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Executive summaryWe provide an overview of diagnostic stewardship with key concepts that include the diagnostic pathway and the multiple points where interventions can be implemented, strategies for interventions, the importance of multidisciplinary collaboration, and key microbiologic diagnostic tests that should be considered for diagnostic stewardship. The document focuses on microbiologic laboratory testing for adult and pediatric patients and is intended for a target audience of healthcare workers involved in diagnostic stewardship interventions and all workers affected by any step of the diagnostic pathway (ie, ordering, collecting, processing, reporting, and interpreting results of a diagnostic test). This document was developed by the Society for Healthcare Epidemiology of America Diagnostic Stewardship Taskforce.

A survey of Veterans' Affairs Medical Centers on control of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-producing CRE (CP-CRE) demonstrated that most facilities use VA guidelines but few screen for CRE/CP-CRE colonization regularly or regularly communicate CRE/CP-CRE status at patient transfer. Most respondents were knowledgeable about CRE guidelines but cited lack of adequate resources.

The RD51 collaboration maintains a common infrastructure at CERN for its R & Dactivities, including two beam telescopes for test beam campaigns. Recently, one of the beamtelescopes has been equipped and commissioned with new multi-channel and charge-sensitivefront-end electronics based on the ATLAS/BNL VMM3a front-end ASIC and the RD51 Scalable ReadoutSystem (SRS). This allows to read out the detectors at high rates (up to the MHz regime) withelectronics time resolutions of the order of 1 ns and the ability to handle different detectortypes and sizes, due to a larger dynamic range compared to the previous front-end electronicsbased on the APV25 ASIC. Having studied and improved the beam telescope's performance over thecourse of three test beam campaigns, the results are presented in this paper. The RD51 collaboration maintains a common infrastructure at CERN for its R & D activities, including two beam telescopes for test beam campaigns. Recently, one of the beam telescopes has been equipped and commissioned with new multi-channel and charge-sensitive front-end electronics based on the ATLAS/BNL VMM3a front-end ASIC and the RD51 Scalable Readout System (SRS). This allows to read out the detectors at high rates (up to the MHz regime) with electronics time resolutions of the order of 1 ns and the ability to handle different detector types and sizes, due to a larger dynamic range compared to the previous front-end electronics based on the APV25 ASIC. Having studied and improved the beam telescope's performance over the course of three test beam campaigns, the results are presented in this paper.

International audience; We describe the development of a position-sensitive Gas Electron Multiplier detector prototype, providing for each ionizing event three coordinates: the cartesian X and Y, and U at 45°. Simultaneous recording of the three projections permits ambiguity-free reconstruction of multiple tracks, and aims at operation in very high intensity radiation fields.

Cardiac allograft vasculopathy (CAV) is the leading cause of late allograft failure and mortality after heart transplantation. As current standards of diagnosis and treatment of CAV have significant limitations, understanding cell-specific responses may prove critical for developing improved detection strategies and novel therapeutics. This study is the first to successfully utilize human endomyocardial biopsy (EMB) samples to isolate large numbers of intact nuclei for single-nuclear transcriptomics. These data also lay the groundwork for ongoing experiments to study serial, routinely-collected EMB specimens after heart transplantation to identify novel biomarkers and pathways through which early CAV pathogenesis can be interrupted, thereby prolonging allograft survival.

Approximately 50% of all heart failure (HF) diagnoses can be classified as HF with preserved ejection fraction (HFpEF). HFpEF is more prevalent in females compared with males, but the underlying mechanisms are unknown. We previously showed that pressure overload (PO) in male felines induces a cardiopulmonary phenotype with essential features of human HFpEF. The goal of this study was to determine if slow progressive PO induces distinct cardiopulmonary phenotypes in females and males in the absence of other pathological stressors. Female and male felines underwent aortic constriction (banding) or sham surgery after baseline echocardiography, pulmonary function testing, and blood sampling. These assessments were repeated at 2 and 4 mo postsurgery to document the effects of slow progressive pressure overload. At 4 mo, invasive hemodynamic studies were also performed. Left ventricle (LV) tissue was collected for histology, myofibril mechanics, extracellular matrix (ECM) mass spectrometry, and single-nucleus RNA sequencing (snRNAseq). The induced pressure overload (PO) was not different between sexes. PO also induced comparable changes in LV wall thickness and myocyte cross-sectional area in both sexes. Both sexes had preserved ejection fraction, but males had a slightly more robust phenotype in hemodynamic and pulmonary parameters. There was no difference in LV fibrosis and ECM composition between banded male and female animals. LV snRNAseq revealed changes in gene programs of individual cell types unique to males and females after PO. Based on these results, both sexes develop cardiopulmonary dysfunction but the phenotype is somewhat less advanced in females.

As part of a multicenter evidence-based intervention for surgical site infection prevention, a qualitative study was conducted with infection control teams and surgical staff members at three Department of Veterans Affairs Healthcare Systems in the USA. This study aimed to identify strategies used by nurses and other facility champions for the implementation of a nasal decolonization intervention. Site visit observations and field notes provided contextual information. Interview data were analyzed with inductive and deductive content analysis. Interview data was mapped to the Expert Recommendations for Implementing Change (ERIC) compilation of implementation strategies. These strategies were then considered in the context of power and relationships as factors that influence implementation. We found that implementation of this evidence-based surgical site infection prevention intervention was successful when nurse champions drove the day-to-day implementation. Nurse champions sustained implementation strategies through all phases of implementation. Findings also suggest that nurse champions leveraged the influence of their role as champion along with their understanding of social networks and relationships to help achieve implementation success. Nurse champions consciously used multiple overlapping and iterative implementation strategies, adapting and tailoring strategies to stakeholders and settings. Commonly used implementation categories included: “train and educate stakeholders,” “use evaluative and iterative strategies,” “adapt and tailor to context,” and “develop stakeholder interrelationships.” Future research should examine the social networks for evidence-based interventions by asking specifically about relationships and power dynamics within healthcare organizations. Implementation of evidence-based interventions should consider if the tasks expected of a nurse champion fit the level of influence or power held by the champion.Trial registrationClinicalTrials.gov, identifier: NCT02216227.

Background Daily use of chlorhexidine gluconate (CHG) has been shown to reduce risk of healthcare-associated infections. We aimed to assess moving CHG bathing into routine practice using a human factors approach. We evaluated implementation in non-intensive care unit (ICU) settings in the Veterans Health Administration. Methods Our multiple case study approach included non-ICU units from 4 Veterans Health Administration settings. Guided by the Systems Engineering Initiative for Patient Safety, we conducted focus groups and interviews to capture barriers and facilitators to daily CHG bathing. We measured compliance using observations and skin CHG concentrations. Results Barriers to daily CHG include time, concern of increasing antibiotic resistance, workflow and product concerns. Facilitators include engagement of champions and unit shared responsibility. We found shortfalls in patient education, hand hygiene and CHG use on tubes and drains. CHG skin concentration levels were highest among patients from spinal cord injury units. These units applied antiseptic using 2% CHG impregnated wipes vs 4% CHG solution/soap. Discussion Non-ICUs implementing CHG bathing must consider human factors and work system barriers to ensure uptake and sustained practice change. Conclusions Well-planned rollouts and a unit culture promoting shared responsibility are key to compliance with daily CHG bathing. Successful implementation requires attention to staff education and measurement of compliance.

Background Carbapenem-resistant Enterobacteriaceae (CRE) cause approximately 13 100 infections, with an 8% mortality rate in the United States annually. Carbapenemase-producing CRE (CP-CRE) a subset of CRE infections infections have much higher mortality rates (40%–50%). There has been little research on characteristics unique to CP-CRE. The goal of the current study was to assess differences between US veterans with non-CP-CRE and those with CP-CRE cultures. Methods A retrospective cohort of veterans with CRE cultures from 2013–2018 and their demographic, medical, and facility level covariates were collected. Clustered multiple logistic regression models were used to assess independent factors associated with CP-CRE. Results The study included 3096 unique patients with cultures positive for either non-CP-CRE or CP-CRE. Being African American (odds ratio, 1.44 [95% confidence interval, 1.15–1.80]), diagnosis in 2017 (3.11 [2.13–4.54]) or 2018 (3.93 [2.64–5.84]), congestive heart failure (1.35 [1.11–1.64]), and gastroesophageal reflux disease (1.39 [1.03–1.87]) were associated with CP-CRE cultures. There was no known antibiotic exposure in the previous year for 752 patients (24.3% of the included patients). Those with no known antibiotic exposure had increased frequency of prolonged proton pump inhibitor use (17.3%) compared to those with known antibiotic exposure (5.6%). Discussion Among a cohort of patients with CRE, African Americans, patients with congestive heart failure, and those with gastroesophageal reflux disease had greater odds of having a CP-CRE culture. Roughly 1 in 4 patients with CP-CRE had no known antibiotic exposure in the year before their positive culture.

ZusammenfassungWiederholt episodenhaft auftretende Atemnot ist im Kindes- und Jugendalter ein häufiges Symptom. Neben anstrengungsinduzierter Bronchialobstruktion im Rahmen eines Asthma bronchiale ist eine funktionelle Genese eine sehr häufige Differenzialdiagnose. Dennoch wird diese Diagnose häufig nicht oder mit langer Latenz gestellt. Unter dem Oberbegriff „ILO“ („inducible laryngeal obstruction“) werden sowohl funktionelle supraglottische Obstruktionen durch Kollaps der Knorpelstrukturen als auch Dysfunktionen auf Glottisebene wie „vocal cord dysfunction“ (VCD) subsumiert. Körperliche Anstrengung ist ein häufiger Auslöser; es werden jedoch auch Beschwerdebilder ohne Anstrengungsbezug beobachtet. Es wird der Erkenntnisstand zur Pathophysiologie referiert und die klinische Präsentation beschrieben. Ein wesentlicher Fokus des Artikels liegt im Folgenden auf der Darstellung eines sinnvollen und Ressourcen-orientierten diagnostischen Vorgehens. Der CLE-Test („continuous laryngoscopy exercise test“) als Provokationsmethode unter Wach-Videolaryngoskopie ist der Goldstandard, jedoch wird diese Diagnostik im deutschsprachigen Raum nicht flächendeckend vorgehalten. Dieses Positionspapier stellt daher die diagnostische Wertigkeit verschiedener anderer Diagnostik-Algorithmen und anamnestischer Informationen heraus. Ein weiterer Schwerpunkt des Papiers besteht in der detaillierten Vorstellung geeigneter atemphysiotherapeutischer Interventionen.

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.

This is an epidemiological study of carbapenem-resistant Enterobacteriaceae (CRE) in Veterans’ Affairs medical centers (VAMCs). In 2017, almost 75% of VAMCs had at least 1 CRE case. We observed substantial geographic variability, with more cases in urban, complex facilities. This supports the benefit of tailoring infection control strategies to facility characteristics.

A survey of Veterans’ Affairs Medical Centers on control of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-producing CRE (CP-CRE) demonstrated that most facilities use VA guidelines but few screen for CRE/CP-CRE colonization regularly or regularly communicate CRE/CP-CRE status at patient transfer. Most respondents were knowledgeable about CRE guidelines but cited lack of adequate resources.

Endoscopic evaluation is frequently performed before bariatric surgery to identify foregut pathology that may alter procedure selection. Transnasal endoscopy (TNE) is an alternative to esophagogastroduodenoscopy (EGD). The objective of this study was to compare TNE to EGD. Patients who underwent TNE or EGD before bariatric surgery from January 2012 through April 2019 were reviewed. Statistical analyses included Chi-square, Wilcoxon two-sample, and Fisher’s exact tests. A p value

BACKGROUND: Variation in clinicians’ diagnostic test utilization is incompletely explained by demographics and likely relates to cognitive characteristics. We explored clinician factors associated with diagnostic test utilization METHODS: Self-administered survey of attitudes, cognitive characteristics and reported likelihood of test ordering in common scenarios; frequency of lipid and liver testing in patients on statin therapy. Participants were 552 primary care physicians, nurse practitioners (NP), and physician assistants [PA] from practices in 8 US states across 3 regions, from Measures included: 1 June 2018 to 26 November 2019. We measured Testing Likelihood Score: the mean of 4 responses to testing frequency and self-reported testing frequency in patients on statins. RESULTS: Respondents were 52.4% residents, 36.6% attendings, and 11.0% NP/PAs; most were White (53.6%) or Asian (25.5%). Median age was 32; 53.1% were female. Participants reported ordering tests for a median of 20% (stress tests) to 90% (mammograms) of patients; Testing Likelihood Scores varied widely (median 54%, IQR 43%−69%). Higher scores were associated with geography, training type, low numeracy, high malpractice fear, high medical maximizer score, high stress from uncertainty, high concern about bad outcomes, and low acknowledgment of medical uncertainty. More frequent testing of lipids and liver tests was associated with low numeracy, high medical maximizer score, high malpractice fear, and low acknowledgment of uncertainty. CONCLUSIONS: Clinician variation in testing was common, with more aggressive testing consistently associated with low numeracy, being a medical maximizer, and low acknowledgment of uncertainty. Efforts to reduce undue variations in testing should consider clinician cognitive drivers.

The European Spallation Source (ESS) in Lund, Sweden willbecome the world's most powerful thermal neutron source. TheMacromolecular Diffractometer (NMX) at the ESS requires three51.2 × 51.2 cm$^{2}$ detectors with reasonable detectionefficiency, sub-mm spatial resolution, a narrow point-spreadfunction (PSF), and good time resolution. This work presentsmeasurements with the improved version of the NMX detector prototypeconsisting of a Triple-GEM (Gas Electron Multiplier) detector with anatural Gd converter and a low material budget readout. The detectorwas successfully tested at the neutron reactor of the BudapestNeutron Centre (BNC) and the D16 instrument at the InstitutLaue-Langevin (ILL) in Grenoble. The measurements with Cadmium andGadolinium masks in Budapest demonstrate that the point-spreadfunction of the detector lacks long tails that could impede themeasurement of diffraction spot intensities. On the D16 instrumentat ILL, diffraction spots from Triose phosphate isomerase w/2-phosphoglycolate (PGA) inhibitor were measured both in the MILANDHelium-3 detector and the Gd-GEM. The comparison between the twodetectors shows a similar point-spread function in both detectors,and the expected efficiency ratio compared to the Helium-3detector. Both measurements together thus give good indications thatthe Gd-GEM detector fits the requirements for the NMX instrument atESS. The European Spallation Source (ESS) in Lund, Sweden will become the world's most powerful thermal neutron source. The Macromolecular Diffractometer (NMX) at the ESS requires three 51.2 x 51.2~cm$^{2}$ detectors with reasonable detection efficiency, sub-mm spatial resolution, a narrow point spread function (PSF) and good time resolution. This work presents measurements with the improved version of the NMX detector prototype consisting of a Triple-GEM detector with natural Gd converter and a low material budget readout. The detector was successfully tested at the neutron reactor of the Budapest Neutron Centre (BNC) and at the D16 instrument at the Institut Laue-Langevin (ILL) in Grenoble. The measurements with Cadmium and Gadolinium masks in Budapest demonstrate that the point spread function of the detector lacks long tails that could impede the measurement of diffraction spot intensities. On the D16 instrument at ILL, diffraction spots from Triose phosphate isomerase w/ 2-phosphoglycolate (PGA) inhibitor were measured both in the D16 Helium-3 detector and the Gd-GEM. The comparison between the two detectors show a similar point spread function in both detectors, and the expected efficiency ratio compared to the Helium-3 detector. Both measurements together thus give good indications that the Gd-GEM detector fits the requirements for the NMX instrument at ESS.

Introduction: Approximately 50% of all heart failure (HF) diagnoses can be classified as HF with preserved ejection fraction (HFpEF), which has no FDA approved therapies. HFpEF is more prevalent in females compared to males, but the underlying mechanisms for the development as a sex-based disorder are unknown. We previously described how slow progressive pressure overload (PO) in male felines recapitulates the HFpEF phenotype but have not investigated the female phenotype. Hypothesis: Females will develop a less severe HFpEF phenotype compared to males under the same pathological stress. Methods & Results: Male (m) and female (f) domestic short felines (age 2mo) underwent aortic constriction (m: n=11; f: n=10) using a customized pre-shaped band or a sham procedure (m: n=7; f: n=7). Before surgery (baseline), there was no difference in body weight (BW) between groups and lung compliance was not different. Echocardiography revealed no significant difference in the ratio of left atrium to aortic root (LA/Ao), LA ejection fraction (LA EF), left ventricle (LV) ejection fraction, LV wall-thickness, and E/A ratio. By 4mo post-surgery, both males and females had developed cardiac dysfunction and decreased lung compliance. At this time, females had significantly smaller BWs than males. Despite the difference in BW, LV wall thickness and changes in E/A ratio were similar in both sexes in banded vs. shams. Importantly, LV EF did not change in any group. There was a decrease in LA EF and increased LA/Ao in all banded animals. Invasive hemodynamics at 4mo post-surgery showed no differences between sexes for the systolic pressure gradient generated by aortic banding. Banded males had higher LV end-diastolic pressure vs. banded females (m: 15.0±2.7mmHg; f: 8.1±1.9mmHg). However, there was a trend towards prolongation of tau and lower dp/dt min in banded females, suggestive of abnormal relaxation. There were no differences between banded males and females in heart weight/BW or cardiomyocyte cross-sectional area and both developed fibrosis. Conclusions: Exposure of male and female felines to PO resulted in similar cardiac hypertrophy, fibrosis, and decreased lung compliance. Females had lower LVEDP than males suggesting they may be protected from diastolic dysfunction.

The RD51 collaboration developed the Scalable Readout System (SRS) as part of its R&D activities on Micro-Pattern Gaseous Detectors. This common multi-purpose readout system allows to read out small R&D detectors (0.2k channels) up to mid-sized experiments with multiple detectors (2.5k to 5k channels). To cope with increased demands on detectors, electronics and readout speed, a new front-end ASIC—the VMM3a—was integrated into the SRS. This led to the development of a scalable, self-triggered high-rate readout system that provides energy, space and time information of the interacting particles at the same time.

Cardiac injury is associated with critical COVID-19, yet its etiology remains debated. To elucidate the pathogenic mechanisms of COVID-19-associated cardiac injury, we conducted a single-center prospective cohort study of 69 COVID-19 decedents. Of six cardiac histopathologic features, microthrombi was the most commonly detected (n=48, 70%). We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with in-hospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak ESR and CRP during hospitalization were independently associated with higher odds of microthrombi. Using single nuclei RNA-sequence analysis, we discovered an enrichment of pro-thrombotic/anti-fibrinolytic, extracellular matrix remodeling, and immune-potentiating signaling amongst cardiac fibroblasts in microthrombi-positive COVID-19 hearts relative to microthrombi-negative COVID-19. Non-COVID-19 non-failing hearts were used as reference controls. Our cumulative findings identify the specific transcriptomic changes in cardiac fibroblasts as salient features of COVID-19-associated cardiac microthrombi.

In 2014, Oregon implemented an interfacility transfer communication law requiring notification of multidrug-resistant organism status on patient transfer. Based on 2015 and 2016 statewide facility surveys, compliance was 77% and 87% for hospitals, and 67% and 68% for skilled nursing facilities. Methods for complying with the rule were heterogeneous, and fewer than half of all facilities surveyed reported use of a standardized interfacility transfer communication form to assess a patient's multidrug-resistant organism status on transfer.

Automated diagnosis of tuberculosis (TB) from chest X-Rays (CXR) has been tackled with either hand-crafted algorithms or machine learning approaches such as support vector machines (SVMs) and convolutional neural networks (CNNs). Most deep neural network applied to the task of tuberculosis diagnosis have been adapted from natural image classification. These models have a large number of parameters as well as high hardware requirements, which makes them prone to overfitting and harder to deploy in mobile settings. We propose a simple convolutional neural network optimized for the problem which is faster and more efficient than previous models but preserves their accuracy. Moreover, the visualization capabilities of CNNs have not been fully investigated. We test saliency maps and grad-CAMs as tuberculosis visualization methods, and discuss them from a radiological perspective.

Laboratory identification of carbapenem-resistant Enterobacteriaceae (CRE) is a key step in controlling its spread. Our survey showed that most Veterans Affairs laboratories follow VA guidelines for initial CRE identification, whereas 55.0% use PCR to confirm carbapenemase production. Most respondents were knowledgeable about CRE guidelines. Barriers included staffing, training, and financial resources.

Syllabi are usually required by institutions of higher education and often are the first exposure that students have to a particular course. Instructors can use syllabi as a mechanism to convey important information to students. Moreover, a syllabus can be considered a tool to create inclusive biology courses by transmitting information to all students equitably. In this study, we examined 75 biology course syllabi collected from a research-intensive institution to examine what content instructors include. We reviewed the syllabi to determine the presence or absence of elements and assessed to what extent there were differences in the presence or absence of certain syllabus elements based on course level and course size. We found that instructors are most likely to include content about course expectations and least likely to include content about creating positive classroom climate on their course syllabi. Despite university requirements, many instructors did not include the university-mandated criteria and they did not include elements that could increase how inclusive students perceive the course to be. However, instructors more often included inclusive content when it was required by the university. We also found that students enrolled in upper level courses and small enrollment courses are provided with less content on their syllabi, which we would then interpret as a less inclusive syllabus. We discuss the implications of how these results may differentially impact students in these courses and how the syllabus can be a tool for creating more inclusive college biology courses.

New York State, in particular the New York City metropolitan area, was the early epicenter of the SARS-CoV-2 pandemic in the United States. Similar to initial pandemic dynamics in many metropolitan areas, multiple introductions from various locations appear to have contributed to the swell of positive cases. However, representation and analysis of samples from New York regions outside the greater New York City area were lacking, as were SARS-CoV-2 genomes from the earliest cases associated with the Westchester County outbreak, which represents the first outbreak recorded in New York State. The Wadsworth Center, the public health laboratory of New York State, sought to characterize the transmission dynamics of SARS-CoV-2 across the entire state of New York from March to September with the addition of over 600 genomes from under-sampled and previously unsampled New York counties and to more fully understand the breadth of the initial outbreak in Westchester County. Additional sequencing confirmed the dominance of B.1 and descendant lineages (collectively referred to as B.1.X) in New York State. Community structure, phylogenetic, and phylogeographic analyses suggested that the Westchester outbreak was associated with continued transmission of the virus throughout the state, even after travel restrictions and the on-pause measures of March, contributing to a substantial proportion of the B.1 transmission clusters as of September 30th, 2020.