Pediatric Sepsis in General Emergency Departments: Association Between Pediatric Sepsis Case Volume, Care Quality, and Outcome.

STUDY OBJECTIVE: To assess whether a general emergency department's (ED) annual pediatric sepsis volume increases the odds of delivering care concordant with Surviving Sepsis pediatric guidelines. METHODS: A retrospective cohort study of children <18 years with sepsis presenting to 29 general EDs. Emergency department and hospital data were abstracted from the medical records of 2 large health care systems, including all hospitals to which children were transferred. Guideline-concordant care was defined as intravenous antibiotics within 3 hours, intravenous fluid bolus within 3 hours, and lactate measured. The association between annual ED pediatric sepsis encounters and the probability of receiving guideline-concordant care was assessed. RESULTS: We included 1,527 ED encounters between January 1, 2015, and September 30, 2021. Three hundred and one (19%) occurred in 25 EDs with <10 pediatric sepsis encounters annually, 466 (31%) in 3 EDs with 11 to 100 pediatric sepsis encounters annually, and 760 (50%) in an ED with more than 100 pediatric sepsis encounters annually. Care was concordant in 627 (41.1%) encounters. In multivariable analysis, annual pediatric sepsis volume was minimally associated with the probability of guideline-concordant care (odds ratio 1.002 [95% confidence interval 1.001 to 1.00]). Care concordance increased from 23.1% in 2015 to 52.8% in 2021. CONCLUSION: Guideline-concordant sepsis care was delivered in 41% of pediatric sepsis cases in general EDs, and annual ED pediatric sepsis encounters had minimal association with the odds of concordant care. Care concordance improved over time. This study suggests that factors other than pediatric sepsis volume are important in driving care quality and identifying drivers of improvement is important for children first treated in general EDs.

Evaluation of an Antimicrobial Stewardship Decision Support for Pediatric Infections.

OBJECTIVES: Clinical decision support (CDS) has promise for the implementation of antimicrobial stewardship programs (ASPs) in the emergency department (ED). We sought to assess the usability of a newly developed automated CDS to improve guideline-adherent antibiotic prescribing for pediatric community-acquired pneumonia (CAP) and urinary tract infection (UTI). METHODS: We conducted comparative usability testing between an automated, prototype CDS-enhanced discharge order set and standard order set, for pediatric CAP and UTI antibiotic prescribing. After an extensive user-centered design process, the prototype CDS was integrated into the electronic health record, used passive activation, and embedded locally adapted prescribing guidelines. Participants were randomized to interact with three simulated ED scenarios of children with CAP or UTI, across both systems. Measures included task completion, decision-making and usability errors, clinical actions (order set use and correct antibiotic selection), as well as objective measures of system usability, utility, and workload using the National Aeronautics and Space Administration Task Load Index (NASA-TLX). The prototype CDS was iteratively refined to optimize usability and workflow. RESULTS: Usability testing in 21 ED clinical providers demonstrated that, compared to the standard order sets, providers preferred the prototype CDS, with improvements in domains such as explanations of suggested antibiotic choices (p < 0.001) and provision of additional resources on antibiotic prescription (p < 0.001). Simulated use of the CDS also led to overall improved guideline-adherent prescribing, with a 31% improvement for CAP. A trend was present toward absolute workload reduction. Using the NASA-TLX, workload scores for the current system were median 26, interquartile ranges (IQR): 11 to 41 versus median 25, and IQR: 10.5 to 39.5 for the CDS system (p = 0.117). CONCLUSION: Our CDS-enhanced discharge order set for ED antibiotic prescribing was strongly preferred by users, improved the accuracy of antibiotic prescribing, and trended toward reduced provider workload. The CDS was optimized for impact on guideline-adherent antibiotic prescribing from the ED and end-user acceptability to support future evaluative trials of ED ASPs.

Addressing disparities in pharmacogenomics through rural and underserved workforce education.

Introduction: While pharmacogenomic (PGx) testing is routine in urban healthcare institutions or academic health centers with access to existing expertise, uptake in medically-underserved areas is lagging. The primary objective of this workforce education program is to extend access to didactic, case-based and clinical PGx training for pharmacists serving rural Minnesota and populations experiencing health disparities in Minnesota. Methods: A PGx workforce training program funded through the Minnesota Department of Health was offered through the University of Minnesota College of Pharmacy (COP) to pharmacists working in rural and/or underserved areas in the state of Minnesota. Learning activities included a 16-week, asynchronous PGx didactic course covering PGx topics, a 15-min recorded presentation, an in-person PGx case-based workshop, and a live international PGx Conference hosted by the University of Minnesota COP and attendance at our PGx Extension of Community Health Outcomes (ECHO). Results: Twenty-nine pharmacists applied for the initial year of the program, with 12 (41%) being accepted. Four (33%) practiced in a hospital setting, four (33%) in retail pharmacy, two (17%) in managed care, and two (17%) in other areas. The majority had not implemented a PGx program as part of their practice, although nearly all responded definitely or probably yes when asked if they expected their organization to increase its use of PGx testing services over the next three years. All participants either strongly or somewhat agreed that this program helped them identify how and where to access clinical PGx guidelines and literature and improved their ability to read and interpret PGx test results. Eight participants (67%) strongly or somewhat agreed that they expected to increase the number of PGx consultations in their practice, while ten (83%) strongly or somewhat agreed they would be able to apply what they learned in this program to their practice in the next six months to a year. Discussion: This novel PGx training program focused exclusively on pharmacists in rural and/or underserved areas with a delivery method that could be accomplished conveniently and remotely. Although most participants' organizations had yet to implement PGx testing routinely, most anticipated this to change in the next few years.

Development and Implementation of In-House Pharmacogenomic Testing Program at a Major Academic Health System.

Pharmacogenomics (PGx) studies how a person's genes affect the response to medications and is quickly becoming a significant part of precision medicine. The clinical application of PGx principles has consistently been cited as a major opportunity for improving therapeutic outcomes. Several recent studies have demonstrated that most individuals (> 90%) harbor PGx variants that would be clinically actionable if prescribed a medication relevant to that gene. In multiple well-conducted studies, the results of PGx testing have been shown to guide therapy choice and dosing modifications which improve treatment efficacy and reduce the incidence of adverse drug reactions (ADRs). Although the value of PGx testing is evident, its successful implementation in a clinical setting presents a number of challenges to molecular diagnostic laboratories, healthcare systems, providers and patients. Different molecular methods can be applied to identify PGx variants and the design of the assay is therefore extremely important. Once the genotyping results are available the biggest technical challenge lies in turning this complex genetic information into phenotypes and actionable recommendations that a busy clinician can effectively utilize to provide better medical care, in a cost-effective, efficient and reliable manner. In this paper we describe a successful and highly collaborative implementation of the PGx testing program at the University of Minnesota and MHealth Fairview Molecular Diagnostic Laboratory and selected Pharmacies and Clinics. We offer detailed descriptions of the necessary components of the pharmacogenomic testing implementation, the development and technical validation of the in-house SNP based multiplex PCR based assay targeting 20 genes and 48 SNPs as well as a separate CYP2D6 copy number assay along with the process of PGx report design, results of the provider and pharmacists usability studies, and the development of the software tool for genotype-phenotype translation and gene-phenotype-drug CPIC-based recommendations. Finally, we outline the process of developing the clinical workflow that connects the providers with the PGx experts within the Molecular Diagnostic Laboratory and the Pharmacy.

Pharmacogenomics education, research and clinical implementation in the state of Minnesota.

Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare professional and student education is strong and there are multiple opportunities in the state for learners to gain workforce skills and develop advanced competency in PGx. Implementation planning is occurring at several organizations and others have incorporated structured utilization of PGx into routine workflows. Laboratory-based and translational PGx research in Minnesota has driven important discoveries in several therapeutic areas. This article reviews the state of PGx activities in Minnesota including educational programs, research, national consortia involvement, technology, clinical implementation and utilization and reimbursement, and outlines the challenges and opportunities in equitable implementation of these advances.

Recommendations to researchers for aiding in increasing American Indian representation in genetic research and personalized medicine.

Increasing American Indian/Alaska Native (AI/AN) representation in genetic research is critical to ensuring that personalized medicine discoveries do not widen AI/AN health disparities by only benefiting well-represented populations. One reason for the under-representation of AIs/ANs in research is warranted research distrust due to abuse of some AI/AN communities in research. An approach to easing the tension between protecting AI/AN communities and increasing the representation of AI/AN persons in genetic research is community-based participatory research. This approach was used in a collaboration between a tribe and academic researchers in efforts to increase AI/AN participation in genetic research. From the lessons learned, the authors propose recommendations to researchers that may aid in conducting collaborative and respectful research with AI/AN tribes/communities and ultimately assist in increasing representation of AIs/ANs in personalized medicine discoveries.

Antimicrobial Resistance in Invasive Bacterial Infections in Hospitalized Children, Cambodia, 2007-2016.

To determine trends, mortality rates, and costs of antimicrobial resistance in invasive bacterial infections in hospitalized children, we analyzed data from Angkor Hospital for Children, Siem Reap, Cambodia, for 2007-2016. A total of 39,050 cultures yielded 1,341 target pathogens. Resistance rates were high; 82% each of Escherichia coli and Klebsiella pneumoniae isolates were multidrug resistant. Hospital-acquired isolates were more often resistant than community-acquired isolates; resistance trends over time were heterogeneous. K. pneumoniae isolates from neonates were more likely than those from nonneonates to be resistant to ampicillin-gentamicin and third-generation cephalosporins. In patients with community-acquired gram-negative bacteremia, third-generation cephalosporin resistance was associated with increased mortality rates, increased intensive care unit admissions, and 2.26-fold increased healthcare costs among survivors. High antimicrobial resistance in this setting is a threat to human life and the economy. In similar low-resource settings, our methods could be reproduced as a robust surveillance model for antimicrobial resistance.

Water avoidance stress results in an altered voiding phenotype in male mice.

AIMS: We set out to characterize the voiding phenotypes of male mice to a water avoidance stress (WAS) protocol and compare the molecular changes with those induced by surgically induced partial bladder outlet obstruction (pBOO). METHODS: Six-week-old male Swiss Webster mice housed with sibling littermates were individually placed on a platform centered in the middle of a water filled basin for 1 hr daily for 4 weeks. A non stressed cohort of sibling littermates served as controls. Measured end points included voiding frequency, voided volume, bladder mass, and in vivo cystometry. Molecular end points included myosin heavy chain (MHC) isoform distribution by PCR, and nuclear translocation of hypoxia inducible factor (HIF1α) and the nuclear factor of activated T-cells (NFAT) by gel shift assay. These molecular endpoints were compared with samples from male mice undergoing anatomic pBOO. RESULTS: WAS resulted in increased average voided volumes and bladder mass, and a decrease in voiding frequency (P < 0.05). The slower MHC A isoform was only expressed in the pBOO group that developed severe hypertrophy. Gel shift assays revealed substantial increases in HIF1-α nuclear translocation in the group subjected to pBOO that developed severe hypertrophy but minimal changes in the pBOO group that developed minimal hypertrophy and the swim stress groups. CONCLUSIONS: The WAS model induces moderate bladder wall hypertrophy in the absence of any surgical manipulation.