Role of the circadian clock in the statistics of locomotor activity in Drosophila

In many animals the circadian rhythm of locomotor activity is controlled by an endogenous circadian clock. Using custom made housing and video tracking software in order to obtain high spatial and temporal resolution, we studied the statistical properties of the locomotor activity of wild type and two clock mutants of Drosophila melanogaster. We show here that the distributions of activity and quiescence bouts for the clock mutants in light-dark conditions (LD) are very different from the distributions obtained when there are no external cues from the environment (DD). In the wild type these distributions are very similar, showing that the clock controls this aspect of behavior in both regimes (LD and DD). Furthermore, the distributions are very similar to those reported for Wistar rats. For the timing of events we also observe important differences, quantified by how the event rate distributions scale for increasing time windows. We find that for the wild type these distributions can be rescaled by the same function in DD as in LD. Interestingly, the same function has been shown to rescale the rate distributions in Wistar rats. On the other hand, for the clock mutants it is not possible to rescale the rate distributions, which might indicate that the extent of circadian control depends on the statistical properties of activity and quiescence.Fil: Cascallares, Maria Guadalupe. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Riva, Sabrina Carla. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Franco, Diana Lorena. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Risau Gusman, Sebastian Luis. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Gleiser, Pablo Martin. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentin

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Mating disrupts morning anticipation in Drosophila melanogaster females

After mating, the physiology of Drosophila females undergo several important changes, some of which are reflected in their rest-activity cycles. To explore the hypothesis that mating modifies the temporal organization of locomotor activity patterns, we recorded fly activity by a video tracking method. Monitoring rest-activity patterns under light/dark (LD) cycles indicated that mated females lose their ability to anticipate the night-day transition, in stark contrast to males and virgins. This postmating response is mediated by the activation of the sex peptide receptor (SPR) mainly on pickpocket (ppk) expressing neurons, since reducing expression of this receptor in these neurons restores the ability to anticipate the LD transition in mated females. Furthermore, we provide evidence of connectivity between ppk+ neurons and the pigment-dispersing factor (PDF)-positive ventral lateral neurons (sLNv), which play a central role in the temporal organization of daily activity. Since PDF has been associated to the generation of the morning activity peak, we hypothesized that the mating signal could modulate PDF levels. Indeed, we confirm that mated females have reduced PDF levels at the dorsal protocerebrum; moreover, SPR downregulation in ppk+ neurons mimics PDF levels observed in males. In sum, our results are consistent with a model whereby mating-triggered signals reach clock neurons in the fly central nervous system to modulate the temporal organization of circadian behavior according to the needs of the new status.Fil: Riva, Sabrina Carla. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Ispizua, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Breide, María Trinidad. Comisión Nacional de Energía Atómica; ArgentinaFil: Polcowñuk, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Lobera, José Ricardo. Comisión Nacional de Energía Atómica; ArgentinaFil: Ceriani, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Risau Gusman, Sebastian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Franco, Diana Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentin

A Translational Approach to Spinal Neurofibromatosis: Clinical and Molecular Insights from a Wide Italian Cohort

Spinal neurofibromatosis (SNF), a phenotypic subclass of neurofibromatosis 1 (NF1), is characterized by bilateral neurofibromas involving all spinal roots. In order to deepen the understanding of SNF's clinical and genetic features, we identified 81 patients with SNF, 55 from unrelated families, and 26 belonging to 19 families with at least 1 member affected by SNF, and 106 NF1 patients aged >30 years without spinal tumors. A comprehensive NF1 mutation screening was performed using NGS panels, including NF1 and several RAS pathway genes. The main features of the SNF subjects were a higher number of internal neurofibromas (p < 0.001), nerve root swelling (p < 0.001), and subcutaneous neurofibromas (p = 0.03), while hyperpigmentation signs were significantly less frequent compared with the classical NF1-affected cohorts (p = 0.012). Fifteen patients underwent neurosurgical intervention. The histological findings revealed neurofibromas in 13 patients and ganglioneuromas in 2 patients. Phenotypic variability within SNF families was observed. The proportion of missense mutations was higher in the SNF cases than in the classical NF1 group (21.40% vs. 7.5%, p = 0.007), conferring an odds ratio (OR) of 3.34 (CI = 1.33-10.78). Two unrelated familial SNF cases harbored in trans double NF1 mutations that seemed to have a subclinical worsening effect on the clinical phenotype. Our study, with the largest series of SNF patients reported to date, better defines the clinical and genetic features of SNF, which could improve the management and genetic counseling of NF1

A Translational Approach to Spinal Neurofibromatosis: Clinical and Molecular Insights from a Wide Italian Cohort

Spinal neurofibromatosis (SNF), a phenotypic subclass of neurofibromatosis 1 (NF1), is characterized by bilateral neurofibromas involving all spinal roots. In order to deepen the understanding of SNF’s clinical and genetic features, we identified 81 patients with SNF, 55 from unrelated families, and 26 belonging to 19 families with at least 1 member affected by SNF, and 106 NF1 patients aged >30 years without spinal tumors. A comprehensive NF1 mutation screening was performed using NGS panels, including NF1 and several RAS pathway genes. The main features of the SNF subjects were a higher number of internal neurofibromas (p < 0.001), nerve root swelling (p < 0.001), and subcutaneous neurofibromas (p = 0.03), while hyperpigmentation signs were significantly less frequent compared with the classical NF1-affected cohorts (p = 0.012). Fifteen patients underwent neurosurgical intervention. The histological findings revealed neurofibromas in 13 patients and ganglioneuromas in 2 patients. Phenotypic variability within SNF families was observed. The proportion of missense mutations was higher in the SNF cases than in the classical NF1 group (21.40% vs. 7.5%, p = 0.007), conferring an odds ratio (OR) of 3.34 (CI = 1.33–10.78). Two unrelated familial SNF cases harbored in trans double NF1 mutations that seemed to have a subclinical worsening effect on the clinical phenotype. Our study, with the largest series of SNF patients reported to date, better defines the clinical and genetic features of SNF, which could improve the management and genetic counseling of NF1

Corpus callosum abnormalities: neuroimaging, cytogenetics and clinical characterization of a very large multicenter Italian series

Corpus callosum abnormalities (CCA) have an estimated prevalence ranging from 0.3% up to 0.7% in patients undergoing brain imaging. CCA can be identified incidentally, or can be part of a developmental disease. We performed a retrospective study of 551 patients, identified non-syndromic (NS) CCA and syndromic (S) CCA, reviewing clinical features, neuroradiological aspects, genetic etiology, and chromosomal microarray (CMA) results. Syndromic CCA subjects were prevalent (60%) and they showed the most severe clinical features. Cortical malformations and cerebellar anomalies were 23% of cerebral malformation associated to CCA (plus), 23 and 14% respectively in syndromic forms. A clinical and/or genetic diagnosis was obtained in 37% of syndromic CCA including chromosomal rearrangements on high-resolution karyotype (18%), microdeletion/microduplication syndromes (31%) and monogenic diseases (51%). Non-syndromic CCA anomalies had mildest clinical features, although intellectual disability was present in 49% of cases and epilepsy in 13%. CMA diagnostic rate in our cohort of patients ranged from 11 to 23% (NS to S). A high percentage of patients (76% 422/551) remain without a diagnosis. Combined high resolution CMA studies and next-generation sequencing (NGS) strategies will increase the probability to identify new causative genes of CCA and to redefine genotype–phenotype correlation

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

Prognostic value of degree and types of anaemia on clinical outcomes for hospitalised older patients

Study objective This study investigated in a large sample of in-patients the impact of mild-moderate-severe anaemia on clinical outcomes such as in-hospital mortality, re-admission, and death within three months after discharge. Methods A prospective multicentre observational study, involving older people admitted to 87 internal medicine and geriatric wards, was done in Italy between 2010 and 2012. The main clinical/laboratory data were obtained on admission and discharge. Based on haemoglobin (Hb), subjects were classified in three groups: group 1 with normal Hb, (reference group), group 2 with mildly reduced Hb (10.0–11.9 g/dL in women; 10.0–12.9 g/dL in men) and group 3 with moderately-severely reduced Hb (<10 g/dL in women and men). Results Patients (2678; mean age 79.2 ± 7.4 y) with anaemia (54.7%) were older, with greater functional impairment and more comorbidity. Multivariable analysis showed that mild but not moderate-severe anaemia was associated with a higher risk of hospital re-admission within three months (group 2: OR = 1.62; 95%CI 1.21–2.17). Anaemia failed to predict in-hospital mortality, while a higher risk of dying within three months was associated with the degree of Hb reduction on admission (group 2: OR = 1.82;95%CI 1.25–2.67; group 3: OR = 2.78;95%CI 1.82–4.26) and discharge (group 2: OR = 2.37;95%CI 1.48–3.93; group 3: OR = 3.70;95%CI 2.14–6.52). Normocytic and macrocytic, but not microcytic anaemia, were associated with adverse clinical outcomes. Conclusions Mild anaemia predicted hospital re-admission of older in-patients, while three-month mortality risk increased proportionally with anaemia severity. Type and severity of anaemia affected hospital re-admission and mortality, the worst prognosis being associated with normocytic and macrocytic anaemia

Hospital Care of Older Patients With COPD: Adherence to International Guidelines for Use of Inhaled Bronchodilators and Corticosteroids

313noObjectives: We aimed to analyze the prevalence and impact of COPD in older patients hospitalized in internal medicine or geriatric wards, and to investigate adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, associated clinical factors, and outcomes. Design: Data were obtained from REgistro POliterapie SIMI (REPOSI), a prospective multicenter observational registry that enrolls inpatients aged 65 years. Setting and Participants: Older hospitalized patients enrolled from 2008 to 2016 with a diagnosis of COPD. Measures: We evaluated adherence to the 2018 GOLD guidelines at admission and discharge, by examining the prescription of inhaled bronchodilators and corticosteroids in COPD patients. We also evaluated the occurrence of outcomes and its association with COPD and guideline adherence. Results: At hospital admission, COPD was diagnosed in 1302 (21.5%) of 6046 registered patients. COPD patients were older, with more impaired clinical and functional status and multiple comorbidities. Overall, 34.3% of COPD patients at admission and 35.6% at discharge were adherent to the GOLD guidelines. Polypharmacy (5 drugs) at admission [odds ratio (OR): 3.28, 95% confidence interval (CI): 2.24-4.81], a history of acute COPD exacerbation (OR: 2.65, 95% CI: 1.44-4.88) at admission, smoking habit (OR: 1.45, 95% CI: 1.08-1.94), and polypharmacy at discharge (OR: 6.76, 95% CI: 4.15-11.0) were associated with adherence to guidelines. COPD was independently associated with the risk of cardiovascular and respiratory death and rehospitalization occurrence compared to patients without COPD during follow-up. Adherence to guidelines was inversely associated with the occurrence of death from all causes (OR: 0.12, 95% CI: 0.02-0.90). Conclusions/Implications: COPD was common in older patients acutely hospitalized, showing an impaired functional and clinical status. Prescriptions for older COPD patients were often not adherent to GOLD guidelines. Poor adherence to guidelines was associated with a worse clinical status. There is a need to improve adherence to guidelines in treating COPD patients, with the ultimate goal of reducing clinical events.reservedmixedProietti, Marco; Agosti, Pasquale; Lonati, Chiara; Corrao, Salvatore; Perticone, Francesco; Mannucci, Pier Mannuccio; Nobili, Alessandro; Harari, Sergio; Tettamanti, Mauro; Pasina, Luca; Franchi, Carlotta; Marengoni, Alessandra; Salerno, Francesco; Cesari, Matteo; Licata, Giuseppe; Violi, Francesco; Corazza, Gino Roberto; Cortesi, Laura; Ardoino, Ilaria; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Emmi, Giacomo; Biolo, Gianni; Zanetti, Michela; Guadagni, Martina; Zaccari, Michele; Vanoli, Massimo; Grignani, Giulia; Pulixi, Edoardo Alessandro; Bernardi, Mauro; Bassi, Silvia Li; Santi, Luca; Zaccherini, Giacomo; Mannarino, Elmo; Lupattelli, Graziana; Bianconi, Vanessa; Paciullo, Francesco; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Palazzuoli, Alberto; Olivieri, Oliviero; Girelli, Domenico; Matteazzi, Thomas; Barbagallo, Mario; Dominguez, Ligia; Cocita, Floriana; Beneduce, Vincenza; Plances, Lidia; Zoli, Marco; Lazzari, Ilaria; Brunori, Mattia; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Palasciano, Giuseppe; Modeo, Maria Ester; Di Gennaro, Carla; Cappellini, Maria Domenica; Maira, Diletta; Di Stefano, Valeria; Fabio, Giovanna; Seghezzi, Sonia; Mancarella, Marta; Rossi, Paolo Dionigi; Damanti, Sarah; Clerici, Marta; Conti, Federica; Miceli, Emanuela; Lenti, Marco Vincenzo; Pisati, Martina; Dominioni, Costanza Caccia; Murialdo, Giovanni; Marra, Alessio; Cattaneo, Federico; Pontremoli, Roberto; Secchi, Maria Beatrice; Ghelfi, Davide; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria; Cipollone, Francesco; Guagnano, Maria Teresa; Angelucci, Ermanno; Valeriani, Emanuele; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Delitala, Giuseppe; Berria, Maria; Muscaritoli, Maurizio; Molfino, Alessio; Petrillo, Enrico; Zuccalà, Giuseppe; D'Aurizio, Gabriella; Romanelli, Giuseppe; Zucchelli, Alberto; Picardi, Antonio; Gentilucci, Umberto Vespasiani; Gallo, Paolo; Dell'Unto, Chiara; Annoni, Giorgio; Corsi, Maurizio; Bellelli, Giuseppe; Zazzetta, Sara; Mazzola, Paolo; Szabo, Hajnalka; Bonfanti, Alessandra; Arturi, Franco; Succurro, Elena; Rubino, Mariangela; Serra, Maria Grazia; Bleve, Maria Antonietta; Gasbarrone, Laura; Sajeva, Maria Rosaria; Brucato, Antonio; Ghidoni, Silvia; Fabris, Fabrizio; Bertozzi, Irene; Bogoni, Giulia; Rabuini, Maria Victoria; Cosi, Elisabetta; Manfredini, Roberto; Fabbian, Fabio; Boari, Benedetta; De Giorgi, Alfredo; Tiseo, Ruana; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Borghi, Claudio; Strocchi, Enrico; De Sando, Valeria; Pareo, Ilenia; Sabbà, Carlo; Vella, Francesco Saverio; Suppressa, Patrizia; Schilardi, Andrea; Loparco, Francesca; Fenoglio, Luigi; Bracco, Christian; Giraudo, Alessia Valentina; Fargion, Silvia; Periti, Giulia; Porzio, Marianna; Tiraboschi, Slivia; Peyvandi, Flora; Rossio, Raffaella; Ferrari, Barbara; Colombo, Giulia; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Ceriani, Giuliana; Pallini, Giada; Dallegri, Franco; Ottonello, Luciano; Liberale, Luca; Caserza, Lara; Salam, Kassem; Liberato, Nicola Lucio; Tognin, Tiziana; Bianchi, Giovanni Battista; Giaquinto, Sabrina; Purrello, Francesco; Di Pino, Antonino; Piro, Salvatore; Rozzini, Renzo; Falanga, Lina; Spazzini, Elena; Ferrandina, Camillo; Montrucchio, Giuseppe; Petitti, Paolo; Salmi, Raffaella; Gaudenzi, Piergiorgio; Perri, Ludovica; Landolfi, Raffaele; Montalto, Massimo; Mirijello, Antonio; Guasti, Luigina; Castiglioni, Luana; Maresca, Andrea; Squizzato, Alessandro; Molaro, Marta; Grossi, Alessandra; Bertolotti, Marco; Mussi, Chiara; Libbra, Maria Vittoria; Dondi, Giulia; Pellegrini, Elisa; Carulli, Lucia; Colangelo, Lidia; Falbo, Tania; Stanghellini, Vincenzo; De Giorgio, Roberto; Ruggeri, Eugenio; Vecchio, Sara del; Salvi, Andrea; Leonardi, Roberto; Damiani, Giampaolo; Gabrielli, Armando; Capeci, William; Mattioli, Massimo; Martino, Giuseppe Pio; Biondi, Lorenzo; Pettinari, Pietro; Ghio, Riccardo; Col, Anna Dal; Minisola, Salvatore; Colangelo, Luciano; Afeltra, Antonella; Marigliano, Benedetta; Pipita, Maria Elena; Castellino, Pietro; Blanco, Julien; Zanoli, Luca; Pignataro, Samuele; Saracco, Valter; Fogliati, Marisa; Bussolino, Carlo; Mete, Francesca; Gino, Miriam; Cittadini, Antonio; Vigorito, Carlo; Arcopinto, Michele; Salzano, Andrea; Bobbio, Emanuele; Marra, Alberto Maria; Sirico, Domenico; Moreo, Guido; Gasparini, Francesca; Prolo, Silvia; Pina, Gloria; Ballestrero, Alberto; Ferrando, Fabio; Berra, Sergio; Dassi, Simonetta; Nava, Maria Cristina; Graziella, Bruno; Baldassarre, Stefano; Fragapani, Salvatore; Gruden, Gabriella; Galanti, Giorgio; Mascherini, Gabriele; Petri, Cristian; Stefani, Laura; Girino, Margherita; Piccinelli, Valeria; Nasso, Francesco; Gioffrè, Vincenza; Pasquale, Maria; Scattolin, Giuseppe; Martinelli, Sergio; Turrin, Mauro; Sechi, Leonardo; Catena, Cristina; Colussi, Gianluca; Passariello, Nicola; Rinaldi, Luca; Berti, Franco; Famularo, Giuseppe; Patrizia, Tarsitani; Castello, Roberto; Pasino, Michela; Ceda, Gian Paolo; Maggio, Marcello Giuseppe; Morganti, Simonetta; Artoni, Andrea; Del Giacco, Stefano; Firinu, Davide; Losa, Francesca; Paoletti, Giovanni; Montalto, Giuseppe; Licata, Anna; Malerba, Valentina; Antonino, Lasco; Basile, Giorgio; Antonino, Catalano; Malatino, Lorenzo; Stancanelli, Benedetta; Terranova, Valentina; Di Marca, Salvatore; Mecocci, Patrizia; Ruggiero, Carmelinda; Boccardi, Virginia; Meschi, Tiziana; Lauretani, Fulvio; Ticinesi, Andrea; Minuz, Pietro; Fondrieschi, Luigi; Pirisi, Mario; Fra, Gian Paolo; Sola, Daniele; Porta, Massimo; Riva, Piero; Quadri, Roberto; Scanzi, Giorgio; Mengoli, Caterina; Provini, Stella; Ricevuti, Laura; Simeone, Emilio; Scurti, Rosa; Tolloso, Fabio; Tarquini, Roberto; Valoriani, Alice; Dolenti, Silvia; Vannini, Giulia; Tedeschi, Alberto; Trotta, Lucia; Volpi, Riccardo; Bocchi, Pietro; Vignali, Alessandro; Cattaneo, MaraProietti, Marco; Agosti, Pasquale; Lonati, Chiara; Corrao, Salvatore; Perticone, Francesco; Mannucci, Pier Mannuccio; Nobili, Alessandro; Harari, Sergio; Tettamanti, Mauro; Pasina, Luca; Franchi, Carlotta; Marengoni, Alessandra; Salerno, Francesco; Cesari, Matteo; Licata, Giuseppe; Violi, Francesco; Corazza, Gino Roberto; Cortesi, Laura; Ardoino, Ilaria; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Emmi, Giacomo; Biolo, Gianni; Zanetti, Michela; Guadagni, Martina; Zaccari, Michele; Vanoli, Massimo; Grignani, Giulia; Pulixi, Edoardo Alessandro; Bernardi, Mauro; Bassi, Silvia Li; Santi, Luca; Zaccherini, Giacomo; Mannarino, Elmo; Lupattelli, Graziana; Bianconi, Vanessa; Paciullo, Francesco; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Palazzuoli, Alberto; Olivieri, Oliviero; Girelli, Domenico; Matteazzi, Thomas; Barbagallo, Mario; Dominguez, Ligia; Cocita, Floriana; Beneduce, Vincenza; Plances, Lidia; Zoli, Marco; Lazzari, Ilaria; Brunori, Mattia; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Palasciano, Giuseppe; Modeo, Maria Ester; Di Gennaro, Carla; Cappellini, Maria Domenica; Maira, Diletta; Di Stefano, Valeria; Fabio, Giovanna; Seghezzi, Sonia; Mancarella, Marta; Rossi, Paolo Dionigi; Damanti, Sarah; Clerici, Marta; Conti, Federica; Miceli, Emanuela; Lenti, Marco Vincenzo; Pisati, Martina; Dominioni, Costanza Caccia; Murialdo, Giovanni; Marra, Alessio; Cattaneo, Federico; Pontremoli, Roberto; Secchi, Maria Beatrice; Ghelfi, Davide; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria; Cipollone, Francesco; Guagnano, Maria Teresa; Angelucci, Ermanno; Valeriani, Emanuele; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Delitala, Giuseppe; Berria, Maria; Muscaritoli, Maurizio; Molfino, Alessio; Petrillo, Enrico; Zuccalà, Giuseppe; D'Aurizio, Gabriella; Romanelli, Giuseppe; Zucchelli, Alberto; Picardi, Antonio; Gentilucci, Umberto Vespasiani; Gallo, Paolo; Dell'Unto, Chiara; Annoni, Giorgio; Corsi, Maurizio; Bellelli, Giuseppe; Zazzetta, Sara; Mazzola, Paolo; Szabo, Hajnalka; Bonfanti, Alessandra; Arturi, Franco; Succurro, Elena; Rubino, Mariangela; Serra, Maria Grazia; Bleve, Maria Antonietta; Gasbarrone, Laura; Sajeva, Maria Rosaria; Brucato, Antonio; Ghidoni, Silvia; Fabris, Fabrizio; Bertozzi, Irene; Bogoni, Giulia; Rabuini, Maria Victoria; Cosi, Elisabetta; Manfredini, Roberto; Fabbian, Fabio; Boari, Benedetta; De Giorgi, Alfredo; Tiseo, Ruana; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Borghi, Claudio; Strocchi, Enrico; De Sando, Valeria; Pareo, Ilenia; Sabbà, Carlo; Vella, Francesco Saverio; Suppressa, Patrizia; Schilardi, Andrea; Loparco, Francesca; Fenoglio, Luigi; Bracco, Christian; Giraudo, Alessia Valentina; Fargion, Silvia; Periti, Giulia; Porzio, Marianna; Tiraboschi, Slivia; Peyvandi, Flora; Rossio, Raffaella; Ferrari, Barbara; Colombo, Giulia; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Ceriani, Giuliana; Pallini, Giada; Dallegri, Franco; Ottonello, Luciano; Liberale, Luca; Caserza, Lara; Salam, Kassem; Liberato, Nicola Lucio; Tognin, Tiziana; Bianchi, Giovanni Battista; Giaquinto, Sabrina; Purrello, Francesco; Di Pino, Antonino; Piro, Salvatore; Rozzini, Renzo; Falanga, Lina; Spazzini, Elena; Ferrandina, Camillo; Montrucchio, Giuseppe; Petitti, Paolo; Salmi, Raffaella; Gaudenzi, Piergiorgio; Perri, Ludovica; Landolfi, Raffaele; Montalto, Massimo; Mirijello, Antonio; Guasti, Luigina; Castiglioni, Luana; Maresca, Andrea; Squizzato, Alessandro; Molaro, Marta; Grossi, Alessandra; Bertolotti, Marco; Mussi, Chiara; Libbra, Maria Vittoria; Dondi, Giulia; Pellegrini, Elisa; Carulli, Lucia; Colangelo, Lidia; Falbo, Tania; Stanghellini, Vincenzo; De Giorgio, Roberto; Ruggeri, Eugenio; Vecchio, Sara del; Salvi, Andrea; Leonardi, Roberto; Damiani, Giampaolo; Gabrielli, Armando; Capeci, William; Mattioli, Massimo; Martino, Giuseppe Pio; Biondi, Lorenzo; Pettinari, Pietro; Ghio, Riccardo; Col, Anna Dal; Minisola, Salvatore; Colangelo, Luciano; Afeltra, Antonella; Marigliano, Benedetta; Pipita, Maria Elena; Castellino, Pietro; Blanco, Julien; Zanoli, Luca; Pignataro, Samuele; Saracco, Valter; Fogliati, Marisa; Bussolino, Carlo; Mete, Francesca; Gino, Miriam; Cittadini, Antonio; Vigorito, Carlo; Arcopinto, Michele; Salzano, Andrea; Bobbio, Emanuele; Marra, Alberto Maria; Sirico, Domenico; Moreo, Guido; Gasparini, Francesca; Prolo, Silvia; Pina, Gloria; Ballestrero, Alberto; Ferrando, Fabio; Berra, Sergio; Dassi, Simonetta; Nava, Maria Cristina; Graziella, Bruno; Baldassarre, Stefano; Fragapani, Salvatore; Gruden, Gabriella; Galanti, Giorgio; Mascherini, Gabriele; Petri, Cristian; Stefani, Laura; Girino, Margherita; Piccinelli, Valeria; Nasso, Francesco; Gioffrè, Vincenza; Pasquale, Maria; Scattolin, Giuseppe; Martinelli, Sergio; Turrin, Mauro; Sechi, Leonardo; Catena, Cristina; Colussi, Gianluca; Passariello, Nicola; Rinaldi, Luca; Berti, Franco; Famularo, Giuseppe; Patrizia, Tarsitani; Castello, Roberto; Pasino, Michela; Ceda, Gian Paolo; Maggio, Marcello Giuseppe; Morganti, Simonetta; Artoni, Andrea; Del Giacco, Stefano; Firinu, Davide; Losa, Francesca; Paoletti, Giovanni; Montalto, Giuseppe; Licata, Anna; Malerba, Valentina; Antonino, Lasco; Basile, Giorgio; Antonino, Catalano; Malatino, Lorenzo; Stancanelli, Benedetta; Terranova, Valentina; Di Marca, Salvatore; Mecocci, Patrizia; Ruggiero, Carmelinda; Boccardi, Virginia; Meschi, Tiziana; Lauretani, Fulvio; Ticinesi, Andrea; Minuz, Pietro; Fondrieschi, Luigi; Pirisi, Mario; Fra, Gian Paolo; Sola, Daniele; Porta, Massimo; Riva, Piero; Quadri, Roberto; Scanzi, Giorgio; Mengoli, Caterina; Provini, Stella; Ricevuti, Laura; Simeone, Emilio; Scurti, Rosa; Tolloso, Fabio; Tarquini, Roberto; Valoriani, Alice; Dolenti, Silvia; Vannini, Giulia; Tedeschi, Alberto; Trotta, Lucia; Volpi, Riccardo; Bocchi, Pietro; Vignali, Alessandro; Cattaneo, Mar

Antibiotic use and associated factors in a large sample of hospitalised older people.

OBJECTIVES: The aims of this study were to assess (i) the prevalence of antibiotic use, (ii) factors associated with their use and (iii) the association with in-hospital mortality in a large sample of hospitalised older people in Italy. METHODS: Data were obtained from the 2010-2017 REPOSI register held in more than 100 internal medicine and geriatric wards in Italy. Patients aged ≥65 years with at least one antibiotic prescription during their hospitalisation were selected. Multivariable logistic regression models were used to determine factors associated with antibiotic use. RESULTS: A total of 5442 older patients were included in the analysis, of whom 2786 (51.2%) were prescribed antibiotics during their hospitalisation. The most frequently prescribed antibiotic class was β- lactams, accounting for 50% of the total prescriptions. Poor physical independence, corticosteroid use and being hospitalised in Northern Italy were factors associated with a higher likelihood of being prescribed antibiotics. Antibiotic use was associated with an increased risk of in-hospital mortality (odds ratio=2.52, 95% confidence interval 1.82-3.48) also when accounting for factors associated with their use. CONCLUSION: Hospitalised older people are often prescribed antibiotics. Factors related to poor physical independence and corticosteroid use are associated with increased antibiotic use. Being prescribed antibiotics is also associated with an increased risk of in-hospital death. These results demand the implementation of specific stewardship programmes to improve the correct use of antibiotics in hospital settings and to reduce the risk of antimicrobial resistance