Estimating the burden of antimicrobial resistance: a systematic literature review.

Background: Accurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base. Methods: MEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD. Results: Out of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to $1 billion per year, whilst economic burden ranged from$21,832 per case to over $3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively. Conclusions: This study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review. Trial registration: This systematic review is registered with PROSPERO (PROSPERO CRD42016037510)

Segmentation of the Aortic Valve Apparatus in 3D Echocardiographic Images: Deformable Modeling of a Branching Medial Structure

3D echocardiographic (3DE) imaging is a useful tool for assessing the complex geometry of the aortic valve apparatus. Segmentation of this structure in 3DE images is a challenging task that benefits from shape-guided deformable modeling methods, which enable inter-subject statistical shape comparison. Prior work demonstrates the efficacy of using continuous medial representation (cm-rep) as a shape descriptor for valve leaflets. However, its application to the entire aortic valve apparatus is limited since the structure has a branching medial geometry that cannot be explicitly parameterized in the original cm-rep framework. In this work, we show that the aortic valve apparatus can be accurately segmented using a new branching medial modeling paradigm. The segmentation method achieves a mean boundary displacement of 0.6 ± 0.1 mm (approximately one voxel) relative to manual segmentation on 11 3DE images of normal open aortic valves. This study demonstrates a promising approach for quantitative 3DE analysis of aortic valve morphology

Combining statistical shape modeling, CFD

Background: Advances in medical imaging, segmentation techniques, and high performance computing have stimulated the use of complex, patient-specific, three-dimensional Computational Fluid Dynamics (CFD) simulations. Patient-specific, CFD-compatible geometries of the aortic valve are readily obtained. CFD can then be used to obtain the patient-specific pressure-flow relationship of the aortic valve. However, such CFD simulations are computationally expensive, and real-time alternatives are desired. Aim: The aim of this work is to evaluate the performance of a meta-model with respect to high-fidelity, three-dimensional CFD simulations of the aortic valve. Methods: Principal component analysis was used to build a statistical shape model (SSM) from a population of 74 iso-topological meshes of the aortic valve. Synthetic meshes were created with the SSM, and steady-state CFD simulations at flow-rates between 50 and 650 mL/s were performed to build a meta-model. The meta-model related the statistical shape variance, and flow-rate to the pressure-drop. Results: Even though the first three shape modes account for only 46% of shape variance, the features relevant for the pressure-drop seem to be captured. The three-mode shape-model approximates the pressure-drop with an average error of 8.8% to 10.6% for aortic valves with a geometric orifice area below 150 mm2. The proposed methodology was least accurate for aortic valve areas above 150 mm2. Further reduction to a meta-model introduces an additional 3% error. Conclusions: Statistical shape modeling can be used to capture shape variation of the aortic valve. Meta-models trained by SSM-based CFD simulations can provide an estimate of the pressure-flow relationship in real-time