Historic clinical trial external control arm provides actionable GEN-1 efficacy estimate before a randomized trial

PURPOSE: To inform continued development of the novel immune agent GEN-1, we compared ovarian cancer patients\u27 end points from a neoadjuvant single-arm phase IB study with those of similar historic clinical trial (HCT) patients who received standard neoadjuvant chemotherapy. METHODS: Applying OVATION-1 trial (ClinicalTrials.gov identifier: NCT02480374) inclusion and exclusion criteria to Medidata HCT data, we identified historical trial patients for comparison. Integrating patient-level Medidata historic trial data (N = 41) from distinct neoadjuvant ovarian phase I-III trials with patient-level OVATION-1 data (N = 18), we selected Medidata patients with similar baseline characteristics as OVATION-1 patients using propensity score methods to create an external control arm (ECA). RESULTS: Fifteen OVATION-1 patients (15 of 18, 83%) were matched to 15 (37%, 15 of 41) Medidata historical trial control patients. Matching attenuated preexisting differences in attributes between the groups. The median progression-free survival time was not reached by the OVATION-1 group and was 15.8 months (interquartile range, 11.40 months to nonestimable) for the ECA. The hazard of progression was 0.53 (95% CI, 0.16 to 1.73), favoring GEN-1 patients. Compared with ECA patients, OVATION-1 patients had more nausea, fatigue, chills, and infusion-related reactions. CONCLUSION: Comparing results of a single-arm early-phase trial to those of a rigorously matched HCT ECA yielded insights regarding comparative efficacy prior to a randomized controlled trial. The effect size estimate itself informed both the decision to continue development and the randomized phase II trial (ClinicalTrials.gov identifier: NCT03393884) sample size. The work illustrates the potential of HCT data to inform drug development

The impact of the COVID-19 pandemic and governor mandated stay at home order on emergency department super utilizers

BACKGROUND: Despite the trend of rising Emergency Department (ED) visits over the past decade, researchers have observed drastic declines in number of ED visits due to the COVID-19 pandemic. The purpose of the current study was to examine the impact of the COVID-19 pandemic and governor mandated Stay at Home Order on ED super utilizers. METHODS: This was a retrospective chart review of patients presenting to the 12 emergency departments of the Franciscan Mission of Our Lady Hospital System in Louisiana between January 1, 2018 and December 31, 2020. Patients who were 18 years of age or older and had four ED visits within a one-year period (2018, 2019, or 2020) were classified as super-utilizers. We examined number and category of visits for the baseline period (January 2018 - March 2020), the governor\u27s Stay at Home Order, and the subsequent Reopening Phases through December 31, 2020. RESULTS: The number of visits by super utilizers decreased by over 16% when the Stay at Home Order was issued. The average number of visits per week rose from 1010.63 during the Stay at Home Order to 1198.09 after the Stay at Home Order was lifted, but they did not return to Pre-COVID levels of approximately 1400 visits per week in 2018 and 2019. When categories of visits were examined, this trend was found for emergent visits (p \u3c 0.001) and visits related to injuries (p \u3c 0.001). Non-emergent visits declined during the Stay at Home Order compared to the baseline period (p \u3c 0.001), and did not increase significantly during reopening compared to the Stay at Home Order (p = 0.87). There were no changes in number of visits for psychiatric purposes, alcohol use, or drug use during the pandemic. CONCLUSIONS: Significant declines in emergent visits raise concerns that individuals who needed ED treatment did not seek it due to COVID-19. However, the finding that super utilizers with non-emergent visits continued to visit the ED less after the Stay at Home Order was lifted raises questions for future research that may inform policy and interventions for inappropriate ED use

Residents\u27 Preferences and Performance of Three Techniques for Ultrasound-Guided Central Venous Cannulation After Simulation Training

BACKGROUND: Obtaining central venous cannulation of the internal jugular vein is an important skill for physicians to master. To our knowledge, no studies to date have examined residents\u27 preferences or the safety of the oblique approach compared to other approaches. This study compared medical residents\u27 preferences for and performance of ultrasound-guided central venous access using the transverse, longitudinal, and oblique approaches. METHODS: Emergency medicine and internal medicine residents (n = 72) at an urban community hospital participated in a central venous access course. To assess the residents\u27 preferences, residents were asked to rank the transverse, longitudinal, and oblique approaches as first, second, or third. In addition to preference, skin-to-vein time, carotid artery puncture, and successful completion on the first attempt during a final skills analysis were measured. RESULTS: During the final skills analysis, the majority (87.5%) of residents preferred the transverse approach. The oblique approach had a significantly larger proportion of failures of technique than the transverse approach ( 0.02). No significant differences in successful cannulation on the first attempt, skin-to-vein time, or carotid artery puncture among the 3 approaches were found during the final skills assessment. CONCLUSION: The majority of residents preferred the transverse approach to the longitudinal and oblique approaches. Although no significant differences among the 3 approaches were found in performance measures, more failures of technique occurred with the oblique approach. This study suggests that novices may require in-depth training and supervision to become proficient with the oblique approach

Simulation-Based Education Enhances Patient Safety Behaviors During Central Venous Catheter Placement

OBJECTIVE: We describe the effect of simulation-based education on residents\u27 adherence to protocols for and performance of central venous access. METHODS: Internal medicine and emergency medicine residents underwent a central venous access course that included a lecture, video presentation, readings, and simulation demonstrations presented by faculty. Baseline data were collected before the course was initiated. After a skills session where they rehearsed their ultrasound-guided central venous access skills, residents were evaluated using a procedural checklist and written knowledge exam. Residents also completed questionnaires regarding confidence in performing ultrasound-guided central venous access and opinions about the training course. RESULTS: Residents demonstrated significant improvement on the written knowledge exam (P \u3c 0.0001) and Standard Protocol Checklist (P \u3c 0.0001) after the training course. Training improved a number of patient safety elements, including adherence to sterile technique, transparent dressing, discarding sharps, and ordering postprocedure x-rays. However, a number of residents failed to wash their hands, prepare with chlorhexidine, drape the patient using a sterile technique, anesthetize the site, and perform a preprocedure time-out. Significant improvement in procedural skills was also noted for reduction in skin-to-vein time (P \u3c 0.003) as well as a reduction in number of residents who punctured the carotid artery (P \u3c 0.02). CONCLUSIONS: Simulation-based education significantly improved residents\u27 knowledge and procedural skills along with their confidence. Adherence to the protocol also improved. This study illustrates that simulation-based education can improve patient safety through training and protocols