Immune-related adverse event in the emergency department: methodology of the immune-related emergency disposition index (IrEDi).

For many cancer patients, immune checkpoint inhibitors (ICIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICIs can be debilitating and can quickly become severe or even be fatal. Often, irAEs will precipitate visits to the emergency department (ED). Therefore, early recognition and the decision to admit, observe, or discharge these patients from the ED can be key to a cancer patient's morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe, or discharge) within 2-6 h from their patient's ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the absence of classic symptoms, the delayed availability of diagnostic tests during the ED encounter, and the fast pace in the ED setting. At present, there is no single sufficiently large ED data source with clinical, biological, laboratory, and imaging data that will allow for the development of a tool that will guide early recognition and appropriate ED disposition of patients with potential irAEs. We describe an ongoing federally funded project that aims to develop an immune-related emergency disposition index (IrEDi). The project capitalizes on a multi-site collaboration among 4 members of the Comprehensive Oncologic Emergency Research Network (CONCERN): MD Anderson Cancer Center, Ohio State University, Northwestern University, and University of California San Diego. If the aims are achieved, the IrEDi will be the first risk stratification tool derived from a large racial/ethnically and geographically diverse population of cancer patients. The future goal is to validate irEDi in general EDs to improve emergency care of cancer patients on ICIs.

A case series of adrenal insufficiency (likely due to hypophysitis) in cancer patients treated with immune checkpoint inhibitors.

The number of approved immune checkpoint inhibitors (ICIs) and their indications have significantly increased over the past decade. Immune-related adverse effects (irAEs) of ICIs vary widely in presentation and symptoms and can present diagnostic challenges to emergency department (ED) physicians. Moreover, when ICIs are combined with radiotherapy, cytotoxic chemotherapy, or targeted therapy, the attribution of signs and symptoms to an immune-related cause is even more difficult. Here, we report a series of 5 ED cases of adrenal insufficiency in ICI-treated cancer patients. All 5 patients presented with severe fatigue and nausea. Four patients definitely had and one patient possibly had central adrenal insufficiency, and 4 patients had undetectable serum cortisol levels. The majority of the patients had nonspecific symptoms that were not recognized at their first ED presentation. These cases illustrate the need for a heightened level of suspicion for adrenal insufficiency in ICI-treated cancer patients with hypotension, nausea and/or vomiting, abdominal pain, fatigue, or hypoglycemia. As ICI use increases, irAE-associated oncologic emergencies will become more prevalent. Thus, ED physicians must update their knowledge regarding the diagnosis and management of irAEs and routinely inquire about the specific antineoplastic therapies that their ED patients with cancer are receiving. A random cortisol level (results readily available in most EDs) with interpretation taking the circadian rhythm and the current level of physiological stress into consideration can inform the differential diagnosis and whether further investigation of this potential irAE is warranted.

A reference standard for urinary tract infection research: a multidisciplinary Delphi consensus study.

The absence of a consensus-based reference standard for urinary tract infection (UTI) research adversely affects the internal and external validity of diagnostic and therapeutic studies. This omission hinders the accumulation of evidence for a disease that imposes a substantial burden on patients and society, particularly in an era of increasing antimicrobial resistance. We did a three-round Delphi study involving an international, multidisciplinary panel of UTI experts (n=46) and achieved a high degree of consensus (94%) on the final reference standard. New-onset dysuria, urinary frequency, and urinary urgency were considered major symptoms, and non-specific symptoms in older patients were not deemed indicative of UTI. The reference standard distinguishes between UTI with and without systemic involvement, abandoning the term complicated UTI. Moreover, different levels of pyuria were incorporated in the reference standard, encouraging quantification of pyuria in studies done in all health-care settings. The traditional bacteriuria threshold (105 colony-forming units per mL) was lowered to 104 colony-forming units per mL. This new reference standard can be used for UTI research across many patient populations and has the potential to increase homogeneity between studies.

Emergency department patient and physician survey accuracy compared to chart abstraction in patients with acute respiratory illness.

BACKGROUND: High-quality research studies in older adults are needed. Unfortunately, the accuracy of chart review data in older adult patients has been called into question by previous studies. Little is known on this topic in patients with suspected pneumonia, a disease with 500,000 annual older adult U.S. emergency department (ED) visits that presents a diagnostic challenge to ED physicians. The study objective was to compare direct interview and chart abstraction as data sources. METHODS: We present a preplanned secondary analysis of a prospective, observational cohort of ED patients ≥65 years of age with suspected pneumonia in two Midwest EDs. We describe the agreement between chart review and a criterion standard of prospective direct patient survey (symptoms) or direct physician survey (examination findings). Data were collected by chart review and from the patient and treating physician by survey. RESULTS: The larger study enrolled 135 older adults; 134 with complete symptom data and 129 with complete examination data were included in this analysis. Pneumonia symptoms (confusion, malaise, rapid breathing, any cough, new/worse cough, any sputum production, change to sputum) had agreement between patient/legally authorized representative survey and chart review ranging from 47.8% (malaise) to 80.6% (confusion). All examination findings (rales, rhonchi, wheeze) had percent agreement between physician survey and chart review of ≥80%. However, all kappas except wheezing were less than 0.60, indicating weak agreement. CONCLUSIONS: Both patient symptoms and examination findings demonstrated discrepancies between chart review and direct survey with larger discrepancies in symptoms reported. Researchers should consider these potential discrepancies during study design and data interpretation.

Establishment of baseline urinary antimicrobial peptide levels by age: a prospective observational study.

BACKGROUND: Antimicrobial peptides (AMPs) are key effectors of urinary tract innate immunity. Identifying differences in urinary AMP levels between younger and older adults is important in understanding older adults' susceptibility and response to urinary tract infections (UTI) and AMP use as diagnostic biomarkers. We hypothesized that uninfected older adults have higher urinary human neutrophil peptides 1-3 (HNP 1-3), human alpha-defensin-5 (HD-5), and human beta-defensin-2 (hBD-2), but lower urinary cathelicidin (LL-37) than younger adults. METHODS: We conducted a cross-sectional study of patients age ≥18 years completing a family medicine clinic non-acute visit. Enzyme-linked immunosorbent assays (ELISA) were performed for AMPs. We identified associations between age and AMPs using unadjusted and multivariable linear regression models. RESULTS: Of the 308 subjects, 144 (46.8%) were ≥65 years of age. Comparing age ≥65 versus <65 years, there were no significant differences in HNP 1-3 (p=0.371), HD5 (p=0.834) or LL-37 (p=0.348) levels. Values for hBD-2 were lower in older adults versus younger (p <0.001). In multivariable analyses, older males and females had significantly lower hBD-2 levels (p<0.001 and p=0.004). Models also showed urine leukocyte esterase was associated with increased levels of HNP 1-3 and HD5; hematuria with increased hBD-2; and urine cultures with contamination with increased HNP 1-3 and hBD-2. CONCLUSIONS: Baseline urinary HNP 1-3, HD5, and LL-37 did not vary with age. Older adults had lower baseline hBD-2. This finding has implications for the potential use of urinary AMPs as diagnostic markers and will facilitate further investigation into the role of innate immunity in UTI susceptibility in older adults.

Definitions of Urinary Tract Infection in Current Research: A Systematic Review.

Defining urinary tract infection (UTI) is complex, as numerous clinical and diagnostic parameters are involved. In this systematic review, we aimed to gain insight into how UTI is defined across current studies. We included 47 studies, published between January 2019 and May 2022, investigating therapeutic or prophylactic interventions in adult patients with UTI. Signs and symptoms, pyuria, and a positive urine culture were required in 85%, 28%, and 55% of study definitions, respectively. Five studies (11%) required all 3 categories for the diagnosis of UTI. Thresholds for significant bacteriuria varied from 103 to 105 colony-forming units/mL. None of the 12 studies including acute cystitis and 2 of 12 (17%) defining acute pyelonephritis used identical definitions. Complicated UTI was defined by both host factors and systemic involvement in 9 of 14 (64%) studies. In conclusion, UTI definitions are heterogeneous across recent studies, highlighting the need for a consensus-based, research reference standard for UTI.

Implementation of geriatric screening in the emergency department using the Consolidated Framework for Implementation Research.

OBJECTIVE: Implementation of evidence-based care processes (EBP) into the emergency department (ED) is challenging and there are only a few studies of real-world use of theory-based implementation frameworks. We report final implementation results and sustainability of an EBP geriatric screening program in the ED using the Consolidated Framework for Implementation Research (CFIR). METHODS: The EBP involved nurses screening older patients for delirium (Delirium Triage Screen), fall risk (4-Stage Balance Test), and vulnerability (Identification of Seniors at Risk score) with subsequent appropriate referrals to physicians, therapy specialists, or social workers. The proportions of screened adults ≥65 years old were tracked monthly. Outcomes are reported January 2021-December 2022. Barriers encountered were classified according to CFIR. Implementation strategies were classified according to the CFIR-Expert Recommendations for Implementing Change (ERIC). RESULTS: Implementation strategies increased geriatric screening from 5% to 68%. This did not meet our prespecified goal of 80%. Change was sustained through several COVID-19 waves. Inner setting barriers included culture and implementation climate. Initially, the ED was treated as a single inner setting, but we found different cultures and uptake between ED units, including night versus day shifts. Characteristics of individuals barriers included high levels of staff turnover in both clinical and administrative roles and very low self-efficacy from stress and staff turnover. Initial attempts with individualized audit and feedback were not successful in improving self-efficacy and may have caused moral injury. Adjusting feedback to a team/unit level approach with unitwide stretch goals worked better. Identifying early adopters and conducting on-shift education increased uptake. Lessons learned regarding ED culture, implementation in interconnected health systems, and rapid cycle process improvement are reported. CONCLUSIONS: The pandemic exacerbated barriers to implementation in the ED. Cognizance of a large ED as a sum of smaller units and using the CFIR model resulted in improvements.

Cardiac Magnetic Resonance Imaging Versus Invasive-Based Strategies in Patients With Chest Pain and Detectable to Mildly Elevated Serum Troponin: A Randomized Clinical Trial.

BACKGROUND: The optimal diagnostic strategy for patients with chest pain and detectable to mildly elevated serum troponin is not known. The objective was to compare clinical outcomes among an early decision for a noninvasive versus an invasive-based care pathway. METHODS: The CMR-IMPACT trial (Cardiac Magnetic Resonance Imaging Strategy for the Management of Patients with Acute Chest Pain and Detectable to Elevated Troponin) was conducted at 4 United States tertiary care hospitals from September 2013 to July 2018. A convenience sample of 312 participants with acute chest pain symptoms and a contemporary troponin between detectable and 1.0 ng/mL were randomized early in their care to 1 of 2 care pathways: invasive-based (n=156) or cardiac magnetic resonance (CMR)-based (n=156) with modification allowed as the patient condition evolved. The primary outcome was a composite including death, myocardial infarction, and cardiac-related hospital readmission or emergency visits. RESULTS: Participants (N=312, mean age, 60.6 years, SD 11.3; 125 women [59.9%]), were followed over a median of 2.6 years (95% CI, 2.4-2.9). Early assigned testing was initiated in 102 out of 156 (65.3%) CMR-based and 110 out of 156 (70.5%) invasive-based participants. The primary outcome (CMR-based versus invasive-based) occurred in 59% versus 52% (hazard ratio, 1.17 [95% CI, 0.86-1.57]), acute coronary syndrome after discharge 23% versus 22% (hazard ratio, 1.07 [95% CI, 0.67-1.71]), and invasive angiography at any time 52% versus 74% (hazard ratio, 0.66 [95% CI, 0.49-0.87]). Among patients completing CMR imaging, 55 out of 95 (58%) were safely identified for discharge based on a negative CMR and did not have angiography or revascularization within 90 days. Therapeutic yield of angiography was higher in the CMR-based arm (52 interventions in 81 angiographies [64.2%] versus 46 interventions in 115 angiographies [40.0%] in the invasive-based arm [P=0.001]). CONCLUSIONS: Initial management with CMR or invasive-based care pathways resulted in no detectable difference in clinical and safety event rates. The CMR-based pathway facilitated safe discharge, enriched the therapeutic yield of angiography, and reduced invasive angiography utilization over long-term follow-up. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01931852.

Estimating treatment effects for time-to-treatment antibiotic stewardship in sepsis.

Sepsis is a life-threatening condition with a high in-hospital mortality rate. The timing of antibiotic administration poses a critical problem for sepsis management. Existing work studying antibiotic timing either ignores the temporality of the observational data or the heterogeneity of the treatment effects. Here we propose a novel method (called T4) to estimate treatment effects for time-to-treatment antibiotic stewardship in sepsis. T4 estimates individual treatment effects by recurrently encoding temporal and static variables as potential confounders, and then decoding the outcomes under different treatment sequences. We propose mini-batch balancing matching that mimics the randomized controlled trial process to adjust the confounding. The model achieves interpretability through a global-level attention mechanism and a variable-level importance examination. Meanwhile, we equip T4 with an uncertainty quantification to help prevent overconfident recommendations. We demonstrate that T4 can identify effective treatment timing with estimated individual treatment effects for antibiotic stewardship on two real-world datasets. Moreover, comprehensive experiments on a synthetic dataset exhibit the outstanding performance of T4 compared with the state-of-the-art models on estimation of individual treatment effect.

Diagnosis of cancer in the Emergency Department: A scoping review.

BACKGROUND: The Emergency Department (ED) plays a key role in the identification and care of acute medical conditions, including cancer. In this scoping review, we aimed to determine the role of the ED in the acute diagnosis of cancer. METHODS: We conducted a scoping review of articles according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) using PubMed and Google Scholar. We screened studies of adults with a new diagnosis of cancer in the ED. We included randomized control trials, prospective, retrospective, and cross-sectional observational studies, and case reports published in English since 2000. We grouped the articles into categories based on their objectives and findings. RESULTS: Of the 4459 articles, we included 47 in the review. The identified studies fell into three major categories: (1) studies describing the incidental diagnosis of cancer in the ED (n = 11, 23%), (2) studies characterizing the acute initial presentation of cancer in the ED (n = 19, 41%), and (3) studies describing the ED as a pathway to cancer diagnosis in the healthcare system (n = 17, 36%). Across the studies, cancer diagnoses in the ED were more likely in patients with higher comorbidities, occurred at later stages, and resulted in worse survival rates. CONCLUSIONS: The ED plays a prominent role in the initial diagnosis of cancer. Efforts must be made to integrate the ED within the cancer care continuum.

Barriers to and recommendations for integrating the age-friendly 4-Ms framework into electronic health records.

BACKGROUND: The Institute for Healthcare Improvement's 4-Ms framework of care for older adults recommends a multidisciplinary assessment of a patient's Medications, Mentation, Mobility, and What Matters Most. Electronic health record (EHR) systems were developed prior to this emphasis on the 4-Ms. We sought to understand how healthcare providers across the healthcare system perceive their EHRs and to identify any current best practices and ideas for improvement regarding integration of the 4-Ms. METHODS: Anonymous survey of healthcare providers who care for older adults. The survey aimed to evaluate efficiency, error tolerance, and satisfaction (usefulness and likeability). The survey was distributed through organizational list serves that focus on the care of older adults and through social media. RESULTS: Sixty-six respondents from all geographic segments of the U.S. (n = 62) and non-U.S. practices (n = 4) responded. Most (82%) were physicians. Respondents used a range of EHRs and 82% had >5 years of experience with their current EHR. Over half of respondents agreed that their EHR had easy to find contact information (56%) and advance directives. Finding a patient's prior cognitive status (26% agreement), goals of care (24%), functional status (14%), and multidisciplinary geriatric assessments (27%) was more difficult. Only 3% were satisfied with how their EHR handles geriatric syndromes. In free text responses, respondents (79%) described three areas that the EHR assists in the care of older adults: screening tied to actions or orders; advance care planning, and medication alerts or review. Common suggestions on how to improve the EHR included incorporating geriatric assessments in notes, establishing a unified place to review the 4-Ms, and creating age-specific best practice alerts. CONCLUSIONS: The majority of healthcare providers were not satisfied with how their EHR handles multidisciplinary geriatric assessment and geriatric care. EHR modifications would aide in reporting, communicating, and tracking the 4-Ms in EHRs.

A comprehensive assessment of statin discontinuation among patients who concurrently initiate statins and CYP3A4-inhibitor drugs; a multistate transition model.

AIMS: The aim of this study was to describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs. METHODS: A retrospective new-user cohort study design was used to identify (N = 160 828) patients who concurrently initiated CYP3A4 inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104 774) vs. other statins (unexposed to statin DDI, n = 56 054) from the MarketScan commercial claims database (2012-2017). The statin DDI exposed and unexposed groups were matched (2:1) through propensity score matching techniques. We applied a multistate transition model to compare the 1-year transition probabilities involving four distinct states (start, adverse drug events [ADEs], discontinuation of CYP3A4-inhibitor drugs, and discontinuation of statin therapy) between those exposed to statin DDIs vs. those unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities. RESULTS: After concurrently starting stains and CYP3A, patients exposed to statin DDIs, vs. unexposed, were significantly less likely to discontinue statin therapy (71.4% [95% CI: 71.1, 71.6] vs. 73.3% [95% CI: 72.9, 73.6]) but more likely to experience an ADE (3.4% [95% CI: 3.3, 3.5] vs. 3.2% [95% CI: 3.1, 3.3]) and discontinue with CYP3A4-inhibitor therapy (21.0% [95% CI: 20.8, 21.3] vs. 19.5% [95% CI: 19.2, 19.8]). ADEs did not change these associations because those exposed to statin DDIs, vs. unexposed, were still less likely to discontinue statin therapy but more likely to discontinue CYP3A4-inhibitor therapy after experiencing an ADE. CONCLUSION: We did not observe any meaningful clinical differences in the probability of premature statin discontinuation between statin users exposed to statin DDIs and those unexposed.

"Treat Them Like a Human Being They are Somebody's Somebody": Providers' Perspectives on Treating Patients in the Emergency Department After Self-Injurious Behavior.

To understand ED providers' perspective on how to best care for individuals who present to US emergency departments (EDs) following self-injurious behavior, purposive recruitment identified nursing directors, medical directors, and social workers (n = 34) for telephone interviews from 17 EDs. Responses and probes to "What is the single most important thing ED providers and staff can do for patients who present to the ED after self-harm?" were analyzed using directed content analysis approach. Qualitative analyses identified four themes: treat patients with respect and compassion; listen carefully and be willing to ask sensitive personal questions; provide appropriate care during mental health crises; connect patients with mental health care. Participants emphasized treating patients who present to the ED after self-injurious behavior with respect and empathy. Hospitals could incentivize provider mental health training, initiatives promoting patient-provider collaboration, and reimbursement strategies ensuring adequate staffing of providers with time to listen carefully.

Challenges associated with the integration of immuno-oncology agents in clinical practice.

BACKGROUND: The availability of new immuno-oncology therapeutics markedly impacts oncology clinicians' treatment decision-making. To effectively support healthcare professionals (HCPs) in their practice, it is important to better understand the challenges and barriers that can accompany the introduction of these agents. This study aimed to establish the types and causes of clinical challenges posed by the introduction of new immuno-oncology agents. METHODS: The mixed-methods design included qualitative in-depth interviews and group discussions with HCPs, in which participants discussed clinical challenges and potential underlying reasons for these challenges. Qualitative findings informed a quantitative survey. This survey investigated the extent and distribution of challenges using HCPs' self-rating of knowledge, skill, confidence, and exposure to system-level effects. These two phases were conducted sequentially with distinctly stratified samples of oncologists, nurse practitioners (NPs), physician assistants (PAs), pathologists, clinical pharmacists, interventional radiologists, rheumatologists, pulmonologists, and emergency department physicians. Participants were from the United States and had various levels of clinical experience and represented both academic and community-based settings. RESULTS: The final sample included 107 HCPs in the qualitative phase and 554 in the quantitative phase. Analyses revealed clinical challenges related to the use of pharmacodiagnostics. For example, 47% of pathologists and 42% of oncologists reported skill gaps in identifying the appropriate marker and 46% of oncologists, 61% of PAs, 66% of NPs, 74% of pulmonologists and 81% of clinical pharmacists reported skill gaps in selecting treatment based on test results. Challenges also emerged regarding the integration of immuno-oncology agents, as oncologists, rheumatologists, pulmonologists, clinical pharmacists, PAs, and NPs reported knowledge gaps (74-81%) of the safety profiles of recently approved agents. In addition, 90% of clinical pharmacists reported skill gaps weighing the risks and benefits of treating patients with immuno-oncology agents while affected by lupus. Finally, patient communication challenges were identified: HCPs reported difficulties discussing essential aspects of immunotherapy to patients as well as how they might compare to other types of therapies. CONCLUSION: The challenges highlighted in this study reveal substantial educational gaps related to the integration of immuno-oncology agents into practice for various groups of HCPs. These findings provide a strong base of evidence for future educational initiatives.

Automated referral to community paramedicine during 9-1-1 fall calls for resource activation.

BACKGROUND: We sought to improve the referral process to a community paramedicine (CP) program following a 9-1-1 encounter. METHODS: An electronic health record (EHR) for CP records with the ability to link to emergency EHR was identified and implemented with a single-click referral to the CP program. Referrals were tracked for 15 months before and after implementation. RESULTS: Referral capacity increased from an average of 14.2 referrals per month to 44.9 referrals per month. CONCLUSION: The results of this study suggest an EHR is a useful investment for CP programs and may be integral to efficient program operations.

Characterization of older adults with cancer seeking acute emergency department care: A prospective observational study.

INTRODUCTION: Disparities in care of older adults in cancer treatment trials and emergency department (ED) use exist. This report provides a baseline description of older adults ≥65 years old who present to the ED with active cancer. MATERIALS AND METHODS: Planned secondary analysis of the Comprehensive Oncologic Emergencies Research Network observational ED cohort study sponsored by the National Cancer Institute. Of 1564 eligible adults with active cancer, 1075 patients were prospectively enrolled, of which 505 were ≥ 65 years old. We recruited this convenience sample from eighteen participating sites across the United States between February 1, 2016 and January 30, 2017. RESULTS: Compared to cancer patients younger than 65 years of age, older adults were more likely to be transported to the ED by emergency medical services, have a higher Charlson Comorbidity Index score, and be admitted despite no significant difference in acuity as measured by the Emergency Severity Index. Despite the higher admission rate, no significant difference was noted in hospitalization length of stay, 30-day mortality, ED revisit or hospital admission within 30 days after the index visit. Three of the top five ED diagnoses for older adults were symptom-related (fever of other and unknown origin, abdominal and pelvic pain, and pain in throat and chest). Despite this, older adults were less likely to report symptoms and less likely to receive symptomatic treatment for pain and nausea than the younger comparison group. Both younger and older adults reported a higher symptom burden on the patient reported Condensed Memorial Symptom Assessment Scale than to ED providers. When treating suspected infection, no differences were noted in regard to administration of antibiotics in the ED, admissions, or length of stay ≤2 days for those receiving ED antibiotics. DISCUSSION: We identified several differences between older (≥65 years old) and younger adults with active cancer seeking emergency care. Older adults frequently presented for symptom-related diagnoses but received fewer symptomatic interventions in the ED suggesting that important opportunities to improve the care of older adults with cancer in the ED exist.

Palliative Care Needs and Clinical Outcomes of Patients with Advanced Cancer in the Emergency Department.

Background: Older adults with cancer use the emergency department (ED) for acute concerns. Objectives: Characterize the palliative care needs and clinical outcomes of advanced cancer patients in the ED. Design: A planned secondary data analysis of the Comprehensive Oncologic Emergencies Research Network (CONCERN) data. Settings/Subjects: Cancer patients who presented to the 18 CONCERN affiliated EDs in the United States. Measurements: Survey included demographics, cancer type, functional status, symptom burden, palliative and hospice care enrollment, and advance directive code status. Results: Of the total (674/1075, 62.3%) patients had advanced cancer and most were White (78.6%) and female (50.3%); median age was 64 (interquartile range 54-71) years. A small proportion of them were receiving palliative (6.5% [95% confidence interval; CI 3.0-7.6]; p = 0.005) and hospice (1.3% [95% CI 1.0-3.2]; p = 0.52) care and had a higher 30-day mortality rate (8.3%, [95% CI 6.2-10.4]). Conclusions: Patients with advanced cancer continue to present to the ED despite recommendations for early delivery of palliative care.

Suspect screening of exogenous compounds using multiple reaction screening (MRM) profiling in human urine samples.

Thousands of chemical compounds produced by industry are dispersed in the human environment widely enough to reach the world population, and the introduction of new chemicals constantly occurs. As new synthetic molecules emerge, rapid analytical workflows for screening possible presence of exogenous compounds in biofluids can be useful as a first pass analysis to detect chemical exposure and guide the development and application of more elaborate LC-MS/MS methods for quantification. In this study, a suspect screening workflow using the multiple reaction monitoring (MRM) profiling method is proposed as a first pass exploratory technique to survey selected exogenous molecules in human urine samples. The workflow was applied to investigate 12 human urine samples using 310 MRMs related to the chemical functionalities of 87 exogenous compounds present in the METLIN database and reported in the literature. A total of 11 MRMs associated with five different compounds were detected in the samples. Product ion scans for the precursor ions of the selected MRMs were acquired as a further identification step for these chemicals. The suspect screening results suggested the presence of five exogenous compounds in the human urine samples analyzed, namely metformin, metoprolol, acetaminophen, paraxanthine and acrylamide. LC-MS/MS was applied as a last step to confirm these results, and the presence of four out of the five targets selected by MRM profiling were corroborated, indicating that this workflow can support the selection of suspect compounds to screen complex samples and guide more time-consuming and specific quantification analyses.