Hox gene-specific cellular targeting using split intein Trojan exons.

The Trojan exon method, which makes use of intronically inserted T2A-Gal4 cassettes, has been widely used in Drosophila to create thousands of gene-specific Gal4 driver lines. These dual-purpose lines provide genetic access to specific cell types based on their expression of a native gene while simultaneously mutating one allele of the gene to enable loss-of-function analysis in homozygous animals. While this dual use is often an advantage, the truncation mutations produced by Trojan exons are sometimes deleterious in heterozygotes, perhaps by creating translation products with dominant negative effects. Such mutagenic effects can cause developmental lethality as has been observed with genes encoding essential transcription factors. Given the importance of transcription factors in specifying cell type, alternative techniques for generating specific Gal4 lines that target them are required. Here, we introduce a modified Trojan exon method that retains the targeting fidelity and plug-and-play modularity of the original method but mitigates its mutagenic effects by exploiting the self-splicing capabilities of split inteins. "Split Intein Trojan exons" (siTrojans) ensure that the two truncation products generated from the interrupted allele of the native gene are trans-spliced to create a full-length native protein. We demonstrate the efficacy of siTrojans by generating a comprehensive toolkit of Gal4 and Split Gal4 lines for the segmentally expressed Hox transcription factors and illustrate their use in neural circuit mapping by targeting neurons according to their position along the anterior-posterior axis. Both the method and the Hox gene-specific toolkit introduced here should be broadly useful.

Enteric neurons increase maternal food intake during reproduction.

Reproduction induces increased food intake across females of many animal species1-4, providing a physiologically relevant paradigm for the exploration of appetite regulation. Here, by examining the diversity of enteric neurons in Drosophila melanogaster, we identify a key role for gut-innervating neurons with sex- and reproductive state-specific activity in sustaining the increased food intake of mothers during reproduction. Steroid and enteroendocrine hormones functionally remodel these neurons, which leads to the release of their neuropeptide onto the muscles of the crop-a stomach-like organ-after mating. Neuropeptide release changes the dynamics of crop enlargement, resulting in increased food intake, and preventing the post-mating remodelling of enteric neurons reduces both reproductive hyperphagia and reproductive fitness. The plasticity of enteric neurons is therefore key to reproductive success. Our findings provide a mechanism to attain the positive energy balance that sustains gestation, dysregulation of which could contribute to infertility or weight gain.

split-intein Gal4 provides intersectional genetic labeling that is repressible by Gal80.

The split-Gal4 system allows for intersectional genetic labeling of highly specific cell types and tissues in Drosophila. However, the existing split-Gal4 system, unlike the standard Gal4 system, cannot be repressed by Gal80, and therefore cannot be controlled temporally. This lack of temporal control precludes split-Gal4 experiments in which a genetic manipulation must be restricted to specific timepoints. Here, we describe a split-Gal4 system based on a self-excising split-intein, which drives transgene expression as strongly as the current split-Gal4 system and Gal4 reagents, yet which is repressible by Gal80. We demonstrate the potent inducibility of "split-intein Gal4" in vivo using both fluorescent reporters and via reversible tumor induction in the gut. Further, we show that our split-intein Gal4 can be extended to the drug-inducible GeneSwitch system, providing an independent method for intersectional labeling with inducible control. We also show that the split-intein Gal4 system can be used to generate highly cell type-specific genetic drivers based on in silico predictions generated by single-cell RNAseq (scRNAseq) datasets, and we describe an algorithm ("Two Against Background" or TAB) to predict cluster-specific gene pairs across multiple tissue-specific scRNA datasets. We provide a plasmid toolkit to efficiently create split-intein Gal4 drivers based on either CRISPR knock-ins to target genes or using enhancer fragments. Altogether, the split-intein Gal4 system allows for the creation of highly specific intersectional genetic drivers that are inducible/repressible.

The Value of an Emergency Medicine Virtual Observation Unit.

STUDY OBJECTIVE: We implemented a virtual observation unit in which emergency department (ED) patients receive observation-level care at home. Our primary aim was to compare this new care model to in-person observation care in terms of brick-and-mortar ED length of stay (inclusive of ED observation unit time) as well as secondarily on inpatient admission and 72-hour return visits (overall and with admission). METHODS: In a retrospective analysis of electronic health record data on ED observation patients from January 1, 2022 to December 29, 2022 from an academic urban ED, we used propensity matching to compare virtual to in-person observation patients on outcomes of interest. Patients were matched 1:1 based on age, sex, Charlson Comorbidity Index, and reason for observation. We also conducted real-time review of all virtual observation cases for potential safety concerns. RESULTS: Of 8,218 observation stays, 361 virtual observation patients were matched with 361 in-person observation patients. Virtual observation patients experienced lower median brick-and-mortar ED + EDOU LOS [14.6 (IQR 10.2, 18.9) versus 33.3 (IQR 28.1, 38.1) hours] and lower inpatient admission rates (10.2% [SD 5.0] versus 24.7% [SD 11.3]). The 72-hour return rate was higher for virtual observation patients (3.6% [SD 3.0] versus 2.5% [SD 3.0]). Among those with return visits, the rate of inpatient admission was higher among virtual observation patients (53.8% [SD 3.2] versus 11.1% [13.0]). There were no significant patient safety events recorded. CONCLUSION: Virtual observation unit patients used fewer hours in ED and ED observation relative to on-site observation patients. This new care delivery model warrants further study because it has the potential to positively impact ED capacity.

An Electronic Medical Record Intervention to Increase Pharmacologic Prophylaxis for Venous Thromboembolism in Emergency Department Observation Patients.

STUDY OBJECTIVE: The role of venous thromboembolism (VTE) prophylaxis among patients receiving emergency department (ED) observation unit care is unclear. We investigated an electronic health record-based clinical decision support tool aimed at increasing pharmacologic VTE prophylaxis use among at-risk patients placed in ED observation units. METHODS: We conducted an interrupted time-series study of an Epic-based best practice advisory implemented in May 2019 at a health care system comprising 2 academic medical centers and 4 community hospitals with dedicated ED observation units. The best practice advisory alerted staff at 24 hours to conduct a risk assessment and linked to a VTE prophylaxis order set. We used an interrupted time series, Bayesian structured time series, and a multivariable mixed-effect regression model to estimate the intervention effect. RESULTS: Prior to the best practice advisory implementation, there were 8,895 ED observation unit patients with a length of stay more than or equal to 24 hours, and 0.9% received pharmacologic VTE prophylaxis. Afterward, there were 12,664 ED observation unit patients with a length of stay more than or equal to 24 hours, and 4.8% received pharmacologic VTE prophylaxis. The interrupted time series and causal impact analysis showed a statistically significant increase in VTE prophylaxis (eg, absolute percent difference 3.8%, 95% confidence interval 3.5 to 4.1). In a multivariable model, only the intervention was significantly associated with receiving VTE prophylaxis (odds ratio 4.56, 95% confidence interval 2.22 to 9.37). CONCLUSION: An electronic health record-based alert helped to prompt staff caring for ED observation unit patients at risk for VTE with prolonged visits to order recommended pharmacologic prophylaxis. The best risk assessment model to use and the true incidence of VTE events in this population are unclear.

A neural circuit mechanism integrating motivational state with memory expression in Drosophila.

Behavioral expression of food-associated memory in fruit flies is constrained by satiety and promoted by hunger, suggesting an influence of motivational state. Here, we identify a neural mechanism that integrates the internal state of hunger and appetitive memory. We show that stimulation of neurons that express neuropeptide F (dNPF), an ortholog of mammalian NPY, mimics food deprivation and promotes memory performance in satiated flies. Robust appetitive memory performance requires the dNPF receptor in six dopaminergic neurons that innervate a distinct region of the mushroom bodies. Blocking these dopaminergic neurons releases memory performance in satiated flies, whereas stimulation suppresses memory performance in hungry flies. Therefore, dNPF and dopamine provide a motivational switch in the mushroom body that controls the output of appetitive memory.

Wide Institutional Variability in the Treatment of Pediatric Critical Asthma: A Multicenter Retrospective Study.

OBJECTIVES: Children with status asthmaticus refractory to first-line therapies of systemic corticosteroids and inhaled beta-agonists often receive additional treatments. Because there are no national guidelines on the use of asthma therapies in the PICU, we sought to evaluate institutional variability in the use of adjunctive asthma treatments and associations with length of stay (LOS) and PICU use. DESIGN: Multicenter retrospective cohort study. SETTING: Administrative data from the Pediatric Health Information Systems (PHIS) database. PATIENTS: All inpatients 2-18 years old were admitted to a PHIS hospital between 2013 and 2021 with a diagnostic code for asthma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study included 213,506 inpatient encounters for asthma, of which 29,026 patient encounters included care in a PICU from 39 institutions. Among these PICU encounters, large variability was seen across institutions in both the number of adjunctive asthma therapies used per encounter (min: 0.6, median: 1.7, max: 2.5, p < 0.01) and types of adjunctive asthma therapies (aminophylline, ipratropium, magnesium, epinephrine, and terbutaline) used. The center-level median hospital LOS ranged from 1 (interquartile range [IQR]: 1, 3) to 4 (3, 6) days. Among all the 213,506 inpatient encounters for asthma, the range of asthma admissions that resulted in PICU admission varied between centers from 5.2% to 47.3%. The average number of adjunctive therapies used per institution was not significantly associated with hospital LOS ( p = 0.81) nor the percentage of encounters with PICU admission ( p = 0.47). CONCLUSIONS: Use of adjunctive therapies for status asthmaticus varies widely among large children's hospitals and was not associated with hospital LOS or the percentage of encounters with PICU admission. Wide variance presents an opportunity for standardizing care with evidence-based guidelines to optimize outcomes and decrease adverse treatment effects and hospital costs.

Patient Perceptions of Emergency Department Observation Care at Home.

Introduction: The Virtual Observation Unit (VOU) utilizes telehealth and community paramedicine to provide observation-level care in patients' homes. Patients' experience of this novel program has not been reported. Methods: A phone-based patient experience survey was administered to the patients who were admitted to the VOU at an urban, academic Emergency Department in the Northeast United States. The survey asked about patient's perception of the program's quality of care (0 = worst care possible, 10 = best care possible). t Tests with a Bonferroni adjustment assessed for differences between patient demographic groups. Results: The survey response rate was 40% (124/307). Overall mean scores for perceived quality of care were very high (9.51 ± 1.19). There were no significant differences in patient's perception of quality of care between demographic cohorts of age, gender, race, or ethnicity. Conclusions: Patient experience with a novel VOU program was very positive and did not differ significantly by demographic cohort. Further research is warranted.

The impact of COVID-19 on school nursing: A qualitative survey of stressors faced by school nurses.

BACKGROUND: As students returned to school, school nurses were responsible for infection control, communication, and the preparation of supplies and facilities. School nurses in the Pacific Northwest US demonstrated a higher prevalence of mental health symptoms in the years since the pandemic began, suggesting that their experience may have been unique. OBJECTIVE: This study aimed to explore the stressors of school nurses in the Pacific Northwest at two time points. DESIGN: This study is a qualitative, descriptive analysis of anonymous survey responses collected in June of 2021 (n = 333) and between October and December 2021 (n = 284). SAMPLE: Self-identifying school nurses working in K-12 schools in Washington State were invited to participate. MEASUREMENTS: Participants completed open-ended survey questions designed to elicit their experiences during the pandemic. RESULTS: Four themes emerged from the data: (1) isolation from administration and the school community, (2) COVID-19-related workload, (3) disorganized and inconsistent communication, and (4) concern for students, themselves, and others. CONCLUSIONS: School nurses played a vital public health role during the pandemic. However, their effectiveness may not have been fully utilized and sometimes undermined. Lastly, our findings highlight the difficulties encountered in implementing the changing scientific and public health guidance during the pandemic.

Second Primary Malignancies in Patients with a Neuroendocrine Neoplasm in England.

INTRODUCTION: Patients with neuroendocrine neoplasms (NENs) may often develop other malignancies. This study aimed to identify the frequency at which these second malignancies occurred in England. METHODS: Data were extracted from the National Cancer Registration and Analysis Service (NCRAS) on all patients diagnosed with a NEN at one of eight NEN site groups between 2012 and 2018: appendix, caecum, colon, lung, pancreas, rectum, small intestine, and stomach. WHO International Classification of Disease Edition-10 (ICD-10) codes were used to identify patients who had been diagnosed with an additional non-NEN cancer. Standardized incidence ratios (SIRs) for tumours diagnosed after the index NEN were produced for each non-NEN cancer type by sex and site. RESULTS: A total of 20,579 patients were included in the study. The most commonly occurring non-NEN cancers after NEN diagnosis were the prostate (20%), lung (20%), and breast (15%). Statistically significant SIRs were observed for non-NEN cancer of the lung (SIR = 1.85, 95% CI: 1.55-2.22), colon (SIR = 1.78, 95% CI: 1.40-2.27), prostate (SIR = 1.56, 95% CI: 1.31-1.86), kidney (SIR = 3.53, 95% CI: 2.72-4.59), and thyroid (SIR = 6.31, 95% CI: 4.26-9.33). When stratified by sex, statistically significant SIRs remained for the lung, renal, colon, and thyroid tumours. Additionally, females had a statistically significant SIR for stomach cancer (2.65, 95% CI: 1.26-5.57) and bladder cancer (SIR = 2.61, 95% CI: 1.36-5.02). CONCLUSION: This study found that patients with a NEN experienced a metachronous tumour of the lung, prostate, kidney, colon, and thyroid at a higher rate than the general population of England. Surveillance and engagement in existing screening programmes are required to enable earlier diagnosis of second non-NEN tumours in these patients.

Machine Learning Methods for Predicting Patient-Level Emergency Department Workload.

BACKGROUND: Work Relative Value Units (wRVUs) are a component of many compensation models, and a proxy for the effort required to care for a patient. Accurate prediction of wRVUs generated per patient at triage could facilitate real-time load balancing between physicians and provide many practical operational and clinical benefits. OBJECTIVE: We examined whether deep-learning approaches could predict the wRVUs generated by a patient's visit using data commonly available at triage. METHODS: Adult patients presenting to an urban, academic emergency department from July 1, 2016-March 1, 2020 were included. Deidentified triage information included structured data (age, sex, vital signs, Emergency Severity Index score, language, race, standardized chief complaint) and unstructured data (free-text chief complaint) with wRVUs as outcome. Five models were examined: average wRVUs per chief complaint, linear regression, neural network and gradient-boosted tree on structured data, and neural network on unstructured textual data. Models were evaluated using mean absolute error. RESULTS: We analyzed 204,064 visits between July 1, 2016 and March 1, 2020. The median wRVUs were 3.80 (interquartile range 2.56-4.21), with significant effects of age, gender, and race. Models demonstrated lower error as complexity increased. Predictions using averages from chief complaints alone demonstrated a mean error of 2.17 predicted wRVUs per visit (95% confidence interval [CI] 2.07-2.27), the linear regression model: 1.00 wRVUs (95% CI 0.97-1.04), gradient-boosted tree: 0.85 wRVUs (95% CI 0.84-0.86), neural network with structured data: 0.86 wRVUs (95% CI 0.85-0.87), and neural network with unstructured data: 0.78 wRVUs (95% CI 0.76-0.80). CONCLUSIONS: Chief complaints are a poor predictor of the effort needed to evaluate a patient; however, deep-learning techniques show promise. These algorithms have the potential to provide many practical applications, including balancing workloads and compensation between emergency physicians, quantify crowding and mobilizing resources, and reducing bias in the triage process.

Epidemiology and Outcomes of Critically Ill Children at Risk for Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

OBJECTIVES: Interventional trials aimed at pediatric acute respiratory distress syndrome prevention require accurate identification of high-risk patients. In this study, we aimed to characterize the frequency and outcomes of children meeting "at risk for pediatric acute respiratory distress syndrome" criteria as defined by the Pediatric Acute Lung Injury Consensus Conference. DESIGN: Planned substudy of the prospective multicenter, international Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study conducted during 10 nonconsecutive weeks (May 2016-June 2017). SETTING: Thirty-seven international PICUs. PATIENTS: Three-hundred ten critically ill children meeting Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the frequency of children at risk for pediatric acute respiratory distress syndrome and rate of subsequent pediatric acute respiratory distress syndrome diagnosis and used multivariable logistic regression to identify factors associated with subsequent pediatric acute respiratory distress syndrome. Frequency of at risk for pediatric acute respiratory distress syndrome was 3.8% (95% CI, 3.4-5.2%) among the 8,122 critically ill children who were screened and 5.8% (95% CI, 5.2-6.4%) among the 5,334 screened children on positive pressure ventilation or high-flow oxygen. Among the 310 at-risk children, median age was 2.1 years (interquartile range, 0.5-7.3 yr). Sixty-six children (21.3%) were subsequently diagnosed with pediatric acute respiratory distress syndrome, a median of 22.6 hours (interquartile range, 9.8-41.0 hr) later. Subsequent pediatric acute respiratory distress syndrome was associated with increased mortality (21.2% vs 3.3%; p < 0.001) and longer durations of invasive ventilation and PICU care. Subsequent pediatric acute respiratory distress syndrome rate did not differ by respiratory support modality at the time of meeting at risk criteria but was independently associated with lower initial saturation:Fio2 ratio, progressive tachycardia, and early diuretic administration. CONCLUSIONS: The Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria identify critically ill children at high risk of pediatric acute respiratory distress syndrome and poor outcomes. Interventional trials aimed at pediatric acute respiratory distress syndrome prevention should target patients early in their illness course and include patients on high-flow oxygen and positive pressure ventilation.

Mechanical power in pediatric acute respiratory distress syndrome: a PARDIE study.

BACKGROUND: Mechanical power is a composite variable for energy transmitted to the respiratory system over time that may better capture risk for ventilator-induced lung injury than individual ventilator management components. We sought to evaluate if mechanical ventilation management with a high mechanical power is associated with fewer ventilator-free days (VFD) in children with pediatric acute respiratory distress syndrome (PARDS). METHODS: Retrospective analysis of a prospective observational international cohort study. RESULTS: There were 306 children from 55 pediatric intensive care units included. High mechanical power was associated with younger age, higher oxygenation index, a comorbid condition of bronchopulmonary dysplasia, higher tidal volume, higher delta pressure (peak inspiratory pressure-positive end-expiratory pressure), and higher respiratory rate. Higher mechanical power was associated with fewer 28-day VFD after controlling for confounding variables (per 0.1 J·min-1·Kg-1 Subdistribution Hazard Ratio (SHR) 0.93 (0.87, 0.98), p = 0.013). Higher mechanical power was not associated with higher intensive care unit mortality in multivariable analysis in the entire cohort (per 0.1 J·min-1·Kg-1 OR 1.12 [0.94, 1.32], p = 0.20). But was associated with higher mortality when excluding children who died due to neurologic reasons (per 0.1 J·min-1·Kg-1 OR 1.22 [1.01, 1.46], p = 0.036). In subgroup analyses by age, the association between higher mechanical power and fewer 28-day VFD remained only in children < 2-years-old (per 0.1 J·min-1·Kg-1 SHR 0.89 (0.82, 0.96), p = 0.005). Younger children were managed with lower tidal volume, higher delta pressure, higher respiratory rate, lower positive end-expiratory pressure, and higher PCO2 than older children. No individual ventilator management component mediated the effect of mechanical power on 28-day VFD. CONCLUSIONS: Higher mechanical power is associated with fewer 28-day VFDs in children with PARDS. This association is strongest in children < 2-years-old in whom there are notable differences in mechanical ventilation management. While further validation is needed, these data highlight that ventilator management is associated with outcome in children with PARDS, and there may be subgroups of children with higher potential benefit from strategies to improve lung-protective ventilation. TAKE HOME MESSAGE: Higher mechanical power is associated with fewer 28-day ventilator-free days in children with pediatric acute respiratory distress syndrome. This association is strongest in children <2-years-old in whom there are notable differences in mechanical ventilation management.

Clinical Decision Support Reduces Unnecessary Tetanus Vaccinations in the Emergency Department.

STUDY OBJECTIVE: Tetanus is the most common vaccination given in the emergency department; yet, administrations of tetanus vaccine boosters in the ED may not comply with the US Centers for Disease Control and Prevention's recommended vaccination schedule. We implemented a clinical decision support alert in the electronic health record that warned providers when ordering a tetanus vaccine if a prior one had been given within 10 years and studied its efficacy to reduce potentially unnecessary vaccines in the ED. METHODS: This was a retrospective, quasi-experimental, 1-group, pretest-posttest study in 3 hospital EDs in Boston, MA. We studied adult patients for whom tetanus vaccines were ordered despite a history of vaccination within the prior 10 years. We compared the number of potentially unnecessary tetanus vaccine administrations in a baseline phase (when the clinical decision support alert was not visible) versus an intervention phase. RESULTS: Of eligible patients, 22.1% (95% confidence interval [CI] 21.8% to 22.4%) had prior tetanus vaccines within 5 years, 12.8% (95% CI 12.5% to 13.0%) within 5 to 10 years, 3.8% (95% CI 3.6% to 3.9%) more than 10 years ago, and 61.3% (95% CI 60.9% to 61.7%) had no prior tetanus vaccination documentation. Of 60,983 encounters, 337 met the inclusion criteria. A tetanus vaccination was administered in 91% (95% CI 87% to 96%) of encounters in the baseline phase, compared to 55% (95% CI 47% to 62%) during the intervention. The absolute risk reduction was 36.7% (95% CI 28.0% to 45.4%), and the number of encounters needed to alert to avoid 1 potentially unnecessary tetanus vaccine (number needed to treat) was 2.7 (95% CI 2.2% to 3.6%). For patients with tetanus vaccines within the prior 5 years, the absolute risk reduction was 47.9% (95% CI 35.5 % to 60.3%) and the number needed to treat was 2.1 (95% CI 1.7% to 2.8%). CONCLUSION: A clinical decision support alert that warns ED clinicians that a patient may have an up-to-date tetanus vaccination status reduces potentially unnecessary vaccinations.

Health-related quality of life outcome measures for children surviving critical care: a scoping review.

PURPOSE: Health-related quality of life (HRQL) has been identified as one of the core outcomes most important to assess following pediatric critical care, yet there are no data on the use of HRQL in pediatric critical care research. We aimed to determine the HRQL instruments most commonly used to assess children surviving critical care and describe study methodology, patient populations, and instrument characteristics to identify areas of deficiency and guide investigators conducting HRQL research. METHODS: We queried PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Registry for studies evaluating pediatric critical care survivors published 1970-2017. We used dual review for article selection and data extraction. RESULTS: Of 60,349 citations, 66 articles met inclusion criteria. The majority of studies were observational (89.4%) and assessed HRQL at one post-discharge time-point (86.4%), and only 10.6% of studies included a baseline assessment. Time to the first follow-up assessment ranged from 1 month to 10 years post-hospitalization (median 3 years, IQR 0.5-6). For 26 prospective studies, the median follow-up time was 0.5 years [IQR 0.25-1]. Parent/guardian proxy-reporting was used in 83.3% of studies. Fifteen HRQL instruments were employed, with four used in >5% of articles: the Health Utility Index (n = 22 articles), the Pediatric Quality of Life Inventory (n = 17), the Child Health Questionnaire (n = 16), and the 36-Item Short Form Survey (n = 9). CONCLUSION: HRQL assessment in pediatric critical care research has been centered around four instruments, though existing literature is limited by minimal longitudinal follow-up and infrequent assessment of baseline HRQL.

Emergency physicians' active patient queues over the course of a shift.

OBJECTIVES: When emergency physicians see new patients in an ad libitum system, they see fewer patients as the shift progresses. However, it is unclear if this reflects a decreasing workload, as patient assessments often span many hours. We sought to investigate whether the size of a physician's queue of active patients similarly declines over a shift. METHODS: Retrospective cohort study, conducted over two years in three community hospitals in the Northeastern United States, with 8 and 9-h shifts. Timestamps of all encounters were recorded electronically. Generalized estimating equations were constructed to predict the number of active patients a physician concurrently managed per hour. RESULTS: We evaluated 64 physicians over a two-year period, with 9822 physician-shifts. Across all sites, physicians managed an increasing queue of active patients in the first several hours. This queue plateaued in the middle of the shift, declining in the final hours, independently of other factors. Physicians' queues of active patients increased slightly with greater volume and acuity, but did not affect the overall pattern of work. Similarly, working alone or with colleagues had little effect on the number of active patients managed. CONCLUSIONS: Emergency physicians in an ad libitum system tend to see new patients until reaching a stable roster of active patients. This pattern may help explain why physicians see fewer new patients over the course of a shift, should be factored into models of throughput, and suggests new avenues for evaluating relationships between physician workload, patient safety, physicians' well-being, and the quality of care.

The cases not seen: Patterns of emergency department visits and procedures in the era of COVID-19.

OBJECTIVE: Prior data suggest Emergency Department (ED) visits for many emergency conditions decreased during the initial COVID-19 surge. However, the pandemic's impact on the wide range of conditions seen in EDs, and the resources required for treating them, has been less studied. We sought to provide a comprehensive analysis of ED visits and associated resource utilization during the initial COVID-19 surge. METHODS: We performed a retrospective analysis from 5 hospitals in a large health system in Massachusetts, comparing ED encounters from 3/1/2020-4/30/2020 to identical weeks from the prior year. Data collected included demographics, ESI, diagnosis, consultations ordered, bedside procedures, and inpatient procedures within 48 h. We compared raw frequencies between time periods and calculated incidence rate ratios. RESULTS: ED volumes decreased by 30.9% in 2020 compared to 2019. Average acuity of ED presentations increased, while most non-COVID-19 diagnoses decreased. The number and incidence rate of all non-critical care ED procedures decreased, while the occurrence of intubations and central lines increased. Most subspecialty consultations decreased, including to psychiatry, trauma surgery, and cardiology. Most non-elective procedures related to ED encounters also decreased, including craniotomies and appendectomies. CONCLUSION: Our health system experienced decreases in nearly all non-COVID-19 conditions presenting to EDs during the initial phase of the pandemic, including those requiring specialty consultation and urgent inpatient procedures. Findings have implications for both public health and health system planning.

Inflammation-The role of ATP in pre-eclampsia.

Sterile inflammation may be initiated by molecules in the host organism that signal "damage" or "danger" also known as danger-associated molecular pattern (DAMPs). In pre-eclampsia (PE), a variety of DAMPs may be involved in the etiology or exacerbation of the disorder. Adenosine 5'-triphosphate (ATP) is a key intracellular energy molecule as well as a ligand for purinergic receptors. In humans, under physiological conditions, extracellular ATP (eATP) levels are distinctly low, but can rise to several hundred fold when cells become injured, stressed, or even necrotic. This often initiates a sterile inflammatory response with eATP acting as a DAMP. Extracellular ATP and its derivative nucleotides synthetized by endonucleotidases exhibit many of their effects through purinergic receptors, via inflammatory cascades and the production of proinflammatory molecules. This is clearly seen in the P2X7 gated receptor, which is linked to release of cytokines of the interleukin-1 family. Considering its fundamental role in innate immunity, an imbalance of P2X7 receptor activation may lead to deleterious effects in the coordination of placental vessel tone via the synthesis of various proinflammatory cytokines. This review explores the implication of DAMPs, specifically ATP and uric acid in the inflammation associated with PE.

One-way-street revisited: Streamlined admission of critically-ill trauma patients.

INTRODUCTION: Emergency department (ED) crowding is associated with increased mortality and delays in care. We developed a rapid admission pathway targeting critically-ill trauma patients in the ED. This study investigates the sustainability of the pathway, as well as its effectiveness in times of increased ED crowding. MATERIALS & METHODS: This was a retrospective cohort study assessing the admission of critically-ill trauma patients with and without the use of a rapid admission pathway from 2013 to 2018. We accessed demographic and clinical data from trauma registry data and ED capacity logs. Statistical analyses included univariate and multivariate testing. RESULTS: A total of 1700 patients were included. Of this cohort, 434 patients were admitted using the rapid admission pathway, whereas 1266 were admitted using the traditional pathway. In bivariate analysis, mean ED LOS was 1.54 h (95% Confidence Interval [CI]: 1.41, 1.66) with the rapid pathway, compared with 5.88 h (95% CI: 5.64, 6.12) with the traditional pathway (p < 0.01). We found no statistically significant relationship between rapid admission pathway use and survival to hospital discharge. During times of increased crowding, rapid pathway use continued to be associated with reduction in ED LOS (p < 0.01). The reduction in ED LOS was sustained when comparing initial results (2013-2014) to recent data (2015-2018). CONCLUSION: This study found that a streamlined process to admit critically-ill trauma patients is sustainable and associated with reduction in ED LOS. As ED crowding remains pervasive, these findings support restructured care processes to limit prolonged ED boarding times for critically-ill patients.