Lisa H. Merck

Very Early Administration of Progesterone for Acute Traumatic Brain Injury

BACKGROUND Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. METHODS We conducted a double-blind, multicenter clinical trial in which patients with severe, moderate-to-severe, or moderate acute TBI (Glasgow Coma Scale score of 4 to 12, on a scale from 3 to 15, with lower scores indicating a lower level of consciousness) were randomly assigned to intravenous progesterone or placebo, with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours. Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome, as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury. Secondary outcomes included mortality and the Disability Rating Scale score. RESULTS A total of 882 of the planned sample of 1140 patients underwent randomization before the trial was stopped for futility with respect to the primary outcome. The study groups were similar with regard to baseline characteristics; the median age of the patients was 35 years, 73.7% were men, 15.2% were black, and the mean Injury Severity Score was 24.4 (on a scale from 0 to 75, with higher scores indicating greater severity). The most frequent mechanism of injury was a motor vehicle accident. There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P=0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). There were no significant differences in the other prespecified safety outcomes. CONCLUSIONS This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI. (Funded by the National Institute of Neurological Disorders and Stroke and others; PROTECT III ClinicalTrials.gov number, NCT00822900.).

Informed consent for computed tomography

Computed tomography (CT) accounts for a large quantity of patient exposure to ionizing radiation. Ionizing radiation is listed by the World Health Organization as a carcinogen [1,2]. Over the last thirty years in the United States, the rate of CT use in medical imaging has increased from 2.3 million to more than 60 million scans/y [3-5]. Between 2000 and 2006, Broder [6] reported a 4-fold increase in utilization within US emergency departments (EDs). For example, abdominal CT delivers a dose of 3.5 to 25 mSv, or 1 to 8 years of background radiation [1,2,6-25]. Ionizing radiation from this routine test is conservatively estimated to induce cancer in 1 per 5000-10 000 patients [8,10,26-28]. Increased utilization of CT leads to higher patient exposure to radiation and subsequent risk of cancer development. In 1957, Paul G. Gebhard first articulated the idea of informed consent, the duty of the physician to disclose all risks and benefits of a medical procedure to the patient. This is routinely practiced before surgical procedures and even the use of intravenous medications, such as CT contrast. However, it is not current standard of care to obtain informed consent for CT imaging [29]. This may be due to the fact that radiation from CT causes no immediately tangible effect or visible scar. However, like surgery, radiation leaves a biologic mark on the patient. Development of cancer may not occur until decades later. To explain this risk to patients, our team designed a 1-page Informed Consent for Computerized Tomography form. The consent defines the risks, benefits, and alternatives to CT imaging. We then conducted a survey to study the effect of informed consent on patient understanding of medical radiation. The consent is written at an eighth-grade reading level and describes radiation dose from chest x-ray, abdominal CT, and background radiation [7,10,26-28]. The consent was reviewed and approved by hospital legal, medical records, and quality/ safety teams. As a quality initiative, the study was exempted from evaluation by the institutional review board. To quantify the educational value of the consent, a 5-question survey was administered to evaluate patient understanding of medical radiation. Patients who presented to the ED waiting room during study times were asked to complete the survey, regardless of chief complaint. Critically ill patients or those who demonstrated language barriers were excluded. Group I (50 patients) completed the survey in May 2010. Fifty additional patients (group II) participated in June 2010. Group II reviewed the consent and then completed the survey. Patients were also asked if they prefer to know the risks and benefits of CT. Differences between groups were measured with Fisher exact tests using OpenEpi (Open

Prehospital Intubation is Associated with Favorable Outcomes and Lower Mortality in ProTECT III

Abstract Objective: Traumatic brain injury (TBI) causes more than 2.5 million emergency department visits, hospitalizations, or deaths annually. Prehospital endotracheal intubation has been associated with poor outcomes in patients with TBI in several retrospective observational studies. We evaluated the relationship between prehospital intubation, functional outcomes, and mortality using high quality data on clinical practice collected prospectively during a randomized multicenter clinical trial. Methods: ProTECT III was a multicenter randomized, double-blind, placebo-controlled trial of early administration of progesterone in 882 patients with acute moderate to severe nonpenetrating TBI. Patients were excluded if they had an index GCS of 3 and nonreactive pupils, those with withdrawal of life support on arrival, and if they had documented prolonged hypotension and/or hypoxia. Prehospital intubation was performed as per local clinical protocol in each participating EMS system. Models for favorable outcome and mortality included prehospital intubation, method of transport, index GCS, age, race, and ethnicity as independent variables. Significance was set at α = 0.05. Favorable outcome was defined by a stratified dichotomy of the GOS-E scores in which the definition of favorable outcome depended on the severity of the initial injury. Results: Favorable outcome was more frequent in the 349 subjects with prehospital intubation (57.3%) than in the other 533 patients (46.0%, p = 0.003). Mortality was also lower in the prehospital intubation group (13.8% v. 19.5%, p = 0.03). Logistic regression analysis of prehospital intubation and mortality, adjusted for index GCS, showed that odds of dying for those with prehospital intubation were 47% lower than for those that were not intubated (OR = 0.53, 95% CI = 0.36–0.78). 279 patients with prehospital intubation were transported by air. Modeling transport method and mortality, adjusted for index GCS, showed increased odds of dying in those transported by ground compared to those transported by air (OR = 2.10, 95% CI = 1.40–3.15). Decreased odds of dying trended among those with prehospital intubation adjusted for transport method, index GCS score at randomization, age, and race/ethnicity (OR = 0.70, 95% CI = 0.37–1.31). Conclusions: In this study that excluded moribund patients, prehospital intubation was performed primarily in patients transported by air. Prehospital intubation and air medical transport together were associated with favorable outcomes and lower mortality. Prehospital intubation was not associated with increased morbidity or mortality regardless of transport method or severity of injury.

Written Informed Consent for Computed Tomography of the Abdomen/Pelvis is Associated with Decreased CT Utilization in Low-Risk Emergency Department Patients

Introduction The increasing rate of patient exposure to radiation from computerized tomography (CT) raises questions about appropriateness of utilization. There is no current standard to employ informed consent for CT (ICCT). Our study assessed the relationship between informed consent and CT utilization in emergency department (ED) patients. Methods An observational multiphase before-after cohort study was completed from 4/2010–5/2011. We assessed CT utilization before and after (Time I/Time II) the implementation of an informed consent protocol. Adult patients were included if they presented with symptoms of abdominal/pelvic pathology or completed ED CT. We excluded patients with pregnancy, trauma, or altered mental status. Data on history, exam, diagnostics, and disposition were collected via standard abstraction tool. We generated a multivariate logistic model via stepwise regression, to assess CT utilization across risk groups. Logistic models, stratified by risk, were generated to include study phase and a propensity score that controlled for potential confounders of CT utilization. Results 7,684 patients met inclusion criteria. In PHASE 2, there was a 24% (95% CI [10–36%]) reduction in CT utilization in the low-risk patient group (p<0.002). ICCT did not affect CT utilization in the high-risk group (p=0.16). In low-risk patients, the propensity score was significant (p<0.001). There were no adverse events reported during the study period. Conclusion The implementation of ICCT was associated with reduced CT utilization in low-risk ED patients. ICCT has the potential to increase informed, shared decision making with patients, as well as to reduce the risks and cost associated with CT.

Reply to: Prehospital Intubation: Further Confounders in Trial Results

We are grateful for Dr. Iqbal et al.’s letter and are encouraged that there are readers who are thoughtfully considering the implications of our work. We are also grateful to have been given an opportunity to reply to their excellent comments and questions. We appreciate their statement that the survival and outcomes for patients with traumatic brain injury (TBI) associated with prehospital intubation and air medical transport is interesting and potentially very important for improving emergency services in the field. We also acknowledge their caveat that our findings raise concerns regarding how the factors examined may have modified the outcomes of the ProTECT III trial. We agree that effect modification is a factor in our study. Effect modification occurs when the magnitude of the effect of the primary exposure on an outcome (i.e., the association) differs depending on the level of a third variable. In our study, we had 2 primary outcomes (favorable outcome and mortality). As we considered the primary exposure of prehospital intubation, we indeed did see the difference of the magnitude of effect depending on air transport with intubation or ground transport. Interestingly, the randomization reasonably separated these groups into the progesterone intervention and control groups, reducing the risk of

Society for Academic Emergency Medicine Statement on Plagiarism

The integrity of the research enterprise is of the utmost importance for the advancement of safe and effective medical practice for patients and for maintaining the public trust in health care. Academic societies and editors of journals are key participants in guarding scientific integrity. Avoiding and preventing plagiarism helps to preserve the scientific integrity of professional presentations and publications. The Society for Academic Emergency Medicine (SAEM) Ethics Committee discusses current issues in scientific publishing integrity and provides a guideline to avoid plagiarism in SAEM presentations and publications.

Is there a Neurologist in the House? A Summary of the Current State of Neurovascular Rotations for Emergency Medicine Residents

Neurovascular and neurocritical care emergencies constitute a leading cause of morbidity/mortality. There has been great evolution in this field, including but not limited to extended time‐window therapeutic interventions for acute ischemic stroke. The intent of this article is to evaluate the goals and future direction of clinical rotations in neurovascular and neurocritical care for emergency medicine (EM) residents.

Machine learning algorithm for automatic detection of CT-identifiable hyperdense lesions associated with traumatic brain injury

Traumatic brain injury (TBI) is a major cause of death and disability in the United States. Time to treatment is often related to patient outcome. Access to cerebral imaging data in a timely manner is a vital component of patient care. Current methods of detecting and quantifying intracranial pathology can be time-consuming and require careful review of 2D/3D patient images by a radiologist. Additional time is needed for image protocoling, acquisition, and processing. These steps often occur in series, adding more time to the process and potentially delaying time-dependent management decisions for patients with traumatic brain injury. Our team adapted machine learning and computer vision methods to develop a technique that rapidly and automatically detects CT-identifiable lesions. Specifically, we use scale invariant feature transform (SIFT)1 and deep convolutional neural networks (CNN)2 to identify important image features that can distinguish TBI lesions from background data. Our learning algorithm is a linear support vector machine (SVM)3. Further, we also employ tools from topological data analysis (TDA) for gleaning insights into the correlation patterns between healthy and pathological data. The technique was validated using 409 CT scans of the brain, acquired via the Progesterone for the Treatment of Traumatic Brain Injury phase III clinical trial (ProTECT_III) which studied patients with moderate to severe TBI4. CT data were annotated by a central radiologist and included patients with positive and negative scans. Additionally, the largest lesion on each positive scan was manually segmented. We reserved 80% of the data for training the SVM and used the remaining 20% for testing. Preliminary results are promising with 92.55% prediction accuracy (sensitivity = 91.15%, specificity = 93.45%), indicating the potential usefulness of this technique in clinical scenarios.