Challenges & barriers for real-time integration of drones in emergency cardiac care: Lessons from the United States, Sweden, & Canada.

Importance: Out-of-hospital cardiac arrest (OHCA) is a leading cause of morbidity and mortality in the US and Europe (∼600,000 incident events annually) and around the world (∼3.8 million). With every minute that passes without cardiopulmonary resuscitation or defibrillation, the probability of survival decreases by 10%. Preliminary studies suggest that uncrewed aircraft systems, also known as drones, can deliver automated external defibrillators (AEDs) to OHCA victims faster than ground transport and potentially save lives. Objective: To date, the United States (US), Sweden, and Canada have made significant contributions to the knowledge base regarding AED-equipped drones. The purpose of this Special Communication is to explore the challenges and facilitators impacting the progress of AED-equipped drone integration into emergency medicine research and applications in the US, Sweden, and Canada. We also explore opportunities to propel this innovative and important research forward. Evidence review: In this narrative review, we summarize the AED-drone research to date from the US, Sweden, and Canada, including the first drone-assisted delivery of an AED to an OHCA. Further, we compare the research environment, emergency medical systems, and aviation regulatory environment in each country as they apply to OHCA, AEDs, and drones. Finally, we provide recommendations for advancing research and implementation of AED-drone technology into emergency care. Findings: The rates that drone technologies have been integrated into both research and real-life emergency care in each country varies considerably. Based on current research, there is significant potential in incorporating AED-equipped drones into the chain of survival for OHCA emergency response. Comparing the different environments and systems in each country revealed ways that each can serve as a facilitator or barrier to future AED-drone research. Conclusions and relevance: The US, Sweden, and Canada each offers different challenges and opportunities in this field of research. Together, the international community can learn from one another to optimize integration of AED-equipped drones into emergency systems of care.

Incorporation of Drone Technology Into the Chain of Survival for OHCA: Estimation of Time Needed for Bystander Treatment of OHCA and CPR Performance.

BACKGROUND: Drone-delivered automated external defibrillators (AEDs) hold promises in the treatment of out-of-hospital cardiac arrest. Our objective was to estimate the time needed to perform resuscitation with a drone-delivered AED and to measure cardiopulmonary resuscitation (CPR) quality. METHODS: Mock out-of-hospital cardiac arrest simulations that included a 9-1-1 call, CPR, and drone-delivered AED were conducted. Each simulation was timed and video-recorded. CPR performance metrics were recorded by a Laerdal Resusci Anne Quality Feedback System. Multivariable regression modeling examined factors associated with time from 9-1-1 call to AED shock and CPR quality metrics (compression rate, depth, recoil, and chest compression fraction). Comparisons were made among those with recent CPR training (≤2 years) versus no recent (>2 years) or prior CPR training. RESULTS: We recruited 51 research participants between September 2019 and March 2020. The median age was 34 (Q1-Q3, 23-54) years, 56.9% were female, and 41.2% had recent CPR training. The median time from 9-1-1 call to initiation of CPR was 1:19 (Q1-Q3, 1:06-1:26) minutes. A median time of 1:59 (Q1-Q3, 01:50-02:20) minutes was needed to retrieve a drone-delivered AED and deliver a shock. The median CPR compression rate was 115 (Q1-Q3, 109-124) beats per minute, the correct compression depth percentage was 92% (Q1-Q3, 25-98), and the chest compression fraction was 46.7% (Q1-Q3, 39.9%-50.6%). Recent CPR training was not associated with CPR quality or time from 9-1-1 call to AED shock. Younger age (per 10-year increase; ß, 9.97 [95% CI, 4.63-15.31] s; P<0.001) and prior experience with AED (ß, -30.0 [95% CI, -50.1 to -10.0] s; P=0.004) were associated with more rapid time from 9-1-1 call to AED shock. Prior AED use (ß, 6.71 [95% CI, 1.62-11.79]; P=0.011) was associated with improved chest compression fraction percentage. CONCLUSION: Research participants were able to rapidly retrieve an AED from a drone while largely maintaining CPR quality according to American Heart Association guidelines. Chest compression fraction was lower than expected.

Recombinant yeast screen for new inhibitors of human acetyl-CoA carboxylase 2 identifies potential drugs to treat obesity.

Acetyl-CoA carboxylase (ACC) is a key enzyme of fatty acid metabolism with multiple isozymes often expressed in different eukaryotic cellular compartments. ACC-made malonyl-CoA serves as a precursor for fatty acids; it also regulates fatty acid oxidation and feeding behavior in animals. ACC provides an important target for new drugs to treat human diseases. We have developed an inexpensive nonradioactive high-throughput screening system to identify new ACC inhibitors. The screen uses yeast gene-replacement strains depending for growth on cloned human ACC1 and ACC2. In "proof of concept" experiments, growth of such strains was inhibited by compounds known to target human ACCs. The screen is sensitive and robust. Medium-size chemical libraries yielded new specific inhibitors of human ACC2. The target of the best of these inhibitors was confirmed with in vitro enzymatic assays. This compound is a new drug chemotype inhibiting human ACC2 with 2.8 muM IC(50) and having no effect on human ACC1 at 100 muM.

Orthopaedic Sports Medicine Podcasts Should Tailor Characteristics Such as Episode Length and Social Media Utilization for Best Audience Engagement.

Purpose: To describe the growth and characteristics of active orthopaedic sports medicine podcasts. Methods: Three common podcasting platforms (Apple, Google, and Spotify) were queried July 24, 2021 using the search term "sports medicine." For each unique active podcast hosted by an orthopaedic surgeon, data were collected on year of the first episode, number of episodes, frequency of episodes, types of guests, topics discussed, episode length, and social media presence. Descriptive characteristics were then calculated. Results: 15 podcasts met inclusion criteria. Seven (46.7%) of these podcasts were started within 12 months of July 24, 2021. The most common episode release schedule was weekly, and podcast lengths averaged 21 minutes, 47 seconds (SD 17:17, range: 11:02-1:49:13). All podcasts featured guests, most often from a variety of sports medicine backgrounds. Social media platforms were commonly used by podcast hosts, with social media account follower numbers as high as over 100,000, and consistent engagement across three major social media platforms for most podcasts. Conclusions: This study found that episodes are typically released weekly and average 21 minutes, 47 seconds long, with most covering a wide array of topics in sports medicine. The Facebook accounts of these podcasts displayed higher numbers of followers compared to other social media platforms; however, Instagram was superior for engagement. Clinical Relevance: Orthopaedic sports medicine podcasts have an increasing presence and can be used to increase trainee engagement and public exposure via tailoring of podcast episode lengths and selection of social media platforms with high audience interaction.

Acute Quadriceps Tendon Rupture: Presentation, Diagnosis, and Management.

¼: The incidence of quadriceps tendon rupture is estimated to be 1.37 cases per 100,000 people/year, with a predilection for these injuries in patients who are ≥40 years of age. ¼: Quadriceps tendon ruptures are more likely to occur in the presence of preexisting comorbidities such as rheumatoid arthritis, systemic lupus erythematosus, gout, chronic kidney disease, secondary hyperparathyroidism, diabetes mellitus, and peripheral vascular disease. The most common mechanism of injury is a simple fall. ¼: Magnetic resonance imaging is the gold-standard test for diagnosing quadriceps tendon ruptures, with a reported sensitivity, specificity, and positive predictive value of 1.0. ¼: Complete tears require prompt surgical intervention; the most common technique is transosseous sutures passed through longitudinal patellar drill holes. Suture anchors have been proposed as an alternative method; they have shown superior biomechanical results in cadaveric models. ¼: Early functional mobilization with full weight-bearing and progressive range-of-motion exercises is recommended for rehabilitation following injury.

Impact of Using Drones in Emergency Medicine: What Does the Future Hold?

The use of unmanned aerial vehicles or "drones" has expanded in the last decade, as their technology has become more sophisticated, and costs have decreased. They are now used routinely in farming, environmental surveillance, public safety, commercial product delivery, recreation, and other applications. Health-related applications are only recently becoming more widely explored and accepted. The use of drone technology in emergency medicine is especially promising given the need for a rapid response to enhance patient outcomes. The purpose of this paper is to describe some of the main current and expanding applications of drone technology in emergency medicine and to describe challenges and future opportunities. Current applications being studied include delivery of defibrillators in response to out-of-hospital cardiac arrest, blood and blood products in response to trauma, and rescue medications. Drones are also being studied and actively used in emergency response to search and rescue operations as well as disaster and mass casualty events. Current challenges to expanding their use in emergency medicine and emergency medical system (EMS) include regulation, safety, flying conditions, concerns about privacy, consent, and confidentiality, and details surrounding the development, operation, and maintenance of a medical drone network. Future research is needed to better understand end user perceptions and acceptance. Continued technical advances are needed to increase payload capacities, increase flying distances, and integrate drone networks into existing 9-1-1 and EMS systems. Drones are a promising technology for improving patient survival, outcomes, and quality of life, particularly for those in areas that are remote or that lack funds or infrastructure. Their cost savings compared with ground transportation alone, speed, and convenience make them particularly applicable in the field of emergency medicine. Research to date suggests that use of drones in emergency medicine is feasible, will be accepted by the public, is cost-effective, and has broad application.

Delivery of Automated External Defibrillators via Drones in Simulated Cardiac Arrest: Users' Experiences and the Human-Drone Interaction.

BACKGROUND: Survival after out-of-hospital cardiac arrest (OHCA) in the United States is approximately 10%. Automatic external defibrillators (AEDs) are effective when applied early, yet public access AEDs are used in <2% of OHCAs. AEDs are often challenging for bystanders to locate and are rarely available in homes, where 70% of OHCAs occur. Drones have the potential to deliver AEDs to bystanders efficiently; however, little is known about the human-drone interface in AED delivery. OBJECTIVES: To describe user experiences with AED-equipped drones in a feasibility study of simulated OHCA in a community setting. METHODS: We simulated an OHCA in a series of trials with age-group/sex-matched participant pairs, with one participant randomized to search for a public access AED and the other to call a mock 9-1-1 telephone number that initiated the dispatch of an AED-equipped drone. We investigated user experience of 17 of the 35 drone recipient participants via semi-structured qualitative interviews and analyzed audio-recordings for key aspects of user experience. RESULTS: Drone recipient participants reported largely positive experiences, highlighting that this delivery method enabled them to stay with the victim and continue cardiopulmonary resuscitation. Concerns were few but included drone arrival timing and direction as well as bystander safety. Participants provided suggestions for improvements in the AED-equipped drone design and delivery procedures. CONCLUSION: Participants reported positive experiences interacting with an AED-equipped drone for a simulated OHCA in a community setting. Early findings suggest a role for drone-delivered AEDs to improve bystander AED use and improve outcomes for OHCA victims.

Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas.

Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs) with mutated histone H3 K27M (H3-K27M)1-5 are aggressive and universally fatal pediatric brain cancers 6 . Chimeric antigen receptor (CAR)-expressing T cells have mediated impressive clinical activity in B cell malignancies7-10, and recent results suggest benefit in central nervous system malignancies11-13. Here, we report that patient-derived H3-K27M-mutant glioma cell cultures exhibit uniform, high expression of the disialoganglioside GD2. Anti-GD2 CAR T cells incorporating a 4-1BBz costimulatory domain 14 demonstrated robust antigen-dependent cytokine generation and killing of DMG cells in vitro. In five independent patient-derived H3-K27M+ DMG orthotopic xenograft models, systemic administration of GD2-targeted CAR T cells cleared engrafted tumors except for a small number of residual GD2lo glioma cells. To date, GD2-targeted CAR T cells have been well tolerated in clinical trials15-17. Although GD2-targeted CAR T cell administration was tolerated in the majority of mice bearing orthotopic xenografts, peritumoral neuroinflammation during the acute phase of antitumor activity resulted in hydrocephalus that was lethal in a fraction of animals. Given the precarious neuroanatomical location of midline gliomas, careful monitoring and aggressive neurointensive care management will be required for human translation. With a cautious multidisciplinary clinical approach, GD2-targeted CAR T cell therapy for H3-K27M+ diffuse gliomas of pons, thalamus and spinal cord could prove transformative for these lethal childhood cancers.