The PulsePoint Respond mobile device application to crowdsource basic life support for patients with out-of-hospital cardiac arrest: Challenges for optimal implementation.

BACKGROUND: PulsePoint Respond is a novel mobile device application that notifies citizens within 400 m (∼ 1/4 mile) of a suspected cardiac arrest to facilitate resuscitation. Our objectives were to (1) characterize users, and (2) understand their behavior after being sent a notification. We sought to identify challenges for optimal implementation of PulsePoint-mediated bystander resuscitation. METHODS: PulsePoint Respond users who sent a notification between 04/07/2012 and 06/16/2014 were invited to participate in an online survey. At the beginning of our study, PulsePoint Respond was active in more than 600 US communities. RESULTS: There were 1274 completed surveys (response rate 1448/6777, 21.4%). Respondents were firefighters (28%), paramedics (18%), emergency medical technicians (9%), nurses (7%), MDs (1%), other health care professionals (12%), and non-health care professionals (42%). Of those who received a PulsePoint notification, only 23% (189/813) responded to the PulsePoint notification. Of those who responded, 28% (52/187) did not arrive on scene. Of those who did arrive on scene, only 32% (44/135) found a person unconscious and not breathing normally. Of those who arrived on scene prior to emergency medical services and found a cardiac arrest victim, 79% (11/14) performed bystander cardiopulmonary resuscitation. CONCLUSIONS: Challenges for optimal implementation of PulsePoint Respond include technical aspects of the notifications (audio volume, precision of location information), excessive activation radii, insufficient user density in the community, and suboptimal cardiac arrest notification specificity. PulsePoint Respond has the potential to improve the community response to cardiac arrest, with 80% of responders attempting basic life support when they found a cardiac arrest victim prior to EMS.

Immunogenic HSV-mediated oncolysis shapes the antitumor immune response and contributes to therapeutic efficacy.

Within the oncolytic virus field, the extent of virus replication that is essential for immune stimulation to control tumor growth remains unresolved. Using infected cell protein 0 (ICP0)-defective oncolytic Herpes simplex virus type 1 (HSV-1) and HSV-2 viruses (dICP0 and dNLS) that show differences in their in vitro replication and cytotoxicity, we investigated the inherent features of oncolytic HSV viruses that are required for potent antitumor activity. In vitro, the HSV-2 vectors showed rapid cytotoxicity despite lower viral burst sizes compared to HSV-1 vectors. In vivo, although both of the dICP0 vectors initially replicated to a similar level, HSV-1 dICP0 was rapidly cleared from the tumors. In spite of this rapid clearance, HSV-1 dICP0 treatment conferred significant survival benefit. HSV-1 dICP0-treated tumors showed significantly higher levels of danger-associated molecular patterns that correlated with higher numbers of antigen-presenting cells within the tumor and increased antigen-specific CD8+ T-cell levels in the peripheral blood. This study suggests that, at least in the context of oncolytic HSV, the initial stages of immunogenic virus replication leading to activation of antitumor immunity are more important than persistence of a replicating virus within the tumor. This knowledge provides important insight for the design of therapeutically successful oncolytic viruses.