The benzoquinoid ansamycin geldanamycin interferes with many cell signaling pathways and is currently being evaluated as an anticancer agent. The main intracellular target of geldanamycin is the 90-kDa heat shock protein, hsp90. In this... more
The benzoquinoid ansamycin geldanamycin interferes with many cell signaling pathways and is currently being evaluated as an anticancer agent. The main intracellular target of geldanamycin is the 90-kDa heat shock protein, hsp90. In this report we demonstrate that geldanamycin is effective at preventing glutamate-induced oxidative toxicity in the HT22 mouse hippocampal cell line, even if given 4 h after glutamate treatment. Geldanamycin prevents glutamate-induced internucleosomal DNA cleavage in the HT22 cells but does not reverse the depletion of glutathione levels brought about by glutamate treatment. Both anabolic and catabolic effects are generated by geldanamycin treatment of HT22 cells, as evidenced by the induction of hsp70 expression and degradation of c-Raf-1 protein, respectively. Thus, geldanamycin may provide an effective strategy for manipulating signaling pathways in neuronal cells that use hsp90 as they proceed through a programmed cell death pathway in response to oxidative stress.
Research Interests:
In acute stroke due to large vessel occlusion, faster reperfusion leads to better outcomes. We analyzed the effect of optimization steps aimed to reduce treatment delays at our center. Consecutive patients with ischemic stroke treated... more
In acute stroke due to large vessel occlusion, faster reperfusion leads to better outcomes. We analyzed the effect of optimization steps aimed to reduce treatment delays at our center. Consecutive patients with ischemic stroke treated with endovascular therapy were prospectively analyzed. We divided the patients into pre-optimization (20 April 2012 to 8 October 2013) and post-optimization (9 October 2013 to 29 July 2014) periods. The main interventions included: (1) continuous feedback; (2) standardized immediate emergency department attending to stroke attending communication with interventional team activation for all potential interventions; (3) pre-notification by the emergency medical service; (4) minimizing additional diagnostic testing; (5) direct transport to the CT scanner; (6) transport directly from the CT scanner to the angiography suite. The main metric used to measure improvement was door to groin puncture time (D2P). We included a total of 286 patients (178 pre-optimization, 108 post-optimization). There were no significant differences between major baseline characteristics between the groups with the exception of higher median CT Alberta Stroke Program Early CT Score in the pre-optimization group (p=0.01). Median D2P improved from 105 min pre-optimization to 67 min post-optimization (p=0.0002). Rates of good clinical outcomes (modified Rankin Scale 0-2 at 3 months) were similar in both groups, with a trend toward a better outcome in the post-optimization group in a subgroup analysis of patients with anterior circulation occlusion who received intravenous tissue plasminogen activator. This pilot study demonstrates that D2P times can be significantly reduced with a standardized multidisciplinary approach. There was no significant difference in the rate of 3-month good outcome, which is most likely due to the small sample size and confounding baseline patient characteristics.
Research Interests: Treatment Outcome, Medicine, Stroke, Humans, Female, and 14 moreMale, Brain Ischemia, Two Stroke Engine, Aged, Middle Aged, Time Factors, Tissue Plasminogen Activator, Pilot Projects, Emergency Department, Thrombolytic Therapy, Endovascular Procedures, Thrombectomy, Reperfusion, and modified Rankin Scale
Research Interests:
Research Interests: Nursing, Cardiology, Medicine, Prehospital Emergency Care, Humans, and 15 moreInternal Medicine, Female, Resuscitation, Male, Recurrence, Clinical Sciences, Cardiopulmonary Resuscitation, Aged, Middle Aged, Public health systems and services research, Asystole, Ventricular Fibrillation, Prehospital, Population surveillance, and Outcome Assessment Health Care
Research Interests:
Mitogen-activated protein kinases are signal transduction mediators that have been implicated in cell survival and cell death. This study characterized the activation of pathways in the hippocampus during reperfusion after global cerebral... more
Mitogen-activated protein kinases are signal transduction mediators that have been implicated in cell survival and cell death. This study characterized the activation of pathways in the hippocampus during reperfusion after global cerebral ischemia, as well as the influence of a regimen of hypothermia that reduces ischemic cell death in the hippocampus. Circulatory arrest was induced in rats by 8 min of asphyxia. Relative levels of phosphorylated and total extracellular signal-regulated kinase, stress-activated protein kinase/c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were measured in the hippocampus after 6, 12 or 24h of reperfusion using immunoblotting. Asphyxia induced a progressive increase in phosphorylated extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun N-terminal kinase, but no change in phosphorylated p38 mitogen-activated protein kinase. Induction of mild hypothermia (33 degrees C) during reperfusion increased extracellular signal-regulated kinase phosphorylation and produced a smaller increase in stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation at 24h. Hypothermia did not alter extracellular signal-regulated kinase activation in rats not subjected to ischemia. Extracellular signal-regulated kinase activation was associated with an increase in phosphorylation of the mitogen-activated protein kinase kinase 1/2, and was inhibited by administration of the specific mitogen-activated protein kinase kinase 1/2 inhibitor SL327. Immunohistochemical staining showed an increase in active extracellular signal-regulated kinase in the CA1, CA2, CA3 and dentate gyrus regions of the hippocampus after ischemia and reperfusion. In contrast, active stress-activated protein kinase/c-Jun N-terminal kinase immunoreactivity was most intense in the CA3 and dentate gyrus regions. These data demonstrate that both extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun N-terminal kinase pathways are activated during the first 24h of reperfusion after global cerebral ischemia, and that hypothermia increases the activation of extracellular signal-regulated kinase relative to stress-activated protein kinase/c-Jun N-terminal kinase. Thus, an increase in extracellular signal-regulated kinase activation may be associated with improved neuronal survival after ischemic injury.
Research Interests: Neuroscience, Psychology, Biology, Medicine, Hippocampus, and 15 moreCardiac arrest, Hypothermia, Animals, Cell Death, Phosphorylation, Mitogen Activated Protein Kinase, Dentate Gyrus, Cerebral Ischemia, Cell Survival, Neurosciences, Ask, Enzyme Induction, Phosphate Buffer Saline, Asphyxia, and Heart arrest
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Objective:Elucidate how physicians formulate a neurological prognosis after cardiac arrest and compare differences between experts and general providers.Methods:We performed semi-structured interviews with experts in post-arrest care and... more
Objective:Elucidate how physicians formulate a neurological prognosis after cardiac arrest and compare differences between experts and general providers.Methods:We performed semi-structured interviews with experts in post-arrest care and general physicians. We created an initial model and interview guide based on professional society guidelines. Two authors independently coded interviews based on this initial model, then identified new topics not included in it. To describe individual physicians’ cognitive approach to prognostication, we created a graphical representation. We summarized these individual “mental models” into a single overall model, as well as two models stratified by expertise.Results:We performed 36 interviews (17 experts and 19 generalists), most of whom practice in Europe (23) or North America (12). Participants described their approach to prognosis formulation as complex and iterative, with sequential and repeated data acquisition, interpretation, and prognosis formulation. Eventually, this cycle results in a final prognosis and treatment recommendation. Commonly mentioned factors were diagnostic test performance, time from arrest, patient characteristics. Participants also discussed factors rarely discussed in prognostication research including physician and hospital characteristics. We found no substantial differences between experts and general physicians.Conclusion:Physicians’ cognitive approach to neurologic prognostication is complex and influenced by many factors, including some rarely considered in current research. Understanding these processes better could inform interventions designed to aid physicians in prognostication.
Research Interests:
Introduction: For pediatric patients with out-of-hospital cardiac arrest (OHCA) who do not achieve return of spontaneous circulation (ROSC), it remains unclear whether patients should be transported to a hospital with ongoing... more
Introduction: For pediatric patients with out-of-hospital cardiac arrest (OHCA) who do not achieve return of spontaneous circulation (ROSC), it remains unclear whether patients should be transported to a hospital with ongoing resuscitation or remain on-scene for further resuscitation. We therefore evaluated: (1) the association between intra-arrest transport, with reference to continued on-scene resuscitation, and survival to hospital discharge; and, (2) whether the association differs across the timing of intra-arrest transport. Methods: We conducted a secondary analysis of the Resuscitation Outcomes Consortium Epidemiologic Registry. We included pediatrics (<18 years) with emergency medical services (EMS)-treated OHCA between 2005 and 2015. Our exposure of interest was intra-arrest transport, defined as transport to a hospital prior to ROSC. Patients who had intra-arrest transport at any minute after EMS arrival underwent risk-set matching with patients who had continued on-scene resuscitation within the same minute using time-dependent propensity score calculated from patient demographics, arrest characteristics, and EMS interventions. We repeated the main analysis with 5-minute strata by the time of matching. Results: Of 2,854 included patients, the median age was 1 year (IQR, 0-9), 59.3% were male, 9.8% were public location, 22.1% were bystander witnessed, 6.0% had initial shockable rhythms, and 66.3% underwent intra-arrest transport at a median of 15 minutes (IQR 9-22) after EMS arrival. In the propensity-matched cohort including 2,080 patients, 5.5 % (57/1040) in intra-arrest transport group and 5.9% (61/1040) in continued on-scene resuscitation group had survival to hospital discharge (risk ratio [RR]=0.94, 95% CI 0.65-1.37). We did not detect an association within the time-based strata: 0-5 minutes (RR=0.74, 95% CI 0.19-2.85), 5-10 minutes (RR=0.52, 95% CI 0.23-1.16), 10-15 minutes (RR=1.13, 95% CI 0.58-2.22), 15-20 minutes, (RR=1.70, 95% CI 0.78-3.71), or >20 minutes (RR=0.73, 95% CI 0.32-1.63) after EMS arrival. Conclusions: Among pediatric patients with OHCA, intra-arrest transport was not associated with survival to hospital discharge. The findings persisted across the timing of intra-arrest transport.
Research Interests:
Introduction: Patients resuscitated from out-of-hospital cardiac arrest (OHCA) have variable severity of brain injury. Signatures of severe injury on brain imaging and EEG including diffuse cerebral edema and burst suppression with... more
Introduction: Patients resuscitated from out-of-hospital cardiac arrest (OHCA) have variable severity of brain injury. Signatures of severe injury on brain imaging and EEG including diffuse cerebral edema and burst suppression with identical bursts (BSIB). Current therapies for these patterns of injury are inadequate and patient outcomes are poor. Hypothesis: We hypothesize distinct phenotypes of brain injury are associated with increasing CPR duration. Methods: We identified from our prospective registry OHCA patients treated between January 2010 to July 2019. We abstracted CPR duration, best neurological examination < 6 hours from OHCA, initial brain CT grey-to-white ratio (GWR), and initial EEG pattern. We defined cerebral edema as GWR <1.20. We defined BSIB according to American Clinical Neurophysiology Society guidelines. We considered four phenotypes on presentation: awake; comatose with neither BSIB nor cerebral edema; BSIB; and cerebral edema. BSIB and cerebral edema were considered as non-mutually exclusive outcomes. We compared duration of CPR across groups using Kruskal-Wallis tests with Bonferroni correction for multiple hypothesis testing. We report the probability of presenting phenotype at the median CPR duration for each group using local regression. Results: We included 2,721 patients, of whom 582 (21%) were awake, 1,428 (52%) had coma without BSIB or edema, 372 (14%) had BSIB and 356 (13%) had cerebral edema. Only 47 (2%) had both BSIB and edema. Median CPR duration was 16 [IQR 8-28] minutes overall. Median CPR duration increased in a stepwise manner across groups: awake 6 [3-12] minutes; comatose without BSIB or edema 16 [9-27] minutes; BSIB 21 [14-30] minutes; cerebral edema 32 [22-46] minutes (all P <0.001). The probability of observing each phenotype at the median CPR duration for each was: awake (0.42); comatose without BSIB or edema (0.72); BSIB (0.34); cerebral edema (0.29). Conclusions: The brain injury phenotype is related to CPR duration, which is a surrogate for severity of ischemic injury. The sequence of most likely brain injury phenotype with progressively longer CPR duration is awake, coma without BSIB or edema, BSIB, and finally cerebral edema.
Research Interests:
Background: In patients resuscitated from out of hospital cardiac arrest (OHCA) with severe functional disability, life support is often limited. However, long-term outcomes in such patients are largely unknown, leaving little data to... more
Background: In patients resuscitated from out of hospital cardiac arrest (OHCA) with severe functional disability, life support is often limited. However, long-term outcomes in such patients are largely unknown, leaving little data to guide this decision. Methods: We performed a retrospective cohort study of OHCA survivors ≥ 18 years of age, treated at a single center in Western Pennsylvania from 01/01/2010-05/20/2021, with a modified Rankin scale (mRS) of 5 and cerebral performance category (CPC) of 4 at hospital discharge. We recorded demographics, arrest characteristics, and neurological exam at hospital discharge. We reviewed records from index hospitalization to the present to determine the date and type of subsequent healthcare encounters and whether or not subjects followed commands in subsequent neurological exams. National Death Index query and internet search for obituary until 5/20/2021. Survival time and hazard ratios were estimated using Kaplan-Meier curves. Results: Among 2,460 OHCA patients treated, 857 (35%) survived to hospital discharge. Of survivors, 83 (9.6%) had mRS 5 and CPC 4, and 69 (85%) did not follow commands. One year mortality was 59% (n=48) with median survival time of 166 days (IQR 77-1083). Age ≥ 65 years was not associated with survival [HR 1.51, 95%CI 0.79 - 2.89]. We found 361 subsequent medical encounters (median per patient =1, IQR 0-4), most often ED visits (n=131, 41%). Visits comprised 87 (28%) well patient visit/medication refills, 60 (22%) infections, and 38 (12%) tracheostomy/feeding tube issues. Average frequency of healthcare encounters was about once every 3 months (.30 encounters per month, SD .799). Of subjects who did not follow commands at hospital discharge, 4 (6%) followed commands on subsequent encounters. Conclusions: About 10% of OHCA survivors were discharged from the hospital with severe functional disability. They had a 59% 1-year mortality and frequent visits to the ED. Few (6%) patients regained the ability to follow commands.
Research Interests:
Background: Cognitive deficits may detract from quality of life after cardiac arrest (CA). The pattern and prevalence of these deficits are not well documented. We used the Computer Assessment of Mild Cognitive Impairment (CAMCI), the... more
Background: Cognitive deficits may detract from quality of life after cardiac arrest (CA). The pattern and prevalence of these deficits are not well documented. We used the Computer Assessment of Mild Cognitive Impairment (CAMCI), the Montreal Cognitive Assessment (MOCA) and the 41 Cent Test to assess cognitive impairment in survivors of CA. We hypothesized that CAMCI subscales and other scores that were highly correlated could identify specific domains of impairment in CA survivors. Methods: Four researchers administered the CAMCI, MOCA, and/or the 41 Cent Test to CA survivors after discharge from the intensive care unit between 2010 and 2014. Physicians screened patients with the Mini-Mental State Exam to determine when this cognitive testing was feasible. We compared the distribution of scores between patients who presented with coma and those who awoke immediately after CA. Pairwise correlations between the different subscales and tests were considered significant with alpha error of 0.05. Results: Ninety-two participants completed the CAMCI, of which 18 participants completed the CAMCI, MOCA and 41 Cent Test. The mean (SD) percentile score for CAMCI was 32.2 (20.3) out of possible 100, for the MOCA was 20.3 (5.2) out of a possible 30 points and the 41 Cent Test was 5.4 (1.1) out of a possible 7 points. MOCA correlated strongly with the overall CAMCI score (r = 0.82) and with the executive accuracy subscale of the CAMCI (r = 0.75). The executive accuracy subscale and overall CAMCI score correlated with one another (r = 0.81) when all 92 CAMCI exams were considered. The MOCA and 41 Cent Test were correlated with each other (r = 0.63). Conclusion: The CAMCI detects cognitive impairment after CA; the MOCA correlates strongly with the overall CAMCI and the executive function subscale of the CAMCI. The 41 Cent Test may not be as effective as the MOCA in detecting cognitive deficits.
Research Interests:
STUDY OBJECTIVE While often prioritized in the resuscitation of patients with out-of-hospital cardiac arrest, the optimal timing of advanced airway insertion is unknown. We evaluated the association between the timing of advanced airway... more
STUDY OBJECTIVE While often prioritized in the resuscitation of patients with out-of-hospital cardiac arrest, the optimal timing of advanced airway insertion is unknown. We evaluated the association between the timing of advanced airway (laryngeal tube and endotracheal intubation) insertion attempt and survival to hospital discharge in adult out-of-hospital cardiac arrest. METHODS We performed a secondary analysis of the Pragmatic Airway Resuscitation Trial (PART), a clinical trial comparing the effects of laryngeal tube and endotracheal intubation on outcomes after adult out-of-hospital cardiac arrest. We stratified the cohort by randomized airway strategy (laryngeal tube or endotracheal intubation). Within each subset, we defined a time-dependent propensity score using patients, arrest, and emergency medical services systems characteristics. Using the propensity score, we matched each patient receiving an initial attempt of laryngeal tube or endotracheal intubation with a patient at risk of receiving laryngeal tube or endotracheal intubation attempt within the same minute. RESULTS Of 2,146 eligible patients, 1,091 (50.8%) and 1,055 (49.2%) were assigned to initial laryngeal tube and endotracheal intubation strategies, respectively. In the propensity score-matched cohort, timing of laryngeal tube insertion attempt was not associated with survival to hospital discharge: 0 to lesser than 5 minutes (risk ratio [RR]=1.35, 95% confidence interval [CI] 0.53 to 3.44); 5 to lesser than10 minutes (RR=1.07, 95% CI 0.66 to 1.73); 10 to lesser than 15 minutes (RR=1.17, 95% CI 0.60 to 2.31); or 15 to lesser than 20 minutes (RR=2.09, 95% CI 0.35 to 12.47) after advanced life support arrival. Timing of endotracheal intubation attempt was also not associated with survival: 0 to lesser than 5 minutes (RR=0.50, 95% CI 0.05 to 4.87); 5 to lesser than10 minutes (RR=1.20, 95% CI 0.51 to 2.81); 10 to lesser than15 minutes (RR=1.03, 95% CI 0.49 to 2.14); 15 to lesser than 20 minutes (RR=0.85, 95% CI 0.30 to 2.42); or more than/equal to 20 minutes (RR=0.71, 95% CI 0.07 to 7.14). CONCLUSION In the PART, timing of advanced airway insertion attempt was not associated with survival to hospital discharge.
Research Interests:
Background Computed tomography (CT) can identify the etiology of cardiac arrest and injuries related cardiopulmonary resuscitation (CPR). Diagnostic yield of CT has only been characterized in a few small cohort studies with varied imaging... more
Background Computed tomography (CT) can identify the etiology of cardiac arrest and injuries related cardiopulmonary resuscitation (CPR). Diagnostic yield of CT has only been characterized in a few small cohort studies with varied imaging practices. Purpose To determine diagnostic yield of CT imaging after out-of-hospital cardiac arrest (OHCA). Methods We included non-traumatic OHCA patients treated at a single center February 2019 to February 2021. Our practice during the study period was to obtain unenhanced head CT in all comatose patients and CT of the cervical spine, chest, abdomen, and pelvis in most cases. We abstracted patient age and sex, CPR duration, and initial neurological examination from our prospective registry. We reviewed clinical records and identified CT imaging obtained within 24 hours of arrival. We reviewed radiology reports, and summarized findings for each body region. Results We included 505 subjects. Mean age was 60 [SD 16] years and 144 (29%) had an initial shockable rhythm. Median CPR duration was 21 [IQR 12-35] minutes and 448 (89%) subjects were comatose on presentation. Almost all subjects had brain imaging (n=481, 95%), of which 33 (7% [95% CI 5-9%]) had intracranial hemorrhage and 157 (33% [95% CI 28-37%]) had cerebral edema. Fewer subjects had a cervical spine CT (n=202, 40%) though 4 (2% [95% CI 0-4%]) had vertebral fractures. Most subjects had a CT of the chest (n=396, 76%), and abdomen and pelvis (n= 347, 69%). Identified chest pathologies included rib or sternal fractures (222, 56% [95% CI 51-61%]), pneumothorax (27, 7% [95% CI 5-10%]), aspiration or pneumonia (300, 76% [95% CI 71-80%]), mediastinal hematoma (18, 5% [95% CI 3-7%]), and pulmonary embolism (13, 3% [95% CI 2-6%]). Significant abdomen and pelvis findings were bowel ischemia (23, 7% [95% CI 4-10%]), and splenic or liver laceration (7, 2% [95% CI 1-4%]). Conclusions Cross sectional imaging identifies clinically important pathology that informs early management.
Research Interests:
Cardiopulmonary resuscitation (CPR) is physically demanding and must also be performed under emotional distress. Most cardiac arrests (CA) occur at home, making it likely that only one rescuer is available to perform CPR until emergency... more
Cardiopulmonary resuscitation (CPR) is physically demanding and must also be performed under emotional distress. Most cardiac arrests (CA) occur at home, making it likely that only one rescuer is available to perform CPR until emergency medical services (EMS) or other lay rescuers arrive. We performed a study to quantify the physical exertion required of lay-providers performing compression-only CPR for 10 minutes both with (WFB) and without (WOFB) real-time CPR quality feedback. We recruited healthy, CPR certified lay individuals to perform 10-minute rounds of CPR on two occasions: once WFB and once WOFB. We collected heart rate (HR), oxygen consumption (VO 2 ), and rating of perceived exertion (RPE) at baseline and throughout each round of CPR and collected capillary lactate and blood pressures pre- and post-CPR. We used Kruskal Wallis, Wilcoxon signed rank and rank sum tests to compare changes in measures during CPR. Participants were 15 females and 11 males, age 25 (IQR 22-37). All measures except for diastolic blood pressure, significantly changed over time. Systolic blood pressure increased both WFB (mean difference (MD) 8mmHg; 95% CI 12-5) and WOFB (MD 8mmHg; 95% CI 12-3). VO 2 and HR increased over time, but peak VO 2 and HR did not differ by group. RPE significantly increased WFB and WOFB (WFB MD 8; 95% CI 10-7; WOFB MD 8; 95% CI 9-7) WFB and WOFB, with females reporting a higher RPE immediately post-CPR WFB than males (MD 2; 95% CI 5-1). Lactate increased from baseline immediately post (WFB MD 2.3mmol/L; 95% CI 0.9-3.7; WOFB MD 1.8mmol/L; 95%CI 2.6-1) and 5-minutes post CPR (WFB MD 0.8mmol/L; 95% CI 2.3-0.7; WOFB MD2.1 mmol/L; 95% CI 0.9-3.3). CPR produces subjective and objective signs of strenuous exertion in both men and women. The presence of feedback does not alter physiologic response to prolonged CPR. However, females reported higher RPEs when performing CPR WFB, despite no significant difference in physiologic response.
Research Interests:
Research Interests:
Research Interests: Cornea, Medicine, Cardiac arrest, Humans, Female, and 15 moreMale, Glasgow Coma Scale, Clinical Sciences, Cardiopulmonary Resuscitation, Intensive Care Unit, Aged, Middle Aged, Adult, Rehabilitation Centers, Intensive Care Units, Pupil, Cohort Studies, Neurologic Examination, Patient discharge, and Heart arrest
Research Interests:
Research Interests:
Figure S1. Proportion of patients across the range of prehospital risk scores with various healthcare use. Table S1. Proportion of patients with abnormal first versus worst vital signs within variable strata, and correlation between first... more
Figure S1. Proportion of patients across the range of prehospital risk scores with various healthcare use. Table S1. Proportion of patients with abnormal first versus worst vital signs within variable strata, and correlation between first and worst vital signs for each variable. Table S2. Multivariable logistic regression model output of prehospital risk score variables with critical illness showing reweighting in sensitivity analysis. (DOCX 76 kb)
Research Interests:
OBJECTIVE: We hypothesized malignant EEG patterns (nonconvulsive status epilepticus (NCSE), myoclonic status epilepticus (MSE), and generalized periodic epileptiform discharges (GPEDs)) are found in post-cardiac arrest (CA) survivors and... more
OBJECTIVE: We hypothesized malignant EEG patterns (nonconvulsive status epilepticus (NCSE), myoclonic status epilepticus (MSE), and generalized periodic epileptiform discharges (GPEDs)) are found in post-cardiac arrest (CA) survivors and those with good neurologic outcome. BACKGROUND: Therapeutic hypothermia (TH) improves outcomes in comatose post-CA patients. Continuous EEG (cEEG) monitoring improves detection of malignant patterns but the role for aggressive treatment is unclear. Limited survival and outcome data are available in subjects who develop malignant patterns and receive a standardized antiepileptic treatment protocol. DESIGN/METHODS: cEEG recordings were obtained in subjects treated with TH between 8/1/2009 and 06/01/2012. Clinical, survival and outcome data were recorded. A good outcome was defined as discharge to home or acute rehabilitation facility. Each cEEG file was analyzed for prevailing EEG patterns in the first 48 hours post-CA. 9Pure9 patterns were defined as only demonstrating one malignant pattern during monitoring. Outcomes for subjects in burst-suppression (BS) were also recorded. RESULTS: 242 subjects received TH and cEEG. 67 patients survived (23%) and 34 (14%) had a good outcome. Malignant rhythms were seen in 25 (37%) survivors and in 10 (29%) subjects with good outcome. Five survivors had seizures, 4 met criteria for NCSE with one good outcome. Of the 13 survivors with MSE 5 had good outcomes. A 9pure9 GPEDs pattern was present in 7 survivors with 3 good outcomes. A 9pure9 BS was found in 19 (28%) survivors with 9 good outcomes. Significant EEG findings were found in 24/34 (70%) subjects with good outcomes (10 malignant rhythms, 9 pure BS, 5 pure triphasic or epileptiform discharges). CONCLUSIONS: 37 % of subjects with malignant EEG patterns treated with TH and a standardized antiepileptic protocol can be found among survivors. Subjects with malignant patterns represent almost one third of all survivors with good neurologic outcome. Disclosure: Dr. Popescu has nothing to disclose. Dr. Amorim has nothing to disclose. Dr. Baldwin has nothing to disclose. Dr. Callaway has received royalty payments from Medtronic, Inc. Dr. Rittenberger has nothing to disclose.
Research Interests:
Introduction: Cormack-Lehane (C-L) view is common method for grading difficult endotracheal intubation (ETI). Although until recently, C-L view could not be analyzed by the individuals other than the provider performing ETI. Video... more
Introduction: Cormack-Lehane (C-L) view is common method for grading difficult endotracheal intubation (ETI). Although until recently, C-L view could not be analyzed by the individuals other than the provider performing ETI. Video laryngoscopy (VL) is a relatively new device primarily to facilitate ETI. VL can also provide recorded data for objective review of the technique. Hypothesis: We tested whether C-L view evaluated by prehospital provider (paramedic/nurse) correlates with the true C-L view verified by with VL video recorded data. Methods: A retrospective review of the patients transported from Mar 2010 to Oct 2015 by air critical care medical service. The VL used in the study has the ability to display and digitally record the procedure which can be reviewed after the incident. True C-L view was confirmed by medical doctors using VL recorded data. Prehospital provider C-L view was obtained from self-reported medical charts description. We defined prehospital provider C-L view grading of I or II as “easy view” and provider C-L view grading of III or IV as “difficult view”. For the primary outcome, Cohen’s kappa was used to evaluate the reliability of prehospital provider C-L view. For the secondary outcome, characteristics between “easy view” and “difficult view” were compared. Results: Results: 236 patients were included in the study. Overall ETI success rate was 93%. True C-L view grades were (I: 159 [67%], II: 72 [31%], III: 4 [2%], IV: 1 [0%]) whereas, prehospital providers graded (I: 129 [55%], II: 80 [34%], III: 24 [10%], IV: 3 [1%]). There was 57% agreement: kappa 0.21 ( p p = 0.33), total attempt time for ETI (59±35 s vs 26±27 s, p p p Conclusions: C-L view grading only had “fair” agreement between prehospital provider and VL video recorded data. Self-reported description of C-L view grading may contain recall bias and observer bias influenced by ETI difficulty besides true C-L view.
Research Interests:
Research Interests:
Objectives: As demand outpaces supply of organs for transplantation in the US, donation after cardiac death is increasing. Select patients resuscitated from cardiac arrest may be an under-recognize...
Research Interests:
Research Interests:
Ten normal adult human subjects received a rapid intravenous infusion of two liters of cold (4ºC) isotonic saline on two separate test days, and we measured their core body temperature, shivering, hemodynamics and sedation for two hours.... more
Ten normal adult human subjects received a rapid intravenous infusion of two liters of cold (4ºC) isotonic saline on two separate test days, and we measured their core body temperature, shivering, hemodynamics and sedation for two hours. On one test day, fluid infusion was preceded by placebo infusion. On the other test day, fluid infusion was preceded by 1.0 µg/kg bolus of dexmedetomidine over 10 minutes.
Research Interests:
Research Interests:
See Article by Lilja et al To improve outcomes, it is essential to measure outcomes. A study in this issue of Circulation: Cardiovascular Quality and Outcomes highlights the need to improve the rigor and texture by which we measure... more
See Article by Lilja et al To improve outcomes, it is essential to measure outcomes. A study in this issue of Circulation: Cardiovascular Quality and Outcomes highlights the need to improve the rigor and texture by which we measure outcomes after cardiac arrest.1 Historically, clinical research on cardiac arrest characterized the quality of survival using an ordinal scale of performance, the Cerebral Performance Category (CPC). CPC was developed originally as an ad hoc measure for an early clinical trial, based on the then-current version of the Glasgow Outcome Score, a common instrument for trauma research.2 CPC has many descriptions, but it has no single instrument, has moderate inter-rater reliability, and has not proven reliable when estimated in different manners (eg, in-person examination versus over the telephone interview versus chart review). Many papers incorrectly describe CPC as a measure of neurological outcome, but the levels of the CPC contain descriptions of functional capacity and participation in activities and neurological impairment.3 It is, thus, a mixed measure of multiple domains of patient health. Lilja et al1 studied a cohort of patients who survived cardiac arrest in the large TTM (Targeted Temperature Management) clinical trial that compared 2 temperature management regimens. The TTM trial detected no differences in primary outcomes between temperature management strategies, making it possible to examine long-term survival in all survivors. Using detailed and rigorous neuropsychological, functional, and social assessments at 180 days after the cardiac arrest in 287 subjects, this study revealed that one half of survivors experience reduced participation in employment or other premorbid activities. This …
Research Interests:
Background:Novel temporal-spatial features of the 12-lead ECG can conceptually optimize culprit lesions’ detection beyond that of classical ST amplitude measurements. We sought to develop a data-driven approach for ECG feature selection... more
Background:Novel temporal-spatial features of the 12-lead ECG can conceptually optimize culprit lesions’ detection beyond that of classical ST amplitude measurements. We sought to develop a data-driven approach for ECG feature selection to build a clinically relevant algorithm for real-time detection of culprit lesion.Methods:This was a prospective observational cohort study of chest pain patients transported by emergency medical services to three tertiary care hospitals in the US. We obtained raw 10-s, 12-lead ECGs (500 s/s, HeartStart MRx, Philips Healthcare) during prehospital transport and followed patients 30 days after the encounter to adjudicate clinical outcomes. A total of 557 global and lead-specific features of P-QRS-T waveform were harvested from the representative average beats. We used Recursive Feature Elimination and LASSO to identify 35/557, 29/557, and 51/557 most recurrent and important features for LAD, LCX, and RCA culprits, respectively. Using the union of these features, we built a random forest classifier with 10-fold cross-validation to predict the presence or absence of culprit lesions. We compared this model to the performance of a rule-based commercial proprietary software (Philips DXL ECG Algorithm).Results:Our sample included 2400 patients (age 59 ± 16, 47% female, 41% Black, 10.7% culprit lesions). The area under the ROC curves of our random forest classifier was 0.85 ± 0.03 with sensitivity, specificity, and negative predictive value of 71.1%, 84.7%, and 96.1%. This outperformed the accuracy of the automated interpretation software of 37.2%, 95.6%, and 92.7%, respectively, and corresponded to a net reclassification improvement index of 23.6%. Metrics of ST80; Tpeak-Tend; spatial angle between QRS and T vectors; PCA ratio of STT waveform; T axis; and QRS waveform characteristics played a significant role in this incremental gain in performance.Conclusions:Novel computational features of the 12-lead ECG can be used to build clinically relevant machine learning-based classifiers to detect culprit lesions, which has important clinical implications.
Research Interests:
Endogenous adenosine (ADO) is known to be cardioprotective during acute myocardial ischemia. Coronary sinus ADO concentration has recently been shown to increase nearly 13-fold over baseline levels after 5 min of untreated ventricular... more
Endogenous adenosine (ADO) is known to be cardioprotective during acute myocardial ischemia. Coronary sinus ADO concentration has recently been shown to increase nearly 13-fold over baseline levels after 5 min of untreated ventricular fibrillation (VF). The role of ADO in VF has never been previously examined. The objective of this study was to determine the effect of ADO receptor antagonism, as measured by the scaling exponent (ScE), on the degeneration of VF over time during the circulatory phase of cardiac arrest. A well-established swine model of prolonged VF arrest was used for this experiment. Eighteen domestic mixed-breed swine were assigned by block randomization to receive either DTI-0017 (5mg/kg), a potent ADO A(1) receptor antagonist or placebo in a double-blind fashion. The animals were instrumented under general anesthesia and acclimatized. The assigned solution was infused over 5 min. One minute after the infusion was completed, VF was induced with a 3s, 60 Hz, 100 mA transthoracic shock and left untreated. Lead II ECG was monitored continuously and recorded at 1000 samples/s. It was determined a priori that evaluation of the plots would be limited to a previously observed plateau phase historically occurring between 5 and 8 min corresponding to the circulatory phase of cardiac arrest. The scaling exponent values over this period were calculated for each of the 18 recordings using custom MATLAB routines. Using the Wald statistic to produce the Chi square distributions the null hypothesis, that there was no difference between the two groups, was tested. The Wald statistic calculation based on eight epochs from 300 to 475 s in placebo and DTI groups was significant to reject the null hypothesis of no difference in the groupxtime interaction at the 0.015 level (Chi square distribution for Wald=17.49, d.f.=7). In this swine model, adenosine A(1) receptor antagonism accelerated the natural decay in the ECG VF waveform during the circulatory phase of cardiac arrest. Our findings would suggest that endogenous adenosine has cardioprotective effects during sudden cardiac arrest by slowing the time-dependent degeneration of VF.
Research Interests: Cardiology, Medicine, Electrocardiography, Cardiac arrest, Female, and 11 moreAnimals, Resuscitation, Male, Behavioral Animal Models, Clinical Sciences, Cardiopulmonary Resuscitation, Public health systems and services research, Swine, Ventricular Fibrillation, Random Allocation, and Adenosine receptor
Aim:To quantify the accuracy of health care providers’ predictions of survival and function at hospital discharge in a prospective cohort of patients resuscitated from cardiac arrest. To test whether self-reported confidence in their... more
Aim:To quantify the accuracy of health care providers’ predictions of survival and function at hospital discharge in a prospective cohort of patients resuscitated from cardiac arrest. To test whether self-reported confidence in their predictions was associated with increased accuracy and whether this relationship varied across providers.Methodology:We presented critical care and neurology providers with clinical vignettes using real data from post-arrest patients. We asked providers to predict survival, function at discharge, and report their confidence in these predictions. We used mixed effects models to explore predictors of confidence, accuracy, and the relationship between the two.Results:We completed 470 assessments of 62 patients with 65 providers. Of patients, 49 (78%) died and 9 (15%) had functionally favourable survival. Providers accurately predicted survival in 308/470 (66%) assessments. In most errors (146/162, 90%), providers incorrectly predicted survival. Providers accurately predicted function in 349/470 (74%) assessments. In most errors (114/121, 94%), providers incorrectly predicted favourable functional recovery. Providers were confident (median confidence predicting survival 80 [IQR 60 – 90]; median confidence predicting function 80 [IQR 60 – 95]). Confidence explained 9% and 18% of variation in accuracy predicting survival and function, respectively. We observed significant between-provider variability in accuracy (median odds ratio (MOR) for predicting survival 2.93, 95%CI 1.94 – 5.52; MOR for predicting function 5.42, 95%CI 3.01 – 13.2).Conclusions:Providers varied in accuracy predicting post-arrest outcomes and most errors were optimistic. Self-reported confidence explained little variation in accuracy.
Research Interests:
Research Interests:
Background Classical ST‐T waveform changes on standard 12‐lead ECG have limited sensitivity in detecting acute coronary syndrome (ACS) in the emergency department. Numerous novel ECG features have been previously proposed to augment... more
Background Classical ST‐T waveform changes on standard 12‐lead ECG have limited sensitivity in detecting acute coronary syndrome (ACS) in the emergency department. Numerous novel ECG features have been previously proposed to augment clinicians' decision during patient evaluation, yet their clinical utility remains unclear. Methods and Results This was an observational study of consecutive patients evaluated for suspected ACS (Cohort 1 n=745, age 59±17, 42% female, 15% ACS; Cohort 2 n=499, age 59±16, 49% female, 18% ACS). Out of 554 temporal‐spatial ECG waveform features, we used domain knowledge to select a subset of 65 physiology‐driven features that are mechanistically linked to myocardial ischemia and compared their performance to a subset of 229 data‐driven features selected by multiple machine learning algorithms. We then used random forest to select a final subset of 73 most important ECG features that had both data‐ and physiology‐driven basis to ACS prediction and compared their performance to clinical experts. On testing set, a regularized logistic regression classifier based on the 73 hybrid features yielded a stable model that outperformed clinical experts in predicting ACS, with 10% to 29% of cases reclassified correctly. Metrics of nondipolar electrical dispersion (ie, circumferential ischemia), ventricular activation time (ie, transmural conduction delays), QRS and T axes and angles (ie, global remodeling), and principal component analysis ratio of ECG waveforms (ie, regional heterogeneity) played an important role in the improved reclassification performance. Conclusions We identified a subset of novel ECG features predictive of ACS with a fully interpretable model highly adaptable to clinical decision support applications. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT04237688.
Research Interests:
For nearly 51 million persons in the United States who lack health care insurance, the emergency department (ED) functions as a safety net where no patient is denied care based on ability to pay, and much public rhetoric has characterized... more
For nearly 51 million persons in the United States who lack health care insurance, the emergency department (ED) functions as a safety net where no patient is denied care based on ability to pay, and much public rhetoric has characterized ED utilization by uninsured patients. We estimated national ED utilization by uninsured patients and compared uninsured and insured ED patients in terms of demographics, diagnostic testing, disposition and final diagnoses. We analyzed data from the National Hospital Ambulatory Medical Care Survey (2006-2009) stratified by insurance status. Demographic data, diagnoses, testing, and procedures performed in the ED were tabulated for each visit. Weighted percentages provided by National Hospital Ambulatory Medical Care Survey were used to estimate national rates for each variable, and multivariate models were constructed for predicting testing, procedures, and admission. The 135085 ED visits represent 475 million patients visits, of which 78.9 million (16.6%) were uninsured. Compared with insured patients, uninsured patients were more often male (51.1% vs 44.3%) and younger (age 18-44 years, 66.2% vs 35.4%). Uninsured patients had lower rates of circulatory/cardiovascular (7.5% vs 4.1%) and respiratory diagnoses (14.6% vs 11.8%). Uninsured patients had fewer diagnostic tests and procedures and fewer hospital admissions than those with insurance. In our multivariate models, insurance status was predictive of testing and procedures but not hospital admission. Uninsured patients account for approximately 20 million or 1 in 6 ED visits annually in the United States and have differences in demographics, diagnoses, and ED utilization patterns from those with insurance.
Research Interests: Business, Emergency Medicine, Health insurance, Adolescent, Medicine, and 15 moreHumans, Human Resources for Health, United States, Female, Male, Clinical Sciences, Ambulatory, Medical Diagnosis, Aged, Middle Aged, Adult, Emergency Department, Insurance Coverage, Health Care Surveys, and Health Resources
Research Interests: Cardiology, Electrocardiography, California, Complications, Female, and 15 moreDiagnosis, Hospital, Ecg, Ambulatory, Aged, Acute Coronary Syndrome, Chi Square Distribution, Differential, Action Potentials, Angina, Heart Ventricles, Chest Pain, Emergency Department, Emergency service, and Computer Assisted
Research Interests:
Research Interests:
Research Interests: Medicine, Cardiac arrest, Epinephrine, Female, Animals, and 15 moreResuscitation, Male, Anesthesia, Animal Model, Clinical Sciences, Cardiopulmonary Resuscitation, Time Factors, Swine, Retrospective Studies, Drug Therapy, Coronary Circulation, Propranolol, Ventricular Fibrillation, Recovery of Function, and Drug combinations
Abstract Objective. We evaluated video laryngoscopy (VL) (C-MAC, Karl Storz, Tuttlingen, Germany) for use in a critical care transport system. We hypothesized that the total number of airway attempts would decrease when using a video... more
Abstract Objective. We evaluated video laryngoscopy (VL) (C-MAC, Karl Storz, Tuttlingen, Germany) for use in a critical care transport system. We hypothesized that the total number of airway attempts would decrease when using a video laryngoscope versus use of direct laryngoscopy (DL). Methods. We performed a nonrandomized group-controlled trial where six aircraft were outfitted with VL and the remainder utilized DL responding to a mix of scene runs and interfacility transports. Our primary outcome measure was the number of intubation attempts. We also compared the first-pass success (FPS) rates, laryngoscopic grades, and frequencies of rescue device use (including utilization of surgical airways) between VL and DL. Results. Crews intubated 348 patients with VL and 510 with DL. Successful endotracheal intubation within three attempts occurred 97.6% (confidence interval [CI] 96.5–98.6) of the time. The FPS rate was 85.8% (CI 83.4–88.1). In this cohort of patients, VL did not differ from DL with respect to total number of airway attempts (1.17 [CI 1.11–1.22] vs. 1.16 [CI 1.12–1.20]), FPS rate (85.6% [CI 82–89%] vs. 86.1% [CI 83-89]), or use of rescue airways (2.6% vs. 2.2%). The laryngoscopic view was superior in the VL group relative to the DL group (median Cormack-Lehane grade 1 [interquartile range (IQR) 1, 2] vs. 2 [IQR 1, 2]). Conclusion. VL using the C-MAC video laryngoscope did not reduce the total number of airway attempts or improve intubation compared with DL in a system of highly trained providers.
Research Interests:
Research Interests: Emergency Medicine, Hyperthermia, Medicine, Canada, Cardiac arrest, and 15 moreHypothermia, Humans, Female, Male, Confidence intervals, Body Temperature, Clinical Sciences, Cardiopulmonary Resuscitation, Aged, Middle Aged, Analysis of Variance, Odds ratio, Confidence Interval, Heart arrest, and Outcome Assessment Health Care
Recent data suggest that using vasopressin in combination with epinephrine (adrenaline) may improve treatment of out-of-hospital cardiac arrest. This study examined local experience with the combination of epinephrine and vasopressin... more
Recent data suggest that using vasopressin in combination with epinephrine (adrenaline) may improve treatment of out-of-hospital cardiac arrest. This study examined local experience with the combination of epinephrine and vasopressin administration. Data were obtained from an urban, municipal emergency medical service that does not include vasopressin in its formulary. A physician is dispatched to the scene of all cardiac arrest patients treated by this system. Vasopressin could be administered in addition to epinephrine to subjects with out-of-hospital cardiac arrest by the on-scene physician. Demographic information, drug administration and return of pulses were abstracted from patient care records for a 1-year interval. Multivariate logistic regression was used to assess the relationship between vasopressin use and outcomes. During the study period, data were available for 298 subjects receiving epinephrine-only (n=231, 78%), a combination of 40 IU vasopressin and epinephrine (n=37, 12%) or no vasopressor drugs (n=30, 10%). Among patients receiving vasopressor drugs, pulse was restored for 74 subjects (28%), and 56 subjects (21%) had a pulse on arrival at the hospital. Return of pulses was associated with witnessed collapse, bystander CPR, and an initial ECG rhythm of ventricular fibrillation or tachycardia. Subjects receiving vasopressin and epinephrine were more likely to have a return of pulses during the resuscitation (LR: 2.73; 95% CI: 1.24, 6.03) and at hospital arrival (3.85; 1.71, 8.65) than subjects treated with epinephrine alone. There is an association between using vasopressin in combination with epinephrine and restoration of circulation after out-of-hospital cardiac arrest.
Research Interests: Medicine, Logistic Regression, Cardiac arrest, Humans, Epinephrine, and 15 moreFemale, Resuscitation, Male, Anesthesia, Clinical Sciences, Cardiopulmonary Resuscitation, Aged, Middle Aged, Public health systems and services research, Patient Care, Retrospective Studies, Pulse, Combination drug therapy, Advanced Cardiac Life Support, and Emergency medical service
Vasopressin administration has been suggested during cardiopulmonary resuscitation, and a previous clinical trial has suggested that vasopressin is most effective when administered with epinephrine. Adult subjects (n = 325) who received... more
Vasopressin administration has been suggested during cardiopulmonary resuscitation, and a previous clinical trial has suggested that vasopressin is most effective when administered with epinephrine. Adult subjects (n = 325) who received > or =1 dose of intravenous epinephrine during cardiopulmonary resuscitation for nontraumatic, out-of-hospital cardiac arrest were randomly assigned to receive 40 IU of vasopressin (n = 167) or placebo (n = 158) as soon as possible after the first dose of epinephrine. The rate of return of pulses was similar between the vasopressin and placebo groups (31% vs 30%), as was the presence of pulses at the emergency department (19% vs 23%). No subgroup appeared to be differentially affected, and no effect of vasopressin was evident after adjustment for other clinical variables. Additional open-label vasopressin was administered by a physician after the study drug for 19 subjects in the placebo group and 27 subjects in the vasopressin group. Results were similar if these subjects were excluded or were assigned to an actual drug received. Survival duration for subjects admitted to the hospital did not differ between groups. In conclusion, vasopressin administered with epinephrine does not increase the rate of return of spontaneous circulation.
Research Interests: Treatment Outcome, Medicine, Emergency Medical Services, Humans, Epinephrine, and 15 morePlacebo, Vasopressin, Female, Resuscitation, Male, Anesthesia, Cardiopulmonary Resuscitation, Aged, Survival Rate, Combination drug therapy, Chi Square Distribution, Logistic Models, The American, Heart arrest, and Cardiovascular medicine and haematology
Research Interests: Pediatrics, Epidemiology, Incidence Geometry, Adolescent, Medicine, and 15 moreLogistic Regression, Emergency Medical Services, Humans, Child, Female, Male, Infant, Incidence, Registries, Clinical Sciences, North America, Cardiopulmonary Resuscitation, Hospital Mortality, Asystole, and Child preschool
Research Interests: Psychology, Brief Psychotherapy, Adolescent, Medicine, Humans, and 13 moreFemale, Text Messaging, Alcohol Drinking, Male, Psychological Intervention, Young Adult, Pennsylvania, Clinical Sciences, Randomized Controlled Trial, Guidance and Counseling Intervention Programs, Neurosciences, Brief Intervention, and Emergency Department
Cardiac arrest (CA) survivors often suffer physical and cognitive deficits. Unlike survivors of myocardial infarction or stroke, CA survivors are inconsistently referred to rehabilitation services. Social and structural determinants of... more
Cardiac arrest (CA) survivors often suffer physical and cognitive deficits. Unlike survivors of myocardial infarction or stroke, CA survivors are inconsistently referred to rehabilitation services. Social and structural determinants of health affects access to care. We investigated if rehabilitation referral rates for CA survivors differed across race, ethnicity, sex and socioeconomic status (SES) based on median income of patient’s zip code of residence. We included consecutive CA survivors discharged from a single academic medical center 2014-2019. We performed a structured chart review to identify referrals to inpatient or outpatient rehabilitation. Outpatient services included cardiac rehabilitation, PT/OT, and speech therapy. We used Census data to determine median household income for each patient’s zip code of residence. We used Fisher’s Exact test and Kruskal Wallis tests to investigate the difference in referral rates based on income brackets identified from Census data, age, sex, race, and ethnicity. We included 674 CA patients, of whom 367 (54%) arrested out of hospital, 418 (62%) were male, median age was 60 (IQR 49-69) years, 526 (78%) were white, 553 (82%) were non-Hispanic or Latin-x. Overall 387 (57%) were referred to rehabilitation ( n=316 (47%) inpatient-only, n=42 (6%) outpatient-only, n=29 (4%) both). Rehabilitation referral differed across categories of income (p=0.023) (Figure) but showed no consistent trend across consecutive categories. Age was positively associated with referral (odds ratio per decade 1.33; 95% CI 1.21-1.47, p=0.015). There was no association of race, ethnicity or sex with rehabilitation referral. In our single center data, referral to rehabilitation increased with age and was less frequent for patients from neighborhoods with the lowest median income. It did not differ based on sex, race or ethnicity. Future studies should investigate rehabilitation attendance rates in comparison to SES.