GAPDH mediates drug resistance and metabolism in Plasmodium falciparum malaria parasites.

Efforts to control the global malaria health crisis are undermined by antimalarial resistance. Identifying mechanisms of resistance will uncover the underlying biology of the Plasmodium falciparum malaria parasites that allow evasion of our most promising therapeutics and may reveal new drug targets. We utilized fosmidomycin (FSM) as a chemical inhibitor of plastidial isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway. We have thus identified an unusual metabolic regulation scheme in the malaria parasite through the essential glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Two parallel genetic screens converged on independent but functionally analogous resistance alleles in GAPDH. Metabolic profiling of FSM-resistant gapdh mutant parasites indicates that neither of these mutations disrupt overall glycolytic output. While FSM-resistant GAPDH variant proteins are catalytically active, they have reduced assembly into the homotetrameric state favored by wild-type GAPDH. Disrupted oligomerization of FSM-resistant GAPDH variant proteins is accompanied by altered enzymatic cooperativity and reduced susceptibility to inhibition by free heme. Together, our data identifies a new genetic biomarker of FSM-resistance and reveals the central role of GAPDH in MEP pathway control and antimalarial sensitivity.

Use of Real-Time Information to Predict Future Arrivals in the Emergency Department.

STUDY OBJECTIVE: We aimed to build prediction models for shift-level emergency department (ED) patient volume that could be used to facilitate prediction-driven staffing. We sought to evaluate the predictive power of rich real-time information and understand 1) which real-time information had predictive power and 2) what prediction techniques were appropriate for forecasting ED demand. METHODS: We conducted a retrospective study in an ED site in a large academic hospital in New York City. We examined various prediction techniques, including linear regression, regression trees, extreme gradient boosting, and time series models. By comparing models with and without real-time predictors, we assessed the potential gain in prediction accuracy from real-time information. RESULTS: Real-time predictors improved prediction accuracy on models without contemporary information from 5% to 11%. Among extensive real-time predictors examined, recent patient arrival counts, weather, Google trends, and concurrent patient comorbidity information had significant predictive power. Out of all the forecasting techniques explored, SARIMAX (Seasonal Autoregressive Integrated Moving Average with eXogenous factors) achieved the smallest out-of-sample the root mean square error (RMSE) of 14.656 and mean absolute prediction error (MAPE) of 8.703%. Linear regression was the second best, with out-of-sample RMSE and MAPE equal to 15.366 and 9.109%, respectively. CONCLUSION: Real-time information was effective in improving the prediction accuracy of ED demand. Practice and policy implications for designing staffing paradigms with real-time demand forecasts to reduce ED congestion were discussed.

Comparing the Timeliness of Treatment in Younger vs. Older Patients with ST-Segment Elevation Myocardial Infarction: A Multi-Center Cohort Study.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) predominantly affects older adults. Lower incidence among younger patients may challenge diagnosis. OBJECTIVES: We hypothesize that among patients ≤ 50 years old, emergent percutaneous coronary intervention (PCI) for STEMI is delayed when compared with patients aged > 50 years. METHODS: This 3-year, 10-center retrospective cohort study included emergency department (ED) STEMI patients ≥ 18 years of age treated with emergent PCI. We excluded patients with an electrocardiogram (ECG) completed prior to ED arrival or a nondiagnostic initial ECG. Our primary outcome was door-to-balloon (D2B) time. We compared characteristics and outcomes among younger vs. older STEMI patients, and among age subgroups. RESULTS: There were 576 ED STEMI PCI patients, of whom 100 were ≤ 50 years old and 476 were > 50 years old. Median age was 44 years in the younger cohort (interquartile range [IQR] 41-47) vs. 62 years (IQR 57-70) among older patients. Median D2B time for the younger cohort was 76.5 min (IQR 67.5-102.5) vs. 81.0 min (IQR 65.0-105.5) in the older cohort (p = 0.91). This outcome did not change when ages 40 or 45 years were used to demarcate younger vs. older. The younger cohort had a higher prevalence of nonwhite races (38% vs. 21%; p < 0.001) and those currently smoking (36% vs. 23%; p = 0.005). The very young (≤30 years; 6/576) and very old (>80 years; 45/576) had 5.51 and 2.2 greater odds of delays. CONCLUSION: We found no statistically significant difference in D2B times between patients ≤ 50 years old and those > 50 years old. Nonwhite patients and those who smoke were disproportionately represented within the younger population. The very young and very old had higher odds of D2B times > 90 min.

Design and implementation of a clinical decision support tool for primary palliative Care for Emergency Medicine (PRIM-ER).

BACKGROUND: The emergency department is a critical juncture in the trajectory of care of patients with serious, life-limiting illness. Implementation of a clinical decision support (CDS) tool automates identification of older adults who may benefit from palliative care instead of relying upon providers to identify such patients, thus improving quality of care by assisting providers with adhering to guidelines. The Primary Palliative Care for Emergency Medicine (PRIM-ER) study aims to optimize the use of the electronic health record by creating a CDS tool to identify high risk patients most likely to benefit from primary palliative care and provide point-of-care clinical recommendations. METHODS: A clinical decision support tool entitled Emergency Department Supportive Care Clinical Decision Support (Support-ED) was developed as part of an institutionally-sponsored value based medicine initiative at the Ronald O. Perelman Department of Emergency Medicine at NYU Langone Health. A multidisciplinary approach was used to develop Support-ED including: a scoping review of ED palliative care screening tools; launch of a workgroup to identify patient screening criteria and appropriate referral services; initial design and usability testing via the standard System Usability Scale questionnaire, education of the ED workforce on the Support-ED background, purpose and use, and; creation of a dashboard for monitoring and feedback. RESULTS: The scoping review identified the Palliative Care and Rapid Emergency Screening (P-CaRES) survey as a validated instrument in which to adapt and apply for the creation of the CDS tool. The multidisciplinary workshops identified two primary objectives of the CDS: to identify patients with indicators of serious life limiting illness, and to assist with referrals to services such as palliative care or social work. Additionally, the iterative design process yielded three specific patient scenarios that trigger a clinical alert to fire, including: 1) when an advance care planning document was present, 2) when a patient had a previous disposition to hospice, and 3) when historical and/or current clinical data points identify a serious life-limiting illness without an advance care planning document present. Monitoring and feedback indicated a need for several modifications to improve CDS functionality. CONCLUSIONS: CDS can be an effective tool in the implementation of primary palliative care quality improvement best practices. Health systems should thoughtfully consider tailoring their CDSs in order to adapt to their unique workflows and environments. The findings of this research can assist health systems in effectively integrating a primary palliative care CDS system seamlessly into their processes of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03424109. Registered 6 February 2018, Grant Number: AT009844-01.

Novel Use of Telepalliative Care in a New York City Emergency Department During the COVID-19 Pandemic.

BACKGROUND: Coronavirus-2 (COVID-19) is a global pandemic. As of August 21, mortality from COVID-19 has reached almost 200,000 people, with the United States leading the globe in levels of morbidity and mortality. Large volumes of high-acuity patients, particularly those of advanced age and with chronic comorbidities, have significantly increased the need for palliative care resources beyond usual capacity. More specifically, COVID-19 has changed the way we approach patient and family member interactions. DISCUSSION: Concern for nosocomial spread of this infection has resulted in strict visitation restrictions that have left many patients to face this illness, make difficult decisions, and even die, alone in the hospital. To meet the needs of COVID patients, services such as Emergency Medicine and Palliative Care have responded rapidly by adopting novel ways of practicing medicine. We describe the use of telepalliative medicine (TM) implemented in an emergency department (ED) setting to allow family members the ability to interact with their loved ones during critical illness, and even during the end of life. Use of this technology has helped facilitate goals of care discussions, in addition to providing contact and closure for both patients and their loved ones. CONCLUSION: We describe our rapid and ongoing implementation of TM consultation for our ED patients and discuss lessons learned and recommendations for others considering similar care models.

Team-based Pod System Reduces Lengths of Stay for Treat-and-Release Patients.

To boost performance on a range of metrics, the 55-bed ED at NYU Lutheran Medical Center in Brooklyn, NY, transitioned to a pod system in August 2016. The approach, which is designed to foster team-based care, involves assigning physicians and nurses to designated geographic areas throughout the day, minimizing the movement of physicians as well as the need for phone communication. When coupled with other changes, including the introduction of point-of- care testing, the pod initiative has enabled the ED to reduce lengths of stay for all treat-and-release patients to less than three hours for the first time in the history of the department, according to administrators. There were multiple challenges involved with the transition to a pod system, including the need to match physician schedules with patient volume, but clinicians note the approach has produced improved physician-nurse communications. Administrators credit the creation of a process improvement team with giving frontline staff a voice in planned improvements while also facilitating the change process.

Observation Units as Substitutes for Hospitalization or Home Discharge.

STUDY OBJECTIVE: Observation unit admissions have been increasing, a trend that will likely continue because of recent changes in reimbursement policies. The purpose of this study is to determine the effect of the availability of observation units on hospitalizations and discharges to home for emergency department (ED) patients. METHODS: We studied ED visits with a final diagnosis of chest pain in the National Hospital Ambulatory Medical Care Survey from 2007 to 2010. ED visits that resulted in an observation unit admission were propensity-score matched to visits at hospitals without an observation unit. We used logistic regression to develop a prediction model for hospitalization versus discharge home for matched patients treated at nonobservation hospitals. The model was applied to matched observation unit patients to determine the likely alternative disposition had the observation unit not been available. RESULTS: There were 1,325 eligible visits that represented 5,079,154 visits in the United States. Two hundred twenty-seven visits resulted in an observation unit admission. The predictive model for hospitalization had a c statistic of 0.91; variables significantly associated with subsequent hospitalization included age, history of coronary atherosclerosis, systolic blood pressure less than 115 beats/min, and administration of antianginal medications. When the model was applied to matched observation unit patients, 49.9% of them were categorized as discharge home likely. CONCLUSION: In this study, we estimated that half of ED visits for chest pain that resulted in an observation unit admission were made by patients who may have been discharged home had the observation unit not been available. Increased availability of observation units may result in both decreased hospitalizations and decreased discharges to home.

Influence of time-to-diagnosis on time-to-percutaneous coronary intervention for emergency department ST-elevation myocardial infarction patients: Time-to-electrocardiogram matters.

Objectives: Earlier electrocardiogram (ECG) acquisition for ST-elevation myocardial infarction (STEMI) is associated with earlier percutaneous coronary intervention (PCI) and better patient outcomes. However, the exact relationship between timely ECG and timely PCI is unclear. Methods: We quantified the influence of door-to-ECG (D2E) time on ECG-to-PCI balloon (E2B) intervention in this three-year retrospective cohort study, including patients from 10 geographically diverse emergency departments (EDs) co-located with a PCI center. The study included 576 STEMI patients excluding those with a screening ECG before ED arrival or non-diagnostic initial ED ECG. We used a linear mixed-effects model to evaluate D2E's influence on E2B with piecewise linear terms for D2E times associated with time intervals designated as ED intake (0-10 min), triage (11-30 min), and main ED (>30 min). We adjusted for demographic and visit characteristics, past medical history, and included ED location as a random effect. Results: The median E2B interval was longer (76 vs 68 min, p < 0.001) in patients with D2E >10 min than in those with timely D2E. The proportion of patients identified at the intake, triage, and main ED intervals was 65.8%, 24.9%, and 9.7%, respectively. The D2E and E2B association was statistically significant in the triage phase, where a 1-minute change in D2E was associated with a 1.24-minute change in E2B (95% confidence interval [CI]: 0.44-2.05, p = 0.003). Conclusion: Reducing D2E is associated with a shorter E2B. Targeting D2E reduction in patients currently diagnosed during triage (11-30 min) may be the greatest opportunity to improve D2B and could enable 24.9% more ED STEMI patients to achieve timely D2E.

Shorter Door-to-ECG Time Is Associated with Improved Mortality in STEMI Patients.

Background: Delayed intervention for ST-segment elevation myocardial infarction (STEMI) is associated with higher mortality. The association of door-to-ECG (D2E) with clinical outcomes has not been directly explored in a contemporary US-based population. Methods: This was a three-year, 10-center, retrospective cohort study of ED-diagnosed patients with STEMI comparing mortality between those who received timely (<10 min) vs. untimely (>10 min) diagnostic ECG. Among survivors, we explored left ventricular ejection fraction (LVEF) dysfunction during the STEMI encounter and recovery upon post-discharge follow-up. Results: Mortality was lower among those who received a timely ECG where one-week mortality was 5% (21/420) vs. 10.2% (26/256) among those with untimely ECGs (p = 0.016), and in-hospital mortality was 6.0% (25/420) vs. 10.9% (28/256) (p = 0.028). Data to compare change in LVEF metrics were available in only 24% of patients during the STEMI encounter and 46.5% on discharge follow-up. Conclusions: D2E within 10 min may be associated with a 50% reduction in mortality among ED STEMI patients. LVEF dysfunction is the primary resultant morbidity among STEMI survivors but was infrequently assessed despite low LVEF being an indication for survival-improving therapy. It will be difficult to assess the impact of STEMI care interventions without more consistent LVEF assessment.

2021 SAEM Consensus Conference Proceedings: Research Priorities for Implementing Emergency Department Screening for Social Risks and Needs.

INTRODUCTION: Despite literature on a variety of social risks and needs screening interventions in emergency department (ED) settings, there is no universally accepted or evidence-based process for conducting such interventions. Many factors hamper or promote implementation of social risks and needs screening in the ED, but the relative impact of these factors and how best to mitigate/leverage them is unknown. METHODS: Drawing on an extensive literature review, expert assessment, and feedback from participants in the 2021 Society for Academic Emergency Medicine Consensus Conference through moderated discussions and follow-up surveys, we identified research gaps and rated research priorities for implementing screening for social risks and needs in the ED. We identified three main knowledge gaps: 1) screening implementation mechanics; 2) outreach and engagement with communities; and 3) addressing barriers and leveraging facilitators to screening. Within these gaps, we identified 12 high-priority research questions as well as research methods for future studies. RESULTS: Consensus Conference participants broadly agreed that social risks and needs screening is generally acceptable to patients and clinicians and feasible in an ED setting. Our literature review and conference discussion identified several research gaps in the specific mechanics of screening implementation, including screening and referral team composition, workflow, and use of technology. Discussions also highlighted a need for more collaboration with stakeholders in screening design and implementation. Additionally, discussions identified the need for studies using adaptive designs or hybrid effectiveness-implementation models to test multiple strategies for implementation and sustainability. CONCLUSION: Through a robust consensus process we developed an actionable research agenda for implementing social risks and needs screening in EDs. Future work in this area should use implementation science frameworks and research best practices to further develop and refine ED screening for social risks and needs and to address barriers as well as leverage facilitators to such screening.

Interstate Licensure: Has The Time Come?

In the midst of the unprecedented public health emergency of COVID-19, many states developed programs to recognize out-of-state practitioners' licenses for in-state practice. This rapid expansion had a profound impact on care during periods of surge and offers lessons for future disasters as well as usual operating periods. As technology improves and care delivery evolves, interstate licensure offers immense opportunities, but there are also risks that must be mitigated.

Fallacy of Median Door-to-ECG Time: Hidden Opportunities for STEMI Screening Improvement.

Background ST-segment elevation myocardial infarction (STEMI) guidelines recommend screening arriving emergency department (ED) patients for an early ECG in those with symptoms concerning for myocardial ischemia. Process measures target median door-to-ECG (D2E) time of 10 minutes. Methods and Results This 3-year descriptive retrospective cohort study, including 676 ED-diagnosed patients with STEMI from 10 geographically diverse facilities across the United States, examines an alternative approach to quantifying performance: proportion of patients meeting the goal of D2E≤10 minutes. We also identified characteristics associated with D2E>10 minutes and estimated the proportion of patients with screening ECG occurring during intake, triage, and main ED care periods. We found overall median D2E was 7 minutes (IQR:4-16; range: 0-1407 minutes; range of ED medians: 5-11 minutes). Proportion of patients with D2E>10 minutes was 37.9% (ED range: 21.5%-57.1%). Patients with D2E>10 minutes, compared to those with D2E≤10 minutes, were more likely female (32.8% versus 22.6%, P=0.005), Black (23.4% versus 12.4%, P=0.005), non-English speaking (24.6% versus 19.5%, P=0.032), diabetic (40.2% versus 30.2%, P=0.010), and less frequently reported chest pain (63.3% versus 87.4%, P<0.001). ECGs were performed during ED intake in 62.1% of visits, ED triage in 25.3%, and main ED care in 12.6%. Conclusions Examining D2E>10 minutes can identify opportunities to improve care for more ED patients with STEMI. Our findings suggest sex, race, language, and diabetes are associated with STEMI diagnostic delays. Moving the acquisition of ECGs completed during triage to intake could achieve the D2E≤10 minutes goal for 87.4% of ED patients with STEMI. Sophisticated screening, accounting for differential risk and diversity in STEMI presentations, may further improve timely detection.

Lessons learned and challenges in building a Filipino health coalition.

In recent years, community-based coalitions have become an effective channel to addressing various health problems within specific ethnic communities. The purpose of this article is twofold: (a) to describe the process involved in building the Kalusugan Coalition (KC), a Filipino American health coalition based in New York City, and (b) to highlight the lessons learned and the challenges from this collaborative venture. The challenges described also offer insights on how the coalition development process can be greatly affected by the partnership with an academic institution on a community-based research project. Because each cultural group has unique issues and concerns, the theoretical framework used by KC offers creative alternatives to address some of the challenges regarding coalition infrastructures, leadership development, unexpected change of coalition dynamics, and cultural nuances.

Lean Process Improvement in the Emergency Department.

Lean engineering is based on a process improvement strategy originally developed at Toyota and has been used in many different industries to maximize efficiency by minimizing waste. Lean improvement projects are frequently instituted in emergency departments in an effort to improve processes and thereby improve patient care. Such projects have been undertaken with success in many emergency departments in order to improve metrics such as door-to-provider time, left without being seen rate, and patient length of stay. By reducing waste in the system, Lean processes aim to maximize efficiency and minimize delay and redundancy to the extent possible.