1238. A National Comparison of Antibiograms Between Veterans Affairs Long-Term Care Facilities and Affiliated Hospitals

Background: Long-term care facilities (LTCFs) face several barriers to creating antibiograms. Here, we evaluate if LTCFs can use antibiograms from affiliated hospitals as their own antibiogram. Methods: Facility-specific antibiograms were created for all Veterans Affairs (VA) LTCFs and VA Medical Centers (VAMCs) for 2017. LTCFs and affiliated VAMCs were paired and classified as being on the same campus or geographically distinct campuses based on self-report. For each pair, Escherichia colisusceptibility rates (%S) to cefazolin, ceftriaxone, cefepime, ciprofloxacin, nitrofurantoin, sulfamethoxazole/trimethoprim, ampicillin/sulbactam, piperacillin/tazobactam, and imipenem were compared. As guidelines discourage empiric use of antibiotics if susceptibility rates are Results: A total of 119 LTCFs and their affiliated VAMCs were included in this analysis, with 70.6% (n = 84) of facilities located on the same campus and 29.4% (n = 35) on geographically distinct campuses. The table below shows the overall clinical concordance (agreement) of LTCFs with their affiliated VAMC in regards to E. coli %S to the compared antibiotics. No significant differences were found when comparing LTCFs on the same campus vs. geographically distinct campuses. [Abstract contains a chart of Agreement Rates between LTCFs and Affiliated VAMCs and Antibiotics ] Conclusion: Antibiograms between LTCFs and affiliated VAMCs had a high concordance, except for sulfamethoxazole/trimethoprim, cefazolin and ceftriaxone in regards to susceptibility rates of E. coli. Facilities on the same campus were found to have similar concordance rates to geographically distinct facilities. Future studies are needed to investigate how the various approaches to creating LTCF-specific antibiograms are associated with clinical outcomes

1437. Family Duty and Safety Linked to Overcoming Attitudinal Barriers to Adult Pneumococcal Vaccination in Disparate Populations

Background: Minority adult populations are at a higher risk for invasive pneumococcal disease and also have significantly lower vaccination rates when compared with the general population. Ingrained attitudes are a significant barrier to receipt of pneumococcal vaccine in these disparate populations, and therefore we tested targeted informational messaging to overcome these. Methods: A survey instrument of attitudinal questions related to pneumococcal vaccination was administered via YouGov, an online public national survey house in 2017. Socioeconomic information was captured and linked to baseline Likert scale attitudinal question responses. Respondents were randomly assigned into subsamples that received different science-based messages that included information on pneumococcal vaccines related to: pneumonia prevention, fatality/consequences, vaccine safety information, family duty/safety, and a combined vignette including all of these. Because of the random assignment, any differences observed in the respondents’ outcomes across subsamples can be attributed to the messages. Descriptive statistics were used to compare the persuasive effectiveness of these messages to conventional vaccine information across racial and ethnic groups. Results: A total of 2,608 respondents, 1,327 (51%) white and 1,281 (49%) non-white (over-sampled) were represented. Of the total respondents as well as in white, and non-white respondents, the combined vignette was associated with positive coefficients of b = 0.26, b = 0.24, and b = 0.32, respectively (P-values all \u3c0.05). In whites, the vaccine safety information and family duty/safety also had significant coefficients b = 0.24 ( = P = 0.012) and b = 0.24 (P = 0016), respectively. In non-Whites, family duty/safety was the only additional message with a significant coefficient b = 0.25 (P = 0.007). Conclusion: In this survey assessing attitudes toward pneumococcal vaccination across racial and ethnic subpopulations, the disparate population was persuaded to receive the vaccine only when family duty and safety were linked within the informational messages. Future studies implementing this informational messaging strategy should be performed to validate this finding

Multiple-constraint inversion of SCOPE. Evaluating the potential of GPP and SIF for the retrieval of plant functional traits

The most recent efforts to provide remote sensing (RS) estimates of plant function rely on the combination of Radiative Transfer Models (RTM) and Soil-Vegetation-Atmosphere Transfer (SVAT) models, such as the Soil-Canopy Observation Photosynthesis and Energy fluxes (SCOPE) model. In this work we used ground spectroradiometric and chamber-based CO2 flux measurements in a nutrient manipulated Mediterranean grassland in order to: 1) develop a multiple-constraint inversion approach of SCOPE able to retrieve vegetation biochemical, structural as well as key functional traits, such as chlorophyll concentration (Cab), leaf area index (LAI), maximum carboxylation rate (Vcmax) and the Ball-Berry sensitivity parameter (m); and 2) compare the potential of the of gross primary production (GPP) and sun-induced fluorescence (SIF), together with up-welling Thermal Infrared (TIR) radiance and optical reflectance factors (RF), to estimate such parameters. The performance of the proposed inversion method as well as of the different sets of constraints was assessed with contemporary measurements of water and heat fluxes and leaf nitrogen content, using pattern-oriented model evaluation. The multiple-constraint inversion approach proposed together with the combination of optical RF and diel GPP and TIR data provided reliable estimates of parameters, and improved predicted water and heat fluxes. The addition of SIF to this scheme slightly improved the estimation of m. Parameter estimates were coherent with the variability imposed by the fertilization and the seasonality of the grassland. Results revealed that fertilization had an impact on Vcmax, while no significant differences were found for m. The combination of RF, SIF and diel TIR data weakly constrained functional traits. Approaches not including GPP failed to estimate LAI; however GPP overestimated Cab in the dry period. These problems might be related to the presence of high fractions of senescent leaves in the grassland. The proposed inversion approach together with pattern-oriented model evaluation open new perspectives for the retrieval of plant functional traits relevant for land surface models, and can be utilized at various research sites where hyperspectral remote sensing imagery and eddy covariance flux measurements are simultaneously taken

ANKRD26 and Its Interacting Partners TRIO, GPS2, HMMR and DIPA Regulate Adipogenesis in 3T3-L1 Cells

Partial inactivation of the Ankyrin repeat domain 26 (Ankrd26) gene causes obesity and diabetes in mice and increases spontaneous and induced adipogenesis in mouse embryonic fibroblasts. However, it is not yet known how the Ankrd26 protein carries out its biological functions. We identified by yeast two-hybrid and immunoprecipitation assays the triple functional domain protein (TRIO), the G protein pathway suppressor 2 (GPS2), the delta-interacting protein A (DIPA) and the hyaluronan-mediated motility receptor (HMMR) as ANKRD26 interacting partners. Adipogenesis of 3T3-L1 cells was increased by selective down-regulation of Ankrd26, Trio, Gps2, Hmmr and Dipa. Furthermore, GPS2 and DIPA, which are normally located in the nucleus, were translocated to the cytoplasm, when the C-terminus of ANKRD26 was introduced into these cells. These findings provide biochemical evidence that ANKRD26, TRIO, GPS2 and HMMR are novel and important regulators of adipogenisis and identify new targets for the modulation of adipogenesis

Rhamm-/- mice are defective in skin wound repair due to aberrantERK1,2 signaling in fibroblast migration

Rhamm (receptor for hyaluronan-mediated motility) is an hyaluronan binding protein with limited expression in normal tissues and high expression in advanced cancers. To understand its physiological functions and identify the molecular mechanisms underlying these functions, we created mice with a genetic deletion of Rhamm. We show that Rhamm(−/−) fibroblasts fail to resurface scratch wounds >3 mm or invade hyaluronan-supplemented collagen gels in culture. We identify a requirement for Rhamm in the localization of CD44 to the cell surface, formation of CD44–ERK1,2 (extracellular-regulated kinase 1,2) complexes, and activation/subcellular targeting of ERK1,2 to the cell nucleus. We also show that cell surface Rhamm, restricted to the extracellular compartment by linking recombinant protein to beads, and expression of mutant active mitogen-activated kinase kinase 1 (Mek1) are sufficient to rescue aberrant signaling through CD44–ERK1,2 complexes in Rh(−/−) fibroblasts. ERK1,2 activation and fibroblast migration/differentiation is also defective during repair of Rh(−/−) excisional skin wounds and results in aberrant granulation tissue in vivo. These results identify Rhamm as an essential regulator of CD44–ERK1,2 fibroblast motogenic signaling required for wound repair

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Antiarrhythmic and antioxidant activity of novel pyrrolidin-2-one derivatives with adrenolytic properties

A series of novel pyrrolidin-2-one derivatives (17 compounds) with adrenolytic properties was evaluated for antiarrhythmic, electrocardiographic and antioxidant activity. Some of them displayed antiarrhythmic activity in barium chloride-induced arrhythmia and in the rat coronary artery ligation-reperfusion model, and slightly decreased the heart rate, prolonged P–Q, Q–T intervals and QRS complex. Among them, compound EP-40 (1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one showed excellent antiarrhythmic activity. This compound had significantly antioxidant effect, too. The present results suggest that the antiarrhythmic effect of compound EP-40 is related to their adrenolytic and antioxidant properties. A biological activity prediction using the PASS software shows that compound EP-35 and EP-40 can be characterized by antiischemic activity; whereas, compound EP-68, EP-70, EP-71 could be good tachycardia agents

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially