Fewer emergency department alarms is associated with reduced use of medications for acute agitation.

BACKGROUND AND OBJECTIVES: Patient monitoring systems provide critical information but often produce loud, frequent alarms that worsen patient agitation and stress. This may increase the use of physical and chemical restraints with implications for patient morbidity and autonomy. This study analyzes how augmenting alarm thresholds affects the proportion of alarm-free time and the frequency of medications administered to treat acute agitation. METHODS: Our emergency department's patient monitoring system was modified on June 28, 2022 to increase the tachycardia alarm threshold from 130 to 150 and to remove alarm sounds for several arrhythmias, including bigeminy and premature ventricular beats. A pre-post study was performed lasting 55 days before and 55 days after this intervention. The primary outcome was change in number of daily patient alarms. The secondary outcomes were alarm-free time per day and median number of antipsychotic and benzodiazepine medications administered per day. The safety outcome was the median number of patients transferred daily to the resuscitation area. We used quantile regression to compare outcomes between the pre- and post-intervention period and linear regression to correlate alarm-free time with the number of sedating medications administered. RESULTS: Between the pre- and post-intervention period, the median number of alarms per day decreased from 1332 to 845 (-37%). This was primarily driven by reduced low-priority arrhythmia alarms from 262 to 21 (-92%), while the median daily census was unchanged (33 vs 32). Median hours per day free from alarms increased from 1.0 to 2.4 (difference 1.4, 95% CI 0.8-2.1). The median number of sedating medications administered per day decreased from 14 to 10 (difference - 4, 95% CI -1 to -7) while the number of escalations in level of care to our resuscitation care area did not change significantly. Multivariable linear regression showed a 60-min increase of alarm-free time per day was associated with 0.8 (95% CI 0.1-1.4) fewer administrations of sedating medication while an additional patient on the behavioral health census was associated with 0.5 (95% CI 0.0-1.1) more administrations of sedating medication. CONCLUSION: A reasonable change in alarm parameter settings may increase the time patients and healthcare workers spend in the emergency department without alarm noise, which in this study was associated with fewer doses of sedating medications administered.

An ultrafast brain MRI technique for evaluating acute neurologic deficits in the emergency department.

Herein we share our preliminary experience with an ultrafast brain MRI technique for use in the ED consisting of axial T1-weighted (40 s), axial T2-weighted (62 s), axial diffusion-weighted (80 s), axial FLAIR (96 s), axial T2* (6 s), and axial susceptibility-weighted (108 s) imaging for a total scan time of 6 min and 53 s. Utilization of this ultrafast technique yields an efficient assessment of the brain, decreases ED length of stay and inpatient observation admissions, and may obviate the need for vascular imaging with either CTA or MRA in the ED.

CT utilization in evaluation of skin and soft tissue extremity infections in the ED: Retrospective cohort study.

OBJECTIVE: Skin and soft tissue infections (SSTI) are commonly diagnosed in the emergency department (ED). While most SSTI are diagnosed with patient history and physical exam alone, ED clinicians may order CT imaging when they suspect more serious or complicated infections. Patients who inject drugs are thought to be at higher risk for complications from SSTI and may undergo CT imaging more frequently. The objective of this study is to characterize CT utilization when evaluating for SSTI in ED patients particularly in patients with intravenous drug use (IVDU), the frequency of significant and actionable findings from CT imaging, and its impact on subsequent management and ED operations. METHODS: We performed a retrospective analysis of encounters involving a diagnosis of SSTI in seven EDs across an integrated health system between October 2019 and October 2021. Descriptive statistics were used to assess overall trends, compare CT utilization frequencies, actionable imaging findings, and surgical intervention between patients who inject drugs and those who do not. Multivariable logistic regression was used to analyze patient factors associated with higher likelihood of CT imaging. RESULTS: There were 4833 ED encounters with an ICD-10 diagnosis of SSTI during the study period, of which 6% involved a documented history of IVDU and 30% resulted in admission. 7% (315/4833) of patients received CT imaging, and 22% (70/315) of CTs demonstrated evidence of possible deep space or necrotizing infections. Patients with history of IVDU were more likely than patients without IVDU to receive a CT scan (18% vs 6%), have a CT scan with findings suspicious for deep-space or necrotizing infection (4% vs 1%), and undergo surgical drainage in the operating room within 48 h of arrival (5% vs 2%). Male sex, abnormal vital signs, and history of IVDU were each associated with higher likelihood of CT utilization. Encounters involving CT scans had longer median times to ED disposition than those without CT scans, regardless of whether these encounters resulted in admission (9.0 vs 5.5 h), ED observation (5.5 vs 4.1 h), or discharge (6.8 vs 2.9 h). DISCUSSION: ED clinicians ordered CT scans in 7% of encounters when evaluating for SSTI, most frequently in patients with abnormal vital signs or a history of IV drug use. Patients with a history of IVDU had higher rates of CT findings suspicious for deep space infections or necrotizing infections and higher rates of incision and drainage procedures in the OR. While CT scans significantly extended time spent in the ED for patients, this appeared justified by the high rate of actionable findings found on imaging, particularly for patients with a history of IVDU.

Impact of iodinated contrast allergies on emergency department operations.

OBJECTIVES: Adverse reactions to intravenous (IV) iodinated contrast media are classified by the American College of Radiology (ACR) Manual on Contrast Media as either allergic-like (ALR) or physiologic (PR). Premedication may be beneficial for patients who have prior documented mild or moderate ALR. We sought to perform a retrospective analysis of patients who received computed tomography (CT) imaging in our emergency department (ED) to establish whether listing of an iodinated contrast media allergy results in a delay in care, increases the use of non-contrast studies, and to quantify the incidence of listing iodinated contrast allergies which do not necessitate premedication. METHODS: We performed a retrospective analysis of CT scans performed in our academic medical center ED during a 6-month period. There were 12,737 unique patients of whom 454 patients had a listed iodinated contrast allergy. Of these, 106 received IV contrast and were categorized as to whether premedication was necessary. Descriptive statistics were used to evaluate patient demographics, clinical characteristics, and operational outcomes. A multivariate linear regression model was used to predict time from order to start (OTS time) of CT imaging while controlling for co-variates. RESULTS: Non-allergic patients underwent contrast-enhanced CT imaging at a significantly higher rate than allergic patients (45.9% vs. 23.3%, p < 0.01). The OTS time for allergic patients who underwent contrast-enhanced CT imaging was 360 min and significantly longer than the OTS time for non-allergic patients who underwent contrast-enhanced CT imaging (118 min, p < 0.001). Of the 106 allergic patients who underwent contrast-enhanced CT imaging, 27 (25.5%) did not meet ACR criteria for necessitating premedication. The average OTS time for these 27 patients was 296 min, significantly longer than the OTS for non-allergic patients (118 min, p < 0.01) and did not differ from the OTS time for the 79 patients who did meet premedication criteria (382 min, p = 0.23). A multivariate linear regression showed that OTS time was significantly longer if a contrast allergy was present (p < 0.001). CONCLUSION: A chart-documented iodinated contrast allergy resulted in a significant increase in time to obtain a contrast-enhanced CT study. This delay persisted among patients who did not meet ACR criteria for premedication. Appropriately deferring premedication could potentially reduce the ED length-of-stay by over 4 h for these patients.

Level-loading a health system by transferring emergency department patients to a community hospital: Prospective cohort study.

BACKGROUND: Emergency department boarding and crowding lead to worse patient outcomes and patient satisfaction. OBJECTIVE: We describe the implementation of a program to transfer patients requiring medical admission from an academic emergency department to a community hospital's medical floor and analyze its effects on patient outcomes. METHODS: A prospective cohort study was performed. Data was collected on patient flow through the transfer program. Patient characteristics, boarding time in the emergency department, and hospital-based outcome measures were compared between patients in the transfer program who were successfully transferred to the community hospital and patients who were admitted to the academic medical center. RESULTS: 79 patients were successfully transferred to the community hospital between November 23, 2020 and August 5, 2021, resulting in 279 bed days in the community hospital. Successfully transferred patients experienced a statistically shorter ED boarding time (5.7 vs. 10.9 h, p < 0.0001), ED length of stay (10.5 vs 16.1 h, p < 0.0001), and hospital length of stay (3.5 vs 5.7 days, p < 0.0001) compared to patients initially referred to the transfer program who were admitted to the academic medical center. There were no reported adverse events during transfer, upgrades to the ICU within 24 h of admission, or inpatient deaths for patients who were transferred. CONCLUSION: We implemented an academic emergency department to partner community hospital transfer program that safely level-loads medical patients in a healthcare system.

Evaluation of a COVID-19 emergency department observation protocol.

OBJECTIVES: Caring for patients with COVID-19 has resulted in a considerable strain on hospital capacity. One strategy to mitigate crowding is the use of ED-based observation units to care for patients who may have otherwise required hospitalization. We sought to create a COVID-19 Observation Protocol for our ED Observation Unit (EDOU) for patients with mild to moderate COVID-19 to allow emergency physicians (EP) to gather more data for or against admission and intervene in a timely manner to prevent clinical deterioration. METHODS: This was a retrospective cohort study which included all patients who were positive for SARS-CoV-2 at the time of EDOU placement for the primary purpose of monitoring COVID-19 disease. Our institution updated the ED Observation protocol partway into the study period. Descriptive statistics were used to characterize demographics. We assessed for differences in demographics, clinical characteristics, and outcomes between admitted and discharged patients. Multivariate logistic regression models were used to assess whether meeting criteria for the ED observation protocols predicted disposition. RESULTS: During the time period studied, 120 patients positive for SARS-CoV-2 were placed in the EDOU for the primary purpose of monitoring COVID-19 disease. The admission rate for patients in the EDOU during the study period was 35%. When limited to patients who met criteria for version 1 or version 2 of the protocol, this dropped to 21% and 25% respectively. Adherence to the observation protocol was 62% and 60% during the time of version 1 and version 2 implementation, respectively. Using a multivariate logistic regression, meeting criteria for either version 1 (OR = 3.17, 95% CI 1.34-7.53, p < 0.01) or version 2 (OR = 3.18, 95% CI 1.39-7.30, p < 0.01) of the protocol resulted in a higher likelihood of discharge. There was no difference in EDOU LOS between admitted and discharged patients. CONCLUSION: An ED observation protocol can be successfully created and implemented for COVID-19 which allows the EP to determine which patients warrant hospitalization. Meeting protocol criteria results in an acceptable admission rate.

Impact of Emergency Department Crowding on Discharged Patient Experience.

INTRODUCTION: While emergency department (ED) crowding has deleterious effects on patient care outcomes and operational efficiency, impacts on the experience for patients discharged from the ED are unknown. We aimed to study how patient-reported experience is affected by ED crowding to characterize which factors most impact discharged patient experience. METHODS: This institutional review board-exempt, retrospective, cohort study included all discharged adult ED patients July 1, 2020-June 30, 2021 with at least some response data to the the National Research Corporation Health survey, sent to most patients discharged from our large, academic medical center ED. Our query yielded 9,401 unique encounters for 9,221 patients. Based on responses to the summary question of whether the patient was likely to recommend our ED, patients were categorized as "detractors" (scores 0-6) or "non-detractors" (scores 7-10). We assessed the relationship between census and patient experience by 1) computing percentage of detractors within each care area and assessing for differences in census and boarder burden between detractors and non-detractors, and 2) multivariable logistic regression assessing the relationship between likelihood of being a detractor in terms of the ED census and the patient's last ED care area. A second logistic regression controlled for additional patient- and encounter-specific covariates. RESULTS: Survey response rate was 24.8%. Overall, 13.9% of responders were detractors. There was a significant difference in the average overall ED census for detractors (average 3.70 more patients physically present at the time of arrival, 95% CI 2.33-5.07). In unadjusted multivariable analyses, three lower acuity ED care areas showed statistically significant differences of detractor likelihood with changes in patient census. The overall area under the curve (AUC) for the unadjusted model was 0.594 (CI 0.577-0.610). The adjusted model had higher AUC (0.673, CI 0.657-.690]; P<0.001), with the same three care areas having significant differences in detractor likelihood based on patient census changes. Length of stay (OR 1.71, CI 1.50-1.95), leaving against medical advice/without being seen (OR 5.15, CI 3.84-6.89), and the number of ED care areas a patient visited (OR 1.16, CI 1.01-1.33) was associated with an increase in detractor likelihood. CONCLUSION: Patients arriving to a crowded ED and ultimately discharged are more likely to have negative patient experience. Future studies should characterize which variables most impact patient experience of discharged ED patients.

Patient Experiences With Transfer for Community Hospital Inpatient Admission From an Academic Emergency Department.

Emergency department (ED) crowding continues to be a major challenge and has important ramifications for patient care quality. One strategy to decrease ED crowding has been to implement alternative pathways to traditional hospital admission. Through a survey-based retrospective cohort study, we aimed to assess the patient experience for those who agreed to transfer and admission to an affiliated community hospital from a large, academic center's ED. In all, 85% of participants rated their overall experience as either great or good, 92% did not find it hard to make the decision to be transferred, and 95% found the transfer process itself to be easy.

Utilization of head CT during injury visits to United States emergency departments: 2012-2015.

INTRODUCTION: Studies have shown increasing utilization of head computed tomography (CT) imaging of emergency department (ED) patients presenting with an injury-related visit. Multiple initiatives, including the Choosing Wisely™ campaign and evidence-based clinical decision support based on validated decision rules, have targeted head CT use in patients with injuries. Therefore, we investigated national trends in the use of head CT during injury-related ED visits from 2012 to 2015. METHODS: This was a secondary analysis of data from the annual United States (U.S.) National Hospital Ambulatory Medical Care Survey from 2012 to 2015. The study population was defined as injury-related ED visits, and we sought to determine the percentage in which a head CT was ordered and, secondarily, to determine both the diagnostic yield of clinically significant intracranial findings and hospital characteristics associated with increased head CT utilization. RESULTS: Between 2012 and 2015, 12.25% (95% confidence interval [CI] 11.48-13.02%) of injury-related visits received at least one head CT. Overall head CT utilization showed an increased trend during the study period (2012: 11.7%, 2015: 13.23%, p = 0.09), but the results were not statistically significant. The diagnostic yield of head CT for a significant intracranial injury over the period of four years was 7.4% (9.68% in 2012 vs. 7.67% in 2015, p = 0.23). CONCLUSIONS: Head CT use along with diagnostic yield has remained stable from 2012 to 2015 among patients presenting to the ED for an injury-related visit.

A Dementia-Associated Risk Variant near TMEM106B Alters Chromatin Architecture and Gene Expression.

Neurodegenerative diseases pose an extraordinary threat to the world's aging population, yet no disease-modifying therapies are available. Although genome-wide association studies (GWASs) have identified hundreds of risk loci for neurodegeneration, the mechanisms by which these loci influence disease risk are largely unknown. Here, we investigated the association between common genetic variants at the 7p21 locus and risk of the neurodegenerative disease frontotemporal lobar degeneration. We showed that variants associated with disease risk correlate with increased expression of the 7p21 gene TMEM106B and no other genes; co-localization analyses implicated a common causal variant underlying both association with disease and association with TMEM106B expression in lymphoblastoid cell lines and human brain. Furthermore, increases in the amount of TMEM106B resulted in increases in abnormal lysosomal phenotypes and cell toxicity in both immortalized cell lines and neurons. We then combined fine-mapping, bioinformatics, and bench-based approaches to functionally characterize all candidate causal variants at this locus. This approach identified a noncoding variant, rs1990620, that differentially recruits CTCF in lymphoblastoid cell lines and human brain to influence CTCF-mediated long-range chromatin-looping interactions between multiple cis-regulatory elements, including the TMEM106B promoter. Our findings thus provide an in-depth analysis of the 7p21 locus linked by GWASs to frontotemporal lobar degeneration, nominating a causal variant and causal mechanism for allele-specific expression and disease association at this locus. Finally, we show that genetic variants associated with risk of neurodegenerative diseases beyond frontotemporal lobar degeneration are enriched in CTCF-binding sites found in brain-relevant tissues, implicating CTCF-mediated gene regulation in risk of neurodegeneration more generally.

Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype.

OBJECTIVE: Parkinson's disease (PD) presents clinically with several motor subtypes that exhibit variable treatment response and prognosis. Here, we investigated genetic variants for their potential association with PD motor phenotype and progression. METHODS: We screened 10 SNPs, previously associated with PD risk, for association with tremor-dominant (TD) versus postural-instability gait disorder (PIGD) motor subtypes. SNPs that correlated with the TD/PIGD ratio in a discovery cohort of 251 PD patients were then evaluated in a multi-site replication cohort of 559 PD patients. SNPs associated with motor phenotype in both cross-sectional cohorts were next evaluated for association with (1) rates of motor progression in a longitudinal subgroup of 230 PD patients and (2) brain alpha-synuclein (SNCA) expression in the GTEx (Genotype-Tissue Expression project) consortium database. RESULTS: Genotype at rs356182, near SNCA, correlated with the TD/PIGD ratio in both the discovery (Bonferroni-corrected P = 0.04) and replication cohorts (P = 0.02). The rs356182 GG genotype was associated with a more tremor-predominant phenotype and predicted a slower rate of motor progression (1-point difference in annual rate of UPDRS-III motor score change, P = 0.01). The rs356182 genotype was associated with SNCA expression in the cerebellum (P = 0.005). INTERPRETATION: Our study demonstrates that the GG genotype at rs356182 provides molecular definition for a clinically important endophenotype associated with (1) more tremor-predominant motor phenomenology, (2) slower rates of motor progression, and (3) decreased brain expression of SNCA. Such molecularly defined endophenotyping in PD may benefit both clinical trial design and tailoring of clinical care as we enter the era of precision medicine.

An Alzheimer's Disease-Derived Biomarker Signature Identifies Parkinson's Disease Patients with Dementia.

Biomarkers from multiple modalities have been shown to correlate with cognition in Parkinson's disease (PD) and in Alzheimer's disease (AD). However, the relationships of these markers with each other, and the use of multiple markers in concert to predict an outcome of interest, are areas that are much less explored. Our objectives in this study were (1) to evaluate relationships among 17 biomarkers previously reported to associate with cognition in PD or AD and (2) to test performance of a five-biomarker classifier trained to recognize AD in identifying PD with dementia (PDD). To do this, we evaluated a cross-sectional cohort of PD patients (n = 75) across a spectrum of cognitive abilities. All PD participants had 17 baseline biomarkers from clinical, genetic, biochemical, and imaging modalities measured, and correlations among biomarkers were assessed by Spearman's rho and by hierarchical clustering. We found that internal correlation among all 17 candidate biomarkers was modest, showing a maximum pairwise correlation coefficient of 0.51. However, a five-marker subset panel derived from AD (CSF total tau, CSF phosphorylated tau, CSF amyloid beta 42, APOE genotype, and SPARE-AD imaging score) discriminated cognitively normal PD patients vs. PDD patients with 80% accuracy, when employed in a classifier originally trained to recognize AD. Thus, an AD-derived biomarker signature may identify PDD patients with moderately high accuracy, suggesting mechanisms shared with AD in some PDD patients. Based on five measures readily obtained during life, this AD-derived signature may prove useful in identifying PDD patients most likely to respond to AD-based crossover therapies.

Plasma apolipoprotein A1 associates with age at onset and motor severity in early Parkinson's disease patients.

BACKGROUND: Development of robust plasma-based biomarkers in Parkinson's disease (PD) could lead to new approaches for identifying those at risk for PD and developing novel therapies. Here, we validate plasma apolipoprotein A1 (ApoA1) as a correlate of age at onset and motor severity in PD. METHODS: Plasma ApoA1 and high-density lipoprotein at baseline, 6 months, and 12 months were measured in 254 research volunteers (154 patients with PD and 100 normal controls) enrolled in the Parkinson's Progression Markers Initiative (PPMI) study. RESULTS: Lower baseline plasma ApoA1 levels associate with an earlier age at PD onset in early-stage, drug-naïve PPMI PD patients (P = 0.023). Moreover, lower baseline ApoA1 levels trend toward association with worse motor severity in PPMI PD patients (p = 0.080). Over 12 months of follow-up, plasma ApoA1 levels do not predict motor decline in the PPMI PD cohort. Finally, a meta-analysis of five PD cohorts encompassing >1,000 patients confirms significant association of lower plasma ApoA1 with earlier age at PD onset (P < 0.001) and greater motor severity (P < 0.001). CONCLUSIONS: Our results confirm the previously reported association of lower plasma ApoA1 levels with two clinical features suggesting poorer dopaminergic system integrity-earlier age at PD onset and greater motor severity-in early-stage, drug-naïve PD patients. This is the first report of a plasma-based biomarker evaluated in the PPMI study. Future investigations are warranted evaluating plasma ApoA1 as a longitudinal correlate of disease progression as well as investigating the potential of ApoA1 as a therapeutic target in PD.

Traffic lines: new tools for genetic analysis in Arabidopsis thaliana.

Genetic analysis requires the ability to identify the genotypes of individuals in a segregating population. This task is straightforward if each genotype has a distinctive phenotype, but is difficult if these genotypes are phenotypically similar or identical. We show that Arabidopsis seeds homozygous or heterozygous for a mutation of interest can be identified in a segregating family by placing the mutation in trans to a chromosome carrying a pair of seed-expressed green and red fluorescent transgenes (a "traffic line") that flank the mutation. Nonfluorescent seeds in the self-pollinated progeny of such a heterozygous plant are usually homozygous for the mutation, whereas seeds with intermediate green and red fluorescence are typically heterozygous for the mutation. This makes it possible to identify seedlings homozygous for mutations that lack an obvious seedling phenotype, and also facilitates the analysis of lethal or sterile mutations, which must be propagated in heterozygous condition. Traffic lines can also be used to identify progeny that have undergone recombination within a defined region of the genome, facilitating genetic mapping and the production of near-isogenic lines. We produced 488 transgenic lines containing single genome-mapped insertions of NAP:dsRED and NAP:eGFP in Columbia (330 lines) and Landsberg erecta (158 lines) and generated sets of traffic lines that span most regions of the Arabidopsis genome. We demonstrated the utility of these lines for identifying seeds of a specific genotype and for generating near-isogenic lines using mutations of WUSCHEL and SHOOTMERISTEMLESS. This new resource significantly decreases the effort and cost of genotyping segregating families and increases the efficiency of experiments that rely on the ability to detect recombination in a defined chromosomal segment.