Cost-effectiveness of an Emergency Department-Based Intensive Care Unit.

Importance: Value in health care is quality per unit cost (V = Q/C), and an emergency department-based intensive care unit (ED-ICU) model has been associated with improved quality. To assess the value of this care delivery model, it is essential to determine the incremental direct cost of care. Objective: To determine the association of an ED-ICU with inflation-adjusted change in mean direct cost of care, net revenue, and direct margin per ED patient encounter. Design, Setting, and Participants: This retrospective economic analysis evaluated the cost of care delivery to patients in the ED before and after deployment of the Joyce and Don Massey Family Foundation Emergency Critical Care Center, an ED-ICU, on February 16, 2015, at a large academic medical center in the US with approximately 75 000 adult ED visits per year. The pre-ED-ICU cohort was defined as all documented ED visits by patients 18 years or older with a complete financial record from September 8, 2012, through June 30, 2014 (660 days); the post-ED-ICU cohort, all visits from July 1, 2015, through April 21, 2017 (660 days). Fiscal year 2015 was excluded from analysis to phase in the new care model. Statistical analysis was performed March 1 through December 30, 2021. Exposures: Implementation of an ED-ICU. Main Outcomes and Measures: Inflation-adjusted direct cost of care, net revenue, and direct margin per patient encounter in the ED. Results: A total of 234 884 ED visits during the study period were analyzed, with 115 052 patients (54.7% women) in the pre-ED-ICU cohort and 119 832 patients (54.5% women) in the post-ED-ICU cohort. The post-ED-ICU cohort was older (mean [SD] age, 49.1 [19.9] vs 47.8 [19.6] years; P < .001), required more intensive respiratory support (2.2% vs 1.1%; P < .001) and more vasopressor use (0.5% vs 0.2%; P < .001), and had a higher overall case mix index (mean [SD], 1.7 [2.0] vs 1.5 [1.7]; P < .001). Implementation of the ED-ICU was associated with similar inflation-adjusted total direct cost per ED encounter (pre-ED-ICU, mean [SD], $4875 [$15 175]; post-ED-ICU, $4877 [$17 400]; P = .98). Inflation-adjusted net revenue per encounter increased by 7.0% (95% CI, 3.4%-10.6%; P < .001), and inflation-adjusted direct margin per encounter increased by 46.6% (95% CI, 32.1%-61.2%; P < .001). Conclusions and Relevance: Implementation of an ED-ICU was associated with no significant change in inflation-adjusted total direct cost per ED encounter. Holding delivery costs constant while improving quality demonstrates improved value via the ED-ICU model of care.

Impact of Providing a Tape Measure on the Provision of Lung-protective Ventilation.

INTRODUCTION: Emergency department (ED) patients are frequently ventilated with excessively large tidal volumes for predicted body weight based on height, which has been linked to poorer patient outcomes. We hypothesized that supplying tape measures to respiratory therapists (RT) would improve measurement of actual patient height and adherence to a lung-protective ventilation strategy in an ED-intensive care unit (ICU) environment. METHODS: On January 14, 2019, as part of a ventilator-associated pneumonia prevention bundle in our ED-based ICU, we began providing RTs with tape measures and created a best practice advisory reminding them to record patient height. We then retrospectively collected data on patient height and tidal volumes before and after the intervention. RESULTS: We evaluated 51,404 tidal volume measurements in 1,826 patients over the 4 year study period; of these patients, 1,579 (86.5%) were pre-intervention and 247 (13.5%) were post-intervention. The intervention was associated with a odds of the patient's height being measured were 10 times higher post-intervention (25.1% vs 3.2%, P <0.05). After the bundle was initiated, we observed a significantly higher percentage of patients ventilated with mean tidal volumes less than 8 cubic centimeters per kilogram (93.9% vs 84.5% P < 0.05). CONCLUSION: Patients in an ED-ICU environment were ventilated with a lung-protective strategy more frequently after an intervention reminding RTs to measure actual patient height and providing a tape measure to do so. A significantly higher percentage of patients had height measured rather than estimated after the intervention, allowing for more accurate determination of ideal body weight and calculation of lung-protective ventilation volumes. Measuring all mechanically ventilated patients' height with a tape measure is an example of a simple, low-cost, scalable intervention in line with guidelines developed to improve the quality of care delivered to critically ill ED patients.

Descriptive Analysis of Extubations Performed in an Emergency Department-based Intensive Care Unit.

INTRODUCTION: Extubation of appropriate patients in the emergency department (ED) may be a strategy to avoid preventable or short-stay intensive care unit (ICU) admissions, and could allow for increased ventilator and ICU bed availability when demand outweighs supply. Extubation is infrequently performed in the ED, and a paucity of outcome data exists. Our objective was to descriptively analyze characteristics and outcomes of patients extubated in an ED-ICU setting. METHODS: We conducted a retrospective observational study at an academic medical center in the United States. Adult ED patients extubated in the ED-ICU from 2015-2019 were retrospectively included and analyzed. RESULTS: We identified 202 patients extubated in the ED-ICU; 42% were female and median age was 60.86 years. Locations of endotracheal intubation included the ED (68.3%), outside hospital ED (23.8%), and emergency medical services/prehospital (7.9%). Intubations were performed for airway protection (30.2%), esophagogastroduodenoscopy (27.7%), intoxication/ingestion (17.3%), respiratory failure (13.9%), seizure (7.4%), and other (3.5%). The median interval from ED arrival to extubation was 9.0 hours (interquartile range 6.2-13.6). One patient (0.5%) required unplanned re-intubation within 24 hours of extubation. The attending emergency physician (EP) at the time of extubation was not critical care fellowship trained in the majority (55.9%) of cases. Sixty patients (29.7%) were extubated compassionately; 80% of these died in the ED-ICU, 18.3% were admitted to medical-surgical units, and 1.7% were admitted to intensive care. Of the remaining patients extubated in the ED-ICU (n = 142, 70.3%), zero died in the ED-ICU, 61.3% were admitted to medical-surgical units, 9.9% were admitted to intensive care, and 28.2% were discharged home from the ED-ICU. CONCLUSION: Select ED patients were safely extubated in an ED-ICU by EPs. Only 7.4% required ICU admission, whereas if ED extubation had not been pursued most or all patients would have required ICU admission. Extubation by EPs of appropriately screened patients may help decrease ICU utilization, including when demand for ventilators or ICU beds is greater than supply. Future research is needed to prospectively study patients appropriate for ED extubation.

Association of an Emergency Department-Based Intensive Care Unit With Survival and Inpatient Intensive Care Unit Admissions.

Importance: Increased patient acuity, decreased intensive care unit (ICU) bed availability, and a shortage of intensivist physicians have led to strained ICU capacity. The resulting increase in emergency department (ED) boarding time for patients requiring ICU-level care has been associated with worse outcomes. Objective: To determine the association of a novel ED-based ICU, the Emergency Critical Care Center (EC3), with 30-day mortality and inpatient ICU admission. Design, Setting, and Participants: This retrospective cohort study used electronic health records of all ED visits between September 1, 2012, and July 31, 2017, with a documented clinician encounter at a large academic medical center in the United States with approximately 75 000 adult ED visits per year. The pre-EC3 cohort included ED patients from September 2, 2012, to February 15, 2015, when the EC3 opened, and the post-EC3 cohort included ED patients from February 16, 2015, to July 31, 2017. Data analyses were conducted from March 2, 2018, to May 28, 2019. Exposures: Implementation of EC3, an ED-based ICU designed to provide rapid initiation of ICU-level care in the ED setting and seamless transition to inpatient ICUs. Main Outcomes and Measures: The main outcomes were 30-day mortality among ED patients and rate of ED to ICU admission. Results: A total of 349 310 visits from a consecutive sample of ED patients (mean [SD] age, 48.5 [19.7] years; 189 709 [54.3%] women) were examined; the pre-EC3 cohort included 168 877 visits and the post-EC3 cohort included 180 433 visits. Implementation of EC3 was associated with a statistically significant reduction in risk-adjusted 30-day mortality among all ED patients (pre-EC3, 2.13%; post-EC3, 1.83%; adjusted odds ratio, 0.85; 95% CI, 0.80-0.90; number needed to treat, 333 patient encounters; 95% CI, 256-476). The risk-adjusted rate of ED admission to ICU decreased with implementation of EC3 (pre-EC3, 3.2%; post-EC3, 2.7%; adjusted odds ratio, 0.80; 95% CI, 0.76-0.83; number needed to treat, 179 patient encounters; 95% CI, 149-217). Conclusions and Relevance: Implementation of a novel ED-based ICU was associated with improved 30-day survival and reduced inpatient ICU admission. Additional research is warranted to further explore the value of this novel care delivery model in various health care systems.

Laboratory evolution of one disulfide isomerase to resemble another.

It is often difficult to determine which of the sequence and structural differences between divergent members of multigene families are functionally important. Here we use a laboratory evolution approach to determine functionally important structural differences between two distantly related disulfide isomerases, DsbC and DsbG from Escherichia coli. Surprisingly, we found single amino acid substitutions in DsbG that were able to complement dsbC in vivo and have more DsbC-like isomerase activity in vitro. Crystal structures of the three strongest point mutants, DsbG K113E, DsbG V216M, and DsbG T200M, reveal changes in highly surface-exposed regions that cause DsbG to more closely resemble the distantly related DsbC. In this case, laboratory evolution appears to have taken a direct route to allow one protein family member to complement another, with single substitutions apparently bypassing much of the need for multiple changes that took place over approximately 0.5 billion years of evolution. Our findings suggest that, for these two proteins at least, regions important in determining functional differences may represent only a tiny fraction of the overall protein structure.

Mammalian Crumbs3 is a small transmembrane protein linked to protein associated with Lin-7 (Pals1).

Drosophila Crumbs is a transmembrane protein that plays an important role in epithelial cell polarity and photoreceptor development. Overexpression of Crumbs in Drosophila epithelia expands the apical surface and leads to disruption of cell polarity. Drosophila Crumbs also interacts with two other polarity genes, Stardust and Discs Lost. Recent work has identified a human orthologue of Drosophila Crumbs, known as CRB1, that is mutated in the eye disorders, retinitis pigmentosa and Leber congenital amaurosis. Our work has demonstrated that human CRB1 can form a complex with mammalian orthologues of Stardust and Discs Lost, known as protein associated with Lin-7 (Pals1) and Pals1 associated tight junction (PATJ), respectively. In the current report we have cloned a full length cDNA for a human paralogue of CRB1 called Crumbs3 (CRB3). In contrast to Drosophila Crumbs and CRB1, CRB3 has a very short extracellular domain but like these proteins it has a conserved intracellular domain that allows it to complex with Pals1 and PATJ. Mouse and human CRB3 have identical intracellular domains but divergent extracellular domains except for a conserved N-glycosylation site. CRB3 is localized to the apical surface and tight junctions but the conserved N linked glycosylation site does not appear to be necessary for CRB3 apical targeting. CRB3 is a specialized isoform of the Crumbs protein family that is expressed in epithelia and can tie the apical membrane to the tight junction.

The carboxyl terminus of zona occludens-3 binds and recruits a mammalian homologue of discs lost to tight junctions.

Mammalian homologues of the Drosophila polarity proteins Stardust, Discs Lost, and Crumbs have been identified as Pals1, Pals1-associated tight junction protein (PATJ), and human Crumbs homologue 1 (CRB1), respectively. We have previously demonstrated that PATJ, Pals1, and CRB1 can form a tripartite tight junction complex in epithelial cells and that PATJ recruits Pals1 to tight junctions. Here, we observed that the Pals1/PATJ interaction was not crucial for the ultimate targeting of PATJ itself to tight junctions. This prompted us to examine if any of the 10 post-synaptic density-95/Discs Large/zona occludens-1 (PDZ) domains of PATJ could bind to the carboxyl termini of known tight junction constituents. We found that the 6th and 8th PDZ domains of PATJ can interact with the carboxyl termini of zona occludens-3 (ZO-3) and claudin 1, respectively. PATJ missing the 6th PDZ domain was found to mislocalize away from cell contacts. Surprisingly, deleting the 8th PDZ domain had little effect on PATJ localization. Finally, reciprocal co-immunoprecipitation experiments revealed that full-length ZO-3 can associate with PATJ. Hence, the PATJ/ZO-3 interaction is likely important for recruiting PATJ and its associated proteins to tight junctions.

The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost.

Membrane-associated guanylate kinase (Maguk) proteins are scaffold proteins that contain PSD-95-Discs Large-zona occludens-1 (PDZ), Src homology 3, and guanylate kinase domains. A subset of Maguk proteins, such as mLin-2 and protein associated with Lin-7 (Pals)1, also contain two L27 domains: an L27C domain that binds mLin-7 and an L27N domain of unknown function. Here, we demonstrate that the L27N domain targets Pals1 to tight junctions by binding to a PDZ domain protein, Pals1-associated tight junction (PATJ) protein, via a unique Maguk recruitment domain. PATJ is a homologue of Drosophila Discs Lost, a protein that is crucial for epithelial polarity and that exists in a complex with the apical polarity determinant, Crumbs. PATJ and a human Crumbs homologue, CRB1, colocalize with Pals1 to tight junctions, and CRB1 interacts with PATJ albeit indirectly via binding the Pals1 PDZ domain. In agreement, we find that a Drosophila homologue of Pals1 participates in identical interactions with Drosophila Crumbs and Discs Lost. This Drosophila Pals1 homologue has been demonstrated recently to represent Stardust, a crucial polarity gene in Drosophila. Thus, our data identifies a new multiprotein complex that appears to be evolutionarily conserved and likely plays an important role in protein targeting and cell polarity.