Public access defibrillators: Gender-based inequities in access and application.

AIM: While public access automated external defibrillator (AED) programs appear to improve outcomes in out-of-hospital cardiac arrest (OHCA) it is unclear if men and women benefit equally. We examined gender-based differences in OHCA location to determine what proportion were potentially eligible for public access AED application, and if patient gender was associated with AED utilization. METHODS: We analyzed data from the Resuscitation Outcomes Consortium registry (2011-2015). We compared differences in OHCA locations by gender. We fit multivariate logistic regression models, restricted to public location OHCAs and public-location cases with bystander intervention, to calculate the association between gender and public access AED application. RESULTS: Among 61 473 cases, 34% were female and 50% had bystander resuscitation. The incidence of public OHCA was 8.8% for women and 18% for men (risk difference 9.2%, 95% CI 8.7-9.7%). Women had significantly fewer OHCAs on roadways, in public buildings, places of recreation, and farms, but more in homes, non-acute healthcare facilities, and residential institutions. Female gender was associated with a lower odds of AED application in public OHCA (adjusted OR 0.76, 95% CI 0.64-0.90) and public-location cases with bystander interventions (adjusted OR 0.83, 95% CI 0.71-0.99). CONCLUSION: Women had fewer OHCA in public locations that may have public access AEDs. Even among public location OHCA with bystander interventions, women were less likely to have public access AED applied. Initiatives to optimize AED locations and to engage the public with gender-specific resuscitation training may improve outcomes in women with OHCA.

A Local Sensitivity Analysis of the Trial of Continuous or Interrupted Chest Compressions during Cardiopulmonary Resuscitation: Is a Local Protocol Change Required?

Objective The "Trial of Continuous (CCC) or Interrupted Chest Compressions (ICC) during Cardiopulmonary Resuscitation (CPR)" compared two CPR strategies for out-of-hospital cardiac arrest (OHCA). Although results were neutral, there was suggestion of benefit for ICC. However, nearly 50% of study patients had a protocol violation; regional variations may have played a role in protocol adherence and outcomes. We analyzed our British Colombia (BC) cohort to decide whether a protocol change from CCC to ICC was justified. Methods This was a post-hoc analysis of BC-enrolled study patients. The primary between-group comparison was favorable neurological outcome (modified Rankin scale ≤ 3) using intention-to-treat. Secondary analyses compared those treated per-protocol (adjusted) and the top compliant clusters (unadjusted). We classified protocol violations using a structured algorithm. We used logistic regression and computed the difference in probabilities using the marginal standardization method with bootstrapping to calculate confidence intervals. Results There were 3769 patients included, with a median age of 69 years (IQR: 56-80). There were protocol violations in 3.2% of those in the CCC group and 27% of those in the ICC group. In patients randomized to CCC or ICC, 11.2% and 10.8% (risk difference 0.42%; 95% CI -1.58, 2.41) had favorable neurological outcomes, respectively. In the per-protocol and top compliant clusters comparisons, risk differences were 0.25% (95% CI -1.70, 2.25) and 2.95% (95% CI -0.68, 6.58). Conclusion Our comparisons suggest that CCC may be the preferred strategy in our region and is likely not resulting in worse outcomes. Based on the original study and our local analysis, we found no compelling reasons to change our local strategy from CCC to ICC.

Relationship between Time-to-ROSC and Survival in Out-of-hospital Cardiac Arrest ECPR Candidates: When is the Best Time to Consider Transport to Hospital?

OBJECTIVE: Extracorporeal cardiopulmonary resuscitation (ECPR) may improve outcomes for refractory out-of-hospital cardiac arrest (OHCA). Transport of intra-arrest patients to hospital however, may decrease CPR quality, potentially reducing survival for those who would have achieved return-of-spontaneous-circulation (ROSC) with further on-scene resuscitation. We examined time-to-ROSC and patient outcomes for the optimal time to consider transport. METHODS: From a prospective registry of consecutive adult non-traumatic OHCA's, we identified a hypothetical ECPR-eligible cohort of EMS-treated patients with age ≤ 65, witnessed arrest, and bystander CPR or EMS arrival < 10 minutes. We assessed the relationship between time-to-ROSC and survival, and constructed a ROC curve to illustrate the ability of a pulseless state to predict non-survival with conventional resuscitation. RESULTS: Of 6,571 EMS-treated cases, 1,206 were included with 27% surviving. Increasing time-to-ROSC (per minute) was negatively associated with survival (adjusted OR 0.91; 95%CI 0.89-0.93%). The yield of survivors per minute of resuscitation increased from commencement and started to decline in the 8th minute. Fifty percent and 90% of survivors had achieved ROSC by 8.0 and 24 min, respectively, at which times the probability of survival for those with initial shockable rhythms was 31% and 10%, and for non-shockable rhythms was 5.2% and 1.6%. The ROC curve illustrated that the 16th minute of resuscitation maximized sensitivity and specificity (AUC = 0.87, 95% CI 0.85-0.89). CONCLUSION: Transport for ECPR should be considered between 8 to 24 minutes of professional on-scene resuscitation, with 16 minutes balancing the risks and benefits of early and later transport. Earlier transport within this window may be preferred if high quality CPR can be maintained during transport and for those with initial non-shockable rhythms.

Potential Candidates for a Structured Canadian ECPR Program for Out-of-Hospital Cardiac Arrest.

OBJECTIVE: Extracorporeal cardiopulmonary resuscitation (ECPR), while resource-intensive, may improve outcomes in selected patients with refractory out-of-hospital cardiac arrest (OHCA). We sought to identify patients who fulfilled a set of ECPR criteria in order to estimate: (1) the proportion of patients with refractory cardiac arrest who may have benefited from ECPR; and (2) the outcomes achieved with conventional resuscitation. METHODS: We performed a secondary analysis from a 52-month prospective registry of consecutive adult non-traumatic OHCA cases from a single urban Canadian health region serving one million patients. We developed a hypothetical ECPR-eligible cohort including adult patients <60 years of age with a witnessed OHCA, and either bystander CPR or EMS arrival within five minutes. The primary outcome was the proportion of ECPR-eligible patients who had refractory cardiac arrest, defined as termination of resuscitation pre-hospital or in the ED. The secondary outcome was the proportion of EPCR-eligible patients who survived to hospital discharge. RESULTS: Of 1,644 EMS-treated OHCA, 168 (10.2%) fulfilled our ECPR criteria. Overall, 54/1644 (3.3%; 95% CI 2.4%-4.1%) who were ECPR-eligible had refractory cardiac arrest. Of ECPR-eligible patients, 114/168 (68%, 95% CI 61%-75%) survived to hospital admission, and 70/168 (42%; 95% CI 34-49%) survived to hospital discharge. CONCLUSION: In our region, approximately 10% of EMS-treated cases of OHCA fulfilled our ECPR criteria, and approximately one-third of these (an average of 12 patients per year) were refractory to conventional resuscitation. The integration of an ECPR program into an existing high-performing system of care may have a small but clinically important effect on patient outcomes.

Comparing the prognosis of those with initial shockable and non-shockable rhythms with increasing durations of CPR: Informing minimum durations of resuscitation.

AIM: There is little data to inform the appropriate duration of resuscitation attempts for out-of-hospital cardiac arrest (OHCA). We assessed the relationship of elapsed duration since commencement of resuscitation and outcomes, highlighting differences between initial shockable and non-shockable rhythms. METHODS: We examined consecutive adult non-traumatic EMS-treated OHCA in a single health region. We plotted the time-dependent accrual of patients with ROSC, as well as dynamic estimates of outcomes as a function of duration from commencement of professional resuscitation, and compared subgroups dichotomized by initial rhythm. Logistic regression tested the association between time-to-ROSC and outcomes. RESULTS: Of 1627 adult EMS-treated cases of OHCA, 1617 patients were included; 14% survivors and 10% with favorable neurological outcomes. Time-to-ROSC (per minute increase) was independently associated with survival in those with initial shockable (aOR 0.95, 95% CI 0.92-0.97) and non-shockable (aOR 0.83; 95% CI 0.78-0.88) rhythms. Similar associations were seen with favorable neurologic outcome. The elapsed duration at which the probability of survival fell below 1% was 48 and 15 min in the shockable and non-shockable groups, respectively. Median time-to-termination of resuscitation was 36 and 26 min in the shockable and non-shockable groups, respectively. CONCLUSION: The subgroup of initial shockable rhythms showed a less pronounced association of time-to-ROSC with outcomes, and demonstrated higher resilience for neurologically intact survival after prolonged periods of resuscitation. This data can guide minimum durations of resuscitation, however should not be considered as evidence for termination of resuscitation as survival in this cohort may have been improved with longer resuscitation attempts.

Perishock pause: an independent predictor of survival from out-of-hospital shockable cardiac arrest.

BACKGROUND: Perishock pauses are pauses in chest compressions before and after defibrillatory shock. We examined the relationship between perishock pauses and survival to hospital discharge. METHODS AND RESULTS: We included out-of-hospital cardiac arrest patients in the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest who suffered arrest between December 2005 and June 2007, presented with a shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia), and had cardiopulmonary resuscitation process data for at least 1 shock (n=815). We used multivariable logistic regression to determine the association between survival and perishock pauses. In an analysis adjusted for Utstein predictors of survival, the odds of survival were significantly lower for patients with preshock pause ≥20 seconds (odds ratio, 0.47; 95% confidence interval, 0.27 to 0.82) and perishock pause ≥40 seconds (odds ratio, 0.54; 95% confidence interval, 0.31 to 0.97) compared with patients with preshock pause <10 seconds and perishock pause <20 seconds. Postshock pause was not independently associated with a significant change in the odds of survival. Log-linear modeling depicted a decrease in survival to hospital discharge of 18% and 14% for every 5-second increase in both preshock and perishock pause interval (up to 40 and 50 seconds, respectively), with no significant association noted with changes in the postshock pause interval. CONCLUSIONS: In patients with cardiac arrest presenting in a shockable rhythm, longer perishock and preshock pauses were independently associated with a decrease in survival to hospital discharge. The impact of preshock pause on survival suggests that refinement of automatic defibrillator software and paramedic education to minimize preshock pause delays may have a significant impact on survival.

Manual chest compression vs use of an automated chest compression device during resuscitation following out-of-hospital cardiac arrest: a randomized trial.

CONTEXT: High-quality cardiopulmonary resuscitation (CPR) may improve both cardiac and brain resuscitation following cardiac arrest. Compared with manual chest compression, an automated load-distributing band (LDB) chest compression device produces greater blood flow to vital organs and may improve resuscitation outcomes. OBJECTIVE: To compare resuscitation outcomes following out-of-hospital cardiac arrest when an automated LDB-CPR device was added to standard emergency medical services (EMS) care with manual CPR. DESIGN, SETTING, AND PATIENTS: Multicenter, randomized trial of patients experiencing out-of-hospital cardiac arrest in the United States and Canada. The a priori primary population was patients with cardiac arrest that was presumed to be of cardiac origin and that had occurred prior to the arrival of EMS personnel. Initial study enrollment varied by site, ranging from late July to mid November 2004; all sites halted study enrollment on March 31, 2005. INTERVENTION: Standard EMS care for cardiac arrest with an LDB-CPR device (n = 554) or manual CPR (n = 517). MAIN OUTCOME MEASURES: The primary end point was survival to 4 hours after the 911 call. Secondary end points were survival to hospital discharge and neurological status among survivors. RESULTS: Following the first planned interim monitoring conducted by an independent data and safety monitoring board, study enrollment was terminated. No difference existed in the primary end point of survival to 4 hours between the manual CPR group and the LDB-CPR group overall (N = 1071; 29.5% vs 28.5%; P = .74) or among the primary study population (n = 767; 24.7% vs 26.4%, respectively; P = .62). However, among the primary population, survival to hospital discharge was 9.9% in the manual CPR group and 5.8% in the LDB-CPR group (P = .06, adjusted for covariates and clustering). A cerebral performance category of 1 or 2 at hospital discharge was recorded in 7.5% of patients in the manual CPR group and in 3.1% of the LDB-CPR group (P = .006). CONCLUSIONS: Use of an automated LDB-CPR device as implemented in this study was associated with worse neurological outcomes and a trend toward worse survival than manual CPR. Device design or implementation strategies require further evaluation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00120965.

Implementation of community-based public access defibrillation in the PAD trial.

BACKGROUND: The Public Access Defibrillation (PAD) Trial was a randomized, controlled trial designed to measure survival to hospital discharge following out-of-hospital cardiac arrest (OOH-CA) in community facilities trained and equipped to provide PAD, compared with community facilities trained to provide cardiopulmonary resuscitation (CPR) without any capacity for defibrillation. OBJECTIVES: To report the implementation of community-based lay responder emergency response programs in 1,260 participating facilities recruited for the PAD Trial in the United States and Canada. METHODS: This was a descriptive study of the characteristics of participating facilities, volunteers, and automated external defibrillator (AED) placements compiled by the PAD Trial, and a qualitative study of factors that facilitated or impeded implementation of emergency lay responder programs using focus groups of PAD Trial site coordinators. RESULTS: The PAD Trial enrolled 1,260 community facilities (14.8% residential), with 20,400 lay volunteers (mean +/- standard deviation = 13.4 +/- 10.7 per facility) trained to respond to OOH-CA. The 598 locations randomized to receive AEDs required 2.7 +/- 1.8 AEDs per facility. Volunteer attrition was high, 36% after two years. Barriers to recruitment and implementation included identification of appropriate "at-risk" facilities, lack of interest or fear of litigation by a facility key decision maker, lack of motivated potential volunteer responders, training and retraining resource requirements, and lack of an existing communication/response infrastructure. CONCLUSIONS: These data indicate that implementation of community-based lay responder programs is feasible in many types of facilities, although these programs require substantial resources and commitment, and many barriers to implementation of effective PAD programs exist.

A potential antitumor peptide therapeutic derived from antineoplastic urinary protein.

New therapies in cancer treatment are focusing on multifaceted approaches to starve and kill tumors utilizing both antiangiogenic and chemotherapeutic compounds. Antineoplastic Urinary Protein (ANUP), a 32k Da protein normally secreted in human urine, has been previously described as a molecule possessing both antiproliferative and antiangiogenic activities. Two synthetic peptides complimentary to the N-terminus of ANUP were designed to test their ability to reproduce these beneficial effects but ultimately to provide a more useful small molecule therapeutic. The results show that the peptides reduced tumor burden by up to 70% in a nude mouse model and demonstrated the ability to inhibit blood vessel formation in a chick chorioallantoic membrane assay (CAM).