A whole-health-economy approach to antimicrobial stewardship: Analysis of current models and future direction.

Antimicrobial stewardship (AMS) strategies are widely implemented in single healthcare sectors and organisations; however, the extent and impact of integrated AMS initiatives across the whole health economy are unknown. Assessing degree of integration of AMS across the whole health economy and its impact is essential if we are to achieve a ‘One Health’ approach to addressing antimicrobial resistance (AMR), and therefore we searched systematically for and analysed published examples of integrated AMS initiatives to address this gap. Application of a system-level framework to analyse integration of AMS initiatives across and within healthcare sectors shows that integration is emerging but needs strengthening. Findings from a small number of evaluations in high-income countries suggest that antimicrobial prescribing and healthcare-associated infections can be reduced using a multisectoral integrated AMS approach. More robust research designs to evaluate and understand the impact of multisectoral integrated AMS are needed, particularly with respect to differing health systems in different countries and local organisational contexts. Our analysis highlights a number of challenges and ways forward for enhancing the delivery of AMS through an integrated approach

Tallaba

Ġabra ta’ poeżiji u proża li tinkludi: Il-Bravi fid-Dar ta’ Luċija ta’ Dun Pawl – X’Qasma ta’ Qalb ta’ C. M. D – Innu ta’ G. M. A. – Ġens il-Malti ta’ R. Briffa – It-Tallaba minn ta’ Matilde Serao ta’ Ġużè Micallef GoggiN/

Examination of the risk of reinfection with hepatitis C among injecting drug users who have been tested in Glasgow

Unsafe injecting practices put injecting drug users (IDUs) at repeat exposure to infection with the hepatitis C virus (HCV). It has not yet been determined if spontaneously clearing one's primary infection influences the risk of reinfection; our aim was to estimate the relative risk of reinfection in IDUs who have cleared the virus. We conducted a retrospective study using a large database of HCV test results covering Greater Glasgow Health Board during 1993–2007 to calculate rates of infection and reinfection in current/former IDUs. The relative risk of (re)infection in previously infected compared with never-infected IDUs was estimated using Poisson regression, adjusting for age at study entry, sex, and calendar period of test. Although the rate of reinfection in IDUs who were HCV antibody-positive, RNA-negative at baseline was lower (7/100 person-years, 95% CI: 5–9) than the rate of acute infection in IDUs who were HCV antibody-negative at baseline (10/100 person-years, 95% CI: 9–12), the risk of reinfection was not significantly different than the risk of initial infection (adjusted rate ratio = 0.78, 95% CI: 0.57–1.08). We found only weak evidence for a reduced risk of HCV reinfection in IDUs who had cleared their previous infection. Further research among those who have cleared infection through antiviral therapy is needed to help inform decisions regarding treatment of IDUs

Political risk in light rail transit PPP projects

Since 2003 public-private partnerships (PPPs) have represented between 10 and 13.5% of the total investment in public services in the UK. The macro-economic and political benefits of PPPs were among the key drivers for central government's decision to promote this form of procurement to improve UK public services. Political support for a PPP project is critical and is frequently cited as the most important critical success factor. This paper investigates the significance of political support and reviews the treatment of political risk in a business case by the public sector project sponsor for major UK-based light rail transit PPP projects during their development stage. The investigation demonstrates that in the early project stages it is not traditional quantitative Monte Carlo risk analysis that is important; rather it is the identification and representation of political support within a business case together with an understanding of how this information is then used to inform critical project decisions

Nanoindentation Response of 3D Printed PEGDA Hydrogels in a Hydrated Environment

Hydrogels are commonly used materials in tissue engineering and organ-on-chip devices. This study investigated the nanomechanical properties of monolithic and multilayered poly(ethylene glycol) diacrylate (PEGDA) hydrogels manufactured using bulk polymerization and layer-by-layer projection lithography processes, respectively. An increase in the number of layers (or reduction in layer thickness) from 1 to 8 and further to 60 results in a reduction in the elastic modulus from 5.53 to 1.69 and further to 0.67 MPa, respectively. It was found that a decrease in the number of layers induces a lower creep index (CIT) in three-dimensional (3D) printed PEGDA hydrogels. This reduction is attributed to mesoscale imperfections that appear as pockets of voids at the interfaces of the multilayered hydrogels attributed to localized regions of unreacted prepolymers, resulting in variations in defect density in the samples examined. An increase in the degree of cross-linking introduced by a higher dosage of ultraviolet (UV) exposure leads to a higher elastic modulus. This implies that the elastic modulus and creep behavior of hydrogels are governed and influenced by the degree of cross-linking and defect density of the layers and interfaces. These findings can guide an optimal manufacturing pathway to obtain the desirable nanomechanical properties in 3D printed PEGDA hydrogels, critical for the performance of living cells and tissues, which can be engineered through control of the fabrication parameters

Feasibility of multimodal 3D neuroimaging to guide implantation of intracranial EEG electrodes

Since intracranial electrode implantation has limited spatial sampling and carries significant risk, placement has to be effective and efficient. Structural and functional imaging of several different modalities contributes to localising the seizure onset zone (SoZ) and eloquent cortex. There is a need to summarise and present this information throughout the pre/intra/post-surgical course

Real-world financial and clinical impact of diagnostic-driven and empirical-treatment strategies in high-risk immunocompromised patients with suspected Aspergillus infection in the United Kingdom

A diagnostic-driven (DD) treatment strategy has proven successful for treating invasive fungal infections (IFIs) caused by Aspergillus. However, uptake of this treatment strategy is not fully embraced. This study compares the economic and clinical impact of DD and empirical-treatment (ET) strategies used within hospitals. Methods: a decision-analytic model was developed to compare costs and clinical outcomes associated with ET or a DD strategy of identifying infections caused by Aspergillus via galactomannan-antigen testing or Aspergillus polymerase chain reaction (PCR) in neutropenic patients with unexplained fever. Patients were treated prophylactically with antifungal treatments as seen in United Kingdom (UK) hospitals. The IFI incidence, response, mortality, resource use, and adverse events were obtained from meta-analyses and other clinical studies. Analyses were performed from the U.K. hospital perspective, and costs were obtained from standard costing sources. Although diagnostic-testing costs increased, total cost and length of stay were reduced by £1,121 and 1.54 days when treating via a DD strategy. Intensive care and general ward days accounted for . 40% of total costs and . 58% of the cost reduction came from reduced antifungal costs. Treating with a DD strategy reduced the number of patients being treated with antifungal agents while survival was increased. Thus, a DD strategy was cost savings (-£136,787 cost per death avoided) compared with an ET strategy. Conclusion: this study suggests that incorporating a DD strategy as the preferred treatment protocol may be a cost-saving and clinically improved treatment strategy for managing neutropenic patients with unexplained fever. IMPORTANCE Patients at risk of invasive fungal infections (IFIs), such as Aspergillus spp., tend to be immunocompromised and usually take several medications which may generate many side effects. Prescribing is further complicated by comorbidities, drug interactions and challenges accessing diagnostics. Therefore, adding another agent may be neither straightforward nor the best option for these types of patients. A diagnostic-driven (DD) treatment strategy has proven successful for treating IFIs. However, uptake of this treatment strategy is not fully embraced in clinical practice perhaps because this strategy is thought to be more costly and/or to result in higher mortality relative to treating empirically. We developed a decision-analytic model to examine the impact of these 2 strategies on costs and health outcomes. This study indicates that incorporating a DD strategy as the preferred treatment protocol may be a cost-saving and clinically improved treatment strategy for managing neutropenic patients with unexplained fever

Nonlinearity and disorder: Classification and stability of nonlinear impurity modes

We study the effects produced by competition of two physical mechanisms of energy localization in inhomogeneous nonlinear systems. As an example, we analyze spatially localized modes supported by a nonlinear impurity in the generalized nonlinear Schr\"odinger equation and describe three types of nonlinear impurity modes --- one- and two-hump symmetric localized modes and asymmetric localized modes --- for both focusing and defocusing nonlinearity and two different (attractive or repulsive) types of impurity. We obtain an analytical stability criterion for the nonlinear localized modes and consider the case of a power-law nonlinearity in detail. We discuss several scenarios of the instability-induced dynamics of the nonlinear impurity modes, including the mode decay or switching to a new stable state, and collapse at the impurity site.Comment: 18 pages, 22 figure

PIONIER: a visitor instrument for the VLTI

PIONIER is a 4-telescope visitor instrument for the VLTI, planned to see its first fringes in 2010. It combines four ATs or four UTs using a pairwise ABCD integrated optics combiner that can also be used in scanning mode. It provides low spectral resolution in H and K band. PIONIER is designed for imaging with a specific emphasis on fast fringe recording to allow closure-phases and visibilities to be precisely measured. In this work we provide the detailed description of the instrument and present its updated status.Comment: Proceedings of SPIE conference Optical and Infrared Interferometry II (Conference 7734) San Diego 201