CA FIRST (California Febrile Infant Risk Stratification Tool) Algorithm Development in a Learning Health System.

Introduction There is considerable variation in the approach to infants presenting to the emergency department (ED) with fever. The authors' primary aim was to develop a robust set of algorithms using community ED data to inform modifications of broader clinical guidance. Methods The authors report the development of California Febrile Infant Risk Stratification Tool (CA FIRST) using key components of the Roseville Protocol (ROS) and American Academy of Pediatrics (AAP) Clinical Practice Guideline (CPG). Expanded guidance was derived using a retrospective analysis of a cohort of 3527 febrile infants aged 7-90 days presenting to any Kaiser Permanente Northern California ED between 2010 and 2019 who underwent a core febrile infant evaluation. Results Melding ROS and AAP CPG algorithms in infants 7-60 days old, CA FIRST Algorithms had comparable performance characteristics to ROS and AAP CPG. CA FIRST enhancements included guidance on febrile infants 61-90 days old, high-risk infants, infants with bronchiolitis, and infants who received immunizations within the prior 48 hours. This retrospective analysis revealed that of 235 febrile infants 22-90 days old with respiratory syncytial virus and 221 who had fever in the 48 hours following vaccination, there were no cases of invasive bacterial infection. Discussion CA FIRST is a set of 13 algorithms providing a thoughtful and flexible approach to the febrile infant while minimizing unnecessary interventions. Conclusions CA FIRST Algorithms empower clinicians to manage most febrile infants. Algorithms are being modified as new data become available, imparting useful and ever-current educational information within a learning health care system.

Bilateral Emboli and Highest Heart Rate Predict Hospitalization of Emergency Department Patients With Acute, Low-Risk Pulmonary Embolism.

STUDY OBJECTIVE: Some patients with acute pulmonary embolism (PE) will suffer adverse clinical outcomes despite being low risk by clinical decision rules. Emergency physician decisionmaking processes regarding which low-risk patients require hospitalization are unclear. Higher heart rate (HR) or embolic burden may increase short-term mortality risk, and we hypothesized that these variables would be associated with an increased likelihood of hospitalization for patients designated as low risk by the PE Severity Index. METHODS: This was a retrospective cohort study of 461 adult emergency department (ED) patients with a PE Severity Index score of fewer than 86 points. Primary exposures were the highest observed ED HR, most proximal embolus location (proximal vs distal), and embolism laterality (bilateral vs unilateral PE). The primary outcome was hospitalization. RESULTS: Of 461 patients meeting inclusion criteria, most (57.5%) were hospitalized, 2 patients (0.4%) died within 30 days, and 142 (30.8%) patients were at elevated risk by other criteria (Hestia criteria or biochemical/radiographic right ventricular dysfunction). Variablesassociated with an increased likelihood of admission were highest observed ED HR of ≥110 beats/minute (vs HR <90 beats/min) (adjusted odds ratio [aOR] 3.11; 95% confidence interval [CI] 1.07 to 9.57), highest ED HR 90 to 109 (aOR 2.03; 95% CI 1.18-3.50) and bilateral PE (aOR 1.92; 95% CI 1.13 to 3.27). Proximal embolus location was not associated with the likelihood of hospitalization (aOR 1.19; 95% CI 0.71 to 2.00). CONCLUSIONS: Most patients were hospitalized, often with recognizable high-risk characteristics not accounted for by the PE Severity Index. Highest ED HR of ≥90 beats/min and bilateral PE were associated with a physician's decision for hospitalization.

Giving superabsorbent polymers a second life as pressure-sensitive adhesives.

An estimated 6.3 billion metric tons of post-consumer polymer waste has been produced, with the majority (79%) in landfills or the environment. Recycling methods that utilize these waste polymers could attenuate their environmental impact. For many polymers, recycling via mechanical processes is not feasible and these materials are destined for landfills or incineration. One salient example is the superabsorbent material used in diapers and feminine hygiene products, which contain crosslinked sodium polyacrylates. Here we report an open-loop recycling method for these materials that involves (i) decrosslinking via hydrolysis, (ii) an optional chain-shortening via sonication, and (iii) functionalizing via Fischer esterification. The resulting materials exhibit low-to-medium storage and loss moduli, and as such, are applicable as general-purpose adhesives. A life cycle assessment demonstrates that the adhesives synthesized via this approach outcompete the same materials derived from petroleum feedstocks on nearly every metric, including carbon dioxide emissions and cumulative energy demand.

Germinant Synergy Facilitates Clostridium difficile Spore Germination under Physiological Conditions.

Clostridium difficile is a Gram-positive obligate anaerobe that forms spores in order to survive for long periods in the unfavorable environment outside a host. C. difficile is the leading cause of nosocomial infectious diarrhea worldwide. C. difficile infection (CDI) arises after a patient treated with broad-spectrum antibiotics ingests infectious spores. The first step in C. difficile pathogenesis is the metabolic reactivation of dormant spores within the gastrointestinal (GI) tract through a process known as germination. In this work, we aim to elucidate the specific conditions and the location within the GI tract that facilitate this process. Our data suggest that C. difficile germination occurs through a two-step biochemical process that is regulated by pH and bile salts, amino acids, and calcium present within the GI tract. Maximal germination occurs at a pH ranging from 6.5 to 8.5 in the terminal small intestine prior to bile salt and calcium reabsorption by the host. Germination can be initiated by lower concentrations of germinants when spores are incubated with a combination of bile salts, calcium, and amino acids, and this synergy is dependent on the availability of calcium. The synergy described here allows germination to proceed in the presence of inhibitory bile salts and at physiological concentrations of germinants, effectively decreasing the concentrations of nutrients required to initiate an essential step of pathogenesis.IMPORTANCEClostridium difficile is an anaerobic spore-forming human pathogen that is the leading cause of nosocomial infectious diarrhea worldwide. Germination of infectious spores is the first step in the development of a C. difficile infection (CDI) after ingestion and passage through the stomach. This study investigates the specific conditions that facilitate C. difficile spore germination, including the following: location within the gastrointestinal (GI) tract, pH, temperature, and germinant concentration. The germinants that have been identified in culture include combinations of bile salts and amino acids or bile salts and calcium, but in vitro, these function at concentrations that far exceed normal physiological ranges normally found in the mammalian GI tract. In this work, we describe and quantify a previously unreported synergy observed when bile salts, calcium, and amino acids are added together. These germinant cocktails improve germination efficiency by decreasing the required concentrations of germinants to physiologically relevant levels. Combinations of multiple germinant types are also able to overcome the effects of inhibitory bile salts. In addition, we propose that the acidic conditions within the GI tract regulate C. difficile spore germination and could provide a biological explanation for why patients taking proton pump inhibitors are associated with increased risk of developing a CDI.

Updates to Clostridium difficile Spore Germination.

Germination of Clostridium difficile spores is a crucial early requirement for colonization of the gastrointestinal tract. Likewise, C. difficile cannot cause disease pathologies unless its spores germinate into metabolically active, toxin-producing cells. Recent advances in our understanding of C. difficile spore germination mechanisms indicate that this process is both complex and unique. This review defines unique aspects of the germination pathways of C. difficile and compares them to those of two other well-studied organisms, Bacillus anthracis and Clostridium perfringensC. difficile germination is unique, as C. difficile does not contain any orthologs of the traditional GerA-type germinant receptor complexes and is the only known sporeformer to require bile salts in order to germinate. While recent advances describing C. difficile germination mechanisms have been made on several fronts, major gaps in our understanding of C. difficile germination signaling remain. This review provides an updated, in-depth summary of advances in understanding of C. difficile germination and potential avenues for the development of therapeutics, and discusses the major discrepancies between current models of germination and areas of ongoing investigation.

Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores.

Clostridium difficile (C. difficile) is an anaerobic gram-positive pathogen that is the leading cause of nosocomial bacterial infection globally. C. difficile infection (CDI) typically occurs after ingestion of infectious spores by a patient that has been treated with broad-spectrum antibiotics. While CDI is a toxin-mediated disease, transmission and pathogenesis are dependent on the ability to produce viable spores. These spores must become metabolically active (germinate) in order to cause disease. C. difficile spore germination occurs when spores encounter bile salts and other co-germinants within the small intestine, however, the germination signaling cascade is unclear. Here we describe a signaling role for Ca2+ during C. difficile spore germination and provide direct evidence that intestinal Ca2+ coordinates with bile salts to stimulate germination. Endogenous Ca2+ (released from within the spore) and a putative AAA+ ATPase, encoded by Cd630_32980, are both essential for taurocholate-glycine induced germination in the absence of exogenous Ca2+. However, environmental Ca2+ replaces glycine as a co-germinant and circumvents the need for endogenous Ca2+ fluxes. Cd630_32980 is dispensable for colonization in a murine model of C. difficile infection and ex vivo germination in mouse ileal contents. Calcium-depletion of the ileal contents prevented mutant spore germination and reduced WT spore germination by 90%, indicating that Ca2+ present within the gastrointestinal tract plays a critical role in C. difficile germination, colonization, and pathogenesis. These data provide a biological mechanism that may explain why individuals with inefficient intestinal calcium absorption (e.g., vitamin D deficiency, proton pump inhibitor use) are more prone to CDI and suggest that modulating free intestinal calcium is a potential strategy to curb the incidence of CDI.