Optimal Screening Strategies for Healthcare Associated Infections in a Multi-Institutional Setting

Health institutions may choose to screen newly admitted patients for the presence of disease in order to reduce disease prevalence within the institution. Screening is costly, and institutions must judiciously choose which patients they wish to screen based on the dynamics of disease transmission. Since potentially infected patients move between different health institutions, the screening and treatment decisions of one institution will affect the optimal decisions of others; an institution might choose to “free-ride” off the screening and treatment decisions of neighboring institutions. We develop a theoretical model of the strategic decision problem facing a health care institution choosing to screen newly admitted patients. The model incorporates an SIS compartmental model of disease transmission into a game theoretic model of strategic decision-making. Using this setup, we are able to analyze how optimal screening is influenced by disease parameters, such as the efficacy of treatment, the disease recovery rate and the movement of patients. We find that the optimal screening level is lower for diseases that have more effective treatments. Our model also allows us to analyze how the optimal screening level varies with the number of decision makers involved in the screening process. We show that when institutions are more autonomous in selecting whom to screen, they will choose to screen at a lower rate than when screening decisions are more centralized. Results also suggest that centralized screening decisions have a greater impact on disease prevalence when the availability or efficacy of treatment is low. Our model provides insight into the factors one should consider when choosing whether to set a mandated screening policy. We find that screening mandates set at a centralized level (i.e. state or national) will have a greater impact on the control of infectious disease.     

Healthcare Associated Infections of Methicillin-Resistant Staphylococcus aureus: A Case-Control-Control Study

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most widespread and dangerous pathogens in healthcare settings. We carried out this case-control-control study at a tertiary care hospital in Guangzhou, China, to examine the antimicrobial susceptibility patterns, risk factors and clinical outcomes of MRSA infections.

Methods

A total of 57 MRSA patients, 116 methicillin-susceptible Staphylococcus aureus (MSSA) patients and 102 S. aureus negative patients were included in this study. We applied the disk diffusion method to compare the antimicrobial susceptibilities of 18 antibiotics between MRSA and MSSA isolates. Risk factors of MRSA infections were evaluated using univariate and multivariate logistic regression models. We used Cox proportional hazards models and logistic regression analysis to assess the hospital stay duration and fatality for patients with MRSA infections.

Results

The MRSA group had significantly higher resistance rates for most drugs tested compared with the MSSA group. Using MSSA patients as controls, the following independent risk factors of MRSA infections were identified: 3 or more prior hospitalizations (OR 2.8, 95% CI 1.3–5.8, P = 0.007), chronic obstructive pulmonary disease (OR 5.9, 95% CI 1.7–20.7, P = 0.006), and use of a respirator (OR 3.6, 95% CI 1.0–12.9, P = 0.046). With the S. aureus negative patients as controls, use of a respirator (OR 3.8, 95% CI 1.0–13.9, P = 0.047) and tracheal intubation (OR 8.2, 95% CI 1.5–45.1, P = 0.016) were significant risk factors for MRSA infections. MRSA patients had a longer hospital stay duration and higher fatality in comparison with those in the two control groups.

Conclusions

MRSA infections substantially increase hospital stay duration and fatality. Thus, MRSA infections are serious issues in this healthcare setting and should receive more attention from clinicians.     

Nursing Workload as a Risk Factor for Healthcare Associated Infections in ICU: A Prospective Study

Introduction

Nurse understaffing is frequently hypothesized as a potential risk factor for healthcare-associated infections (HAI). This study aimed to evaluate the role of nursing workload in the occurrence of HAI, using Nursing Activities Score (NAS).

Methods

This prospective cohort study enrolled all patients admitted to 3 Medical ICUs and one step-down unit during 3 months (2009). Patients were followed-up until HAI, discharge or death. Information was obtained from direct daily observation of medical and nursing rounds, chart review and monitoring of laboratory system. Nursing workload was determined using NAS. Non-compliance to the nurses’ patient care plans (NPC) was identified. Demographic data, clinical severity, invasive procedures, hospital interventions, and the occurrence of other adverse events were also recorded. Patients who developed HAI were compared with those who did not.

Results

195 patients were included and 43 (22%) developed HAI: 16 pneumonia, 12 urinary-tract, 8 bloodstream, 2 surgical site, 2 other respiratory infections and 3 other. Average NAS and average proportion of non compliance with NPC were significantly higher in HAI patients. They were also more likely to suffer other adverse events. Only excessive nursing workload (OR: 11.41; p: 0.019) and severity of patient’s clinical condition (OR: 1.13; p: 0.015) remained as risk factors to HAI.

Conclusions

Excessive nursing workload was the main risk factor for HAI, when evaluated together with other invasive devices except mechanical ventilation. To our knowledge, this study is the first to evaluate prospectively the nursing workload as a potential risk factor for HAI, using NAS.     

External Validation of a Predictive Model for Acute Pancreatitis Risk in Patients with Severe Hypertriglyceridemia

Objective: We previously developed a predictive model to assess the risk of developing acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG). In this study, we aimed to externally validate this model.Methods: The validation cohort included cross-sectional data between 2013 and 2017. Adult patients (≥18 years old) with triglyceride levels ≥1,000 mg/dL were identified. Based on our previous 4-factor predictive model (age, triglyceride &lsqb;TG], excessive alcohol use, and gallstone disease), we estimated the probability of developing AP. Model performance was assessed using area under receiver operating characteristic curve (AUROC).Results: In comparison to the original cohort, patients in the validation cohort had more prevalent acute pancreatitis (16.2% versus 9.2%; P<.001) and gallstone disease (7.5% versus 2.1%; P<.001). Other characteristics were comparable and not statistically significant. The AUROCs were almost identical: 0.8337 versus 0.8336 in the validation and the original cohorts, respectively. In univariable analyses, the highest increase in odds of AP was associated with HTG, followed by gallstones, excessive alcohol use, and younger age.Conclusion: This study externally validates the 4-factor predictive model to estimate the risk of AP in adult patients with severe HTG (TG ≥1,000 mg/dL). Younger age was confirmed to place patients at high risk of AP. The clinical risk categories suggested in this study may be useful to guide treatment options.Abbreviations: AP = acute pancreatitis; ASCVD = atherosclerotic cardiovascular disease; AUROC = area under the receiver operating characteristic curve; FRAX = fracture risk assessment tool; HTG = hypertriglyceridemia; OR = odds ratio; TG = triglyceride level     

Validation of eDNA Surveillance Sensitivity for Detection of Asian Carps in Controlled and Field Experiments

In many North American rivers, populations of multiple species of non-native cyprinid fishes are present, including black carp (Mylpharyngodon piceus), grass carp (Ctenopharyngodon idella), bighead carp (Hypophthalmichthys nobilis), silver carp (Hypophthalmichthys molitrix), common carp (Cyprinus carpio), and goldfish (Carassius auratus). All six of these species are found in the Mississippi River basin and tracking their invasion has proven difficult, particularly where abundance is low. Knowledge of the location of the invasion front is valuable to natural resource managers because future ecological and economic damages can be most effectively prevented when populations are low. To test the accuracy of environmental DNA (eDNA) as an early indicator of species occurrence and relative abundance, we applied eDNA technology to the six non-native cyprinid species putatively present in a 2.6 river mile stretch of the Chicago (IL, USA) canal system that was subsequently treated with piscicide. The proportion of water samples yielding positive detections increased with relative abundance of the six species, as indicated by the number of carcasses recovered after poisoning. New markers for black carp, grass carp, and a common carp/goldfish are reported and details of the marker testing to ensure specificity are provided.     

Validation of an Automated Cough Detection Algorithm for Tracking Recovery of Pulmonary Tuberculosis Patients

Background

A laboratory-free test for assessing recovery from pulmonary tuberculosis (TB) would be extremely beneficial in regions of the world where laboratory facilities are lacking. Our hypothesis is that analysis of cough sound recordings may provide such a test. In the current paper, we present validation of a cough analysis tool.

Methodology/Principal Findings

Cough data was collected from a cohort of TB patients in Lima, Peru and 25.5 hours of recordings were manually annotated by clinical staff. Analysis software was developed and validated by comparison to manual scoring. Because many patients cough in bursts, coughing was characterized in terms of cough epochs. Our software correctly detects 75.5% of cough episodes with a specificity of 99.6% (comparable to past results using the same definition) and a median false positive rate of 4 false positives/hour, due to the noisy, real-world nature of our dataset. We then manually review detected coughs to eliminate false positives, in effect using the algorithm as a pre-screening tool that reduces reviewing time to roughly 5% of the recording length. This cough analysis approach provides a foundation to support larger-scale studies of coughing rates over time for TB patients undergoing treatment.     

The Incidence Patterns Model to Estimate the Distribution of New HIV Infections in Sub-Saharan Africa: Development and Validation of a Mathematical Model

BackgroundProgrammatic planning in HIV requires estimates of the distribution of new HIV infections according to identifiable characteristics of individuals. In sub-Saharan Africa, robust routine data sources and historical epidemiological observations are available to inform and validate such estimates.ConclusionsIt is possible to reliably predict the distribution of new HIV infections acquired using data routinely available in many countries in the sub-Saharan African region with a single relatively simple mathematical model. This tool would complement more specific analyses to guide resource allocation, data collection, and programme planning.     

Validation of Normal Human Bronchial Epithelial Cells as a Model for Influenza A Infections in Human Distal Trachea

Primary normal human bronchial/tracheal epithelial (NHBE) cells, derived from the distal-most aspect of the trachea at the bifurcation, have been used for a number of studies in respiratory disease research. Differences between the source tissue and the differentiated primary cells may impact infection studies based on this model. Therefore, we examined how well-differentiated NHBE cells compared with their source tissue, the human distal trachea, as well as the ramifications of these differences on influenza A viral pathogenesis research using this model. We employed a histological analysis including morphological measurements, electron microscopy, multi-label immunofluorescence confocal microscopy, lectin histochemistry, and microarray expression analysis to compare differentiated NHBEs to human distal tracheal epithelium. Pseudostratified epithelial height, cell type variety and distribution varied significantly. Electron microscopy confirmed differences in cellular attachment and paracellular junctions. Influenza receptor lectin histochemistry revealed that α2,3 sialic acids were rarely present on the apical aspect of the differentiated NHBE cells, but were present in low numbers in the distal trachea. We bound fluorochrome bioconjugated virus to respiratory tissue and NHBE cells and infected NHBE cells with human influenza A viruses. Both indicated that the pattern of infection progression in these cells correlated with autopsy studies of fatal cases from the 2009 pandemic.     

Independent Validation of an Existing Model Enables Prediction of Hearing Loss after Childhood Bacterial Meningitis

Objective

This study aimed external validation of a formerly developed prediction model identifying children at risk for hearing loss after bacterial meningitis (BM). Independent risk factors included in the model are: duration of symptoms prior to admission, petechiae, cerebral spinal fluid (CSF) glucose level, Streptococcus pneumoniae and ataxia. Validation helps to evaluate whether the model has potential in clinical practice.

Study design

116 Dutch school-age BM survivors were included in the validation cohort and screened for sensorineural hearing loss (>25 dB). Risk factors were obtained from medical records. The model was applied to the validation cohort and its performance was compared with the development cohort. Validation was performed by application of the model on the validation cohort and by assessment of discrimination and goodness of fit. Calibration was evaluated by testing deviations in intercept and slope. Multiple imputation techniques were used to deal with missing values.

Results

Risk factors were distributed equally between both cohorts. Discriminative ability (Area Under the Curve, AUC) of the model was 0.84 in the development and 0.78 in the validation cohort. Hosmer-Lemeshow test for goodness of fit was not significant in the validation cohort, implying good fit concerning the similarity of expected and observed cases. There were no significant differences in calibration slope and intercept. Sensitivity and negative predicted value were high, while specificity and positive predicted value were low which is comparable with findings in the development cohort.

Conclusions

Performance of the model remained good in the validation cohort. This prediction model might be used as a screening tool and can help to identify those children that need special attention and a long follow-up period or more frequent auditory testing.     

Infant Male Circumcision: Healthcare Provider Knowledge and Associated Factors

Background and Objectives

The emerging science demonstrates various health benefits associated with infant male circumcision and adult male circumcision; yet rates are declining in the United States. The American Academy of Pediatrics and the Centers for Disease Control and Prevention recommend that healthcare providers present evidence-based risk and benefit information for infant male circumcision to parent(s) and guardian(s). The purpose of this study was to assess providers’ level of infant male circumcision knowledge and to identify the associated characteristics.

Methods

An online survey was administered to healthcare providers in the family medicine, obstetrics, and pediatrics medical specialties at an urban academic health center. To assess infant male circumcision knowledge, a 17 point summary score was constructed to identify level of provider knowledge within the survey.

Results

Ninety-two providers completed the survey. Providers scored high for the following knowledge items: adverse event rates, protects against phimosis and urinary tract infections, and does not prevent hypospadias. Providers scored lower for items related to more recent research: protection against cervical cancer, genital ulcer disease, bacterial vaginosis, and reduction in HIV acquisition. Two models were constructed looking at (1) overall knowledge about male circumcision, and (2) knowledge about male circumcision reduction in HIV acquisition. Pediatricians demonstrated greater overall infant male circumcision knowledge, while obstetricians exhibited significantly greater knowledge for the HIV acquisition item.

Conclusion

Providers’ knowledge levels regarding the risks and benefits of infant male circumcision are highly variable, indicating the need for system-based educational interventions.     

Validation of a Demographic Model for Woodland Caribou

Abstract: Wildlife population models are potentially valuable for conservation planning. Validation is necessary to ensure that models are sufficiently robust for predicting management outcomes consistent with conservation objectives. Sorensen et al. (2008) produced a model of woodland caribou (Rangifer tarandus) population growth rate that was recently modified and used as a predictive tool at several scales. We computed confidence intervals and evaluated the performance of this model using novel data. Confidence intervals were wide, and results suggested that the model may have a positive bias, resulting in over-estimation of population growth rates, as well as low predictive power. Wide confidence intervals mean that current understanding of factors governing woodland caribou herd dynamics is not sufficient for wildlife managers to make reliable projections of responses to management.     

Validation of a Rapid Rabies Diagnostic Tool for Field Surveillance in Developing Countries

BackgroundOne root cause of the neglect of rabies is the lack of adequate diagnostic tests in the context of low income countries. A rapid, performance friendly and low cost method to detect rabies virus (RABV) in brain samples will contribute positively to surveillance and consequently to accurate data reporting, which is presently missing in the majority of rabies endemic countries.Conclusion/SignificanceThe RIDT shows excellent performance qualities both in regard to user friendliness and reliability of the result. In addition, the test cassettes can be used as a vehicle to ship viral RNA to reference laboratories for further laboratory confirmation of the diagnosis and for epidemiological investigations using nucleotide sequencing. The potential for satisfactory use in remote locations is therefore very high to improve the global knowledge of rabies epidemiology. However, we suggest some changes to the protocol, as well as careful further validation, before promotion and wider use.     

实时定量RT-PCR对乙型肝炎病毒全长RNA(fRNA)的定量检测

目的:建立一种简便的定量检测慢性乙型肝炎患者血清中终止于聚腺苷酸化位点的乙型肝炎病毒全长RNA(f RNA)的方法。方法:选取53例未治疗的乙型肝炎患者及22例HBs Ag阴性的健康者为研究对象,使用锚定oligo-d T的引物对其血清中f RNA进行实时定量反转录PCR检测,统计分析其与HBV DNA、HBcr Ag和HBe Ag的相关性。结果:对f RNA进行实时荧光定量RT-PCR检测的下线为2.3 log copies/ml,标准曲线的相关系数为0.99(P0.0001)。53例乙型肝炎患者中,29例(54.7%)可以检测到f RNA,22例正常对照中没有检测到f RNA。27例HBe Ag阳性和/或高水平HBV DNA的患者全部检测到f RNA,26例HBe Ag阴性并且低水平HBV DNA的乙型肝炎患者中有2例(7.7%)检测到f RNA(P0.0001)。HBe Ag阳性患者血清中f RNA水平高于HBe Ag阴性患者(5.0±0.3 vs.2.9±0.4 log copies/ml,P0.001)。f RNA与HBV DNA/HBcr Ag具有显著相关性(r=0.905、0.881,P0.0001)。Hayashi's定量分析法I显示f RNA与HBV DNA相关性强于其与HBcr Ag的相关性。结论:与HBV DNA和HBe Ag一样,f RNA可作为常规检测判断HBV的复制水平并指导用药。     

嵌合RNA检测和验证技术

嵌合RNA(chimeric RNA)是由来自不同基因的外显子片段组成的融合转录本。传统的嵌合RNA检测方法有染色体核型分析、荧光原位杂交（FISH）等,但这些技术的特异性、灵敏性和准确性较差。随着测序技术的发展,二代测序技术展现出强大的数据处理能力,可以通过高通量序列分析来检测嵌合RNA,目前基于高通量测序的检测方法有FusionCatcher、SOAPfuse、EricScript等。目前较为常用的对检测到的嵌合RNA的验证方法有聚合酶链反应（PCR）、核糖核酸酶保护实验（RPA）、琼脂糖凝胶电泳、Sanger测序等。多种检测技术的开发使得越来越多的嵌合RNA被发现,但现有的检测技术各有优劣,主要体现于检测成本、假阳性率、检测时间等方面的差异。本文对嵌合RNA的检测方法、验证方法及各方法的优劣性进行阐述。     

External Quality Assurance of Malaria Nucleic Acid Testing for Clinical Trials and Eradication Surveillance

Nucleic acid testing (NAT) for malaria parasites is an increasingly recommended diagnostic endpoint in clinical trials of vaccine and drug candidates and is also important in surveillance of malaria control and elimination efforts. A variety of reported NAT assays have been described, yet no formal external quality assurance (EQA) program provides validation for the assays in use. Here, we report results of an EQA exercise for malaria NAT assays. Among five centers conducting controlled human malaria infection trials, all centers achieved 100% specificity and demonstrated limits of detection consistent with each laboratory''s pre-stated expectations. Quantitative bias of reported results compared to expected results was generally <0.5 log₁₀ parasites/mL except for one laboratory where the EQA effort identified likely reasons for a general quantitative shift. The within-laboratory variation for all assays was low at <10% coefficient of variation across a range of parasite densities. Based on this study, we propose to create a Molecular Malaria Quality Assessment program that fulfills the need for EQA of malaria NAT assays worldwide.     

Central Pressure Appraisal: Clinical Validation of a Subject-Specific Mathematical Model

IntroductionCurrent evidence suggests that aortic blood pressure has a superior prognostic value with respect to brachial pressure for cardiovascular events, but direct measurement is not feasible in daily clinical practice.AimThe aim of the present study is the clinical validation of a multiscale mathematical model for non-invasive appraisal of central blood pressure from subject-specific characteristics.MethodsA total of 51 young male were selected for the present study. Aortic systolic and diastolic pressure were estimated with a mathematical model and were compared to the most-used non-invasive validated technique (SphygmoCor device, AtCor Medical, Australia). SphygmoCor was calibrated through diastolic and systolic brachial pressure obtained with a sphygmomanometer, while model inputs consist of brachial pressure, height, weight, age, left-ventricular end-systolic and end-diastolic volumes, and data from a pulse wave velocity study.ResultsModel-estimated systolic and diastolic central blood pressures resulted to be significantly related to SphygmoCor-assessed central systolic (r = 0.65 p <0.0001) and diastolic (r = 0.84 p<0.0001) blood pressures. The model showed a significant overestimation of systolic pressure (+7.8 (-2.2;14) mmHg, p = 0.0003) and a significant underestimation of diastolic values (-3.2(-7.5;1.6), p = 0.004), which imply a significant overestimation of central pulse pressure. Interestingly, model prediction errors mirror the mean errors reported in large meta-analysis characterizing the use of the SphygmoCor when non-invasive calibration is performed.ConclusionIn conclusion, multi-scale mathematical model predictions result to be significantly related to SphygmoCor ones. Model-predicted systolic and diastolic aortic pressure resulted in difference of less than 10 mmHg in the 51% and 84% of the subjects, respectively, when compared with SphygmoCor-obtained pressures.     

AutoTT: Automated Detection and Analysis of T-Tubule Architecture in Cardiomyocytes

Cardiac transverse (T)-tubules provide a specialized structure for synchronization and stabilization of sarcoplasmic reticulum Ca²⁺ release in healthy cardiomyocytes. The application of laser scanning confocal microscopy and the use of fluorescent lipophilic membrane dyes have boosted the discoveries that T-tubule remodeling is a significant factor contributing to cardiac contractile dysfunction. However, the analysis and quantification of the remodeling of T-tubules have been a challenge and remain inconsistent among different research laboratories. Fast Fourier transformation (FFT) is the major analysis method applied to calculate the spatial frequency spectrum, which is used to represent the regularity of T-tubule systems. However, this approach is flawed because the density of T-tubules as well as non-T-tubule signals in the images influence the spectrum power generated by FFT. Preprocessing of images and topological architecture extracting is necessary to remove non-T-tubule noise from the analysis. In addition, manual analysis of images is time consuming and prone to errors and investigator bias. Therefore, we developed AutoTT, an automated analysis program that incorporates image processing, morphological feature extraction, and FFT analysis of spectrum power. The underlying algorithm is implemented in MATLAB (The MathWorks, Natick, MA). The program outputs the densities of transversely oriented T-tubules and longitudinally oriented T-tubules, power spectrum of the overall T-tubule systems, and averaged spacing of T-tubules. We also combined the density and regularity of T-tubules to give an index of T-tubule integrity (TT_int), which provides a global evaluation of T-tubule alterations. In summary, AutoTT provides a reliable, easy to use, and fast approach for analyzing myocyte T-tubules. This program can also be applied to measure the density and integrity of other cellular structures.