Search

Background Inappropriate diagnosis of infections results in antibiotic overuse and may delay diagnosis of underlying conditions. Here we describe the development and characteristics of 2 safety measures of inappropriate diagnosis of urinary tract infection (UTI) and community-acquired pneumonia (CAP), the most common inpatient infections on general medicine services. Methods Measures were developed from guidelines and literature and adapted based on data from patients hospitalized with UTI and CAP in 49 Michigan hospitals and feedback from end-users, a technical expert panel (TEP), and a patient focus group. Each measure was assessed for reliability, validity, feasibility, and usability. Results Two measures, now endorsed by the National Quality Forum (NQF), were developed. Measure reliability (derived from 24 483 patients) was excellent (0.90 for UTI; 0.91 for CAP). Both measures had strong validity demonstrated through (a) face validity by hospital users, the TEPs, and patient focus group, (b) implicit case review (ĸ 0.72 for UTI; ĸ 0.72 for CAP), and (c) rare case misclassification (4% for UTI; 0% for CAP) due to data errors (<2% for UTI; 6.3% for CAP). Measure implementation through hospital peer comparison in Michigan hospitals (2017 to 2020) demonstrated significant decreases in inappropriate diagnosis of UTI and CAP (37% and 32%, respectively, P <.001), supporting usability. Conclusions We developed highly reliable, valid, and usable measures of inappropriate diagnosis of UTI and CAP for hospitalized patients. Hospitals seeking to improve diagnostic safety, antibiotic use, and patient care should consider using these measures to reduce inappropriate diagnosis of CAP and UTI. [ABSTRACT FROM AUTHOR]

Background Despite antibiotic stewardship programs existing in most acute care hospitals, there continues to be variation in appropriate antibiotic use. While existing research examines individual prescriber behavior, contextual reasons for variation are poorly understood. Methods We conducted an explanatory, sequential mixed-methods study of a purposeful sample of 7 hospitals with varying discharge antibiotic overuse. For each hospital, we conducted surveys, document analysis, and semi-structured interviews with antibiotic stewardship and clinical stakeholders. Data were analyzed separately and mixed during the interpretation phase, where each hospital was examined as a case, with findings organized across cases using a strengths, weaknesses, opportunities, and threats framework to identify factors accounting for differences in antibiotic overuse across hospitals. Results Surveys included 85 respondents. Interviews included 90 respondents (31 hospitalists, 33 clinical pharmacists, 14 stewardship leaders, 12 hospital leaders). On surveys, clinical pharmacists at hospitals with lower antibiotic overuse were more likely to report feeling: respected by hospitalist colleagues (P =.001), considered valuable team members (P =.001), and comfortable recommending antibiotic changes (P =.02). Based on mixed-methods analysis, hospitals with low antibiotic overuse had 4 distinguishing characteristics: (1) robust knowledge of and access to antibiotic stewardship guidance; (2) high-quality clinical pharmacist–physician relationships; (3) tools and infrastructure to support stewardship; and (4) highly engaged infectious diseases physicians who advocated stewardship principles. Conclusions This mixed-methods study demonstrates the importance of organizational context for high performance in stewardship and suggests that improving antimicrobial stewardship requires attention to knowledge, interactions, and relationships between clinical teams and infrastructure that supports stewardship and team interactions. [ABSTRACT FROM AUTHOR]

Simple Summary: This study focuses on the spontaneous lesions observed in a captive colony of geriatric Julia Creek dunnarts, an endangered carnivorous marsupial. Despite their conservation status, no prior research has focused on the conditions affecting captive individuals attaining senescence. We examined one wild and thirty-five captive-born, mostly elderly dunnarts that failed to reproduce over several breeding periods. From these, ten dunnarts had normal findings. Among females, the most common issue was cystic glandular hyperplasia (eight cases); cutaneous lesions were infrequent (two cases). Males showed testicular degeneration, aspermatogenesis, or atrophy (three cases). Cutaneous lesions compatible with epitheliotropic T cell lymphomas were observed in both sexes (five cases) and thus, an underlying oncogenic viral etiology is suspected. This is the first study that documents spontaneous diseases in aging Julia Creek dunnarts, shedding light on geriatric conditions within a conservation context. Julia Creek dunnarts are an endangered species of carnivorous marsupials and the focus of multiple conservation strategies involving significant resources such as captive breeding programs. Despite the relevance for conservation, no study to date has focused on evaluating geriatric diseases in dunnarts. This study describes the pathology findings in a group of one wild and thirty-five captive-born, mostly geriatric Julia Creek dunnarts that failed to produce offspring over multiple breeding periods. A total of 20 females and 16 males were submitted for a postmortem examination, with ages ranging from 9 to 42 and 12 to 42 months for females and males, respectively. Of these, 10 had unremarkable findings. The most common condition in females was cystic glandular hyperplasia (n = 8), typical of hormonal dysregulation profiles in senescence, particularly hyperestrogenism. Rarely, cutaneous disease represented by unidentified dermal round cell infiltrates was observed in females (n = 2). Primary reproductive hormonal dysregulation was also suspected in males diagnosed with testicular degeneration, aspermatogenesis and/or atrophy (n = 3). Cutaneous round cell infiltrates, possibly compatible with epitheliotropic lymphomas, were seen in males (n = 3), and 2/3 affected males also had concurrent testicular degeneration or atrophy, indicating male sex could be a predictor for lymphoid neoplasia in aged dunnarts, especially in individuals with concurrent testosterone-luteinizing hormone dysregulation as it occurs in gonadectomized animals. The role of an underlying viral etiology is also explored. This study is the first to describe major spontaneous diseases in endangered aged Julia Creek dunnarts, providing an important understanding of senescence and geriatric diseases within a conservation context. [ABSTRACT FROM AUTHOR]

Joseph Conrad. The Rover. Edited by Alexandre Fachard and J. H. Stape. The Cambridge Edition of the Works of Joseph Conrad. Cambridge: Cambridge University Press, 2018. ISBN: 9781107149021. The Cambridge [...]

Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset produces the chemokine CCL21, thereby attracting positively selected thymocytes from the cortex to the medulla. Both self-antigen-displaying and thymocyte-attracting mTEC subsets are essential for self-tolerance. Here, we identify a developmental pathway by which mTECs gain their diversity in functionally distinct subsets. We show that CCL21-expressing mTECs arise early during thymus ontogeny in mice. Fate-mapping analysis reveals that self-antigen-displaying mTECs, including Aire-expressing mTECs and thymic tuft cells, are derived from CCL21-expressing cells. The differentiation capability of CCL21-expressing embryonic mTECs is verified in reaggregate thymus experiments. These results indicate that CCL21-expressing embryonic mTECs carry a developmental potential to give rise to self-antigen-displaying mTECs, revealing that the sequential conversion of thymocyte-attracting subset into self-antigen-displaying subset serves to assemble functional diversity in the thymus medulla epithelium. [ABSTRACT FROM AUTHOR]

The thymus is a unique primary lymphoid organ that supports the production of self‐tolerant T‐cells essential for adaptive immunity. Intrathymic microenvironments are microanatomically compartmentalised, forming defined cortical, and medullary regions each differentially supporting critical aspects of thymus‐dependent T‐cell maturation. Importantly, the specific functional properties of thymic cortical and medullary compartments are defined by highly specialised thymic epithelial cells (TEC). For example, in the medulla heterogenous medullary TEC (mTEC) contribute to the enforcement of central tolerance by supporting deletion of autoreactive T‐cell clones, thereby counterbalancing the potential for random T‐cell receptor generation to contribute to autoimmune disease. Recent advances have further shed light on the pathways and mechanisms that control heterogeneous mTEC development and how differential mTEC functionality contributes to control self‐tolerant T‐cell development. Here we discuss recent findings in relation to mTEC development and highlight examples of how mTEC diversity contribute to thymus medulla function. [ABSTRACT FROM AUTHOR]

Exploratory analysis to conceptualize and evaluate the potential cost-effectiveness and economic drivers of using a novel tissue valve compared with mechanical heart valves for surgical aortic valve replacement (SAVR) in people aged 55–64 and 65+ with aortic stenosis (AS) from a National Health Service (NHS) UK perspective. A decision-analytic model was developed using a partitioned survival model. Parameter inputs were obtained from published literature. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted to explore the uncertainty around the parameters. The novel tissue valve was potentially associated with higher quality-adjusted life years (QALYs) of 0.01 per person. Potential cost savings were greatest for those aged 55–64 (£408) versus those aged 65+(£53). DSA indicated the results to be most dependent on relative differences in general mortality, procedure costs, and reoperation rates. PSA estimated around 75% of the iterations to be cost-effective at £20,000 per QALY for those aged 55–64, and 57% for those aged 65+. The exploratory analysis suggests that the novel tissue valve could be a cost-effective intervention for people over the age of 55 with AS who are suitable for SAVR in the UK. [ABSTRACT FROM AUTHOR]

γδT cells are produced in the thymus throughout life and provide immunity at epithelial‐rich sites. Unlike conventional αβT cells, γδT‐cell development involves intrathymic acquisition of effector function, with priming for either IL17 or IFN‐γ production occurring during embryonic or adult life, respectively. How the thymus controls effector‐primed γδT‐cell generation in adulthood is poorly understood. Here, we distinguished de novo γδT cells from those undergoing thymus recirculation and/or retention using Rag2GFP mice alongside markers of maturation/effector priming including CD24, CD25, CD73, and IFN‐γ, the latter by crossing with IFN‐γYFP GREAT mice. We categorize newly developing γδT‐cells into an ordered sequence where CD25+CD73−IFN‐γYFP− precursors are followed sequentially by CD25−CD73+IFN‐γYFP− intermediates and CD25−CD73+IFN‐γYFP+ effectors. To determine intrathymic requirements controlling this sequence, we examined γδT‐cell development in Relb−/− thymus grafts that lack medullary microenvironments. Interestingly, medulla deficiency did not alter CD25+ γδT‐cell precursor generation, but significantly impaired development of effector primed stages. This impact on γδT‐cell priming was mirrored in plt/plt mice lacking the medullary chemoattractants CCL19 and CCL21, and also Ccl21a−/− but not Ccl19−/− mice. Collectively, we identify the medulla as an important site for effector priming during adult γδT‐cell development and demonstrate a specific role for the medullary epithelial product CCL21 in this process. [ABSTRACT FROM AUTHOR]

This paper presents an innovative and fully automatic solution of generating as-built computer-aided design (CAD) drawings for landscape architecture (LA) with three dimensional (3D) reality data scanned via drone, camera, and LiDAR. To start with the full pipeline, 2D feature images of ortho-image and elevation-map are converted from the reality data. A deep learning-based light convolutional encoder–decoder was developed, and compared with U-Net (a binary segmentation model), for image pixelwise segmentation to realize automatic site surface classification, object detection, and ground control point identification. Then, the proposed elevation clustering and segmentation algorithms can automatically extract contours for each instance from each surface or object category. Experimental results showed that the developed light model achieved comparable results with U-Net in landing pad segmentation with average intersection over union (IoU) of 0.900 versus 0.969. With the proposed data augmentation strategy, the light model had a testing pixel accuracy of 0.9764 and mean IoU of 0.8922 in the six-class segmentation testing task. Additionally, for surfaces with continuous elevation changes (i.e., ground), the developed algorithm created contours only have an average elevation difference of 1.68 cm compared to dense point clouds using drones and image-based reality data. For objects with discrete elevation changes (i.e., stair treads), the generated contours accurately represent objects' elevations with zero difference using light detection and ranging (LiDAR) data. The contribution of this research is to develop algorithms that automatically transfer the scanned LA scenes to contours with real-world coordinates to create as-built computer-aided design (CAD) drawings, which can further assist building information modeling (BIM) model creation and inspect the scanned LA scenes with augmented reality. The optimized parameters for the developed algorithms are analyzed and recommended for future applications. [ABSTRACT FROM AUTHOR]

An analysis of the budget impact of using a bovine pericardial aortic bioprosthesis (BPAB) or a mechanical valve (MV) in aortic stenosis (AS) patients in Romania. A decision-tree with a partitioned survival model was used to predict the financial outcomes of using either a BPAB (the Carpentier-Edwards Perimount Magna Ease Valve) or MV in aortic valve replacement (AVR) procedure over a 5-year period. The budget impact of various resource consumption including disabling strokes, reoperations, minor thromboembolic events, major bleeding, endocarditis, anticoagulation treatment and monitoring, and echocardiogram assessments were compared for both types of valves. One-way sensitivity analyses (OWSA) were conducted on the input costs and probabilities. The use of BPAB compared to MV approaches budget neutrality due to incremental savings year-on-year. The initial surgical procedure and reoperation costs for BPAB are offset by savings in acenocoumarol use, disabling strokes, major bleeding, minor thromboembolic events, and anticoagulation complications. The cost of the initial procedure per patient is 460 euros higher for a BPAB due to the higher valve acquisition cost, although this is partially offset by a shorter hospital stay. The OWSA shows that the total procedure costs, including the hospital stay, are the primary cost drivers in the model. Results are limited by cost data aggregation in the DRG system, exclusion of costs for consumables and capital equipment use, possible underestimation of outpatient complication costs, age-related variations of event rates, and valve durability. Adopting BPAB as a treatment option for AS patients in Romania can lead to cost savings and long-term economic benefits. By mitigating procedure costs and increasing anticoagulation treatment costs, BPAB offers a budget-neutral option that can help healthcare providers, policymakers, and patients alike manage the growing burden of AS in Romania. [ABSTRACT FROM AUTHOR]