Single transducer for measurement of small displacements or forces

Introduction: One of the limits to characterization of tissues at the microscopic level is the substantial costs associated with the instrumentation required for such investigations. The use of strain gages for displacement or force measurements can be adapted to this microscopic scale provided the gages are incorporated into a transducer consisting of a curved geometry. Materials and Methods: Uniaxial strain gages 13 mm (L) × 6 mm (W) were secured to 0.2-mm thick brass shim stock fabricated to yield a 12.5-mm diameter semicircle with mounting tabs on either end. The terminal ends of the strain gage mounting pads were connected to an adjustable strain gage amplifier with adjustable gain and offset. For displacement calibration, the transducer was secured to the jaws of a digital caliper. Caliper displacement was set to ±0.25 mm increments from 0 to a maximum of ±1.5 mm. In this configuration, positive represents tension. Amplifier Gains were set to 500, 1000, and 5000 to observe nonlinearity. For each of three displacement calibration runs, output voltage from the transducer was recorded at each distance with the mean output at absolute distances averaged across each of three runs for each of six transducers. Using the same transducers, a mass balance was used to identify the unique individual mass associated with a total of 10 masses to within ±10 μg. The masses were sequentially secured to the transducer and the respective output voltage recorded. Amplifier Gains were set to 500, 1000 and 5000. For each of three force calibration runs, output voltage from the transducer was recorded with respect to the force generated by the suspended masses. The mean output across each of three runs for each of six transducers was subjected to linear regression. Results and Discussion: All transducers displayed good linearity when calibrated for displacement with regression R2 values of 0.9994, 0.9967, and 0.9941 for amplifier gains of 500, 1000, and 5000, respectively. Further, in displacement mode, the transducers provided a mean output of 0.66, 1.01, and 3.86 V/mm at amplifier gains of 500, 1000, and 5000, respectively. In force mode, regression R2 in excess of 0.9995 were observed over all amplifier gain settings examined. When employed as force transducers, the devices provided mean outputs of 0.60, 1.15, and 5.85 V/N at amplifier gains of 500, 1000, and 5000, respectively. The response of these devices to either applied displacement or force permits the use of a single device type to be used as either a displacement or force transducer. The electrical output in either mode at modest amplification gains of 5000 combined with excellent linearity affords the use of these devices for studies where characterization of tissues requires mN and μm level resolution. Conclusions: A transducer employing a strain gage had been configured so as to function as either a displacement or force measuring instrument. The resulting device displays high linearity and electrical output even at modest amplifier gains

Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure

Introduction: Although checkpoint inhibitors (CPIs) have improved outcomes for patients with metastatic melanoma, those progressing on CPIs have limited therapeutic options. To address this unmet need and overcome CPI resistance mechanisms, novel immunotherapies, such as T-cell engaging agents, are being developed. The use of these agents has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs), which is challenging to predict preclinically and can lead to neutralization of the drug and loss of efficacy. Methods: TYRP1-TCB (RO7293583; RG6232) is a T-cell engaging bispecific (TCB) antibody that targets tyrosinase-related protein 1 (TYRP1), which is expressed in many melanomas, thereby directing T cells to kill TYRP1-expressing tumor cells. Preclinical studies show TYRP1-TCB to have potent anti-tumor activity. This first-in-human (FIH) phase 1 dose-escalation study characterized the safety, tolerability, maximum tolerated dose/optimal biological dose, and pharmacokinetics (PK) of TYRP1-TCB in patients with metastatic melanoma (NCT04551352). Results: Twenty participants with cutaneous, uveal, or mucosal TYRP1-positive melanoma received TYRP1-TCB in escalating doses (0.045 to 0.4 mg). All participants experienced ≥1 treatment-related adverse event (TRAE); two participants experienced grade 3 TRAEs. The most common toxicities were grade 1–2 cytokine release syndrome (CRS) and rash. Fractionated dosing mitigated CRS and was associated with lower levels of interleukin-6 and tumor necrosis factor-alpha. Measurement of active drug (dual TYPR1- and CD3-binding) PK rapidly identified loss of active drug exposure in all participants treated with 0.4 mg in a flat dosing schedule for ≥3 cycles. Loss of exposure was associated with development of ADAs towards both the TYRP1 and CD3 domains. A total drug PK assay, measuring free and ADA-bound forms, demonstrated that TYRP1-TCB-ADA immune complexes were present in participant samples, but showed no drug activity in vitro. Discussion: This study provides important insights into how the use of active drug PK assays, coupled with mechanistic follow-up, can inform and enable ongoing benefit/risk assessment for individuals participating in FIH dose-escalation trials. Translational studies that lead to a better understanding of the underlying biology of cognate T- and B-cell interactions, ultimately resulting in ADA development to novel biotherapeutics, are needed

Accumulation of α-synuclein mediates podocyte injury in Fabry nephropathy

Current therapies for Fabry disease are based on reversing intracellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization of the defective enzyme, thereby alleviating lysosomal dysfunction. However, their effect in the reversal of end-organ damage, like kidney injury and chronic kidney disease, remains unclear. In this study, ultrastructural analysis of serial human kidney biopsies showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not reverse podocyte injury. Then, a CRISPR/Cas9–mediated α-galactosidase knockout podocyte cell line confirmed ERT-mediated reversal of Gb3 accumulation without resolution of lysosomal dysfunction. Transcriptome-based connectivity mapping and SILAC-based quantitative proteomics identified α-synuclein (SNCA) accumulation as a key event mediating podocyte injury. Genetic and pharmacological inhibition of SNCA improved lysosomal structure and function in Fabry podocytes, exceeding the benefits of ERT. Together, this work reconceptualizes Fabry-associated cell injury beyond Gb3 accumulation, and introduces SNCA modulation as a potential intervention, especially for patients with Fabry nephropathy.publishedVersio

Yolk sac cell atlas reveals multiorgan functions during human early development

The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference of the human YS from 3 to 8 postconception weeks by integrating single-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis, we highlight roles in metabolism, coagulation, vascular development, and hematopoietic regulation. We reconstructed the emergence and decline of YS hematopoietic stem and progenitor cells from hemogenic endothelium and revealed a YS-specific accelerated route to macrophage production that seeds developing organs. The multiorgan functions of the YS are superseded as intraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancy proceeds

Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

Objectives: Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design: This is a cross-sectional study nested in the \u201cDelirium Day\u201d study, a nationwide Italian point-prevalence study. Setting and Participants: Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures: Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholinesterase inhibitors or memantine prior to admission. Results: Of the 1057 patients with dementia, 35% had delirium, with 25.6% hyperactive, 33.1% hypoactive, 34.5% mixed, and 6.7% nonmotor subtype. There were higher odds of having venous catheters in the hypoactive (OR 1.82, 95% CI 1.18-2.81) and mixed type of delirium (OR 2.23, CI 1.43-3.46), whereas higher odds of urinary catheters in the hypoactive (OR 2.91, CI 1.92-4.39), hyperactive (OR 1.99, CI 1.23-3.21), and mixed types of delirium (OR 2.05, CI 1.36-3.07). We found higher odds of antipsychotics both in the hyperactive (OR 2.87, CI 1.81-4.54) and mixed subtype (OR 1.84, CI 1.24-2.75), whereas higher odds of antibiotics was present only in the mixed subtype (OR 1.91, CI 1.26-2.87). Conclusions and Implications: In patients with dementia, the mixed delirium subtype is the most prevalent followed by the hypoactive, hyperactive, and nonmotor subtype. Motor subtypes of delirium may be triggered by clinical factors, including the use of venous and urinary catheters, and the use of antipsychotics. Future studies are necessary to provide further insights on the possible pathophysiology of delirium in patients with dementia and to address the optimization of the management of potential risk factors

Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016

reserved1229noObjective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P =.009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship.mixedAloisi Gaetano, Marengoni Alessandra, Morandi Alessandro, Zucchelli, Alberto, Cherubini Antonio, Mossello Enrico, Bo Mario, Di Santo Simona, Mazzone Andrea, Trabucchi Marco, Cappa Stefano, Fimognari Filippo, Antonelli Incalzi Raffaele, Gareri Pietro, Perticone Francesco, Campanini Mauro, Montorsi Marco, Latronico Nicola, Zambon Antonella, Bellelli Giuseppe, Rispoli Vincenzo, Malara Alba, Spadea Fausto, Di Cello Serena, Ceravolo Francesco, Fabiano Francesco, Chiaradia Giuseppe, Gabriele Amedeo, Lenino Peluso, Andrea Taristano, Settembrini Vincenzo, Capomolla Domenico, Citrino Antonella, Scriva Antonietta, Bruno Irene, Secchi Roberto, De Martino Eugenio, Muccinelli Roberto, Lupi Gerardo, Paonessa Patrizio, Fabbri Andrea, Passuti Maria Teresa, Castellari Sofia, Po Andrea, Gaggioli Guido, Varesi Massimo, Moneti Paolo, Capurso Sebastiano, Latini Vincenzo, Ghidotti Stefano, Riccardelli Francesco, Macchi Maurizio, Rigo Rosaria, Claudio Pascale, Bosio Angelo, Cerrato Flavio, Bardelli Benedetta, Boffelli Stefano, Cassinadri Angela, Franzoni Simone, Spazzini Elena, Andretto Daniela, Tonini Gabriele, Andreani Laura, Coralli Mirco, Balotta Antonio, Cancelliere Roberto, Ballardini Giorgio, Simoncelli Margherita, Mancini Annarita, Strazzacapa Mara, Fabio Stefano, De Filippi Francesco, Giudice Chiara, Dentizzi Cosimo, Azzini Margherita, Cazzadori Marco, Mastroeni Valeria, Bertassello Paolo, Santana Helena, Benati Claudia, Nesta Elisa, Tobaldini Chiara, Guerini Fabio, Tambara Elena, Mombelloni Paolo, Fontanini Fulvio, Lassa Gabriella, Lassa, Pizzorni Crosio, Oliverio Martina, del Grosso, Luciano Luca, Giavedoni Cristina, Bidoli Giuliano, Mazzei Bruno, Corsonello Andrea, Fusco Sergio, Vena Silvio, De Vuono Tommaso, Maiuri Giorgio, Fimognari Filippo Luca, Arone Andrea, Sgro Giovanni, Nicolazzo Rossella, Castegnaro Eugenio, De Rosa Salvatore, Sechi Bazzano Rossella, Benvenuti Enrico, Del Lungo Ilaria, Giardini Sante, Giulietti Chiara, Di Bari Mauro, Barghini Eleonora, Paoli Martina, Fiordelli Irene, Barucci Riccardo, Sgrilli Federica, Del Lungo Ilaria, Bertoletti Erik, D'Amico Ferdinando, Caronzolo Francesco, Grippa Alessandro, Lombardo Giuseppina, Pipicella Tiziana, Saitta Antonino, Corica Francesco, Cucinotta Valeria, Giaritta Prestipino, Larosa Daniela, Cucinotta Domenico, Basile Giorgio, March Albert, Nitti Maria Teresa, Felici Alessandro, Pavan Silvia, Piazzani Fabrizio, Lunelli Alessandra, Dimori Sergio, Margotta Alessandro, Soglia Tiziano, Postacchini Demetrio, Brunelli Roberto, Santini Silvia, Francavilla Monia, Macchiati Ilenia, Sorvillo Francesca, Giuli Cinzia, Mecocci Patrizia, Longo Annalisa, Perticone Francesco, Addesi Desiree, Rosa Paola Cerra, Bencardino Giuseppe, Falbo Tania, Grillo Nadia, Filice Marco, Mirella Filippo, Fanto Fausto, Isaia Gianluca, Pezzilli Stella, Bergamo Daniele, Furno Elisabetta, Rrodhe Sokol, Lucarini Simonetta, Dijk Babette, Dall'Acqua Francesca, Cappelletto Francesco, Calvani Donatella, Becheri Dimitri, Mottino Giuseppe, Mitidieri Costanza, Antonio Vito, Bartalucci Francesca, Magherini Lorenza, Malin Novella, Boni Franca, Gambardella Paoli Martina Lucia, Valente Carlo, Bracali Ilaria, Bracali, Foschini Alice, Bo Mario, Porrino Paola, Ceci Giacomo, Bottignole Giuliana, Tibaldi Michela, Coppo Eleonora, Ettore Evaristo, Camellini Cinzia, Servello Adriana, Grassi Alessandro, Rozzini Renzo, Tironi Sara, Grassi Maria Grazia, Troisi Elio, Caltagirone Carlo, Di Santo Simona, Franchini Flaminia, Ratto Federica, Pavoni Beatrice, Toniolo Sofia, Gabutto Anna, Quazzo Loredana, Rosatello Annalisa, Suraci Domenico, Tagliabue Benedetta, Perrone Chiara, Ferrara Lucia, Castagna Alberto, Tremolada Maria Luisa, Castoldi Giuseppe, Barbero Stefano, Oltramonti Davide, Piano Simonetta, Serviddio Gaetano, Lo Buglio Aurelio, Gurrera Tiziana, Merlo Valeria, Rovai Carla, Cotroneo Antonino Maria, Carlucci Rosaria, Abbaldo Anna, Monzani Fabio, Qasem Ahmad Amedeo, Bini Giacomo, Tafuto Silvia, Galli Giovanni, Bruni Amalia Cecilia, Mancuso Giovanna, Mancuso Gerardo, Calipari Daniela. De Luca Giuseppe Massimiliano, Bernardini Bruno, Corsini Carla, Ciccarelli Michele, Dal Farra Sara, Dal Farra, Cagnin Annachiara, Fragiacomo Federica, Pompanin Sara, Amodio Piero, Cagnin Marco, Zurlo Amedeo, Guerra Gianluca, Pala Marco, Menozzi Luca, Delli Gatti Chiara, Magon Stefania, Manfredini Roberto, De Giorgi Alfredo, Fabbian Fabio, Tiseo Ruana, Misurati Elisa, Boari Benedetta, Molino, Christian, Gallerani Massimo, Di Francesco Vincenzo, Faccioli Silvia, Pellizzari Luca, Fontana Giorgia, Barbagallo Giuseppe, Lunardelli Maria Lia, Martini Emilio, Ferrari Eleonora, Macchiarulo Maria, Corneli Maria, Bacci Monica, Battaglia Giuseppe, Anastasio Luigi, Lo Storto Mario Sostene, Seresin Chiara, Simonato Matteo, Loreggian Michele, Cestonaro Fausta, Durando Mario, Latella Raffaele, Mazzoleni Marta, Russo Giuseppe, Ponte Martino, Valchera Alessandro, Salustri Giuseppe, Petritola Donatella, Costa Alfredo, Sinforiani Elena, Cotta Matteo Ramusino, Piano Simonetta, Pizio Renato Nicola, Cester Alberto, Formilan Marino, Bonometto Pietro, Carbone Pasqualina, Cazzaniga Ilaria, Appollonio Ildebrando, Cereda Diletta, Stabile Andrea, Xhani Rubjona, Acampora Roberto, Tremolizzo Lucio, Pieruzzi Federico, Ciaccio Antonio, Pontecorvi Valerio, Burti Cesare, Mokini Zhirajr, Vitale Giovanni, Amigoni Maria, Sparacino Mariaelena, Bottacchi Edo, Bucciantini Elisabetta, Di Giovanni Marco, Franchi Fabrizio, Lucchetti Lucio, Mariani Claudio, Grande Giulia, Rapazzini Piero, Mauri Marco, Romanelli Giuseppe, Marengoni Alessandra, Nicosia Franco, Margola Alessio, Bonardelli Stefano, Latronico Nicola, Porcella Laura, Portolani Nazario, Concoreggi Carlo, Grassini Chiara, Salvi Andrea, Bianchetti Luca, Spagnoli Francesca, Apuzzo Roberto, Fontanella, Ceraso Anna, Castelli Francesco, Fugazza Luciano, Guerrini Chiara, De Paduanis Giovanna, Iallonardo Lucia, Palumbo Pasquale, Zuliani Giovanni, Ortolani Beatrice, Capatti Eleonora, Soavi Cecilia, Bianchi Lara, Francesconi Daniela, Miselli, Agata, Brombo Gloria, Romagnoli Tommaso, Pazzaglini Chiara, Miselli Maria Agata, Dall'Agata Marco, Suardi Teresa, Mazzone Andrea, Zaccarini Cinzia, Riva Manuela, Mirra Gianluca, Muti Ettore, Bottura Renato, Moretti Gianpaolo, Secreto Piero, Bisio Erika, Cecchettani Marco, Naldi Tamara, Pallavicino Alessandra, Pugliese Michela, Iozzo Rosaria Cosima, Grassi Guido, Bombelli Michele, DellOro Raffaella, Quarti Trevano Fosca, Giussani Carlo Giorgio, Paterno Giovanni, Contro Ernesto, Mannironi Antonio, Giorli Elisa, Oberti Sara, Fierro Brigida, Piccoli Tommaso, Giacalone Fabio, Mandas Antonella, Serchisu Luca, Costaggiu Diego, Pinna Elisa, Orru Francesca, Mannai Martina, Cordioli Zeno, Pelizzari Luca, Turcato Emanuela, Arduini Pietro, Cacace Carlo, Chiloiro Roberta, Cimino Rosella, Ruberto Carmen, Ruotolo Giovanni, Gareri Pietro, Greco Laura, Castagna Alberto, Dal Santo Pierluigi, Andriolli Antonino, Burattin Giuseppe, Rossi Laura, Andreolli Antonino, Cervati Giovanna, Catalano Giuseppe, Tezza Fabiana, Pizzardini Maddalena, Stievano Laura, Crippa Patrizia, Aloisio Paola, Di Monda Tiziana, Malighetti Alessandro, Galbassini Gloria, Ivaldi Claudio, Russo Anna Maria, Bennati Ettore, Pino Elisabetta, Zavarise Gianmaria, Pesci Alberto, Suigo Giulia, Faverio Paola, Gori Andrea, Perego Sabrina Perego, Zanasi Massimo, Moniello Giovanni, Rostagno Carlo, Cartei Alessandro, Polidori Gianluca, Ungar Andrea, Melis Maria Ramona, Martellini Eleonora, Mossello Enrico, Torrini Monica, Giordano Antonella, Leone Giovanna, Migliorini Marta, Caramelli Francesca, Battiston Bruno, Berardino Maurizio, Cavallo Simona, Masse Alessandro, Santoro Anna, Lombardi Bruna, D'Ippolito Pierpaolo, Furini Angela, Villani Daniele, Raimondi Clara, Guarneri Massimo, Paolucci Stefano, Bassi Andrea, Coiro Paola, De Angelis Domenico, Morone Giovanni, Venturiero Vincenzo, Palleschi Lorenzo, Raganato Paolo, Di Niro Giuseppina, Casini Anna Rosa, Bove Loredana, Imoscopi Alessandra, Isaia Giancarlo, Tibaldi Vittoria, Bottignole Giuliana, Calvi Elisa, Clementi Carlotta, Zanocchi Mauro, Agosta Luca, Criasia Antonio, Spertino Elena, Nortarelli Antonella, Provenzano Giuseppe, Principato Pietro, Rizzo Anita, Cellura Eleonora, Mari Daniela, Romano Federica Ylenia, Rosini Francesca, Mansi Marta, Rossi Silvia, Riccardelli Alex, Inzaghi Lorenzo, Bonini Giulia, Rossi Paolo, Potena Alfredo, Lichii Mihaela, Candiani Tiziana, Grimaldi William, Bertani Emiliano, Porta Alessandra, Calogero Pietro, Pinto Daniela, Bernardi Roberto, Nicolino Francesco, Galetti Caterina, Gianstefani Alice, Corvalli Giulia, Mulazzani Lorenzo, Odetti Patrizio, Monacelli Fiammetta, Prefumo Matteo, Monacelli Fiammetta, Canepa Marta, Minaglia Cecilia, Paolisso Giuseppe, Rizzo Maria Rosaria, Prestano Raffaele, Dalise Anna Maria, Barra Davide, Dal Bosco Livio, Asprinio Vincenzo, Dallape Luciana, Maina Paola, Perina Elisa, Bartoli Rossi Isaura, Pluderi Alice, Maina Antonella, Pecoraro Elisabetta, Sciarra Michela, Prudente Angela, Mete Francesca, Ventura Manuel, Cesari Luisella, Pernigotti Luigi Maria, Santangelo Tina, Benini Lucia, Levato Francesco, Mhiuta Victor, Alius Florin, Davidoaia Diana, Giardini Vittorio, Garancini Mattia, Bellamoli Claudio, Terranova Luciano, Bozzini Claudia, Tosoni Paolo, Provoli Emma, Cascone Luisa, Dioli Andrea, Ferrarin Gianfranco, Gabutto Anna, Bucci Adelmo, Bua Guido, Fenu Sara, Bianchi Giovanna, Casella Silvia, Romano Valentina, Poli Maurizio, Mascherona Ilenia, Belotti Gloria, Cavaliere Sabina, Cuni Estella, Merciuc Nina, Oberti Rosella, Veneziani Silvia, Capoferri Emanuela, De Bernardi Elisabetta, Colombo Katia, Bravi Marco, Negrinotti Nicoletta, D'Arcangelo Paolo, Montenegro Nicola, Galli Giovanni, Montanari Roberto, Lamanna Pierpaolo, Gasperini Beatrice, Montesi Isabella, Diotallevi Stefania, Altobelli Gaia, Cacinaro Filippo, Palama Chiara, Di Emidio Chiara, Scarpini Elio, Arighi Andrea, Scrimieri Antonia, Fumagalli Giorgio, Basilico Paola, Migone De Amicis Margherita, Mancarella Marta, Maira Diletta, D'Amico Ferdinando, Granata Antonino, Ranalli Claudia, Cammilli Alessandra, Cavallini Maria Chiara, Tricca Manola, Natella Daniela, Gabbani Luciano, Tesi Francesca, Martella Letizia, Gurrera Tiziana, Imbrici Rosalba, Pacchioni Maurizio, Gianbattista Guerrini, Scotuzzi Anna Maria, Sozzi Ferdinando, Valenti Luigi, Chiarello Antonino, Monella Monia, Pilotto Alberto, Prete Camilla, Senesi Barbara, Meta Anna Cristina, Pendenza Enrico, Monzani Fabio, Pasqualetti Giuseppe, Polini Antonio, Tognini Sara, Ballino Elena, Cherubini Antonio, Dell'Aquila Giuseppina, Gasparrini Pina Maria, Marotti Elisabetta, Migale Monica, Falsetti Lorenzo, Salvi Aldo, Toigo Gabriele, Ceschia Giuliano, Rosso Alessia, Tongiorgi Chiara, Scarpa Cristina, De Dominicis Luigino, Pucci Eugenio, Renzi Sara, Cartechini Elisabetta, Tomassini Pia Francesca, Del Gobbo Maurizio, Ugenti Francesca, Romeo Pasquale, Nardelli Anna, Lauretani Fulvio, Visioli Sandra, Montanari Ilaria, Ermini Francesca, Giordano Antonio, Pigato Giorgio, Simeone Emilio, Colameco Franco, Cecamore Antonella, Scurti Rosa, Lupinetti Maria Cristina, Barbujani Mario, Perazzi Beatrice, Giampieri Marina, Amoruso Raffaele, Piccinini Maristella, Ferrari Camilla, Gambetti Claudio, Sfrappini Mario, Semeraro Letizia, Striuli Rinaldo, Mariani Claudia, Pelliccioni Giuseppe, Marinelli Donatella, Fabi Katia, Rossi Tommaso, Pesallaccia Martina, Sabbatini Debora, Gobbi Beatrice, Cerqua Raffaella, Tagliani Giancarla, Schlauser Elena, Caser Luciano, Caramello Elisa, Sandigliano Franca, Rosso Giorgio, Bendini Chiara, Davoli Maria, Casella Monica, Prampolini Raffaella, Scevola Moreno, Vitale Enrico, Brugiolo Roberto, Brugiolo, Fagherazzi Carlo, Fusco Sergio, Scarpa Alberto, Zara Daniela, Bertozzo Giulia, Granziera Serena, Barazzuol Michele, Maugeri Domenico, Sorace Rosaria, Anzaldi Massimiliano, De Gesu Roberto, Morrone Giuseppe, Davolio Federica, Fabbo Andrea, Palmieri Marina, Forti Paola, Pirazzoli Luca, Fabbri Elisa, Terenzi Laura, Bergolari Federica, Wenter Christian, Ruffini Ingrid, Insam Miriam, Abraham Elisabeth, Kirchlechner Christine, Lasco Antonino, Basile Giorgio, Arena Maria Grazia, Parise Pasquale, Boccali Andrea, Amici Serena, Gambacorta Maurizia, Ferrari Alberto, Lasagni Anna, Lovati Roberto, Giovinazzo Francesca, Kimak Elzbieta, Zappa Paolo, Medici Francesco, Lo Castro Marika, Mauro Flavia, De Luca Alessandro, Sancesario Giuseppe, Martorana Alessandro, Scaricamazza Beatrice, Toniolo Sofia, Di Lorenzo Francesco, Liguori Claudio, Lasco Antonino, Basile Giorgio, Vita Natale, Giomi Mirna, Dimori Sergio, Forte Floriana, Padovani Alessandro, Rozzini Luca, Ceraso Anna, Caratozzolo Salvatore, Padovani Alessandro, Cottino Maria, Vitali Silvia, Marelli Eleonora, Tripi Gabriele, Miceli Salvatore, Urso Giovanni, Grioni Giuseppe, Vezzadini Giuliana, Misaggi Giulia, Forlani Chiara, Avanzi Stefano, Saulle Serena, Casarini Claudia, Viggiano Marilena, Alberto Luisa, Ghianda Diego, Giordano Alessandro, Iemolo Francesco, Giordano, Antonello, Sanzaro Enzo, D'Asta Gabriele, Proietto Maria, Carnemolla Anna, Razza Grazia, Spadaro Daniela, Bertolotti Marco, Mussi Chiara, Neviani Francesca, Chiesa Roberto, Guerzoni Valentina, Morselli Linda, Venturelli Francesca, Tarozzi Adriano, Balestri Francesca, Torrini Monica, Mannarino Giulio, Tesi Francesca, Bigolari Michela, Natale Alessia, Grassi Simona, Bottaro Cinzia, Stefanelli Sara, Bovone Ugo, Tortorolo Umberto, Quadri Roberto, Leone Giuseppe, Ponzetto Maria, Frasson Paola, Annoni Giorgio, Bellelli Giuseppe, Bruni Adriana, Confalonieri Roberto, Corsi Maurizio, Moretti Daniela, Teruzzi Fabiola, Umidi Simona, Mazzola Paolo, Perego Sabrina, Persico Ilaria, Olivieri Giulia, Bonfanti Alessandra, Hajnalka Szabo, Galeazzi Marianna, Massariello Francesca, Anzuini Alessandra, Caffarra Paolo, Barocco Federica, Spallazzi Marco, Ceda Gian Paolo, Morganti Simonetta, Artoni Andrea, Chioatto Paolo, Bortolamei Sandra, Soattin Lucia, Ruotolo Giovanni, Beneamino Borelli, Gareri Pietro, Barilaro Giuseppe, Ruberto Carmen, Castagna Alberto, Bertazzoli Marco, Rota Elisabetta, Adobati Annamaria, Scarpa Alberto, Granziera Serena, Zuccher Paola, Dal Fabbro Angela, Zara Daniela, Lo Nigro Ambra, Franchetti Lorena, Toniolo Marika, Marcuzzo Cinzia, Piano Simonetta, Rollone Marco, Guerriero Fabio, Sgarlata Carmelo, Masse Alessandro, Berardino Maurizio, Cavallo Simona, Anna Santoro, Zatti Giovanni, Piatti Massimiliano, Graci Jole, Benati Giuseppe, Boschi Federica, Biondi Mario, Fiumi Nicoletta, Erika Tamburini, Locatelli Sergio Mario, Mauri Sabrina, Beretta Mauro, Margheritis Laura, Desideri Giovanbattista, Liberatore Ester, Carucci Anna Cecilia, Bonino Paolo, Caput Margherita, Antonietti Maria Paola, Polistena Giuseppe, De la Pierre Franz, Mari Marcello, Massignani Paola, Tombesi Fabio, Selvaggio Fabio, Verbo Brunella, Bodoni Paolo, Marchionni Niccolo, Mossello Enrico, Cavallini Maria Chiara, Sabatini Tony, Mussio Eleonora, Magni Eugenio, Bianchetti Angelo, Crucitti Andrea, Titoldini Giulia, Cossu Beatrice, Fascendini Sara, Licini Cristina, Tomasoni Angela, Calderazzo Massimo, Tropiano Daniela, Lagana Valentina, Ferrari Alberto, Prampolini Raffaella, Melotti Rita Maria, Lilli Albina, Buda Simona, Adversi Marco, Noro Gabriele, Turco Renato, Ubezio M. 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Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016

Objective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P =.009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship