Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. Objective: To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Design, Setting, and Participants: Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Interventions: Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). Main Outcomes and Measures: The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Results: Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Conclusions and Relevance: Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. Trial Registration: ClinicalTrials.gov Identifier: NCT01990768.

The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: a subgroup analysis from the prehospital TXA for TBI trial.

BACKGROUND: In the Prehospital Tranexamic Acid (TXA) for TBI Trial, TXA administered within two hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT). METHODS: This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial (ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale<13) and systolic blood pressure > =90 mmHg within two hours of injury to a 2-gram out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-gram out-of-hospital TXA bolus/1-gram in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) < = 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors. RESULTS: The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-gram TXA bolus group (17%) compared to the other two groups (1-gram bolus/1-gram infusion 26%, placebo 27%). The estimated adjusted difference between the 2-gram bolus and placebo groups was -8·5 percentage points (95% CI, -15.9 to -1.0) and between the 2-gram bolus and 1-gram bolus/1-gram infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). DRS at 6 months was lower in the 2-gram TXA bolus group than the 1-gram bolus/1-gram infusion (estimated difference -2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups. CONCLUSIONS: A 2-gram out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level II.

Thermodynamic Studies on a Hydrogen Bonded Acidic 3,5-Bis(trifluoromethyl)phenol-functionalized Polymer as a Gas Chromatography Stationary Phase for Selectively Speciating Chemical Warfare Agents.

We describe for the first time hydrogen bonded acid (HBA) polymer, poly{methyl[3-(2-hydroxyl, 4,6-bistrifluoromethyl)phenyl]propylsiloxane}, (DKAP), as stationary phase for gas chromatography (µGC) of organophosphate (OP), chemical warfare agent (CWA) surrogates, dimethylmethylphosphonate (DMMP), diisopropylmethylphosphonate (DIMP), diethylmethylphosphonate (DEMP), and trimethylphosphate (TMP), with high selectivity. Absorption of OPs to DKAP was one-to-several orders of magnitude higher relative to commercial polar, mid-polar, and nonpolar stationary phases. We also present for the first-time thermodynamic studies on the absorption of OP vapors and quantitative binding energy data for interactions with various stationary phases. These data help to identify the best pair of hetero-polar columns for a two-dimensional GC system, employing a nonpolar stationary phase as GC1 and DKAP as the GC2 stationary phase, for selective and rapid field detection of CWAs.

A high-speed, high-performance, microfabricated comprehensive two-dimensional gas chromatograph.

A small, consumable-free, low-power, ultra-high-speed comprehensive GC×GC system consisting of microfabricated columns, nanoelectromechanical system (NEMS) cantilever resonators for detection, and a valve-based stop-flow modulator is demonstrated. The separation of a highly polar 29-component mixture covering a boiling point range of 46 to 253 °C on a pair of microfabricated columns using a Staiger valve manifold in less than 7 seconds, and just over 4 seconds after the ensemble holdup time is demonstrated with a downstream FID. The analysis time of the second dimension was 160 ms, and peak widths in the second dimension range from 10-60 ms. A peak capacity of just over 300 was calculated for a separation of just over 6 s. Data from a continuous operation testing over 40 days and 20 000 runs of the GC×GC columns with the NEMS resonators using a 4-component test set is presented. The GC×GC-NEMS resonator system generated second-dimension peak widths as narrow as 8 ms with no discernable peak distortion due to under-sampling from the detector.

Novel one-dimensional nanogap created with standard optical lithography and evaporation procedures.

This article details a simple four-step procedure to create a one-dimensional nanogap on a buried oxide substrate that relies on conventional photolithography performed on a stack of silicon/silicon oxide/silicon, metal evaporation, and hydrofluoric acid oxide removal. Once the nanogap was fabricated it was bridged with an assembly of 1,8-octanedithiol and 5 nm Au nanoparticles capped with a sacrificial dodecylamine coating. Before assembly, characterization of the nanogaps was performed through electrical measurements and SEM imaging. Post assembly, the resistance of the nanogaps was evaluated. The current increased from 70 fA to 200 microA at +1 V bias, clearly indicating a modification due to nanoparticle molecule assembly. Control experiments without nanoparticles or octanedithiol did not show an increase in current.