Intraretinal hemorrhages and detailed retinal phenotype of three patients with Alagille syndrome.

PURPOSE: To explore patterns of disease expression in Alagille syndrome (ALGS). METHODS: Patients underwent ophthalmic examination, optical coherence tomography (OCT) imaging, fundus intravenous fluorescein angiography (IVFA), perimetry and full-field electroretinograms (ffERGs). An adult ALGS patient had multimodal imaging and specialized perimetry. RESULTS: The proband (P1) had a heterozygous pathogenic variant in JAG1; (p.Gln410Ter) and was incidentally diagnosed at age 7 with a superficial retinal hemorrhage, vascular tortuosity, and midperipheral pigmentary changes. The hemorrhage recurred 15 months later. Her monozygotic twin sister (P2) had a retinal hemorrhage at the same location at age 11. Visual acuities for both patients were 20/30 in each eye. IVFA was normal. OCT showed thinning of the outer nuclear in the peripapillary retina. A ffERG showed normal cone-mediated responses in P1 (rod-mediated ERGs not documented), normal ffERGs in P2. Coagulation and liver function were normal. An unrelated 42-year-old woman with a de-novo pathogenic variant (p. Gly386Arg) in JAG1 showed a similar pigmentary retinopathy and hepatic vascular anomalies; rod and cone function was normal across large expanses of structurally normal retina that sharply transitioned to a blind atrophic peripheral retina. CONCLUSION: Nearly identical recurrent intraretinal hemorrhages in monozygotic twins with ALGS suggest a shared subclinical microvascular abnormality. We hypothesize that the presence of large areas of functionally and structurally intact retina surrounded by severe chorioretinal degeneration, is against a predominant involvement of JAG1 in the function of the neurosensory retina, and that instead, primary abnormalities of chorioretinal vascular development and/or homeostasis may drive the peculiar phenotypes.

Parenteral Antibiotic Use Among Ambulatory Children in United States Children's Hospital Emergency Departments.

BACKGROUND: Despite increasing recognition of the importance of optimal antibiotic selection and expansion of antimicrobial stewardship activities to ambulatory settings, few studies have examined the frequency of parenteral antibiotic use among ambulatory children. We assessed the prevalence and patterns of parenteral antibiotic administration among ambulatory children in pediatric emergency departments (EDs). METHODS: We conducted a cross-sectional assessment of parenteral antibiotic use among ambulatory children aged 0-18 years in 49 US children's hospital EDs in 2018. We assessed the prevalence rates of parenteral antibiotic use and stratified these by patient-, clinic-, and hospital-level characteristics. We also assessed the prevalence of use of specific antibiotics by age and diagnosis category. Among encounters associated with an infection diagnosis, we identified factors associated with parenteral antibiotic use using multivariable logistic regression. RESULTS: Among 3 452 011 ambulatory ED encounters in 2018, parenteral antibiotics were administered in 62 648 (1.8%). The highest proportion of parenteral antibiotic use occurred in the 15-18-year age group (3.3%) and among encounters in children with complex chronic conditions (8.9%) and with primary diagnoses of neoplasms (36%). Ceftriaxone was the most commonly administered parenteral antibiotic (61%). In multivariable analysis, several factors including age ≤2 months, White race, private insurance, complex chronic conditions, digestive and genitourinary system diseases, and encounters attributed to emergency medicine providers were significantly associated with higher odds of parenteral antibiotic use. CONCLUSIONS: This study demonstrates substantial variability in the frequency of parenteral antibiotic administration by age and diagnosis in the ambulatory ED setting and highlights potential opportunities to target stewardship activities.

"Your Finger or Mine?"-Patient Preferences in the Collection of Fecal Occult Blood Testing in the Emergency Department.

INTRODUCTION: There are a number of presenting Emergency Department complaints that may necessitate the testing of stool for the presence of blood. A provider-performed digital rectal examination is frequently performed solely for the collection of stool for a fecal occult blood testing (FOBT). With increased emphasis on patient autonomy and shared decision-making, it is appropriate to consider patient preferences with regard to who performs the invasive collection of stool. Our objective was to determine patient preference in regard to provider versus self-collection of stool sample for use in FOBT and identify patient demographics associated with those more likely to self-collect. Finally, we examined specimen adequacy and patient satisfaction by open-ended comment. MATERIALS AND METHODS: We conducted a 1-year, prospective, non-randomized, observational trial with a convenience sample of 100 patients. After enrollment, study participants were offered the choice of self-collection versus provider collection. Stool collection proceeded according to participant preference. Simple descriptive statistics were used to analyze the primary outcome. The secondary proportional univariate outcomes were evaluated with chi-square testing (alpha level-0.05). We used a multivariable logistic regression model to evaluate the association of independent variables with the likelihood to perform self-collection. RESULTS: A total of 100 patients were enrolled over 1 year, with 51% choosing to collect their own sample. Younger age was the only statistically significant predictor for self-collection (p < 0.001); furthermore, for every year of increasing age, patients were 3% less likely to choose self-collection. All self-collected samples were adequate for testing. In univariate analyses, patients younger than 35 were more likely to perform self-collection (66%) compared with those over 35 (36%). Those over 64 self-collected only 24% of the time. Neither sex nor race were associated with collection method preference. CONCLUSIONS: When offered the choice between self-directed or provider-performed stool sample collection, more than half of participants chose to obtain their own sample; furthermore, age was the only statistically significant predictor of preference for collection method. All patients who self-collected were able to provide an adequate sample. Our evidence suggests the offer of FOBT self-collection is a feasible method to enhance patient autonomy and improve therapeutic alliances.

Electronic personal protective equipment: A strategy to protect emergency department providers in the age of COVID-19.

Emergent policy changes related to telemedicine and the Emergency Medical Treatment and Labor Act during the novel coronavirus disease 2019 (COVID-19) pandemic have created opportunities for technology-based clinical evaluation, which serves to conserve personal protective equipment (PPE) and protect emergency providers. We define electronic PPE as an approach using telemedicine tools to perform electronic medical screening exams while satisfying the Emergency Medical Treatment and Labor Act. We discuss the safety, legal, and technical factors necessary for implementing such a pathway. This approach has the potential to conserve PPE and protect providers while maintaining safe standards for medical screening exams in the emergency department for low-risk patients in whom COVID-19 is suspected.

Lessons Learned From the Development and Parameterization of a Computer Simulation Model to Evaluate Task Modification for Health Care Providers.

Computer simulation is a highly advantageous method for understanding and improving health care operations with a wide variety of possible applications. Most computer simulation studies in emergency medicine have sought to improve allocation of resources to meet demand or to assess the impact of hospital and other system policies on emergency department (ED) throughput. These models have enabled essential discoveries that can be used to improve the general structure and functioning of EDs. Theoretically, computer simulation could also be used to examine the impact of adding or modifying specific provider tasks. Doing so involves a number of unique considerations, particularly in the complex environment of acute care settings. In this paper, we describe conceptual advances and lessons learned during the design, parameterization, and validation of a computer simulation model constructed to evaluate changes in ED provider activity. We illustrate these concepts using examples from a study focused on the operational effects of HIV screening implementation in the ED. Presentation of our experience should emphasize the potential for application of computer simulation to study changes in health care provider activity and facilitate the progress of future investigators in this field.

Application of Quasi-Steady-State Methods to Nonlinear Models of Intracellular Transport by Molecular Motors.

Molecular motors such as kinesin and dynein are responsible for transporting material along microtubule networks in cells. In many contexts, motor dynamics can be modelled by a system of reaction-advection-diffusion partial differential equations (PDEs). Recently, quasi-steady-state (QSS) methods have been applied to models with linear reactions to approximate the behaviour of the full PDE system. Here, we extend this QSS reduction methodology to certain nonlinear reaction models. The QSS method relies on the assumption that the nonlinear binding and unbinding interactions of the cellular motors occur on a faster timescale than the spatial diffusion and advection processes. The full system dynamics are shown to be well approximated by the dynamics on the slow manifold. The slow manifold is parametrized by a single scalar quantity that satisfies a scalar nonlinear PDE, called the QSS PDE. We apply the QSS method to several specific nonlinear models for the binding and unbinding of molecular motors, and we use the resulting approximations to draw conclusions regarding the parameter dependence of the spatial distribution of motors for these models.

Cost-effectiveness analysis of early point-of-care lactate testing in the emergency department.

PURPOSE: To determine the cost-effectiveness of implementing a point-of-care (POC) Lactate Program in the emergency department (ED) for patients with suspected sepsis to identify patients who can benefit from early resuscitation. MATERIALS AND METHODS: We constructed a cost-effectiveness model to examine an ED with 30 000 patients annually. We evaluated a POC lactate program screening patients with suspected sepsis for an elevated lactate ≥4 mmol/L. Those with elevated lactate levels are resuscitated and their lactate clearance is evaluated by serial POC lactate measurements. The POC Lactate Program was compared with a Usual Care Strategy in which all patients with sepsis and an elevated lactate are admitted to the intensive care unit. Costs were estimated from the 2014 Medicare Inpatient and National Physician Fee schedules, and hospital and industry estimates. RESULTS: In the base-case, the POC Lactate Program cost $39.53/patient whereas the Usual Care Strategy cost $33.20/patient. The screened patients in the POC arm resulted in 1.07 quality-adjusted life years for an incremental cost-effectiveness ratio of $31 590 per quality-adjusted life year gained, well below accepted willingness-to-pay-thresholds. CONCLUSIONS: Implementing a POC Lactate Program for screening ED patients with suspected sepsis is a cost-effective intervention to identify patients responsive to early resuscitation.

Performance of a multi-disciplinary emergency department observation protocol for acetaminophen overdose.

The availability of 20-h N-acetylcysteine (NAC) infusion for low-risk acetaminophen (APAP) overdose enabled our center to implement an Emergency Department observation unit (OU) protocol as an alternative to hospitalization. Our objective was to evaluate our early experience with this protocol. This retrospective cohort study included all patients treated for low-risk APAP overdose in our academic hospital between 2006 and 2011. Cases were identified using OU and pharmacy records. Successful OU discharge was defined as disposition with no inpatient admission. Differences in medians with 95 % confidence intervals were used for comparisons. One hundred ninety-six patients received NAC for APAP overdose with a mean age of 35 years (SD 14); 73 % were white, and 43 % were male. Twenty (10 %) received care in the OU; 3/20(15 %) met criteria for inclusion in the OU protocol and 13/20(65 %) were discharged successfully. Out of the 196 patients, 10 met criteria for inclusion in the OU protocol but instead received care in the inpatient setting. The median total length of stay from presentation to ED discharge was 41 h for all patients treated in the OU, compared to 68 h for ten patients who met criteria for inclusion in the OU protocol but who were admitted (difference 27 h, 95 % CI 18-72 h). ED observation for APAP overdose can be a viable alternative to inpatient admission. Most patients were successfully discharged from the OU. This evaluation identified both over- and under-utilization of the OU. OU treatment resulted in shorter median length of stay than inpatient admission.

The mortality benefit threshold for patients with suspected pulmonary embolism.

OBJECTIVES: The mortality benefit for pulmonary embolism (PE) is the difference in mortality between treated and untreated patients. The mortality benefit threshold is the mortality benefit above which testing for a condition should be initiated and below which it should not. To illustrate this concept, the authors developed a decision model to estimate the mortality benefit threshold at several pretest probabilities for low-risk emergency department (ED) patients with possible PE and compare those thresholds with contemporary management of PE in the United States and what is known and not known about treatment benefits with anticoagulation. METHODS: The authors built a decision model of a 25-year-old female with suspected PE. Model inputs were obtained from the literature or clinical judgment when data were unavailable. One-way sensitivity analysis was used to derive the mortality benefit threshold at several fixed pretest probabilities, and two-way sensitivity analysis was used to determine drivers of the mortality benefit threshold. RESULTS: At a 15% pretest probability, the mortality benefit threshold was 3.7%; at 10% it was 5.2%; at 5% it was 9.8%; at 2% it was 23.5%; at 1% it was 46.3%; and at 0.5% it was 92.1%. In two-way sensitivity analyses, D-dimer specificity, CT angiography (CTA)/CT venography (CTV) sensitivity, annual cancer risk, probability of death from renal failure, and probability of major bleeding were major model drivers. CONCLUSIONS: The mortality benefit threshold for initiating PE testing is very high at low pretest probabilities of PE, which should be considered by clinicians in their diagnostic approach to PE in the ED. The mortality benefit threshold is a novel way of exploring the benefits and risks of ED-based testing, particularly in situations like PE where testing (i.e., CT use) carries real risks and the benefits of treatment are uncertain.

Cost-effectiveness of lower extremity compression ultrasound in emergency department patients with a high risk of hemodynamically stable pulmonary embolism.

BACKGROUND: Computed tomography angiograms (CTAs) for patients with suspected pulmonary embolism (PE) are being ordered with increasing frequency from the emergency department (ED). Strategies are needed to safely decrease the utilization of CTs to control rising health care costs and minimize the associated risks of anaphylaxis, contrast-induced nephropathy, and radiation-induced carcinogenesis. The use of compression ultrasonography (US) to identify deep vein thromboses (DVTs) in hemodynamically stable patients with signs and symptoms suggestive of PE is highly specific for the diagnosis of PE and may represent a cost-effective alternative to CT imaging. OBJECTIVES: The objective was to analyze the cost-effectiveness of a selective CT strategy incorporating the use of compression US to diagnose and treat DVT in patients with a high pretest probability of PE. METHODS: The authors constructed a decision analytic model to evaluate the scenario of an otherwise healthy 59-year-old female in whom PE was being considered as a diagnosis. Two strategies were used. The selective CT strategy began with a screening compression US. Negative studies were followed up with a CTA, while patients with positive studies identifying a DVT were treated as though they had a PE and were anticoagulated. The universal CT strategy used CTA as the initial test, and anticoagulation was based on the CT result. Costs were estimated from the 2009 Medicare data for hospital reimbursement, and professional fees were obtained from the 2009 National Physician Fee Schedule. Clinical probabilities were obtained from existing published data, and sensitivity analyses were performed across plausible ranges for all clinical variables. RESULTS: In the base case, the selective CT strategy cost $1,457.70 less than the universal CT strategy and resulted in a gain of 0.0213 quality-adjusted life-years (QALYs). Sensitivity analyses confirm that the selective CT strategy is dominant above both a pretest probability for PE of 8.3% and a compression US specificity of 87.4%. CONCLUSIONS: A selective CT strategy using compression US is cost-effective for patients provided they have a high pretest probability of PE. This may reduce the need for, and decrease the adverse events associated with, CTAs.