prostatic stroma involvement was found. Conclusions: The NPC test could handle any type of variable (categorical and quantitative) and take into account the multivariate relation among variables. This newer methodology offers a significant contribution in biomedical studies with several endpoints and is recommended in presence of non-normal data and missing values, as well as solving high-dimensional data and problems relating to small sample sizes. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2015
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18. Epidemiological survey on severe infectious diseases,Progetto SETIG: La sorveglianza prospettica

Author

Di Sabatino, G., Romero, M., Arboretti, R., Sasso, E., Spoltore, C., Tognoni, G., Orsini, A., Spolaor, A., Fantone, G., D Antonio, D., Castellaneta, E., Parruti, G., Maretti, S., Di Biase, E., Ciarrocchi, M., Gatti, G., Evangelista, P., Altamura, G., Di Giammartino, D., Zaccagna, A., Forestieri, M., Trana, L., Berardi, S., Scaramozzino, A., Megna, A. S., Maio, G., D Alessio, G., Apperti, M., Iannuzzi, E., Langella, S., Matteis, V. A., Perillo, G., Pasi, E., Martuzzi, F., Fasulo, G., Pizzardi, C. A., Bersani, G., Bonsi, P., Sangiorgi, G., Potena, A., Ballerin, L., Petocchi, B., Vaccari, C., Pellegrino, F., Damonti, E., Civardi, G., Montagni, F., Bellvardo, C., Alberici, F., Ratti, G., Viani, N., Dallasta, A., Gabbi, E., Plescia, A., Corvetta, A., Imola, M., Pivi, P., Martelli, L. T., D Orlando, L., Mercante, W., Silvestri, L., Poldini, F., Gullo, A., Cattaruzzi, C., Salmaso, F., Bertone, A., Vergine, C., Chierichini, A., Nardelli, S., Spiezia, R., Zanini, R., Vetica, A., Iaiani, G., Tirimbelli, L., Cudillo, L., Cannata, D., Nardo, D., Buonomo, O., Curatola, D., Testore, G., Pavan, R., Rinaldi, P., Pagani, R., Mennini, M. S., Ciacco, E., Miano, C., Bianchi, R., Cinquini, S., Guarany, G., Parenzi, A., Sbordoni, L., Valentini, G. B., Artioli, S., Cassano, V., Goglio, A., Gonda, F., Lorenzi, N., Gnecchi, F., Acquarolo, A., and Gianfranco Parati

19. Heparin in COVID-19 patients is associated with reduced in-hospital mortality: the multicentre Italian CORIST Study

Author

Walter Ageno, Raffaele Pesavento, Marinella Astuto, Katleen de Gaetano Donati, Francesca Santilli, Filippo Aucella, Eleonora Taddei, Marianna Meschiari, Laura Scorzolini, Biagio Pinchera, Giustino Parruti, Licia Iacoviello, Andrea Vianello, Gabriella Guarnieri, Arturo Montineri, Crizia Colombo, Carlo Signorelli, Lorenzo Blandi, Raffaele De Caterina, Maria Musso, Francesco Petri, Stefano Maitan, Anna Odone, Lucia Caiano, Francesca Crosta, Lorenzo Marra, Giuseppe Patti, Emanuela Pasi, Jovana Milic, Marco Olivieri, Claudia Colomba, Francesco Maria Fusco, Claudia Ravaglia, Alexandra Virano, Carlo Torti, Samir Al Moghazi, Venerino Poletti, Riccardo Maragna, Carlo Sanrocco, Sandro Mancarella, Greta Barbieri, Arturo Ciccullo, Leonardo Grisafi, Paola Simeone, Lorenzo Menicanti, Antonella Palimodde, Gloria Maccagni, Alessandra Vergori, Daniela Niola, Marco G. Mennuni, Gianpiero D'Offizi, Claudia Marotta, Damiano D'Ardes, Vincenzo Sangiovanni, Paolo Bonfanti, Giovanni Larizza, Francesco Di Gennaro, Alessandro Mengozzi, Massimo Mapelli, Giuseppe Di Tano, Laura Carrozzi, Antonella Agodi, Francesco Menichetti, Marialaura Bonaccio, Andrea Antinori, Marco Vinceti, Armando Leone, Franco Mastroianni, Silvia Marongiu, Filippo Minutolo, Giulio Maresca, Beatrice Molena, Nausicaa Berselli, Francesco Cipollone, Massimo Fantoni, Antonella Cingolani, Giovanni Guaraldi, Raffaella Sgariglia, Piergiuseppe Agostoni, Antonio Cascio, Maria Mazzitelli, Roberta Parisi, Augusto Di Castelnuovo, Gian Battista Danzi, Luca Aiello, Roberto Vettor, Elvira Grandone, Laura Vocciante, Emauele Graziani, Cristina Mussini, Marianna Rossi, Marco Rossato, Roberto Cauda, Rosa Arboretti, Alessandro Bartoloni, Simona Costanzo, Francesco Gianfagna, Andrea Rognoni, Ferruccio Madaro, Rossella Marcucci, Pasquale Abete, Francesco Cacciatore, Ivan Gentile, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Guaraldi, G, Menicanti, L, Mennuni, M, Parruti, G, Patti, G, Santilli, F, Signorelli, C, Vergori, A, Abete, P, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fantoni, M, Fusco, F, Gentile, I, Gianfagna, F, Grandone, E, Graziani, E, Grisafi, L, Guarnieri, G, Larizza, G, Leone, A, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Montineri, A, Mussini, C, Musso, M, Niola, D, Odone, A, Olivieri, M, Palimodde, A, Parisi, R, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Poletti, V, Ravaglia, C, Rognoni, A, Rossato, M, Rossi, M, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Taddei, E, Torti, C, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, De Caterina, R, Iacoviello, L, Danzi, G. B, De Gaetano Donati, K, Fusco, F. M, Simeone, P. G, Iacoviello, L., Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Parruti, Giustino, Patti, Giuseppe, Santilli, Francesca, Signorelli, Carlo, Vergori, Alessandra, Abete, Pasquale, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Astuto, Marinella, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fantoni, Massimo, Fusco, Francesco Maria, Gentile, Ivan, Gianfagna, Francesco, Grandone, Elvira, Graziani, Emauele, Grisafi, Leonardo, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Montineri, Arturo, Mussini, Cristina, Musso, Maria, Niola, Daniela, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Parisi, Roberta, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Poletti, Venerino, Ravaglia, Claudia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Taddei, Eleonora, Torti, Carlo, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo A., Costanzo S., Antinori A., Berselli N., Blandi L., Bonaccio M., Cauda R., Guaraldi G., Menicanti L., Mennuni M., Parruti G., Patti G., Santilli F., Signorelli C., Vergori A., Abete P., Ageno W., Agodi A., Agostoni P., Aiello L., Al Moghazi S., Arboretti R., Astuto M., Aucella F., Barbieri G., Bartoloni A., Bonfanti P., Cacciatore F., Caiano L., Carrozzi L., Cascio A., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Colombo C., Crosta F., Danzi G.B., D'Ardes D., De Gaetano Donati K., Di Gennaro F., Di Tano G., D'Offizi G., Fantoni M., Fusco F.M., Gentile I., Gianfagna F., Grandone E., Graziani E., Grisafi L., Guarnieri G., Larizza G., Leone A., MacCagni G., Madaro F., Maitan S., Mancarella S., Mapelli M., Maragna R., Marcucci R., Maresca G., Marongiu S., Marotta C., Marra L., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Meschiari M., Milic J., Minutolo F., Molena B., Montineri A., Mussini C., Musso M., Niola D., Odone A., Olivieri M., Palimodde A., Parisi R., Pasi E., Pesavento R., Petri F., Pinchera B., Poletti V., Ravaglia C., Rognoni A., Rossato M., Rossi M., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P.G., Taddei E., Torti C., Vettor R., Vianello A., Vinceti M., Virano A., Vocciante L., De Caterina R., and Iacoviello L.

Subjects
Male, medicine.medical_specialty, Settore MED/17 - Malattie Infettive, coronavirus, heparin, 030204 cardiovascular system & hematology, Lower risk, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Clinical endpoint, medicine, Humans, Thrombophilia, 030212 general & internal medicine, Hospital Mortality, Blood Coagulation, Survival analysis, Aged, Retrospective Studies, treatment, business.industry, Heparin, Mortality rate, COVID-19,mortality, Low-Molecular-Weight, Anticoagulants, COVID-19, Retrospective cohort study, Hematology, Heparin, Low-Molecular-Weight, Middle Aged, mortality, Survival Analysis, COVID-19 Drug Treatment, coagulation activation, coronaviru, Italy, treatments, Propensity score matching, Female, business, medicine.drug
Abstract

Introduction A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. Results Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49–0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusion In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Published
2021

20. Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering

Author

Anna Sabena, Gabriele Giuliano, Raffaele Bruno, Francesco Cacciatore, Carlo Torti, Silvia Marongiu, Gloria Maccagni, Claudia Marotta, Giovanni Larizza, Francesco Petri, Massimo Mapelli, Giulio Maresca, Giulia Righetti, Alessandra Vergori, Ilaria Rossi, Damiano D'Ardes, Nicola Schiano Moriello, Ivan Gentile, Enrica Tamburrini, Luca Aiello, Piergiuseppe Agostoni, Antonio Cascio, Jovana Milic, Carlo Andrea Pivato, Agostino Virdis, Stefano Maitan, Francesco Cannata, Simona Costanzo, Carlo Signorelli, Franco Mastroianni, Federica Magni, Crizia Colombo, Giulio G. Stefanini, Lucia Caiano, Francesca Crosta, Lorenzo Marra, Giuseppe Patti, Katleen de Gaetano Donati, Valerio Langella, Annalisa Crisetti, Filippo Aucella, Antonella Cingolani, Francesco Salinaro, Augusto Di Castelnuovo, Giacomo Castiglione, Alessandro Gialluisi, Anna Odone, Cristina Mussini, Samir Al Moghazi, Lorenzo Blandi, Maria Musso, Marialaura Bonaccio, Raffaele De Caterina, Marco Olivieri, Roberto Cauda, Emanuela Pasi, Arturo Ciccullo, Stefano Perlini, Claudia Colomba, Antonella Palimodde, Gianpiero D'Offizi, Marco G. Mennuni, Walter Ageno, Raffaele Pesavento, Rosa Manuele, Roberta Mussinelli, Vincenzo Sangiovanni, Paolo Bonfanti, Andrea Antinori, Francesco Gianfagna, Andrea Rognoni, Laura Scorzolini, Riccardo Maragna, Rossella Marcucci, Filippo Minutolo, Armando Leone, Giustino Parruti, Licia Iacoviello, Lorenzo Menicanti, Sandro Mancarella, Rosa Arboretti, Greta Barbieri, Carlo Gaudiosi, Marco Rossato, Claudia Ravaglia, Andrea Vianello, Marianna Rossi, Emauele Graziani, Martina Barchitta, Giovanni Guaraldi, Enrico Maria Trecarichi, Gian Battista Danzi, Francesco Cipollone, Carlo Sanrocco, Marco Vinceti, Francesca Santilli, Marianna Meschiari, Gabriella Guarnieri, Antonella Agodi, Roberto Vettor, Raffaella Sgariglia, Ilaria My, Francesco Di Gennaro, Alessandro Mengozzi, Giuseppe Di Tano, Laura Carrozzi, Michele Spinicci, Venerino Poletti, Paola Simeone, Nausicaa Berselli, Francesco Maria Fusco, Di Castelnuovo A., Gialluisi A., Antinori A., Berselli N., Blandi L., Bonaccio M., Bruno R., Cauda R., Costanzo S., Guaraldi G., Menicanti L., Mennuni M., My I., Parruti G., Patti G., Perlini S., Santilli F., Signorelli C., Stefanini G., Vergori A., Ageno W., Agodi A., Agostoni P., Aiello L., Moghazi S.A., Arboretti R., Aucella F., Barbieri G., Barchitta M., Bonfanti P., Cacciatore F., Caiano L., Cannata F., Carrozzi L., Cascio A., Castiglione G., Cicullo A., Cingolani A., Cipollone F., Colomba C., Colombo C., Crisetti A., Crosta F., Danzi G.B., D'Ardes D., de Gaetano Donati K., Di Gennaro F., Di Tano G., D'Offizi G., Fusco F.M., Gaudiosi C., Gentile I., Gianfagna F., Giuliano G., Graziani E., Guarnieri G., Langella V., Larizza G., Leone A., Maccagni G., Magni F., Maitan S., Mancarella S., Manuele R., Mapelli M., Maragna R., Marcucci R., Maresca G., Marongiu S., Marotta C., Marra L., Mastroianni F., Mengozzi A., Meschiari M., Milic J., Minutolo F., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Palimodde A., Pasi E., Pesavento R., Petri F., Pivato C.A., Poletti V., Ravaglia C., Righetti G., Rognoni A., Rossato M., Rossi I., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Moriello N.S., Scorzolini L., Sgariglia R., Simeone P.G., Spinicci M., Tamburrini E., Torti C., Trecarichi E.M., Vettor R., Vianello A., Vinceti M., Virdis A., de Caterina R., Iacoviello L., Di Castelnuovo, A, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Costanzo, S, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Castiglione, G, Cicullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gaudiosi, C, Gentile, I, Gianfagna1, F, Giuliano, G, Graziani, E, Guarnieri, G, Langella, V, Larizza, G, Leone, A, Maccagni, G, Magni, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Meschiari, M, Milic, J, Minutolo, F, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pivato, C, Poletti, V, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Schiano Moriello, N, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Tamburrini, E, Torti, C, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virdis, A, De Caterina, R, Iacoviello, L, Di Castelnuovo, A., Gialluisi, A., Antinori, A., Berselli, N., Blandi, L., Bonaccio, M., Bruno, R., Cauda, R., Costanzo, S., Guaraldi, G., Menicanti, L., Mennuni, M., My, I., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G., Vergori, A., Ageno, W., Agodi, A., Agostoni, P., Aiello, L., Moghazi, S. A., Arboretti, R., Aucella, F., Barbieri, G., Barchitta, M., Bonfanti, P., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Castiglione, G., Cicullo, A., Cingolani, A., Cipollone, F., Colomba, C., Colombo, C., Crisetti, A., Crosta, F., Danzi, G. B., D’Ardes, D., de Gaetano Donati, K., Di Gennaro, F., Di Tano, G., D’Offizi, G., Fusco, F. M., Gaudiosi, C., Gentile, I., Gianfagna, F., Giuliano, G., Graziani, E., Guarnieri, G., Langella, V., Larizza, G., Leone, A., Maccagni, G., Magni, F., Maitan, S., Mancarella, S., Manuele, R., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marongiu, S., Marotta, C., Marra, L., Mastroianni, F., Mengozzi, A., Meschiari, M., Milic, J., Minutolo, F., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Palimodde, A., Pasi, E., Pesavento, R., Petri, F., Pivato, C. A., Poletti, V., Ravaglia, C., Righetti, G., Rognoni, A., Rossato, M., Rossi, I., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Moriello, N. S., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinicci, M., Tamburrini, E., Torti, C., Trecarichi, E. M., Vettor, R., Vianello, A., Vinceti, M., Virdis, A., de Caterina, R., and Iacoviello, L.

Subjects
Male, Medicine (General), Antimalarial, 030204 cardiovascular system & hematology, Severity of Illness Index, Hospital Mortality, 0302 clinical medicine, Retrospective Studie, 80 and over, Cluster Analysis, 030212 general & internal medicine, Aged, Aged, 80 and over, Antimalarials, COVID-19, Female, Humans, Hydroxychloroquine, Italy, Middle Aged, Retrospective Studies, SARS-CoV-2, Treatment Outcome, Biotechnology, medicine.drug, Research Article, medicine.medical_specialty, Article Subject, Biomedical Engineering, Renal function, Health Informatics, 03 medical and health sciences, R5-920, Internal medicine, Diabetes mellitus, Severity of illness, medicine, Medical technology, R855-855.5, Cluster Analysi, business.industry, Cancer, Retrospective cohort study, medicine.disease, Obesity, COVID-19 Drug Treatment, Surgery, Observational study, business
Abstract

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001 ). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Published
2021
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21. Lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: Findings from the multicenter italian corist study

Author

Augusto Di Castelnuovo, Simona Costanzo, Andrea Antinori, Nausicaa Berselli, Lorenzo Blandi, Marialaura Bonaccio, Raffaele Bruno, Roberto Cauda, Alessandro Gialluisi, Giovanni Guaraldi, Lorenzo Menicanti, Marco Mennuni, Ilaria My, Agostino Parruti, Giuseppe Patti, Stefano Perlini, Francesca Santilli, Carlo Signorelli, Giulio G. Stefanini, Alessandra Vergori, Walter Ageno, Luca Aiello, Piergiuseppe Agostoni, Samir Al Moghazi, Rosa Arboretti, Filippo Aucella, Greta Barbieri, Martina Barchitta, Alessandro Bartoloni, Carolina Bologna, Paolo Bonfanti, Lucia Caiano, Laura Carrozzi, Antonio Cascio, Giacomo Castiglione, Mauro Chiarito, Arturo Ciccullo, Antonella Cingolani, Francesco Cipollone, Claudia Colomba, Crizia Colombo, Francesco Crosta, Giovanni Dalena, Chiara Dal Pra, Gian Battista Danzi, Damiano D'Ardes, Katleen de Gaetano Donati, Francesco Di Gennaro, Giuseppe Di Tano, Gianpiero D'Offizi, Tommaso Filippini, Francesco Maria Fusco, Carlo Gaudiosi, Ivan Gentile, Giancarlo Gini, Elvira Grandone, Gabriella Guarnieri, Gennaro L. F. Lamanna, Giovanni Larizza, Armando Leone, Veronica Lio, Angela Raffaella Losito, Gloria Maccagni, Stefano Maitan, Sandro Mancarella, Rosa Manuele, Massimo Mapelli, Riccardo Maragna, Lorenzo Marra, Giulio Maresca, Claudia Marotta, Franco Mastroianni, Maria Mazzitelli, Alessandro Mengozzi, Francesco Menichetti, Jovana Milic, Filippo Minutolo, Beatrice Molena, R. Mussinelli, Cristina Mussini, Maria Musso, Anna Odone, Marco Olivieri, Emanuela Pasi, Annalisa Perroni, Francesco Petri, Biagio Pinchera, Carlo A. Pivato, Venerino Poletti, Claudia Ravaglia, Marco Rossato, Marianna Rossi, Anna Sabena, Francesco Salinaro, Vincenzo Sangiovanni, Carlo Sanrocco, Laura Scorzolini, Raffaella Sgariglia, Paola Giustina Simeone, Michele Spinicci, Enrico Maria Trecarichi, Giovanni Veronesi, Roberto Vettor, Andrea Vianello, Marco Vinceti, Elena Visconti, Laura Vocciante, Raffaele De Caterina, Licia Iacoviello, The COVID-19 RISK and Treatments (CORIST) Collaboration, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Agostino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Ageno, Walter, Aiello, Luca, Agostoni, Piergiuseppe, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Chiarito, Mauro, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesco, Dalena, Giovanni, Dal Pra, Chiara, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Filippini, Tommaso, Maria Fusco, Francesco, Gaudiosi, Carlo, Gentile, Ivan, Gini, Giancarlo, Grandone, Elvira, Guarnieri, Gabriella, Lamanna, Gennaro L F, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Losito, Angela Raffaella, Maccagni, Gloria, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marra, Lorenzo, Maresca, Giulio, Marotta, Claudia, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussinelli, R, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Perroni, Annalisa, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Trecarichi, Enrico Maria, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Visconti, Elena, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Aiello, L, Agostoni, P, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bologna, C, Bonfanti, P, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Chiarito, M, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Dalena, G, Dal Pra, C, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Filippini, T, Maria Fusco, F, Gaudiosi, C, Gentile, I, Gini, G, Grandone, E, Guarnieri, G, Lamanna, G, Larizza, G, Leone, A, Lio, V, Losito, A, Maccagni, G, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Milic, J, Minutolo, F, Molena, B, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Perroni, A, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Visconti, E, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, A., Costanzo, S., Antinori, A., Berselli, N., Blandi, L., Bonaccio, M., Bruno, R., Cauda, R., Gialluisi, A., Guaraldi, G., Menicanti, L., Mennuni, M., My, I., Parruti, A., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Ageno, W., Aiello, L., Agostoni, P., Moghazi, S. A., Arboretti, R., Aucella, F., Barbieri, G., Barchitta, M., Bartoloni, A., Bologna, C., Bonfanti, P., Caiano, L., Carrozzi, L., Cascio, A., Castiglione, G., Chiarito, M., Ciccullo, A., Cingolani, A., Cipollone, F., Colomba, C., Colombo, C., Crosta, F., Dalena, G., Dal Pra, C., Danzi, G. B., D'Ardes, D., Donati, K. G., Di Gennaro, F., Di Tano, G., D'Offizi, G., Filippini, T., Fusco, F. M., Gaudiosi, C., Gentile, I., Gini, G., Grandone, E., Guarnieri, G., Lamanna, G. L. F., Larizza, G., Leone, A., Lio, V., Losito, A. R., Maccagni, G., Maitan, S., Mancarella, S., Manuele, R., Mapelli, M., Maragna, R., Marra, L., Maresca, G., Marotta, C., Mastroianni, F., Mazzitelli, M., Mengozzi, A., Menichetti, F., Milic, J., Minutolo, F., Molena, B., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Perroni, A., Petri, F., Pinchera, B., Pivato, C. A., Poletti, V., Ravaglia, C., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinicci, M., Trecarichi, E. M., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., Visconti, E., Vocciante, L., Caterina, R. D., Iacoviello, L., Di Castelnuovo A., Costanzo S., Antinori A., Berselli N., Blandi L., Bonaccio M., Bruno R., Cauda R., Gialluisi A., Guaraldi G., Menicanti L., Mennuni M., My I., Parruti A., Patti G., Perlini S., Santilli F., Signorelli C., Stefanini G.G., Vergori A., Ageno W., Aiello L., Agostoni P., Moghazi S.A., Arboretti R., Aucella F., Barbieri G., Barchitta M., Bartoloni A., Bologna C., Bonfanti P., Caiano L., Carrozzi L., Cascio A., Castiglione G., Chiarito M., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Colombo C., Crosta F., Dalena G., Dal Pra C., Danzi G.B., D'ardes D., Donati K.G., Di Gennaro F., Di Tano G., D'offizi G., Filippini T., Fusco F.M., Gaudiosi C., Gentile I., Gini G., Grandone E., Guarnieri G., Lamanna G.L.F., Larizza G., Leone A., Lio V., Losito A.R., Maccagni G., Maitan S., Mancarella S., Manuele R., Mapelli M., Maragna R., Marra L., Maresca G., Marotta C., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Milic J., Minutolo F., Molena B., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Pasi E., Perroni A., Petri F., Pinchera B., Pivato C.A., Poletti V., Ravaglia C., Rossato M., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P.G., Spinicci M., Trecarichi E.M., Veronesi G., Vettor R., Vianello A., Vinceti M., Visconti E., Vocciante L., Caterina R.D., and Iacoviello L.

Subjects
Medicine (General), medicine.medical_specialty, Lopinavir/ritonavir, Lopinavir, R5-920, Internal medicine, medicine, Darunavir, Original Research, COVID-19, In-hospital mortality, SARS-CoV-2, darunavir, in-hospital mortality, lopinavir, business.industry, Cobicistat, Mortality rate, General Medicine, medicine.disease, Propensity score matching, Medicine, Ritonavir, business, medicine.drug, Kidney disease
Abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores.Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs.Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Published
2021

22. RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

Author

Francesca Santilli, Marianna Meschiari, Gabriella Guarnieri, Francesco Petri, Anna Sabena, Gloria Maccagni, Giovanni Larizza, Massimo Mapelli, Maria Mazzitelli, Gian Battista Danzi, Katleen de Gaetano Donati, Annalisa Crisetti, Jovana Milic, Raffaele Pesavento, Biagio Pinchera, Riccardo Maragna, Carlo Andrea Pivato, Lorenzo Menicanti, Francesco Maria Fusco, Luca Aiello, Sandro Mancarella, Carlo Sanrocco, Alessandra Vergori, Greta Barbieri, Filippo Aucella, Silvia Marongiu, Giulio Maresca, Marianna Rossi, Andrea Antinori, Venerino Poletti, Francesco Cacciatore, Giacomo Castiglione, Enrico Maria Trecarichi, Lucia Caiano, Francesca Crosta, Roberto Vettor, Francesco Menichetti, Maria Musso, Francesco Salinaro, Marco Olivieri, Stefano Perlini, Claudia Colomba, Crizia Colombo, Ottavia Cozzi, Stefano Maitan, Marialaura Bonaccio, Ilaria My, Alexandra Virano, Paola Simeone, Marco Vinceti, Antonella Cingolani, Gianpiero D'Offizi, Damiano D'Ardes, Claudia Marotta, M. B. Lucia, Carlo Signorelli, Lorenzo Marra, Giuseppe Patti, Raffaele De Caterina, Armando Leone, Veronica Lio, Beatrice Molena, Giustino Parruti, Giulio G. Stefanini, Licia Iacoviello, Laura Vocciante, Franco Mastroianni, Raffaella Sgariglia, Cristina Mussini, Francesco Cipollone, Marco Rossato, Lorenzo Blandi, Emanuela Pasi, Samir Al Moghazi, Andrea Vianello, Filippo Minutolo, Ivan Gentile, Giovanni Guaraldi, Rosa Manuele, Pasquale Abete, Arturo Ciccullo, Antonella Palimodde, Giancarlo Scoppettuolo, Walter Ageno, Marco G. Mennuni, Roberta Mussinelli, Vincenzo Sangiovanni, Roberto Cauda, Laura Scorzolini, Paolo Bonfanti, Alessandro Gialluisi, Stefania Cianfrone, Piergiuseppe Agostoni, Antonio Cascio, Simona Costanzo, Augusto Di Castelnuovo, Nausicaa Berselli, Rosa Arboretti, Emauele Graziani, Martina Barchitta, Anna Odone, Francesco Di Gennaro, Alessandro Mengozzi, Alessandro Bartoloni, Giuseppe Di Tano, Laura Carrozzi, Ferruccio Madaro, Rossella Marcucci, Claudia Ravaglia, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Mussinelli, Roberta, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G., Vergori, Alessandra, Abete, Pasquale, Ageno, Walter, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cianfrone, Stefania, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Cozzi, Ottavia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gentile, Ivan, Graziani, Emauele, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Lucia, Mothanje Barbara, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A., Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scoppettuolo, Giancarlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A., Costanzo, S., Antinori, A., Berselli, N., Bl, I, L., Bonaccio, M., Cauda, R., Gialluisi, A., Guaraldi, G., Menicanti, L., Mennuni, M., Mussinelli, R., My, I., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Abete, P., Ageno, W., Agostoni, P., Aiello, L., Al Moghazi, S., Arboretti, R., Aucella, F., Barbieri, G., Barchitta, M., Bartoloni, A., Bonfanti, P., Cacciatore, F., Caiano, L., Carrozzi, L., Cascio, A., Castiglione, G., Cianfrone, S., Ciccullo, A., Cingolani, A., Cipollone, F., Colomba, C., Colombo, C., Cozzi, O., Crisetti, A., Crosta, F., Danzi, G. B., D'Ardes, D., de Gaetano Donati, K., Di Gennaro, F., Di Tano, G., D'Offizi, G., Fusco, F. M., Gentile, I., Graziani, E., Guarnieri, G., Larizza, G., Leone, A., Lio, V., Lucia, M. B., Maccagni, G., Madaro, F., Maitan, S., Mancarella, S., Manuele, R., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marongiu, S., Marotta, C., Marra, L., Mastroianni, F., Mazzitelli, M., Mengozzi, A., Menichetti, F., Meschiari, M., Milic, J., Minutolo, F., Molena, B., Mussini, C., Musso, M., Odone, A., Olivieri, M., Palimodde, A., Pasi, E., Pesavento, R., Petri, F., Pinchera, B., Pivato, C. A., Poletti, V., Ravaglia, C., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scoppettuolo, G., Scorzolini, L., Sgariglia, R., Simeone, P. G., Trecarichi, E. M., Vettor, R., Vianello, A., Vinceti, M., Virano, A., Vocciante, L., De Caterina, R., Iacoviello, L., Blandi, L., Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, Mussinelli, R, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abete, P, Ageno, W, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Cianfrone, S, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Cozzi, O, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gentile, I, Graziani, E, Guarnieri, G, Larizza, G, Leone, A, Lio, V, Lucia, M, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scoppettuolo, G, Scorzolini, L, Sgariglia, R, Simeone, P, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, Iacoviello, L, and De Caterina, R

Subjects
0301 basic medicine, Male, Physiology, Middle Aged, Renin-Angiotensin System, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, ACE-I, ARB, COVID-19, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, mortality, sartans, Severity of Illness Index, Renin-Angiotensin System, 0302 clinical medicine, Risk Factors, 80 and over, Medicine, Hospital Mortality, Sartan, Aged, 80 and over, Incidence (epidemiology), Incidence, Hazard ratio, Angiotensin Receptor Antagonist, Middle Aged, Hospitalization, Antihypertensive Agent, Italy, Meta-analysis, Hypertension, Sartans, Molecular Medicine, Female, Risk assessment, Human, medicine.medical_specialty, Angiotensin converting enzyme inhibitors, Angiotensin receptor blockers, Mortality, Coronavirus disease 2019 (COVID-19), Risk Assessment, Article, COVID−19, 03 medical and health sciences, Angiotensin Receptor Antagonists, Meta-Analysis as Topic, Internal medicine, Severity of illness, Humans, Angiotensin receptor blocker, Antihypertensive Agents, Aged, Pharmacology, business.industry, Risk Factor, Angiotensin-Converting Enzyme Inhibitor, Confidence interval, 030104 developmental biology, COVID-19, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, mortality, sartans, Observational study, Angiotensin converting enzyme inhibitor, business
Abstract

Objective The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418 ) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting–enzyme inhibitors (ACE I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results Out of 4069 COVID−19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID−19 treatments: 0.96, 95% confidence interval 0.77–1.20 and HR = 0.89, 0.67–1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78–1.26 and HR = 0.88, 0.65–1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID−19 adult patients, 9700 with hypertension) confirmed the absence of association. Conclusions In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID−19 patients.

Published
2020

23. Personalized prediction of optimal water intake in adult population by blended use of machine learning and clinical data.

Author

Dolci A, Vanhaecke T, Qiu J, Ceccato R, Arboretti R, and Salmaso L

Subjects
Adult, Humans, Algorithms, Nutrition Policy, Osmolar Concentration, Randomized Controlled Trials as Topic, Non-Randomized Controlled Trials as Topic, Drinking, Machine Learning
Abstract

Growing evidence suggests that sustained concentrated urine contributes to chronic metabolic and kidney diseases. Recent results indicate that a daily urinary concentration of 500 mOsm/kg reflects optimal hydration. This study aims at providing personalized advice for daily water intake considering personal intrinsic (age, sex, height, weight) and extrinsic (food and fluid intakes) characteristics to achieve a target urine osmolality (U Osm ) of 500 mOsm/kg using machine learning and optimization algorithms. Data from clinical trials on hydration (four randomized and three non-randomized trials) were analyzed. Several machine learning methods were tested to predict U Osm . The predictive performance of the developed algorithm was evaluated against current dietary guidelines. Features linked to urine production and fluid consumption were listed among the most important features with relative importance values ranging from 0.10 to 0.95. XGBoost appeared the most performing approach (Mean Absolute Error (MAE) = 124.99) to predict U Osm . The developed algorithm exhibited the highest overall correct classification rate (85.5%) versus that of dietary guidelines (77.8%). This machine learning application provides personalized advice for daily water intake to achieve optimal hydration and may be considered as a primary prevention tool to counteract the increased incidence of chronic metabolic and kidney diseases., (© 2022. The Author(s).)

Published
2022
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24. Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study.

Author

Di Castelnuovo A, Costanzo S, Antinori A, Berselli N, Blandi L, Bonaccio M, Cauda R, Guaraldi G, Menicanti L, Mennuni M, Parruti G, Patti G, Santilli F, Signorelli C, Vergori A, Abete P, Ageno W, Agodi A, Agostoni P, Aiello L, Al Moghazi S, Arboretti R, Astuto M, Aucella F, Barbieri G, Bartoloni A, Bonfanti P, Cacciatore F, Caiano L, Carrozzi L, Cascio A, Ciccullo A, Cingolani A, Cipollone F, Colomba C, Colombo C, Crosta F, Danzi GB, D'Ardes D, de Gaetano Donati K, Di Gennaro F, Di Tano G, D'Offizi G, Fantoni M, Fusco FM, Gentile I, Gianfagna F, Grandone E, Graziani E, Grisafi L, Guarnieri G, Larizza G, Leone A, Maccagni G, Madaro F, Maitan S, Mancarella S, Mapelli M, Maragna R, Marcucci R, Maresca G, Marongiu S, Marotta C, Marra L, Mastroianni F, Mazzitelli M, Mengozzi A, Menichetti F, Meschiari M, Milic J, Minutolo F, Molena B, Montineri A, Mussini C, Musso M, Niola D, Odone A, Olivieri M, Palimodde A, Parisi R, Pasi E, Pesavento R, Petri F, Pinchera B, Poletti V, Ravaglia C, Rognoni A, Rossato M, Rossi M, Sangiovanni V, Sanrocco C, Scorzolini L, Sgariglia R, Simeone PG, Taddei E, Torti C, Vettor R, Vianello A, Vinceti M, Virano A, Vocciante L, De Caterina R, and Iacoviello L

Subjects
Aged, Blood Coagulation drug effects, COVID-19 blood, Female, Hospital Mortality, Humans, Italy epidemiology, Male, Middle Aged, Retrospective Studies, Survival Analysis, Thrombophilia blood, COVID-19 Drug Treatment, Anticoagulants therapeutic use, COVID-19 complications, Heparin therapeutic use, Heparin, Low-Molecular-Weight therapeutic use, Thrombophilia etiology, Thrombophilia prevention & control
Abstract

Introduction: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality., Aim: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients., Methods: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores., Results: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation., Conclusion: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations., Competing Interests: None declared., (Thieme. All rights reserved.)

Published
2021
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25. Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

Author

Di Castelnuovo A, Gialluisi A, Antinori A, Berselli N, Blandi L, Bonaccio M, Bruno R, Cauda R, Costanzo S, Guaraldi G, Menicanti L, Mennuni M, My I, Parruti G, Patti G, Perlini S, Santilli F, Signorelli C, Stefanini G, Vergori A, Ageno W, Agodi A, Agostoni P, Aiello L, Al Moghazi S, Arboretti R, Aucella F, Barbieri G, Barchitta M, Bonfanti P, Cacciatore F, Caiano L, Cannata F, Carrozzi L, Cascio A, Castiglione G, Ciccullo A, Cingolani A, Cipollone F, Colomba C, Colombo C, Crisetti A, Crosta F, Danzi GB, D'Ardes D, de Gaetano Donati K, Di Gennaro F, Di Tano G, D'Offizi G, Fusco FM, Gaudiosi C, Gentile I, Gianfagna F, Giuliano G, Graziani E, Guarnieri G, Langella V, Larizza G, Leone A, Maccagni G, Magni F, Maitan S, Mancarella S, Manuele R, Mapelli M, Maragna R, Marcucci R, Maresca G, Marongiu S, Marotta C, Marra L, Mastroianni F, Mengozzi A, Meschiari M, Milic J, Minutolo F, Mussinelli R, Mussini C, Musso M, Odone A, Olivieri M, Palimodde A, Pasi E, Pesavento R, Petri F, Pivato CA, Poletti V, Ravaglia C, Righetti G, Rognoni A, Rossato M, Rossi I, Rossi M, Sabena A, Salinaro F, Sangiovanni V, Sanrocco C, Schiano Moriello N, Scorzolini L, Sgariglia R, Simeone PG, Spinicci M, Tamburrini E, Torti C, Trecarichi EM, Vettor R, Vianello A, Vinceti M, Virdis A, De Caterina R, and Iacoviello L

Subjects
Aged, Aged, 80 and over, COVID-19 physiopathology, Cluster Analysis, Female, Humans, Italy, Male, Middle Aged, Retrospective Studies, SARS-CoV-2 drug effects, Severity of Illness Index, Treatment Outcome, Antimalarials adverse effects, Antimalarials therapeutic use, COVID-19 mortality, Hospital Mortality, Hydroxychloroquine adverse effects, Hydroxychloroquine therapeutic use, COVID-19 Drug Treatment
Abstract

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Augusto Di Castelnuovo et al.)

Published
2021
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26. Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study.

Author

Di Castelnuovo A, Costanzo S, Antinori A, Berselli N, Blandi L, Bonaccio M, Bruno R, Cauda R, Gialluisi A, Guaraldi G, Menicanti L, Mennuni M, My I, Parruti A, Patti G, Perlini S, Santilli F, Signorelli C, Stefanini GG, Vergori A, Ageno W, Aiello L, Agostoni P, Al Moghazi S, Arboretti R, Aucella F, Barbieri G, Barchitta M, Bartoloni A, Bologna C, Bonfanti P, Caiano L, Carrozzi L, Cascio A, Castiglione G, Chiarito M, Ciccullo A, Cingolani A, Cipollone F, Colomba C, Colombo C, Crosta F, Dalena G, Dal Pra C, Danzi GB, D'Ardes D, de Gaetano Donati K, Di Gennaro F, Di Tano G, D'Offizi G, Filippini T, Maria Fusco F, Gaudiosi C, Gentile I, Gini G, Grandone E, Guarnieri G, Lamanna GLF, Larizza G, Leone A, Lio V, Losito AR, Maccagni G, Maitan S, Mancarella S, Manuele R, Mapelli M, Maragna R, Marra L, Maresca G, Marotta C, Mastroianni F, Mazzitelli M, Mengozzi A, Menichetti F, Milic J, Minutolo F, Molena B, Mussinelli R, Mussini C, Musso M, Odone A, Olivieri M, Pasi E, Perroni A, Petri F, Pinchera B, Pivato CA, Poletti V, Ravaglia C, Rossato M, Rossi M, Sabena A, Salinaro F, Sangiovanni V, Sanrocco C, Scorzolini L, Sgariglia R, Simeone PG, Spinicci M, Trecarichi EM, Veronesi G, Vettor R, Vianello A, Vinceti M, Visconti E, Vocciante L, De Caterina R, and Iacoviello L

Abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Di Castelnuovo, Costanzo, Antinori, Berselli, Blandi, Bonaccio, Bruno, Cauda, Gialluisi, Guaraldi, Menicanti, Mennuni, My, Parruti, Patti, Perlini, Santilli, Signorelli, Stefanini, Vergori, Ageno, Aiello, Agostoni, Al Moghazi, Arboretti, Aucella, Barbieri, Barchitta, Bartoloni, Bologna, Bonfanti, Caiano, Carrozzi, Cascio, Castiglione, Chiarito, Ciccullo, Cingolani, Cipollone, Colomba, Colombo, Crosta, Dalena, Dal Pra, Danzi, D'Ardes, de Gaetano Donati, Di Gennaro, Di Tano, D'Offizi, Filippini, Maria Fusco, Gaudiosi, Gentile, Gini, Grandone, Guarnieri, Lamanna, Larizza, Leone, Lio, Losito, Maccagni, Maitan, Mancarella, Manuele, Mapelli, Maragna, Marra, Maresca, Marotta, Mastroianni, Mazzitelli, Mengozzi, Menichetti, Milic, Minutolo, Molena, Mussinelli, Mussini, Musso, Odone, Olivieri, Pasi, Perroni, Petri, Pinchera, Pivato, Poletti, Ravaglia, Rossato, Rossi, Sabena, Salinaro, Sangiovanni, Sanrocco, Scorzolini, Sgariglia, Simeone, Spinicci, Trecarichi, Veronesi, Vettor, Vianello, Vinceti, Visconti, Vocciante, De Caterina, Iacoviello and The COVID-19 RISK and Treatments (CORIST) Collaboration.)

Published
2021
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27. Machine learning and design of experiments with an application to product innovation in the chemical industry.

Author

Arboretti R, Ceccato R, Pegoraro L, Salmaso L, Housmekerides C, Spadoni L, Pierangelo E, Quaggia S, Tveit C, and Vianello S

Abstract

Industrial statistics plays a major role in the areas of both quality management and innovation. However, existing methodologies must be integrated with the latest tools from the field of Artificial Intelligence. To this end, a background on the joint application of Design of Experiments (DOE) and Machine Learning (ML) methodologies in industrial settings is presented here, along with a case study from the chemical industry. A DOE study is used to collect data, and two ML models are applied to predict responses which performance show an advantage over the traditional modeling approach. Emphasis is placed on causal investigation and quantification of prediction uncertainty, as these are crucial for an assessment of the goodness and robustness of the models developed. Within the scope of the case study, the models learned can be implemented in a semi-automatic system that can assist practitioners who are inexperienced in data analysis in the process of new product development., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 Informa UK Limited, trading as Taylor & Francis Group.)

Published
2021
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28. Multivariate permutation tests for two sample testing in presence of nondetects with application to microarray data.

Author

Arboretti R, Bathke AC, Carrozzo E, Pesarin F, and Salmaso L

Subjects
Computer Simulation, Humans, Hypersensitivity immunology, Immunoglobulin E immunology, Research Design, Microarray Analysis statistics & numerical data, Models, Statistical
Abstract

Very often, data collected in medical research are characterized by censored observations and/or data with mass on the value zero. This happens for example when some measurements fall below the detection limits of the specific instrument used. This type of left censored observations is called "nondetects". Such a situation of an excessive number of zeros in a data set is also referred to as zero-inflated data. In the present work, we aim at comparing different multivariate permutation procedures in two-sample testing for data with nondetects. The effect of censoring is investigated with regard to the different values that may be attributed to nondetected values, both under the null hypothesis and under alternative. We motivate the problem using data from allergy research.

Published
2020
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29. Nonparametric combination tests for comparing two survival curves with informative and non-informative censoring.

Author

Arboretti R, Fontana R, Pesarin F, and Salmaso L

Subjects
Data Interpretation, Statistical, Humans, Statistics, Nonparametric, Survival Analysis
Abstract

This paper looks at permutation methods used to deal with hypothesis testing within the survival analysis framework. In the literature, several attempts have been made to deal with the comparison of survival curves and, depending on the survival and hazard functions of two groups, they can be more or less efficient in detecting differences. Furthermore, in some situations, censoring can be informative in that it depends on treatment effect. Our proposal is based on the nonparametric combination approach and has proven to be very effective under different configurations of survival and hazard functions. It allows the practitioner to test jointly on primary and censoring events and, by using multiple testing methods, to assess the significance of the treatment effect separately on the survival and the censoring process.

Published
2018
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30. [Statistical tests in medical research: traditional methods vs. multivariate NPC permutation tests].

Author

Arboretti R, Bordignon P, Corain L, Palermo G, Pesarin F, and Salmaso L

Subjects
Analysis of Variance, Evidence-Based Medicine statistics & numerical data, Humans, Italy, Multivariate Analysis, Observational Studies as Topic statistics & numerical data, Statistics, Nonparametric, Biomedical Research statistics & numerical data, Models, Statistical, Randomized Controlled Trials as Topic statistics & numerical data
Abstract

Statistical tests in medical research: traditional methods vs. multivariate npc permutation tests.Within medical research, a useful statistical tool is based on hypotheses testing in terms of the so-called null, that is the treatment has no effect, and alternative hypotheses, that is the treatment has some effects. By controlling the risks of wrong decisions, empirical data are used in order to possibly reject the null hypotheses in favour of the alternative, so that demonstrating the efficacy of a treatment of interest. The multivariate permutation tests, based on the nonparametric combination - NPC method, provide an innovative, robust and effective hypotheses testing solution to many real problems that are commonly encountered in medical research when multiple end-points are observed. This paper discusses the various approaches to hypothesis testing and the main advantages of NPC tests, which consist in the fact that they require much less stringent assumptions than traditional statistical tests. Moreover, the related results may be extended to the reference population even in case of selection-bias, that is non-random sampling. In this work, we review and discuss some basic testing procedures along with the theoretical and practical relevance of NPC tests showing their effectiveness in medical research. Within the non-parametric methods, NPC tests represent the current "frontier" of statistical research, but already widely available in the practice of analysis of clinical data.

Published
2015
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31. Rehabilitation and outcome of severe profound deafness in a group of 16 infants affected by congenital cytomegalovirus infection.

Author

Ciorba A, Bovo R, Trevisi P, Bianchini C, Arboretti R, and Martini A

Subjects
Audiometry, Evoked Response, Brain Stem physiopathology, Child, Child, Preschool, Deafness diagnosis, Deafness physiopathology, Evoked Potentials, Auditory, Brain Stem physiology, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Language Development Disorders diagnosis, Language Development Disorders physiopathology, Language Development Disorders rehabilitation, Male, Patient Care Team, Speech Reception Threshold Test, Cochlear Implantation, Cytomegalovirus Infections congenital, Deafness congenital, Deafness rehabilitation, Hearing Aids
Abstract

The aim of the study was to characterize the audiological consequences of congenital cytomegalovirus infection (CMV) and to evaluate the outcome of rehabilitation with hearing aids and/or cochlear implant (CI), associated with an adequate speech-language therapy. A retrospective review of data was made from a total of 16 infants, affected by severe to profound hearing loss from congenital CMV infection, referred to a tertiary audiological center for rehabilitation. Audiological evaluation was performed using behavioral audiometry, auditory brainstem responses (ABR) and/or electrocochleography (ECochG). Of the 16 children (median age at diagnosis of hearing loss: 21.33 +/- 0.7 months) with CMV hearing loss, 14 were affected by profound bilateral hearing loss and received a CI, while 2 were affected by bilateral severe hearing loss and received hearing aids. Cochlear implants can provide useful speech comprehension to patients with CMV-related deafness, even if language development is lower when compared to a group of Connexin (Cx) 26+ cochlear-implanted children (eight subjects), matched for age. Congenital CMV infection still represents a serious clinical condition, as well as an important cause of hearing loss in children. More studies have claimed to identify the pathophysiological mechanisms of damage and thus to ensure a better therapeutic approach. Nonetheless, in cases of CMV-deafened babies, the overall outcome of cochlear implantation is good.

Published
2009
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32. Association between magnetic resonance signs of temporomandibular joint effusion and disk displacement.

Author

Manfredini D, Basso D, Arboretti R, and Guarda-Nardini L

Subjects
Adolescent, Adult, Aged, Female, Humans, Joint Dislocations pathology, Magnetic Resonance Imaging, Male, Middle Aged, Synovial Fluid, Young Adult, Hydrarthrosis pathology, Temporomandibular Joint Disc pathology, Temporomandibular Joint Disorders pathology
Abstract

Objective: The aim of the present study was to evaluate the association between temporomandibular joint (TMJ) effusion and disk displacement by means of magnetic resonance (MR) imaging., Methods: One hundred and ninety-four patients were included in the study and underwent a bilateral MR of the TMJ at both closed mouth and maximum mouth opening positions. The association between TMJ effusion and disk displacement with or without reduction was assessed by means of 2 x 2 contingency tables and a permutation test for a categorical variable., Results: The results showed a statistically significant association between joint effusion and disk displacement without reduction (DDNR) (P = .008). There was no statistically significant association between TMJ effusion and normal disk position (P = .99) or disk displacement with reduction (DDR) (P = .43)., Conclusions: Although these results show a significant association between joint effusion and disk displacement without reduction, there remains uncertainty as to if the nonreducing displacement causes the effusion or vice versa. The present investigation also pointed out the absence of association between reducing disk displacement and effusion. These findings have to be put into relation with clinical and hystological findings.

Published
2009
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33. Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction.

Author

Iacoviello L, Di Castelnuovo A, De Knijff P, D'Orazio A, Amore C, Arboretti R, Kluft C, and Benedetta Donati M

Subjects
Analysis of Variance, Blood Coagulation genetics, Case-Control Studies, Factor VII analysis, Factor VII physiology, Female, Genotype, Humans, Male, Middle Aged, Myocardial Infarction blood, Odds Ratio, Risk, Thrombosis genetics, Factor VII genetics, Myocardial Infarction genetics, Polymorphism, Genetic
Abstract

Background: High blood levels of coagulation factor VII are associated with a risk of ischemic vascular disease. Although factor VII levels may be genetically determined, the relation between genetic polymorphisms of factor VII, factor VII blood levels, and the risk of myocardial infarction has not been established., Methods: We performed a case-control study of 165 patients with familial myocardial infarction (mean [+/-SD] age, 55+/-9 years) and 225 controls without a personal or family history of cardiovascular disease (mean age, 56+/-8 years). The polymorphisms involving R353Q and hypervariable region 4 of the factor VII gene were studied. Factor VII clotting activity and antigen levels were also measured., Results: Patients with the QQ or H7H7 genotype had a decreased risk of myocardial infarction (odds ratios, 0.08 [95 percent confidence interval, 0.01 to 0.9] and 0.22 [95 percent confidence interval, 0.08 to 0.63], respectively). For the R353Q polymorphism, the RR genotype was associated with the highest risk, followed by the RQ genotype and then by the QQ genotype (P<0.001). For the polymorphism involving hypervariable region 4, the combined H7H5 and H6H5 genotypes were associated with the highest risk, followed in descending order by the H6H6, H6H7, and H7H7 genotypes (P<0.001). Patients with the QQ or H7H7 genotype had lower levels of both factor VII antigen and factor VII clotting activity than those with the RR or H6H6 genotype. Patients with the lowest level of factor VII clotting activity had a lower risk of myocardial infarction than those with the highest level (odds ratio, 0.13; 95 percent confidence interval, 0.05 to 0.34)., Conclusions: Our findings suggest that certain polymorphisms of the factor VII gene may influence the risk of myocardial infarction. It is possible that this effect may be mediated by alterations in factor VII levels.

Published
1998
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