An all-inclusive model for predicting invasive bacterial infection in febrile infants age 7-60 days.

BACKGROUND: Invasive bacterial infections (IBIs) in febrile infants are rare but potentially devastating. We aimed to derive and validate a predictive model for IBI among febrile infants age 7-60 days. METHODS: Data were abstracted retrospectively from electronic records of 37 emergency departments (EDs) for infants with a measured temperature >=100.4 F who underwent an ED evaluation with blood and urine cultures. Models to predict IBI were developed and validated respectively using a random 80/20 dataset split, including 10-fold cross-validation. We used precision recall curves as the classification metric. RESULTS: Of 4411 eligible infants with a mean age of 37 days, 29% had characteristics that would likely have excluded them from existing risk stratification protocols. There were 196 patients with IBI (4.4%), including 43 (1.0%) with bacterial meningitis. Analytic approaches varied in performance characteristics (precision recall range 0.04-0.29, area under the curve range 0.5-0.84), with the XGBoost model demonstrating the best performance (0.29, 0.84). The five most important variables were serum white blood count, maximum temperature, absolute neutrophil count, absolute band count, and age in days. CONCLUSION: A machine learning model (XGBoost) demonstrated the best performance in predicting a rare outcome among febrile infants, including those excluded from existing algorithms. IMPACT: Several models for the risk stratification of febrile infants have been developed. There is a need for a preferred comprehensive model free from limitations and algorithm exclusions that accurately predicts IBIs. This is the first study to derive an all-inclusive predictive model for febrile infants aged 7-60 days in a community ED sample with IBI as a primary outcome. This machine learning model demonstrates potential for clinical utility in predicting IBI.

CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity.

BACKGROUND: Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation. METHODS: Murine models of NSCLC with distinct driver mutations (KrasG12D/P53+/-/Lkb1-/- (KPL); KrasG12D/P53+/- (KP); and KrasG12D (K)) and varying tumor mutational burden were used to evaluate the efficacy of combination therapy with CCL21-DC ISV plus ICI. Comprehensive analyses of longitudinal preclinical samples by flow cytometry, single cell RNA-sequencing (scRNA-seq) and whole-exome sequencing were performed to assess mechanisms of combination therapy. RESULTS: ISV with CCL21-DC sensitized immune-resistant murine NSCLCs to ICI and led to the establishment of tumor-specific immune memory. Immunophenotyping revealed that CCL21-DC obliterated tumor-promoting neutrophils, promoted sustained infiltration of CD8 cytolytic and CD4 Th1 lymphocytes and enriched progenitor T cells in the TME. Addition of ICI to CCL21-DC further enhanced the expansion and effector function of T cells both locally and systemically. Longitudinal evaluation of tumor mutation profiles revealed that CCL21-DC plus ICI induced immunoediting of tumor subclones, consistent with the broadening of tumor-specific T cell responses. CONCLUSIONS: CCL21-DC ISV synergizes with anti-PD-1 to eradicate murine NSCLC. Our data support the clinical application of CCL21-DC ISV in combination with checkpoint inhibition for patients with NSCLC.

Consecutive antibiotic shortages highlight discrepancies between microbiology and prescribing practices for intra-abdominal infections.

Piperacillin-tazobactam (TZP) is frequently used for intra-abdominal infection (IAI). Our institution experienced consecutive shortages of TZP and cefepime, providing an opportunity to review prescribing patterns and microbiology for IAI. Hospitalized adult patients treated for IAI, based on provider selection of IAI as the indication within the antibiotic order, between March 2014 and February 2018 were identified from the University of Virginia Clinical Data Repository and Infection Prevention and Control Database. Antimicrobial utilization, microbiologic data, and clinical outcomes were compared across four year-long periods: pre-shortage, TZP shortage, cefepime shortage, and post-shortage. There were 7,668 episodes of antimicrobial prescribing for an indication of IAI during the study period. Cefepime use for IAI increased 190% during the TZP shortage; meanwhile ceftriaxone use increased by only 57%. There was no increase in in-house mortality, colonization with resistant organisms, or Clostridiodes difficile infection among patients treated with IAI during the shortage periods. Among a subset of cases randomly selected for review, Pseudomonas sp. was a rare cause of IAI, but anti-pseudomonal antibiotics were commonly prescribed empirically. We observed a large increase in cefepime utilization for IAI during a TZP shortage that was not warranted based on the observed frequency of identification of Pseudomonas sp. as the causative organism in IAI, suggesting a need to revisit national guideline recommendations.

Colistin - That Was Fun, But Now We're Done.

Antimicrobial resistance (AMR) is an increasing global threat with estimates that drug-resistant infections contribute to nearly 5 million deaths worldwide every year.1 In particular, carbapenem-resistant Acinetobacter baumannii (CRAB) is emerging as a challenging pathogen to treat and has been designated by the World Health Organization as a priority pathogen for the development of new antimicrobial agents.2 Studies evaluating the efficacy of therapeutic strategies are vitally important in the fight against drug-resistant A. baumannii and other drug-resistant infections.

Outbreak of Burkholderia stabilis Infections Associated with Contaminated Nonsterile, Multiuse Ultrasound Gel - 10 States, May-September 2021.

In July 2021, the Virginia Department of Health notified CDC of a cluster of eight invasive infections with Burkholderia stabilis, a bacterium in the Burkholderia cepacia complex (BCC), among hospitalized patients at hospital A. Most patients had undergone ultrasound-guided procedures during their admission. Culture of MediChoice M500812 nonsterile ultrasound gel used in hospital A revealed contamination of unopened product with B. stabilis that matched the whole genome sequencing (WGS) of B. stabilis strains found among patients. CDC and hospital A, in collaboration with partner health care facilities, state and local health departments, and the Food and Drug Administration (FDA), identified 119 B. stabilis infections in 10 U.S. states, leading to the national recall of all ultrasound gel products produced by Eco-Med Pharmaceutical (Eco-Med), the manufacturer of MediChoice M500812. Additional investigation of health care facility practices revealed frequent use of nonsterile ultrasound gel to assist with visualization in preparation for or during invasive, percutaneous procedures (e.g., intravenous catheter insertion). This practice could have allowed introduction of contaminated ultrasound gel into sterile body sites when gel and associated viable bacteria were not completely removed from skin, leading to invasive infections. This outbreak highlights the importance of appropriate use of ultrasound gel within health care settings to help prevent patient infections, including the use of only sterile, single-use ultrasound gel for ultrasonography when subsequent percutaneous procedures might be performed.

Reducing Repeat Blood Cultures in Febrile Neutropenia: A Single-Center Experience.

Background: Limited data exist to guide blood culture ordering in persistent febrile neutropenia (FN), resulting in substantial variation in practice. Unnecessary repeat blood cultures have been associated with patient harm including increased antimicrobial exposure, hospital length of stay, catheter removal, and overall cost. Methods: We conducted a single-center study of adult hematology-oncology patients with ≥3 days of FN. The yield of blood cultures was first evaluated in a 2-year historical cohort. Additionally, a pilot pre-/postintervention study was performed in non-stem cell transplant (SCT) patients following a change in our population clinical practice guideline from a recommendation of daily blood cultures to a clinically guided approach. The primary outcome was cultures collected per days of FN after day 3 of persistent FN. Results: One hundred forty-six episodes of ≥3 days of FN in 108 patients were identified during the historical period. Day 1 blood cultures were positive in 23 of 146 (16%) episodes. Blood cultures were drawn on 374 of 513 (73%) subsequent episode-days (day 2-12) and were negative in 366 of 374 (98%). After the intervention, a 53% decrease was observed in the rate of total blood cultures collected (1.4 preintervention vs 0.7 postintervention; P = .03). Blood cultures obtained after 48 hours rarely yielded clinically significant organisms. Conclusions: Repeat blood cultures are low-yield in persistent FN without new clinical change. A pilot intervention in non-SCT patients successfully reduced the frequency of blood culture collection.

Clinical management and outcomes for febrile infants 29-60 days evaluated in community emergency departments.

Objective: Describe emergency department (ED) management and patient outcomes for febrile infants 29-60 days of age who received a lumbar puncture (LP), with focus on timing of antibiotics and type of physician performing LP. Methods: Retrospective observational study of 35 California EDs from January 1, 2010 through December 31, 2019. Primary analysis was among patients with successful LP and primary outcome was hospital length of stay (LOS). Logistic regression analysis included variables associated with LOS of at least 2 days. Secondary outcomes were bacterial meningitis, hospital admission, length of antibiotics, and readmission. Results: Among 2569 febrile infants (median age 39 days), 667 underwent successful LP and 633 received intravenous antibiotics. Most infants (n = 559, 88.3%) had their LP before intravenous antibiotic administration. Pediatricians performed 54% of LPs and emergency physicians 34%. Sixteen infants (0.6% of 2569) were diagnosed with bacterial meningitis, and none died. Five hundred and fifty-eight (88%) infants receiving an LP were hospitalized. Among patients receiving an LP and antibiotics (n = 633), 6.5% were readmitted within 30 days. Patients receiving antibiotics before LP had a longer length of antibiotics (+ 7.9 hours, 95% confidence interval [CI] 3.8-13.4). Primary analysis found no association between timing of antibiotics and LOS (odds ratio [OR] 0.67, 95% CI 0.34-1.30), but shorter LOS when emergency physicians performed the LP (OR 0.66, 95% CI 0.45-0.97). Conclusions: Febrile infants in the ED had no deaths and few cases of bacterial meningitis. In community EDs, where a pediatrician is often not available, successful LP by emergency physician was associated with reduced inpatient LOS.

Are Mental Health and Substance Use Disorders Risk Factors for Missed Acute Myocardial Infarction Diagnoses Among Chest Pain or Dyspnea Encounters in the Emergency Department?

STUDY OBJECTIVE: To assess if having a mental health and/or substance use disorder is associated with a missed acute myocardial infarction diagnosis in the emergency department (ED). METHODS: This was a retrospective cohort analysis (2009 to 2017) of adult ED encounters at Kaiser Permanente Southern California. We used the validated symptom-disease pair analysis of diagnostic error methodological approach to "look back" and "look forward" and identify missed acute myocardial infarctions within 30 days of a treat-and-release ED visit. We use adjusted logistic regression to report the odds of missed acute myocardial infarction among patients with a history of mental health and/or substance use disorders. RESULTS: The look-back analysis identified 44,473 acute myocardial infarction hospital encounters; 574 (1.3%) diagnoses were missed. The odds of missed diagnoses were higher in patients with mental health disorders (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.23 to 1.77) but not in those with substance abuse disorders (OR 1.22, 95% CI 0.91 to 1.62). The highest risk was observed in those with co-occurring disorders (OR 1.90, 95% CI 1.30 to 2.76). The look-forward analysis identified 325,088 chest pain/dyspnea ED encounters; 508 (0.2%) were missed acute myocardial infarctions. No significant associations of missed acute myocardial infarction were revealed in either group (mental health disorder: OR 0.92, 95% CI 0.71 to 1.18; substance use disorder: OR 1.22, 95% CI 0.80 to 1.85). CONCLUSION: The look-back analysis identified patients with mental illness at increased risk of missed acute myocardial infarction diagnosis, with the highest risk observed in those with a history of comorbid substance abuse. Having substance use disorders alone did not increase this risk in either cohort. The look-forward analysis revealed challenges in prospectively identifying high-risk patients to target for improvement.

Does Hospital Admission/Observation for Chest Pain Improve Patient Outcomes after Emergency Department Evaluation for Suspected Acute Coronary Syndrome?

BACKGROUND: Chest pain is the top reason for hospitalization/observation in the USA, but it is unclear if this strategy improves patient outcomes. OBJECTIVE: The objective of this study was to compare 30-day outcomes for patients admitted versus discharged after a negative emergency department (ED) evaluation for suspected acute coronary syndrome. DESIGN: A retrospective, multi-site, cohort study of adult encounters with chest pain presenting to one of 13 Kaiser Permanente Southern California EDs between January 1, 2015, and December 1, 2017. Instrumental variable analysis was used to mitigate potential confounding by unobserved factors. PATIENTS: All adult patients presenting to an ED with chest pain, in whom an acute myocardial infarction was not diagnosed in the ED, were included. MAIN MEASURES: The primary outcome was 30-day acute myocardial infarction or all-cause mortality, and secondary outcomes included 30-day revascularization and major adverse cardiac events. KEY RESULTS: In total, 77,652 patient encounters were included in the study (n=11,026 admitted, 14.2%). Three hundred twenty-two (0.4%) had an acute myocardial infarction (n=193, 0.2%) or death (n=137, 0.2%) within 30 days of ED visit (1.5% hospitalized versus 0.2% discharged). Very few (0.3%) patients underwent coronary revascularization within 30 days (0.7% hospitalized versus 0.2% discharged). Instrumental variable analysis found no adjusted differences in 30-day patient outcomes between the hospitalized cohort and those discharged (risk reduction 0.002, 95% CI -0.002 to 0.007). Similarly, there were no differences in coronary revascularization (risk reduction 0.003, 95% CI -0.002 to 0.007). CONCLUSION: Among ED patients with chest pain not diagnosed with an acute myocardial infarction, risk of major adverse cardiac events is quite low, and there does not appear to be any benefit in 30-day outcomes for those admitted or observed in the hospital compared to those discharged with outpatient follow-up.

High School Basketball Coach and Player Perspectives on Warm-Up Routines and Lower Extremity Injuries.

BACKGROUND: While participation in sports-related activities results in improved health outcomes, high school athletes are at risk for lower extremity injuries, especially ankle, knee, and thigh injuries. Efforts to promote the adoption and implementation of evidence-driven approaches to reduce injury risk among school-aged athletes are needed. However, there is limited research regarding the perceived barriers, facilitators, and adherence factors that may influence the successful implementation of effective warm-up routines among this population. METHODS: We conducted a qualitative study using semi-structured interviews and focus groups to assess high school basketball coach and player current practices, knowledge, and perspectives about warm-ups and lower-extremity injuries (LEIs). We interviewed coaches (n = 12) and players (n = 30) from May to October 2019. Participants were recruited from public high schools in a joint school district in Southern California. Multiple coders employed thematic analysis of the data using validated methods. RESULTS: Coaches and players reported regular engagement (e.g., daily) in warm-up routines, but the time dedicated (range 5-45 min), types of exercises, and order varied substantially. Players often co-lead the warm-up practice with the coach or assistant coach. Despite regular engagement in warm-up, players and coaches report multiple challenges, including (1) limited time and space to warm-up effectively at games, (2) a perception that young players are not prone to injury, (3) competing demands for coaches' time during practice, and (4) coaches' lack of knowledge. Coaches and players perceive that warming up before practice will result in fewer injuries, and many players are motivated to warm up as a result of their personal injury experience; however, they desire guidance on the ideal exercises for preventing injury and training on the proper form for each exercise. CONCLUSIONS: Regular involvement in basketball warm-up routines is common among high school teams, but the methods and time dedicated to these practices varied. Players and coaches are eager for more information on warm-up programs shown to reduce LEIs.

Inhibition of Granulocytic Myeloid-Derived Suppressor Cells Overcomes Resistance to Immune Checkpoint Inhibition in LKB1-Deficient Non-Small Cell Lung Cancer.

LKB1 inactivating mutations are commonly observed in patients with KRAS-mutant non-small cell lung cancer (NSCLC). Although treatment of NSCLC with immune checkpoint inhibitors (ICI) has resulted in improved overall survival in a subset of patients, studies have revealed that co-occurring KRAS/LKB1 mutations drive primary resistance to ICIs in NSCLC. Effective therapeutic options that overcome ICI resistance in LKB1-mutant NSCLC are limited. Here, we report that loss of LKB1 results in increased secretion of the C-X-C motif (CXC) chemokines with an NH2-terminal Glu-Leu-Arg (ELR) motif in premalignant and cancerous cells, as well as in genetically engineered murine models (GEMM) of NSCLC. Heightened levels of ELR+ CXC chemokines in LKB1-deficient murine models of NSCLC positively correlated with increased abundance of granulocytic myeloid-derived suppressor cells (G-MDSC) locally within the tumor microenvironment and systemically in peripheral blood and spleen. Depletion of G-MDSCs with antibody or functional inhibition via all-trans-retinoic acid (ATRA) led to enhanced antitumor T-cell responses and sensitized LKB1-deficent murine tumors to PD-1 blockade. Combination therapy with anti-PD-1 and ATRA improved local and systemic T-cell proliferation and generated tumor-specific immunity. Our findings implicate ELR+ CXC chemokine-mediated enrichment of G-MDSCs as a potential mediator of immunosuppression in LKB1-deficient NSCLC and provide a rationale for using ATRA in combination with anti-PD-1 therapy in patients with LKB1-deficient NSCLC refractory to ICIs. SIGNIFICANCE: These findings show that accumulation of myeloid-derived suppressor cells in LKB1-deficient non-small cell lung cancer can be overcome via treatment with all-trans-retinoic acid, sensitizing tumors to immunotherapy.

Novel Kras-mutant murine models of non-small cell lung cancer possessing co-occurring oncogenic mutations and increased tumor mutational burden.

Conditional genetically engineered mouse models (GEMMs) of non-small cell lung cancer (NSCLC) harbor common oncogenic driver mutations of the disease, but in contrast to human NSCLC these models possess low tumor mutational burden (TMB). As a result, these models often lack tumor antigens that can elicit host adaptive immune responses, which limits their utility in immunotherapy studies. Here, we establish Kras-mutant murine models of NSCLC bearing the common driver mutations associated with the disease and increased TMB, by in vitro exposure of cell lines derived from GEMMs of NSCLC [KrasG12D (K), KrasG12DTp53-/-(KP), KrasG12DTp53+/-Lkb1-/- (KPL)] to the alkylating agent N-methyl-N-nitrosourea (MNU). Increasing the TMB enhanced host anti-tumor T cell responses and improved anti-PD-1 efficacy in syngeneic models across all genetic backgrounds. However, limited anti-PD-1 efficacy was observed in the KPL cell lines with increased TMB, which possessed a distinct immunosuppressed tumor microenvironment (TME) primarily composed of granulocytic myeloid-derived suppressor cells (G-MDSCs). This KPL phenotype is consistent with findings in human KRAS-mutant NSCLC where LKB1 loss is a driver of primary resistance to PD-1 blockade. In summary, these novel Kras-mutant NSCLC murine models with known driver mutations and increased TMB have distinct TMEs and recapitulate the therapeutic vulnerabilities of human NSCLC. We anticipate that these immunogenic models will facilitate the development of innovative immunotherapies in NSCLC.

Improving Utilization of Lung Cancer Screening Through Incorporating a Video-Based Educational Tool Into Smoking Cessation Counseling.

BACKGROUND: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) reduces lung cancer mortality in high-risk patients, but most of those eligible are not referred for screening, and most eligible smokers are not aware of LCS. Smoking cessation counseling may be an opportune time to educate smokers about LCS. Here we investigate the effect of LCS educational information on LDCT utilization and smoking cessation in LCS-eligible patients receiving smoking cessation counseling. PATIENTS AND METHODS: We randomized 1281 smokers aged 55-80 who underwent smoking cessation services to view a web-based educational video about LCS (n = 1026) or to receive usual care (n = 255). Outcomes included the utilization of chest computed tomographic (CT) scan during 6 months of follow-up, responses to survey questions, and patient-reported abstinence from smoking at 6 months. RESULTS: One hundred forty-six participants (14%) watched the video. Overall, 87 participants (8.5%) in the intervention group underwent any chest CT and 37 (3.6%) underwent LDCT compared to 22 (8.6%) and 11 (4.3%) in the control group during the 6-month follow-up period (P = .94 and .59, respectively). Among participants who completed watching the video, 27 (18.5%) underwent any chest CT and 13 (8.9%) underwent LDCT, compared to 22 (8.6%) and 11 (4.3%) in controls during follow-up (P = .0037 and .062, respectively). There was no difference in abstinence from smoking between groups. CONCLUSION: An LCS educational intervention may be effective in improving utilization of LDCT in eligible individuals who currently smoke at the time of smoking cessation counseling. Further research on the effect of LCS education in the context of smoking cessation counseling is needed.

Missed acute myocardial infarction in the emergency department-standardizing measurement of misdiagnosis-related harms using the SPADE method.

OBJECTIVES: Diagnostic error is a serious public health problem. Measuring diagnostic performance remains elusive. We sought to measure misdiagnosis-related harms following missed acute myocardial infarctions (AMI) in the emergency department (ED) using the symptom-disease pair analysis of diagnostic error (SPADE) method. METHODS: Retrospective administrative data analysis (2009-2017) from a single, integrated health system using International Classification of Diseases (ICD) coded discharge diagnoses. We looked back 30 days from AMI hospitalizations for antecedent ED treat-and-release visits to identify symptoms linked to probable missed AMI (observed > expected). We then looked forward from these ED discharge diagnoses to identify symptom-disease pair misdiagnosis-related harms (AMI hospitalizations within 30-days, representing diagnostic adverse events). RESULTS: A total of 44,473 AMI hospitalizations were associated with 2,874 treat-and-release ED visits in the prior 30 days. The top plausibly-related ED discharge diagnoses were "chest pain" and "dyspnea" with excess treat-and-release visit rates of 9.8% (95% CI 8.5-11.2%) and 3.4% (95% CI 2.7-4.2%), respectively. These represented 574 probable missed AMIs resulting in hospitalization (adverse event rate per AMI 1.3%, 95% CI 1.2-1.4%). Looking forward, 325,088 chest pain or dyspnea ED discharges were followed by 508 AMI hospitalizations (adverse event rate per symptom discharge 0.2%, 95% CI 0.1-0.2%). CONCLUSIONS: The SPADE method precisely quantifies misdiagnosis-related harms from missed AMIs using administrative data. This approach could facilitate future assessment of diagnostic performance across health systems. These results correspond to ∼10,000 potentially-preventable harms annually in the US. However, relatively low error and adverse event rates may pose challenges to reducing harms for this ED symptom-disease pair.

Identifying Patients with Low Risk of Acute Coronary Syndrome Without Troponin Testing: Validation of the HEAR Score.

BACKGROUND: Current guidelines for patients with suspected acute myocardial infarction are mainly based on troponin testing, commonly requiring an emergency department visit. HEAR score (History, Electrocardiogram, Age, and Risk factors) is a risk stratification tool validated in Europe, deduced from the HEART score (History, Electrocardiogram, Age, Risk factors, and Troponin), already implemented in clinical practice. We aimed to validate the HEAR score to rule out an acute myocardial infarction without needing biomarker testing. METHODS: Retrospective cohort study at 15 emergency departments between May 2016 and December 2017. All adult encounters evaluated for possible acute myocardial infarction with a physician-documented HEART score for health plan members of Kaiser Permanente Southern California were included. Patients with an ST-segment elevation myocardial infarction, those under hospice care, or with a "do not resuscitate" status were excluded. HEAR scores from 0-8 were calculated for each encounter and used to report 30-day acute myocardial infarction or all-cause mortality for each score. RESULTS: There were 22,109 patient encounters included in the study. Overall, 30-day acute myocardial infarction or death occurred in 1.1% of patients. Among the 4106 patients (19%) with a HEAR score <2, 3 died and 2 experienced an acute myocardial infarction within 30 days (0.1%; 95% confidence interval, 0.1-0.3). Sensitivity and specificity were 97.9% and 18.8%, respectively. CONCLUSIONS: A low HEAR score may accurately identify patients with a very low risk of 30-day acute myocardial infarction or death, representing a cohort of patients who might appropriately forego biomarker testing. Future research is warranted to assess the impact of implementing the HEAR score into routine clinical practice.

Effect of Using an Age-adjusted D-dimer to Assess for Pulmonary Embolism in Community Emergency Departments.

BACKGROUND: The objective of this study was to evaluate the effect of changing the laboratory-reported D-dimer reference intervals to age-adjusted reference intervals on the use of advanced chest imaging and 30-day adverse events among emergency department (ED) encounters. METHODS: A retrospective interrupted time-series analysis of ED encounters for patients > 50 years evaluated for suspected pulmonary embolism (PE) from April 2014 to April 2016. The primary outcome was use of advanced diagnostic imaging, and the secondary outcome was 30-day mortality or PE diagnosis. Secondary analyses also quantified delayed PE diagnoses pre- and postintervention. A generalized estimating equation segmented logistic regression model, adjusting for patient and facility characteristics, was used to determine changes in odds of diagnostic imaging and 30-day mortality or PE diagnoses. RESULTS: A total of 10,534 (5,153 pre- and 5,381 postimplementation) ED encounters were included. Advanced imaging was obtained in 35.9% of pre- versus 33% of postimplementation encounters. Age-adjusted D-dimer (AADD) showed a small and nonsignificant decrease in month-to-month trends of advanced chest imaging postimplementation (odds ratio [OR] = 0.98, 95% confidence interval [CI] = 0.96 to 1.00). Use of advanced imaging in patients with D-dimer values lower than 500 ng/mL fibrinogen-equivalent units (FEU) was similar in the preintervention (5.8%) and postintervention (6.8%) periods. However, imaging was obtained in 30% of patients postintervention with a D-dimer result less than AADD reference interval , but more than the historical 500 ng/mL FEU reference interval. Implementing an AADD threshold demonstrated no change in the rate of 30-day adverse events (missed PE or mortality). CONCLUSION: Changing the laboratory-reported D-dimer reference intervals for evaluation of PE was not associated with reduction in advanced chest imaging and did not increase 30-day adverse events. However, there was substantial noncompliance with the age-adjusted reference intervals in the postintervention period likely blunting the impact of this intervention.

Evaluating Sex Disparities in the Emergency Department Management of Patients With Suspected Acute Coronary Syndrome.

STUDY OBJECTIVE: We compare clinical management and outcomes of emergency department (ED) encounters by sex after implementation of a clinical care pathway in 15 community EDs that standardized recommendations based on patient risk, using the History, ECG, Age, Risk Factors, and Troponin (HEART) score. METHODS: This was a retrospective analysis of adult ED encounters evaluated for suspected acute coronary syndrome with a documented HEART score from May 20, 2016, to December 1, 2017. The primary outcomes were hospitalization or 30-day stress testing. Secondary outcomes included 30-day acute myocardial infarction or all-cause death (major adverse cardiac event). A generalized estimating equation regression model was used to compare the odds of hospitalization or stress testing by sex; we report HEART scores (0 to 10) stratified by sex and describing major adverse cardiac events. RESULTS: A total of 34,715 adult ED encounters met the inclusion criteria (56.0% women). A higher proportion of women were classified as low risk (60.5% versus 52.4%; odds ratio [OR] 1.39; 95% confidence interval [CI] 1.33 to 1.45). Women were hospitalized or received stress testing less frequently than men for low HEART scores (18.8% versus 22.8%; OR 0.79; 95% CI 0.73 to 0.84) and intermediate ones (46.7% versus 49.7%; OR 0.88; 95% CI 0.83 to 0.95), but similarly for high-risk ones (74.1% versus 74.4%; OR 0.99; 95% CI 0.77 to 1.28). Women had 18% lower odds of hospitalization or noninvasive cardiac testing (OR 0.82; 95% CI 0.78 to 0.86), even after adjusting for HEART score and comorbidities. Men had higher risks of major adverse cardiac events than women for all HEART score categories but the risk for men was significantly higher among low-risk HEART scores (0.4% versus 0.1%). CONCLUSION: Women with low-risk HEART scores are hospitalized or stress tested less than men, which is likely appropriate, and women have better outcomes than men. Use of the HEART score has the potential to reduce sex disparities in acute coronary syndrome care.

Risk Factors Associated with Carbapenemase-Producing Enterobacterales (CPE) Positivity in the Hospital Wastewater Environment.

Hospital wastewater is an increasingly recognized reservoir for resistant Gram-negative organisms. Factors involved in establishment and persistence of Klebsiella pneumoniae carbapenemase-producing organisms (KPCOs) in hospital wastewater plumbing are unclear. This study was conducted at a hospital with endemic KPCOs linked to wastewater reservoirs and robust patient perirectal screening for silent KPCO carriage. Over 5 months, both rooms occupied and rooms not occupied by KPCO-positive patients were sampled at three wastewater sites within each room (sink drain, sink P-trap, and toilet or hopper). Risk factors for KPCO positivity were assessed using logistic regression. Whole-genome sequencing (WGS) identified environmental seeding by KPCO-positive patients. A total of 219/475 (46%) room sampling events were KPCO positive in at least one wastewater site. KPCO-positive patient exposure was associated with increased risk of environmental positivity for the room and toilet/hopper. Previous positivity and intensive care unit room type were consistently associated with increased risk. Tube feeds were associated with increased risk for the drain, while exposure to patients with Clostridioides difficile was associated with decreased risk. Urinary catheter exposure was associated with increased risk of P-trap positivity. P-trap heaters reduced risk of P-trap and sink drain positivity. WGS identified genomically linked environmental seeding in 6 of 99 room occupations by 40 KPCO-positive patients. In conclusion, KPCO-positive patients seed the environment in at least 6% of opportunities; once positive for KPCOs, wastewater sites are at greater risk of being positive subsequently. Increased nutrient exposure, e.g., due to tube food disposal down sinks, may increase risk; frequent flushing may be protective.IMPORTANCEKlebsiella pneumoniae carbapenemase-producing organisms (KPCOs) are bacteria that are resistant to most antibiotics and thus are challenging to treat when they cause infections in patients. These organisms can be acquired by patients who are hospitalized for other reasons, complicating their hospital stay and even leading to death. Hospital wastewater sites, such as sink drains and toilets, have played a role in many reported outbreaks over the past decade. The significance of our research is in identifying risk factors for environmental positivity for KPCOs, which will facilitate further work to prevent transmission of these organisms to patients from the hospital environment.

Incorporating lung cancer screening education into tobacco cessation group counseling.

INTRODUCTION: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) reduces lung cancer mortality, yet few people who are eligible for LCS get screened. In the present study, we studied the feasibility of tobacco cessation counselors to inform about LCS during tobacco cessation group counseling. METHODS: Four tobacco cessation counselors at two different facilities offering group tobacco cessation counseling were trained to administer an educational intervention about LCS. The intervention was administered to 25 participants during May 2019 who completed surveys that assessed how much the information provided helped with understanding various aspects of lung cancer screening including benefits, risks, eligibility criteria, and insurance coverage. The intervention also provided information on how to learn more about LCS and assessed the acceptability of the information. RESULTS: The median score for understanding of all components of the intervention was 5 ('completely understand'). Most participants (92%) felt that the information provided about LCS was the right amount. Most participants (72%) were aged 55-80 years, the age range for LCS eligibility. Four participants (16%) reported undergoing LCS in the past. When we reanalyzed the subset of participants who reported no prior LCS, the results of surveys were similar. CONCLUSIONS: Our findings suggest that it is feasible to train tobacco cessation counselors to educate smokers, attending group tobacco cessation counseling classes, also about LCS. The education provided in this study was both understood and well received by the large majority of smokers surveyed. Further study is needed to understand the effect of LCS education on utilization of LDCT among smokers enrolled in tobacco cessation counseling.

Author Correction: Chronic IL-1ß-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.