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Background: In August 2021, Saint Luke’s Health System (SLHS) transitioned Clostridioides difficile (C. diff.) testing from polymerase chain reaction (PCR)-only to two-step enzyme immunoassay (EIA) reflex following PCR+ for suspected C. diff. infection. Uncertainty in patient management may arise when PCR and EIA testing differ. Previous studies suggested that disease severity varies when a patient’s results demonstrate PCR+ and EIA- due to possible colonization. Clinicians may not treat if diarrhea self-resolves, patients remain stable, or alternate causes of diarrhea exist. We compared clinical outcomes of patients who received treatment to those who did not. Methods: This was a retrospective cross-sectional study from August 2021-August 2023 in a multi-site, integrated health system, comparing 181 inpatients with PCR+/EIA- C. diff. test results stratified by no treatment (0-48 hours of C. diff. targeted treatment), partial treatment (2-9 days), or full treatment (10+ days). The primary outcome was length of stay. Secondary outcomes were readmission rates, need for colectomy, intensive care unit (ICU) admission, and diarrhea resolution on day of discharge. Results: Of the 181 patients, 144 received full treatment, 17 had partial, and 20 had no treatment. Baseline characteristics were similar between groups. No significant difference was found for length of stay or any secondary outcomes (Table 1). Table 2 provides a subgroup of patients who received no treatment vs those receiving partial or full treatment. Conclusion: In this study, treatment exposure did not affect clinical outcomes for patients with PCR+/EIA- results, though sample sizes may limit generalizability. Further research is warranted regarding the clinical approach to PCR+/EIA-

Background: The FIRST Trial is a 5-year study funded by the Agency for Healthcare Research and Quality. Our investigation is situated within a more extensive study to restrict fluoroquinolone antibiotics by requiring providers to obtain authorization from an infectious disease physician before prescribing fluoroquinolones. Our research team is performing a systematic evaluation to identify organizational characteristics and influencers of the fluoroquinolone preprescription authorization implementation process to understand variables that may facilitate or hinder implementation success. Methods: To address this critical gap, we present a qualitative analysis from our ongoing, multisite research project aimed at systematically assessing the adoption of an antimicrobial stewardship intervention in the form of an EHR-integrated best-practice alert (BPA) at each site to identify work system factors that impact uptake and variability in the implementation of the BPA at each location. The evaluation provides a detailed explanation of activities through the implementation process (eg, before implementation, during implementation, and after implementation) to assess how an organization effectively negotiates the phases and transitions, ultimately influencing the impact of the intervention. We have used a contextual determinant framework (CFIR) that has enabled us to perform a systematic and comprehensive exploration and identification of potential explanatory themes or variables to shed light on the complex social phenomenon of implementation. Results: Participants who will be a part of our poster presentation will learn about implementing a BPA, the potential barriers to implementation, and strategies for overcoming these barriers. Stakeholders within our study include site coordinators, medical doctors, nurses, pharmacists, and clinical informaticists. Our analysis synthesizes their experiences implementing and sustaining this evidence-based antimicrobial stewardship intervention. It includes (1) a detailed description of the process of change, (2) work-system factors (eg, inner setting and outer setting) that they believe influenced the success of the intervention, (3) barriers and facilitators (eg, CFIR constructs) within the implementation process; and (4) description of how these could have influenced the outcomes of interest (eg, implementation and intervention effectiveness). Conclusions: Our research is expected to advance patient safety research and initiatives by providing a more robust approach to performing systematic intervention evaluations. By outlining stakeholders’ experiences within our study, implementation leaders within healthcare systems will utilize our findings to aid them in their design and implementation process when designing and implementing similar types of healthcare interventions.

This study assessed outcomes prior to and after electronic medical record-based clinical decision support implementation combined with prospective audit in patients with COVID-19. This multimodal stewardship intervention was associated with a decrease in antibiotic exposure for patients with COVID-19 (44.4% vs 61.8%, p = 0.002) within the first 7 days of hospitalization.

Abstract Background Clinical team composition for prehospital paediatric intubation may affect success and complication rates. We performed a systematic review and meta-analysis to determine the success and complication rates by type of clinical team. Methods We searched MEDLINE, EMBASE, and CINAHL for interventional and observational studies describing prehospital intubation attempts in children with overall success, first-pass success, and complication rates. Eligible studies, data extraction, and assessment of risk of bias were assessed independently by two reviewers. We performed a random-effects meta-analysis of proportions. Results Forty studies (1989 to 2019) described three types of clinical teams: non-physician teams with no relaxants (22 studies, n = 7602), non-physician teams with relaxants (12 studies, n = 2185), and physician teams with relaxants (12 studies, n = 1780). Twenty-two (n = 3747) and 18 (n = 7820) studies were at low and moderate risk of bias, respectively. Non-physician teams without relaxants had lower overall intubation success rate (72%, 95% CI 67–76%) than non-physician teams with relaxants (95%, 95% CI 93–98%) and physician teams (99%, 95% CI 97–100%). Physician teams had higher first-pass success rate (91%, 95% CI 86–95%) than non-physicians with (75%, 95% CI 69–81%) and without (55%, 95% CI 48–63%) relaxants. Overall airway complication rate was lower in physician teams (10%, 95% CI 3–22%) than non-physicians with (30%, 95% CI 23–38%) and without (39%, 95% CI 28–51%) relaxants. Conclusion Physician teams had higher rates of intubation success and lower rates of overall airway complications than other team types. Physician prehospital teams should be utilised wherever practicable for critically ill children requiring prehospital intubation.

Abstract Objective: To evaluate the effect of templated microbiology reporting comments on antifungal utilization in patients with candiduria. Design: In this retrospective, quasi-experimental study, we evaluated a preimplementation cohort (June 2018–January 2019) compared with a postimplementation cohort (June 2019–January 2020). Setting: A multisite health system including 1 academic hospital and 4 community hospitals. Patients: Patients were aged ≥18 years, were hospitalized, and had candiduria documented at least once during their admission. The study included 156 patients in the preimplementation period and 141 patients in the postimplementation period. Methods: In June 2019, Saint Luke’s Health System implemented the use of templated comments for urine cultures with Candida spp growth. When Candida is isolated, the following comment appears in the microbiology result section: “In the absence of symptoms, Candida is generally considered normal flora. No therapy indicated unless high risk (pregnant, neonate, or neutropenic) or undergoing urologic procedure. If Foley catheter present, remove or replace when able.” The primary outcome was rate of antifungal prescribing. Results: Antifungal administration within 72 hours of a culture identifying a Candida spp occurred in 75 patients in the preimplementation group and 48 patients in the postimplementation group (48.1% vs 34.0%; P = .02). We did not detect a difference between groups in antifungal administration between 73 and 240 hours (1.3% vs 3.5%; P = .26), nor did we detect a difference in median antifungal duration (4 vs 3 days; P = .43). Conclusion: Using a templated comment with urine cultures reduced antifungal prescription rates in hospitalized patients with candiduria. This strategy is a low-resource technique to improve antimicrobial stewardship.

Objective The aim of this study was to identify the prevalence of prescribing topical beta-blockers (TBB) despite documented contraindications in general practice and whether patients were involved in decisions about treatment. Design This was a primary-care-based cross-sectional descriptive study. Introduction Glaucoma is one of the commonest causes of irreversible blindness in the United Kingdom, causing ∼5.9% of blind registration. TBB are currently considered the best adjunctive treatment and are well known for their systemic effects. The effect of concurrent prescription of TBB with systemic contraindications was found to significantly increase the rate of hospitalization and emergency room visits. Patients and methods Electronic medical records of four primary care providers in the North East of England were searched for primary open-angle glaucoma, use of TBB, and known systemic contraindications. Included records were further searched for correspondence from ophthalmology departments to primary care. We contacted those patients whose records showed no documentation of communicating potential risks with patients and rationale of using TBB. Results Of the 49 816 patients registered with the four primary health care providers, 798 (1.6%) had primary open-angle glaucoma. Of these, 279 (35%) were prescribed TBB; 260 (93.2%) of whom had no systemic contraindications. Conclusion Nineteen (6.8%) patients with systemic contraindications were prescribed TBB despite alerts from electronic medical records. Furthermore, these patients were not made aware of the potential risk.

Viral polymerases are important targets in drug discovery and development efforts. Most antiviral compounds that are currently approved for treatment of infection with members of the herpesviridae family were shown to inhibit the viral DNA polymerase. However, biochemical studies that shed light on mechanisms of drug action and resistance are hampered primarily due to technical problems associated with enzyme expression and purification. In contrast, the orthologous bacteriophage RB69 polymerase gp43 has been crystallized in various forms and therefore serves as a model system that provides a better understanding of structure–function relationships of polymerases that belong the type B family. This review aims to discuss strengths, limitations, and opportunities of the phage surrogate with emphasis placed on its utility in the discovery and development of anti-herpetic drugs.

The analysis of neural systems leverages tools from many different fields. Drawing on techniques from the study of critical phenomena in statistical mechanics, several studies have reported signatures of criticality in neural systems, including power-law distributions, shape collapses, and optimized quantities under tuning. Independently, neural complexity - an information theoretic measure - has been introduced in an effort to quantify the strength of correlations across multiple scales in a neural system. This measure represents an important tool in complex systems research because it allows for the quantification of the complexity of a neural system. In this analysis, we studied the relationships between neural complexity and criticality in neural culture data. We analyzed neural avalanches in 435 recordings from dissociated hippocampal cultures produced from rats, as well as neural avalanches from a cortical branching model. We utilized recently developed maximum likelihood estimation power-law fitting methods that account for doubly truncated power-laws, an automated shape collapse algorithm, and neural complexity and branching ratio calculation methods that account for sub-sampling, all of which are implemented in the freely available Neural Complexity and Criticality MATLAB toolbox. We found evidence that neural systems operate at or near a critical point and that neural complexity is optimized in these neural systems at or near the critical point. Surprisingly, we found evidence that complexity in neural systems is dependent upon avalanche profiles and neuron firing rate, but not precise spiking relationships between neurons. In order to facilitate future research, we made all of the culture data utilized in this analysis freely available online.