Biology subjects

Meurer, W. J.

Publications and source records attributed to Meurer, W. J..

3 recordsLinked to original sources

bioRxiv2025

Comparing Neuroprotective Drug Efficacy in Rodent Neonatal Brain Injury Models

BackgroundA challenge in preclinical neonatal neuroprotection research is implementation of study designs that enable direct comparison of multiple potentially effective drugs. We used adaptive design to test four FDA approved drugs (azithromycin, erythropoietin, caffeine, melatonin) concurrently and determine which best combined safety and efficacy. MethodsSeven-day-old (P7) rats underwent hypoxia-ischemia (HI; right carotid ligation + timed 8% O2 exposure); some experiments included pre-treatment with agents that induced inflammation, and some included post-HI brief moderate hypothermia. Sensorimotor and neuropathology measures were incorporated into a Composite Score that also accounted for deaths. Outcome was initially evaluated at P21 and in confirmatory studies at P35. A pre-specified Bayesian algorithm with futility and efficacy stopping rules was devised to analyze emerging data and adjust subsequent animal allocation among drug groups. ResultsIn all models either azithromycin or erythropoietin (EPO) offered superior neuroprotection at P21 and the other was "runner-up". Caffeine and melatonin conferred modest neuroprotection in pure HI but were quickly eliminated in hypothermia-treated HI. At P35 azithromycin and EPO outcomes were generally similar. ConclusionThese results support azithromycin or erythropoietin as candidate neuroprotective agents and warrant future studies in large animal neonatal cerebral hypoxia-ischemia models. ImpactO_LIOur preclinical comparative efficacy strategy using adaptive design tested four clinically available drugs (azithromycin, caffeine, erythropoietin and melatonin) in multiple preclinical rodent brain injury models and consistently identified differences in efficacy among drugs. C_LIO_LIThree key factors differentiating our approach from existing reports were direct within-litter comparisons, evaluation in multiple injury models and inclusion of both function and neuropathology outcomes. C_LIO_LIEither azithromycin or erythropoietin, even with a 2-hour initiation delay, was the most neuroprotective drug in all models, with the other a close "runner-up". C_LIO_LILess effective drugs were recognized and eliminated early by the prespecified Bayesian algorithm. C_LIO_LIThese results support azithromycin or erythropoietin as candidate neuroprotective agents and support future studies in large animal neonatal cerebral hypoxia-ischemia models. C_LI

neuroscience↗

bioRxiv2016

Optimizing Communication of Emergency Response Adaptive Randomization Clinical Trials to Potential Participants

Introduction: Acute clinical stroke trials are challenging to communicate to patients and families considering participation. Response adaptive randomization (RAR) is a technique that alters the proportion of trial subjects receiving active treatment, based on the outcomes of previous subjects. We aimed to determine how well interactive videos would improve understanding of a simulated acute stroke trial scenario that incorporated a design with RAR. Methods: We performed a cross-sectional study of emergency department patients who were without stroke, altered mental status, or critical illness. Subjects viewed a hypothetical stroke and clinical trial scenario. They were randomized into one of four groups with either an RAR or fixed randomization clinical trial design and with either a standard consent video, or an interactive video. Results: We enrolled 720 participants. In the RAR group with interactive video, 128 out of 149 (85.9%) of the subjects were able to correctly identify the allocation method, compared to the 172 out of 285 (61.6%) in the RAR group with the uninterrupted video for an absolute increase of 25.6% (95% CI 17,33%). The RAR group with interactive video had a higher odds of correct identification of allocation method (O.R. 2.767, 95% CI [1.011,7.570] while controlling for age, sex, ethnicity, education, self-reported understanding of protocol, stroke awareness and agreement to participate in trial. Conclusions: The interactive video increased participant understanding of an RAR design in a simulated stroke scenario. Future research should focus on whether acute trial recruitment can be enhanced using similar techniques.

clinical trials↗

bioRxiv2016

Pre-Hospital Midazolam for Treatment of Status Epilepticus Before and After the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART): A National Observational Cohort Study

BackgroundImplementation of evidence-based treatment for pre-hospital status epilepticus can improve outcomes. We hypothesized that publication of a pivotal pre-hospital clinical trial (RAMPART), demonstrating superiority of intramuscular midazolam over intravenous lorazepam, altered the national utilization rates of midazolam for pre-hospital treatment of status epilepticus, while upholding its safety and efficacy outside the trial setting.\n\nMethods and FindingsThis is a retrospective, observational cohort study of pre-hospital patient encounters throughout the United States in the National Emergency Medicine Services Information System database, from January 2010 through December 2014. We compared the rates and odds of midazolam use as the first-line treatment for status epilepticus among all adult and pediatric benzodiazepine-treated seizures before and after RAMPART publication (February 2012). Secondary analyses were conducted for rates of airway interventions and rescue therapy, as proxies for safety and efficacy of seizure termination. 156,539 benzodiazepine-treated seizures were identified. Midazolam use increased from 26.1% in January 2010 to 61.7% in December 2014 (difference +35.6%, 95% CI, 32.7%-38.4%). The annual rate of midazolam adoption increased significantly from 5.9% per year to 8.9% per year after the publication of RAMPART (difference +3.0% per year; 95%CI, 1.6%-4.5% per year; adjusted OR 1.24; 95%CI, 1.17-1.32). Overall frequency of rescue therapy and airway interventions changed little after the publication of RAMPART.\n\nConclusionsThese data are consistent with effective, ongoing, but incomplete clinical translation of the RAMPART results. The effects of the trial, however, cannot be isolated. The safety and effectiveness of midazolam for treatment of seizures in prehospital clinical practice appear consistent with trial data, which should encourage continuing increases in utilization.

epidemiology↗