A Model for Competency-Based Grading and Its Effect on Student Outcomes in a Biomechanics Course.

Competency-based grading (CBG) can take different forms in different subject areas. We present a method for implementing CBG in a biomechanics course with nine primary learning objectives. Competency in each learning objective is measured by the student's ability to correctly answer knowledge questions and solve analytical problems in the field of biomechanics. The primary goal of implementing CBG was to provide more opportunities for lower-performing students to learn the material and to demonstrate that learning. To determine the efficacy of CBG to improve student learning, the primary measure was course grade distribution before and after implementation of CBG. The course grade distribution data indicated that CBG has primarily helped midperforming students to improve their grades. Because of the limitations of course grades as a measure of learning, we also performed analysis of student performance on successive attempts which indicated initial and secondary attempts are best, with student success declining on subsequent attempts. Anecdotally, many students improved performance, and thus their grade, on the (optional) final exam attempts. Limitations of the study include the limited course offerings with CBG (three), and that effects of COVID-19 may be confounding CBG data. Also, the approach places nearly all the grade on quizzes or exams. However, the approach could be modified to include homework grades, projects, and the like. Overall, the student learning in this course and implementation appears to be only positively affected, so this approach appears to have benefits in a biomechanics course.

Kinetics of ATP/ADP binding to the gp16 ATPase.

The gp16 ATPase is the constituent subunit of the pentameric dsDNA (double-stranded deoxyribonucleic acid) translocation motor of the Bacillus subtilis Φ29 bacteriophage. Although recent single-molecule studies have provided tantalizing clues about the activity of this motor, the mechanism by which the gp16 subunits couple the energy obtained from the binding and hydrolysis of ATP to the mechanical work of dsDNA translocation remains unknown. To address this need, we have characterized the binding of fluorophore-labeled ATP and ADP to monomeric gp16 using a stopped-flow fluorescence assay. These experiments show that the binding of ATP/ADP occurs through a single-step mechanism with corresponding affinities of 523.8 ± 247.3 nM for ATP and a lower limit of 30 µM for ADP. When analyzed through the lens of changes in free energy of the system, this difference in binding affinities is reasonable for a cyclical process of binding, hydrolysis, and product release. In addition to answering questions about the activity of monomeric gp16, these results are also a necessary step in constructing a model for intersubunit communication within the pentameric gp16 motor.

Remodeler Catalyzed Nucleosome Repositioning: Influence of Structure and Stability.

The packaging of the eukaryotic genome into chromatin regulates the storage of genetic information, including the access of the cell's DNA metabolism machinery. Indeed, since the processes of DNA replication, translation, and repair require access to the underlying DNA, several mechanisms, both active and passive, have evolved by which chromatin structure can be regulated and modified. One mechanism relies upon the function of chromatin remodeling enzymes which couple the free energy obtained from the binding and hydrolysis of ATP to the mechanical work of repositioning and rearranging nucleosomes. Here, we review recent work on the nucleosome mobilization activity of this essential family of molecular machines.

Low processivity for DNA translocation by the ISWI molecular motor.

The motor protein ISWI (Imitation SWItch) is the conserved catalytic ATPase domain of the ISWI family of chromatin remodelers. Members of the ISWI family are involved in regulating the structure of cellular chromatin during times of transcription, translation, and repair. Current models for the nucleosome repositioning activity of ISWI and other chromatin remodelers require the translocation of the remodeling protein along double-stranded DNA through an ATP-dependent mechanism. Here we report results from spectrofluorometric stopped-flow experiments which demonstrate that ISWI displays very low processivity for free DNA translocation. By combining these results with those from experiments monitoring the DNA stimulated ATPase activity of ISWI we further demonstrate that the DNA translocation by ISWI is tightly coupled to ATP hydrolysis. The calculated coupling efficiency of 0.067±0.018 ATP/ISWI/bp is seemingly quite low in comparison to similar DNA translocases and we present potential models to account for this. Nevertheless, the tight coupling of ATP hydrolysis to DNA translocation suggests that DNA translocation is not energetically rate limiting for nucleosome repositioning by ISWI.

ISWI remodels nucleosomes through a random walk.

The chromatin remodeler ISWI is capable of repositioning clusters of nucleosomes to create well-ordered arrays or moving single nucleosomes from the center of DNA fragments toward the ends without disrupting their integrity. Using standard electrophoresis assays, we have monitored the ISWI-catalyzed repositioning of different nucleosome samples each containing a different length of DNA symmetrically flanking the initially centrally positioned histone octamer. We find that ISWI moves the histone octamer between distinct and thermodynamically stable positions on the DNA according to a random walk mechanism. Through the application of a spectrophotometric assay for nucleosome repositioning, we further characterized the repositioning activity of ISWI using short nucleosome substrates and were able to determine the macroscopic rate of nucleosome repositioning by ISWI. Additionally, quantitative analysis of repositioning experiments performed at various ISWI concentrations revealed that a monomeric ISWI is sufficient to obtain the observed repositioning activity as the presence of a second ISWI bound had no effect on the rate of nucleosome repositioning. We also found that ATP hydrolysis is poorly coupled to nucleosome repositioning, suggesting that DNA translocation by ISWI is not energetically rate-limiting for the repositioning reaction. This is the first calculation of a microscopic ATPase coupling efficiency for nucleosome repositioning and also further supports our conclusion that a second bound ISWI does not contribute to the repositioning reaction.

Quantitative determination of binding of ISWI to nucleosomes and DNA shows allosteric regulation of DNA binding by nucleotides.

The regulation of chromatin structure is controlled by a family of molecular motors called chromatin remodelers. The ability of these enzymes to remodel chromatin structure is dependent on their ability to couple ATP binding and hydrolysis into the mechanical work that drives nucleosome repositioning. The necessary first step in determining how these essential enzymes perform this function is to characterize both how they bind nucleosomes and how this interaction is regulated by ATP binding and hydrolysis. With this goal in mind, we monitored the interaction of the chromatin remodeler ISWI with fluorophore-labeled nucleosomes and DNA through associated changes in fluorescence anisotropy of the fluorophore upon binding of ISWI to these substrates. We determined that one ISWI molecule binds to a 20 bp double-stranded DNA substrate with an affinity of 18 ± 2 nM. In contrast, two ISWI molecules can bind to the core nucleosome with short linker DNA with stoichiometric macroscopic equilibrium constants: 1/ß1 = 1.3 ± 0.6 nM, and 1/ß2 = 13 ± 7 nM(2). Furthermore, to improve our understanding of the mechanism of DNA translocation by ISWI, and hence nucleosome repositioning, we determined the effect of nucleotide analogues on substrate binding by ISWI. While the affinity of ISWI for the nucleosome substrate with short lengths of flanking DNA was not affected by the presence of nucleotides, the affinity of ISWI for the DNA substrate is weakened in the presence of nonhydrolyzable ATP analogues but not by ADP.

Patient care transitions from the emergency department to the medicine ward: evaluation of a standardized electronic signout tool.

OBJECTIVE: To evaluate the impact of a new electronic handoff tool for emergency department to medicine ward patient transfers over a 1-year period. DESIGN: Prospective mixed-methods analysis of data submitted by medicine residents following admitting shifts before and after eSignout implementation. SETTING: University-based, tertiary-care hospital. PARTICIPANTS: Internal medicine resident physicians admitting patients from the emergency department. INTERVENTION: An electronic handoff tool (eSignout) utilizing automated paging communication and responsibility acceptance without mandatory verbal communication between emergency department and medicine ward providers. MAIN OUTCOME MEASURES: (i) Incidence of reported near misses/adverse events, (ii) communication of key clinical information and quality of verbal communication and (iii) characterization of near misses/adverse events. RESULTS: Seventy-eight of 80 surveys (98%) and 1058 of 1388 surveys (76%) were completed before and after eSignout implementation. Compared with pre-intervention, residents in the post-intervention period reported similar number of shifts with a near miss/adverse event (10.3 vs. 7.8%; P = 0.27), similar communication of key clinical information, and improved verbal signout quality, when it occurred. Compared with the former process requiring mandatory verbal communication, 93% believed the eSignout was more efficient and 61% preferred the eSignout. Patient safety issues related to perceived sufficiency/accuracy of diagnosis, treatment or disposition, and information quality. CONCLUSIONS: The eSignout was perceived as more efficient and preferred over the mandatory verbal signout process. Rates of reported adverse events were similar before and after the intervention. Our experience suggests electronic platforms with optional verbal communication can be used to standardize and improve the perceived efficiency of patient handoffs.

Subunit Communication within Dimeric SF1 DNA Helicases.

Monomers of the Superfamily (SF) 1 helicases, E. coli Rep and UvrD, can translocate directionally along single stranded (ss) DNA, but must be activated to function as helicases. In the absence of accessory factors, helicase activity requires Rep and UvrD homo-dimerization. The ssDNA binding sites of SF1 helicases contain a conserved aromatic amino acid (Trp250 in Rep and Trp256 in UvrD) that stacks with the DNA bases. Here we show that mutation of this Trp to Ala eliminates helicase activity in both Rep and UvrD. Rep(W250A) and UvrD(W256A) can still dimerize, bind DNA, and monomers still retain ATP-dependent ssDNA translocase activity, although with ∼10-fold lower rates and lower processivities than wild type monomers. Although neither wtRep monomers nor Rep(W250A) monomers possess helicase activity by themselves, using both ensemble and single molecule methods, we show that helicase activity is achieved upon formation of a Rep(W250A)/wtRep hetero-dimer. An ATPase deficient Rep monomer is unable to activate a wtRep monomer indicating that ATPase activity is needed in both subunits of the Rep hetero-dimer. We find the same results with E. coli UvrD and its equivalent mutant (UvrD(W256A)). Importantly, Rep(W250A) is unable to activate a wtUvrD monomer and UvrD(W256A) is unable to activate a wtRep monomer indicating that specific dimer interactions are required for helicase activity. We also demonstrate subunit communication within the dimer by virtue of Trp fluorescence signals that only are present within the Rep dimer, but not the monomers. These results bear on proposed subunit switching mechanisms for dimeric helicase activity.

Bicycle helmet laws are associated with a lower fatality rate from bicycle-motor vehicle collisions.

OBJECTIVE: To assess the association between bicycle helmet legislation and bicycle-related deaths sustained by children involved in bicycle-motor vehicle collisions. STUDY DESIGN: We conducted a cross-sectional study of all bicyclists aged 0-16 years included in the Fatality Analysis Reporting System who died between January 1999 and December 2010. We compared fatality rates in age-specific state populations between states with helmet laws and those without helmet laws. We used a clustered Poisson multivariate regression model to adjust for factors previously associated with rates of motor vehicle fatalities: elderly driver licensure laws, legal blood alcohol limit (<0.08% vs ≥ 0.08%), and household income. RESULTS: A total of 1612 bicycle-related fatalities sustained by children aged <16 years were evaluated. There were no statistically significant differences in median household income, the proportion of states with elderly licensure laws, or the proportion of states with a blood alcohol limit of >0.08% between states with helmet laws and those without helmet laws. The mean unadjusted fatality rate was lower in states with helmet laws (2.0/1,000,000 vs 2.5/1,000,000; P = .03). After adjusting for potential confounding factors, lower fatality rates persisted in states with mandatory helmet laws (adjusted incidence rate ratio, 0.84; 95% CI, 0.70-0.98). CONCLUSION: Bicycle helmet safety laws are associated with a lower incidence of fatalities in child cyclists involved in bicycle-motor vehicle collisions.

Kinetic mechanism of DNA translocation by the RSC molecular motor.

ATP-dependent nucleosome repositioning by chromatin remodeling enzymes requires the translocation of these enzymes along the nucleosomal DNA. Using a fluorescence stopped-flow assay we monitored DNA translocation by a minimal RSC motor and through global analysis of these time courses we have determined that this motor has a macroscopic translocation rate of 2.9 bp/s with a step size of 1.24 bp. From the complementary quantitative analysis of the associated time courses of ATP consumption during DNA translocation we have determined that this motor has an efficiency of 3.0 ATP/bp, which is slightly less that the efficiency observed for several genetically related DNA helicases and which likely results from random pausing by the motor during translocation. Nevertheless, this motor is able to exert enough force during translocation to displace streptavidin from biotinylated DNA. Taken together these results are the necessary first step for quantifying both the role of DNA translocation in nucleosome repositioning by RSC and the efficiency at which RSC couples ATP binding and hydrolysis to nucleosome repositioning.

Safety Factors and Patterns of Bicycle Trauma in a Tertiary Level 1 Trauma Center in Boston, Massachusetts: A Retrospective Review and Survey Study.

Objectives: Increasing bicycle ridership is accompanied by ongoing bicycle-related accidents in many urban cities. There is a need for improved understanding of patterns and risks of urban bicycle usage. We describe the injuries and outcomes of bicycle-related trauma in Boston, Massachusetts, and determine accident-related factors and behaviors associated with injury severity. Methods: We conducted a retrospective review via chart review of 313 bicycle-related injuries presenting to a Level 1 trauma center in Boston, Massachusetts. These patients were also surveyed regarding accident-related factors, personal safety practices, and road and environmental conditions during the accident. Results: Over half of all cyclists biked for commuting and recreational purposes (54%), used a road without a bike lane (58%), and a majority wore a helmet (91%). The most common injury pattern involved the extremities (42%) followed by head injuries (13%). Bicycling for commuting rather than recreation, cycling on a road with a dedicated bicycle lane, the absence of gravel or sand, and use of bicycle lights were all factors associated with decreased injury severity (p<0.05). After any bicycle injury, the number of miles cycled decreased significantly regardless of cycling purpose. Conclusion: Our results suggest that physical separation of cyclists from motor vehicles via bicycle lanes, regular cleaning of these lanes, and usage of bicycle lights are modifiable factors protective against injury and injury severity. Safe bicycling practices and understanding of factors involved in bicycle-related trauma can reduce injury severity and guide effective public health initiatives and urban planning.

Prevalence of bicycle helmet use by users of public bikeshare programs.

STUDY OBJECTIVE: Public bikeshare programs are becoming increasingly common in the United States and around the world. These programs make bicycles accessible for hourly rental to the general public. We seek to describe the prevalence of helmet use among adult users of bikeshare programs and users of personal bicycles in 2 cities with recently introduced bikeshare programs (Boston, MA, and Washington, DC). METHODS: We performed a prospective observational study of adult bicyclists in Boston, MA, and Washington, DC. Trained observers collected data during various times of the day and days of the week. Observers recorded the sex of the bicycle operator, type of bicycle, and helmet use. All bicycles that passed a single stationary location in any direction for a period of between 30 and 90 minutes were recorded. RESULTS: There were 43 observation periods in 2 cities at 36 locations; 3,073 bicyclists were observed. There were 562 (18.3%; 95% confidence interval [CI] 16.4% to 20.3%) bicyclists riding shared bicycles. Overall, 54.5% of riders were unhelmeted (95% CI 52.7% to 56.3%), although helmet use varied significantly with sex, day of use, and type of bicycle. Bikeshare users were unhelmeted at a higher rate compared with users of personal bicycles (80.8% versus 48.6%; 95% CI 77.3% to 83.8% versus 46.7% to 50.6%). Logistic regression, controlling for type of bicycle, sex, day of week, and city, demonstrated that bikeshare users had higher odds of riding unhelmeted (odds ratio [OR] 4.4; 95% CI 3.5 to 5.5). Men had higher odds of riding unhelmeted (OR 1.6; 95% CI 1.4 to 1.9), as did weekend riders (OR 1.3; 95% CI 1.1 to 1.6). CONCLUSION: Use of bicycle helmets by users of public bikeshare programs is low. As these programs become more popular and prevalent, efforts to increase helmet use among users should increase.

The neuropsychiatric manifestations of Huntington's disease-like 2.

Huntington's disease-like 2 (HDL2) is a rare neuropsychiatric disorder that resembles HD but results from a distinct mutation. The authors present a patient with HDL2, hospitalized for psychiatric management, and they review the neuropsychiatric manifestations of this disorder. Depression, irritability/aggression, and frontal lobe personality changes are common presentations of HDL2 and are comparable to classic HD. Patients with HDL2 may differ from those with HD in having a lower incidence of obsessive-compulsive acts, known suicides, antisocial acts, and changes in sexuality. Clinicians should be aware of the psychiatric presentations of this disorder, when to obtain genetic testing, and how to manage problematic behaviors.

The use of mechanical ventilation in the ED.

OBJECTIVES: Although EDs are responsible for the initial care of critically ill patients and the amount of critical care provided in the ED is increasing, there are few data examining mechanical ventilation (MV) in the ED. In addition, characteristics of ED-based ventilation may affect planning for ventilator shortages during pandemic influenza or bioterrorist events. The study examined the epidemiology of MV in US EDs, including demographic, clinical, and hospital characteristics; indications for MV; ED length of stay (LOS); and in-hospital mortality. METHODS: This study was a retrospective review of the 1993 to 2007 National Hospital Ambulatory Medical Care Survey ED data sets. Ventilated patients were compared with ED patients admitted to the intensive care unit (ICU) and to all other ED visits. RESULTS: There were 3.6 million ED MV visits (95% confidence interval [CI], 3.2-4.0 million) over the study period. Sex, age, race, and payment source were similar for mechanically ventilated and ICU patients (P > .05 for all). Approximately 12.5% of ventilated patients underwent cardiopulmonary resuscitation compared with 1.7% of ICU admissions and 0.2% of all other ED visits (P < .0001). Accordingly, in-hospital mortality was significantly higher for ventilated patients (24%; 95% CI, 13.1%-34.9%) than both comparison groups (9.3% and 2.5%, respectively). Median LOS for ventilated patients was 197 minutes (interquartile range, 112-313 minutes) compared with 224 minutes for ICU admissions and 140 minutes for all other ED visits. CONCLUSIONS: Patients undergoing ED MV have particularly high in-hospital mortality rates, but their ED LOS is sufficient for implementation of evidence-based ventilator interventions.

Abnormal coagulation tests obtained in the emergency department are associated with mortality in patients with suspected infection.

BACKGROUND: Early recognition of acute organ dysfunction in emergency department (ED) patients with suspected infection may help select patients at increased risk of mortality. The hematologic system is often overlooked in the evaluation and management of patients with infection because it is poorly circumscribed and serves a multitude of functions. STUDY OBJECTIVES: We examine the hypothesis that abnormalities in commonly and easily obtained markers of coagulation function (international normalized ratio [INR], partial thromboplastin time [PTT], and platelet count [PLT]) are associated with mortality in ED patients admitted to the hospital with suspected infection. DESIGN: Secondary analysis of a prospective observational cohort study. SETTING: Urban tertiary care university hospital with 50,000 annual ED visits. PATIENTS: Included patients: adults (age 18 ≥ years) evaluated in the ED for a suspected infection, had an INR, PTT, and PLT obtained during the ED stay, admitted to the hospital. Excluded patients: on oral anticoagulant therapy, received heparin, or pre-existing severe liver disease. RESULTS: There were 1688 patients included. The in-hospital mortality rate was 5.9%. After adjusting for elderly status, comorbid illness burden, and severity of illness, elevated INR was associated with a 2.9 (95% confidence interval [CI] 1.6-5.2) increased odds of death, and a low platelet count (< 150,000/uL) was associated with 2.0 (95% CI 1.2-3.3) increased odds of death. The C-statistic for the model was 0.80. CONCLUSION: We found an independent association between abnormalities in the coagulation system and mortality in ED patients with suspected infection. These findings underscore the close interaction between inflammation and coagulation and provide evidence that these simple laboratory tests should be routinely considered during the early evaluation of the infected patient.

Reducing admissions utilizing the Boston Syncope Criteria.

BACKGROUND: We previously developed criteria to identify patients with syncope at risk for adverse events. Although we proposed a theoretical substantial reduction in admission, these criteria were untested in actual practice. OBJECTIVE: To perform a prospective effectiveness study testing the hypothesis that using the Boston Syncope Criteria as a clinical guideline will safely reduce the proportion of patients admitted with syncope. METHODS: A prospective, before-and-after cohort study of consecutive Emergency Department (ED) patients presenting with syncope. After in-service training, the Boston Syncope Criteria were implemented as a clinical guideline for emergency physicians who were encouraged to make admission decisions based on the criteria adverse outcomes at 30-day follow-up, including death, myocardial infarction/intervention, dysrhythmia or alterations in dysrhythmics, pulmonary embolus, stroke, or hemorrhage. Operating characteristics of the rule and 95% confidence intervals (CI) were calculated. RESULTS: In the "before" phase, 201/293 (69%; 95% CI 63-74%) patients with syncope were admitted, compared to 160/277 (58%; 95% CI 52-64%) after the criteria were introduced; an 11% reduction in admission. Among the 160 patients admitted after the intervention, 64 (40%) had adverse events during hospitalization, compared to none in the discharged group. At 30-day follow-up, 6 additional patients (4%) had adverse outcomes; all were admitted initially. Real-time application of the criteria had a sensitivity of 100% (95% CI 94-100%), a specificity of 57% (95% CI 50-63%), and a negative predictive value of 100%. CONCLUSION: In our ED, implementing the Boston Syncope Criteria safely reduced admissions to the hospital. Future studies are needed to test external validity and generalizability.

Allosteric interactions of DNA and nucleotides with S. cerevisiae RSC.

RSC (remodel the structure of chromatin) is an essential chromatin remodeler of Saccharomyces cerevisiae that has been shown to have DNA translocase properties. We studied the DNA binding properties of a "trimeric minimal RSC" (RSCt) of the RSC chromatin remodeling complex and the effect of nucleotides on this interaction using fluorescence anisotropy. RSCt binds to 20 bp fluorescein-labeled double-stranded DNA with a K(d) of ∼100 nM. The affinity of RSCt for DNA is reduced in the presence of AMP-PNP and ADP in a concentration-dependent manner with the addition of AMP-PNP having more pronounced effect. These differences in the magnitude at which the binding of ADP and AMP-PNP affects the affinity of DNA binding by RSCt suggest that the physical movement of the enzyme along DNA begins between the binding of ATP and its subsequent hydrolysis. Furthermore, the fact that the highest affinity for DNA binding by RSCt occurs in the absence of bound nucleotide offers a mechanistic explanation for the apparent low processivity of DNA translocation by the enzyme.

Reducing heterophilic antibody interference in immunoassays using single-chain antibodies.

Sandwich enzyme-linked immunosorbent assay (ELISA) microarrays can simultaneously quantify the levels of multiple diagnostic targets in a biological sample. However, as with traditional ELISA diagnostics, endogenous antibodies in patient sera can cause interference. We demonstrate here that reducing the diagnostic capture antibody to its minimal functional unit (i.e., a single-chain antibody fragment [scFv]) is an effective strategy for reducing assay interference. Our finding illustrates a source of error introduced by the reliance on immunoglobulin-based capture reagents in sandwich immunoassays with human serum samples. We demonstrate that scFvs can be used in such assays to improve reliability by reducing heterophilic antibody interference, thereby improving biomarker analysis and validation.

Ensemble methods for monitoring enzyme translocation along single stranded nucleic acids.

We review transient kinetic methods developed to study the mechanism of translocation of nucleic acid motor proteins. One useful stopped-flow fluorescence method monitors arrival of the translocase at the end of a fluorescently labeled nucleic acid. When conducted under single-round conditions the time courses can be analyzed quantitatively using n-step sequential models to determine the kinetic parameters for translocation (rate, kinetic step size and processivity). The assay and analysis discussed here can be used to study enzyme translocation along a linear lattice such as ssDNA or ssRNA. We outline the methods for experimental design and two approaches, along with their limitations, that can be used to analyze the time courses. Analysis of the full time courses using n-step sequential models always yields an accurate estimate of the translocation rate. An alternative semi-quantitative "time to peak" analysis yields accurate estimates of translocation rates only if the enzyme initiates translocation from a unique site on the nucleic acid. However, if initiation occurs at random sites along the nucleic acid, then the "time to peak" analysis can yield inaccurate estimates of even the rates of translocation depending on the values of other kinetic parameters, especially the rate of dissociation of the translocase. Thus, in those cases analysis of the full time course is needed to obtain accurate estimates of translocation rates.

Can benign etiologies predict benign outcomes in high-risk syncope patients?

BACKGROUND: We previously studied and validated risk factors for adverse outcomes or need for critical intervention in syncope. OBJECTIVE: To determine whether high-risk patients, diagnosed with benign etiologies of syncope after a normal emergency department (ED) work-up, sustain favorable outcomes. METHODS: Prospective, observational cohort of consecutive ED patients aged ≥ 18 years with syncope. Benign etiology was defined as vasovagal syncope or dehydration. Patients were followed up to 30 days to identify adverse outcomes including death, myocardial infarction, dysrhythmia, alterations in antidysrhythmics, percutaneous intervention, pulmonary embolus, stroke, metabolic catastrophe, or significant hemorrhage. RESULTS: Patients presented with benign etiologies in 164/293, 56% (95% confidence interval [CI] 50-62%) of cases. Of these, pathologic conditions were identified during ED evaluation in 11/164, 7% (95% CI 3-11%) of cases. This includes ED findings/treatments of blood transfusion, severe electrolyte disturbance, incarcerated hernia, rhabdomyolysis, subarachnoid hemorrhage, bowel obstruction, dysrhythmia, and transient ischemic attack. The remaining 153 with benign presentations had no adverse outcomes at 30 days, while 57/129 (44%) patients with non-benign etiologies had adverse outcomes in the hospital or within 30 days. Previously, we demonstrated a 48% reduction in admission rate if only patients with risk factors for adverse outcome were admitted. If patients with both benign etiologies and a negative ED work-up were sent home, even if they had risk factors for an adverse outcome, an additional 19% (95% CI 14-25%) reduction in hospital admissions would have occurred. CONCLUSIONS: In patients with presentations consistent with a benign etiology of syncope (vasovagal or dehydration) where the ED work-up was normal, we found no patients who would benefit from hospitalization based on risk factors alone.