BACKGROUND:In the prehospital tranexamic acid (TXA) for traumatic brain injury (TBI) trial, TXA administered within 2 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 score < 13) and systolic blood pressure ≥ 90 mm Hg within 2 hours of injury to a 2-g out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-g out-of-hospital TXA bolus/1-g 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-g TXA bolus group (17%) compared with the other two groups (1-g bolus/1-g infusion 26%, placebo 27%). The estimated adjusted difference between the 2-g bolus and placebo groups was -8·5 percentage points (95% confidence interval [CI], -15.9 to -1.0) and between the 2-g bolus and 1-g bolus/1-g infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). Disability Rating Scale at 6 months was lower in the 2-g TXA bolus group than the 1-g bolus/1-g 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. CONCLUSION:A 2-g 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.

Background Patients receiving oral anticoagulation who experience a traumatic intracranial hemorrhage (ICH) should receive anticoagulation reversal. Four factor prothrombin complex concentrate (4FPCC) is indicated for reversal of warfarin, and is frequently used for reversal of direct-acting oral anticoagulants (DOACs). The purpose of this study is to compare the safety and efficacy of 4FPCC reversal for traumatic ICH in DOAC- and warfarin-anticoagulated patients. Methods This was a single-center, retrospective review of adult patients with traumatic ICH who received 4FPCC for reversal of anticoagulation between April 2013 and August 2018. The ICH volume on the pre- and post-reversal head CT scans was measured. The primary endpoint was the incidence of expansion of ICH volume of blood using pre-and post-4FPCC imaging. Results A total of 102 patients meeting inclusion criteria were identified with 75 patients in the warfarin group and 27 patients in the DOAC group. There were no significant differences in baseline characteristics between the groups except DOAC patients had larger ICH volumes at baseline as compared to warfarin patients (23.4 mm 3 vs 3.7 mm 3 , p = 0.0001). There was neither a statistical difference in change in ICH volume pre-and post-4FPCC administration, nor in the rate of >20% ICH expansion between the warfarin and DOAC groups. There was no difference in the rate of adverse events compared between groups. Conclusion There was no difference in the either the change in ICH volume or the rate of >20% ICH expansion in patients receiving 4FPCC for reversal DOAC versus warfarin anticoagulation. Rates of complications were low in both groups.

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. This randomized clinical trial compares the effects of an out-of-hospital tranexamic acid bolus vs placebo within 2 hours of traumatic brain injury (TBI) on 6-month functional neurologic outcome (Glasgow Coma Scale-Extended score >4) in patients with moderate or severe TBI. Question Does early administration of tranexamic acid to patients with moderate or severe traumatic brain injury improve neurologic outcome at 6 months? Findings In this randomized multicenter clinical trial that included 966 participants enrolled in the out-of-hospital setting by paramedics, treatment with tranexamic acid as an out-of-hospital bolus with or without in-hospital infusion, compared with placebo as an out-of-hospital bolus and in-hospital infusion, resulted in a favorable neurologic outcome (defined as Glasgow Outcome Scale-Extended score >4) in 65% vs 62% of patients at 6 months, a difference that was not statistically significant. Meaning Among participants suspected of having moderate or severe traumatic brain injury, out-of-hospital administration of tranexamic acid compared with placebo did not significantly improve 6-month neurologic recovery.

OBJECTIVE: The primary aim of this study was to determine if donepezil (a centrally acting cholinesterase inhibitor) improves measures of balance in persons with Parkinson's disease (PD) compared to a placebo. BACKGROUND: Cholinesterase inhibitors have a positive impact on cognitive function in persons with PD and cognitive impairment or dementia.(Cochrane 2012) A small study also showed a reduction in falls in persons with PD without dementia.(Chung 2010) DESIGN/METHODS: This was a double-blind placebo controlled crossover study. Participants received 6 weeks of treatment with either placebo or donepezil, then a month washout, then another 6 weeks of treatment opposite to the first. Inclusion criteria were an MMSE>27 and balance impairment on clinical and posturography assessments (SOT <70). RESULTS: Ten participants' data was used in the analysis. The mean age, UPDRS motor score, and PD disease duration were 69.6+5.9 years, 24+7, and 10.5+8 years at the initial visit. Mean scores on Stroop conflict time and trails B-A at baseline were 105+48s and 59+32s respectively. The mean composite SOT scores improved from 60+16 to 61+15 during the placebo phase and 59+11 to 62+14 during the donepezil phase. This change was not significant, p=0.7. However, in looking at the single conditions of the SOT, there was a statically significant change seen in condition 4 (Eyes Open, Sway referenced, p<0.03). Out of 10 participants, 4 improved more than 40[percnt], 4 improved mildly (between 15[percnt] and 30[percnt]), and 2 didn't show improvements in C4 during the active phase of the study. In addition, there was a significant correlation between improvement in cognitive performance and balance, r=0.8, p=0.001. CONCLUSION:In this pilot study there was statistically significant improvement in one component of the SOT. A subset of patients appeared to have an improvement in balance. It appears that improvements in balance and executive functions are related.

BACKGROUNDStudies suggest that freezing of gait (FoG) in people with Parkinson's disease (PD) is associated with declines in executive function (EF). However, EF is multi-faceted, including three dissociable components: inhibiting prepotent responses, switching between task sets, and updating working memory.OBJECTIVEThis study investigated which aspect of EF is most strongly associated with FoG in PD.METHODThree groups were studied: adults with PD (with and without FoG) and age-matched, healthy adults. All participants completed a battery of cognitive tasks previously shown to discriminate among the three EF components. Participants also completed a turning-in-place task that was scored for FoG by neurologists blind to subjects' self-reported FoG.RESULTSCompared to both other groups, participants with FoG showed significant performance deficits in tasks associated with inhibitory control, even after accounting for differences in disease severity, but no significant deficits in task-switching or updating working memory. Surprisingly, the strongest effect was an intermittent tendency of participants with FoG to hesitate, and thus miss the response window, on go trials in the Go-Nogo task. The FoG group also made slower responses in the conflict condition of the Stroop task. Physician-rated FoG scores were correlated both with failures to respond on go trials and with failures to inhibit responses on nogo trials in the Go-Nogo task.CONCLUSIONThese results suggest that FoG is associated with a specific inability to appropriately engage and release inhibition, rather than with a general executive deficit.

AbstractAllyl‐3‐butenyl‐äther (I) reagiert oberhalb 400°C zu einem Gemisch aus Propen (II) und Vinylacetaldehyd (III) einerseits und geringen Anteilen an 6‐Heptenal (V) andererseits.