Association Between Use of a Flying Intervention Team vs Patient Interhospital Transfer and Time to Endovascular Thrombectomy Among Patients With Acute Ischemic Stroke in Nonurban Germany.

Importance: The benefit of endovascular thrombectomy (EVT) for acute ischemic stroke is highly time-dependent, and it is challenging to expedite treatment for patients in remote areas. Objective: To determine whether deployment of a flying intervention team, compared with patient interhospital transfer, is associated with a shorter time to endovascular thrombectomy and improved clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This was a nonrandomized controlled intervention study comparing 2 systems of care in alternating weeks. The study was conducted in a nonurban region in Germany including 13 primary telemedicine-assisted stroke centers within a telestroke network. A total of 157 patients with acute ischemic stroke for whom decision to pursue thrombectomy had been made and deployment of flying intervention team or patient interhospital transfer was initiated were enrolled between February 1, 2018, and October 24, 2019. The date of final follow-up was January 31, 2020. Exposures: Deployment of a flying intervention team for EVT in a primary stroke center vs patient interhospital transfer for EVT to a referral center. Main Outcomes and Measures: The primary outcome was time delay from decision to pursue thrombectomy to start of the procedure in minutes. Secondary outcomes included functional outcome after 3 months, determined by the distribution of the modified Rankin Scale score (a disability score ranging from 0 [no deficit] to 6 [death]). Results: Among the 157 patients included (median [IQR] age, 75 [66-80] y; 80 [51%] women), 72 received flying team care and 85 were transferred. EVT was performed in 60 patients (83%) in the flying team group vs 57 (67%) in the transfer group. Median (IQR) time from decision to pursue EVT to start of the procedure was 58 (51-71) minutes in the flying team group and 148 (124-177) minutes in the transfer group (difference, 90 minutes [95% CI, 75-103]; P < .001). There was no significant difference in modified Rankin Scale score after 3 months between patients in the flying team (n = 59) and transfer (n = 57) groups who received EVT (median [IQR] score, 3 [2-6] vs 3 [2-5]; adjusted common odds ratio for less disability, 1.91 [95% CI, 0.96-3.88]; P = .07). Conclusions and Relevance: In a nonurban stroke network in Germany, deployment of a flying intervention team to local stroke centers, compared with patient interhospital transfer to referral centers, was significantly associated with shorter time to EVT for patients with acute ischemic stroke. The findings may support consideration of a flying intervention team for some stroke systems of care, although further research is needed to confirm long-term clinical outcomes and to understand applicability to other geographic settings.

Nickel nanoparticles supported on a covalent triazine framework as electrocatalyst for oxygen evolution reaction and oxygen reduction reactions.

Covalent triazine frameworks (CTFs) are little investigated, albeit they are promising candidates for electrocatalysis, especially for the oxygen evolution reaction (OER). In this work, nickel nanoparticles (from Ni(COD)2) were supported on CTF-1 materials, which were synthesized from 1,4-dicyanobenzene at 400 °C and 600 °C by the ionothermal method. CTF-1-600 and Ni/CTF-1-600 show high catalytic activity towards OER and a clear activity for the electrochemical oxygen reduction reaction (ORR). Ni/CTF-1-600 requires 374 mV overpotential in OER to reach 10 mA/cm2, which outperforms the benchmark RuO2 catalyst, which requires 403 mV under the same conditions. Ni/CTF-1-600 displays an OER catalytic activity comparable with many nickel-based electrocatalysts and is a potential candidate for OER. The same Ni/CTF-1-600 material shows a half-wave potential of 0.775 V for ORR, which is slightly lower than that of commercial Pt/C (0.890 V). Additionally, after accelerated durability tests of 2000 cycles, the material showed only a slight decrease in activity towards both OER and ORR, demonstrating its superior stability.

Outcomes Associated With Clopidogrel-Aspirin Use in Minor Stroke or Transient Ischemic Attack: A Pooled Analysis of Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trials.

Importance: Dual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA. Objective: To obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA. Design, Setting, and Participants: This analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019. Interventions: In the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset. Main Outcomes and Measures: The primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage. Results: The study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P < .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P < .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant. Conclusions and Relevance: In this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA.

Idarucizumab administration in emergency situations: the Munich Registry of Reversal of Pradaxa® in clinical routine (MR REPAIR).

OBJECTIVES: To evaluate daily life management and functional outcome of Idarucizumab administration in case of emergency situations in patients with Dabigatran treatment. DESIGN: Multicenter observational registry study. SETTING: All hospitals with full neurological departments (n = 6) in Munich, Germany INCLUDED PATIENTS: All patients treated with Idarucizumab from 01/2016 to 03/2019. ANALYZED DATA: Indication and application of Idarucizumab, demographics and clinical parameters, and further interventions and treatments; clinical outcome was assessed with the modified Rankin scale (mRS) at 3 months after Idarucizumab administration RESULTS: Idarucizumab was administered to 32 patients for severe bleeding complications and ischemic strokes, more precisely for the following specific indications: intracranial bleeding (17 patients, 53%), ischemic stroke (8 patients, 25%), gastrointestinal bleeding (3 patients, 9%), femoral fracture, aortic dissection, and abdominal trauma and ileus (1 patient each, 3%). Additional coagulation management was performed in 7 patients (22%). Nine patients (28%) underwent emergency surgery. Seven patients (22%) received Idarucizumab before intravenous thrombolysis due to ischemic stroke and 4 of these 7 patients (13%) received mechanical thrombectomy in addition. Indication was mainly based on the history of Dabigatran intake and was irrespective of laboratory testing. At follow-up, 25% of the investigated patients had a mRS 0-2, while 25% had an unfavorable outcome (mRS 4-5). Mortality was 31%. CONCLUSION: In our study, we have shown that the administration of Idarucizumab is a rare intervention and restricted to patients with severe bleeding complications or ischemic stroke. The clinical outcome of patients who received Idarucizumab in emergency situations was poor.

Metal-Organic Gels Based on a Bisamide Tetracarboxyl Ligand for Carbon Dioxide, Sulfur Dioxide, and Selective Dye Uptake.

A metal-organic gel (metallogel) based on the new tetracarboxyl ligand N1, N4-(diterephthalic acid)terephthalamide in combination with chromium(III) has been converted into its xero- and aerogel and demonstrated to have excellent specific sorption properties for dyes in its metallogel state, where fuchsine is adsorbed faster than the two other dyes, calcein and disulfine blue, and for water, sulfur dioxide and carbon dioxide in its xero- and aerogel state. The metallogel showed very good shape retention and could be extruded from molds in designed shapes. In a rheology experiment, the storage modulus was determined to be 1440 Pa, and the metallogel is elastic up to 3 Hz, breaking at strains higher than 0.3%. Additional metallogels utilizing the same ligand with a wide range of metal ions (Al(III), Fe(III), Co(III), In(III), and Hg(II)) have also been synthesized, and the aluminum and mixed aluminum-chromium derivative were also converted into its aerogel. The highly porous Cr, Al, and AlCr metal-organic aerogels proved stable against water vapor in a physisorption experiment and were used to model breakthrough curves for SO2/CO2 gas mixtures with the idealized adsorbed solution theory from their physisorption isotherms. The breakthrough simulation utilized SO2/CO2 equivalencies from a real world application and showed effective retention of SO2 from the gas mixture. Furthermore, the materials in this work exhibit the highest SO2 uptake values for metal-organic aerogels so far (up to 116.8 cm3 g-1, or 23.4 wt %).

Role of Filler Porosity and Filler/Polymer Interface Volume in Metal-Organic Framework/Polymer Mixed-Matrix Membranes for Gas Separation.

Metal-organic frameworks (MOFs) and inorganic fillers are frequently incorporated into mixed-matrix membranes (MMMs) to overcome the traditional trade-off in permeability ( P) and selectivity for pure organic polymer membranes. Therefore, it is of great interest to examine the influence of porous and nonporous fillers in MMMs with respect to the possible role of the polymer-filler interface, that is, the void volume. In this work, we compare the same MOF filler in a porous and nonporous state, so that artifacts from a different polymer-filler interface are excluded. MMMs with the porous MOF aluminum fumarate (Al-fum) and with a nonporous dimethyl sulfoxide solvent-filled aluminum fumarate (Al-fum(DMSO)), both with Matrimid as polymer, were prepared. Filler contents ranged from 4 to 24 wt %. Gas separation performances of both MMMs were studied by mixed gas measurements using a binary mixture of CO2/CH4 with gas permeation following the theoretical prediction by the Maxwell model for both porous and nonporous dispersed phase (filler). MMMs with the porous Al-fum filler showed increased CO2 and CH4 permeability with a moderate rise in selectivity upon increasing filler fraction. The MMMs with the nonporous Al-fum(DMSO) filler displayed a reduction in permeability while maintaining the selectivity of the neat polymer. A linear dependence of log P versus the reciprocal specific free fractional volume (sFFV) rules out a significant contribution from a void volume. The sFFV includes the free volume of the polymer and the MOF, but not the polymer-filler interface volume (so-called void volume). The sFFV for the MMM was calculated between 0.23 cm3/g for a 24 wt % Al-fum/Matrimid MMM and 0.12 cm3/g for a 24 wt % Al-fum(DMSO)/Matrimid MMM. The negligible effect of an interface volume is supported by a good matching of theoretical and experimental density of the Al-fum and Al-fum/(DMSO) MMMs which gave a specific void volume below 0.02 cm3/g, often even below 0.01 cm3/g.

GLACIER: An open-label, randomized, multicenter study to assess the safety and tolerability of glatiramer acetate 40 mg three-times weekly versus 20 mg daily in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: The efficacy and safety of glatiramer acetate (GA) 20 mg/mL once-daily subcutaneous injections (GA20) in relapsing-remitting multiple sclerosis (RRMS) is well-established. However, injection-related adverse events (IRAEs) may impede treatment adherence and tolerability. GA 40 mg/mL three-times weekly (GA40) also has a favorable efficacy and safety profile. OBJECTIVE: To evaluate the safety, tolerability, and patient experience when converting from GA20 to GA40. METHODS/TRIAL DESIGN: GLACIER was an open-label, randomized, parallel-group trial conducted at 31 sites in the US between June 2013 and December 2013. Stable RRMS patients on GA20 were randomized in a 1:1 ratio to continue with GA20 or convert to GA40. The adjusted mean annualized rate of IRAEs was the primary endpoint for this study. Additionally, the severity of IRAEs, rate of injection-site reactions (ISRs), and patient-reported MS impact and treatment satisfaction were compared for the two treatment groups over the 4-month core study. RESULTS: A total of 209 patients were randomized to convert to GA40 (n=108) or continue with GA20 (n=101). The adjusted mean annualized rate of IRAEs was reduced by 50% with GA40 (35.3 events per year; n=108) versus GA20 (70.4 events per year; n=101) (risk ratio (RR)=0.50; 95% confidence interval [CI]=0.34-0.74; p=0.0006). There was a 60% reduction in the rate of moderate/severe events (GA40 (n=108): 0.9 events per year versus GA20 (n=101): 2.2 events per year; RR=0.40; p=0.0021). Perception of treatment convenience improved for GA40-treated patients soon after converting and was sustained. CONCLUSIONS: The GLACIER study demonstrates a favorable IRAE and convenience profile of GA40 for RRMS patients. TRIAL REGISTRATION: NCT01874145 available at clinicaltrial.gov.

Island of stability for consistent deformations of Einstein's gravity.

We construct deformations of general relativity that are consistent and phenomenologically viable, since they respect, in particular, cosmological backgrounds. These deformations have unique symmetries in accordance with their Minkowski cousins (Fierz-Pauli theory for massive gravitons) and incorporate a background curvature induced self-stabilizing mechanism. Self-stabilization is essential in order to guarantee hyperbolic evolution in and unitarity of the covariantized theory, as well as the deformation's uniqueness. We show that the deformation's parameter space contains islands of absolute stability that are persistent through the entire cosmic evolution.

Cosmological classicalization: maintaining unitarity under relevant deformations of the Einstein-Hilbert action.

Generic relevant deformations of Einstein's gravity theory contain additional degrees of freedom that have a multifaceted stabilization dynamics on curved spacetimes. We show that these relevant degrees of freedom are self-protected against unitarity violations by the formation of classical field lumps that eventually merge to a new background geometry. The transition is heralded by the massive decay of the original vacuum and evolves through a strong coupling regime. This process fits in the recently proposed classicalization mechanism and extends it further to free field dynamics on curved backgrounds.

Statewide efforts to narrow the rural-urban gap in acute stroke care.

BACKGROUND: Rural-urban gaps in stroke care remain challenging in part because of the lack of resources, personnel, and necessary infrastructure. PURPOSE: The purpose of this study was to assess changes in the acute stroke diagnosis and treatment capacity among rural hospitals before and after implementation of a regionwide stroke initiative. METHODS: In 2004, the Montana Cardiovascular Health Program partnered with stroke stakeholders throughout the state and surveyed hospitals in Montana and northern Wyoming to assess the availability of technology, services, and personnel for acute stroke care. The Montana Stroke Initiative (MSI) developed protocols, educational material, and stroke awareness campaigns to address the geographic disparities identified in the survey. From 2004 to 2006, protocols and educational material were made available on a website and distributed to rural and critical-access hospitals throughout the region. Stroke awareness campaigns were completed, and MSI members conducted acute stroke care training of prehospital, nursing, and primary providers throughout the region. A follow-up survey in 2008 assessed changes in the stroke systems of care between 2004 and 2008. Data were analyzed in 2009. RESULTS: There were significant increases in availability of prehospital stroke screens, written emergency department protocols, computed tomographic scanning capability, acute stroke teams, and community stroke awareness programs. CONCLUSIONS: A systematic statewide effort to improve stroke care led to improved acute stroke care capabilities in necessary infrastructure in rural facilities and a narrowing of the gap between these facilities and the urban facilities.

Stroke knowledge among urban and frontier first responders and emergency medical technicians in Montana.

PURPOSE: To assess stroke knowledge and practice among frontier and urban emergency medical services (EMS) providers and to evaluate the need for additional prehospital stroke training opportunities in Montana. METHODS: In 2006, a telephone survey of a representative sample of EMS providers was conducted in Montana. Respondents were stratified into 2 groups: those working in urban and frontier counties. FINDINGS: Compared to EMS providers from urban counties, those from frontier counties were significantly more likely to be older (mean age 44.7 vs 40.1 years), have fewer personnel working in their service (mean 17.7 vs 28.6), to be located farther away from a computed tomography scan (CT scan) (mean 41.3 vs 17.6 miles), and to be volunteers (84% vs 49%). They were also less likely to have a stroke protocol (58% vs 66%) and use a stroke screening tool (36% vs 47%) than their urban counterparts. There were no significant differences between frontier and urban EMS respondents' ability to correctly identify 4 or more stroke warning signs (58% vs 61%), 4 or more stroke risk factors (46% vs 43%), or the 3-hour recombinant tissue plasminogen activator (rt-PA) treatment window (56% vs 57%). Approximately two thirds of respondents from urban and frontier counties believed they had adequate stroke knowledge, but 90% indicated they were interested in additional stroke-related training. CONCLUSIONS: Although stroke knowledge did not differ between urban and frontier groups, stroke screens and stroke protocols were less likely to be used in the frontier areas. Training opportunities and the implementation of stroke protocols and screening tools are needed for EMS providers, particularly in frontier counties.

Availability of diagnostic and treatment services for acute stroke in frontier counties in Montana and Northern Wyoming.

CONTEXT: Rapid diagnosis and treatment of ischemic stroke can lead to improved patient outcomes. Hospitals in rural and frontier counties, however, face unique challenges in providing diagnostic and treatment services for acute stroke. PURPOSE: The aim of this study was to assess the availability of key diagnostic technology and programs for acute stroke evaluation and treatment in Montana and northern Wyoming. METHODS: In 2004, hospital medical directors or their designees were mailed a survey about the availability of diagnostic technology, programs, and personnel for acute stroke care. FINDINGS: Fifty-eight of 67 (87%) hospitals responded to the survey. Seventy-nine percent (46/58) of responding hospitals were located in frontier counties, with an average bed size of 18 (11 SD). Of the hospitals in frontier counties, 44% reported emergency medical services prehospital stroke identification programs, 39% had 24-hour computed tomography capability, 44% had an emergency department stroke protocol, and 61% had a recombinant tissue plasminogen activator protocol. Thirty percent of hospitals in frontier counties reported that they met 6-10 of the criteria established by the Brain Attack Coalition to improve acute stroke care compared to 67% of hospitals in the nonfrontier counties. CONCLUSION: A stroke network model could enhance care and improve outcomes for stroke victims in frontier counties.

Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of DM/Q (capsules containing dextromethorphan [DM] and quinidine [Q]) compared with placebo, taken twice daily, for the treatment of pseudobulbar affect over a 12-week period in multiple sclerosis patients. METHODS: A total of 150 patients were randomized in a double-blind, placebo-controlled study to assess pseudobulbar affect with the validated Center for Neurologic Study-Lability Scale. Each patient also recorded the number of episodes experienced between visits, estimated quality of life and quality of relationships on visual analog scales, and completed a pain rating scale. RESULTS: Patients receiving DM/Q had greater reductions in Center for Neurologic Study-Lability Scale scores than those receiving placebo (p < 0.0001) at all clinic visits (days 15, 29, 57, and 85). All secondary end points also favored DM/Q, including the number of crying or laughing episodes (p

Perceived risk for developing stroke among older adults.

BACKGROUND: Persons who perceive their risk for stroke accurately may be more likely to engage in prevention practices to reduce their risk. METHODS: In 2004, 800 adults aged 45 years and older in two counties participated in a telephone survey to assess their perceived risk for stroke and their history of stroke risk factors. RESULTS: Overall, 39% of respondents perceived themselves to be at risk for having a stroke. In the multivariate analyses, younger age, current smoking, and a history of diabetes, high blood pressure, high cholesterol, heart disease, and stroke/TIA were independently associated with perceived risk for stroke. Respondents with atrial fibrillation were no more likely to report being at risk for stroke compared to respondents without atrial fibrillation. Perceived risk for stroke increased as the number of risk factors increased. However, 46% of respondents with three or more risk factors did not perceive themselves to be at risk. CONCLUSIONS: Many adults with multiple risk factors do not perceive themselves to be at risk for stroke. Clinical and public health efforts are needed to increase awareness of the risk for stroke.

Rural community knowledge of stroke warning signs and risk factors.

INTRODUCTION: Rapid identification and treatment of ischemic stroke can lead to improved patient outcomes. Public education campaigns in selected communities have helped to increase knowledge about stroke, but most data represent large metropolitan centers working with academic institutions. Much less is known about knowledge of stroke among residents in rural communities. METHODS: In 2004, 800 adults aged 45 years and older from two Montana counties participated in a telephone survey using unaided questions to assess awareness of stroke warning signs and risk factors. The survey also asked respondents if they had a history of atrial fibrillation, diabetes, high blood pressure, high cholesterol, smoking, heart disease, or stroke. RESULTS: More than 70% of survey participants were able to correctly report two or more warning signs for stroke: numbness on any side of the face/body (45%) and speech difficulties (38%) were reported most frequently. More than 45% were able to correctly report two or more stroke risk factors: smoking (50%) and high blood pressure (44%) were reported most frequently. Respondents aged 45 to 64 years (odds ratio [OR] 2.44; 95% confidence interval [CI], 1.78-3.46), women (OR 2.02; 95% CI, 1.46-2.80), those with 12 or more years of education (OR 1.96; 95% CI, 1.08-3.56), and those with high cholesterol (OR 1.68; 95% CI, 1.17-2.42) were more likely to correctly identify two or more warning signs compared with respondents without these characteristics. Women (OR 1.48; 95% CI, 1.07-2.05) and respondents aged 45 to 64 years (OR 1.35; 95% CI, 1.01-1.81) were also more likely to correctly identify two or more stroke risk factors compared with men and older respondents. CONCLUSION: Residents of two rural counties were generally aware of stroke warning signs, but their knowledge of stroke risk factors was limited.