Out-of-hospital cardiac arrest outcomes with "pit crew" resuscitation and scripted initiation of mechanical CPR.

OBJECTIVE: To compare OHCA outcomes in patients managed with mechanical versus manual CPR in an EMS system with a "pit crew" approach to resuscitation and a scripted sequence for the initiation of mechanical CPR. METHODS: Through a year-long quality improvement effort we standardized the initial resuscitative efforts for OHCA, prioritizing a "pit crew" approach to high quality manual CPR, early defibrillation and basic airway management ahead of a scripted sequence for initiating mechanical CPR. We then analyzed outcomes for adult, non-traumatic OHCA attended in the following year (2016). We used a propensity score matched analysis to compare ROSC, survival to discharge, and neurologic status among patients managed with manual versus mechanical CPR while controlling for patient demographics and arrest characteristics. RESULTS: Of 444 eligible OHCAs, 217 received manual and 227 received mechanical CPR. Crude ROSC (39.2% vs. 29.1%) and survival to discharge (13.8% vs. 5.7%) were higher with manual CPR. In the propensity matched analysis (n = 176 manual CPR; 176 mechanical CPR), both ROSC (38.6% vs. 28.4%; difference: 10.2%; CI: 0.4% to 20.0%) and survival to discharge (13.6% vs. 6.8%; difference: 6.8%; CI: 0.5% to 13.3%) remained significantly higher for patients receiving manual CPR. CONCLUSIONS: In this EMS system with a standardized, "pit crew" approach to OHCA that prioritized initial high-quality initial resuscitative efforts and scripted the sequence for initiating mechanical CPR, use of mechanical CPR was associated with decreased ROSC and decreased survival to discharge.

PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome.

Fragile X syndrome (FXS) is the leading cause of both intellectual disability and autism resulting from a single gene mutation. Previously, we characterized cognitive impairments and brain structural defects in a Drosophila model of FXS and demonstrated that these impairments were rescued by treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented biochemical defect observed in fly and mouse FXS models and FXS patients is low cAMP levels. cAMP levels can be regulated by mGluR signaling. Herein, we demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate memory impairments and brain structural defects in the Drosophila model of fragile X. Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic treatment in the fragile X mouse model. We demonstrate that acute inhibition of PDE-4 by pharmacologic treatment in hippocampal slices rescues the enhanced mGluR-dependent LTD phenotype observed in FXS mice. Additionally, we find that chronic treatment of FXS model mice, in adulthood, also restores the level of mGluR-dependent LTD to that observed in wild-type animals. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of FXS is an important advance, in that this identifies and validates PDE-4 inhibition as potential therapeutic intervention for the treatment of individuals afflicted with FXS.

Prehospital endotracheal intubation vs extraglottic airway device in blunt trauma.

OBJECTIVE: The objective of the study is to compare outcomes in blunt trauma patients managed with prehospital insertion of an extraglottic airway device (EGD) vs endotracheal intubation (ETI). The null hypothesis was that there would be no difference in mortality for the 2 groups. METHODS: This is a retrospective study of blunt trauma patients with Glasgow Coma Scale score less than or equal to 8 transported by ground emergency medical services directly from the scene of injury to a single urban level 1 trauma center. Patients managed with only noninvasive airway techniques were excluded, leaving patients undergoing either EGD placement or ETI. Outcomes included in-emergency department (ED) traumatic arrest and hospital mortality. Multivariable logistic regression was used to control for the potential confounding effects of demographic and clinical variables. For all analyses, P < .05 was used to establish statistical significance. RESULTS: In bivariate analysis, patients managed with EGD were more likely than those managed with ETI to have an in-ED traumatic arrest (36.5% vs 17.1%; P = .005), but eventual hospital mortality did not significantly differ between the 2 groups (75.7% vs 67.1%; P = .228). After controlling for demographic and clinical characteristics, patients managed with EGD were no more likely than patients managed with ETI to experience traumatic arrest in the ED (adjusted odds ratio, 1.67; 95% confidence interval, 0.72-3.89), and there was also no difference in overall hospital mortality (adjusted odds ratio, 0.912; 95% confidence interval, 0.36-2.30). CONCLUSION: In this preliminary, retrospective analysis, we found no difference in overall survival among trauma patients managed with prehospital EGD and those managed with prehospital ETI.

Short- and long-term memory are modulated by multiple isoforms of the fragile X mental retardation protein.

The diversity of protein isoforms arising from alternative splicing is thought to modulate fine-tuning of synaptic plasticity. Fragile X mental retardation protein (FMRP), a neuronal RNA binding protein, exists in isoforms as a result of alternative splicing, but the contribution of these isoforms to neural plasticity are not well understood. We show that two isoforms of Drosophila melanogaster FMRP (dFMR1) have differential roles in mediating neural development and behavior functions conferred by the dfmr1 gene. These isoforms differ in the presence of a protein interaction module that is related to prion domains and is functionally conserved between FMRPs. Expression of both isoforms is necessary for optimal performance in tests of short- and long-term memory of courtship training. The presence or absence of the protein interaction domain may govern the types of ribonucleoprotein (RNP) complexes dFMR1 assembles into, with different RNPs regulating gene expression in a manner necessary for establishing distinct phases of memory formation.

Pharmacological and genetic reversal of age-dependent cognitive deficits attributable to decreased presenilin function.

Alzheimer's disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced.

Field-induced therapeutic hypothermia for neuroprotection after out-of hospital cardiac arrest: a systematic review of the literature.

BACKGROUND: Emergency Medical Services (EMS) has started to embrace the early use of therapeutic hypothermia as standard treatment to improve neurological recovery in out-of hospital cardiac arrest (OHCA) survivors. OBJECTIVE: We conducted a systematic review to provide an overall description of the current literature on the use of therapeutic hypothermia in OHCA and to identify possible gaps in the literature. METHODS: Comprehensive searches of MEDLINE, PubMed, CINAHL, and ISI Web of Science from 1950 to March 2009, and EMBASE from 1988 to March 2009 were performed. Bibliographies of selected articles were hand searched. Two reviewers independently selected studies on the basis of three inclusion criteria. Two additional independent reviewers assessed selected studies for quality. RESULTS: Of more than 800 screened citations, a total of 11 published studies were included in the systematic review. Three studies were conducted in the United States, three in Finland, and one each in Australia, France, Germany, Austria, and Norway. Four of the studies were pilot clinical trials that provided prehospital mild therapeutic hypothermia during active cardiopulmonary resuscitation. The remaining seven studies performed cooling after return of spontaneous circulation. Significant differences in research methodology and outcome measures were noted. Eight studies scored poor for quality. CONCLUSIONS: The use of mild therapeutic hypothermia is gaining acceptance within the EMS community. It seems that hypothermia can be efficiently induced in the prehospital environment. There is a need for more research in this area to understand the effectiveness and timing of early therapeutic hypothermia in the prehospital environment.

Air medical providers' physiological response to a simulated trauma scenario.

INTRODUCTION: We assessed heart rate as a surrogate measure of psychological response to determine whether high-fidelity simulation reproduces a stressful atmosphere for air medical providers. METHODS: A prospective simulation study of air-medical providers at a level 1 trauma center randomized to adult or pediatric trauma scenarios in an ambulance. Continuous closed circuit video and wireless heart rate monitoring was conducted from the time of initial patient simulator contact to completion of packaging for transport. RESULTS: The 19 air-medical providers had the following characteristics: younger than 40 years of age 90%; male 63%; registered nurses (RN) 37%, emergency medical technician-paramedics (EMT-P) 53%; mean time in practice 9 years; mean resting heart rate 71 beats per minute (bpm). Heart rate increased during study intake through start of the scenario, plateaued, and then increased abruptly on scenario completion. "Anticipatory" heart rate (during study intake) and peak heart rate were higher in less versus more experienced providers 106 bpm versus 92 bpm and 132 versus 123 bpm. CONCLUSION: Providers demonstrated increased heart rates when exposed to high-fidelity simulation of critically injured trauma patients. Future studies should determine whether simulation continues to provoke this physiological response, and whether this response occurs during live operations.

Age-dependent cognitive impairment in a Drosophila fragile X model and its pharmacological rescue.

Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms.

Improved out-of-hospital cardiac arrest survival after the sequential implementation of 2005 AHA guidelines for compressions, ventilations, and induced hypothermia: the Wake County experience.

STUDY OBJECTIVE: We assess survival from out-of-hospital cardiac arrest after community-wide implementation of 2005 American Heart Association guidelines. METHODS: This was an observational multiphase before-after cohort in an urban/suburban community (population 840,000) with existing advanced life support. Included were all adults treated for cardiac arrest by emergency responders. Excluded were patients younger than 16 years and trauma patients. Intervention phases in months were baseline 16; phase 1, new cardiopulmonary resuscitation 12; phase 2, impedance threshold device 6; and phase 3, full implementation including out-of-hospital-induced hypothermia 12. Primary outcome was survival to discharge. Other survival and neurologic outcomes were compared between study phases, and adjusted odds ratios with 95% confidence intervals (CIs) for survival by phase were determined by multivariate regression. RESULTS: One thousand three hundred sixty-five cardiac arrest patients were eligible for inclusion: baseline n=425, phase 1 n=369, phase 2 n=161, phase 3 n=410. Across phases, patients had similar demographic, clinical, and emergency medical services characteristics. Overall and witnessed ventricular fibrillation and ventricular tachycardia survival improved throughout the study phases: respectively, baseline 4.2% and 13.8%, phase 1 7.3% and 23.9%, phase 2 8.1% and 34.6%, and phase 3 11.5% and 40.8%. The absolute increase for overall survival from baseline to full implementation was 7.3% (95% CI 3.7% to 10.9%); witnessed ventricular fibrillation/ventricular tachycardia survival was 27.0% (95% CI 13.6% to 40.4%), representing an additional 25 lives saved annually in this community. CONCLUSION: In the context of a community-wide focus on resuscitation, the sequential implementation of 2005 American Heart Association guidelines for compressions, ventilations, and induced hypothermia significantly improved survival after cardiac arrest. Further study is required to clarify the relative contribution of each intervention to improved survival outcomes.

Triage performance of first-year medical students using a multiple-casualty scenario, paper exercise.

INTRODUCTION: Large-scale events may overwhelm the capacity of even the most advanced emergency medical systems. When patient volume outweighs the number of available emergency medical services (EMS) providers, a mass-casualty incident may require the aid of non-medical volunteers. These individuals may be utilized to perform field disaster triage, lessening the burden on EMS personnel. OBJECTIVE: The purpose of this study was to evaluate the accuracy of triage decisions made by newly enrolled first-year medical students after receiving a brief educational intervention. METHODS: A total of 315 first-year medical students from two successive classes participated in START triage training and completed a paper-based triage exercise as part of orientation. This questionnaire consisted of 15 clinical scenarios providing brief but sufficient details for prioritization. Subjects assigned each scenario a triage category of Red, Yellow, Green, or Black, based on the START protocol and were allowed four minutes to complete the exercise. Participants from the Class of 2009 were provided with printed START reference cards, while those from the Class of 2008 were not. Two test types varying in the order of patient age values were created to determine whether patient age was a factor in triage assessment. RESULTS: The mean accuracy score of triage assignment by medical student volunteers after a brief START training session was 64.3%. The overall rate of over-triage was 17.8%, compared to an under-triage rate of 12.6%. There were no significant differences in triage accuracy between subjects with and without printed materials (63.9% vs. 64.6%, p = 0.729) or those completing the age-variant test types (64.4% vs. 64.1%, p = 0.889). CONCLUSIONS: First-year medical students who received brief START training achieved triage accuracy scores similar to those of emergency physicians, registered nurses, and paramedics in previous studies. Observed rates of under and over-triage suggest that a need exists for improving the accuracy of triage decisions made by medical and non-medical personnel. This study did not find that printed materials significantly improved triage accuracy, nor did it find that patient age affected the ability of participants to correctly assign triage categories. Future research might further evaluate disaster triage by non-medical volunteers.

Pneumothorax as a complication after TASER activation.

Use of the TASER electronic control device by law enforcement and civilians is increasing. Advocates for the use of the device believe that it has reduced the number of officer and suspect injuries. However, the use of the device is not without complications. Many of these injuries to superficial body structures or those sustained in the postactivation fall have been described in the literature. Injury to deep structures of the abdomen and chest were previously thought to be unlikely given the length of the TASER barb. This case report of a 16-year-old male patient who suffered a pneumothorax after TASER activation is thought to be the first reported in the literature.

TAKE10: A community approach to teaching compression-only CPR to high-risk zip codes.

OBJECTIVE: Bystander cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) has the ability to improve patient survival. However, the rates at which CPR occurs are suboptimal. We hypothesized that targeted CPR training in neighborhoods with low bystander CPR and high incidence of cardiac arrests would increase the incidence of bystander CPR for adult OHCA. METHODS: This study is a descriptive observation and analysis of the TAKE 10 program, which recruited City of Austin and Travis County residents to teach fellow community members compression-only CPR. Twelve zip codes in Austin and Travis County were identified as "high-risk," based on low bystander CPR rates and high incidences of cardiac arrest. Data was collected on bystander CPR for OHCA over the study period of July 2008 to September 2013. Incidence of cardiac arrest and bystander CPR were calculated yearly and overall. RESULTS: Over the study period, a total of 11,242 community members completed compression-only CPR training. While there was no significant difference in the number of individuals trained in high-risk zip codes compared to the other zip codes (High-Risk [n±sd] 263±235; General 212±193; p-value 0.46), the amount of people trained in the high-risk zip codes did trend upwards over the study period. Additionally, there was an increase in percent of bystander CPR per eligible cardiac arrest in the high-risk zip codes (2009: [n±sd] 0.28±0.34 to 2013: 0.39±0.28). CONCLUSIONS: Targeted compression-only CPR training in high-risk neighborhoods may be associated with increased bystander CPR rates over time.

Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models.

Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted with executive dysfunction, ADHD, seizure disorder and sleep disturbances. Fragile X is caused by loss of FMRP expression, which is encoded by the FMR1 gene. Both the fly and mouse models of fragile X are also based on having no functional protein expression of their respective FMR1 homologs. The fly model displays well defined cognitive impairments and structural brain defects and the mouse model, although having subtle behavioral defects, has robust electrophysiological phenotypes and provides a tool to do extensive biochemical analysis of select brain regions. Decreased cAMP signaling has been observed in samples from the fly and mouse models of fragile X as well as in samples derived from human patients. Indeed, we have previously demonstrated that strategies that increase cAMP signaling can rescue short term memory in the fly model and restore DHPG induced mGluR mediated long term depression (LTD) in the hippocampus to proper levels in the mouse model (McBride et al., 2005; Choi et al., 2011, 2015). Here, we demonstrate that the same three strategies used previously with the potential to be used clinically, lithium treatment, PDE-4 inhibitor treatment or mGluR antagonist treatment can rescue long term memory in the fly model and alter the cAMP signaling pathway in the hippocampus of the mouse model.

Derivation and initial application of a standard population for out-of-hospital cardiac arrest (SPOHCA).

AIM: While adjusting data for age, sex, race and/or socio-economic status is well established in out-of-hospital cardiac arrest (OHCA) research, there are shortcomings to reporting and comparing population-based OHCA outcomes. The purpose of this study was to derive a case-based standard population specific to EMS treated adult OHCA (SPOHCA) in the U.S., and demonstrate its application. METHODS: The proposed SPOHCA was developed from three sources of multi-site OHCA data: the Cardiac Arrest Registry to Enhance Survival (CARES); the National EMS Information System (NEMSIS); and a published report from the Resuscitation Outcomes Consortium (ROC). OHCA data from a single EMS system were then used to demonstrate the application of SPOHCA. We report raw survival, population-based survival adjusted to the U.S. population, and the new SPOHCA-adjusted survival. RESULTS: Observed raw survival was 12.3%. Adjustment to the demographic make-up of the adult U.S. population produced an adjusted incidence of 94.2 OHCA per 100,000 p-y, with a survival rate of 9.8 per 100,000 p-y. Using the proposed SPOHCA to adjust survival data produced an adjusted survival rate of 12.4%. CONCLUSION: A case-based standard population provides for more practical interpretation of reported OHCA outcomes. We encourage a more widespread effort involving multiple stakeholders to further explore the effects of adjusting OHCA outcomes using the proposed SPOHCA instead of population-based demographics.

Profiles in patient safety: when an error occurs.

Medical error is now clearly established as one of the most significant problems facing the American health care system. Anecdotal evidence, studies of human cognition, and analysis of high-reliability organizations all predict that despite excellent training, human error is unavoidable. When an error occurs and is recognized, providers have a duty to disclose the error. Yet disclosure of error to patients, families, and hospital colleagues is a difficult and/or threatening process for most physicians. A more thorough understanding of the ethical and social contract between physicians and their patients as well as the professional milieu surrounding an error may improve the likelihood of its disclosure. Key among these is the identification of institutional factors that support disclosure and recognize error as an unavoidable part of the practice of medicine. Using a case-based format, this article focuses on the communication of error with patients, families, and colleagues and grounds error disclosure in the cultural milieu of medial ethics.

A tale of two cities: the role of neighborhood socioeconomic status in spatial clustering of bystander CPR in Austin and Houston.

BACKGROUND: Despite evidence to suggest significant spatial variation in out-of-hospital cardiac arrest (OHCA) and bystander cardiopulmonary resuscitation (BCPR) rates, geographic information systems (GIS) and spatial analysis have not been widely used to understand the reasons behind this variation. This study employs spatial statistics to identify the location and extent of clusters of bystander CPR in Houston and Travis County, TX. METHODS: Data were extracted from the Cardiac Arrest Registry to Enhance Survival for two U.S. sites - Austin-Travis County EMS and the Houston Fire Department - between October 1, 2006 and December 31, 2009. Hierarchical logistic regression models were used to assess the relationship between income and racial/ethnic composition of a neighborhood and BCPR for OHCA and to adjust expected counts of BCPR for spatial cluster analysis. The spatial scan statistic was used to find the geographic extent of clusters of high and low BCPR. RESULTS: Results indicate spatial clusters of lower than expected BCPR rates in Houston. Compared to BCPR rates in the rest of the community, there was a circular area of 4.2km radius where BCPR rates were lower than expected (RR=0.62; p<0.0001 and RR=0.55; p=0.037) which persist when adjusted for individual-level patient characteristics (RR=0.34; p=0.027) and neighborhood-level race (RR=0.34; p=0.034) and household income (RR=0.34; p=0.046). We also find a spatial cluster of higher than expected BCPR in Austin. Compared to the rest of the community, there was a 23.8km radius area where BCPR rates were higher than expected (RR=1.75; p=0.07) which disappears after controlling for individual-level characteristics. CONCLUSIONS: A geographically targeted CPR training strategy which is tailored to individual and neighborhood population characteristics may be effective in reducing existing disparities in the provision of bystander CPR for out-of-hospital cardiac arrest.