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Objective: To compare the sensitivity of current field triage practices for identifying high-risk trauma patients to strict guideline adherence, including changes in triage specificity, ambulance transport patterns, and trauma center volumes. Methods: This was a pre-planned secondary analysis of an out-of-hospital prospective cohort of injured children and adults transported by 44 EMS agencies to 28 trauma and non-trauma hospitals in 7 Northwest U.S. counties from January 1, 2011 through December 31, 2011. Outcomes included Injury Severity Score (ISS) ≥16 (primary) and early critical resource use. Strict adherence of the triage guidelines was based on evidence in the EMS chart for patients meeting any current field triage criteria, calculated with and without strict interpretation of the age criterion (55 years). Due to the probability sampling nature of the cohort, strata and weights were included in all analyses. Results: 17,633 injured patients were transported by EMS (weighted to represent 53,487 transported patients), including 3.1% with ISS ≥16 and 1.7% requiring early critical resources. Field triage sensitivity for identifying patients with ISS ≥16 increased from the current 66.2% (95% CI 60.2–71.7%) to 87.3% (95% CI 81.9–91.2%) for strict adherence without age and to 91.0% (95% CI 86.4–94.2%) for strict adherence with age. Specificity decreased with increasing adherence, from 87.8% (current) to 47.6% (strict adherence without age) and 35.8% (strict adherence with age). Areas under the curve (AUC) were 0.78, 0.73, and 0.72, respectively. Results were similar for patients requiring early critical resources. We estimate the number of triage-positive patients transported each year by EMS to an individual major trauma center (on average) to increase from 1,331 (current) to 5,139 (strict adherence without age) and to 6,256 (strict adherence with age). Conclusions: The low sensitivity of current triage practices would be expected to improve with strict adherence to current triage guidelines, with a commensurate decrease in triage specificity and an increase in the number of triage-positive patients transported to major trauma centers.

Author(s): Hansen, MD, MCR, Matthew; Loker, MD, William; Warden, MD, MPH, MS, Craig | Abstract: Introduction: The association between geographic factors, including transport distance, and pediatricemergency medical services (EMS) run clustering on out-of-hospital pediatric endotracheal intubation isunclear. The objective of this study was to determine if endotracheal intubation procedures are more likely tooccur at greater distances from the hospital and near clusters of pediatric calls.Methods: This was a retrospective observational study including all EMS runs for patients less than 18years of age from 2008 to 2014 in a geographically large and diverse Oregon county that includes denselypopulated urban areas near Portland and remote rural areas. We geocoded scene addresses using theautomated address locator created in the cloud-based mapping platform ArcGIS, supplemented with manualaddress geocoding for remaining cases. We then use the Getis-Ord Gi spatial statistic feature in ArcGIS tomap statistically significant spatial clusters (hot spots) of pediatric EMS runs throughout the county. We thensuperimposed all intubation procedures performed during the study period on maps of pediatric EMS-runhot spots, pediatric population density, fire stations, and hospitals. We also performed multivariable logisticregression to determine if distance traveled to the hospital was associated with intubation after controlling forseveral confounding variables.Results: We identified a total of 7,797 pediatric EMS runs during the study period and 38 endotrachealintubations. In univariate analysis we found that patients who were intubated were similar to those who werenot in gender and whether or not they were transported to a children’s hospital. Intubated patients tendedto be transported shorter distances and were older than non-intubated patients. Increased distance fromthe hospital was associated with reduced odds of intubation after controlling for age, sex, scene location,and trauma system entry status in a multivariate logistic regression. The locations of intubations weresuperimposed on hot spots of all pediatric EMS runs. This map demonstrates that most of the intubationsoccurred within areas where pediatric EMS calls were highly clustered. By mapping the intubationprocedures and pediatric population density, we found that intubation procedures were not clustered in asimilar distribution to the pediatric population in the county.Conclusion: In this geographically diverse county the location of intubation procedures was similar to theclustering of pediatric EMS calls, and increased distance from the hospital was associated with reducedodds of intubation after controlling for several potential confounding variables. [West J Emerg Med.2016;17(5)656-661.]

Airway management is an important component of resuscitation from out-of-hospital cardiac arrest (OHCA). The optimal approach to advanced airway management is unknown. The Pragmatic Airway Resuscitation Trial (PART) will compare the effectiveness of endotracheal intubation (ETI) and Laryngeal Tube (LT) insertion upon 72-hour survival in adult OHCA. Encompassing United States Emergency Medical Services agencies affiliated with the Resuscitation Outcomes Consortium (ROC), PART will use a cluster-crossover randomized design. Participating subjects will include adult, non-traumatic OHCA requiring bag-valve-mask ventilation. Trial interventions will include 1) initial airway management with ETI and 2) initial airway management with LT. The primary and secondary trial outcomes are 72-hour survival and return of spontaneous circulation. Additional clinical outcomes will include airway management process and adverse events. The trial will enroll a total of 3,000 subjects. Results of PART may guide the selection of advanced airway management strategies in OHCA.

Approximately 25.5 million pediatric patients are treated in Emergency Departments around the United States annually. Roughly 7% of these patients are transported by ambulance; of these, approximately 7% arrive in ambulances running red lights and sirens (RLS). Compared to those transporting without RLS, emergency vehicles employing RLS are involved in more accidents and are associated with more fatalities.To characterize the use of RLS in pediatric transports and identify factors associated with unnecessary use of RLS.As part of the Children's Safety Initiative (CSI-EMS), a large, multi-phased National Institutes of Health-funded study, we conducted a medical record review of all pediatric RLS transports in an urban EMS system over a 4-year period (2008-11). A standardized chart abstraction tool was adapted for the out-of-hospital setting and pilot tested. Charts were independently reviewed by physicians and paramedics, with disagreements arbitrated by a pediatric emergency physician. Reviewers were asked to judge whether RLS transport was necessary and to provide comments justifying their position. Descriptive statistics were used to measure the frequency of unnecessary transports and logistic regression analysis was employed to identify factors associated with unnecessary use of RLS.Of 490 RLS transports, experts identified 96 (19.6%) as unnecessary use of RLS. Necessary and unnecessary RLS transports had similar patient sex and duration of transport, though unnecessary use of RLS tended to increase with patient age. The call reasons that represented the largest proportion of unnecessary RLS transports were trauma (49.0%), respiratory distress (16.7%), and seizure/altered mental status (11.5%). Compared with necessary RLS transports, unnecessary RLS transports were less likely to require resuscitation, airway management, or medication administration. Univariate analysis revealed that patient vital signs within normal limits were associated with increased risk of unnecessary RLS transport, with the most pronounced effect seen in the normal GCS score group (odds ratio 7.74, p-value 0.001).This analysis identified patient and transport characteristics associated with unnecessary use of RLS. Our results could help serve as the basis for designing and prospectively evaluating protocols for use of RLS, potentially mitigating the risk associated with transport in pediatric patients.

Objective The objective of this study was to characterize pediatric out-of-hospital airway management interventions, success rates, and complications in the United States using the 2012 National Emergency Medical Services Information System (NEMSIS) dataset. Methods In 2012, NEMSIS collected data from Emergency Medical Services (EMS) encounters in 40 states. We included all patients less than 18 years of age and identified all patients who had airway interventions including endotracheal intubation (ETI), bag-valve-mask ventilation (BVM), continuous positive airway pressure/bilevel positive airway pressure (CPAP/BiPAP) and alternate airways (Combitube, King LT, Laryngeal Mask Airway (LMA), esophageal obturator airway, and cricothyroidotomy). Success and complication rates were analyzed and compared across pediatric age groups, by race, ethnicity, clinical condition, and geographic region. Results We identified a total of 949,301 pediatric patient care events in the NEMSIS 2012 dataset. 4.5% had airway management procedures (42,936 events). Invasive airway management or ventilation (ETI, cricothyroidotomy, alternate airway, CPAP/BiPAP, BVM and other ventilation) took place in 1.5% of patient care events (14,107). Of those who had invasive airway management, 29.9% were less than 1 year of age, 58.1% were male, 42.3% were white, and 83.6% were in urban areas. ETI occurred in 3124 of patient care events (329 per 100,000; 95% CI 318–341). Overall success of ETI was 81.1% (95% CI 79.7–82.6). Lower success was noted in patients with cardiac arrest (75.5%, 95% CI 72.6–78.3) and those aged 1–12 months (72.1%, 95% CI 68.3–75.6). Conclusions Out-of-hospital pediatric advanced airway procedures were infrequently performed. Success rates are lowest in patients aged 1–12 months.

Introduction Outdoor education (OE) expeditions travel far from definitive care and have unique epidemiology. Most OE expedition studies have examined a single organization and results may not generalize. This study examines the injuries, illnesses, medical evacuations, and nonmedical incidents of the Northwest Outward Bound School (NWOBS) to broaden our understanding and demonstrate commonalities within the field. Methods This retrospective database review examined incidents and evacuations on NWOBS expeditions from June 1, 2014 through October 31, 2016. Incident rates, evacuation rates, and incident type frequencies were calculated. Frequencies of incidents during different expedition time periods were compared with a 1-sample χ2 test. The odds ratio that each type of incident would require evacuation was calculated and compared with other incident types using Fisher exact test. Results The study period included 59,058 program days, 277 incidents, 143 medical incidents, 75 medical evacuations, and no fatalities. Injuries occurred at a rate of 1.64 per 1000 program days and illnesses at a rate of 0.78 per 1000 program days. The most common injuries were strains, sprains, and trauma or infection of the skin and soft tissue. Most injuries occurred while backpacking, hiking, or moving around camp. The most common illnesses were nausea, vomiting, diarrhea, abdominal pain, asthma, respiratory infections, and urinary tract infections. The medical incidents with the highest odds of evacuation were fractures, urinary tract infections, abdominal pain, and asthma. Conclusions Results from the NWOBS database are consistent with those from other expeditionary OE programs. These findings should guide risk-management strategies and staff medical training.

Advocacy for maintaining and expanding Emergency Medical Services for Children is needed on many fronts. Pediatric emergency medicine (PEM) physicians are uniquely qualified to serve this role due to their expertise in the acute care of sick or injured pediatric patients. Given this, in addition to maintaining the highest standards in the emergency departments in which they work, PEM physicians also have responsibilities in the education, training, and practice of emergency medical services providers in their region. These providers are also well positioned to advocate for Emergency Medical Services for Children on a policy level at local, regional, and state governments and in organizations that deal with the care of children in both the prehospital and hospital arenas. Greater engagement by PEM physicians in such activities is required to optimize pediatric care across the spectrum of emergency services.

To derive and validate a model that accurately predicts ambulance arrival time that could be implemented as a Google Maps web application.This was a retrospective study of all scene transports in Multnomah County, Oregon, from January 1 through December 31, 2008. Scene and destination hospital addresses were converted to coordinates. ArcGIS Network Analyst was used to estimate transport times based on street network speed limits. We then created a linear regression model to improve the accuracy of these street network estimates using weather, patient characteristics, use of lights and sirens, daylight, and rush-hour intervals. The model was derived from a 50% sample and validated on the remainder. Significance of the covariates was determined by p0.05 for a t-test of the model coefficients. Accuracy was quantified by the proportion of estimates that were within 5 minutes of the actual transport times recorded by computer-aided dispatch. We then built a Google Maps-based web application to demonstrate application in real-world EMS operations.There were 48,308 included transports. Street network estimates of transport time were accurate within 5 minutes of actual transport time less than 16% of the time. Actual transport times were longer during daylight and rush-hour intervals and shorter with use of lights and sirens. Age under 18 years, gender, wet weather, and trauma system entry were not significant predictors of transport time. Our model predicted arrival time within 5 minutes 73% of the time. For lights and sirens transports, accuracy was within 5 minutes 77% of the time. Accuracy was identical in the validation dataset. Lights and sirens saved an average of 3.1 minutes for transports under 8.8 minutes, and 5.3 minutes for longer transports.An estimate of transport time based only on a street network significantly underestimated transport times. A simple model incorporating few variables can predict ambulance time of arrival to the emergency department with good accuracy. This model could be linked to global positioning system data and an automated Google Maps web application to optimize emergency department resource use. Use of lights and sirens had a significant effect on transport times.

Most genetic human obesity is due to multiple genes interacting with each other and with environment. Sequencing exomes, genome-wide associations with single nucleotide polymorphisms, sequencing methylations, and sequencing genomic DNA have revealed hundreds of obesity-causing polymorphisms that all together account for a small percent of total heritability. Pathway analyses reveal that most body mass index genes are expressed in the brain whereas most waist-to-hip ratio fat distribution genes are expressed in adipose tissue. Most mouse obesity genes are also human obesity genes and vice versa. Studies in mice demonstrate that quantitating fat mass, individual fat depots, responses of individual fat depots to dieting and exercise, and parental effects will reveal many new obesity genes. These topics have been explored superficially or not at all in studies of humans. Genetic and randomized controlled diet data are presently inadequate for development of personalized obesity therapy.

Linkage mapping in a backcross of {Brown Norway [BN/Crl (BN)] × ZUC- LeprfaSte(ZUC)} × ZUC identified a male-specific quantitative trait locus (QTL) for urinary albumin excretion (UAE) on rat chromosome 1. A homozygous ZUC.BN-( D1Rat42- D1Rat90)/Ste congenic was produced containing BN donor alleles from 135 to 276 Mb from chromosome 1 on the ZUC background. We observed threefold higher urinary albumin-to-creatinine ratios (ACR) in 15-wk-old Zucker background strain males than in same sex and age congenic animals when both strains are also homozygous for the ZUC leptin receptor fatty mutation ( LeprfaSte) ( P < 0.0001). We then linkage mapped within the donor region without confounded effects from other chromosomes. Phenotypes were collected in 248 F2 male rats in a population made by crossing parents heterozygous for both the BN donor region and ZUC LeprfaSte. Significant interactions were observed between the Lepr genotype and chromosome 1 QTL for six renal traits: urine volume, UAE at 10 and 15 wk, ACR, right kidney weight, and plasma urea nitrogen. A few traits, such as UAE and ACR, exhibit a second peak at the distal end of the chromosome. Hydronephrosis exhibited one or two QTLs contingent on adjustment for body weight. The results now demonstrate at least two sets of coincident traits with different correlations to kidney function.

Improving survival rates for out of hospital cardiac arrest (OHCA) at the neighborhood level is increasingly seen as priority in US cities. Since wide disparities exist in OHCA rates at the neighborhood level, it is necessary to locate neighborhoods where people are at elevated risk for cardiac arrest and target these for educational outreach and other mitigation strategies. This paper describes a GIS-based methodology that was used to identify communities with high risk for cardiac arrests in Franklin County, Ohio during the period 2004-2009. Prior work in this area used a single criterion, i.e., the density of OHCA events, to define the high-risk areas, and a single analytical technique, i.e., kernel density analysis, to identify the high-risk communities. In this paper, two criteria are used to identify the high-risk communities, the rate of OHCA incidents and the level of bystander CPR participation. We also used Local Moran's I combined with traditional map overlay techniques to add robustness to the methodology for identifying high-risk communities for OHCA. Based on the criteria established for this study, we successfully identified several communities that were at higher risk for OHCA than neighboring communities. These communities had incidence rates of OHCA that were significantly higher than neighboring communities and bystander rates that were significantly lower than neighboring communities. Other risk factors for OHCA were also high in the selected communities. The methodology employed in this study provides for a measurement conceptualization of OHCA clusters that is much broader than what has been previously offered. It is also statistically reliable and can be easily executed using a GIS.

ACADEMIC EMERGENCY MEDICINE 2012; 19:139–146 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: The objective was to identify high-risk census tracts, defined as those areas that have both a high incidence of out-of-hospital cardiac arrest (OHCA) and a low prevalence of bystander cardiopulmonary resuscitation (CPR), by using three spatial statistical methods. Methods: This was a secondary analysis of two prospectively collected registries in the city of Columbus, Ohio. Consecutive adult (≥18 years) OHCA patients, restricted to those of cardiac etiology and treated by emergency medical services (EMS) from April 1, 2004, to April 30, 2009, were studied. Three different spatial analysis methods (Global Empirical Bayes, Local Moran’s I, and SaTScan’s spatial scan statistic) were used to identify high-risk census tracts. Results: A total of 4,553 arrests in 200 census tracts occurred during the study period, with 1,632 arrests included in the final sample after exclusions for no resuscitation attempt, noncardiac etiology, etc. The overall incidence for OHCA was 0.70 per 1,000 people for the 6-year study period (SD = ±0.52). Bystander CPR occurred in 20.2% (n = 329), with 10.0% (n = 167) surviving to hospital discharge. Five high-risk census tracts were identified by all three analytic methods. Conclusions: The five high-risk census tracts identified may be possible sites for high-yield targeted community-based interventions to improve CPR training and cardiovascular disease education efforts and ultimately improve survival from OHCA.

We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C- D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B ( St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a ( Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b ( Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 ( Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions.

Crashes on highways frequently cause hazardous material exposure to the public and the environment. We evaluated differences in hazardous materials-related crashes vs. non-hazardous-material-related commercial motor vehicle crashes occurring from 2000 to 2006 on the Oregon state highway network. The two groups were compared for crash characteristics by χ2 analysis, and spatial clustering was tested using Ripley's K-function and kernel density estimator analyses. There were 8,622 total commercial motor vehicle crashes, 232 being hazardous-materials related. Hazardous materials-related crashes were not significantly associated with different road surface conditions, weather conditions or cause of crash. Hazardous materials-related crashes were associated more frequently with late evening/early morning hours and under artificial lights or at dusk. The commercial motor vehicle drivers in hazardous materials-related crashes were less frequently at fault than ones in the non-hazardous materials-related crashes....

Objectives. We sought to identify and characterize areas with high rates of major trauma events in 9 diverse cities and counties in the United States and Canada. Methods. We analyzed a prospective, population-based cohort of injured individuals evaluated by 163 emergency medical service agencies transporting patients to 177 hospitals across the study sites between December 2005 and April 2007. Locations of injuries were geocoded, aggregated by census tract, assessed for geospatial clustering, and matched to sociodemographic measures. Negative binomial models were used to evaluate population measures. Results. Emergency personnel evaluated 8786 major trauma patients, and data on 7326 of these patients were available for analysis. We identified 529 (13.7%) census tracts with a higher than expected incidence of major trauma events. In multivariable models, trauma events were associated with higher unemployment rates, larger percentages of non-White residents, smaller percentages of foreign-born residents, lower educational levels, smaller household sizes, younger age, and lower income levels. Conclusions. Major trauma events tend to cluster in census tracts with distinct population characteristics, suggesting that social and contextual factors may play a role in the occurrence of significant injury events.

To determine clusters of trauma incidents with high injury severity and resource utilization and to test their association with census demographic information.Using "trauma band" unique identifiers and probabilistic linkage for unmatched cases, we matched injury location information collected from a centralized regional trauma communications center to the state trauma system registry for patients directly transported to two level I trauma centers for the years 2001-2003 in a three-county area. The injury locations were aggregated at the census tract level using a geographic information system (GIS). Moran's I analysis was used to determine clusters of census tracts that had a high incidence of either total trauma injuries, Injury Severity Scores (ISSs)15, or high resource use (in-hospital mortality, admission to the intensive care unit, or major nonorthopedic surgery). These clusters were then tested for association with census tract demographics using logistic regression.Eight thousand seven hundred fifty-one injured persons were directly transported from the tricounty area to a trauma center during the study period. The mean (+/- standard deviation) age was 37 +/- 21 years, 67.4% were male, 18.9% had ISSs15, and 29.8% had a high-resource-use indicator. Moran's I analysis demonstrated a single large cluster of incidents for total injuries, ISS15, and occurrence of a high-resource-use indictor that overlapped except for one small census tract. Logistic regression revealed that the high-risk cluster was associated with a higher prevalence of nonwhite population and vacant housing and a lower prevalence of foreign-born residents and family housing.GIS cluster analysis demonstrated high-risk census tracts for trauma incidents and associated population demographics. Geospatial analyses may assist injury prevention interventions and emergency medical services deployment strategies for trauma.

Objectives: Patients of all ages use emergency departments (EDs) for primary care. Several studies have evaluated patient and system characteristics that influence pediatric ED use. However, the issue of proximity as a predictor of ED use has not been well studied. The authors sought to determine whether ED use by pediatric Medicaid enrollees was associated with the distance to their primary care providers (PCPs), distance to the nearest ED, and distance to the nearest children’s hospital. Methods: This historical cohort study included 26,038 children age 18 and under, assigned to 332 primary care practices affiliated with a Medicaid health maintenance organization (HMO). Predictor variables were distance from the child’s home to his or her PCP site, distance from home to the nearest ED, and distance from home to the nearest children’s hospital. The outcome variable was each child’s ED use. A negative binomial model was used to determine the association between distance variables and ED use, adjusted for age, sex, and race, plus medical and primary care site characteristics previously found to influence ED use. Distance variables were divided into quartiles to test for nonlinear associations. Results: On average, children made 0.31 ED visits/person/year. In the multivariable model, children living greater than 1.19 miles from the nearest ED had 11% lower ED use than those living within 0.5 miles of the nearest ED (risk ratio [RR] = 0.89, 95% CI = 0.81 to 0.99). Children living between 1.54 and 3.13 miles from their PCPs had 13% greater ED use (RR = 1.13, 95% CI = 1.03 to 1.24) than those who lived within 0.7 miles of their PCP. Conclusions: Geographical variables play a significant role in ED utilization in children, confirming the importance of system-level determinants of ED use and creating the opportunity for interventions to reduce geographical barriers to primary care.

Background— Population-based data for pediatric cardiac arrest are scant and largely from urban areas. The Resuscitation Outcomes Consortium (ROC) Epistry–Cardiac Arrest is a population-based emergency medical services registry of out-of-hospital nontraumatic cardiac arrest (OHCA). This study examined age-stratified incidence and outcomes of pediatric OHCA. We hypothesized that survival to hospital discharge is less frequent from pediatric OHCA than adult OHCA. Methods and Results— This prospective population-based cohort study in 11 US and Canadian ROC sites included persons P =0.03). Unadjusted odds ratio for pediatric survival to discharge compared with adults was 0.71 (95% confidence interval, 0.37 to 1.39) for infants, 2.11 (95% confidence interval, 1.21 to 3.66) for children, and 2.04 (95% confidence interval, 1.24 to 3.38) for adolescents. Conclusions— This study demonstrates that the incidence of OHCA in infants approaches that observed in adults but is lower among children and adolescents. Survival to discharge was more common among children and adolescents than infants or adults.

Summary Study objective For trials involving exception from informed consent, some IRBs require that community members be allowed to “opt out” prior to enrollment. We tested for geospatial clustering of opt-out requests and the associated census tract characteristics in one study region. Methods This was a retrospective study at a single site of a multicenter exception from informed consent resuscitation trial. We collected and geocoded mailing addresses for persons requesting opt-out bracelets over 16 months, then tested for geospatial clustering using geographic information systems (GIS) analysis. Characteristics for tracts with and without bracelet clustering were compared using univariate tests, multivariable regression, and classification and regression tree (CART) analysis. Results We received 395 phone calls requesting 718 bracelets, of which 673 were analyzable. Of 397 census tracts in the region, 208 (52%) had at least one request and 38 (10%) demonstrated clustering. In multivariable models, an increasing proportion of family households (OR .90, 95%CI .85–.93), veterans (OR .91, 95%CI .81–1.02), and renters (OR .96, 95%CI .92–.99) were associated with lower odds of requesting an opt-out bracelet, while census tracts with higher income had higher odds of opting-out (OR 1.07, 95%CI 1.02–1.11). Using CART, the proportion of family households and graduate education identified the majority of opt-out requests by census tracts (cross-validation sensitivity 92%, specificity 56%). Conclusions Opt-out requests for an exception from informed consent trial at one study site were geographically clustered and associated with certain population demographics. These findings may help identify key target groups for community consultation in future trials.

In the present investigation we describe the life span characteristics and phenotypic traits of ad libitum-fed mice that overexpress UCP2/3 (Positive-TG), their non-overexpressing littermates (Negative-TG), mice that do not expression UCP2 (UCP2KO) or UCP3 (UCP3KO), and wild-type C57BL/6J mice (WT-Control). We also included a group of C57BL/6J mice calorie-restricted to 70% of ad libitum-fed mice in order to test partially the hypothesis that UCPs contribute to the life extension properties of CR. Mean survival was slightly, but significantly, greater in Positive-TG, than that observed in Negative-TG or WT-Control; mean life span did not significantly differ from that of the UCP3KO mice. Maximal life span did not differ among the ad libitum-fed groups. Genotype did not significantly affect body weight, food intake, or the type of pathology at time of death. Calorie restriction increased significantly mean and maximal life span, and the expression of UCP2 and UCP3. The lack of difference in maximal life spans among the Positive-TG, Negative-TG, and UCP3KO suggests that UCP3 does not significantly affect longevity in mice.

Gastric bypass surgery is the most commonly performed bariatric surgical procedure in the United States. Variable weight loss following this relatively standardized intervention has been reported. To date, a method for reliable profiling of patients who will successfully sustain weight loss for the long term has not been established. In addition, the mechanisms of action in accomplishing major weight loss as well as the explanation for the variable weight loss have not been established. To examine whether gene expression in perioperative omental adipose is associated with gastric bypass-induced weight loss. Cross-sectional study of gene expression in perisurgical omental adipose tissues taken/available at the time of operation and total excess weight loss (EWL). Fifteen overweight individuals who underwent Roux-en-Y gastric bypass (RYGB) surgery at the University of California Davis Medical Center (BMI: 40.6–72.8 kg/m2). Body weight before and following weight stabilization 18–42 months after surgery. Perioperative omental adipose RNA isolated from 15 subjects was hybridized to Affymetrix HG-U133A chips for 22 283 transcript expression measurements. Downstream analysis identified a set of genes whose expression was significantly correlated with RYGB-induced weight loss. The significant individual genes include acyl-coenzyme A oxidase 1 (ACOX1), phosphodiesterase 3A cGMP-inhibited (PDE3A) and protein kinase, AMP-activated, beta 1 non-catalytic subunit (PRKAB1). Specifically, ACOX1 plays a role in fatty acid metabolism. PDE3A is involved in purine metabolism and hormone-stimulated lipolysis. PRKAB1 is involved in adipocytokine signaling pathway. Gene network analysis revealed that pathways for glycerolipid metabolism, breast cancer and apoptosis were significantly correlated with long-term weight loss. This study demonstrates that RNA expression profiles from perioperative adipose tissue are associated with weight loss outcome following RYGB surgery. Our data suggest that EWL could be predicted from preoperative samples, which would allow for informed decisions about whether or not to proceed to surgery.

To evaluate the change in nausea scales and incidence of vomiting with the use of ondansetron in the treatment of nausea and vomiting in the prehospital setting.Data were prospectively collected on all emergency medical service patients who received ondansetron for undifferentiated nausea and vomiting during a 6-month study period. Added outcome measures for this study were verbal quantitative (scale of 1-10) and qualitative "nausea scales," incidence of vomiting prior to and after administration of ondansetron, and adverse events. Patients who had this additional data collected and ones who did not were compared. Changes in the "nausea scales" and incidence of vomiting before and after administration and correlation among these measures were also compared. There was no control or placebo group.Ondansetron was administered to 952 patients of 20,054 patients transported during this time period (5%); of these 472 had at least some of the outcome measures documented. There were minimal differences in the two cohorts; 198 patients had paired before and after quantitative "nausea scales" documented: 7.6 +/- 2.4 and 4.6 +/- 3.1, respectively (Delta = 2.9, 95% CI: 2.5-3.4); 447 patients had a qualitative change in nausea level documented: 0.4% "a lot worse," 1.3% "a little worse," 34% "unchanged," 40% "a little better," and 25% "a lot better"; 187 patients had all three measures documented with a Pearson correlation coefficient of 0.63 between the change in the quantitative scale and the qualitative scale (95% CI: 0.14-0.20, R(2) 0.39). In 462 patients, vomiting decreased from 60% to 30% (Wilcoxon signed ranks test p0.001). The Pearson correlation coefficients for the change in vomiting incidence with the qualitative and quantitative "nausea scales" were poor: 0.012 (95% CI: -0.015 to 0.039, R(2) 0.00014) and 0.051 (95% CI: -0.032 to 0.118, R(2) 0.00026), respectively. There were no reported adverse events.Ondansetron appears to be moderately effective in decreasing nausea and vomiting in undifferentiated prehospital patients. Additional controlled trials may be needed to compare it with other antiemetics.

Tumor suppressor candidate 5 (Tusc5, also termed brain endothelial cell derived gene-1 or BEC-1), a CD225 domain-containing, cold-repressed gene identified during brown adipose tissue (BAT) transcriptome analyses was found to be robustly-expressed in mouse white adipose tissue (WAT) and BAT, with similarly high expression in human adipocytes. Tusc5 mRNA was markedly increased from trace levels in pre-adipocytes to significant levels in developing 3T3-L1 adipocytes, coincident with several mature adipocyte markers (phosphoenolpyruvate carboxykinase 1, GLUT4, adipsin, leptin). The Tusc5 transcript levels were increased by the peroxisome proliferator activated receptor- (PPAR) agonist GW1929 (1g/mL, 18 h) by >10-fold (pre-adipocytes) to ∼1.5-fold (mature adipocytes) versus controls (p < 0.0001). Taken together, these results suggest an important role for Tusc5 in maturing adipocytes. Intriguingly, we discovered robust co-expression of the gene in peripheral nerves (primary somatosensory neurons). In light of the marked repression of the gene observed after cold exposure, these findings may point to participation of Tusc5 in shared adipose–nervous system functions linking environmental cues, CNS signals, and WAT–BAT physiology. Characterization of such links is important for clarifying the molecular basis for adipocyte proliferation and could have implications for understanding the biology of metabolic disease-related neuropathies. Published by Elsevier Ireland Ltd.

Background Glutamate carboxypeptidase II (GCPII) encodes for intestinal folate hydrolase and brain N-acetylated alpha-linked acidic dipeptidase. Previous studies provided conflicting results on the effect of the GCPII 1561C-->T polymorphism on folate and total homocysteine (tHcy) concentrations. Objective We aimed to determine the potential effects of 2 polymorphisms of GCPII on plasma folate and tHcy concentrations, cognition, anxiety, and depression in a large aging cohort of Norwegians enrolled in the Hordaland Homocysteine Study. Design DNA samples were genotyped for the GCPII 1561C-->T and 484A-->G polymorphisms, and the results were linked to plasma folate and tHcy concentrations and to scores for cognition, anxiety, and depression. Results The 2 polymorphisms were in linkage disequilibrium and were associated with concentrations of tHcy. After adjustment for covariates, persons in the CT or combined CT and TT groups of the 1561C-->T polymorphism had higher plasma folate concentrations and lower tHcy concentrations than did those in the CC group. Subjects with the TT genotype had lower Symbol Digit Modalities Test (SDMT) scores than did subjects with the CC genotype. Compared with abstainers, moderate alcohol drinkers had higher plasma folate concentrations and higher scores on the Mini Mental State Examination. However, women abstainers with the CT genotype had lower SDMT scores than did abstainers with the CC genotype or moderate drinkers with the CT genotype. Conclusions The 1561C-->T polymorphism is associated with higher plasma folate and lower tHcy concentrations and with lower SDMT cognitive scores in women who abstain from alcohol.

There are many chemical respiratory agents suitable for use by terrorists. They are the oldest chemical agents used and have caused the most casualties throughout the 20th century. Many are available in large quantities for industrial use and are susceptible to potential sabotage. This paper will concentrate on respiratory agents that are readily available and have the potential to cause a large number of casualties and panic. These agents have a lower rate of lethality when compared to other chemical agents but could produce many casualties that may overwhelm the emergency medical system.

Objective: Effects of ectopic expression of the agouti signaling protein were studied on responses to diet restriction and exercise in C57BL/6J (B6) mice and obese B6 mice congenic for the yellow agouti mutation [B6.Cg-Ay (Ay)]. Research Methods and Procedures: Adult male Ay mice were either kept sedentary or exercised on a running wheel and fed ad libitum or diet restricted until weight matched to ad libitum-fed B6 control mice. Body composition, plasma lipids, leptin, and adiponectin were measured. mRNA levels for leptin, adiponectin, lipoprotein lipase, and pyruvate dehydrogenase kinase 4 were measured in a visceral (epididymal) and a subcutaneous (femoral) fat depot by real-time polymerase chain reaction. Results: Correlations among traits exhibited one of three patterns: similar lines for B6 and Ay mice, different slopes for B6 and Ay mice, and/or different intercepts for B6 and Ay mice. Correlations involving plasma leptin, mesenteric and epididymal adipose weights, or low-density lipoprotein-cholesterol were most likely to have different slopes and/or intercepts in B6 and Ay mice. mRNA levels for leptin, Acrp30, pyruvate dehydrogenase kinase 4, and lipoprotein lipase in epididymal adipose tissue were not correlated with corresponding levels in femoral adipose tissue. Discussion: The agouti protein interferes with leptin signaling at melanocortin receptors in the hypothalamus of Ay mice. Our results are consistent with the hypothesis that the melanocortin portion of the leptin-signaling pathway mediates effects primarily on certain fat depots and on some, but not all, components of cholesterol homeostasis.

Linkage studies have identified many chromosomal regions containing obesity genes in mice. However, only a few of these quantitative trait loci (QTLs) have been used to guide the production of congenic mouse strains that retain obesity phenotypes. We seek to identify chromosomal regions containing obesity genes in the BSB model of spontaneous obesity because the BSB model is a multigenic obesity model. Previous studies identified QTLs on Chromosomes (Chrs) 2, 6, 7,12, and 15. BSB mice are made by backcross of lean C57BL/6J x Mus spretus. F(1)s were backcrossed to C57BL/6J mice to produce BSB progeny. We have constructed a new BSB cross and produced congenic mice with obesity phenotypes by marker-directed selection called B6.S- D2Mit194- D2Mit311. We found a highly significant QTL for percentage body lipid on Chr 2 just proximal to the Agouti locus. Chr 2 congenics were constructed to determine whether the main effects would be detectable. We observed highly significant linkage of the Chr 2 congenic containing Agouti and containing markers distal to D2Mit311 and proximal to D2Mit194. Thus, this congenic contains approximately 14.6 cM or 30 Mb (about 1.1% of the spretus mouse genome) and several hundred genes. The obesity phenotype of the QTL is retained in the congenic. The congenic can now be used to model the genetic and physiological basis for a relatively simple, perhaps monogenic, obesity.

Identification of genes that cause spontaneous mendelian obesity in mice began a new age of obesity studies with the ability to discover mechanisms underlying the biological causes of obesity. Studies in humans quickly confirmed that orthologs of mouse obesity genes also cause monogenic (mendelian) forms of human obesity. However, the six genes that cause mendelian forms of human obesity (leptin, leptin receptor, proopiomelanocortin, prohormone convertase, melanocortin receptor-4, and peroxisome proliferator-activated receptor) each have insignificant effects on common human obesity.1 Common obesity is inherited as a polygenic (quantitative) trait influenced by many genetic and environmental variables. Thus, alleles of genes causing common forms of human obesity are unlikely to produce mendelian pedigrees showing segregation of mutations with obesity. Genes for common obesity will produce small increases in obesity risk ratios or will influence obesity by more complex routes, such as gene gene epistasis and gene environment interactions. The identification of genes underlying complex traits such as obesity, diabetes, and hypertension has been less successful than for simple mendelian traits. One of the reasons for this is the presence of epistasis that can mask the effects of one locus on another locus and reduce the power to identify either locus. Epistasis is generally defined as the interaction between two or more genes or their mRNA or protein products to influence a single trait. Non-additive genetic effects and interactions between genes contribute considerably to the phenotypic variance of body weight and

Summary Although genes causing rare Mendelian forms of human obesity have provided much useful information about underlying causes of obesity, these genes do not explain significant proportions of common obesity. This review presents evidence that animal models can be used to uncover subtle genetic effects on obesity and can provide a powerful rigorous compliment to human association studies. We discuss the advantages of animal models of obesity, various approaches to discovering obesity genes, and the future of mapping and isolating naturally occurring alleles of obesity genes. We review evidence that it is important to map naturally occurring obesity genes using quantitative trait locus (QTL) mapping, instead of mutagenesis and knockout models because the latter do not allow study of interactions and because naturally occurring obesity alleles can interfere with cloning from mutagenesis projects. Because a substantial percentage of human obesity results from complex interactions, the underlying genes can only be identified by direct studies in humans, which are still very difficult, or by studies in mice that begin with QTL mapping. Finally, we emphasize that animal model studies can be used to prove that a specific gene, only associated with obesity in humans, can indeed be the underlying cause of obesity in mammals.

Whereas uncoupling protein 1 (UCP-1) is clearly involved in thermogenesis, the role of UCP-2 is less clear. Using hybridization, cloning techniques and cDNA array analysis to identify inducible neuroprotective genes, we found that neuronal survival correlates with increased expression of Ucp2. In mice overexpressing human UCP-2, brain damage was diminished after experimental stroke and traumatic brain injury, and neurological recovery was enhanced. In cultured cortical neurons, UCP-2 reduced cell death and inhibited caspase-3 activation induced by oxygen and glucose deprivation. Mild mitochondrial uncoupling by 2,4-dinitrophenol (DNP) reduced neuronal death, and UCP-2 activity was enhanced by palmitic acid in isolated mitochondria. Also in isolated mitochondria, UCP-2 shifted the release of reactive oxygen species from the mitochondrial matrix to the extramitochondrial space. We propose that UCP-2 is an inducible protein that is neuroprotective by activating cellular redox signaling or by inducing mild mitochondrial uncoupling that prevents the release of apoptogenic proteins.

Febrile seizures are the most common seizures seen in children younger than 5 years old. Out-of-hospital and emergency department providers need to be familiar with the principles of the evaluation and management of this common disorder. Most febrile seizures are brief, do not require any specific treatment or extensive workup, and have a benign prognosis. Recognizing the pattern of a simple febrile seizure in young children is important to limit interventions and to reassure parents. Patients with febrile seizures are not at higher risk for serious bacterial illnesses than similarly aged febrile patients. Excluding meningitis and encephalitis are the primary clinical interventions through a thorough history and physical examination and, occasionally, a lumbar puncture. Reassuring parents of patients with febrile seizures and arranging primary care follow-up are important roles for the emergency physician.

To evaluate the amount of ambulance diversion in an emergency medical services (EMS) system and to investigate potential predictive factors.Ambulance diversion status of hospitals in the four-county metropolitan Portland, Oregon, area has been recorded for approximately 15 years. These data are used by EMS transporting agencies to determine appropriate hospital destination for their patients. The authors calculated the total yearly hospital ambulance diversion time for "Total Ambulance Divert (TAD)" and "Critical Care Divert (CCD)" for the time period between January 1, 1996, and December 31, 1999. Yearly EMS 9-1-1-generated patient transport volume, hospital emergency department (ED) census volume, total population, amount of health maintenance organization (HMO) penetration, and number of licensed and available hospital beds were calculated for each yearly interval. Kendall's tau-b correlation was used to determine significant secular trends. Potential predictive factors for the amount of ambulance diversion were tested using Pearson's correlation.Total TAD increased 122.5% (p = 0.04), total CCD increased 64.4% (p = 0.50), total EMS transport volume increased 16.1% (p = 0.04), total ED census increased 9.4% (p = 0.04), total licensed beds decreased 5.7% (p = 0.17), total available beds decreased 15.8% (p = 0.17), HMO penetration increased 4.7% (p = 0.04), and total population increased 9.7% (p = 0.04) over the four-year study period. CCD and TAD were not significantly related to each other (p = 0.50). The only significant factor associated with the increase in TAD was number of available beds (p = 0.03). There were no significant factors associated with CCD.TAD increased significantly over time and was associated only with the decrease in available hospital beds.

Objectives: To assess and compare overall satisfaction in pediatric emergency department (ED) patients and their accompanying parents. To identify aspects of health care delivery that influence satisfaction in these groups. Methods: Pediatric patients (ages 5-17 years) and their parents (or guardians) seen at a university hospital pediatric ED were eligible. A convenience sample of English-speaking subject pairs (n = 101 pairs) was enrolled. Questionnaires were administered to both children and their parents at the completion of their ED care. The survey instruments used a modified Wong-Baker FACES Pain Rating Scale and a six-point interval scale. Factors measured included overall satisfaction, perceptions of pain and fear, and other characteristics of the ED visit. Data were analyzed using paired Wilcoxon signed-rank tests, Spearman rank correlation coefficients, and Fischer's exact chi-square tests (α= 0.05) where appropriate. Results: Parent satisfaction was associated with the quality of provider—patient interactions (R = 0.54, p = 0.0001), the adequacy of information provided (R = 0.47, p = 0.0001), and shorter waiting room times (R = -0.24, p = 0.01). Child satisfaction was associated with the quality of provider—patient interactions (R = 0.24, p 0.04), adequacy of information provided (R = 0.51, p = 0.003), and resolution of pain (R = 0.25, p = 0.03). Parent estimates were similar to children's initial pain scores; however, children reported greater resolution of pain than appreciated by their parents (p = 0.006). Conclusions: Satisfaction can be validly and reliably measured in pediatric patients using a visual scale instrument. Factors that influence patient satisfaction were similar among both children and their parents. The influence of pain resolution on pediatric ED satisfaction is a novel finding, which demonstrates the importance of appropriate pain and anxiety assessment and treatment in children.