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Dr. Srinivasan is the Deputy Director for Program Improvement in the Division of Healthcare Quality Promotion at the Centers for Disease Control and Prevention and a recently retired Captain in the United States Public Health Service. Before joining CDC, he was an Assistant Professor of Medicine in the Infectious Diseases Division at the Johns Hopkins School of Medicine where he was the Founding Director of the Johns Hopkins Antibiotic Management Program and the Associate Hospital Epidemiologist. Even as a medical student, I did some work on healthcare policy related to the rollout of TennCare, which I really enjoyed. Healthcare epi was exciting to me because it presented an opportunity to conduct health policy for the healthcare system.

A bstract As the partons in a high energy jet propagate through the droplet of quark-gluon plasma (QGP) produced in a heavy-ion collision they lose energy to, kick, and are kicked by the medium. The resulting modifications to the parton shower encode information about the microscopic nature of QGP. A direct consequence, however, is that the momentum and energy lost by the parton shower are gained by the medium and, since QGP is a strongly coupled liquid, this means that the jet excites a wake in the droplet of QGP. After freezeout, this wake becomes soft hadrons with net momentum in the jet direction meaning that what an experimentalist later reconstructs as a jet includes hadrons originating from both the modified parton shower and its wake. This has made it challenging to find experimental observables that provide an unambiguous view of the dynamical response of a droplet of QGP to a jet shooting through it. Recent years have seen significant substantial advances in the theoretical and experimental understanding of the substructure of jets, in particular, using correlation functions, E n → 1 ⋯ E n → k , of the energy flux operator in proton-proton collisions and, recently, in heavy-ion collisions. So far, such studies have focused primarily on the two-point correlator, which allows for the identification of the angular scale of the underlying dynamics. Higher-point correlators hold the promise of mapping out the dynamics themselves. In this paper we perform the first study of the shape-dependent three-point energy-energy-energy correlator in heavy-ion collisions. Using the Hybrid Model to simulate the interactions of high energy jets with the QGP medium, we show that the three-point correlator presents us with a striking new opportunity. We find that hadrons originating from wakes are the dominant contribution to the three-point correlator in the kinematic regime in which the three points are well-separated in angle, forming a roughly equilateral triangle. This equilateral region of the correlator is far from the region populated by collinear vacuum emissions, making it a canvas on which jet wakes are laid out, where experimentalists can map their shapes. Our work provides a key step towards the systematic use of energy correlators to image and unravel the dynamical response of a droplet of QGP that has been probed by a passing jet, and motivates numerous experimental and theoretical studies.

A bstract The ATLAS collaboration has introduced and implemented a strategy for selecting, and measuring the properties of, large-radius jets composed from skinny subjets in heavy ion collisions at the LHC. We show how measurements of these jets teach us about the resolution length L res of quark-gluon plasma (QGP) and can teach us how jet substructure shapes the wakes that jets excite in the droplets of QGP through which they pass. We begin by using Hybrid Model calculations to reproduce experimental measurements published by ATLAS in 2023 of R AA for large-radius jets in PbPb collisions, identified via first reconstructing skinny anti- k t R = 0.2 subjets and then clustering R = 1 jets using them as constituents. We investigate how R AA for these large-radius jets depends on the angle between the two skinny subjets involved in the final reclustering step of the R = 1 jet. We show how these observables depend on L res and demonstrate that the published ATLAS data rule out L res = ∞: these data are inconsistent with any picture in which an entire parton shower loses energy coherently as if it were a single colored object. Demonstrating that the QGP can resolve partons within a parton shower is central to the broader program of using jet quenching measurements to probe QGP. We make further use of this setup by analyzing the response of the medium to the passage of large-radius R = 2 jets containing two skinny R = 0 . 2 subjets, produced in gamma-jet events, identified as above. We introduce novel jet-shape observables that allow us to visualize the angular shape of the soft hadrons originating from the wakes that wide jets with two skinny subjets excite in the droplet of QGP, as a function of the angular separation between the subjets. We find that even when the two hard subjets are 0.8 to 1.0 radians apart, a single broad wake is produced. Only when the two subjets are even farther apart is the presence of two sub-wakes revealed. We show that the way in which jet structure shapes jet wakes can be visualized with similar clarity in experimental data by measuring the observables we have introduced using only those hadrons with low transverse momenta. These observables thus offer a new and distinctive way of seeing jet wakes in heavy ion collision data.

Indiscriminate antimicrobial use has plagued medicine since antibiotics were first introduced into clinical practice >70 years ago. Infectious diseases physicians and public health officials have advocated for preservation of these life-saving drugs for many years. With rising burden of antimicrobial-resistant organisms and Clostridium difficile infections, halting unnecessary antimicrobial use has become one of the largest public health concerns of our time. Inappropriate antimicrobial use has been quantified in various settings using numerous definitions; however, no established reference standard exists. With mounting national efforts to improve antimicrobial use, a consensus definition and standard method of measuring appropriate antimicrobial use is imperative. We review existing literature on systematic approaches to define and measure appropriate antimicrobial use, and describe a collaborative effort at developing standardized audit tools for assessing the quality of antimicrobial prescribing.

The prevalence and effects of inappropriate empirical antibiotic therapy for bloodstream infections are unclear. We aimed to establish the population-level burden, predictors, and mortality risk of in-vitro susceptibility-discordant empirical antibiotic therapy among patients with bloodstream infections. Our retrospective cohort analysis of electronic health record data from 131 hospitals in the USA included patients with suspected—and subsequently confirmed—bloodstream infections who were treated empirically with systemic antibiotics between Jan 1, 2005, and Dec 31, 2014. We included all patients with monomicrobial bacteraemia caused by common bloodstream pathogens who received at least one systemic antibiotic either on the day blood cultures were drawn or the day after, and for whom susceptibility data were available. We calculated the prevalence of discordant empirical antibiotic therapy—which was defined as receiving antibiotics on the day blood culture samples were drawn to which the cultured isolate was not susceptible in vitro—overall and by hospital type by using regression tree analysis. We used generalised estimating equations to identify predictors of receiving discordant empirical antibiotic therapy, and used logistic regression to calculate adjusted odds ratios for the relationship between in-hospital mortality and discordant empirical antibiotic therapy. 21 608 patients with bloodstream infections received empirical antibiotic therapy on the day of first blood culture collection. Of these patients, 4165 (19%) received discordant empirical antibiotic therapy. Discordant empirical antibiotic therapy was independently associated with increased risk of mortality (adjusted odds ratio 1·46 [95% CI, 1·28–1·66]; p<0·0001), a relationship that was unaffected by the presence or absence of resistance or sepsis or septic shock. Infection with antibiotic-resistant species strongly predicted receiving discordant empirical therapy (adjusted odds ratio 9·09 [95% CI 7·68–10·76]; p<0·0001). Most incidences of discordant empirical antibiotic therapy and associated deaths occurred among patients with bloodstream infections caused by Staphylococcus aureus or Enterobacterales. Approximately one in five patients with bloodstream infections in US hospitals received discordant empirical antibiotic therapy, receipt of which was closely associated with infection with antibiotic-resistant pathogens. Receiving discordant empirical antibiotic therapy was associated with increased odds of mortality overall, even in patients without sepsis. Early identification of bloodstream pathogens and resistance will probably improve population-level outcomes. US National Institutes of Health, US Centers for Disease Control and Prevention, and US Agency for Healthcare Research and Quality.

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

Background. The National Action Plan to Combat Antibiotic Resistant Bacteria calls for all US hospitals to improve antibiotic prescribing as a key prevention strategy for resistance and clostridium difficile. Antibiotic stewardship programs (ASPs) will be important in this effort but implementation is not well understood. Methods. We analyzed the 2014 National Healthcare Safety Network Annual Hospital Survey to describe ASPs in US acute care hospitals as defined by the Center for Disease Control and Prevention's (CDC) Core Elements for Hospital ASPs. Univariate analyses were used to assess stewardship infrastructure and practices by facility characteristics and a multivariate model determined factors associated with meeting all ASP core elements. Results. Among 4184 US hospitals, 39% reported having an ASP that met all 7 core elements. Although hospitals with greater than 200 beds (59%) were more likely to have ASPs, 1 in 4 (25%) of hospitals with less than 50 beds reported achieving all 7 CDC-defined core elements of a comprehensive ASP. The percent of hospitals in each state that reported all seven elements ranged from 7% to 58%. In the multivariate model, written support (adjusted relative risk [RR] 7.2 [95% confidence interval [CI], 6.2–8.4]; P < .0001) or salary support (adjusted RR 1.5 [95% CI, 1.4–1.6]; P < .0001) were significantly associated with having a comprehensive ASP. Conclusions. Our findings show that ASP implementation varies across the United States and provide a baseline to monitor progress toward national goals. Comprehensive ASPs can be established in facilities of any size and hospital leadership support for antibiotic stewardship appears to drive the establishment of ASPs.

Abstract Background To provide a standardized, risk-adjusted method for summarizing antibiotic use (AU), enable hospitals to track their AU over time and compare their AU data to national benchmarks, the Centers for Disease Control and Prevention developed the Standardized Antimicrobial Administration Ratio (SAAR). Methods Hospitals reporting to the National Healthcare Safety Network (NHSN) AU Option collect and submit aggregated AU data electronically as antimicrobial days of therapy per patient days present. SAARs were developed for specific NHSN adult and pediatric patient care locations and cover five antimicrobial agent categories: (1) broad-spectrum agents predominantly used for hospital-onset/multi-drug resistant bacteria; (2) broad-spectrum agents predominantly used for community-acquired infections; (3) anti-methicillin-resistant Staphylococcus aureus agents; (4) agents predominantly used for surgical site infection prophylaxis; and (5) all antibiotic agents. The SAAR is an observed-to-predicted use ratio where predicted use is estimated from a statistical model; a SAAR of 1 indicates that observed use and predicted use are equal. Results Most location-level SAARs were statistically significantly different than 1: adult locations up to 52% lower than 1 and up to 41% higher than 1. Median SAARs in adult and pediatric ICUs had a range of 0.667-1.119. SAAR distributions serve as an external comparison to national SAARs. Conclusions This is the first aggregate AU metric that uses point-of-care, antimicrobial administration data electronically reported to a national surveillance system to enable risk-adjusted, AU comparisons across multiple hospitals. Endorsed by the National Quality Forum, SAARs provide AU benchmarks that stewardship programs can use to help drive improvements. The Centers for Disease Control and Prevention has developed a new metric, the standardized antimicrobial administration ratio, that uses point-of-care, antimicrobial administration data electronically reported to a national surveillance system, to enable risk-adjusted, antibiotic use comparisons across multiple hospitals and health systems.

Background. Better understanding of medical students' perceptions, attitudes, and knowledge about antimicrobial prescribing practices could facilitate more effective education of these future prescribers. Methods. A 24-item electronic survey on antimicrobial prescribing and education was administered to fourth-year medical students at the University of Miami, the Johns Hopkins University, and the University of Washington (January–March 2012). Results. Three hundred seventeen of 519 (61%) students completed the survey; 92% of respondents agreed that strong knowledge of antimicrobials is important in their careers, and 90% said that they would like more education on appropriate use of antimicrobials. Mean correct knowledge score (11 items) was 51%, with statistically significant differences between study sites and sources of information used to learn about antimicrobials. Only 15% had completed a clinical infectious diseases rotation during medical school; those who had done so rated the quality of their antimicrobial education significantly higher compared to those who had not (mean, 3.93 vs 3.44, on a 5-point scale; P = .0003). There were no statistically significant associations between knowledge scores and having had an infectious diseases clinical elective. Only one-third of respondents perceived their preparedness to be adequate in some fundamental principles of antimicrobial use. Conclusions. Differences exist between medical schools in educational resources used, perceived preparedness, and knowledge about antimicrobial use. Variability in formative education could frame behaviors and prescribing practices in future patient care. To help address the growing problem of antimicrobial resistance, efforts should be undertaken to ensure that our future doctors are well educated in the principles and practices of appropriate use of antibiotics and antimicrobial stewardship.

We performed a case–control study across 25 hospitals in India for the period of January–June 2021 to evaluate the reasons for an COVID-19–associated mucormycosis (CAM) outbreak. We investigated whether COVID-19 treatment practices (glucocorticoids, zinc, tocilizumab, and others) were associated with CAM. We included 1,733 cases of CAM and 3,911 age-matched COVID-19 controls. We found cumulative glucocorticoid dose (odds ratio [OR] 1.006, 95% CI 1.004–1.007) and zinc supplementation (OR 2.76, 95% CI 2.24–3.40), along with elevated C-reactive protein (OR 1.004, 95% CI 1.002–1.006), host factors (renal transplantation [OR 7.58, 95% CI 3.31–17.40], diabetes mellitus [OR 6.72, 95% CI 5.45–8.28], diabetic ketoacidosis during COVID-19 [OR 4.41, 95% CI 2.03–9.60]), and rural residence (OR 2.88, 95% CI 2.12–3.79), significantly associated with CAM. Mortality rate at 12 weeks was 32.2% (473/1,471). We emphasize the judicious use of COVID-19 therapies and optimal glycemic control to prevent CAM.