Improved mortality analysis in early-phase dose-ranging clinical trials for emergency medical diseases using Bayesian time-to-event models with active comparators.

Emergency medical diseases (EMDs) are the leading cause of death worldwide. A time-to-death analysis is needed to accurately identify the risks and describe the pattern of an EMD because the mortality rate can peak early and then decline. Dose-ranging Phase II clinical trials are essential for developing new therapies for EMDs.

Selection of a statistical analysis method for the Glasgow Outcome Scale-Extended endpoint for estimating the probability of favorable outcome in future severe TBI clinical trials.

The Glasgow outcome scale-extended (GOS-E), an ordinal scale measure, is often selected as the endpoint for clinical trials of traumatic brain injury (TBI). Traditionally, GOS-E is analyzed as a fixed dichotomy with favorable outcome defined as GOS-E ≥ 5 and unfavorable outcome as GOS-E < 5. More recent studies have defined favorable vs unfavorable outcome utilizing a sliding dichotomy of the GOS-E that defines a favorable outcome as better than a subject's predicted prognosis at baseline.

Functional Magnetic Resonance Imaging and Oculomotor Dysfunction in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is a significant cause of disability, especially when symptoms become chronic. This chronicity is often linked to oculomotor dysfunction (OMD). To our knowledge, this is the first prospective study to localize aberrations in brain function between mTBI cohorts, by comparing patients with mTBI with OMD with an mTBI control group without OMD, using task and resting-state functional magnetic resonance imaging (fMRI).

Hyperbaric Oxygen Therapy in the Treatment of Acute Severe Traumatic Brain Injury: A Systematic Review.

There has been no major advancement in a quarter of a century for the treatment of acute severe traumatic brain injury (TBI). This review summarizes 40 years of clinical and pre-clinical research on the treatment of acute TBI with hyperbaric oxygen therapy (HBO) in the context of an impending National Institute of Neurologic Disorders and Stroke-funded, multi-center, randomized, adaptive Phase II clinical trial -the Hyperbaric Oxygen Brain Injury Treatment (HOBIT) trial. Thirty studies (eight clinical and 22 pre-clinical) that administered HBO within 30 days of a TBI were identified from PubMed searches.

A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury.

Object: Preclinical and clinical investigations indicate that the positive effect of hyperbaric oxygen (HBO2) for severe traumatic brain injury (TBI) occurs after rather than during treatment. The brain appears better able to use baseline O2 levels following HBO2 treatments. In this study, the authors evaluate the combination of HBO2 and normobaric hyperoxia (NBH) as a single treatment.

Hypertonic saline reduces intracranial hypertension in the presence of high serum and cerebrospinal fluid osmolalities.

Background: Osmotherapy has been the cornerstone in the management of patients with elevated intracranial pressure (ICP) following traumatic brain injury (TBI). Several studies have demonstrated that hypertonic saline (HTS) is a safe and effective osmotherapy agent. This study evaluated the effectiveness of HTS in reducing intracranial hypertension in the presence of a wide range of serum and cerebrospinal fluid (CSF) osmolalities.

Hypertonic saline and its effect on intracranial pressure, cerebral perfusion pressure, and brain tissue oxygen.

Objective: Hypertonic saline is emerging as a potentially effective single osmotic agent for control of acute elevations in intracranial pressure (ICP) caused by severe traumatic brain injury. This study examines its effect on ICP, cerebral perfusion pressure (CPP), and brain tissue oxygen tension (PbtO2).

Methods: Twenty-five consecutive patients with severe traumatic brain injury who were treated with 23.

A prospective, randomized clinical trial to compare the effect of hyperbaric to normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen toxicity in severe traumatic brain injury.

Object: Oxygen delivered in supraphysiological amounts is currently under investigation as a therapy for severe traumatic brain injury (TBI). Hyperoxia can be delivered to the brain under normobaric as well as hyperbaric conditions. In this study the authors directly compare hyperbaric oxygen (HBO2) and normobaric hyperoxia (NBH) treatment effects.

Hyperbaric oxygen in traumatic brain injury.

Objectives: This critical literature review examines historical and current investigations on the efficacy and mechanisms of hyperbaric oxygen (HBO) treatment in traumatic brain injury (TBI). Potential safety risks and oxygen toxicity, as well as HBO's future potential, are also discussed.

Methods: Directed literature review.