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Antimicrobial stewardship improves patient care and reduces antimicrobial resistance, inappropriate use, and adverse outcomes. Despite high-profile mandates for antimicrobial stewardship programs across the healthcare continuum, descriptive data, and recommendations for dedicated resources, including appropriate physician, pharmacist, data analytics, and administrative staffing support, are not robust. This review summarizes the current literature on antimicrobial stewardship staffing and calls for the development of minimum staffing recommendations.
Building on current research regarding constitutional migration, this article shows how constitutional provisions protecting religious freedom (“subject to public order”) arrived in the Islamic Republic of Pakistan, not via colonial British or traditional Islamic sources—both explicitly rejected—but via deliberate constitutional borrowing from “anti-colonial” precursors in Ireland and, especially, India. Drawing on Ernesto Laclau's notion of “empty signifiers,” the article highlights the shifting political circumstances that transformed the meaning of Pakistan's borrowed constitutional provisions. Even as core texts guaranteeing an individual's right to peaceful religious practice were imported, political, legal, and conceptual modulations ensured that specific forms of peaceful religious practice were refashioned as a source of religious provocation and, therein, public disorder. Far from protecting religious freedom, this repurposing of imported constitutional clauses tied to “the politics of public order” underpinned the formal legal restriction of an otherwise explicit right.
Gender differences in symptomatology in chronic schizophrenia and first episode psychosis patients have often been reported. However, little is known about gender differences in those at risk of psychotic disorders. This study investigated gender differences in symptomatology, drug use, comorbidity (i.e. substance use, affective and anxiety disorders) and global functioning in patients with an at-risk mental state (ARMS) for psychosis.
The sample consisted of 336 ARMS patients (159 women) from the prodromal work package of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI; 11 centers). Clinical symptoms, drug use, comorbidity and functioning were assessed at first presentation to an early detection center using structured interviews.
In unadjusted analyses, men were found to have significantly higher rates of negative symptoms and current cannabis use while women showed higher rates of general psychopathology and more often displayed comorbid affective and anxiety disorders. No gender differences were found for global functioning. The results generally did not change when corrected for possible cofounders (e.g. cannabis use). However, most differences did not withstand correction for multiple testing.
Findings indicate that gender differences in symptomatology and comorbidity in ARMS are similar to those seen in overt psychosis and in healthy controls. However, observed differences are small and would only be reliably detected in studies with high statistical power. Moreover, such small effects would likely not be clinically meaningful.
In both India and Pakistan, parliament is constitutionally endowed with ‘constituent power’, that is, the power to introduce constitutional amendments via procedures laid down in the constitution itself. Duly promulgated amendments, however, are occasionally struck down when Supreme Court judges see them as violating what the judges themselves define as the ‘essential features’ of each country’s constitutional ‘basic structure’. I trace the migration of basic structure jurisprudence from India to Pakistan, focusing on the ways in which it has elevated the power of judges over that of elected officials in the realm of religion-state relations. Specifically, I highlight the ways in which judicial independence vis-à-vis judicial appointments has been described as an essential feature of each country’s constitution, greatly enhancing the autonomous power of judges to mould constitutional benches that, in turn, define India’s constitutional understanding of secularism and Pakistan’s relationship with Islam.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
OBJECTIVES/SPECIFIC AIMS: Objectives and goals of this study will be to: (1) compare fecal microbiota and fecal organic acids in irritable bowel syndrome (IBS) patients and controls and (2) investigate the association between colonic transit and fecal microbiota in IBS patients and controls. METHODS/STUDY POPULATION: We propose an investigation of fecal organic acids, colonic transit and fecal microbiota in 36 IBS patients and 18 healthy controls. The target population will be adults ages 18–65 years meeting Rome IV criteria for IBS (both diarrhea- and constipation-predominant, IBS-D and IBS-C) and asymptomatic controls. Exclusion criteria are: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, visceral cancer, chronic infectious disease, immunodeficiency, uncontrolled thyroid disease, liver disease, or elevated AST/ALT>2.0× the upper limit of normal, (b) prior radiation therapy of the abdomen or abdominal surgeries with the exception of appendectomy or cholecystectomy >6 months before study initiation, (c) ingestion of prescription, over the counter, or herbal medications affecting gastrointestinal transit or study interpretation within 6 months of study initiation for controls or within 2 days before study initiation for IBS patients, (d) pregnant females, (e) antibiotic usage within 3 months before study participation, (f) prebiotic or probiotic usage within the 2 weeks before study initiation, (g) tobacco users. Primary outcomes will be fecal bile acid excretion and profile, short-chain fatty acid excretion and profile, colonic transit, and fecal microbiota. Secondary outcomes will be stool characteristics based on responses to validated bowel diaries. Stool samples will be collected from participants during the last 2 days of a 4-day 100 g fat diet and split into 3 samples for fecal microbiota, SCFA, and bile acid analysis and frozen. Frozen aliquots will be shipped to the Metabolite Profiling Facility at Purdue University and the Mayo Clinic Department of Laboratory Medicine and Pathology for SCFA and bile acid measurements, respectively. Analysis of fecal microbiota will be performed in the research laboratory of Dr David Nelson in collaboration with bioinformatics expertise affiliated with the Nelson lab. Colonic transit time will be measured with the previously validated method using radio-opaque markers. Generalized linear models will be used as the analysis framework for comparing study endpoints among groups. RESULTS/ANTICIPATED RESULTS: This study seeks to examine the innovative concept that specific microbial signatures are associated with increased fecal excretion of organic acids to provide unique insights on a potential mechanistic link between altered intraluminal organic acids and fecal microbiota. DISCUSSION/SIGNIFICANCE OF IMPACT: Results may lead to development of targets for novel therapies and diagnostic biomarkers for IBS, emphasizing the role of the fecal metabolome.
The purpose of this study was to investigate the 10-year impact of Hurricane Katrina on the incidence of acute myocardial infarction (AMI) along with contributing risk factors and any alteration in chronobiology of AMI.
A single-center, retrospective, comparison study of AMI incidence was performed at Tulane University Health Sciences Center from 2 years before Hurricane Katrina to 10 years after Hurricane Katrina. A 6-year, pre-Katrina and 10-year, post-Katrina cohort were also compared according to pre-specified demographic, clinical, and chronobiological data.
AMI incidence increased from 0.7% (150/21,079) to 2.8% (2,341/84,751) post-Katrina (P<0.001). The post-Katrina cohort had higher rates of coronary artery disease (36.4% vs. 47.9%, P=0.01), diabetes mellitus (31.3% vs. 39.9%, P=0.04), hyperlipidemia (45.4% vs. 59.3%, P=0.005), smoking (34.4% vs. 53.8%, P<0.001), drug abuse (10.2% vs. 15.4%, P=0.02), psychiatric illness (6.7% vs. 14.9%, P<0.001), medication non-adherence (7.3% vs. 15.3%, P<0.001), and lack of employment (7.2% vs. 16.4%, P<0.001). The post-Katrina group had increased rates of AMI during nights (29.8% vs. 47.8%, P<0.001) and weekends (16.1% vs. 29.1%, P<0.001).
Even 10 years after the storm, Hurricane Katrina continues to be associated with increased incidence of AMI, higher prevalence of traditional cardiovascular and psychosocial risk factors, and an altered chronobiology of AMI toward nights and weekends. (Disaster Med Public Health Preparedness. 2019;13:217–222)
To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing.
A convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network.
The following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing.
In total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some “usually” or “always” preferred using the most broad-spectrum empiric antimicrobials possible (32%). Nearly all (99%) reported reviewing antimicrobial appropriateness at 48–72 hours, but only 55% reported “always” doing so. Furthermore, 45% of respondents felt that they had not received adequate training regarding antimicrobial prescribing. Some respondents lacked confidence selecting empiric therapy using antibiograms (30%), interpreting susceptibility results (24%), de-escalating therapy (18%), and determining duration of therapy (31%). Postprescription review and feedback (PPRF) was the most commonly cited AS intervention (79%) with potential to improve patient care.
Barriers to appropriate antimicrobial selection and de-escalation of antimicrobial therapy were identified among front-line prescribers in acute-care hospitals. Prescribers desired more AS-related education and identified PPRF as the most helpful AS intervention to improve patient care. Educational interventions should be preceded by and tailored to local assessment of educational needs.
While our fascination with understanding the past is sufficient to warrant an increased focus on synthesis, solutions to important problems facing modern society require understandings based on data that only archaeology can provide. Yet, even as we use public monies to collect ever-greater amounts of data, modes of research that can stimulate emergent understandings of human behavior have lagged behind. Consequently, a substantial amount of archaeological inference remains at the level of the individual project. We can more effectively leverage these data and advance our understandings of the past in ways that contribute to solutions to contemporary problems if we adapt the model pioneered by the National Center for Ecological Analysis and Synthesis to foster synthetic collaborative research in archaeology. We propose the creation of the Coalition for Archaeological Synthesis coordinated through a U.S.-based National Center for Archaeological Synthesis. The coalition will be composed of established public and private organizations that provide essential scholarly, cultural heritage, computational, educational, and public engagement infrastructure. The center would seek and administer funding to support collaborative analysis and synthesis projects executed through coalition partners. This innovative structure will enable the discipline to address key challenges facing society through evidentially based, collaborative synthetic research.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
This paper aims to situate functional abstraction in light of systems thinking. While function does not extensively appear in systems thinking literature, the literature does identify function as part of systems thinking that enables us to recognize and connect that function has a role in building a systems thinking approach for students. A systems thinking approach is valuable for students since it helps them view a system holistically. In this research, we measure how well students are able to abstract function. We asked students to generate functions for two different products and examined how students taught functional modeling and function enumeration compare to students who are only taught function enumeration. The student responses were examined using a rubric that we developed and validated for assessing function. This rubric may be used to classify functions by correctness (correct, partially correct, and incorrect) and categories (high level, interface, low level, and ambiguous). On questions where students were not explicitly asked to write a high-level function or low-level function, and so on, students who were taught functional modeling were able to better demonstrate systems thinking in their responses (low-level and interface functions) than those students who were only taught function enumeration.
OBJECTIVES/SPECIFIC AIMS: To create a searchable public registry of all Quality Improvement (QI) projects. To incentivize the medical professionals at UF Health to initiate quality improvement projects by reducing startup burden and providing a path to publishing results. To reduce the review effort performed by the internal review board on projects that are quality improvement Versus research. To foster publication of completed quality improvement projects. To assist the UF Health Sebastian Ferrero Office of Clinical Quality & Patient Safety in managing quality improvement across the hospital system. METHODS/STUDY POPULATION: This project used a variant of the spiral software development model and principles from the ADDIE instructional design process for the creation of a registry that is web based. To understand the current registration process and management of quality projects in the UF Health system a needs assessment was performed with the UF Health Sebastian Ferrero Office of Clinical Quality & Patient Safety to gather project requirements. Biweekly meetings were held between the Quality Improvement office and the Clinical and Translational Science – Informatics and Technology teams during the entire project. Our primary goal was to collect just enough information to answer the basic questions of who is doing which QI project, what department are they from, what are the most basic details about the type of project and who is involved. We also wanted to create incentive in the user group to try to find an existing project to join or to commit the details of their proposed new project to a data registry for others to find to reduce the amount of duplicate QI projects. We created a series of design templates for further customization and feature discovery. We then proceed with the development of the registry using a Python web development framework called Django, which is a technology that powers Pinterest and the Washington Post Web sites. The application is broken down into 2 main components (i) data input, where information is collected from clinical staff, Nurses, Pharmacists, Residents, and Doctors on what quality improvement projects they intend to complete and (ii) project registry, where completed or “registered” projects can be viewed and searched publicly. The registry consists of a quality investigator profile that lists contact information, expertise, and areas of interest. A dashboard allows for the creation and review of quality improvement projects. A search function enables certain quality project details to be publicly accessible to encourage collaboration. We developed the Registry Matching Algorithm which is based on the Jaccard similarity coefficient that uses quality project features to find similar quality projects. The algorithm allows for quality investigators to find existing or previous quality improvement projects to encourage collaboration and to reduce repeat projects. We also developed the QIPR Approver Algorithm that guides the investigator through a series of questions that allows an appropriate quality project to get approved to start without the need for human intervention. RESULTS/ANTICIPATED RESULTS: A product of this project is an open source software package that is freely available on GitHub for distribution to other health systems under the Apache 2.0 open source license. Adoption of the Quality Improvement Project Registry and promotion of it to the intended audience are important factors for the success of this registry. Thanks goes to the UW-Madison and their QI/Program Evaluation Self-Certification Tool (https://uwmadison.co1.qualtrics.com/SE/?SID=SV_3lVeNuKe8FhKc73) used as example and inspiration for this project. DISCUSSION/SIGNIFICANCE OF IMPACT: This registry was created to help understand the impact of improved management of quality projects in a hospital system. The ultimate result will be to reduce time to approve quality improvement projects, increase collaboration across the UF Health Hospital system, reduce redundancy of quality improvement projects and translate more projects into publications.
Despite a reported worldwide increase, the incidence of extended-spectrum β-lactamase (ESBL) Escherichia coli and Klebsiella infections in the United States is unknown. Understanding the incidence and trends of ESBL infections will aid in directing research and prevention efforts.
To perform a literature review to identify the incidence of ESBL-producing E. coli and Klebsiella infections in the United States.
Systematic literature review.
MEDLINE via Ovid, CINAHL, Cochrane library, NHS Economic Evaluation Database, Web of Science, and Scopus were searched for multicenter (≥2 sites), US studies published between 2000 and 2015 that evaluated the incidence of ESBL-E. coli or ESBL-Klebsiella infections. We excluded studies that examined resistance rates alone or did not have a denominator that included uninfected patients such as patient days, device days, number of admissions, or number of discharges. Additionally, articles that were not written in English, contained duplicated data, or pertained to ESBL organisms from food, animals, or the environment were excluded.
Among 51,419 studies examined, 9 were included for review. Incidence rates differed by patient population, time, and ESBL definition and ranged from 0 infections per 100,000 patient days to 16.64 infections per 10,000 discharges and incidence rates increased over time from 1997 to 2011. Rates were slightly higher for ESBL-Klebsiella infections than for ESBL-E. coli infections.
The incidence of ESBL-E. coli and ESBL-Klebsiella infections in the United States has increased, with slightly higher rates of ESBL-Klebsiella infections. Appropriate estimates of ESBL infections when coupled with other mechanisms of resistance will allow for the appropriate targeting of resources toward research, drug discovery, antimicrobial stewardship, and infection prevention.
The purpose of this study was to quantify the effect of multidrug-resistant (MDR) gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated infections (HAIs) on mortality following infection, regardless of patient location.
We conducted a retrospective cohort study of patients with an inpatient admission in the US Department of Veterans Affairs (VA) system between October 1, 2007, and November 30, 2010. We constructed multivariate log-binomial regressions to assess the impact of a positive culture on mortality in the 30- and 90-day periods following the first positive culture, using a propensity-score–matched subsample.
Patients identified with positive cultures due to MDR Acinetobacter (n=218), MDR Pseudomonas aeruginosa (n=1,026), and MDR Enterobacteriaceae (n=3,498) were propensity-score matched to 14,591 patients without positive cultures due to these organisms. In addition, 3,471 patients with positive cultures due to MRSA were propensity-score matched to 12,499 patients without positive MRSA cultures. Multidrug-resistant gram-negative bacteria were associated with a significantly elevated risk of mortality both for invasive (RR, 2.32; 95% CI, 1.85–2.92) and noninvasive cultures (RR, 1.33; 95% CI, 1.22–1.44) during the 30-day period. Similarly, patients with MRSA HAIs (RR, 2.77; 95% CI, 2.39–3.21) and colonizations (RR, 1.32; 95% CI, 1.22–1.50) had an increased risk of death at 30 days.
We found that HAIs due to gram-negative bacteria and MRSA conferred significantly elevated 30- and 90-day risks of mortality. This finding held true both for invasive cultures, which are likely to be true infections, and noninvasive infections, which are possibly colonizations.
Information about the health and economic impact of infections caused by vancomycin-resistant enterococci (VRE) can inform investments in infection prevention and development of novel therapeutics.
To systematically review the incidence of VRE infection in the United States and the clinical and economic outcomes.
We searched various databases for US studies published from January 1, 2000, through June 8, 2015, that evaluated incidence, mortality, length of stay, discharge to a long-term care facility, readmission, recurrence, or costs attributable to VRE infections. We included multicenter studies that evaluated incidence and single-center and multicenter studies that evaluated outcomes. We kept studies that did not have a denominator or uninfected controls only if they assessed postinfection length of stay, costs, or recurrence. We performed meta-analysis to pool the mortality data.
Five studies provided incidence data and 13 studies evaluated outcomes or costs. The incidence of VRE infections increased in Atlanta and Detroit but did not increase in national samples. Compared with uninfected controls, VRE infection was associated with increased mortality (pooled odds ratio, 2.55), longer length of stay (3-4.6 days longer or 1.4 times longer), increased risk of discharge to a long-term care facility (2.8- to 6.5-fold) or readmission (2.9-fold), and higher costs ($9,949 higher or 1.6-fold more).
VRE infection is associated with large attributable burdens, including excess mortality, prolonged in-hospital stay, and increased treatment costs. Multicenter studies that use suitable controls and adjust for time at risk or confounders are needed to estimate the burden of VRE infections.
Our objective was to estimate the per-infection and cumulative mortality and cost burden of multidrug-resistant (MDR) Acinetobacter healthcare-associated infections (HAIs) in the United States using data from published studies.
We identified studies that estimated the excess cost, length of stay (LOS), or mortality attributable to MDR Acinetobacter HAIs. We generated estimates of the cost per HAI using 3 methods: (1) overall cost estimates, (2) multiplying LOS estimates by a cost per inpatient-day ($4,350) from the payer perspective, and (3) multiplying LOS estimates by a cost per inpatient-day from the hospital ($2,030) perspective. We deflated our estimates for time-dependent bias using an adjustment factor derived from studies that estimated attributable LOS using both time-fixed methods and either multistate models (70.4% decrease) or matching patients with and without HAIs using the timing of infection (47.4% decrease). Finally, we used the incidence rate of MDR Acinetobacter HAIs to generate cumulative incidence, cost, and mortality associated with these infections.
Our estimates of the cost per infection were $129,917 (method 1), $72,025 (method 2), and $33,510 (method 3). The pooled relative risk of mortality was 4.51 (95% CI, 1.10–32.65), which yielded a mortality rate of 10.6% (95% CI, 2.5%–29.4%). With an incidence rate of 0.141 (95% CI, 0.136–0.161) per 1,000 patient-days at risk, we estimated an annual cumulative incidence of 12,524 (95% CI, 11,509–13,625) in the United States.
The estimates presented here are relevant to understanding the expenditures and lives that could be saved by preventing MDR Acinetobacter HAIs.