Development of a triage protocol for patients presenting with gastrointestinal hemorrhage: a prospective cohort study

Abstract Introduction Many patients presenting with acute gastrointestinal hemorrhage (GIH) are admitted to the intensive care unit (ICU) for monitoring. A simple triage protocol based upon validated risk factors could decrease ICU utilization. Methods Records of 188 patients admitted with GIH from the emergency department (ED) were reviewed for BLEED criteria (visualized red blood, systolic blood pressure below 100 mm Hg, elevated prothrombin time [PT], erratic mental status, and unstable comorbid disease) and complication within the first 24 hours of admission. Variables associated with early complication were reassessed in 132 patients prospectively enrolled as a validation cohort. A triage model was developed using significant predictors. Results We studied 188 patients in the development set and 132 in the validation set. Red blood (relative risk [RR] 4.53, 95% confidence interval [CI] 2.04, 10.07) and elevated PT (RR 3.27, 95% CI 1.53, 7.01) were significantly associated with complication in the development set. In the validation cohort, the combination of red blood or unstable comorbidity had a sensitivity of 0.73, a specificity of 0.55, a positive predictive value of 0.24, and a negative predictive value of 0.91 for complication within 24 hours. In simulation studies, a triage model using these variables could reduce ICU admissions without increasing the number of complications. Conclusion Patients presenting to the ED with GIH who have no evidence of ongoing bleeding or unstable comorbidities are at low risk for complication during hospital admission. A triage model based on these variables should be tested prospectively to optimize critical care resource utilization in this common condition

Bridging the Gap Between the Foreland and Hinterland II: Geochronology and Tectonic Setting of Ordovician Magmatism and Basin Formation on the Laurentian Margin of New England and Newfoundland

Ordovician strata of the Mohawk Valley and Taconic allochthon of New York and the Humber margin of Newfoundland record multiple magmatic and basin-forming episodes associated with the Taconic orogeny. Here we present new U-Pb zircon geochronology and whole rock geochemistry and neodymium isotopes from Early Paleozoic volcanic ashes and siliciclastic units on the northern Appalachian margin of Laurentia. Volcanic ashes in the Table Point Formation of Newfoundland and the Indian River Formation of the Taconic allochthon in New York yield dates between 466.16 ± 0.12 and 464.20 ± 0.13 Ma. Red, bioturbated slate of the Indian River Formation record a shift to more juvenile neodymium isotope values suggesting sedimentary contributions from the Taconic arc-system by 466 Ma. Eight ashes within the Trenton Group in the Mohawk Valley were dated between 452.63 ± 0.06 and 450.68 ± 0.12 Ma. These ashes contain zircon with Late Ordovician magmatic rims and 1.4 to 1.0 Ga xenocrystic cores that were inherited from Grenville basement, suggesting that the parent magmas erupted through the Laurentian margin. The new geochronological and geochemical data are integrated with a subsidence model and data from the hinterland to refine the tectonic model of the Taconic orogeny. Closure of the Iapetus Ocean by 475 Ma via collision of the peri-Gondwanan Moretown terrane with hyperextended distal fragments of the Laurentian margin is not clearly manifested on the autochthon or the Taconic allochthon other than an increase in sediment accumulation. Pro-foreland basins formed during the Middle Ordovician when these terranes were obducted onto the Laurentian margin. 466 to 464 Ma ashes on the Laurentian margin coincide with a late pulse of magmatism in both the Notre Dame arc in Newfoundland and the Shelburne Falls arc of New England that is potentially related to break-off of an east-dipping slab. Following slab reversal, by 455 Ma, the Bronson Hill arc was established on the new composite Laurentian margin. Thus, we conclude that Late Ordovician strata in the Mohawk Valley and Taconic allochthon of New York and on the Humber margin of Newfoundland were deposited in retro-foreland basins

Implementation Evaluation of a Professional Development Program for Comprehensive School Physical Activity Leaders

The purpose of this study was to conduct an implementation monitoring evaluation of a yearlong comprehensive school physical activity program (CSPAP) professional development program across eight multi-state physical education (PE) teacher cohorts. Mixed-method data were collected during a three-year implementation period via workshop attendance sheets and evaluations, post-workshop implementation plans and artifacts, and follow-up phone interviews to enumerate and evaluate the program’s process of recruitment, reach, dose delivered, dose received, fidelity, and context. Recruitment strategies reached a total of 234 PE teacher attendees across eight workshops, with 77 PE teachers (primarily female, elementary, public school teachers) completing all program requirements. Facilitators among full program completers were participation incentives and network opportunities, while common inhibitors were difficulty with online technology and perceptions of added workload. Completers submitted implementation plans with at least three action steps, ranging from 4 to 7 months to accomplish, that predominately commenced with securing administration approval as the first step (81%), focused on implementing student physical activity initiatives beyond PE (76%), and evidenced with mostly picture artifacts (78%). Implementation was facilitated by the presence of multilevel support at school and an elevated image of PE and PE teachers at school, and was inhibited by scheduling constraints, unrealistic planning, and conflicting perceptions of physical activity and PE. Overall, this evaluation reveals unique perspectives of PE teachers regarding schoolwide PA promotion and informs future efforts to target and effectively support CSPAP leaders

Analysis of offsite Emergency Planning Zones (EPZ) for the Rocky Flats Plant

This project plan for Phase II summarizes the design of a project to complete analysis of offsite Emergency Planning Zones (EPZ) for the Rocky Flats Plant. Federal, state, and local governments develop emergency plans for facilities that may affect the public in the event of an accidental release of nuclear or hazardous materials. One of the purposes of these plans is to identify EPZs where actions might be necessary to protect public health. Public protective actions include sheltering, evacuation, and relocation. Agencies use EPZs to develop response plans and to determine needed resources. The State of Colorado, with support from the US Department of Energy (DOE) and Rocky Flats contractors, has developed emergency plans and EPZs for the Rocky Flats Plant periodically beginning in 1980. In Phase II, Interim Emergency Planning Zones Analysis, Maximum Credible Accident'' we will utilize the current Rocky Flats maximum credible accident (MCA), existing dispersion methodologies, and upgraded dosimetry methodologies to update the radiological EPZs. Additionally, we will develop recommendations for EPZs for nonradiological hazardous materials releases and evaluate potential surface water releases from the facility. This project will allow EG G Rocky Flats to meet current commitments to the state of Colorado and make steady, tangible improvements in our understanding of risk to offsite populations during potential emergencies at the Rocky Flats Plant. 8 refs., 5 figs., 4 tabs

The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies.

BACKGROUND: In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment. DESIGN: We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are values routinely recorded in the official renal biopsy pathology report from the 25 participating centers. Two general trends in reporting were noted: total number per biopsy or average number per level/section. Both of these approaches were assessed for their accuracy in comparison to the analogous numbers of annotated glomeruli on WSI. RESULTS: The number of glomeruli annotated was consistently higher than those reported (p CONCLUSIONS: Although glass slides were not available for direct comparison to whole slide image annotation, this study indicates that routine manual light microscopy assessment of number of glomeruli is inaccurate, and the magnitude of this error is proportional to the total number of glomeruli

The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies

In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment

Study protocol for a real-world evaluation of an integrated child and family health hub for migrant and refugee women

Introduction Continuity of child and family healthcare is vital for optimal child health and development for developmentally vulnerable children. Migrant and refugee communities are often at-risk of poor health outcomes, facing barriers to health service attendance including cultural, language, limited health literacy, discrimination and unmet psychosocial needs. 'Integrated health-social care hubs' are physical hubs where health and social services are co-located, with shared referral pathways and care navigation. Aim Our study will evaluate the impact, implementation and cost-benefit of the First 2000 Days Care Connect (FDCC) integrated hub model for pregnant migrant and refugee women and their infants. Materials and methods This study has three components. Component 1 is a non-randomised controlled trial to compare the FDCC model of care with usual care. This trial will allocate eligible women to intervention and control groups based on their proximity to the Hub sites. Outcome measures include: the proportion of children attending child and family health (CFH) nurse services and completing their CFH checks to 12 months of age; improved surveillance of growth and development in children up to 12 months, post partum; improved breastfeeding rates; reduced emergency department presentations; and improved maternal well-being. These will be measured using linked medical record data and surveys. Component 2 will involve a mixed-method implementation evaluation to clarify how and why FDCC was implemented within the sites to inform future roll-out. Component 3 is a within-trial economic evaluation from a healthcare perspective to assess the cost-effectiveness of the Hubs relative to usual care and the implementation costs if Hubs were scaled and replicated

Reproducibility of the NEPTUNE descriptor-based scoring system on whole-slide images and histologic and ultrastructural digital images

The multicenter Nephrotic Syndrome Study Network (NEPTUNE) digital pathology scoring system employs a novel and comprehensive methodology to document pathologic features from whole-slide images, immunofluorescence and ultrastructural digital images. To estimate inter- and intra-reader concordance of this descriptor-based approach, data from 12 pathologists (eight NEPTUNE and four non-NEPTUNE) with experience from training to 30 years were collected. A descriptor reference manual was generated and a webinar-based protocol for consensus/cross-training implemented. Intra-reader concordance for 51 glomerular descriptors was evaluated on jpeg images by seven NEPTUNE pathologists scoring 131 glomeruli three times (Tests I, II, and III), each test following a consensus webinar review. Inter-reader concordance of glomerular descriptors was evaluated in 315 glomeruli by all pathologists; interstitial fibrosis and tubular atrophy (244 cases, whole-slide images) and four ultrastructural podocyte descriptors (178 cases, jpeg images) were evaluated once by six and five pathologists, respectively. Cohen’s kappa for inter-reader concordance for 48/51 glomerular descriptors with sufficient observations was moderate (0.40<kappa ≤0.60) for 17 and good (0.60<kappa ≤0.80) for 8, for 52% with moderate or better kappas. Clustering of glomerular descriptors based on similar pathologic features improved concordance. Concordance was independent of years of experience, and increased with webinar cross-training. Excellent concordance was achieved for interstitial fibrosis and tubular atrophy. Moderate-to-excellent concordance was achieved for all ultrastructural podocyte descriptors, with good-to-excellent concordance for descriptors commonly used in clinical practice, foot process effacement, and microvillous transformation. NEPTUNE digital pathology scoring system enables novel morphologic profiling of renal structures. For all histologic and ultrastructural descriptors tested with sufficient observations, moderate-to-excellent concordance was seen for 31/54 (57%). Descriptors not sufficiently represented will require further testing. This study proffers the NEPTUNE digital pathology scoring system as a model for standardization of renal biopsy interpretation extendable outside the NEPTUNE consortium, enabling international collaborations

Estrogen inhibits the vascular injury response in estrogen receptor beta -deficient female mice

The protective effects of estrogen in the cardiovascular system result from both systemic effects and direct actions of the hormone on the vasculature. Two estrogen receptors have been identified, ERα and ERβ. We demonstrated previously that estrogen inhibits the response to vascular injury in both wild-type and ERα-deficient mice, and that ERβ is expressed in the blood vessels of each, suggesting a role for ERβ in the vascular protective effects of estrogen. In the present study, we examined the effect of estrogen administration on mouse carotid arterial injury in ERβ-deficient mice. Surprisingly, in ovariectomized female wild-type and ERβ knockout mice, 17β-estradiol markedly and equally inhibited the increase in vascular medial area and the proliferation of vascular smooth muscle cells after vascular injury. These data demonstrate that ERβ is not required for estrogen-mediated inhibition of the response to vascular injury, and suggest that either of the two known estrogen receptors is sufficient to protect against vascular injury, or that another unidentified estrogen receptor mediates the vascular protective effects of estrogen