Issues in the management of invasive pulmonary aspergillosis in non-neutropenic patients in the intensive care unit: A role for isavuconazole

Background: Almost half of all cases of invasive aspergillosis (IA) occur in the intensive care unit (ICU), with mortality rates of 70\u201380% for probable or proven cases. IA has become a major concern among non-neutropenic patients in the ICU with chronic obstructive pulmonary disease (COPD) but although prompt, appropriate antifungal therapy is crucial, diagnosis in this situation is challenging. Criteria for a probable diagnosis in critically ill patients have been proposed to help to expedite therapy. Methods: A case of probable invasive pulmonary aspergillosis (IPA) in a non-neutropenic patient admitted to the ICU was used to illustrate potential issues in the diagnostic work-up and management of patients in this setting. Results: A non-neutropenic 69-year-old man with COPD receiving clomipramine was diagnosed in the ICU with probable invasive aspergillosis based on the presence of severe chronic obstructive pulmonary disease, suspected X-linked granulomatous disease, nodular infiltrates and galactogamman positivity on bronchoalveolar lavage (BAL) fluid. Voriconazole was unsuitable due to the patient's prolonged QT interval and risk of a drug\u2013drug interaction with clomipramine. Isavuconazole was initiated and the patient's condition improved. The three-month course of isavuconazole treatment was well-tolerated and resulted in compete recovery of the patient. Conclusions: Voriconazole is a standard first-line treatment for IA but intravenous therapy is associated with toxicity and the potential for drug\u2013drug interactions. Isavuconazole is another first-line therapy which was effective and safe in the management of this critically ill non-neutropenic patient with baseline QT prolongation and potential drug\u2013drug interactions with voriconazole

Emerging treatment options for acute bacterial skin and skin structure infections: Focus on intravenous delafloxacin

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillinresistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care

Impact of new treatment options for hepatitis c virus infection in liver transplantation

Liver transplant candidates and recipients with hepatitis C virus (HCV)-related liver disease greatly benefit from an effective antiviral therapy. The achievement of a sustained virological response before transplantation can prevent the recurrence of post-transplant HCV disease that occurs universally and correlates with enhanced progression to graft cirrhosis. Previous standard-of-care regimens (e.g., pegylated-interferon plus ribavirin with or without first generation protease inhibitors, boceprevir and telaprevir) displayed suboptimal results and poor tolerance in liver transplant recipients. A new class of potent direct-acting antiviral agents (DAA) characterized by all-oral regimens with minimal side effects has been approved and included in the recent guidelines for the treatment of liver transplant recipients with recurrent HCV disease. Association of sofosbuvir with ribavirin and/or ledipasvir is recommended in liver transplant recipients and patients with decompensated cirrhosis. Other regimens include simeprevir, daclatasvir, and combination of other DAA. Possible interactions should be monitored, especially in coinfected human immunodeficiency virus/HCV patients receiving antiretrovirals

Extension of analytical indicial aerodynamics to generic trapezoidal wings in subsonic flow

Analytical indicial aerodynamic functions are calculated for several trapezoidal wings in subsonic flow, with a Mach number 0.3≤ Ma≤ 0.7. The formulation herein proposed extends well-known aerodynamic theories, which are limited to thin aerofoils in incompressible flow, to generic trapezoidal wing planforms. Firstly, a thorough study is executed to assess the accuracy and limitation of analytical predictions, using unsteady results from two state-of-the-art computational fluid dynamics solvers as cross-validated benchmarks. Indicial functions are calculated for a step change in the angle of attack and for a sharp-edge gust, each for four wing configurations and three Mach numbers. Then, analytical and computational indicial responses are used to predict dynamic derivatives and the maximum lift coefficient following an encounter with a one-minus-cosine gust. It is found that the analytical results are in excellent agreement with the computational results for all test cases. In particular, the deviation of the analytical results from the computational results is within the scatter or uncertainty in the data arising from using two computational fluid dynamics solvers. This indicates the usefulness of the developed analytical theories

Model integration. Integrated socio-economic model on food waste

The model architecture described in this deliverable provides the framework through which data and simulations from the data on food waste at a consumer level and at a retail level can be integrated into simulation models. This report highlights the technical approaches followed to achieve model integration. This report highlights the technical approaches followed to achieve model integration. An integrated whole-of-system modelling approach will be developed as a part of the REFRESH project to allow the development of a decision-relevant, and dynamic policy support tool, by which a road map to the reduction of European food waste by 50% by 2030 can be developed. The vital first step (highlighted in this report) is to develop the structures to allow model integration between different model types: Agent-Based Models and Bayesian Networks. These structures were developed and tested to ensure that the model types can be integrated. The architecture described in this deliverable provides the framework through which data and simulations from the data on food waste at a consumer level and at a retail level can be integrated into simulation models. Since a sizable share of the food waste is generated either at the consumer level or at the interaction between consumers and retailers, we address the modelling effort with two integrated ABM-BN models. The first model reproduces the dynamic evolution of food waste choices of consumers as consequence of social interactions. The second focuses instead on the conditions for the successful diffusion and adoption of innovations to reduce food waste at the retailer level. The systemic modelling approach proposed will allow the development of selected simulation scenarios at the consumer and retail level, facilitating decision making in the face of uncertainty. These integrated setups are first iterations of working integrated models, aimed at validating technically the setups as well as the integration process itself. As they are, there are certainly factors that are likely to be important in determining food waste, which are not yet included in the models. However, the latter are flexible and can accommodate further details, and variables. Their construction is purposefully flexible in terms of components of decisions. The integration with Bayesian Networks ensure that Agent-Based models will learn from data originated from the other refresh WPs and will evolve, allowing the introduction of new variables and factors that will lead to the improvement of the different simulation scenarios. The REFRESH project implements a behavioural economics approach in order to identify and measure the most important socio-economic conditions and potential policy interventions driving businesses’ and consumers’ choices in the generation of food waste. More specifically, this work aims to provide new information on consumer and business behaviour by measuring the effects of major tangible factors of food waste, by identifying hidden and emerging profiles of consumer’ and business’ behaviours affecting food waste, and by allowing the detection of intangible food waste drivers. Such an objective is achieved through the development and the testing of Agent-Based Models (ABMs) and Bayesian networks (BNs)

From social interactions to private environmental behaviours: The case of consumer food waste

Consumer food waste, like many environmental behaviours, takes place in private, and is not directly subject to social monitoring. Nevertheless, social interactions can affect private opinions and behaviours. This paper builds an agent-based model of interactions between consumers heterogeneous in their sociability, their initial opinions and behaviours related to food waste, and their willingness to consider different opinions, in order to assess how social interactions can affect private behaviours. Compared to existing models of opinion dynamics, we innovate by including a range of “cognitive dissonance” between stated opinions and actual behaviours that consumers are willing to accept before changing one of the two. We calibrate the model using questionnaire data on household food waste in Italy. We find that a limited degree of mixing between different socio-demographic groups, namely adult and young consumers, is enough to trigger change, but a certain openness of mind is required from more wasteful individuals. Equally, a small group of environmentally committed consumers can attract a sizeable share of the population towards low-waste behaviours if they show a certain variability of opinions and are willing to compromise with individuals in their close neighbourhood in terms of opinions. These findings can help design effective interventions to promote pro-environmental behaviours, taking advantage of the beneficial network effects while anticipating negative externalities

Clinical and therapeutic aspects of candidemia: A five year single centre study

B ackground Candida is an important cause of bloodstream infections (BSI) in nosocomial settings causing significant mortality and morbidity. This study was performed to evaluate contemporary epidemiology, species distribution, antifungal susceptibility and outcome of candida BSI in an Italian hospital. Methods All consecutive patients who developed candidemia at Santa Maria della Misericordia University Hospital (Italy) between January 2009 and June 2014 were enrolled in the study. Results A total of 204 episodes of candidemia were identified during the study period with an incidence of 0.79 episodes/1000 admissions. C. albicans was isolated in 60.3% of cases, followed by C. parapsilosis (16.7%), C. glabrata (11.8%) and C. tropicalis (6.4%). Of all Candida BSI, 124 (60.8 %) occurred in patients admitted to IMW, 31/204 (15.2 %) in ICUs, 33/204 (16.2%) in surgical units and 16/204 (7.8%) in Hematology/Oncology wards. Overall, 47% of patients died within 30 days from the onset of candidemia. C. parapsilosis and C. glabrata candidemia were associated with the lowest mortality rate (36%), while patients with C. tropicalis BSI had the highest mortality rate (58.3%). Lower mortality rates were detected in patients receiving therapy within 48 hours from the time of execution of the blood cultures (57,1% vs 38,9%, P <0.05). At multivariate analysis, steroids treatment (OR= 0.27, p=0.005) and CVC removal (OR=3.77, p=0.014) were independently associated with lower and higher survival probability, respectively. Candidemia in patients with peripherally inserted central catheters (PICC) showed to be associated with higher mortality in comparison with central venous catheters (CVC, Short catheters and Portacath) and no CVC use. For each point increase of APACHE III score, survival probability decreased of 2%. Caspofungin (OR=3.45, p=0.015) and Amphothericin B lipid formulation (OR=15.26, p=0.033) were independently associated with higher survival probability compared with no treatment

Behavioural economics : assessing food waste innovations diffusion through ABM models - insights from Italy and the Netherlands

Food Waste is problem related to all the actors of the Food Value Chain: producers, retailers and consumers. In this context, retail sector plays an important role in tackling the food waste problem. Food waste at the retail level can be reduced through the adoption of food waste reducing innovations. The authors investigate the most relevant factors that promote the adoption of those innovations among retailers

The use of systems models to identify food waste drivers

In developed countries, the largest share of food waste is produced at household level. Most studies on consumers’ food waste use models that identify covariates as significant when in fact they may not be, particularly where these models use many variables. Here, relying on EU-level Eurobarometer data from 2013, we use alternative analytical methods that avoid these problems (Bayesian Networks) to identify the impact of household characteristics and other variables on self-assessed food waste. Our analysis confirms that the country, the age of the respondent, the status (student/non-student), and a belief that the family wastes too much are related to the level of self-assessed food waste. But we found no evidence that waste behaviours differ between people living in urban and rural areas, and little support of a difference between genders. Households from lower-income EU countries (e.g. Portugal, Greece, Bulgaria, Cyprus and Latvia), as well as students and young adults tend to report higher levels of food waste. Hence, the adoption of an EU strategy based on the concept of subsidiarity, and of country-level policy measures targeting different age groups is suggested. Furthermore, our analysis shows that policy makers need to be wary of relying on analysis based on large datasets that do not control for false-positives, particularly when sample sizes are small

Solitary Fibrous Tumours of the Pleura

Solitary fibrous tumours of the pleura (SFTP) are rare neoplasms originating from one of the components of the sub-mesothelial connective layer underlying the pleura. They are the most common non-mesothelial primary pleural neoplasms but still remain relatively rare. Their behaviour is mostly indolent; however, some may de-differentiate into malignant and aggressive tumours. Surgical resection is the mainstay treatment for SFTP, even more so in case of voluminous masses, due to compression onto lung, mediastinum and great vessels. In this chapter, we discuss the disease characteristics reported in the literature with respect to clinical presentation, diagnosis and treatment; also, we will discuss the results of patients treated for SFTP who underwent a surgical treatment in our unit of thoracic surgery