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Background: The high-sensitivity HEART pathway (hs-HP) risk stratifies emergency department (ED) patients with chest pain. It is unknown if its safety and effectiveness vary by sex or race., Methods: We conducted a subgroup analysis of the hs-HP implementation study, a pre-post interrupted time series at five US EDs. The pre-implementation period (January 2019 to April 2020) utilized the traditional HEART pathway with contemporary troponin (Siemens) and the post-implementation period (November 2020 to February 2022) used the hs-HP using hs-cTnI (Beckman Coulter). Patients were risk-stratified using the hs-HP to rule-out, observation, and rule-in groups. Safety and effectiveness outcomes were 30-day all-cause mortality or myocardial infarction (MI) and 30-day hospitalization., Results: Twenty-six thousand and one hundred twenty-six patients were accrued (12 317 pre- and 13 809 post-implementation), of which 35.3% were non-White and 52.7% were female. Among 9703 patients with complete hs-HP assessments, 48.6% of White and 55.4% of non-White patients were ruled-out (p < 0.001). Additionally, 47.3% of males and 54.4% of females were ruled-out (p < 0.001). Among rule-out patients, 0.3% of White versus 0.3% of non-White patients (p = 0.98) and 0.3% of females versus males 0.3% (p = 0.90) experienced 30-day death or MI. Post-implementation, 30-day hospitalization decreased 17.2% among White patients (aOR 0.49, 95% CI: 0.45-0.52), 14.1% among non-White patients (aOR 0.53, 95% CI: 0.48-0.59), 15.6% among females (aOR 0.50, 95% CI: 0.46-0.54), and 16.6% among males (aOR 0.51, 95% CI: 0.47-0.56). The interactions for 30-day hospitalization between hs-HP implementation and race (p = 0.10) and sex (p = 0.69) were not significant., Conclusions: The hs-HP safely decreases 30-day hospitalizations regardless of sex or race. However, it classifies more non-White patients and women to the rule-out group., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Aims: During the COVID-19 public health emergency, we previously identified decreased rates of radiotherapy (RT) peer review (PR) discussion and plan changes in virtual versus in-person PR conferences. To expand on these findings, we continued to prospectively collect data on all PR conferences from 2021 to 2023 and performed a follow-up analysis before and after the transition back to in-person PR., Materials and Methods: A prospectively maintained database of weekly PR cases was queried for consecutive cases reviewed before and after the transition from virtual to in-person conferences. Rates of PR discussion and change recommendations were summarized and compared between the virtual and in-person groups. A survey was developed and administered to assess participants' perceived levels of engagement, opinions on optimal PR format, and preferences for future meetings before and 3 months after the transition back to in-person PR., Results: In total, 2,103 RT plans were reviewed: 1,590 virtually and 513 after the transition back to in-person. There was no difference in faculty attendance between groups. The proportion of cases with PR discussion increased from virtual (9.8%) to in-person (25.5%) format (p < 0.001). In the virtual group, 8.1% of cases had 1 topic and 1.7% had 2+ topics discussed. This increased to 15.8% and 9.7% during in-person PR, respectively (p < 0.001). The rate of change recommendation also increased from 1.5% (virtual) to 3.3% (in-person, p = 0.016). Among cases with at least 1 topic discussed, there was no difference in changes. Survey-reported distraction significantly decreased from virtual to in-person PR (p < 0.001)., Conclusion: Upon returning to in-person PR conferences, peer discussion and plan change recommendations significantly increased and returned to pre-pandemic levels, and participants' perceived levels of distraction were reduced. In an increasingly virtual world, additional efforts to develop best practices that maximize PR discussion and minimize distraction outside virtual conferences are warranted., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Data comparing the performance of sex-specific to overall (non-sex-specific) high-sensitivity cardiac troponin (hs-cTn) cut-points for diagnosing acute coronary syndrome (ACS) are limited. This study aims to compare the safety and efficacy of sex-specific versus overall 99th percentile high-sensitivity cardiac troponin T (hs-cTnT) cut-points., Methods: We conducted a secondary analysis of the STOP-CP cohort, which prospectively enrolled emergency department patients ≥ 21 years old with symptoms suggestive of ACS without ST-elevation on initial electrocardiogram across eight U.S. sites (January 25, 2017-September 6, 2018). Participants with both 0- and 1-h hs-cTnT measures less than or equal to the 99th percentile (sex-specific 22 ng/L for males, 14 ng/L for females; overall 19 ng/L) were classified into the rule-out group. The safety outcome was adjudicated cardiac death or myocardial infarction (MI) at 30 days. Efficacy was defined as the proportion classified to the rule-out group. McNemar's test and a generalized score statistic were used to compare rule-out and 30-day cardiac death or MI rates between strategies. Net reclassification improvement (NRI) index was used to further compare performance., Results: This analysis included 1430 patients, of whom 45.8% (655/1430) were female; the mean ± SD age was 57.6 ± 12.8 years. At 30 days, cardiac death or MI occurred in 12.8% (183/1430). The rule-out rate was lower using sex-specific versus overall cut-points (70.6% [1010/1430] vs. 72.5% [1037/1430]; p = 0.003). Among rule-out patients, the 30-day cardiac death or MI rates were similar for sex-specific (2.4% [24/1010]) vs. overall (2.3% [24/1037]) strategies (p = 0.79). Among patients with cardiac death or MI, sex-specific versus overall cut-points correctly reclassified three females and incorrectly reclassified three males. The sex-specific strategy resulted in a net of 27 patients being incorrectly reclassified into the rule-in group. This led to an NRI of -2.2% (95% CI -5.1% to 0.8%)., Conclusions: Sex-specific hs-cTnT cut-points resulted in fewer patients being ruled out without an improvement in safety compared to the overall cut-point strategy., (© 2024 The Author(s). Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Background: Emergent reperfusion by percutaneous coronary intervention (PCI) within 90 minutes of first medical contact (FMC) is indicated in patients with ST-segment elevation myocardial infarction (STEMI). However, long transport times in rural areas in the Southeast US make meeting this goal difficult. The objective of this study was to determine the number of Southeast US residents with prolonged transport times to the nearest 24/7 primary PCI (PPCI) center., Methods: A cross-sectional study of residents in the Southeastern US was conducted based on geographical and 2022 5-Year American Community Survey data. The geographic information system (GIS) ArcGIS Pro was used to estimate Emergency Medical Services (EMS) transport times for Southeast US residents to the nearest PPCI center. All 24/7 PPCI centers in North Carolina, South Carolina, Georgia, Florida, Mississippi, Alabama, and Tennessee were included in the analysis, as well as nearby PPCI centers in surrounding states. To identify those at risk of delayed FMC-to-device time, the primary outcome was defined as a >30-minute transport time, beyond which most patients would not have PCI within 90 minutes. A secondary outcome was defined as transport >60 minutes, the point at which FMC-to-device time would be >120 minutes most of the time. These cutoffs are based on national median EMS scene times and door-to-device times., Results: Within the Southeast US, we identified 62,880,528 residents and 350 PPCI centers. Nearly 11 million people living in the Southeast US reside greater than 30 minutes from a PPCI center (17.3%, 10,866,710, +/- 58,143), with 2% (1,271,522 +/- 51,858) living greater than 60 minutes from a PPCI hospital. However, most patients reside in short transport zones; 82.7% (52,013,818 +/- 98,741). Within the Southeast region, 8.4% (52/616) of counties have more than 50% of their population in a long transport zone and 42.3% (22/52) of those have more than 90% of their population in long transport areas., Conclusions: Nearly 11 million people in the Southeast US do not have access to timely PCI for STEMI care. This disparity may contribute to increased morbidity and mortality.

Background: To determine if the European Society of Cardiology 0/1-hour (ESC 0/1-h) algorithm with high-sensitivity cardiac troponin T (hs-cTnT) meets the ≥99% negative predictive value (NPV) safety threshold for 30-day cardiac death or myocardial infarction (MI) in older, middle-aged and young subgroups., Methods: We conducted a subgroup analysis of adult emergency department patients with chest pain prospectively enrolled from eight US sites (January 2017 to September 2018). Patients were stratified into rule-out, observation and rule-in zones using the hs-cTnT ESC 0/1-h algorithm and classified as older (≥65 years), middle aged (46-64 years) or young (21-45 years). Patients had 0-hour and 1-hour hs-cTnT measures (Roche Diagnostics) and a History, ECG, Age, Risk factor and Troponin (HEART) score. Fisher's exact tests compared rule-out and 30-day cardiac death or MI rates between ages. NPVs with 95% CIs were calculated for the ESC 0/1-h algorithm with and without the HEART score., Results: Of 1430 participants, 26.9% (385/1430) were older, 57.4% (821/1430) middle aged and 15.7% (224/1430) young. Cardiac death or MI at 30 days occurred in 12.8% (183/1430). ESC 0/1-h algorithm ruled out 35.6% (137/385) of older, 62.1% (510/821) of middle-aged and 79.9% of (179/224) young patients (p<0.001). NPV for 30-day cardiac death or MI was 97.1% (95% CI 92.7% to 99.2%) among older patients, 98.4% (95% CI 96.9% to 99.3%) in middle-aged patients and 99.4% (95% CI 96.9% to 100%) among young patients. Adding a HEART score increased NPV to 100% (95% CI 87.7% to 100%) for older, 99.2% (95% CI 97.2% to 99.9%) for middle-aged and 99.4% (95% CI 96.6% to 100%) for young patients., Conclusions: In older and middle-aged adults, the hs-cTnT ESC 0/1-h algorithm was unable to reach a 99% NPV for 30-day cardiac death or MI unless combined with a HEART score., Trial Registration Number: NCT02984436., Competing Interests: Competing interests: ACS receives funding from Abbott, HRSA (1H2ARH399760100) and AHRQ (R01HS029017). JS receives research funding from HRSA (H2ARH39976-01-00), The Duke Endowment, Roche Diagnostics, Abbott Laboratories, Pathfast, Genetesis, Cytovale, Forest Devices, Vifor Pharma and Chiesi Farmaceutici. SAM receives funding/support from Roche Diagnostics, Abbott Laboratories, QuidelOrtho, Siemens, Grifols, Pathfast, Genetesis, Cytovale, The Duke Endowment, Beckman Coulter, Comprehensive Research Associates, Brainbox, HRSA (1H2ARH399760100) and AHRQ (R01HS029017). He is a consultant for Roche, QuidelOrtho, Abbott, Siemens, Genetesis, Inflammatix, Radiometer and Amgen and is the chief medical officer for Impathiq. BA receives research funding/support from Roche Diagnostics, Siemens and Beckman Coulter. He is a consultant for Roche Diagnostics. BM has research support from the NIH (5K08HL130546) and Roche Diagnostics. She has served as a consultant for Roche Diagnostics. JM receives research funding/support from Beckman Coulter, Roche Diagnostics, Abbott Laboratories and Siemens. He is a consultant for Beckman Coulter, Roche Diagnostics and Siemens. RGW received research funding from Regeneron Pharmaceuticals, Lilly USA, BioAge Labs, Roche Diagnostics, Global Blood Therapeutics, Novartis Pharmaceuticals, Egetis Therapeutics, EndPoint Health, Blade Therapeutics, Janssen R&D, ProvePharma and Pfizer. He has received research funding from CoapTech through an NIH/NIDDK grant (R44DK115325). He has received research support in the form of equipment and supplies from Cepheid and Eldon Biologicals. He is an uncompensated advisor to CSL Behring. RC is a consultant for and receives funding/support from Roche Diagnostics, Siemens Healthineers, Beckman Coulter Diagnostics, Becton Dickinson and Co, Quidel and Sphingotec., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A single dose epinephrine protocol (SDEP) for out-of-hospital cardiac arrest (OHCA) achieves similar survival to hospital discharge (SHD) rates as a multidose epinephrine protocol (MDEP). However, it is unknown if a SDEP improves SHD rates among patients with a shockable rhythm or those receiving bystander cardiopulmonary resuscitation (CPR)., Methods: This pre-post study, spanning 11/01/2016-10/29/2019 at 5 North Carolina EMS systems, compared pre-implementation MDEP and post-implementation SDEP in patients ≥18 years old with non-traumatic OHCA. Data on initial rhythm type, performance of bystander CPR, and the primary outcome of SHD were sourced from the Cardiac Arrest Registry to Enhance Survival. We compared SDEP vs MDEP performance in each rhythm (shockable and non-shockable) and CPR (bystander CPR or no bystander CPR) subgroup using Generalized Estimating Equations to account for clustering among EMS systems and to adjust for age, sex, race, witnessed arrest, arrest location, AED availability, EMS response interval, and presence of a shockable rhythm or receiving bystander CPR. The interaction of SDEP implementation with rhythm type and bystander CPR was evaluated., Results: Of 1690 patients accrued (899 MDEP, 791 SDEP), 19.2% (324/1690) had shockable rhythms and 38.9% (658/1690) received bystander CPR. After adjusting for confounders, SHD was increased after SDEP implementation among patients with bystander CPR (aOR 1.61, 95%CI 1.03-2.53). However, SHD was similar in the SDEP cohort vs MDEP cohort among patients without bystander CPR (aOR 0.81, 95%CI 0.60-1.09), with a shockable rhythm (aOR 0.96, 95%CI 0.48-1.91), and with a non-shockable rhythm (aOR 1.26, 95%CI 0.89-1.77). In the adjusted model, the interaction between SDEP implementation and bystander CPR was significant for SHD ( p  = 0.002)., Conclusion: Adjusting for confounders, the SDEP increased SHD in patients who received bystander CPR and there was a significant interaction between SDEP and bystander CPR. Single dose epinephrine protocol and MDEP had similar SHD rates regardless of rhythm type.

Background: The European Society of Cardiology (ESC) 0/1-h high sensitivity troponin T (hs-cTnT) algorithm does not differentiate risk based on known coronary artery disease (CAD: prior myocardial infarction [MI], coronary revascularization, or ≥ 70% coronary stenosis). We recently evaluated its performance among patients with known CAD at 30-days, but little is known about its longer-term risk prediction. The objective of this study is to determine and compare the performance of the algorithm at 90-days among patients with and without known CAD., Methods: We performed a pre-planned subgroup analysis of the STOP-CP cohort, which prospectively enrolled ED patients ≥21 years old with symptoms suggestive of ACS without ST-elevation on initial ECG across 8 US sites (1/25/2017-9/6/2018). Participants with 0- and 1-h hs-cTnT measures (Roche, Basel, Switzerland) were stratified into rule-out, observe, and rule-in groups using the ESC 0/1-h algorithm. Algorithm performance was tested among patients with or without known CAD, as determined by the treating provider. The primary outcome was cardiac death or MI at 90-days. Fisher's exact tests were used to compare 90-day event and rule-out rates between patients with and without known CAD. Negative predictive values (NPVs) for 90-day cardiac death or MI with exact 95% confidence intervals were calculated and compared using Fisher's exact test., Results: The STOP-CP study accrued 1430 patients, of which 31.4% (449/1430) had known CAD. Cardiac death or MI at 90 days was more common in patients with known CAD than in those without [21.2% (95/449) vs. 10.0% (98/981); p < 0.001]. Using the ESC 0/1-h algorithm, 39.6% (178/449) of patients with known CAD and 66.1% (648/981) of patients without known CAD were ruled-out (p < 0.001). Among rule-out patients, 90-day cardiac death or MI occurred in 3.4% (6/178) of patients with known CAD and 1.2% (8/648) without known CAD (p = 0.09). NPV for 90-day cardiac death or MI was 96.6% (95%CI 92.8-98.8) among patients with known CAD and 98.8% (95%CI 97.6-99.5) in patients without known CAD (p = 0.09)., Conclusion: Patients with known CAD who were ruled-out using the ESC 0/1-h hs-cTnT algorithm had a high rate of missed 90-day cardiac events, suggesting that the ESC 0/1-h hs-cTnT algorithm may not be safe for use among patients with known CAD., Trial Registration: High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP; ClinicalTrials.gov: NCT02984436; https://clinicaltrials.gov/ct2/show/NCT02984436)., Competing Interests: Declaration of competing interest Dr. Ashburn receives funding from AHRQ (R01HS029017). Dr. Snavely receives funding from Abbott, HRSA (1H2ARH399760100), and AHRQ (R01HS029017). Dr. Stopyra receives research funding from HRSA (H2ARH39976–01-00), AHRQ (R01HS029017), AHRQ (1R21HS029234-01A1), The Duke Endowment, Roche Diagnostics, Abbott Laboratories, Pathfast, Genetesis, Cytovale, Forest Devices, Vifor Pharma, and Chiesi Farmaceutici. Dr. Mahler receives funding/support from Roche Diagnostics, Abbott Laboratories, QuidelOrtho, Siemens, Grifols, Pathfast, Beckman Coulter, Genetesis, Cytovale, The Duke Endowment, Brainbox, HRSA (1H2ARH399760100), and AHRQ (R01HS029017). He is a consultant for Roche, Quidel, Abbott, Siemens, Inflammatix, and Radiometer and is the Chief Medical Officer for Impathiq Inc. Dr. Allen receives research funding/support from RocheDiagnostics, Siemens, and Beckman Coulter. He is a consultant for Roche Diagnostics and Beckman Coulter. Dr. Mumma has research support from the NIH (5K08HL130546) and Roche Diagnostics. Dr. McCord receives research funding/support from Beckman Coulter, Roche Diagnostics, Abbott Laboratories, and Siemens. He is a consultant for Beckman Coulter, Roche Diagnostics, and Siemens. Dr. Wilkerson received research funding from Regeneron Pharmaceuticals, Inc., Lilly USA, LLC, BioAge Labs, Inc., Roche Diagnostics, Global Blood Therapeutics, Inc., Novartis Pharmaceuticals, Egetis Therapeutics AB, EndPoint Health, Inc., Blade Therapeutics, Janssen R&D LLC, ProvePharma, Beckton, Dickinson and Company, and Pfizer Inc. He has received research funding from CoapTech, LLC through an NIH/NIDDK grant (R44DK115325). He has received research support in the form of equipment and supplies from Cepheid and Eldon Biologicals A/S. He is an uncompensated advisor to CSL Behring. Dr. Christenson is a consultant for and receives funding/support from Roche Diagnostics, Siemens Healthineers, Beckman Coulter Diagnostics, Beckton Dickinson and Company, Quidel Corp., and Sphingotec GMBH. The other authors report no conflicts., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The American College of Cardiology (ACC) recently published an Expert Consensus Decision Pathway for chest pain., Objectives: The purpose of this study was to validate the ACC Pathway in a multisite U.S., Methods: An observational cohort study of adults with possible acute coronary syndrome was conducted. Patients were accrued from 5 U.S. Emergency Departments (November 1, 2020, to July 31, 2022). ECGs and 0- and 2-hour high-sensitivity troponin (Beckman Coulter) measures were used to stratify patients according to the ACC Pathway. The primary safety outcome was 30-day all-cause death or myocardial infarction (MI). Efficacy was defined as the proportion stratified to the rule-out zone. Negative predictive value for 30-day death or MI was assessed among the whole cohort and in a subgroup of patients with coronary artery disease (CAD) (prior MI, revascularization, or ≥70% coronary stenosis)., Results: ACC Pathway assessments were complete in 14,395 patients, of whom 51.7% (7,437 of 14,395) were women with a median age of 56 years (Q1-Q3: 44-68 years). Known CAD was present in 23.5% (3,386 of 14,395) and 30-day death or MI occurred in 8.1% (1,168 of 14,395). The ACC Pathway had an efficacy of 48.1% (95% CI: 47.3%-49.0%). Among patients in the rule-out zone, 0.3% (22 of 6,930) had death or MI at 30 days, yielding a negative predictive value of 99.7% (95% CI: 99.5%-99.8%). In patients with known CAD, 20.0% (676 of 3,386) were classified to the rule-out zone, of whom 1.5% (10 of 676) had death or MI., Conclusions: The ACC expert consensus decision pathway was safe and efficacious. However, it may not be safe for use among patients with known CAD., Competing Interests: Funding Support and Author Disclosures This study was funded internally by Wake Forest University Health Systems. The Wake Forest Clinical and Translational Science Institute, supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through UL1TR001420. Dr Mahler has received funding/support from Roche Diagnostics, Abbott Laboratories, QuidelOrtho Clinical Diagnostics, Siemens, Grifols, Pathfast, Genetesis, Cytovale, Beckman Coulter, Brainbox, AHRQ (R01HS029017 and R21HS029234), The Duke Endowment, National Foundation of Emergency Medicine, and HRSA (1H2ARH399760100); is a consultant for Roche, Abbott, Siemens, QuidelOrtho, Genetesis, Inflammatix, and Radiometer; and is the Chief Medical Officer for Impathiq Inc. Dr Ashburn has received funding from AHRQ (R01HS029017). Dr Supples has received funding from the National Institutes of Health (UL1TR001420), HRSA (1H2ARH399760100), and the National Foundation of Emergency Medicine. Dr Snavely has received funding from Abbott Laboratories, AHRQ (R01HS029017), and HRSA (1H2ARH399760100). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The HEART Pathway (History, Electrocardiogram, Age, Risk factors, Troponin) can be used with high-sensitivity cardiac troponin to risk stratify emergency department patients with possible acute coronary syndrome. However, data on whether a high-sensitivity HEART Pathway (hs-HP) are safe and effective is lacking., Methods: An interrupted time series study was conducted at 5 North Carolina sites in 26 126 adult emergency department patients being investigated for possible acute coronary syndrome and without ST-segment-elevation myocardial infarction. Patients were accrued into 16-month preimplementation and postimplementation cohorts with a 6-month wash-in phase. Preimplementation (January 2019 to April 2020), the traditional HEART Pathway was used with 0- and 3-hour contemporary troponin measures (Siemens). In the postimplementation period (November 2020 to February 2022), a modified hs-HP was used with 0- and 2-hour high-sensitivity cardiac troponin (Beckman Coulter) measures. The primary safety and effectiveness outcomes were 30-day all-cause death or myocardial infarction and 30-day hospitalizations. These outcomes and early discharge rate (emergency department discharge without stress testing or coronary angiography) were determined from health records and death index data. Outcomes were compared preimplementation versus postimplementation using χ 2 tests and multivariable logistic regression to adjust for potential confounders., Results: Preimplementation and postimplementation cohorts included 12 317 and 13 809 patients, respectively, of them 52.7% (13 767/26 126) were female with a median age of 54 years (interquartile range, 42-66). Rates of 30-day death or MI were 6.8% (945/13 809) postimplementation and 7.7% (948/12 317) preimplementation (adjusted odds ratio, 1.00 [95% CI, 0.90-1.11]). hs-HP implementation was associated with 19.9% (95% CI, 18.7%-21.1%) higher early discharges (post versus pre: 63.6% versus 43.7%; adjusted odds ratio, 2.22 [95% CI, 2.10-2.35]). The hs-HP was also associated with 16.1% (95% CI, 14.9%-17.3%) lower 30-day hospitalizations (postimplementation versus preimplementation, 31.4% versus 47.5%; adjusted odds ratio, 0.51 [95% CI, 0.48-0.54]). Among early discharge patients, death or myocardial infarction occurred in 0.5% (41/8780) postimplementation versus 0.4% (22/5383) preimplementation ( P =0.61)., Conclusions: hs-HP implementation is associated with increased early discharges without increasing adverse events. These findings support the use of a modified hs-HP to improve chest pain care., Competing Interests: Disclosures Dr Mahler receives funding/support from Roche Diagnostics, Abbott Laboratories, Siemens, Grifols, Pathfast, QuidelOrtho, Genetesis, Cytovale, National Foundation of Emergency Medicine, Duke Endowment, Health Resources and Services Administration (1H2ARH399760100), Agency for Healthcare Research and Quality (R01HS029017). Dr Mahler is a consultant for Roche, Abbott, Siemens, QuidelOrtho, Genetesis, Inflammatix, Radiometer, and Amgen and the Chief Medical Officer for Impathiq, Inc. Dr Ashburn receives funding from NHLBI (T32HL076132). Dr Stopyra receives research funding from National Center for Advancing Translational Sciences/National Institutes of Health (KL2TR001421), Health Resources and Services Administration (H2ARH39976-01-00), Roche Diagnostics, Abbott Laboratories, Pathfast, Genetesis, Cytovale, Forest Devices, Vifor Pharma, and Chiesi Farmaceutici. Dr O’Neill receives funding from Cytovale. Dr Snavely receives funding from Abbott Laboratories and Health Resources and Services Administration (1H2ARH399760100).

Background: The diagnostic performance of the high-sensitivity troponin T (hs-cTnT) 0/2-h algorithm is unclear among U.S. emergency department (ED) patients with acute chest pain., Methods: A preplanned subgroup analysis of the STOP-CP cohort study was conducted. Participants with 0- and 2-h hs-cTnT measures prospectively enrolled at eight U.S. EDs from January 2017 to September 2018 were stratified into rule-out, observation, and rule-in zones using the hs-cTnT 0/2-h algorithm alone and combined with the history, electrocardiogram, age, and risk factor (HEAR) score. The primary outcome was adjudicated 30-day cardiac death or myocardial infarction (CDMI). The sensitivity and negative predictive value (NPV) of the 0/2-h rule-out zone and specificity and positive predictive value (PPV) of the rule-in zone for 30-day CDMI were calculated., Results: Of the 1307 patients accrued, 53.6% (700/1307) were male and 58.6% (762/1307) were White, with a mean ± SD age of 57.5 ± 12.7 years. At 30 days, CDMI occurred in 12.9% (168/1307) of participants. The 0/2-h algorithm ruled out 61.4% (802/1307) of patients. Among rule-out patients, 1.9% (15/802) experienced 30-day CDMI, resulting in a sensitivity of 91.1% (95% confidence interval [CI] 85.7%-94.9%) and NPV of 98.1% (95% CI 96.9%-98.9%). The 0/2-h algorithm ruled in 12.4% (162/1307) patients of whom 61.7% (100/162) experienced 30-day CDMI. The rule-in zone specificity was 94.6% (95% CI 93.1%-95.8%) and PPV was 61.7% (95% CI 53.8%-69.2%) for 30-day CDMI. The 0/2-h algorithm combined with HEAR score ruled out 30.7% (401/1307) of patients with a sensitivity and NPV for 30-day CDMI of 98.2% (95% CI 94.9%-99.6%) and 99.3% (95% CI 97.8%-99.8%), respectively., Conclusions: The hs-cTnT 0/2-h algorithm ruled out most patients. With NPV of <99% for 30-day CDMI, the hs-cTnT 0/2-h algorithm, many emergency physicians may not consider it safe to use for U.S. ED patients. When combined with a low-risk HEAR score, NPV was >99% for 30-day CDMI at the cost of reduced efficacy., (© 2024 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Background: Despite their vital roles, informal caregivers of adult cancer patients are commonly overlooked in cancer care. This study describes processes for identifying cancer caregivers and processes for distress screening and management among caregivers and patients in the understudied community oncology setting., Methods: Supportive care leaders from the National Cancer Institute Community Oncology Research Program practices completed online survey questions regarding caregiver identification, caregiver and patient distress screening, and distress management strategies. We described practice group characteristics and prevalence of study outcomes. Multivariable logistic regression explored associations between practice group characteristics and caregiver identification in the electronic health record (EHR)., Results: Most (64.9%, 72 of 111) supportive care leaders reported routine identification and documentation of informal caregivers; 63.8% record this information in the EHR. Only 16% routinely screen caregivers for distress, though 92.5% screen patients. Distress management strategies for caregivers and patients are widely available, yet only 12.6% are routinely identified and screened and had at least 1 referral strategy for caregivers with distress; 90.6% are routinely screened and had at least 1 referral strategy for patients. Practices with a free-standing outpatient clinic (odds ratio [OR] = 0.29, P = .0106) and academic affiliation (OR = 0.01, P = .04) were less likely to identify and document caregivers in the EHR. However, higher oncologist volume was associated with an increased likelihood of recording caregiver information in the EHR (OR = 1.04, P = .02)., Conclusions: Despite high levels of patient distress screening and management, few practices provide comprehensive caregiver engagement practices. Existing patient engagement protocols may provide a promising platform to build capacity to better address caregiver needs., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The diagnostic performance of the high-sensitivity troponin T (hs-cTnT) European Society of Cardiology (ESC) 0/1-h algorithm in sex and race subgroups of US Emergency Department (ED) patients is unclear. A pre-planned subgroup analysis of the STOP-CP cohort study was conducted. Participants with 0- and 1-h hs-cTnT measures from eight US EDs (1/2017 to 9/2018) were stratified into rule-out, observation, and rule-in zones using the hs-cTnT ESC 0/1 algorithm. The primary outcome was adjudicated 30-day cardiac death or MI. The proportion with the primary outcome in each zone was compared between subgroups with Fisher's exact tests. The negative predictive value (NPV) of the ESC 0/1 rule-out zone for 30-day CDMI was calculated and compared between subgroups using Fisher's exact tests. Of the 1422 patients enrolled, 54.2% (770/1422) were male and 58.1% (826/1422) white with a mean age of 57.6 ± 12.8 years. At 30 days, cardiac death or myocardial infarction (MI) occurred in 12.9% (183/1422) of participants. Among patients stratified to the rule-out zone, 30-day cardiac death or MI occurred in 1.1% (5/436) of women versus 2.1% (8/436) of men (p = .40) and 1.2% (4/331) of non-white patients versus 1.8% (9/490) of white patients (p = .58). The NPV for 30-day cardiac death or MI was similar among women versus men (98.9% [95% confidence interval, CI: 97.3-99.6] vs. 97.9% [95% CI: 95.9-99.1]; p = .40) and among white versus non-white patients (98.8% [95% CI: 96.9-99.7] vs. 98.2% [95% CI: 96.5-99.2]; p = .39). NPVs <99% in each subgroup suggest the hs-cTnT ESC 0/1-h algorithm may not be safe for use in US EDs. Trial Registration: High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP; ClinicalTrials.gov: NCT02984436; https://clinicaltrials.gov/ct2/show/NCT02984436)., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Competing Interests: Disclosures Dr Ashburn receives funding from the National Heart, Lung, and Blood Institute (T32HL076132). Dr McCord receives research funding and support from Beckman Coulter, Roche Diagnostics, Abbott Laboratories, and Siemens. He is a consultant for Beckman Coulter, Roche Diagnostics, and Siemens. Dr Snavely receives funding from Abbott and Health Resources and Services Administration (1H2ARH399760100). Dr Christenson is a consultant for and receives funding and support from Roche Diagnostics, Siemens Healthineers, Beckman Coulter Diagnostics, Becton Dickinson and Co, Quidel Corp, and Sphingotec GMBH. Dr Apple reports consulting fees from HyTest Ltd., advisory fees from Werfen and Qorvo Biotechnology, nonsalaried grant support through the Hennepin Healthcare Research Institute from Abbott Diagnostics, Abbott POC, Roche Diagnostics, Siemens Healthcare, Quidel, Ortho-Clinical Diagnostics, Becton Dickinson; and fees for serving as Associate Editor for Clinical Chemistry. Dr Peacock received research grants from Brainbox, RCE, and Salix, served as a consultant for Abbott, Brainbox, Instrument Labs, Janssen, Osler, Roche, Siemens, and Vifor, and has stock/ownership interests in AseptiScope Inc, Brainbox Inc, Braincheck Inc, Coagulo Inc, Comprehensive Research Associates LLC, Comprehensive Research Management Inc, Emergencies in Medicine LLC, Fast Inc, Forrest Devices, Ischemia DX LLC, Lucia Inc, Prevencio Inc, RCE Technologies, ROMTech, ScPharma, Trivirum Inc, Upstream Inc. Dr. deFilippi consults for Abbott Diagnostics, Fujirebio, Ortho Diagnostics, Quidell, Roche Diagnostics and Siemens Healthineers. Dr Mahler receives funding and support from Roche Diagnostics, Abbott Laboratories, Ortho Clinical Diagnostics, Siemens, Grifols, Pathfast, OrthoQuidel, Beckman Coulter, Genetesis, Cytovale, Health Resources and Services Administration (1H2ARH399760100) and AHRQ (R01HS029017). He is a consultant for Roche, Quidel, Abbott, Genetesis, Inflammatix, Radiometer, and Amgen and is the Chief Medical Officer for Impathiq Inc.

Background: Radiation therapy is an integral component of treatment that can predispose to carotid artery stenosis (CAS) and increase the risk of cerebrovascular events for head and neck cancer survivors. The utility of screening for CAS with carotid ultrasound in asymptomatic head and neck cancer survivors is unclear. Methods: In this prospective, cross-sectional pilot study, 60 patients who have no evidence of cancer at least 2 years from completion of RT will undergo screening carotid ultrasound to identify patients with high risk of cardiovascular events. Results: Outcomes will include clinically significant CAS, carotid intima-media thickness, acceptability/feasibility of screening, barriers to care and preliminary data on changes to medical management because of screening. Correlative multi-omics analyses will examine biomarkers of CAS after radiation therapy. Conclusion: The results of this study will provide valuable data on the prevalence of CAS and preliminary patient-centered data that will inform the design of a future large-scale, multi-site clinical trial. Clinical Trial Registration: NCT05490875 (ClinicalTrials.gov).

Background: The objective of this study is to identify patient and EMS agency factors associated with timely reperfusion of patients with ST-elevation myocardial infarction (STEMI)., Methods: We conducted a cohort study of adult patients (≥18 years old) with STEMI activations from 2016 to 2020. Data was obtained from a regional STEMI registry, which included eight rural county EMS agencies and three North Carolina percutaneous coronary intervention (PCI) centers. On each patient, prehospital and in-hospital time intervals were abstracted. The primary outcome was the ability to achieve the 90-minute EMS FMC to PCI time goal (yes vs. no). We used generalized estimating equations accounting for within-agency clustering to evaluate the association between patient and agency factors and meeting first medical contact (FMC) to PCI time goal while accounting for clustering within the agency., Results: Among 365 rural STEMI patients 30.1% were female (110/365) with a mean age of 62.5 ± 12.7 years. PCI was performed within the time goal in 60.5% (221/365) of encounters. The FMC to PCI time goal was met in 45.5% (50/110) of women vs 69.8% (178/255) of men ( p  < 0.001). The median PCI center activation time was 12 min (IQR 7-19) in the group that received PCI within the time goal compared to 21 min (IQR 10-37) in the cohort that did not. After adjusting for loaded mileage and other clinical variables (e.g., pulse rate, hypertension etc.), the male sex was associated with an improved chance of meeting the goal of FMC to PCI (aOR: 2.94; 95% CI 2.11-4.10) compared to the female sex., Conclusion: Nearly 40% of rural STEMI patients transported by EMS failed to receive FMC to PCI within 90 min. Women were less likely than men to receive reperfusion within the time goal, which represents an important health care disparity.

Background: Emergency medical services (EMS) clinicians demonstrate a high prevalence of chronic medical conditions that place them at risk for early mortality. Workplace health promotion programs improve health outcomes, but the availably of such programs for EMS clinicians has not been described. We investigate the availability, scope, and participation of workplace health promotion programs available to EMS clinicians in North Carolina (NC)., Methods: We administered an electronic survey based on the Centers for Disease Control and Prevention Worksite Health ScoreCard to key representatives of EMS agencies within NC that provide primarily transport-capable 9-1-1 response with ground ambulances. We collected information on agency size, rurality, elements of health promotion programs offered, incentives for participation, and participation rate. We calculated descriptive statistics using frequency and percentage for worksite and health promotion program characteristics. We compared the participation rate for agencies who did and did not incentivize participation using Fisher's exact test., Results: Complete responses were received from 69 of 92 agencies (response = 75%) that collectively employ 6679 EMS clinicians [median employees per agency 71 (IQR 50-131)]. Most agencies (88.4%, 61/69) offered at least one element of a worksite health program, but only 13.0% (9/69) offered all elements of a worksite health program. In descending order, the availability of program elements were employee assistance programs (73.9%, 51/69), supportive physical and social environment (66.7%, 46/69), health education (62.3%, 43/69), health risk assessments (52.2%, 36/69), and organization culture of health promotion (20.3%, 14/69). Of agencies with programs, few (11.5%, 7/61) required participation, but most (59.0%, 36/61) offered incentives to participate. Participation rates were <25% among nearly all of the agencies that did not offer incentives, but >50% among most agencies that did offer incentives ( p  < 0.001)., Conclusion: While most agencies offer at least one element of a worksite health promotion program, few agencies offer all elements and participation rates are low.

Objective: The History, Electrocardiogram (ECG), Age, and Risk factor (HEAR) and History and ECG-only Manchester Acute Coronary Syndromes (HE-MACS) risk scores can risk stratify chest pain patients without troponin measures. The objective of this study was to determine if either risk score could achieve the ≥99% negative predictive value (NPV) required to rule out major adverse cardiovascular events (MACE; a composite of all-cause death, myocardial infarction, or coronary revascularization) at 30 days or the ≥50% positive predictive value (PPV) indicative of a patient possibly needing interventional cardiology., Methods: We performed a pre-planned secondary analysis of the prospective multisite PARAHEART ( n  = 462, 12/2016-1/2018) and RESCUE ( n  = 767, 4/2018-1/2019) trials, which accrued adults ≥21 years old with acute non-traumatic chest pain transported by emergency medical services (EMS). Paramedics prospectively completed risk assessment forms. Very low risk was defined by a HEAR score of 0-1 or HE-MACS probability <4%. The primary outcome was 30-day MACE, which was determined by adjudication (PARAHEART) or electronic record review (RESCUE). NPV and PPV with exact 95% confidence intervals (95%CI) for 30-day MACE were calculated for each risk score and compared using McNemar's tests., Results: Among the PARAHEART and RESCUE cohorts, 30-day MACE occurred in 18.8% (87/462) and 6.9% (53/767) of patients, respectively. In PARAHEART, 7.8% (36/462) were very low risk by HEAR score vs. 7.8% (36/462) by HE-MACS ( p  = 1.0). The HEAR score had a NPV of 97.2% (95%CI 91.9-100.0) vs. 91.7% (95%CI 82.6-100.0) for HE-MACS ( p  = 0.15). The HEAR and HE-MACS PPVs were similar [46.4% (95%CI 28.0-64.9) vs. 33.3% (95%CI 13.2-53.5) ( p  = 0.26)]. In RESCUE, the HEAR score identified 14.2% (109/767) as low risk compared to 8.3% (64/767) by HE-MACS ( p  < 0.001). In this cohort, the HEAR and HE-MACS scores had similar NPVs [98.2% (95%CI 95.7-100.0) vs. 98.4% (95%CI 95.4-100.0) ( p  = 0.89)] and PPVs [16.2% (95%CI 6.2-32.0) vs. 22.6% (95%CI 12.3-36.2) ( p  = 0.41)]., Conclusions: In two prehospital chest pain cohorts, neither the HEAR score nor HE-MACS achieved sufficient NPV or PPV to rule out or rule in 30-day MACE.

Background: Hypercholesterolemia (HCL) affects nearly half of Emergency Department (ED) patients who present with possible acute coronary syndrome (ACS). However, it is unknown whether US ED providers obtain lipid panels, calculate 10-year atherosclerotic cardiovascular disease (ASCVD) risk, and prescribe cholesterol-lowering medications for these patients., Methods: We conducted a nationwide cross-sectional ED survey from April 18, 2023, to May 12, 2023. An electronic survey assessing current preventive HCL care practices for patients being evaluated for ACS. A convenience sample was obtained by sharing the survey with ED medical directors, chairs, and senior leaders using emergency medicine professional organization listservs and snowball sampling. Responding EDs were categorized as being associated with an academic medical center (AMC) or not (non-AMC)., Results: During the 4-week study period, 110 EDs (50 AMC and 60 non-AMC EDs) across 39 states responded. Just 1.8% (2/110) stated that their providers obtain a lipid panel on at least half of patients with possible ACS and only one ED (0.9%) responded that its providers calculate 10-year ASCVD risk and prescribe cholesterol medication for the majority of eligible patients. Most reported never obtaining lipid panels (60.9%, 67/110), calculating 10-year ASCVD risk (55.5%, 61/110), or prescribing cholesterol-lowering medications (52.7%, 58/110)., Conclusions: The vast majority of US ED providers do not provide preventive cardiovascular care for patients presenting with possible ACS. Most ED providers do not evaluate for HCL, calculate ASCVD risk, or prescribe cholesterol-lowering medications for these patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale and Objectives: The treatment of locally advanced lung cancer (LALC) with radiotherapy (RT) can be challenging. Multidisciplinary collaboration between radiologists and radiation oncologists (ROs) may optimize RT planning, reduce uncertainty in follow-up imaging interpretation, and improve outcomes., Materials and Methods: In this prospective clinical treatment trial (clinicaltrials.gov NCT04844736), 37 patients receiving definitive RT for LALC, six attending ROs, and three thoracic radiologists were consented and enrolled across four treatment centers. Prior to RT plan finalization, representative computed tomography (CT) slices with overlaid outlines of preliminary irradiation targets were shared with the team of radiologists. The primary endpoint was to assess feasibility of receiving feedback no later than 4 business days of RT simulation on at least 50% of plans., Results: Thirty-seven patients with lung cancer were enrolled, and 35 of 37 RT plans were reviewed. Of the 35 patients reviewed, mean age was 69 years. For 27 of 37 plans (73%), feedback was received within 4 or fewer days (interquartile range 3-4 days). Thirteen of 35 cases (37%) received feedback that the delineated target potentially did not include all sites suspicious for tumor involvement. In total, changes to the RT plan were recommended for over- or undercoverage in 16 of 35 cases (46%) and implemented in all cases. Radiology review resulted in no treatment delays and substantial changes to irradiated volumes: gross tumor volume, -1.9 to +96.1%; planning target volume, -37.5 to +116.5%., Conclusion: Interdisciplinary collaborative RT planning using a simplified workflow was feasible, produced no treatment delays, and prompted substantial changes in RT targets., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: ST-elevation myocardial infarction (STEMI) guidelines recommend an emergency medical services (EMS) first medical contact (FMC) to percutaneous coronary intervention (PCI) time of ≤90 min. The primary objective of this study was to evaluate the association between FMC to PCI time and mortality in rural STEMI patients., Methods: We conducted a cohort study of patients ≥18 years old with STEMI activations from January 2016 to March 2020. Data were obtained from a rural North Carolina Regional STEMI Data Registry, which included eight rural EMS agencies and three PCI centers, the National Cardiovascular Data Registry, and the EMS electronic health record. Prehospital and in-hospital time intervals were digitally abstracted. The outcome of index hospitalization mortality was compared between patients who did and did not meet FMC to PCI time goal using Fisher's exact tests. Negative predictive value (NPV) for index hospitalization death was calculated with 95% confidence intervals (CIs). A receiver operating characteristic curve was constructed and an optimal FMC to PCI time goal was identified by maximizing NPV to prevent index hospitalization death., Results: Among 365 rural EMS STEMI patients, 30.1% (110/365) were female with a mean ± SD age of 62.5 ± 12.7 years. PCI was performed within the 90-min time goal in 60.5% (221/365) of patients. Among these patients, 3% (11/365) died during initial STEMI hospitalization, with 1.4% (3/221) mortality in the group that met the 90-minute time goal compared to 5.6% (8/144) in patients exceeding the time goal (p = 0.03). Meeting the 90-min time goal yielded a 98.6% (95% CI 96.1%-99.7%) NPV for index death. A 78-min FMC to PCI time was the optimal cut point, yielding a NPV for index mortality of 99.3% (95% CI 96.1%-100%)., Conclusions: Death among rural patients with STEMI was four times more likely when they did not receive PCI within 90 min., (© 2023 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Background: Identifying and eliminating racial health care disparities is a public health priority. However, data evaluating race differences in emergency department (ED) chest pain care are limited., Methods: We conducted a secondary analysis of the High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP) cohort, which prospectively enrolled adults with symptoms suggestive of acute coronary syndrome without ST-elevation from eight EDs in the United States from 2017 to 2018. Race was self-reported by patients and abstracted from health records. Rates of 30-day noninvasive testing (NIT), cardiac catheterization, revascularization, and adjudicated cardiac death or myocardial infarction (MI) were determined. Logistic regression was used to evaluate the association between race and 30-day outcomes with and without adjustment for potential confounders., Results: Among 1454 participants, 42.3% (615/1454) were non-White. At 30 days NIT occurred in 31.4% (457/1454), cardiac catheterization in 13.5% (197/1454), revascularization in 6.0% (87/1454), and cardiac death or MI in 13.1% (190/1454). Among Whites versus non-Whites, NIT occurred in 33.8% (284/839) versus 28.1% (173/615; odds ratio [OR] 0.76, 95% confidence interval [CI] 0.61-0.96) and catheterization in 15.9% (133/839) versus 10.4% (64/615; OR 0.62, 95% CI 0.45-0.84). After covariates were adjusted for, non-White race remained associated with decreased 30-day NIT (adjusted OR [aOR] 0.71, 95% CI 0.56-0.90) and cardiac catheterization (aOR 0.62, 95% CI 0.43-0.88). Revascularization occurred in 6.9% (58/839) of Whites versus 4.7% (29/615) of non-Whites (OR 0.67, 95% CI 0.42-1.04). Cardiac death or MI at 30 days occurred in 14.2% of Whites (119/839) versus 11.5% (71/615) of non-Whites (OR 0.79 95% CI 0.57-1.08). After adjustment there was still no association between race and 30-day revascularization (aOR 0.74, 95% CI 0.45-1.20) or cardiac death or MI (aOR 0.74, 95% CI 0.50-1.09)., Conclusions: In this U.S. cohort, non-White patients were less likely to receive NIT and cardiac catheterization compared to Whites but had similar rates of revascularization and cardiac death or MI., (© 2023 Society for Academic Emergency Medicine.)

Background: Hypercholesterolemia (HCL) is common among Emergency Department (ED) patients with chest pain but is typically not addressed in this setting. This study aims to determine whether a missed opportunity for Emergency Department Observation Unit (EDOU) HCL testing and treatment exists., Methods: We conducted a retrospective observational cohort study of patients ≥18 years old evaluated for chest pain in an EDOU from 3/1/2019-2/28/2020. The electronic health record was used to determine demographics and if HCL testing or treatment occurred. HCL was defined by self-report or clinician diagnosis. Proportions of patients receiving HCL testing or treatment at 1-year following their ED visit were calculated. HCL testing and treatment rates at 1-year were compared between white vs. non-white and male vs. female patients using multivariable logistic regression models including age, sex, and race., Results: Among 649 EDOU patients with chest pain, 55.8% (362/649) had known HCL. Among patients without known HCL, 5.9% (17/287, 95% CI 3.5-9.3%) had a lipid panel during their index ED/EDOU visit and 26.5% (76/287, 95% CI 21.5-32.0%) had a lipid panel within 1-year of their initial ED/EDOU visit. Among patients with known or newly diagnosed HCL, 54.0% (229/424, 95% CI 49.1-58.8%) were on treatment within 1-year. After adjustment, testing rates were similar among white vs. non-white patients (aOR 0.71, 95% CI 0.37-1.38) and men vs. women (aOR 1.32, 95% CI 0.69-2.57). Treatment rates were similar among white vs. non-white (aOR 0.74, 95% CI 0.53-1.03) and male vs. female (aOR 1.08, 95% CI 0.77-1.51) patients., Conclusions: Few patients were evaluated for HCL in the ED/EDOU or outpatient setting after their ED/EDOU encounter and only 54% of patients with HCL were on treatment during the 1-year follow-up period after the index ED/EDOU visit. These findings suggest a missed opportunity to reduce cardiovascular disease risk exists by evaluating and treating HCL in the ED or EDOU., Competing Interests: Declaration of Competing Interest Dr. Ashburn receives funding from NHLBI (T32HL076132). Dr. Snavely receives funding from Abbott and HRSA (1H2ARH399760100). Dr. Rikhi receives funding from NHLBI (T32HL076132). Dr. Shapiro has participated in scientific advisory boards with Amgen, Novartis, Ionis, Precision BioSciences and has served as a consultant for Regeneron, Ionis, Novartis, and EmendoBio. Dr. Stopyra receives research funding from NCATS/NIH (KL2TR001421), HRSA (H2ARH39976–01-00), Roche Diagnostics, Abbott Laboratories, Pathfast, Genetesis, Cytovale, Forest Devices, Vifor Pharma, and Chiesi Farmaceutici. Dr. Mahler receives funding/support from Roche Diagnostics, Abbott Laboratories, QuidelOrtho, Siemens, Grifols, Pathfast, Genetesis, Cytovale, and HRSA (1H2ARH399760100). He is a consultant for Roche, Abbott, Beckman Coulter, Siemens, Genetesis, Inflammatix, Radiometer, and Amgen and is the Chief Medical Officer for Impathiq Inc. The other authors report no conflicts., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hypercholesterolemia (HCL) is common among emergency department (ED) and ED observation unit (EDOU) patients with chest pain but is not typically addressed in these settings. The objective of this study was to assess patient attitudes towards EDOU-based HCL care using the Health Belief Model., Methods: We conducted a cross-sectional survey study among 100 EDOU patients ≥18 years-old evaluated for chest pain in the EDOU of a tertiary care center from September 1, 2020, to November 01, 2021. Five-point Likert-scale surveys were used to assess each Health Belief Model domain: Cues to Action, Perceived Susceptibility, Perceived Barriers, Perceived Self-Efficacy, and Perceived Benefits. Responses were categorized as agree or do not agree., Results: The participants were 49.0% (49/100) female, 39.0% (39/100) non-white, and had a mean age of 59.0 ± 12.4 years. Most (83.0% [83/100, 95% confidence interval (CI), 74.2%-89.8%]) agreed the EDOU is an appropriate place for HCL education and 52.0% (52/100, 95% CI, 41.8%-62.1%) were interested in talking with their EDOU care team about HCL. Regarding Perceived Susceptibility, 88.0% (88/100, 95% CI, 80.0%-93.6%) believed HCL to be bad for their health, while 41.0% (41/100, 95% CI, 31.3%-51.3%) believed medication costs could be a barrier. For Perceived Self-Efficacy, 76.0% (76/100, 95% CI, 66.4%-84.0%) were receptive to taking medications. Overall, 95.0% (95/100, 95% CI, 88.7%-98.4%) believed managing HCL would benefit their health., Conclusions: This Health Belief Model-based survey indicates high patient interest in EDOU-initiated HCL care. Patients reported high rates of Perceived Susceptibility, Self-Efficacy, and Benefits and a minority found HCL therapy costs a barrier., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Emergency Department Observation Unit (EDOU) patients with chest pain have a high prevalence of smoking, a key cardiovascular disease risk factor. While in the EDOU, there is an opportunity to initiate smoking cessation therapy (SCT), but this is not standard practice. This study aims to describe the missed opportunity for EDOU-initiated SCT by determining the proportion of smokers who receive SCT in the EDOU and within 1-year of EDOU discharge and to evaluate if SCT rates vary by race or sex., Methods: We performed an observational cohort study of patients ≥18 years old being evaluated for chest pain in a tertiary care center EDOU from 3/1/2019-2/28/2020. Demographics, smoking history, and SCT were determined by electronic health record review. Emergency, family medicine, internal medicine, and cardiology records were reviewed to determine if SCT occurred within 1-year of their initial visit. SCT was defined as behavioral interventions or pharmacotherapy. Rates of SCT in the EDOU, 1-year follow-up period, and the EDOU through 1-year of follow-up were calculated. SCT rates from the EDOU through 1-year were compared between white vs. non-white and male vs. female patients using a multivariable logistic regression model including age, sex, and race., Results: Among 649 EDOU patients, 24.0% (156/649) were smokers. These patients were 51.3% (80/156) female and 46.8% (73/156) white, with a mean age of 54.4 ± 10.5 years. From the EDOU encounter through 1-year of follow-up, only 33.3% (52/156) received SCT. In the EDOU, 16.0% (25/156) received SCT. During the 1-year follow-up period, 22.4% (35/156) had outpatient SCT. After adjusting for potential confounders, SCT rates from the EDOU through 1-year were similar among whites vs. non-whites (aOR 1.19, 95% CI 0.61-2.32) and males vs. females (aOR 0.79, 95% CI 0.40-1.56)., Conclusions: SCT was rarely initiated in the EDOU among chest pain patients who smoke and most patients who did not receive SCT in the EDOU never received SCT at 1-year of follow-up. Rates of SCT were similarly low among race and sex subgroups. These data suggest an opportunity exists to improve health by initiating SCT in the EDOU., Competing Interests: Conflicts of interest Dr. Ashburn receives funding from NHLBI (T32HL076132). Dr. Snavely receives funding from Abbott and HRSA (1H2ARH399760100). Dr. Rikhi receives funding from NHLBI (T32HL076132). Dr. Stopyra receives research funding from NCATS/NIH (KL2TR001421), HRSA (H2ARH39976-01-00), Roche Diagnostics, Abbott Laboratories, Pathfast, Genetesis, Cytovale, Forest Devices, Vifor Pharma, and Chiesi Farmaceutici. Dr. Mahler receives funding/support from Roche Diagnostics, Abbott Laboratories, Ortho Clinical Diagnostics, Siemens, Grifols, Pathfast, Quidel, Genetesis, Cytovale, and HRSA (1H2ARH399760100). He is a consultant for Roche, Quidel, Abbott, Genetesis, Inflammatix, Radiometer, and Amgen and is the Chief Medical Officer for Impathiq Inc. The other authors report no conflicts., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: Disclosures Dr Miller received research funding from Abbott, Research Triangle Institute (RTI) International (COVID-related), and Gifols Therapeutics (COVID-related). Dr Mahler receives funding/support from Roche Diagnostics, Abbott Laboratories, QuidelOrtho, Siemens, Grifols, Pathfast, Genetesis, Cytovale, National Heart, Lung, and Blood Institute (NHLBI; 1 R01 HL118263-01), and Health Resources and Services Administration (HRSA; 1H2ARH399760100). He is a consultant for Roche, Quidel, Abbott, Genetesis, Inflammatix, Radiometer, and Amgen and the Chief Medical Officer for Impathiq Inc. Dr Stopyra receives research funding from National Center for Advancing Translational Sciences (NCATS)/National Institutes of Health (NIH) (KL2TR001421), HRSA (H2ARH39976-01-00), NHLBI (U01HL123027), Roche Diagnostics, and Abbott Point of Care. He has provided paid consulting to Roche Diagnostics. Dr Hiestand receives research funding from Siemens. Dr Caterino receives research funding from National Institute on Aging (NIA)/NIH. Dr Snavely receives research funding from Abbott Laboratories, NHLBI (1 R01 HL118263-01), and HRSA (1 H2ARH399760100).

Background: Screening for colorectal cancer (CRC) is widely recommended but underused, even though CRC is the third most diagnosed cancer and the second leading cause of cancer death in the USA. The mPATH™ program is an iPad-based application designed to identify patients due for CRC screening, educate them on the commonly used screening tests, and help them select their best option, with the goal of increasing CRC screening rates., Methods: The mPATH™ program consists of questions asked of all adult patients at check-in (mPATH™-CheckIn), as well as a module specific for patients due for CRC screening (mPATH™-CRC). In this study, the mPATH™ program is evaluated through a Type III hybrid implementation-effectiveness design. Specifically, the study consists of three parts: (1) a cluster-randomized controlled trial of primary care clinics comparing a "high touch" evidence-based implementation strategy with a "low touch" implementation strategy; (2) a nested pragmatic study evaluating the effectiveness of mPATH-CRC™ on completion of CRC screening; and (3) a mixed-methods study evaluating factors that facilitate or impede the maintenance of interventions like mPATH-CRC™. The primary objective is to compare the proportion of patients aged 50-74 who are eligible for CRC screening who complete mPATH™-CRC in the 6th month following implementation between the "high touch" and "low touch" implementation strategies. Effectiveness of mPATH™-CRC is evaluated by comparing the proportion who complete CRC screening within 16 weeks of their visit to the clinic between a pre-implementation cohort (8 months before implementation) and a post-implementation cohort (8 months after implementation)., Discussion: This study will provide data on both the implementation of the mPATH™ program and its effectiveness in improving screening rates for CRC. In addition, this work has the potential to have an even broader impact by identifying strategies to support the sustained use of other similar technology-based primary care interventions., Trial Registration: ClinicalTrials.gov NCT03843957. Registered on 18 February 2019., (© 2023. The Author(s).)

Importance: The European Society of Cardiology (ESC) 0/1-hour algorithm is a validated high-sensitivity cardiac troponin (hs-cTn) protocol for emergency department patients with possible acute coronary syndrome. However, limited data exist regarding its performance in patients with known coronary artery disease (CAD; prior myocardial infarction [MI], coronary revascularization, or ≥70% coronary stenosis)., Objective: To evaluate and compare the diagnostic performance of the ESC 0/1-hour algorithm for 30-day cardiac death or MI among patients with and without known CAD and determine if the algorithm could achieve the negative predictive value rule-out threshold of 99% or higher., Design, Setting, and Participants: This was a preplanned subgroup analysis of the STOP-CP prospective multisite cohort study, which was conducted from January 25, 2017, through September 6, 2018, at 8 emergency departments in the US. Patients 21 years or older with symptoms suggestive of acute coronary syndrome without ST-segment elevation on initial electrocardiogram were included. Analysis took place between February and December 2022., Interventions/exposures: Participants with 0- and 1-hour high-sensitivity cardiac troponin T (hs-cTnT) measures were stratified into rule-out, observation, and rule-in zones using the ESC 0/1-hour hs-cTnT algorithm., Main Outcomes and Measures: Cardiac death or MI at 30 days determined by expert adjudicators., Results: During the study period, 1430 patients were accrued. In the cohort, 775 individuals (54.2%) were male, 826 (57.8%) were White, and the mean (SD) age was 57.6 (12.8) years. At 30 days, cardiac death or MI occurred in 183 participants (12.8%). Known CAD was present in 449 (31.4%). Among patients with known CAD, the ESC 0/1-hour algorithm classified 178 of 449 (39.6%) into the rule-out zone compared with 648 of 981 (66.1%) without CAD (P < .001). Among rule-out zone patients, 30-day cardiac death or MI occurred in 6 of 178 patients (3.4%) with known CAD and 7 of 648 (1.1%) without CAD (P < .001). The negative predictive value for 30-day cardiac death or MI was 96.6% (95% CI, 92.8-98.8) among patients with known CAD and 98.9% (95% CI, 97.8-99.6) in patients without known CAD (P = .04)., Conclusions and Relevance: Among patients with known CAD, the ESC 0/1-hour hs-cTnT algorithm was unable to safely exclude 30-day cardiac death or MI. This suggests that clinicians should be cautious if using the algorithm in patients with known CAD. The negative predictive value was significantly higher in patients without a history of CAD but remained less than 99%.

Background: The HEART Pathway is widely used for chest pain risk stratification but has yet to be optimized for high sensitivity troponin T (hs-cTnT) assays., Methods: We conducted a secondary analysis of STOP-CP, a prospective cohort study enrolling adult ED patients with symptoms suggestive of acute coronary syndrome at 8 sites in the United States (US). Patients had a 0- and 1-hour hs-cTnT measured and a HEAR score completed. A derivation set consisting of 729 randomly selected participants was used to derive a hs-cTnT HEART Pathway with rule-out, observation, and rule-in groups for 30-day cardiac death or myocardial infarction (MI). Optimal baseline and 1-hour troponin cutoffs were selected using generalized cross validation to achieve a negative predictive value (NPV) >99% for rule out and positive predictive value (PPV) >60% or maximum Youden index for rule-in. Optimal 0-1-hour delta values were derived using generalized cross validation to maximize the NPV for the rule-out group and PPV for the rule-in group. The hs-cTnT HEART Pathway performance was validated in the remaining cohort (n = 723)., Results: Among the 1452 patients, 30-day cardiac death or MI occurred in 12.7% (184/1452). Within the derivation cohort the optimal hs-cTnT HEART Pathway classified 36.5% (266/729) into the rule-out group, yielding a NPV of 99.2% (95% CI: 98.2-100) for 30-day cardiac death or MI. The rule-in group included 15.4% (112/729) with a PPV of 55.4% (95% CI: 46.2-64.6). In the validation cohort, the hs-cTnT HEART Pathway ruled-out 37.6% (272/723), of which 2 had 30-day cardiac death or MI, yielding a NPV of 99.3% (95% CI: 98.3-100). The rule-in group included 14.5% (105/723), yielding a PPV of 57.1% (95% CI: 47.7-66.6)., Conclusions: A novel hs-cTnT HEART Pathway with serial 0- and 1-hour hs-cTnT measures has high NPV and moderate PPV for 30-day cardiac death or MI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The HEART Pathway is a validated accelerated diagnostic protocol (ADP) for patients with possible acute coronary syndrome (ACS). This study aimed to compare the safety and effectiveness of the HEART Pathway based on patient rurality (rural vs. urban) or socioeconomic status (SES)., Methods: We performed a preplanned subgroup analysis of the HEART Pathway Implementation Study. The primary outcomes were death or myocardial infarction (MI) and hospitalization at 30 days. Proportions were compared by SES and rurality with Fisher's exact tests. Logistic regression evaluated for interactions of ADP implementation with SES or rurality and changes in outcomes within subgroups., Results: Among 7245 patients with rurality and SES data, 39.9% (2887/7245) were rural and 22.2% were low SES (1607/7245). The HEART Pathway identified patients as low risk in 32.2% (818/2540) of urban versus 28.1% (425/1512) of rural patients (p = 0.007) and 34.0% (311/915) of low SES versus 29.7% (932/3137) high SES patients (p = 0.02). Among low-risk patients, 30-day death or MI occurred in 0.6% (5/818) of urban versus 0.2% (1/425) rural (p = 0.67) and 0.6% (2/311) with low SES versus 0.4% (4/932) high SES (p = 0.64). Following implementation, 30-day hospitalization was reduced by 7.7% in urban patients (adjusted odds ratio [aOR] 0.76, 95% confidence interval [CI] 0.66-0.87), 10.6% in low SES patients (aOR 0.68, 95% CI 0.54-0.86), and 4.5% in high SES patients (aOR 0.83, 95% CI 0.73-0.94). However, rural patients had a nonsignificant 3.3% reduction in hospitalizations., Conclusions: HEART Pathway implementation decreased 30-day hospitalizations regardless of SES and for urban patients but not rural patients. The 30-day death or MI rate was similar among low-risk patients., (© 2022 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Background: Rural patients with ST-elevation myocardial infarction (STEMI) may be less likely to receive prompt reperfusion therapy. This study's primary objective was to compare rural versus urban time intervals among a national cohort of prehospital patients with STEMI., Methods: The ESO Data Collaborative (Austin, TX), containing records from 1,366 emergency medical services agencies, was queried for adult 9-1-1 responses with suspected STEMI from 1/1/2018-12/31/2019. The scene address for each encounter was classified as either urban or rural using the 2010 US Census Urban Area Zip Code Tabulation Area relationship. The primary outcome was total EMS interval (9-1-1 call to hospital arrival); a key secondary outcome was the proportion of responses that had EMS intervals under 60 minutes. Generalized estimating equations were used to determine whether rural versus urban differences in interval outcomes occurred when adjusting for loaded mileage (distance from scene to hospital) and patient and clinical encounter characteristics., Results: Of 15,915,027 adult 9-1-1 transports, 23,655 records with suspected STEMI were included in the analysis. Most responses (91.6%, n = 21,661) occurred in urban settings. Median EMS interval was 37.6 minutes (IQR 30.0-48.0) in urban settings compared to 57.0 minutes (IQR 46.5-70.7) in rural settings (p < 0.01). Urban responses more frequently had EMS intervals <60 minutes (89.5%, n = 19,130), compared to rural responses (55.5%, n = 1,100, p < 0.01). After adjusting for loaded mileage, age, sex, race/ethnicity, abnormal vital signs, pain assessment, aspirin administration, and IV/IO attempt, rural location was associated with a 5.8 (95%CI 4.2-7.4) minute longer EMS interval than urban, and rural location was associated with a reduced chance of achieving EMS interval < 60 minutes (OR 0.40; 95%CI 0.33-0.49) as compared to urban location., Conclusion: In this large national sample, rural location was associated with significantly longer EMS interval for patients with suspected STEMI, even after accounting for loaded mileage.

Background: Cardiac arrest guidelines recommend epinephrine every 3-5 minutes during cardiac arrest resuscitation. However, it is unclear if multiple epinephrine doses are associated with improved outcomes. The objective of this study was to determine if a single-dose epinephrine protocol was associated with improved survival compared to traditional multidose protocols., Methods: We conducted a pre-post study across five North Carolina EMS agencies from 11/1/2016 to 10/29/2019. Patients ≥18 years old with attempted resuscitation for non-traumatic prehospital cardiac arrest were included. Data were collected 1 year before and after implementation of the single-dose epinephrine protocol. Prior to implementation, all agencies used a multidose epinephrine protocol. The Cardiac Arrest Registry to Enhance Survival (CARES) was used to obtain patient outcomes. Study outcomes were survival to hospital discharge (primary) and return of spontaneous circulation (ROSC). Analysis was by intention to treat. Outcomes were compared pre- vs. post-implementation using generalized estimating equations to account for clustering within EMS agencies. Adjusted analyses included age, sex, race, shockable vs. non-shockable rhythm, witnessed arrest, automatic external defibrillator availability, EMS response interval, and bystander cardiopulmonary resuscitation., Results: During the study period there were 1,690 encounters (899 pre- and 791 post-implementation). The population was 74.7% white, 61.1% male, and had a median age of 65 (IQR 53-76) years. Survival to hospital discharge was similar pre- vs. post-implementation [13.6% (122/899) vs. 15.4% (122/791); OR 1.19, 95%CI 0.89-1.59]. However, ROSC was more common post-implementation [42.3% (380/899) vs. 32.5% (257/791); OR 0.66, 95%CI 0.54-0.81]. After adjusting for covariates, the single-dose protocol was associated with similar survival to discharge rates (aOR 0.88, 95%CI 0.77-1.29), but with decreased ROSC rates (aOR 0.58, 95%CI 0.47-0.72)., Conclusion: A prehospital single-dose epinephrine protocol was associated with similar survival to hospital discharge, but decreased ROSC rates compared to the traditional multidose epinephrine protocol.

Background: Emergency medical services (EMS) assesses millions of patients with chest pain each year. However, tools validated to risk stratify patients for acute coronary syndrome (ACS) and pulmonary embolism (PE) have not been translated to the prehospital setting. The objective of this study is to assess the prehospital performance of risk stratification scores for 30-day major adverse cardiac events (MACE) and PE., Methods: A prospective observational cohort study of patients ≥21 years of age with acute chest pain who were transported by EMS in two North Carolina (NC) counties was conducted from 18 April 2018-2 January 2019. In this convenience sample, paramedics completed HEAR (history, electrocardiogram, age, risk factor), ED Assessment of Chest Pain Score (EDACS), Revised Geneva Score (RGS), and pulmonary embolism rule-out criteria (PERC) assessments on each patient. MACE (all-cause death, myocardial infarction, and revascularization) and PE at 30 days were determined by hospital records and NC Death Index. The positive (+LR) and negative likelihood ratios (-LR) of the risk scores for 30-day MACE and PE were calculated., Results: During the study period, 82.1% (687/837) patients had all four risk score assessments. The cohort was 51.1% (351/687) female, 49.5% (340/687) African American, and had a mean age of 55.0 years (SD 16.0). At 30 days, MACE occurred in 7.4% (51/687), PE occurred in 0.9% (6/687), and the combined outcome occurred in 8.2% (56/687). The HEAR score had a - LR of 0.46 (95% CI 0.27-0.78) and + LR of 1.48 (95% CI 1.26-1.74) for 30-day MACE. EDACS had a - LR of 0.61 (95% CI 0.46-0.81) and + LR of 2.53 (95% CI 1.86-3.46) for 30-day MACE. The PERC score had a - LR of 0 (95% CI 0.0-1.4) and a + LR of 1.38 (95% CI 1.32-1.45) for 30-day PE. The RGS score had a - LR of 0 (95% CI 0.0-0.65) and a + LR of 2.36 (95% CI 2.16-2.57) for 30-day PE. The combination of a low-risk HEAR score and negative PERC evaluation had a - LR of 0.25 (95% CI 0.08-0.76) and a + LR of 1.21 (95% CI 1.21-1.30) for 30-day MACE or PE., Conclusion: The combination of a paramedic-obtained HEAR score and PERC evaluation performed best to exclude 30-day MACE and PE but was not sufficient for directing prehospital decision making.

Background and Aims: Plasma low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are both associated with coronary heart disease (CHD). This study investigated whether elevated plasma Lp(a) concentration was associated with increased CHD risk when LDL-C was low (≤100 mg/dL) in individuals not on statin therapy., Methods: Participants from the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 4,585) were categorized into four groups: Group 1: LDL-C ≤ 100 mg/dL, Lp(a) < 50 mg/dL; Group 2: LDL-C > 100 mg/dL, Lp(a) < 50 mg/dL; Group 3: LDL-C ≤ 100 mg/dL, Lp(a) ≥ 50 mg/dL; and Group 4: LDL-C > 100 mg/dL, Lp(a) ≥ 50 mg/dL. The relationship of Lp(a) and LDL-C with time to CHD events was assessed with Kaplan Meier curves and multivariable Cox proportional hazard models., Results: Participants were followed for a mean of 13.4 years and a total of 315 CHD events occurred. Compared to participants with LDL-C ≤ 100 mg/dL and Lp(a) < 50 mg/dL, those with LDL-C > 100 mg/dL and Lp(a) < 50 mg/dL (Group 2) demonstrated no increased risk for CHD events (HR: 0.92; 95% CI: 0.69, 1.21). However, participants with LDL-C ≤ 100 mg/dL and Lp(a) ≥ 50 mg/dL (Group 3) and those with LDL-C > 100 mg/dL and Lp(a) ≥ 50 mg/dL (Group 4) exhibited significantly increased risk of CHD events compared to Group 1 (HR: 1.83; 95% CI: 1.02, 3.27) and Group 2 (HR: 1.61; 95% CI: 1.15, 2.26), respectively., Conclusions: When Lp(a) was elevated, risk of CHD events increased, regardless of baseline LDL-C., Competing Interests: Declaration of competing interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Shapiro has participated in scientific advisory boards with the following entities: Amgen; Novartis; Novo Nordisk; and has served as a consultant for Regeneron. Dr. Rikhi and Dr. Ashburn are supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL076132. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The remaining authors have nothing to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Brain metastases (BMs) are a common source of morbidity and mortality. Guidelines do not advise brain surveillance for locally advanced non-small cell lung cancer (LA-NSCLC). We describe the incidence, time to development, presentation, and management of BMs after definitive chemoradiotherapy (CRT)., Methods and Materials: We reviewed records of patients with LA-NSCLC treated with CRT within the period from 2013 to 2020. Descriptive statistics were used to characterize the population and the Kaplan-Meier method was used to estimate time to BM. Fisher exact tests and Wilcoxon rank-sum tests were used to compare outcomes between symptomatic and asymptomatic patients., Results: A total of 219 patients were reviewed including 96 with squamous cell carcinoma, 88 with adenocarcinoma, and 35 with large cell/not otherwise specified (LC/NOS). Thirty-nine patients (17.8%) developed BMs: 35 (90%) symptomatic and 4 (10%) asymptomatic. The rate of BM was highest in LC/NOS (34.3%) and adenocarcinoma (23.9%). Ninety percent of BMs occurred within 2 years. All asymptomatic patients underwent stereotactic radiosurgery alone, compared with 40% of symptomatic patients ( P  = .04). Symptomatic patients were more likely to require hospitalization (65.7% vs 0%, P  = .02), craniotomy (25.7% vs 0%, not significant), and steroids (91.4% vs 0%, P < .001). Cumulative BM volume was higher for symptomatic patients (4 vs 0.24 cm 3 , P < .001) as was median greatest axial dimension (2.18 vs 0.52 cm, P < .001)., Conclusions: We identified a high rate of BMs, particularly in LC/NOS and adenocarcinoma histology NSCLC. The majority were symptomatic. These results provide rationale for post-CRT magnetic resonance imaging brain surveillance for patients at high risk of BM., (© 2022 The Authors.)

Background: The HEART Pathway is a validated protocol for risk stratifying emergency department (ED) patients with possible acute coronary syndrome (ACS). Its performance in different age groups is unknown. The objective of this study is to evaluate its safety and effectiveness among older adults., Methods: A pre-planned subgroup analysis of the HEART Pathway implementation study was conducted. This prospective interrupted time series accrued adult ED patients with possible ACS who were without ST-elevation across three US sites from 11/2013-01/2016. After implementation, providers prospectively used the HEART Pathway to stratify patients as low-risk or non-low-risk. Patients were classified as older adults (≥65 years), middle-aged (46-64 years), and young (21-45 years). Primary safety and effectiveness outcomes were 30-day death or MI and hospitalization at 30 days, determined from health records, insurance claims, and death index data. Fisher's exact test compared low-risk proportions between groups. Sensitivity for 30-day death or MI and adjusted odds ratios (aORs) for hospitalization and objective cardiac testing were calculated., Results: The HEART Pathway implementation study accrued 8474 patients, of which 26.9% (2281/8474) were older adults, 45.5% (3862/8474) middle-aged, and 27.5% (2331/8474) were young. The HEART Pathway identified 7.4% (97/1303) of older adults, 32.0% (683/2131) of middle-aged, and 51.4% (681/1326) of young patients as low-risk (p < 0.001). The HEART Pathway was 98.8% (95% CI 97.1-100) sensitive for 30-day death or MI among older adults. Following implementation, the rate of 30-day hospitalization was similar among older adults (aOR 1.25, 95% CI 1.00-1.55) and cardiac testing increased (aOR 1.25, 95% CI 1.04-1.51)., Conclusion: The HEART Pathway identified fewer older adults as low-risk and did not decrease hospitalizations in this age group., (© 2022 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: Despite negative troponins and nonischemic electrocardiograms (ECGs), patients at moderate risk for acute coronary syndrome (ACS) are frequently admitted. The objective of this study was to describe the major adverse cardiac event (MACE) rate in moderate-risk patients and how it differs based on history of coronary artery disease (CAD)., Methods: A secondary analysis of the HEART Pathway implementation study was conducted. This prospective interrupted time-series study accrued adults with possible ACS from three sites (November 2013-January 2016). This analysis excluded low-risk patients determined by emergency providers' HEART Pathway assessments. Non-low-risk patients were further classified as high risk, based on elevated troponin measures or ischemic ECG findings or as moderate risk, based on HEAR score ≥ 4, negative troponin measures, and a nonischemic ECG. Moderate-risk patients were then stratified by the presence or absence of prior CAD (MI, revascularization, or ≥70% coronary stenosis). MACE (death, myocardial infarction, or revascularization) at 30 days was determined from health records, insurance claims, and death index data. MACE rates were compared among groups using a chi-square test and likelihood ratios (LRs) were calculated., Results: Among 4,550 patients with HEART Pathway assessments, 24.8% (1,130/4,550) were high risk and 37.7% (1715/4550) were moderate risk. MACE at 30 days occurred in 3.1% (53/1,715; 95% confidence interval [CI] = 2.3% to 4.0%) of moderate-risk patients. Among moderate-risk patients, MACE occurred in 7.1% (36/508, 95% CI = 5.1% to 9.8%) of patients with known CAD versus 1.4% (17/1,207, 95% CI = 0.9% to 2.3%) in patients without known prior CAD (p < 0.0001). The negative LR for 30-day MACE among moderate-risk patients without prior CAD was 0.08 (95% CI = 0.05 to 0.12)., Conclusion: MACE rates at 30 days were low among moderate-risk patients but were significantly higher among those with prior CAD., (© 2022 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Background: Methicillin-Resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections (HAI). Contact isolation has been traditionally implemented to stop transmission but its impact is increasingly questioned., Methods: A single center, retrospective, nonrandomized, observational, quasi-experimental study compared MRSA HAI rates between pre-/postdiscontinuation of MRSA contact isolation in a tertiary university hospital over 68 months. Data on primary outcomes, Central line-associated bloodstream infections and MRSA LabID bacteremia events, were analyzed by interrupted time series design using segmented Poisson regression modeling. As secondary outcomes catheter-associated urinary tract infections , ventilator-associated pneumonia , surgical site infections and hospital-associated pneumonia were compared using Fisher's exact tests. Current savings due to discontinuation were calculated based on gown use., Results: Two hundred and ninty-five patients developed 399 HAIs. Infection rates between pre- and postinterventions were as follows: Central line-associated bloodstream infections: (0.02% vs 0.02%; P-value = .64), MRSA LabID events: (0.01% vs 0.02%; P-value = .32), hospital-associated pneumonia: (0.01% vs 0.01%; P-value = .64), catheter-associated urinary tract infections: (0% vs 0.01%; P-value = .56), ventilator-associated pneumonia: (0.01% vs 0.01%; P-value = .32), surgical site infections (0.55% vs 0.15%; P-value = .03). Savings amount to $139,228 annually., Conclusions: Discontinuing CP did not negatively impact endemic MRSA HAI rates between pre-postdiscontinuation periods and saved costs for isolation materials., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Delays in care for patients with acute cardiac complaints are associated with increased morbidity and mortality. The objective of this study was to quantify rural and urban differences in prehospital time intervals for patients with cardiac complaints., Methods: The ESO Data Collaborative dataset consisting of records from 1332 EMS agencies was queried for 9-1-1 encounters with acute cardiac problems among adults (age ≥ 18) from 1/1/2013-6/1/2018. Location was classified as rural or urban using the 2010 United States Census. The primary outcome was total prehospital time. Generalized estimating equations evaluated differences in the average times between rural and urban encounters while controlling for age, sex, race, transport mode, loaded mileage, and patient stability., Results: Among 428,054 encounters, the median age was 62 (IQR 50-75) years with 50.7% female, 75.3% white, and 10.3% rural. The median total prehospital, response, scene, and transport times were 37.0 (IQR 29.0-48.0), 6.0 (IQR 4.0-9.0), 16.0 (IQR 12.0-21.0), and 13.0 (IQR 8.0-21.0) minutes. Rural patients had an average total prehospital time that was 16.76 min (95%CI 15.15-18.38) longer than urban patients. After adjusting for covariates, average total time was 5.08 (95%CI 4.37-5.78) minutes longer for rural patients. Average response and transport time were 4.36 (95%CI 3.83-4.89) and 0.62 (95%CI 0.33-0.90) minutes longer for rural patients. Scene time was similar in rural and urban patients (0.09 min, 95%CI -0.15-0.33)., Conclusion: Rural patients with acute cardiac complaints experienced longer prehospital time than urban patients, even after accounting for other key variables, such as loaded mileage., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Chest pain is a common reason for ambulance transport. Acute coronary syndrome (ACS) and pulmonary embolism (PE) risk assessments, such as history, electrocardiogram, age, risk factors (HEAR); Emergency Department Assessment of Chest Pain Score (EDACS); Pulmonary Embolism Rule-out Criteria (PERC); and revised Geneva score, are well validated for emergency department (ED) use but have not been translated to the prehospital setting. The objectives of this study were to evaluate the 1) prehospital completion rate and 2) inter-rater reliability of chest pain risk assessments., Methods: We conducted a prospective observational cohort study in two emergency medical services (EMS) agencies (April 18, 2018 - January 2, 2019). Adults with acute, non-traumatic chest pain without ST-elevation myocardial infarction or unstable vital signs were accrued. Paramedics were trained to use the HEAR, EDACS, PERC, and revised Geneva score assessments. A subset of patients (a priori goal of N = 250) also had the four risk assessments completed by their treating clinicians in the ED, who were blinded to the EMS risk assessments. Outcomes were 1) risk assessments completion rate and 2) inter-rater reliability between EMS and ED assessments. An a priori goal for completion rate was set as >75%. We computed kappa with corresponding 95% confidence intervals (CI) for each risk assessment as a measure of inter-rater reliability. Acceptable agreement was defined a priori as kappa ≥ 0.60., Results: During the study period, 837 patients with acute chest pain were accrued. The median age was 54 years, interquartile range 43-66, with 53% female and 51% Black. Completion rates for each risk assessment were above goal: the HEAR score was completed on 95.1% (796/837), EDACS on 92.0% (770/837), PERC on 89.4% (748/837), and revised Geneva score on 90.7% (759/837) of patients. We assessed agreement in a subgroup of 260 patients. The HEAR score had a kappa of 0.51 (95% CI, 0.41-0.61); EDACS was 0.60 (95% CI, 0.49-0.72); PERC was 0.71 (95% CI, 0.61-0.81); and revised Geneva score was 0.51 (95% CI, 0.39-0.62)., Conclusion: The completion rate of risk assessments for ACS and PE was high for prehospital field personnel. The PERC and EDACS both demonstrated acceptable agreement between paramedics and clinicians in the ED, although assessments with better agreement are likely needed.

Background: Informed decision aids provide information in the context of the patient's values and improve informed decision making (IDM). To overcome barriers that interfere with IDM, our team developed an innovative iPad-based application (aka "app") to help patients make informed decisions about colorectal cancer screening. The app assesses patients' eligibility for screening, educates them about their options, and empowers them to request a test via the interactive decision aid., Objective: The aim of the study is to explore how informed decision aids can be implemented successfully in primary care clinics, including the facilitators and barriers to implementation; strategies for minimizing barriers; adequacy of draft training materials; and any additional support or training desired by clinics., Design: This work deals with a multicenter qualitative study in rural and urban settings., Participants: A total of 48 individuals participated including primary care practice managers, clinicians, nurses, and front desk staff., Approach: Focus groups and semi-structured interviews, with data analysis were guided by thematic analysis., Key Results: Salient emergent themes were time, workflow, patient age, literacy, and electronic health record (EHR) integration. Saving time was important to most participants. Patient flow was a concern for all clinic staff, and they expressed that any slowdown due to patients using the iPad module or perceived additional work to clinic staff would make staff less motivated to use the program. Participants voiced concern about older patients being unwilling or unable to utilize the iPad and patients with low literacy ability being able to read or comprehend the information., Conclusion: Integrating new IDM apps into the current clinic workflow with minimal disruptions would increase the probability of long-term adoption and ultimate sustainability., Nih Trial Registry Number: R01CA218416-A1., Competing Interests: D.P.M. and A.D. are co-inventors of mPATH. D.P.M., A.D., and Wake Forest University Health Sciences would have an ownership interest in the mPATH app if it were commercialized in the future. Neither D.P.M. nor A.D. participated in data collection or analysis. K.L.F. reports grants from National Cancer Institute, during the conduct of the study; A.C.S. reports grants from NIH/NCI, during the conduct of the study; grants and personal fees from Shattuck Labs, outside the submitted work; the other authors declare that they do not have a conflict of interest to report. A.D. reports grants from National Cancer Institute, during the conduct of the study; In addition, A.D. has an ownership interest in the mPATH app. D.P.M. reports grants from National Cancer Institute, during the conduct of the study; In addition, D.P.M. has an ownership interest in the mPATH app., (Thieme. All rights reserved.)

Background: Expediting the measurement of serum troponin by leveraging EMS blood collection could reduce the diagnostic time for patients with acute chest pain and help address Emergency Department (ED) overcrowding. However, this practice has not been examined among an ED chest pain patient population in the United States., Methods: A prospective observational cohort study of adults with non-traumatic chest pain without ST-segment elevation myocardial infarction was conducted in three EMS agencies between 12/2016-4/2018. During transport, paramedics obtained a patient blood sample that was sent directly to the hospital core lab for troponin measurement. On ED arrival HEART Pathway assessments were completed by ED providers as part of standard care. ED providers were blinded to troponin results from EMS blood samples. To evaluate the potential impact on length of stay (LOS), the time difference between EMS blood draw and first clinical ED draw was calculated. To determine the safety of using troponin measures from EMS blood samples, the diagnostic performance of the HEART Pathway for 30-day major adverse cardiac events (MACE: composite of cardiac death, myocardial infarction (MI), coronary revascularization) was determined using EMS troponin plus arrival ED troponin and EMS troponin plus a serial 3-h ED troponin., Results: The use of EMS blood samples for troponin measures among 401 patients presenting with acute chest pain resulted in a mean potential reduction in LOS of 72.5 ± SD 35.7 min. MACE at 30 days occurred in 21.0% (84/401), with 1 cardiac death, 78 MIs, and 5 revascularizations without MI. Use of the HEART Pathway with EMS and ED arrival troponin measures yielded a NPV of 98.0% (95% CI: 89.6-100). NPV improved to 100% (95% CI: 92.9-100) when using the EMS and 3-h ED troponin measures., Conclusions: EMS blood collection used for core lab ED troponin measures could significantly reduce ED LOS and appears safe when integrated into the HEART Pathway., Competing Interests: Declaration of Competing Interest Dr. Stopyra receives research funding from NCATS/NIH (KL2TR001421), HRSA (H2ARH39976-01-00), NHLBI (U01HL123027), Roche Diagnostics and Abbott Point of Care. He has provided paid consulting to Roche Diagnostics. Dr. Snavely receives research funding from NHLBI (1 R01 HL118263-01) and HRSA (1 H2ARH399760100). Dr. Miller receives research funding/support from Siemens, Abbott Point of Care, Creavo Medical Technologies, Marcus Foundation, RTI International, Grifols, and NHLBI1 R01 HL118263. Dr. Mahler receives research funding from the Donaghue Foundation, Abbott Laboratories, Roche Diagnostics, Siemens, Ortho Clinical Diagnostics, Creavo Medical Technologies, PCORI, AHRQ, NHLBI (1 R01 HL118263-01) and HRSA (1 H2ARH399760100). He was a paid consultant for Roche Diagnostics and Amgen. Dr. Mahler is the Chief Medical Officer for Impathiq Inc., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Cancer-related financial hardship is associated with poor care outcomes and reduced quality of life for patients and families. Scalable intervention development to address financial hardship requires knowledge of current screening practices and services within community cancer care., Methods: The NCI Community Oncology Research Program (NCORP) 2017 Landscape Assessment survey assessed financial screening and financial navigation practices within U.S. community oncology practices. Logistic models evaluated associations between financial hardship screening and availability of a cancer-specific financial navigator and practice group characteristics (e.g., safety-net designation, critical access hospital, proportion of racial and ethnic minority patients served)., Results: Of 221 participating NCORP practice groups, 72% reported a financial screening process and 50% had a cancer-specific financial navigator. Practice groups with more than 10% of new patients with cancer enrolled in Medicaid ( adj OR = 2.81, P = 0.02) and with less than 30% racial/ethnic minority cancer patient composition ( adj OR = 3.91, P < 0.01) were more likely to screen for financial concerns. Practice groups with less than 30% racial/ethnic minority cancer patient composition ( adj OR = 2.37, P < 0.01) were more likely to have a dedicated financial navigator or counselor for patients with cancer., Conclusions: Most NCORP practice groups screen for financial concerns and half have a cancer-specific financial navigator. Practices serving more racial or ethnic minority patients are less likely to screen and have a designated financial navigator., Impact: The effectiveness of financial screening and navigation for mitigating financial hardship could be tested within NCORP, along with specific interventions to address cancer care inequities. See related commentary by Yabroff et al., p. 593 ., (©2020 American Association for Cancer Research.)

Importance: National organizations recommend that medical schools train students in the social determinants of health., Objective: To develop and evaluate a longitudinal health equity curriculum that was integrated into third-year clinical clerkships and provided experiential learning in partnership with community organizations., Design, Setting, and Participants: This longitudinal cohort study was conducted from June 2017 to October 2020 to evaluate the association of the curriculum with medical students' self-reported knowledge of social determinants of health and confidence working with underserved populations. Students from 1 large medical school in the southeastern US were included. Students in the class of 2019 and class of 2020 were surveyed at baseline (before the start of their third year), end of the third year, and graduation. The class of 2018 (No curriculum) was surveyed at graduation to serve as a control. Data analysis was conducted from June to September 2020., Exposures: The curriculum began with a health equity simulation followed by a series of modules. The class of 2019 participated in the simulation and piloted the initial 3 modules (pilot), and the class of 2020 participated in the simulation and the full 9 modules (full)., Main Outcomes and Measures: A linear mixed-effects model was used to evaluate the change in the self-reported knowledge and confidence scores over time (potential scores ranged from 0 to 32, with higher scores indicating higher self-reported knowledge and confidence working with underserved populations). In secondary analyses, a Kruskal-Wallis test was conducted to compare graduation scores between the no, pilot, and full curriculum classes., Results: A total of 314 students (160 women [51.0%], 205 [65.3%] non-Hispanic White participants) completed at least 1 survey, including 125 students in the pilot, 121 in the full, and 68 in the no curriculum classes. One hundred forty-one students (44.9%) were interested in primary care. Total self-reported knowledge and confidence scores increased between baseline and end of clerkship (15.4 vs 23.7, P = .001) and baseline and graduation (15.4 vs 23.7, P = .001) for the pilot and full curriculum classes. Total scores at graduation were higher for the pilot curriculum (median, 24.0; interquartile range [IQR], 21.0-27.0; P = .001) and full curriculum classes (median, 23.0; IQR, 20.0-26.0; P = .01) compared with the no curriculum class (median, 20.5; IQR, 16.25-24.0)., Conclusions and Relevance: In this cohort study of medical students, a dedicated health equity curriculum was associated with a significant improvement in students' self-reported knowledge of social determinants of health and confidence working with underserved populations.

Background: Supportive care interventions have demonstrated benefits for both informal and/or family cancer caregivers and their patients, but uptake generally is poor. To the authors' knowledge, little is known regarding the availability of supportive care services in community oncology practices, as well as engagement practices to connect caregivers with these services., Methods: Questions from the National Cancer Institute Community Oncology Research Program (NCORP)'s 2017 Landscape Survey examined caregiver engagement practices (ie, caregiver identification, needs assessment, and supportive care service availability). Logistic regression was used to assess the relationship between the caregiver engagement outcomes and practice group characteristics., Results: A total of 204 practice groups responded to each of the primary outcome questions. Only 40.2% of practice groups endorsed having a process with which to systematically identify and document caregivers, although approximately 76% were routinely using assessment tools to identify caregiver needs and approximately 63.7% had supportive care services available to caregivers. Caregiver identification was more common in sites affiliated with a critical access hospital (odds ratio [OR], 2.44; P = .013), and assessments were less common in safety-net practices (OR, 0.41; P = .013). Supportive care services were more commonly available in the Western region of the United States, in practices with inpatient services (OR, 2.96; P = .012), and in practices affiliated with a critical access hospital (OR, 3.31; P = .010)., Conclusions: Although many practice groups provide supportive care services, fewer than one-half systematically identify and document informal cancer caregivers. Expanding fundamental engagement practices such as caregiver identification, assessment, and service provision will be critical to support recent calls to improve caregivers' well-being and skills to perform caregiving tasks., (© 2020 American Cancer Society.)

Background: The HEART Pathway is an accelerated diagnostic protocol for Emergency Department patients with possible acute coronary syndrome. The objective was to compare the safety and effectiveness of the HEART Pathway among women vs men and whites vs non-whites., Methods: A subgroup analysis of the HEART Pathway Implementation Study was conducted. Adults with chest pain were accrued from November 2013 to January 2016 from 3 Emergency Departments in North Carolina. The primary outcomes were death and myocardial infarction (MI) and hospitalization rates at 30 days. Logistic regression evaluated for interactions of accelerated diagnostic protocol implementation with sex or race and changes in outcomes within subgroups., Results: A total of 8,474 patients were accrued, of which 53.6% were female and 34.0% were non-white. The HEART Pathway identified 32.6% of females as low-risk vs 28.5% of males (P = 002) and 35.6% of non-whites as low-risk vs 28.0% of whites (P < .0001). Among low-risk patients, death or MI at 30 days occurred in 0.4% of females vs 0.5% of males (P = .70) and 0.5% of non-whites vs 0.3% of whites (P = .69). Hospitalization at 30 days was reduced by 6.6% in females (aOR: 0.74, 95% CI: 0.64-0.85), 5.1% in males (aOR: 0.87, 95% CI: 0.75-1.02), 8.6% in non-whites (aOR: 0.72, 95% CI: 0.60-0.86), and 4.5% in whites (aOR: 0.83, 95% CI: 0.73-0.94). Interactions were not significant., Conclusion: Women and non-whites are more likely to be classified as low-risk by the HEART Pathway. HEART Pathway implementation is associated with decreased hospitalizations and a very low death and MI rate among low-risk patients regardless of sex or race., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: High tumor-infiltrating lymphocytes (TILs) and hemorrhage are important prognostic factors in patients who have undergone craniotomy for melanoma brain metastases (MBM) before 2011 at the University of Pittsburgh Medical Center (UPMC). We have investigated the prognostic or predictive role of these histopathologic factors in a more contemporary craniotomy cohort from the University of North Carolina at Chapel Hill (UNC-CH). We have also sought to understand better how various immune cell subsets, angiogenic factors, and blood vessels may be associated with clinical and radiographic features in MBM., Methods: Brain tumors from the UPMC and UNC-CH patient cohorts were (re)analyzed by standard histopathology, tumor tissue imaging, and gene expression profiling. Variables were associated with overall survival (OS) and radiographic features., Results: The patient subgroup with high TILs in craniotomy specimens and subsequent treatment with immune checkpoint inhibitors (ICIs, n=7) trended to have longer OS compared to the subgroup with high TILs and no treatment with ICIs (n=11, p=0.059). Bleeding was significantly associated with tumor volume before craniotomy, high melanoma-specific expression of basic fibroblast growth factor (bFGF), and high density of CD31+αSMA- blood vessels. Brain tumors with high versus low peritumoral edema before craniotomy had low (17%) versus high (41%) incidence of brisk TILs. Melanoma-specific expression of the vascular endothelial growth factor (VEGF) was comparable to VEGF expression by TILs and was not associated with any particular prognostic, radiographic, or histopathologic features. A gene signature associated with gamma delta (gd) T cells was significantly higher in intracranial than same-patient extracranial metastases and primary melanoma. However, gdT cell density in MBM was not prognostic., Conclusions: ICIs may provide greater clinical benefit in patients with brisk TILs in MBM. Intratumoral hemorrhage in brain metastases, a significant clinical problem, is not merely associated with tumor volume but also with underlying biology. bFGF may be an essential pathway to target. VEGF, a factor principally associated with peritumoral edema, is not only produced by melanoma cells but also by TILs. Therefore, suppressing low-grade peritumoral edema using corticosteroids may harm TIL function in 41% of cases. Ongoing clinical trials targeting VEGF in MBM may predict a lack of unfavorable impacts on TIL density and/or intratumoral hemorrhage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Trembath, Davis, Rao, Bradler, Saada, Midkiff, Snavely, Ewend, Collichio, Lee, Karachaliou, Ayvali, Ollila, Krauze, Kirkwood, Vincent, Nikolaishvilli-Feinberg and Moschos.)

Background: The HEART Pathway combines a History ECG Age Risk factor (HEAR) score and serial troponins to risk stratify patients with acute chest pain. However, it is unclear whether patients with HEAR scores of < 1 require troponin testing. The objective of this study is to measure the major adverse cardiac event (MACE) rate among patients with < 1 HEAR scores and determine whether serial troponin testing is needed to achieve a miss rate <1%., Methods: A secondary analysis of the HEART Pathway Implementation Study was conducted. HEART Pathway risk assessments (HEAR scores and serial troponin testing at 0 and 3 hours) were completed by the providers on adult patients with chest pain from three US sites between November 2014 and January 2016. MACE (composite of death, myocardial infarction (MI) and coronary revascularisation) at 30 days was determined. The proportion of patients with HEAR scores of < 1 diagnosed with MACE within 30 days was calculated. The impact of troponin testing on patients with HEAR scores of < 1 was determined using Net Reclassification Improvement Index (NRI)., Results: Providers completed HEAR assessments on 4979 patients and HEAR scores<1 occurred in 9.0% (447/4979) of patients. Among these patients, MACE at 30 days occurred in 0.9% (4/447; 95% CI 0.2% to 2.3%) with two deaths, two MIs and 0 revascularisations. The sensitivity and negative predictive value for MACE in the HEAR < 1 was 97.8% (95%CI 94.5% to 99.4%) and 99.1% (95% CI 97.7% to 99.8%), respectively, and were not improved by troponin testing. Troponin testing in patients with HEAR < 1 correctly reclassified two patients diagnosed with MACE, and was elevated among seven patients without MACE yielding an NRI of 0.9% (95%CI -0.7 to 2.4%)., Conclusion: These data suggest that patients with HEAR scores of 0 and 1 represent a very low-risk group that may not require troponin testing to achieve a missed MACE rate <1%. Trial registration number NCT02056964., Competing Interests: Competing interests: SAM receives research funding from Roche Diagnostics, Abbott Point of Care, Ortho Clinical Diagnostics, Creavo Medical Technologies, PCORI, AHRQ and NHLBI (1 R01 HL11826301). He is a consultant for Roche Diagnostics and Amgen. SAM is the chief medical officer for Impathiq. JPS receives research funding from Roche Diagnostics and Abbott Point of Care. LS receives research funding from Forest Devices and the NHLBI (1 R01 HL144624-01). CDM receives research funding from Abbott, Siemens, NHLBI 118263, Creavo Medical Technologies., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)