Cost-minimization analysis of oral versus intravenous antibiotic treatment for Klebsiella pneumoniae liver abscess.

A cost-minimization analysis was conducted for Klebsiella pneumoniae liver abscess (KLA) patients enrolled in a randomized controlled trial which found oral ciprofloxacin to be non-inferior to intravenous (IV) ceftriaxone in terms of clinical outcomes. Healthcare service utilization and cost data were obtained from medical records and estimated from self-reported patient surveys in a non-inferiority trial of oral ciprofloxacin versus IV ceftriaxone administered to 152 hospitalized adults with KLA in Singapore between November 2013 and October 2017. Total costs were evaluated by category and payer, and compared between oral and IV antibiotic groups over the trial period of 12 weeks. Among the subset of 139 patients for whom cost data were collected, average total cost over 12 weeks was $16,378 (95% CI, $14,620-$18,136) for the oral ciprofloxacin group and $20,569 (95% CI, $18,296-$22,842) for the IV ceftriaxone group, largely driven by lower average outpatient costs, as the average number of outpatient visits was halved for the oral ciprofloxacin group. There were no other statistically significant differences, either in inpatient costs or in other informal healthcare costs. Oral ciprofloxacin is less costly than IV ceftriaxone in the treatment of Klebsiella liver abscess, largely driven by reduced outpatient service costs.Trial registration: ClinicalTrials.gov Identifier NCT01723150 (7/11/2012).

Using Explainable AI to Cross-Validate Socio-economic Disparities Among Covid-19 Patient Mortality.

This paper applies eXplainable Artificial Intelligence (XAI) methods to investigate the socioeconomic disparities in COVID-19 patient mortality. An Extreme Gradient Boosting (XGBoost) prediction model is built based on a de-identified Austin area hospital dataset to predict the mortality of COVID-19 patients. We apply two XAI methods, Shapley Additive exPlanations (SHAP) and Locally Interpretable Model Agnostic Explanations (LIME), to compare the global and local interpretation of feature importance. This paper demonstrates the advantages of using XAI which shows the feature importance and decisive capability. Furthermore, we use the XAI methods to cross-validate their interpretations for individual patients. The XAI models reveal that Medicare financial class, older age, and gender have high impact on the mortality prediction. We find that LIME's local interpretation does not show significant differences in feature importance comparing to SHAP, which suggests pattern confirmation. This paper demonstrates the importance of XAI methods in cross-validation of feature attributions.

Quantitative assessment of renal functions using 68Ga-EDTA dynamic PET imaging in renal injury in mice of different origins.

Background: Early detection of kidney diseases can be challenging as conventional methods such as blood tests or imaging techniques (computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography) may be insufficient to assess renal function. A single-photon emission CT (SPECT) renal scan provides a means of measuring glomerular filtration rates (GFRs), but its diagnostic accuracy is limited due to its planar imaging modality and semi-quantification property. In this study, we aimed to improve the accuracy of GFR measurement by preparing a positron emission tonometry (PET) tracer 68Ga-Ethylenediaminetetraacetic acid (68Ga-EDTA) and comprehensively evaluating its performance in healthy mice and murine models of renal dysfunction. Methods: Dynamic PET scans were performed in healthy C57BL/6 mice and in models of renal injury, including acute kidney injury (AKI) and unilateral ureter obstruction (UUO) using 68Ga-EDTA. In a 30-min dynamic scan, PET images and time-activity curves (TACs) were acquired. Renal function and GFR values were measured using renograms and validated through serum renal function parameters, biodistribution results, and pathological staining. Results: 68Ga-EDTA dynamic PET imaging quantitatively captured the tracer elimination process. The calculated GFR values were 0.25 ± 0.02 ml/min in healthy mice, 0.01 ± 0.00 ml/min in AKI mice, and 0.25 ± 0.04, 0.29 ± 0.03 and 0.24 ± 0.01 ml/min in UUO mice, respectively. Furthermore, 68Ga-EDTA dynamic PET imaging and GFRPET were able to differentiate mild renal impairment before serum parameters indicated any changes. Conclusions: Our findings demonstrate that 68Ga-EDTA dynamic PET provides a reliable and precise means of evaluating renal function in two murine models of renal injury. These results hold promise for the widespread clinical application of 68Ga-EDTA dynamic PET in the near future.

An NLP approach to identify SDoH-related circumstance and suicide crisis from death investigation narratives.

OBJECTIVES: Suicide presents a major public health challenge worldwide, affecting people across the lifespan. While previous studies revealed strong associations between Social Determinants of Health (SDoH) and suicide deaths, existing evidence is limited by the reliance on structured data. To resolve this, we aim to adapt a suicide-specific SDoH ontology (Suicide-SDoHO) and use natural language processing (NLP) to effectively identify individual-level SDoH-related social risks from death investigation narratives. MATERIALS AND METHODS: We used the latest National Violent Death Report System (NVDRS), which contains 267 804 victim suicide data from 2003 to 2019. After adapting the Suicide-SDoHO, we developed a transformer-based model to identify SDoH-related circumstances and crises in death investigation narratives. We applied our model retrospectively to annotate narratives whose crisis variables were not coded in NVDRS. The crisis rates were calculated as the percentage of the group's total suicide population with the crisis present. RESULTS: The Suicide-SDoHO contains 57 fine-grained circumstances in a hierarchical structure. Our classifier achieves AUCs of 0.966 and 0.942 for classifying circumstances and crises, respectively. Through the crisis trend analysis, we observed that not everyone is equally affected by SDoH-related social risks. For the economic stability crisis, our result showed a significant increase in crisis rate in 2007-2009, parallel with the Great Recession. CONCLUSIONS: This is the first study curating a Suicide-SDoHO using death investigation narratives. We showcased that our model can effectively classify SDoH-related social risks through NLP approaches. We hope our study will facilitate the understanding of suicide crises and inform effective prevention strategies.

Analyzing Impact of Socio-Economic Factors on COVID-19 Mortality Prediction Using SHAP Value.

This paper applies multiple machine learning (ML) algorithms to a dataset of de-identified COVID-19 patients provided by the COVID-19 Research Database. The dataset consists of 20,878 COVID-positive patients, among which 9,177 patients died in the year 2020. This paper aims to understand and interpret the association of socio-economic characteristics of patients with their mortality instead of maximizing prediction accuracy. According to our analysis, a patient's household's annual and disposable income, age, education, and employment status significantly impacts a machine learning model's prediction. We also observe several individual patient data, which gives us insight into how the feature values impact the prediction for that data point. This paper analyzes the global and local interpretation of machine learning models on socio-economic data of COVID patients.

2D van der Waals Molecular Crystal ß-HgI2 : Economical, Rapid, and Substrate-Free Liquid-Phase Synthesis and Strong In-Plane Optical Anisotropy.

2D materials have a great potential for wide-range applications due to their adjustable bandgap characteristics and special crystal structures. ß-HgI2 is a new 2D van der Waals inorganic molecular crystal material with a wide bandgap of 4.03 eV, on whose preparation and properties there are few relevant reports due to the feature of instability of molecular crystals. Here, an economical method to control the synthesis of large-size 2D ß-HgI2 single crystal by using a mineralizer-assisted solution is reported. According to angle-resolved polarization Raman spectroscopy and first-principles optical absorption calculation, 2D ß-HgI2 flake has a strong in-plane anisotropic light scattering characteristic and high optical absorption dichroism (az /ay  = 3.4), which is due to a low in-plane symmetry of the orthorhombic structure of ß-HgI2 . More importantly, due to the molecular crystal structure of ß-HgI2 , its sensitivity to temperature is less than that of 2D materials such as MoS2 , which has been confirmed by temperature-dependent Raman spectroscopy. In the work, more 2D inorganic molecular crystals are studied in the aspect of growth, which provides a theoretical basis for 2D molecular crystal optoelectronic devices' potential applications.

Assessment of Microvascular Invasion of Hepatocellular Carcinoma with Diffusion Kurtosis Imaging.

Purpose To evaluate the potential role of diffusion kurtosis imaging and conventional magnetic resonance (MR) imaging findings including standard monoexponential model of diffusion-weighted imaging and morphologic features for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Materials and Methods Institutional review board approval and written informed consent were obtained. Between September 2015 and November 2016, 84 patients (median age, 54 years; range, 29-79 years) with 92 histopathologically confirmed HCCs (40 MVI-positive lesions and 52 MVI-negative lesions) were analyzed. Preoperative MR imaging examinations including diffusion kurtosis imaging (b values: 0, 200, 500, 1000, 1500, and 2000 sec/mm2) were performed and kurtosis, diffusivity, and apparent diffusion coefficient maps were calculated. Morphologic features of conventional MR images were also evaluated. Univariate and multivariate logistic regression analyses were used to evaluate the relative value of these parameters as potential predictors of MVI. Results Features significantly related to MVI of HCC at univariate analysis were increased mean kurtosis value (P < .001), decreased mean diffusivity value (P = .033) and apparent diffusion coefficient value (P = .011), and presence of infiltrative border with irregular shape (P = .005) and irregular circumferential enhancement (P = .026). At multivariate analysis, mean kurtosis value (odds ratio, 6.25; P = .001), as well as irregular circumferential enhancement (odds ratio, 6.92; P = .046), were independent risk factors for MVI of HCC. The mean kurtosis value for MVI of HCC showed an area under the receiver operating characteristic curve of 0.784 (optimal cutoff value was 0.917). Conclusion Higher mean kurtosis values in combination with irregular circumferential enhancement are potential predictive biomarkers for MVI of HCC. © RSNA, 2017.

Usefulness of T1 mapping on Gd-EOB-DTPA-enhanced MR imaging in assessment of non-alcoholic fatty liver disease.

OBJECTIVES: This study evaluates the value of Gd-EOB-DTPA-enhanced MRI for diagnosis and staging of non-alcoholic fatty liver disease (NAFLD) in an animal model by T1 relaxation time measurement. METHODS: Thirty-four rabbits were divided into the control group (n = 10) and NAFLD group, which was split into four groups (n = 6) with a high-fat diet for an interval of 3 weeks. A dual flip angle was performed before and at the hepatobiliary phase (HBP). T1 relaxation times of the liver parenchyma and the decrease rate (∆%) were calculated. Histological findings according to semi-quantitative scoring of steatosis, activity and fibrosis were the standard of reference. RESULTS: HBP and ∆% T1 relaxation time measurement showed significant differences between normal and NAFLD groups, between non-alcoholic steatohepatitis (NASH) and NAFLD without NASH (p = 0.000-0.049), between fibrosis groups (p = 0.000-0.019), but no difference between F1 and F2 (p = 0.834). The areas under the receiver operating characteristic curves (AUCs) of T1 relaxation time for HBP and ∆% were 0.86-0.93 for the selection of NASH and activity score ≥2, and 0.86-0.95 for the selection of F ≥ 1, 2, 3. No significant difference was found for diagnostic performance between HBP and ∆% T1 relaxation time. CONCLUSIONS: HBP T1 relaxation time measurement of Gd-EOB-DTPA-enhanced MRI was useful to evaluate NAFLD according to the SAF score. HBP T1 relaxation time measurement was as accurate as ∆% T1 relaxation time. KEY POINTS: • Gd-EOB-DTPA-enhanced MRI could give useful information on NAFLD. •HBP T 1 relaxation time measurement was useful for the evaluation of NAFLD. • HBP T 1 relaxation time measurement was as accurate as ∆%.

Direct costs associated with febrile neutropenia in inpatients with hematological diseases in Singapore.

PURPOSE: This prospective cohort study aims to investigate the direct hospitalization costs incurred during febrile neutropenia (FN) in inpatients with underlying hematological conditions and also to elucidate the factors associated with a high cost of managing febrile neutropenia. METHODS: Patients with underlying hematological conditions and documented FN were recruited between October 2008 and February 2011. FN-related costs included all costs incurred from the first day of FN until the last day of antibiotics prescribed. Relevant clinical factors were analyzed using generalized estimating equation models to elucidate the factors that were associated with higher costs of FN. RESULTS: A total of 175 patients were recruited with 303 documented episodes of FN. In non-transplant patients, 75.6 % of the FN episodes occurred. The median and mean cost incurred for each FN episode was USD9,060 (interquartile range = USD5,047-16,631) and USD15,298 (standard deviation ± USD17,459), respectively, accounting for approximately 38 % of the median total hospitalization cost and 37 % of the mean total hospitalization cost. The ward charges (44.1 %) constituted the largest component of the cost, followed by the laboratory charges (27.3 %) and medications (18.7 %), of which antimicrobials constituted 9.6 % of the cost of FN. The factors associated with higher costs of FN include cytomegalovirus reactivation (p < 0.001), longer duration of antibiotics (p < 0.001), lower absolute neutrophil count nadir (p < 0.001), allogeneic stem cell transplantation (p < 0.01), and diagnosis of invasive fungal infection (p < 0.05). CONCLUSION: The economic cost of management of FN in hematology inpatients is considerable and in addition to the overall risk of mortality for this condition. Strategies to reduce FN or ameliorate its costs are essential for this group of patients.

Tunable, mixed-resolution modeling using library-based Monte Carlo and graphics processing units.

Building on our recently introduced library-based Monte Carlo (LBMC) approach, we describe a flexible protocol for mixed coarse-grained (CG)/all-atom (AA) simulation of proteins and ligands. In the present implementation of LBMC, protein side chain configurations are pre-calculated and stored in libraries, while bonded interactions along the backbone are treated explicitly. Because the AA side chain coordinates are maintained at minimal run-time cost, arbitrary sites and interaction terms can be turned on to create mixed-resolution models. For example, an AA region of interest such as a binding site can be coupled to a CG model for the rest of the protein. We have additionally developed a hybrid implementation of the generalized Born/surface area (GBSA) implicit solvent model suitable for mixed-resolution models, which in turn was ported to a graphics processing unit (GPU) for faster calculation. The new software was applied to study two systems: (i) the behavior of spin labels on the B1 domain of protein G (GB1) and (ii) docking of randomly initialized estradiol configurations to the ligand binding domain of the estrogen receptor (ERα). The performance of the GPU version of the code was also benchmarked in a number of additional systems.

The excess financial burden of multidrug resistance in severe gram-negative infections in Singaporean hospitals.

INTRODUCTION: Multidrug-resistant (MDR) Gram-negative healthcare-associated infections are prevalent in Singaporean hospitals. An accurate assessment of the socioeconomic impact of these infections is necessary in order to facilitate appropriate resource allocation, and to judge the costeffectiveness of targeted interventions. MATERIALS AND METHODS: A retrospective cohort study involving inpatients with healthcare-associated Gram-negative bacteraemia at 2 large Singaporean hospitals was conducted to determine the hospitalisation costs attributed to multidrug resistance, and to elucidate factors affecting the financial impact of these infections. Data were obtained from hospital administrative, clinical and financial records, and analysed using a multivariate linear regression model. RESULTS: There were 525 survivors of healthcare-associated Gram-negative bacteraemia in the study cohort, with 224 MDR cases. MDR bacteraemia, concomitant skin and soft tissue infection, higher APACHE II score, ICU stay, and appropriate definitive antibiotic therapy were independently associated with higher total hospitalisation costs, whereas higher Charlson comorbidity index and concomitant urinary tract infection were associated with lower costs. The excess hospitalisation costs attributed to MDR infection was $8638.58. In the study cohort, on average, 62.3% of the excess cost attributed to MDR infection was paid for by government subvention. CONCLUSION: Multidrug resistance in healthcare-associated Gram-negative bacteraemia is associated with higher financial costs--a significant proportion of which are subsidised by public funding in the form of governmental subvention. More active interventions aimed at controlling antimicrobial resistance are warranted, and the results of our study also provide possible benchmarks against which the cost-effectiveness of such interventions can be assessed.

Efficient equilibrium sampling of all-atom peptides using library-based Monte Carlo.

We applied our previously developed library-based Monte Carlo (LBMC) to equilibrium sampling of several implicitly solvated all-atom peptides. LBMC can perform equilibrium sampling of molecules using precalculated statistical libraries of molecular-fragment configurations and energies. For this study, we employed residue-based fragments distributed according to the Boltzmann factor of the optimized potential for liquid simulations all-atom (OPLS-AA) forcefield describing the individual fragments. Two solvent models were employed: a simple uniform dielectric and the generalized Born/surface area (GBSA) model. The efficiency of LBMC was compared to standard Langevin dynamics (LD) using three different statistical tools. The statistical analyses indicate that LBMC is more than 100 times faster than LD not only for the simple solvent model but also for GBSA.

General library-based Monte Carlo technique enables equilibrium sampling of semi-atomistic protein models.

We introduce "library-based Monte Carlo" (LBMC) simulation, which performs Boltzmann sampling of molecular systems based on precalculated statistical libraries of molecular-fragment configurations, energies, and interactions. The library for each fragment can be Boltzmann distributed and thus account for all correlations internal to the fragment. LBMC can be applied to both atomistic and coarse-grained models, as we demonstrate in this "proof-of-principle" report. We first verify the approach in a toy model and in implicitly solvated all-atom polyalanine systems. We next study five proteins, up to 309 residues in size. On the basis of atomistic equilibrium libraries of peptide-plane configurations, the proteins are modeled with fully atomistic backbones and simplified Go-like interactions among residues. We show that full equilibrium sampling can be obtained in days to weeks on a single processor, suggesting that more accurate models are well within reach. For the future, LBMC provides a convenient platform for constructing adjustable or mixed-resolution models: the configurations of all atoms can be stored at no run-time cost, while an arbitrary subset of interactions is "turned on".

[Survival and immune response of rural HIV/AIDS patients after free antiretroviral therapy].

OBJECTIVE: To assess the adherence, immunologic and survival responses in HIV-infected patients receiving free antiretroviral therapy (ART). METHODS: All adult HIV-infected patients in Wenxi county who started antiretroviral treatment (ART) between 01 July 2001 and 31 December 2006 and aged above 18 years were included in this study. Epidemiological survey and laboratory tests were performed before, 0.5 months after, 1 months after, 2 months after and every 3 months after initiation of ART to recognize the adherence, efficacy (CD(4)(+) T cell counts) and survival to the regimens. RESULTS: The median follow-up time period was 16.5 months (Interquartile: 15.5 - 20.8 months). At baseline, the median of CD(4)(+) T cell counts were 154 cells/microl (Interquartile: 81 - 212 cells/microl). Treatment was effective in most of the patients, the CD(4)(+) T cell count of patients increased after the initiation of ART. The maximum increase was recorded at month 3, from the median of 154 cells/microl to 220 cells/microl (P < 0.001), and thereafter the count remained stable. When comparing with patients with baseline CD(4)(+) T cell count > or = 100 cells/microl, those with baseline CD(4)(+) T cell count < 100 cells/microl showed a higher mean increase in the first three months of treatment. The cumulative probability rates of remaining alive were 0.94, 0.88 and 0.87 at 3, 12, 24 months, respectively. In multivariate Cox's proportional hazard models, after adjustment for the type ofinitial regimens (NVP vs. EFV/IDV), CD(+)(4) T cell count of less than 50 cells/microl (vs. 50 cells/microl or more) was strongly associated with death hazard ratio 0.21 (95%CI: 0.06 - 0.68). CONCLUSION: Our data showed that ART was effective for improving immunologic response of adult patients with HIV/AIDS. CD(4)(+) T cell count at initiation was associated with survival time in patients starting ART, suggesting that monitoring of CD(4)(+) T count should be strengthened to early initiate antiretroviral therapy for HIV-infected patients.