Building trauma capability: using geospatial analysis to consider military treatment facilities for trauma center development.

Background: The Military Health System must develop and sustain experienced surgical trauma teams while facing decreased surgical volumes both during and between deployments. Military trauma resources may enhance local trauma systems by accepting civilian patients for care at military treatment facilities (MTFs). Some MTFs may be able to augment their regional trauma systems by developing trauma center (TC) capabilities. The aim of this study was to evaluate the geographical proximity of MTFs to the continental US (CONUS) population and relative to existing civilian adult TCs, and then to determine which MTFs might benefit most from TC development. Methods: Publicly available data were used to develop a list of CONUS adult civilian level 1 and level 2 TCs and also to generate a list of CONUS MTFs. Census data were used to estimate adult population densities across zip codes. Distances were calculated between zip codes and civilian TCs and MTFs. The affected population sizes and reductions in distance were tabulated for every zip code that was found to be closer to an MTF than an existing TC. Results: 562 civilian adult level 1 and level 2 TCs and 33 military medical centers and hospitals were identified. Compared with their closest civilian TCs, MTFs showed mean reductions in distance ranging from 0 to 30 miles, affecting populations ranging from 12 000 to over 900 000 adults. Seven MTFs were identified that would offer clinically significant reductions in distance to relatively large population centers. Discussion: Some MTFs may offer decreased transit times and improved care to large adult populations within their regional trauma systems by developing level 1 or level 2 TC capabilities. The results of this study provide recommendations to focus further study on seven MTFs to identify those that merit further development and integration with their local trauma systems. Level of evidence: IV.

Geographic Distance to Extracorporeal Life Support Centers for Pediatric Patients Within the Continental United States.

OBJECTIVES: Distance to subspecialty surgical care is a known impediment to the delivery of high-quality healthcare. Extracorporeal life support is of benefit to pediatric patients with specific medical conditions. Despite a continued increase in the number of extracorporeal life support centers, not all children have equal access to extracorporeal life support due to geographic constraints, creating a potential disparity in healthcare. We attempted to better define the variation in geographic proximity to extracorporeal life support centers for pediatric patients using the U.S. Decennial Census. DESIGN: A publicly available listing of voluntarily reporting extracorporeal life support centers in 2019 and the 2010 Decennial Census were used to calculate straight-line distances between extracorporeal life support zip code centroids and census block centroids. Disparities in distance to care associated with urbanization were analyzed. SETTING: United States. PATIENTS: None. INTERVENTIONS: Large database review. MEASUREMENTS AND MAIN RESULTS: There were 136 centers providing pediatric extracorporeal life support in 2019. The distribution varied by state with Texas, California, and Florida having the most centers. Over 16 million children (23% of the pediatric population) live greater than 60 miles from an extracorporeal life support center. Significant disparity exists between urban and rural locations with over 47% of children in a rural setting living greater than 60 miles from an extracorporeal life support center compared with 17% of children living in an urban setting. CONCLUSIONS: Disparities in proximity to extracorporeal life support centers were present and persistent across states. Children in rural areas have less access to extracorporeal life support centers based upon geographic distance alone. These findings may affect practice patterns and treatment decisions and are important to the development of regionalization strategies to ensure all children have subspecialty surgical care available to them, including extracorporeal life support.

From far and wide: Geographic distance to pediatric surgical care across Canada.

PURPOSE: Canada is the second largest country in the world, with most of the population located in the southern-most portion of its geography. We sought to define the relative distribution of pediatric surgeons to potential pediatric patients using data from the Canadian census. METHODS: The 2011 Canadian Census and a convenience sample of current Canadian pediatric surgeons were used to calculate straight-line distances between pediatric surgeon postal code centroids and census dissemination block centroids. RESULTS: Currently, there are 74 practicing pediatric surgeons in Canada; 493,345 populated census blocks were identified, and 7,752,075 children were enumerated. The median (IQR) kilometers to the closest pediatric surgeon was 27.99 (11.35, 85.47) kilometers, and 22.7% of Canadian children lived more than 100 km from care. Nearly 13% of children lived greater than 200 km from the nearest pediatric surgeon. CONCLUSION: More than 1.7 million Canadian children, nearly one quarter of all Canadian children, live greater than 100 km from the closest pediatric surgeon. This identifies a disparate group of patients who do not have an equal access-to-care as compared to others in the country. LEVEL OF EVIDENCE: Level IV.

Geographic distance to pediatric surgical care within the continental United States.

PURPOSE: Geographic proximity to pediatric surgical care has not been evaluated using the Decennial Census nor have racial, ethnic, gender, or urbanization variations been reported. This study's aim is to describe proximity of children living in the continental U.S. to a pediatric surgeon with respect to these variations. METHODS: The 2010 American Pediatric Surgical Association member file and the 2010 Decennial Census were used to calculate straight-line distances between pediatric surgeons' zip code centroids and census block centroids. RESULTS: In 2010, 716 practicing pediatric surgeons were identified, 6,182,882 populated Census blocks were identified, and 73,690,271 children were enumerated. Of white non-Hispanic children, 30.1% lived greater than 40 miles from care. Of Native American children, 40.5% lived more than 60 miles from care. Among children 0-5 years of age, the median (IQR) miles to closest pediatric surgeon was 14.2 (6.2, 39.6), and 3,010,698 of these children lived more than 60 miles from care. CONCLUSION: More than 10 million children lived greater than 60 miles from a pediatric surgeon in 2010. Racial, ethnic, age, and urbanization variations in proximity to pediatric surgeons were present. This method is feasible to describe distance-to-care with the upcoming 2020 Decennial Census and may benefit future allocation of pediatric surgeons. LEVEL OF EVIDENCE: IV.

A simple in vitro assay for assessing the efficacy, mechanisms and kinetics of anti-prion fibril compounds.

Prion diseases are caused by the conversion of normal cellular prion proteins (PrP) into lethal prion aggregates. These prion aggregates are composed of proteinase K (PK) resistant fibrils and comparatively PK-sensitive oligomers. Currently there are no anti-prion pharmaceuticals available to treat or prevent prion disease. Methods of discovering anti-prion molecules rely primarily on relatively complex cell-based, tissue slice or animal-model assays that measure the effects of small molecules on the formation of PK-resistant prion fibrils. These assays are difficult to perform and do not detect the compounds that directly inhibit oligomer formation or alter prion conversion kinetics. We have developed a simple cell-free method to characterize the impact of anti-prion fibril compounds on both the oligomer and fibril formation. In particular, this assay uses shaking-induced conversion (ShIC) of recombinant PrP in a 96-well format and resolution enhanced native acidic gel electrophoresis (RENAGE) to generate, assess and detect PrP fibrils in a high throughput fashion. The end-point PrP fibrils from this assay can be further characterized by PK analysis and negative stain transmission electron microscopy (TEM). This cell-free, gel-based assay generates metrics to assess anti-prion fibril efficacy and kinetics. To demonstrate its utility, we characterized the action of seven well-known anti-prion molecules: Congo red, curcumin, GN8, quinacrine, chloropromazine, tetracycline, and TUDCA (taurourspdeoxycholic acid), as well as four suspected anti-prion compounds: trans-resveratrol, rosmarinic acid, myricetin and ferulic acid. These findings suggest that this in vitro assay could be useful in identifying and comprehensively assessing novel anti-prion fibril compounds. Abbreviations: PrP, prion protein; PK, proteinase K; ShIC, shaking-induced conversion; RENAGE, resolution enhanced native acidic gel electrophoresis; TEM, transmission electron microscopy; TUDCA, taurourspdeoxycholic acid; BSE, bovine spongiform encephalopathy; CWD, chronic wasting disease; CJD, Creutzfeldt Jakob disease; GSS, Gerstmann-Sträussler-Scheinker syndrome; FFI, fatal familial insomnia; PrPc, cellular prion protein; recPrPC, recombinant monomeric prion protein; PrPSc, infectious particle of misfolded prion protein; RT-QuIC, real-time quaking-induced conversion; PMCA, Protein Misfolding Cyclic Amplification; LPS, lipopolysaccharide; EGCG, epigallocatechin gallate; GN8, 2-pyrrolidin-1-yl-N-[4-[4-(2-pyrrolidin-1-yl-acetylamino)-benzyl]-phenyl]-acetamide; DMSO, dimethyl sulfoxide; ScN2A, scrapie infected neuroblastoma cells; IC50, inhibitory concentration for 50% reduction; recMoPrP 23-231, recombinant full-length mouse prion protein residues 23-231; EDTA; PICUP, photo-induced cross-linking of unmodified protein; BSA, bovine serum albumin;; PMSF, phenylmethanesulfonyl fluoride.

PrP(Sc)-specific antibodies do not induce prion disease or misfolding of PrP(C) in highly susceptible Tga20 mice.

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders caused by misfolding of a cellular protein PrP(C) into an infectious conformation PrP(Sc). Previously our group demonstrated induction of PrP(Sc)-specific antibodies with a SN6b vaccine that targets regions of the protein that are exposed upon misfolding. There are concerns that these antibodies could function as templates to promote misfolding and cause disease. To evaluate the consequences of prolonged exposure to PrP(Sc)-specific antibodies in a prion sensitized animal, tga20 mice were vaccinated with the SN6b vaccine. No clinical signs of disease were detected up to 255 d post-vaccination, and postmortem assay of brains and spleens revealed no proteinase-K resistant PrP. These results suggest that vaccinating against TSEs with the SN6b antigen is safe from the standpoint of prion disease induction.