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Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Daiichi Sankyo Europe GmbH Background Direct oral anticoagulants (DOACs) have been shown to be non-inferior to vitamin K antagonists (VKA) regarding both efficacy and safety outcomes in patients with atrial fibrillation (AF). However, elderly are underrepresented in the underlying clinical trials. Purpose The aim of this study was to compare risks of major bleeding events and compare healthcare resource utilization (HRU) between AF patients treated with edoxaban or VKA in elderly. Methods A cohort study was conducted using claims databases of Caserta and Palermo Local Heath Units in Italy. AF patients starting use of edoxaban or VKA between August 1st, 2016 and December 31st, 2018 were included. Date of the first dispensing was defined as the index date. The study population was matched based on a propensity score based on factors associated with the outcome. We restricted to patients aged ≥65, ≥1 year database history, and no use of the index drug in the year before index date. Incidence rates of bleeding outcomes and rates of HRU were assessed per 1,000 and 100 person-years follow-up (PY), respectively. Cox regression analyses to adjust for baseline covariates were used for comparisons of incidence rates of bleeding outcomes among all edoxaban and VKA users. Poisson regression analyses were used for comparisons of rates of HRU among all edoxaban and VKA users. Both analyses were adjusted for age. Sex, region and year of index date were considered for the adjusted models as well, using a backward stepwise approach to select eligible variables. Results 1,317 edoxaban users and 2,924 VKA users were included in the matched population. Mean age was 79 in both treatments groups, and 43% of the edoxaban users and 45% of the VKA users was male. Bleeding risks were significantly lower among edoxaban users compared to VKA users aged ≥65 (adjusted HR 0.39 (95% CI 0.19-0.83)) and among patients aged ≥75 (adjusted HR 0.37 (95% CI 0.16-0.86)). Among patients aged ≥65, edoxaban users were significantly less often hospitalised (RR 0.56 (95% CI 0.46-0.68)) and the total number of hospitalised days were also significant lower (RR 0.58 (95% CI 0.42-0.80)) compared to VKA users. Among patients aged ≥75, similar results were observed for the number of hospitalisations. Edoxaban users had significant less out-patient visits compared to VKA users (among patients aged ≥65 the RR was 0.44 (95% CI 0.39-0.50) and among patients ≥75 this was 0.40 (95% CI 0.35-0.47). Use of out-patient medication use was significantly lower among edoxaban users compared to VKA users among patients aged ≥65 (adjusted RR 0.91 (95% CI 0.88-0.95)) as well as among patients aged ≥75 (adjusted RR 0.91 (95% CI 0.87-0.95)). Conclusion Study results show a decreased bleeding risk of edoxaban compared to VKA in both age groups of patients with AF. Hospital based HRU has shown to be lower among edoxaban users compared to VKA users in both age groups. Out-patient HRU was also lower among edoxaban users.

Background The International Agency for Research on Cancer evaluated formaldehyde (F) as carcinogenic for human in association with Nasopharyngeal Cancer (NPC). Occupational exposure to F occurs in many industrial sectors also in those non-traditional. For example in Tuscany F was detected in a bakery where a NPC case had ever worked. Methods In this study a) A case control approach (OCCAM) was used for monitoring occupational risks based on current information sources. Three Italian Regional Operating Centres, collected NPC cases from cancer registries and/or hospital discharge records. Controls were randomly sampled from the regional health service population data. Occupational histories were available through record linkage with the social security pension database (INPS). Study results were reported by industrial sectors, area and gender. b) A specific study on F exposure was conducted in bakeries and pastry industry carrying out measurements to determine the concentration of F in specific tasks and positions. Results 717 cases linked with INPS database. Increased ORs for several industrial sectors such as iron and steel, wood and plastic were observed. In two regions also health and veterinary services and hairdressers were at increased risk, but based on few cases of exposed workers. In the non traditional sector of bakeries and pastry industries, where workplaces were monitored, high levels of F in personal air samplings were found, in particular in processes that involve a strong leavening. Conclusions Many productive sectors, in which F exposure could occurred, were observed to be at higher risk. The measurements performed in the non traditional sector monitored, confirmed the F exposure in some phases of the work process. With this study we contributed to increased knowledge on the risk of NPC within the monitoring system of occupational risks, and to deepen exposure to F in a non traditional productive sector such as bakeries and pastry industries. Key messages The epidemiological method used (OCCAM) in this study provides further information on the role of occupational exposure in the development of nasopharyngeal cancer. The measurements performed in the bakeries and pastry industries provide new additional information on the exposure to formaldehyde in some work process phases of a non-traditional productive sector.

Although numerous studies have provided evidence of an association between ambient air pollution and acute cardiac morbidity, little is known regarding susceptibility factors.We conducted a time-stratified case-crossover study in 9 Italian cities between 2001 and 2005 to estimate the short-term association between airborne particles with aerodynamic diameter10 μm (PM10) and cardiac hospital admissions, and to identify susceptible groups. We estimated associations between daily PM10 and all cardiac diseases, acute coronary syndrome, arrhythmias and conduction disorders, and heart failure for 167,895 hospitalized subjects ≥ 65 years of age. Effect modification was assessed for age, sex, and a priori-defined hospital diagnoses (mainly cardiovascular and respiratory conditions) from the previous 2 years as susceptibility factors.The increased risk of cardiac admissions was 1.0% (95% confidence interval [CI] = 0.7% to 1.4%) per 10 μg/m PM10 at lag 0. The effect was slightly higher for heart failure (lag 0, 1.4% [0.7% to 2.0%]) and acute coronary syndrome (lag 0-1, 1.1% [0.4% to 1.9%]) than for arrhythmias (lag 0, 1.0% [0.2% to 1.8%]). Women were at higher risk of heart failure (2.0% [1.2% to 2.8%]; test for interaction, P = 0.022), whereas men were at higher risk of arrhythmias (1.9% [0.8% to 3.0%]; test for interaction, P = 0.020). Subjects aged 75-84 years were at higher risk of admissions for coronary events (2.6% [1.5% to 3.8%]; test for interaction, P = 0.001). None of the identified chronic conditions was a clear marker of susceptibility.An important effect of PM10 on hospitalizations for cardiac diseases was found in Italian cities. Sex and older age were susceptibility factors.

[3H]Flunitrazepam (FNZ) binding to cortical neurons from fetal rat brain was investigated in vitro. The use of a synthetic medium specific for neurons made it possible to plot a developmental curve of3H-FNZ binding in an almost pure neuronal culture. Detectable specific binding was present in vitro at time 0 (that is, the 16th gestational day). A progressive increase of binding, due to an increment in the number of recognition sites, was observed on the subsequent days. The affinity of the specific binding sites to3H-FNZ was enhanced by the addition of exogenous GABA, whereas the density was not affected. © 1990 Plenum Publishing Corporation.

An asymmetric distribution of GABA binding sites was found in the cerebral cortex, hippocampus, cerebellar hemispheres, striatum, and thalamus. Higher levels of [3H]GABA binding were observed in the left-side of most brain areas and in a greater percentage of adult rats, but the opposite asymmetry was found in the thalamus. A similar left-right difference in cerebral hemispheres was also found in five day-old rats, suggesting the genetic predetermination of asymmetry.