RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): A double‐blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86836/1/j.1528-1167.2011.03235.x.pd

Balancing Ethical Goals in Challenging Individual Participant Scenarios Occurring in a Trial Conducted with Exception from Informed Consent

In 1996, federal regulations were put into effect that allowed enrollment of critically ill or injured patients into Food and Drug Administration (FDA)‐regulated clinical trials using an exception from informed consent (EFIC) under narrowly prescribed research circumstances. Despite the low likelihood that a legally authorized representative (LAR) would be present within the interventional time frame, the EFIC regulations require the availability of an informed consent process, to be applied if an LAR is present and able to provide prospective consent for patient enrollment into the trial. The purpose of this article is to describe a series of unanticipated consent‐related questions arising when a potential surrogate decision‐maker appeared to be available at the time of patient enrollment into a trial proceeding under EFIC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110828/1/acem12602.pd

Consulting Communities When Patients Cannot Consent: A Multi-Center Study of Community Consultation for Research in Emergency Settings

OBJECTIVE: To assess the range of responses to community consultation efforts conducted within a large network and the impact of different consultation methods on acceptance of exception from informed consent (EFIC) research and understanding of the proposed study. DESIGN: A cognitively pre-tested survey instrument was administered to 2,612 community consultation participants at 12 US centers participating in a multi-center trial of treatment for acute traumatic brain injury (TBI). SETTING: Survey nested within community consultation for a Phase III, randomized controlled trial of treatment for acute TBI conducted within a multi-center trial network and using EFIC. SUBJECTS: Adult participants in community consultation events. INTERVENTIONS: Community consultation efforts at participating sites. MEASUREMENTS AND MAIN RESULTS: Acceptance of EFIC in general, attitude toward personal EFIC enrollment, and understanding of the study content were assessed. 54% of participants agreed EFIC was acceptable in the proposed study; 71% were accepting of personal EFIC enrollment. Participants in interactive versus non-interactive community consultation events were more accepting of EFIC in general (63% vs. 49%) and personal EFIC inclusion (77% vs. 67%). Interactive community consultation participants had high-level recall of study content significantly more often than non-interactive consultation participants (77% vs. 67%). Participants of interactive consultation were more likely to recall possible study benefits (61% vs. 45%) but less likely to recall potential risks (56% vs. 69%). CONCLUSIONS: Interactive community consultation methods were associated with increased acceptance of EFIC and greater overall recall of study information but lower recall of risks. There was also significant variability in EFIC acceptance among different interactive consultation events. These findings have important implications for IRBs and investigators conducting EFIC research and for community engagement efforts in research more generally

Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the pediatric population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110729/1/epi12905.pd

Newtonian Cosmology in Lagrangian Formulation: Foundations and Perturbation Theory

The ``Newtonian'' theory of spatially unbounded, self--gravitating, pressureless continua in Lagrangian form is reconsidered. Following a review of the pertinent kinematics, we present alternative formulations of the Lagrangian evolution equations and establish conditions for the equivalence of the Lagrangian and Eulerian representations. We then distinguish open models based on Euclidean space $\R^3$ from closed models based (without loss of generality) on a flat torus \T^3. Using a simple averaging method we show that the spatially averaged variables of an inhomogeneous toroidal model form a spatially homogeneous ``background'' model and that the averages of open models, if they exist at all, in general do not obey the dynamical laws of homogeneous models. We then specialize to those inhomogeneous toroidal models whose (unique) backgrounds have a Hubble flow, and derive Lagrangian evolution equations which govern the (conformally rescaled) displacement of the inhomogeneous flow with respect to its homogeneous background. Finally, we set up an iteration scheme and prove that the resulting equations have unique solutions at any order for given initial data, while for open models there exist infinitely many different solutions for given data.Comment: submitted to G.R.G., TeX 30 pages; AEI preprint 01

Phenomenology of the Lense-Thirring effect in the Solar System

Recent years have seen increasing efforts to directly measure some aspects of the general relativistic gravitomagnetic interaction in several astronomical scenarios in the solar system. After briefly overviewing the concept of gravitomagnetism from a theoretical point of view, we review the performed or proposed attempts to detect the Lense-Thirring effect affecting the orbital motions of natural and artificial bodies in the gravitational fields of the Sun, Earth, Mars and Jupiter. In particular, we will focus on the evaluation of the impact of several sources of systematic uncertainties of dynamical origin to realistically elucidate the present and future perspectives in directly measuring such an elusive relativistic effect.Comment: LaTex, 51 pages, 14 figures, 22 tables. Invited review, to appear in Astrophysics and Space Science (ApSS). Some uncited references in the text now correctly quoted. One reference added. A footnote adde

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective.

Benzodiazepines represent the first-line treatment for the acute management of epileptic seizures and status epilepticus. The emergency use of benzodiazepines must be timely, and because most seizures occur outside of the hospital environment, there is a significant need for delivery methods that are easy for nonclinical caregivers to use and administer quickly and safely. In addition, the ideal route of administration should be reliable in terms of absorption. Rectal diazepam is the only licensed formulation in the USA, whereas rectal diazepam and buccal midazolam are currently licensed in the EU. However, the sometimes unpredictable absorption with rectal and buccal administration means they are not ideal routes. Several alternative routes are currently being explored. This is a narrative review of data about delivery methods for benzodiazepines alternative to the intravenous and oral routes for the acute treatment of seizures. Unconventional delivery options such as direct delivery to the central nervous system or inhalers are reported. Data show that intranasal diazepam or midazolam and the intramuscular auto-injector for midazolam are as effective as rectal or intravenous diazepam. Head-to-head comparisons with buccal midazolam are urgently needed. In addition, the majority of trials focused on children and adolescents, and further trials in adults are warranted

Dark energy cosmology with generalized linear equation of state

Dark energy with the usually used equation of state $p=w\rho$, where $w=const<0$ is hydrodynamically unstable. To overcome this drawback we consider the cosmology of a perfect fluid with a linear equation of state of a more general form $p=\alpha(\rho-\rho_0)$, where the constants $\alpha$ and $\rho_0$ are free parameters. This non-homogeneous linear equation of state provides the description of both hydrodynamically stable ($\alpha>0$) and unstable ($\alpha<0$) fluids. In particular, the considered cosmological model describes the hydrodynamically stable dark (and phantom) energy. The possible types of cosmological scenarios in this model are determined and classified in terms of attractors and unstable points by the using of phase trajectories analysis. For the dark energy case there are possible some distinctive types of cosmological scenarios: (i) the universe with the de Sitter attractor at late times, (ii) the bouncing universe, (iii) the universe with the Big Rip and with the anti-Big Rip. In the framework of a linear equation of state the universe filled with an phantom energy, $w<-1$, may have either the de Sitter attractor or the Big Rip.Comment: 12 pages, 11 figures, typos corrected, references adde

Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE).

To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432