Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial.

OBJECTIVE: To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). BACKGROUND: Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit. METHODS: This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study. RESULTS: Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes. CONCLUSION: Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.

Recurrent stroke arrival time.

BACKGROUND: Stroke patients and family members should receive stroke education including recognition of stroke symptoms and prompt activation of emergency medical services (EMS). The impact of this education is unclear. We aimed to measure the associations between EMS use and timing of hospital arrival and first-ever and recurrent strokes as a proxy for stroke education. METHODS: The study analyzed data from validated strokes identified by the Brain Attack Surveillance in Corpus Christi (BASIC) project between 1/1/2000-1/1/2020. We analyzed 5,617 first-ever strokes, 259 instances of recurrent stroke within 1 year of the first (early recurrence), and 451 recurrent strokes over 1 year from the first (late recurrence). Following imputation, associations of both EMS arrival (available starting late 2011) and early arrival (< 3 hours) with first-ever versus recurrent stroke (early and late) were assessed with logistic models, accounting for the clustering of multiple strokes per participant with generalized estimating equations. Full model covariates included stroke type, initial stroke severity, marital status, race/ethnicity, gender, age, insurance, education, and EMS use (early arrival model only). RESULTS: Compared to first-ever stroke, there were significantly higher unadjusted odds of arrival by EMS for the late recurrence group (late recurrence OR = 1.54, 95% CI = 1.18-1.99; early arrival OR = 1.24, 95% CI = 0.87-1.76). The association for late recurrence remained significant after adjustment (aOR = 1.46, 95% CI = 1.09-1.95). The pre-2010 unadjusted odds of early arrival were non-significant for both early and late recurrence groups (late recurrence OR = 1.05, CI = 0.70-1.56; early recurrence OR = 0.85, CI = 0.54-1.33), while late recurrence was associated with early arrival after 2010 (OR = 1.32, 95% CI = 1.03-1.69). After full adjustment, it was no longer significant (aOR = 1.25, 95% CI = 0.96-1.62). Higher initial stroke severity, married status, and EMS use were associated with higher odds of early arrival, while African Americans (AAs) had lower odds than non-Hispanic Whites (NHWs). However, AAs did have higher odds of EMS use relative to NHWs. Those who were married and living together had borderline significant lower odds of EMS use compared to those who were not. CONCLUSIONS: Our study examines the association of repeat stroke on early arrival and EMS use as a surrogate for adequate stroke education. Recurrence at least one year after the first stroke was associated with higher EMS usage, but there was not enough evidence to establish a relationship with early arrival after accounting for EMS usage and possible confounders. By examining subsets, we can identify groups that would benefit from targeted education. For example, younger, non-AA patients with smaller strokes would benefit from more education on EMS use and African American patients would benefit from education related to faster recognition or urgency of presentation.

Improving Prehospital Stroke Diagnosis Using Natural Language Processing of Paramedic Reports.

Background and Purpose: Accurate prehospital diagnosis of stroke by emergency medical services (EMS) can increase treatments rates, mitigate disability, and reduce stroke deaths. We aimed to develop a model that utilizes natural language processing of EMS reports and machine learning to improve prehospital stroke identification. Methods: We conducted a retrospective study of patients transported by the Chicago EMS to 17 regional primary and comprehensive stroke centers. Patients who were suspected of stroke by the EMS or had hospital-diagnosed stroke were included in our cohort. Text within EMS reports were converted to unigram features, which were given as input to a support-vector machine classifier that was trained on 70% of the cohort and tested on the remaining 30%. Outcomes included final diagnosis of stroke versus nonstroke, large vessel occlusion, severe stroke (National Institutes of Health Stroke Scale score >5), and comprehensive stroke center-eligible stroke (large vessel occlusion or hemorrhagic stroke). Results: Of 965 patients, 580 (60%) had confirmed acute stroke. In a test set of 289 patients, the text-based model predicted stroke nominally better than models based on the Cincinnati Prehospital Stroke Scale (c-statistic: 0.73 versus 0.67, P=0.165) and was superior to the 3-Item Stroke Scale (c-statistic: 0.73 versus 0.53, P<0.001) scores. Improvements in discrimination were also observed for the other outcomes. Conclusions: We derived a model that utilizes clinical text from paramedic reports to identify stroke. Our results require validation but have the potential of improving prehospital routing protocols.

Increasing false positive diagnoses may lead to overestimation of stroke incidence, particularly in the young: a cross-sectional study.

BACKGROUND: Stroke incidence is reportedly increasing in younger populations, although the reasons for this are not clear. We explored possible reasons by quantifying trends in neurologically focused emergency department (ED) visits, classification of stroke vs. TIA, and imaging use. METHODS: We performed a retrospective, serial, cross-sectional study using the National Hospital Ambulatory Medical Care Survey to examine time trends in age-stratified primary reasons for visit, stroke/TIA diagnoses, and MRI utilization from 1995 to 2000 and 2005-2015. RESULTS: Five million eight hundred thousand ED visits with a primary diagnosis of stroke (CI 5.3 M-6.4 M) were represented in the data. The incidence of neurologically focused reason for visits (Neuro RFVs) increased over time in both the young and in older adults (young: + 111 Neuro RFVs/100,000 population/year, CI + 94 - + 130; older adults: + 70 Neuro RFVs/100,000 population/year, CI + 34 - + 108). The proportion of combined stroke and TIA diagnoses decreased over time amongst older adults with a Neuro RFV (OR 0.95 per year, p < 0.01, CI 0.94-0.96) but did not change in the young (OR 1.00 per year, p = 0.88, CI 0.95-1.04). Within the stroke/TIA population, no changes in the proportion of stroke or TIA were identified. MRI utilization rates amongst patients with a Neuro RFV increased for both age groups. CONCLUSIONS: We found, but did not anticipate, increased incidence of neurologically focused ED visits in both age groups. Given the lower pre-test probability of a stroke in younger adults, this suggests that false positive stroke diagnoses may be increasing and may be increasing more rapidly in the young than in older adults.

Door-In-Door-Out Process Times at Primary Stroke Centers in Chicago.

STUDY OBJECTIVE: Acute stroke patients often require interfacility transfer from primary stroke centers to comprehensive stroke centers. Given the time-sensitive benefits of endovascular reperfusion, reducing door-in-door-out time at the primary stroke center is a target for quality improvement. We sought to identify modifiable predictors of door-in-door-out times at 3 Chicago-region primary stroke centers. METHODS: We performed a retrospective analysis of consecutive patients with acute stroke from February 1, 2018 to January 31, 2020 who required transfer from 1 of 3 primary stroke centers to 1 of 3 affiliated comprehensive stroke centers in the Chicago region. Stroke coordinators at each primary stroke center abstracted data on type of transport, medical interventions and treatments prior to transfer, and relevant time intervals from patient arrival to departure. We evaluated predictors of door-in-door-out time using median regression models. RESULTS: Of 191 total patients, 67.9% arrived by emergency medical services and 57.4% during off-hours. Telestroke was performed in 84.2%, 30.5% received alteplase, and 48.4% underwent a computed tomography (CT) angiography at the primary stroke center. The median door-in-door-out time was 148.5 (interquartile range 106 to 207.8) minutes. The largest contributors to door-in-door-out time, in minutes, were CT to CT angiography time (22 [7 to 73.5]), transfer center contact to ambulance request time (20 [8 to 53.3]), ambulance request to arrival time (20.5 [14 to 36]), and transfer ambulance time at primary stroke center (26 [21 to 35]). Factors associated with door-in-door-out time were (adjusted median differences, in minutes [95% confidence intervals]): CT angiography performed at primary stroke center (+39 [12.3 to 65.7]), walk-in arrival mode (+53 [4.1 to 101.9]), administration of intravenous alteplase (-29 [-31.3 to -26.7]), intubation at primary stroke center (+23 [7.3 to 38.7]), and ambulance request by primary stroke center (-20 [-34.3 to -5.7]). CONCLUSION: Door-in-door-out times at Chicago-area primary stroke centers average nearly 150 minutes. Reducing time to CT angiography, receipt of alteplase, and ambulance request are likely important modifiable targets for interventions to decrease door-in-door-out times at primary stroke centers.

Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest (EROCA): Results of a Randomized Feasibility Trial of Expedited Out-of-Hospital Transport.

STUDY OBJECTIVE: Outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest depend on time to therapy initiation. We hypothesize that it would be feasible to select refractory out-of-hospital cardiac arrest patients for expedited transport based on real-time estimates of the 911 call to the emergency department (ED) arrival interval, and for emergency physicians to rapidly initiate ECPR in eligible patients. METHODS: In a 2-tiered emergency medical service with an ECPR-capable primary destination hospital, adults with refractory shockable or witnessed out-of-hospital cardiac arrest were randomized 4:1 to expedited transport or standard care if the predicted 911 call to ED arrival interval was less than or equal to 30 minutes. The primary outcomes were the proportion of subjects with 911 call to ED arrival less than or equal to 30 minutes and ED arrival to ECPR flow less than or equal to 30 minutes. RESULTS: Of 151 out-of-hospital cardiac arrest 911 calls, 15 subjects (10%) were enrolled. Five of 12 subjects randomized to expedited transport had an ED arrival time of less than or equal to 30 minutes (overall mean 32.5 minutes [SD 7.1]), and 5 were eligible for and treated with ECPR. Three of 5 ECPR-treated subjects had flow initiated in less than or equal to 30 minutes of ED arrival (overall mean 32.4 minutes [SD 10.9]). No subject in either group survived with a good neurologic outcome. CONCLUSION: The Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest trial did not meet predefined feasibility outcomes for selecting out-of-hospital cardiac arrest patients for expedited transport and initiating ECPR in the ED. Additional research is needed to improve the accuracy of predicting the 911 call to ED arrival interval, optimize patient selection, and reduce the ED arrival to ECPR flow interval.

Telemetry Bed Usage for Patients with Low-Risk Chest Pain: An Updated Review of the Literature for the Clinician.

BACKGROUND: Telemetry monitoring in patients with low-risk chest pain continues to be highly used despite a 2011 literature review and recommendations by the Clinical Practice Committee (CPC) of the American Academy of Emergency Medicine that did not find quality data to support its use. OBJECTIVE: To update the medical literature review on the utility of telemetry monitoring in patients with low-risk chest pain and to offer evidence-based recommendations to emergency physicians. METHODS: A PubMed literature search was performed for systematic reviews in English relevant to low-risk chest pain between 2011 and 2019 and then expanded to all citations by removing the systematic review criteria. Studies identified then underwent a structured review from which results could be evaluated in the context of the associated 2011 literature review and CPC recommendations. RESULTS: The initial search yielded 2 potentially relevant studies, although none directly addressed telemetry. The expanded search resulted in 76 abstracts that were screened. Two addressed telemetry, including the last CPC statement, which were reviewed and recommendations given. CONCLUSIONS: No further quality data were identified to support the use of telemetry monitoring in patients with low-risk chest pains. Telemetry monitoring is unlikely to benefit patients with low-risk chest pain with a low-risk HEART Score.

Is a Lumbar Puncture Required to Rule Out Atraumatic Subarachnoid Hemorrhage in Emergency Department Patients With Headache and Normal Brain Computed Tomography More Than Six Hours After Symptom Onset?

BACKGROUND: Atraumatic subarachnoid hemorrhage (SAH) is a deadly condition that most commonly presents as acute, severe headache. Controversy exists concerning evaluation of SAH based on the time from onset of symptoms, specifically if the headache occurred > 6 h prior to patient presentation. CLINICAL QUESTION: Do patients undergoing evaluation for atraumatic SAH who have a negative computed tomography (CT) scan of the head obtained more than 6 h after symptom onset require a subsequent lumbar puncture to rule out the diagnosis? EVIDENCE REVIEW: Studies retrieved included a retrospective cohort study, two prospective cohort studies, and a case-control study. These studies provide estimates of the diagnostic accuracy of head CT imaging obtained > 6 h from symptom onset and diagnostic test characteristics of subsequent lumbar puncture. CONCLUSION: The probability of SAH above which emergency clinicians should perform a lumbar puncture is 1.0%. This threshold is essentially the same as the estimated probability of SAH in patients with a negative head CT obtained more than 6 h from symptom onset. Emergency physicians might reasonably decide to either perform or forego this procedure. Consequently, we contend that the decision whether to perform lumbar puncture in these instances is an excellent candidate for shared decision-making.

Tissue-Based Stroke Definition Impacts Stroke Incidence but not Ethnic Differences.

OBJECTIVES: We explored how the new, tissue-based stroke definition impacted incidence estimates, including an ethnic comparison, in a population-based study. METHODS: Stroke patients, May, 2014-May, 2016 in Nueces County, Texas were ascertained and validated using source documentation. Overall, ethnic-specific and age-specific Poisson regression models were used to compare first-ever ischemic stroke and intracerebral hemorrhage (ICH) incidence between old and new stroke definitions, adjusting for age, ethnicity, sex, and National Institutes of Health Stroke Scale score. RESULTS: Among 1308 subjects, 1245 (95%) were defined as stroke by the old definition and 63 additional cases (5%) according to the new. There were 12 cases of parenchymal hematoma (PH1 or PH2) that were reclassified from ischemic stroke to ICH. Overall, incidence of ischemic stroke was slightly higher under the new compared to the old definition (RR 1.07; 95% CI 0.99-1.16); similarly higher in both Mexican Americans (RR 1.06; 95% CI 1.00-1.12) and Non Hispanic whites (RR 1.09, 95% CI 0.97-1.22), p(ethnic difference)=0.36. Overall, incidence of ICH was higher under the new definition compared to old definition (RR 1.16; 95% CI 1.05-1.29), similarly higher among both Mexican Americans (RR 1.14; 95% CI 1.06-1.23) and Non Hispanic whites (RR 1.20, 95% CI 1.03-1.39), p(ethnic difference)=0.25. CONCLUSION: Modest increases in ischemic stroke and ICH incidence occurred using the new compared with old stroke definition. There were no differences between Mexican Americans and non Hispanic whites. These estimates provide stroke burden estimates for public health planning.

Trends in Stroke Recurrence in Mexican Americans and Non-Hispanic Whites.

BACKGROUND AND PURPOSE: Stroke incidence and mortality are declining rapidly in developed countries. Little data on ethnic-specific stroke recurrence trends exist. Fourteen-year stroke recurrence trend estimates were evaluated in Mexican Americans and non-Hispanic whites in a population-based study. METHODS: Recurrent stroke was ascertained prospectively in the population-based BASIC (Brain Attack Surveillance in Corpus Christi) project in Texas, between 2000 and 2013. Incident cases were followed forward to determine 1- and 2-year recurrence. Fine & Gray subdistribution hazard models were used to estimate adjusted trends in the absolute recurrence risk and ethnic differences in the secular trends. The ethnic difference in the secular trend was examined using an interaction term between index year and ethnicity in the models adjusted for age, sex, hypertension, diabetes mellitus, smoking, atrial fibrillation, insurance, and cholesterol and relevant interaction terms. RESULTS: From January 1, 2000 to December 31, 2013 (N=3571), the cumulative incidence of 1-year recurrence in Mexican Americans decreased from 9.26% (95% CI, 6.9%-12.43%) in 2000 to 3.42% (95% CI, 2.25%-5.21%) in 2013. Among non-Hispanic whites, the cumulative incidence of 1-year recurrence in non-Hispanic whites decreased from 5.67% (95% CI, 3.74%-8.62%) in 2000 to 3.59% (95% CI, 2.27%-5.68%) in 2013. The significant ethnic disparity in stroke recurrence existed in 2000 (risk difference, 3.59% [95% CI, 0.94%-6.22%]) but was no longer seen by 2013 (risk difference, -0.17% [95% CI, -1.96% to 1.5%]). The competing 1-year mortality risk was stable over time among Mexican Americans, while for non-Hispanic whites it was decreasing over time (difference between 2000 and 2013: -4.67% [95% CI, -8.72% to -0.75%]). CONCLUSIONS: Mexican Americans had significant reductions in stroke recurrence despite a stable death rate, a promising indicator. The ethnic disparity in stroke recurrence present early in the study was gone by 2013.

Coronavirus Disease 2019 (COVID-19) Clinical Trial Oversight at a Major Academic Medical Center: Approach of Michigan Medicine.

Clinicians, eager to offer the best care in the absence of guiding data, have provided patients with coronavirus disease 2019 (COVID-19) diverse clinical interventions. This usage has led to perceptions of efficacy of some interventions that, while receiving media coverage, lack robust evidence. Moving forward, randomized controlled clinical trials are necessary to ensure that clinicians can treat patients effectively during this outbreak and the next. To do so, academic medical centers must address 2 key research issues: (1) how to effectively and efficiently determine which trials have the best chance of benefiting current and future patients and (2) how to establish a transparent and ethical process for subject recruitment while maintaining research integrity and without overburdening patients or staff. We share here the current methods used by Michigan Medicine to address these issues.

Efficacy of Clopidogrel for Prevention of Stroke Based on CYP2C19 Allele Status in the POINT Trial.

BACKGROUND AND PURPOSE: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT. METHODS: Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death. RESULTS: Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09-1.21]; P=0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32-1.34]; P=0.25) among noncarriers. There was no significant interaction by genotype for major ischemia (P=0.36) or stroke (P=0.33). CONCLUSIONS: This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029.

Implementation of Evidence-Based Practice for Benign Paroxysmal Positional Vertigo in the Emergency Department: A Stepped-Wedge Randomized Trial.

STUDY OBJECTIVE: We evaluated a strategy to increase use of the test (Dix-Hallpike's test [DHT]) and treatment (canalith repositioning maneuver [CRM]) for benign paroxysmal positional vertigo in emergency department (ED) dizziness visits. METHODS: We conducted a stepped-wedge randomized trial in 6 EDs. The population was visits with dizziness as a principal reason for the visit. The intervention included educational sessions and decision aid materials. Outcomes were DHT or CRM documentation (primary), head computed tomography (CT) use, length of stay, admission, and 90-day stroke events. The analysis was multilevel logistic regression with intervention, month, and hospital as fixed effects and provider as a random effect. We assessed fidelity with monitoring intervention use and semistructured interviews. RESULTS: We identified 7,635 dizziness visits during 18 months. The DHT or CRM was documented in 1.5% of control visits (45/3,077; 95% confidence interval 1% to 1.9%) and 3.5% of intervention visits (159/4,558; 95% confidence interval 3% to 4%; difference 2%, 95% confidence interval 1.3% to 2.7%). Head CT use was lower in intervention visits compared with control visits (44.0% [1,352/3,077] versus 36.9% [1,682/4,558]). No differences were observed in admission or 90-day subsequent stroke risk. In fidelity evaluations, providers who used the materials typically reported positive clinical experiences but provider engagement was low at facilities without an emergency medicine residency program. CONCLUSION: These findings provide evidence that an implementation strategy of a benign paroxysmal positional vertigo-focused approach to ED dizziness visits can be successful and safe in promoting evidence-based care. Absolute rates of DHT and CRM use, however, were still low, which relates in part to our broad inclusion criteria for dizziness visits.

Reach Out Emergency Department: Partnering With an Economically Disadvantaged Community in the Development of a Text-Messaging Intervention to Address High Blood Pressure.

Background. Hypertension affects nearly 30% of the U.S. adult population. Due to the ubiquitous nature of mobile phone usage, text messaging offers a promising platform for interventions to assist in the management of chronic diseases including hypertension, including among populations that are historically underserved. We present the intervention development of Reach Out, a health behavior theory-based, mobile health intervention to reduce blood pressure among hypertensive patients evaluated in a safety net emergency department primarily caring for African Americans. Aims. To describe the process of designing and refining text messages currently being implemented in the Reach Out randomized controlled trial. Method. We used a five-step framework to develop the text messages used in Reach Out. These steps included literature review and community formative research, conception of a community-centered behavioral theoretical framework, draft of evidence-based text messages, community review, and revision based on community feedback and finalization. Results. The Reach Out development process drew from pertinent evidence that, combined with community feedback, guided the development of a community-centered health behavior theory framework that led to development of text messages. A total of 333 generic and segmented messages were created. Messages address dietary choices, physical activity, hypertension medication adherence, and blood pressure monitoring. Discussion. Our five-step framework is intended to inform future text-messaging-based health promotion efforts to address health issues in vulnerable populations. Conclusion. Text message-based health promotion programs should be developed in partnership with the local community to ensure acceptability and relevance.

Serum NfL (Neurofilament Light Chain) Levels and Incident Stroke in Adults With Diabetes Mellitus.

Background and Purpose- Effective stroke prevention depends on accurate stroke risk prediction. We determined the discriminative ability of NfL (neurofilament light chain) levels for distinguishing between adults with diabetes mellitus who develop incident stroke and those who remain stroke free during a 7-year follow-up period. Methods- We performed a case-control study of participants selected from the previously completed ACCORD trial (Action to Control Cardiovascular Risk in Diabetes). Cases were all ACCORD subjects who were stroke free at enrollment and developed incident stroke during follow-up (n=113). Control subjects (n=250) were randomly selected ACCORD subjects who had no stroke events either before or after randomization. NfL was measured in baseline samples using Single Molecule Array technology (Quanterix). Results- Baseline NfL levels were higher in stroke subjects, compared to controls, after adjusting for age, race, blood pressure, weight, and the Framingham Stroke Risk Score. Relative to the subjects in the lowest quintile of NfL levels, the hazard ratios of incident stroke for subjects in the second to fifth quintiles were 3.91 (1.45-10.53), 4.05 (1.52-10.79), 5.63 (2.16-14.66), and 9.75 (3.84-27.71), respectively, after adjusting for race and Framingham Stroke Risk Score. Incorporating NfL levels into a predictive score that already included race and Framingham Stroke Risk Score increased the score's C statistic from 0.71 (95% CI, 0.66-0.77) to 0.78 (95% CI, 0.73-0.83), P<0.001. Older age, nonwhite race, higher systolic blood pressure, glomerular filtration rate <60, and higher hemoglobin A1C were independent predictors of serum NfL in this cohort but diastolic blood pressure, durations of hypertension or diabetes mellitus, and lipid levels were not. In total, cardiovascular disease risk factors explained 19.2% of the variability in baseline NfL levels. Conclusions- Serum NfL levels predict incident stroke and add considerably to the discriminatory power of the Framingham Stroke Risk Score in a cohort of middle-aged and older adults with diabetes mellitus.

Intravenous Recombinant Tissue Plasminogen Activator and Ischemic Stroke: Focused Update of 2010 Clinical Practice Advisory From the American Academy of Emergency Medicine.

BACKGROUND: Stroke treatment is a continuum that begins with the rapid identification of symptoms and treatment with transition to successful rehabilitation. Therapies for acute ischemic stroke (AIS) may vary based on anatomic location, interval from symptom onset, and coexisting health conditions. Successful therapy requires a seamless systematic approach with coordination from prehospital environment through acute management at medical facilities to disposition and long-term care of the patient. The emergency physician must balance the benefits and risks of alteplase recombinant tissue plasminogen activator (rtPA) for AIS management. OBJECTIVE: We review the recent medical literature on the topic of AIS and assess intravenous rtPA for the following questions: 1) is there any applicable, new, high-quality evidence that the benefits of intravenous rtPA are justified in light of the harms associated with it, and 2) if so, does the evidence clarify which patients, if any, are most likely to benefit from the treatment. METHODS: A MEDLINE literature search from January 2010 to October 2016 and limited to human studies written in English for articles with keywords of cerebrovascular accident and (thromboly* OR alteplase). Guideline statements and nonsystematic reviews were excluded. Studies targeting differences between specific populations (males vs. females) were excluded. Studies identified then underwent a structured review from which results could be evaluated. RESULTS: Three hundred twenty-two papers on thrombolytic use were screened and nine appropriate articles were rigorously reviewed and recommendations given. CONCLUSIONS: No new studies published between 2010 and 2016 meaningfully reduced uncertainty regarding our understanding of the benefits and harms of intravenous rtPA for AIS. Discussions regarding benefit and harm should occur for patients, and risk prediction scores may facilitate the conversation.

Synergism of Short-Term Air Pollution Exposures and Neighborhood Disadvantage on Initial Stroke Severity.

BACKGROUND AND PURPOSE: Little is known about the relation between environment and stroke severity. We investigated associations between environmental exposures, including neighborhood socioeconomic disadvantage and short-term exposure to airborne particulate matter <2.5 µm and ozone, and their interactions with initial stroke severity. METHODS: First-ever ischemic stroke cases were identified from the Brain Attack Surveillance in Corpus Christi project (2000-2012). Associations between pollutants, disadvantage, and National Institutes of Health Stroke Scale were modeled using linear and logistic regression with adjustment for demographics and risk factors. Pollutants and disadvantage were modeled individually, jointly, and with interactions. RESULTS: Higher disadvantage scores and previous-day ozone concentrations were associated with higher odds of severe stroke. Higher levels of particulate matter <2.5 µm were associated with higher odds of severe stroke among those in higher disadvantage areas (odds ratio, 1.24; 95% confidence interval, 1.00-1.55) but not in lower disadvantage areas (odds ratio, 0.82; 95% confidence interval, 0.56-1.22; P interaction =0.097). CONCLUSIONS: Air pollution exposures and neighborhood socioeconomic status may be important in understanding stroke severity. Future work should consider the multiple levels of influence on this important stroke outcome.