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Costa G.,University of Milan | Anelli M.M.,University of Milan | Castellini G.,IRCCS Ca Granda Ospedale Maggiore Policlinico Foundation | Fustinoni S.,University of Milan | Neri L.,University of Milan
Chronobiology International | Year: 2014

We compared two "3 × 8" shift rotas with backward rotation and quick return (morning and night shift in the same day) in a 5- or 6-day shift cycle, and a "2 × 12" shift rota with forward rotation in a 5-d shift cycle. A total of 294 nurses (72.6% women, mean age 33.8) were examined in a survey on work-related stress, including the Standard Shiftwork Index. Ten nurses per each shift roster recorded their activity and rest periods by actigraphy, rated sleepiness and sleep quality, and collected salivary cortisol throughout the whole shift cycle. Nurses engaged in the "2 × 12" rota showed lower levels of sleep disturbances and, according to actigraphy, sleep duration was more balanced and less fragmented than in the "3 × 8" rosters. The counter-clockwise shift rotation and quick return of "3 × 8" schedules reduce possibility of sleep and recovery. The insertion of a morning shift before the day with quick return increases night sleep by about 1 h. Nurses who take a nap during the night shift require 40% less sleep in the morning after. The "2 × 12" clockwise roster, in spite of 50% increased length of shift, allows a better recovery and more satisfying leisure times, thanks to longer intervals between work periods. Sleepiness increased more during the night than day shifts in all rosters, but without significant difference between 8-h and 12-h rosters. However, the significantly higher level at the start of the night shift in the "3 × 8" rotas points out that the fast backward rotation with quick return puts the subjects in less efficient operational conditions. Some personal characteristics, such as morningness, lability to overcome drowsiness, flexibility of sleeping habits and age were significantly associated to sleep disturbances in nurses engaged in the "3 × 8" rotas, but not in the "2 × 12" schedule. © 2014 Informa Healthcare USA, Inc. Source


Castaldi D.,University of Milan Bicocca | Maccagnola D.,University of Milan Bicocca | Mari D.,IRCCS Ca Granda Ospedale Maggiore Policlinico Foundation | Mari D.,University of Milan | Archetti F.,University of Milan Bicocca
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2013

In this paper we developed a Stochastic Petri Net (SPN) based model to introduce uncertainty to capture the variability of biological systems. The coagulation cascade, one of the most complex biochemical networks, has been widely analyzed in literature mostly with ordinary differential equations, outlining the general behavior but without pointing out the intrinsic variability of the system. Moreover, the computer simulation allows the assessment of the reactions over a broad range of conditions and provides a useful tool for the development and management of several observational studies, potentially customizable for each patient. We describe the SPN model for the Tissue Factor induced coagulation cascade, more intuitive and suitable than models hitherto appeared in the literature in terms of bioclinical manageability. The SPN has been simulated using Tau-Leaping Stochastic Simulation Algorithm, and in order to simulate a large number of models, to test different scenarios, we perform them using High Performance Computing. We analyze different settings for model representing the cases of "healthy" and "unhealthy" subjects, comparing their average behavior, their inter- and intra-variability in order to gain valuable biological insights. © 2013 Springer-Verlag. Source


Castaldi D.,University of Milan Bicocca | Maccagnola D.,University of Milan Bicocca | Mari D.,IRCCS Ca Granda Ospedale Maggiore Policlinico Foundation | Mari D.,University of Milan | Archetti F.,University of Milan Bicocca
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2013

In this paper authors perform a variability analysis of a Stochastic Petri Net (SPN) model of the Tissue Factor induced coagulation cascade, one of the most complex biochemical networks. This pathway has been widely analyzed in literature mostly with ordinary differential equations, outlining the general behaviour but without pointing out the intrinsic variability of the system. The SPN formalism can introduce uncertainty to capture this variability and, through computer simulation allows to generate analyzable time series, over a broad range of conditions, to characterize the trend of the main system molecules. We provide a useful tool for the development and management of several observational studies, potentially customizable for each patient. The SPN has been simulated using Tau-Leaping Stochastic Simulation Algorithm, and in order to simulate a large number of models, to test different scenarios, we perform them using High Performance Computing. We analyze different settings for model representing the cases of "healthy" and different " unhealthy" subjects, comparing and testing their variability in order to gain valuable biological insights. © 2013 Springer-Verlag. Source


Tripodi A.,University of Milan | Anstee Q.M.,Northumbria University | Sogaard K.K.,Aarhus University Hospital | Primignani M.,IRCCS Ca Granda Ospedale Maggiore Policlinico Foundation
Journal of Thrombosis and Haemostasis | Year: 2011

Decreased levels of most coagulation factors and thrombocytopenia are the main haemostatic abnormalities of cirrhosis. As a consequence, this condition was, until recently, considered as the prototype acquired coagulopathy responsible for bleeding. However, recent evidence suggests that it should, rather, be regarded as a condition associated with normal or even increased thrombin generation. The bleeding events that occur in these patients should, therefore, be explained by the superimposed conditions that frequently occur in this setting. Due to elevated levels of factor VIII (procoagulant driver) in combination with decreased protein C (anticoagulant driver), which are typically found in patients with cirrhosis, a procoagulant imbalance, defined as a partial resistance to the in vitro anticoagulant action of thrombomodulin, can be demonstrated. Whether this in vitro hypercoagulability is truly representative of what occurs in vivo remains to be established. However, the hypothesis that it may have clinical consequences is attractive and deserves attention. The possible consequences that we discuss herein include whether (i) cirrhosis is a condition associated with increased risk of venous thromboembolism or portal vein thrombosis; (ii) the hypercoagulability associated with cirrhosis has any other role outside coagulation (i.e. progression of liver fibrosis); and (iii) anticoagulation should be used in cirrhosis. Although apparently provocative, considering anticoagulation as a therapeutic option in patients with cirrhosis is now supported by a rationale of increasing strength. There may be subgroups of patients who benefit from anticoagulation to treat or prevent thrombosis and to slow hepatic fibrosis. Clinical studies are warranted to explore these therapeutic options. © 2011 International Society on Thrombosis and Haemostasis. Source


Bendtsen F.,Copenhagen University | D'Amico G.,Cervello | Rusch E.,Copenhagen University | De Franchis R.,IRCCS Ca Granda Ospedale Maggiore Policlinico Foundation | And 4 more authors.
Journal of Hepatology | Year: 2014

Background & Aims Two randomized controlled studies have evaluated the effect of recombinant Factor VIIa (rFVIIa) on variceal bleeding in cirrhosis without showing significant benefit. The aim of the present study was to perform a meta-analysis of the two trials on individual patient data with special focus on high risk patients. Methods The primary outcome measure was the effect of rFVIIa on a composite five day endpoint: failure to control bleeding, 5-day rebleeding or death. Analysis was based on intention to treat. High risk was defined as active bleeding on endoscopy while under vasoactive drug infusion and Child-Pugh score >8. Results 497 patients were eligible for the meta-analysis; 308 (62%) had active variceal bleeding at endoscopy (oozing or spurting) and 283 of these had a Child-Pugh score >8. Analysis on the composite endpoint in all patients with bleeding from oesophageal varices did not show any beneficial treatment effect. However, failure rate for the primary composite end-point was significantly lower in treated patients with active bleeding at endoscopy (17%) compared to placebo (26%, p = 0.049). This difference was highly significant in patients with Child-Pugh score >8 and active bleeding at endoscopy (rFVIIa 16%, placebo 27%; p = 0.023). No significant treatment effect was found at 42 days. Five thromboembolic events occurred in rFVIIa treated patients compared to none in placebo treated patients. Conclusions The current meta-analysis shows a beneficial effect of rFVIIa on the primary composite endpoint of control of acute bleeding, prevention of rebleeding day 1-5 and 5-day mortality in patients with advanced cirrhosis and active bleeding from oesophageal varices at endoscopy. A major drawback of the treatment is a potential increased risk of arterial thrombo-embolic events. This treatment might be considered in patients with lack of control of bleeding after standard treatment. Source

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