Decreases in Antimicrobial Use Associated With Multihospital Implementation of Electronic Antimicrobial Stewardship Tools.

BackgroundAntimicrobial stewards may benefit from comparative data to inform interventions that promote optimal inpatient antimicrobial use.MethodsAntimicrobial stewards from 8 geographically dispersed Veterans Affairs (VA) inpatient facilities participated in the development of antimicrobial use visualization tools that allowed for comparison to facilities of similar complexity. The visualization tools consisted of an interactive web-based antimicrobial dashboard and, later, a standardized antimicrobial usage report updated at user-selected intervals. Stewards participated in monthly learning collaboratives. The percent change in average monthly antimicrobial use (all antimicrobial agents, anti-methicillin-resistant Staphylococcus aureus [anti-MRSA] agents, and antipseudomonal agents) was analyzed using a pre-post (January 2014-January 2016 vs July 2016-January 2018) design with segmented regression and external comparison with uninvolved control facilities (n = 118).ResultsIntervention sites demonstrated a 2.1% decrease (95% confidence interval [CI], -5.7% to 1.6%) in total antimicrobial use pre-post intervention vs a 2.5% increase (95% CI, 0.8% to 4.1%) in nonintervention sites (absolute difference, 4.6%; P = .025). Anti-MRSA antimicrobial use decreased 11.3% (95% CI, -16.0% to -6.3%) at intervention sites vs a 6.6% decrease (95% CI, -9.1% to -3.9%) at nonintervention sites (absolute difference, 4.7%; P = .092). Antipseudomonal antimicrobial use decreased 3.4% (95% CI, -8.2% to 1.7%) at intervention sites vs a 3.6% increase (95% CI, 0.8% to 6.5%) at nonintervention sites (absolute difference, 7.0%; P = .018).ConclusionsComparative data visualization tool use by stewards at 8 VA facilities was associated with significant reductions in overall antimicrobial and antipseudomonal use relative to uninvolved facilities

Intermediate Vancomycin Susceptibility in a Community-associated MRSA Clone

We describe a case of treatment failure caused by a strain of USA300 community-associated methicillin-resistant Staphylococcus aureus (MRSA) with intermediate susceptibility to vancomycin and reduced susceptibility to daptomycin. The strain was isolated from the bone of a 56-year-old man with lumbar osteomyelitis after a 6-week treatment course of vancomycin for catheter-associated septic thrombophlebitis

Wettability decay in an oil-contaminated waste-mineral mixture with dry-wet cycles

The dependency of soil particle wettability on soil water content implies that soils subjected to drying-wetting cycles become wettable with wetting and water repellent with drying. While this has been demonstrated widely, the results are contradictory when water repellent soils are subjected to a sequence of cycles. Added to this, past wettability measurements were seldom done in batches of samples collected from the field at natural or dry water contents, with little appreciation that slight particle size variations, different drying-wetting histories and fabric (as required by different wettability measurement methods) may alter the results. This note presents soil particle wettability—soil water content relations by means of an index test following staged drying and wetting paths over a period of 8 months for an untreated, oil-contaminated anthropogenic soil (a mixture of slag, coal particles, fly ash and mineral particles) from Barry Docks (UK), a site formally used for oil storage, which is to be remediated and redeveloped for housing. The results revealed a decrease in the water repellency and increasing mineralization and bacterial activity with the wetting and drying cycles.postprin

Think twice: A cognitive perspective of an antibiotic timeout intervention to improve antibiotic use

ObjectivesTo understand clinicians' impressions of and decision-making processes regarding an informatics-supported antibiotic timeout program to re-evaluate the appropriateness of continuing vancomycin and piperacillin/tazobactam.MethodsWe implemented a multi-pronged informatics intervention, based on Dual Process Theory, to prompt discontinuation of unwarranted vancomycin and piperacillin/tazobactam on or after day three in a large Veterans Affairs Medical Center. Two workflow changes were introduced to facilitate cognitive deliberation about continuing antibiotics at day three: (1) teams completed an electronic template note, and (2) a paper summary of clinical and antibiotic-related information was provided to clinical teams. Shortly after starting the intervention, six focus groups were conducted with users or potential users. Interviews were recorded and transcribed. Iterative thematic analysis identified recurrent themes from feedback.ResultsThemes that emerged are represented by the following quotations: (1) captures and controls attention ("it reminds us to think about it"), (2) enhances informed and deliberative reasoning ("it makes you think twice"), (3) redirects decision direction ("…because [there was no indication] I just [discontinued] it without even trying"), (4) fosters autonomy and improves team empowerment ("the template… forces the team to really discuss it"), and (5) limits use of emotion-based heuristics ("my clinical concern is high enough I think they need more aggressive therapy…").ConclusionsRequiring template completion to continue antibiotics nudged clinicians to re-assess the appropriateness of specified antibiotics. Antibiotic timeouts can encourage deliberation on overprescribed antibiotics without substantially curtailing autonomy. An effective nudge should take into account clinician's time, workflow, and thought processes

Medical Intensive Care Unit Admission Among Patients With and Without HIV, Hepatitis C Virus, and Alcohol-Related Diagnoses in the United States: A National, Retrospective Cohort Study, 1997-2014.

BACKGROUND: HIV, hepatitis C virus (HCV), and alcohol-related diagnoses (ARD) independently contribute increased risk of all-cause hospitalization. We sought to determine annual medical intensive care unit (MICU) admission rates and relative risk of MICU admission between 1997 and 2014 among people with and without HIV, HCV, and ARD, using data from the largest HIV and HCV care provider in the United States. SETTING: Veterans Health Administration. METHODS: Annual MICU admission rates were calculated among 155,550 patients in the Veterans Aging Cohort Study by HIV, HCV, and ARD status. Adjusted rate ratios and 95% confidence intervals (CIs) were estimated with Poisson regression. Significance of trends in age-adjusted admission rates were tested with generalized linear regression. Models were stratified by calendar period to identify shifts in MICU admission risk over time. RESULTS: Compared to HIV-/HCV-/ARD- patients, relative risk of MICU admission decreased among HIV-mono-infected patients from 61% (95% CI: 1.56 to 1.65) in 1997-2009% to 21% (95% CI: 1.16 to 1.27) in 2010-2014, increased among HCV-mono-infected patients from 22% (95% CI: 1.16 to 1.29) in 1997-2009% to 54% (95% CI: 1.43 to 1.67) in 2010-2014, and remained consistent among patients with ARD only at 46% (95% CI: 1.42 to 1.50). MICU admission rates decreased by 48% among HCV-uninfected patients (P-trend <0.0001) but did not change among HCV+ patients (P-trend = 0.34). CONCLUSION: HCV infection and ARD remain key contributors to MICU admission risk. The impact of each of these conditions could be mitigated with combination of treatment of HIV, HCV, and interventions targeting unhealthy alcohol use

The Inner-Shelf Dynamics Experiment

17 USC 105 interim-entered record; under review.The article of record as published may be found at http://dx.doi.org/10.1175/BAMS-D-19-0281.1The inner shelf, the transition zone between the surfzone and the midshelf, is a dynamically complex region with the evolution of circulation and stratification driven by multiple physical processes. Cross-shelf exchange through the inner shelf has important implications for coastal water quality, ecological connectivity, and lateral movement of sediment and heat. The Inner-Shelf Dynamics Experiment (ISDE) was an intensive, coordinated, multi-institution field experiment from September–October 2017, conducted from the midshelf, through the inner shelf, and into the surfzone near Point Sal, California. Satellite, airborne, shore- and ship-based remote sensing, in-water moorings and ship-based sampling, and numerical ocean circulation models forced by winds, waves, and tides were used to investigate the dynamics governing the circulation and transport in the inner shelf and the role of coastline variability on regional circulation dynamics. Here, the following physical processes are highlighted: internal wave dynamics from the midshelf to the inner shelf; flow separation and eddy shedding off Point Sal; offshore ejection of surfzone waters from rip currents; and wind-driven subtidal circulation dynamics. The extensive dataset from ISDE allows for unprecedented investigations into the role of physical processes in creating spatial heterogeneity, and nonlinear interactions between various inner-shelf physical processes. Overall, the highly spatially and temporally resolved oceanographic measurements and numerical simulations of ISDE provide a central framework for studies exploring this complex and fascinating region of the ocean.U.S. Office of Naval Research (ONR)ONR Departmental Research Initiative (DRI)Inner-Shelf Dynamics Experiment (ISDE

Genetic Networks of Liver Metabolism Revealed by Integration of Metabolic and Transcriptional Profiling

Although numerous quantitative trait loci (QTL) influencing disease-related phenotypes have been detected through gene mapping and positional cloning, identification of the individual gene(s) and molecular pathways leading to those phenotypes is often elusive. One way to improve understanding of genetic architecture is to classify phenotypes in greater depth by including transcriptional and metabolic profiling. In the current study, we have generated and analyzed mRNA expression and metabolic profiles in liver samples obtained in an F2 intercross between the diabetes-resistant C57BL/6 leptinob/ob and the diabetes-susceptible BTBR leptinob/ob mouse strains. This cross, which segregates for genotype and physiological traits, was previously used to identify several diabetes-related QTL. Our current investigation includes microarray analysis of over 40,000 probe sets, plus quantitative mass spectrometry-based measurements of sixty-seven intermediary metabolites in three different classes (amino acids, organic acids, and acyl-carnitines). We show that liver metabolites map to distinct genetic regions, thereby indicating that tissue metabolites are heritable. We also demonstrate that genomic analysis can be integrated with liver mRNA expression and metabolite profiling data to construct causal networks for control of specific metabolic processes in liver. As a proof of principle of the practical significance of this integrative approach, we illustrate the construction of a specific causal network that links gene expression and metabolic changes in the context of glutamate metabolism, and demonstrate its validity by showing that genes in the network respond to changes in glutamine and glutamate availability. Thus, the methods described here have the potential to reveal regulatory networks that contribute to chronic, complex, and highly prevalent diseases and conditions such as obesity and diabetes

Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial

Background Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity. Methods This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3–5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated. Discussion In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19. Trial registration ClinicalTrials.gov NCT04397718. Registered on May 21, 202

The formation and fate of internal waves in the South China Sea

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 521 (2015): 65-69, doi:10.1038/nature14399.Internal gravity waves, the subsurface analogue of the familiar surface gravity waves that break on beaches, are ubiquitous in the ocean. Because of their strong vertical and horizontal currents, and the turbulent mixing caused by their breaking, they impact a panoply of ocean processes, such as the supply of nutrients for photosynthesis1, sediment and pollutant transport2 and acoustic transmission3; they also pose hazards for manmade structures in the ocean4. Generated primarily by the wind and the tides, internal waves can travel thousands of kilometres from their sources before breaking5, posing severe challenges for their observation and their inclusion in numerical climate models, which are sensitive to their effects6-7. Over a decade of studies8-11 have targeted the South China Sea, where the oceans’ most powerful internal waves are generated in the Luzon Strait and steepen dramatically as they propagate west. Confusion has persisted regarding their generation mechanism, variability and energy budget, however, due to the lack of in-situ data from the Luzon Strait, where extreme flow conditions make measurements challenging. Here we employ new observations and numerical models to (i) show that the waves begin as sinusoidal disturbances rather than from sharp hydraulic phenomena, (ii) reveal the existence of >200-m-high breaking internal waves in the generation region that give rise to turbulence levels >10,000 times that in the open ocean, (iii) determine that the Kuroshio western boundary current significantly refracts the internal wave field emanating from the Luzon Strait, and (iv) demonstrate a factor-of-two agreement between modelled and observed energy fluxes that enables the first observationally-supported energy budget of the region. Together, these findings give a cradle-to-grave picture of internal waves on a basin scale, which will support further improvements of their representation in numerical climate predictions.Our work was supported by the U.S. Office of Naval Research and the Taiwan National Science Council.2015-10-2