Background Recent literature suggests that acute rises in blood pressure may precede intracerebral hemorrhage. We therefore hypothesized that patients discharged from the emergency department with ...hypertension face an increased risk of intracerebral hemorrhage in subsequent weeks. Methods Using administrative claims data from California, New York, and Florida, we identified all patients discharged from the emergency department from 2005 to 2011 with a primary diagnosis of hypertension ( ICD-9-CM codes 401-405). We excluded patients if they were hospitalized from the emergency department or had prior histories of cerebrovascular disease at the index visit with hypertension. We used the Mantel–Haenszel estimator for matched data to compare each patient's odds of intracerebral hemorrhage during days 8-38 after emergency department discharge to the same patient's odds during days 373-403 after discharge. This cohort-crossover design with a 1-week washout period enabled individual patients to serve as their own controls, thereby minimizing confounding bias. Results Among the 552,569 patients discharged from the emergency department with a primary diagnosis of hypertension, 93 (.017%) were diagnosed with intracerebral hemorrhage during days 8-38 after discharge compared to 70 (.013%) during days 373-403 (odds ratio 1.33, 95% confidence interval .96-1.84). The odds of intracerebral hemorrhage were increased in certain subgroups of patients (≥60 years of age and those with secondary discharge diagnoses besides hypertension), but absolute risks were low in all subgroups. Conclusions Patients with emergency department discharges for hypertension do not face a substantially increased short-term risk of intracerebral hemorrhage after discharge.
Despite anticoagulation therapy, ischemic stroke risk in atrial fibrillation (AF) remains substantial. We hypothesize that left atrial enlargement (LAE) is more prevalent in AF patients admitted with ...ischemic stroke who are therapeutic, as opposed to nontherapeutic, on anticoagulation.
We included consecutive patients with AF admitted with ischemic stroke between April 1, 2015, and December 31, 2016. Patients were divided into two groups based on whether they were therapeutic (warfarin with an international normalized ratio ≥ 2.0 or non–vitamin K oral anticoagulant with uninterrupted use in the prior 2 weeks) versus nontherapeutic on anticoagulation. Univariable and multivariable models were used to estimate associations between therapeutic anticoagulation and clinical factors, including CHADS2 score and LAE (none/mild versus moderate/severe).
We identified 225 patients during the study period; 52 (23.1%) were therapeutic on anticoagulation. Patients therapeutic on anticoagulation were more likely to have a larger left atrial diameter in millimeters (45.6 ± 9.2 versus 42.3 ± 8.6, P = .032) and a higher CHADS2 score (2.9 ± 1.1 versus 2.4 ± 1.1, P = .03). After adjusting for the CHADS2 score, patients who had a stroke despite therapeutic anticoagulation were more likely to have moderate to severe LAE (odds ratio, 2.05; 95% confidence interval, 1.01-4.16).
LAE is associated with anticoagulation failure in AF patients admitted with an ischemic stroke. This provides indirect evidence that LAE may portend failure of anticoagulation therapy in patients with AF; further studies are needed to delineate the significance of this association and improve stroke prevention strategies.
Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency ...medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied.
In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients.
We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval CI, 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group.
In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.).
Background The impact of mobile stroke units (MSUs) on outcomes in patients with large vessel occlusions eligible for endovascular thrombectomy (EVT) has yet to be characterized. Methods We completed ...a prespecified substudy of patients with EVT‐eligible stroke with anterior and posterior circulation large vessel occlusions on computed tomography and/or computed tomography angiography who were enrolled in BEST‐MSU (Benefits of Stroke Treatment using a Mobile Stroke Unit). Primary outcome was 90‐day utility‐weighted modified Rankin scale. Groups were compared using chi‐square or Fisher's exact tests for categorical variables, and 2‐sample t ‐tests for continuous variables. Multiple logistic regression was used to assess the effect of MSU on binary outcomes after adjusting for other baseline factors. Results Of 1515 trial patients, 293 had large vessel occlusions eligible for EVT: 168 in the MSU group and 125 in the emergency medical services group. Baseline characteristics were comparable, with the exception of baseline National Institutes of Health Stroke Scale score (MSU median 19 interquartile range 13, 23 versus emergency medical services 16 11, 20, P = 0.002) and study site. The mean (±SD) score on the utility‐weighted modified Rankin scale at 90 days was 0.63±0.39 in MSU group and 0.51±0.41 in emergency medical services group (mean difference 0.13, 95% CI 0.03–0.22). After adjustment, MSU had significantly higher odds of functional independence (odds ratio 2.60 95% CI, 1.45–4.77, P = 0.002). Secondary outcomes also favored MSU: early neurologic recovery (30% improvement in National Institutes of Health Stroke Scale score at 24 hours) 68% versus 52%; adjusted odds ratio 1.98 95% CI, 1.19–3.33; time of tissue plasminogen activator bolus from symptom onset 65.0 minutes 50.5–92.0 versus 96.0 79.3–130.0, P ≤0.001. The groups had similar onset to arterial puncture (169.0 minutes 133.5, 210.0 versus 162.0 135.0–207.0, P = 0.83). Conclusions In patients with EVT‐eligible large vessel occlusion stroke, MSU management was associated with better clinical outcomes compared with standard emergency medical services management. MSU management sped thrombolysis but did not expedite EVT treatment times. Future MSU processes should include efforts to capitalize on the potential of MSUs to provide earlier EVT.
Visceral leishmaniasis is responsible for up to 30,000 deaths every year. Current treatments have shortcomings that include toxicity and variable efficacy across endemic regions. Previously, we ...reported the discovery of GNF6702, a selective inhibitor of the kinetoplastid proteasome, which cleared parasites in murine models of leishmaniasis, Chagas disease, and human African trypanosomiasis. Here, we describe the discovery and characterization of LXE408, a structurally related kinetoplastid-selective proteasome inhibitor currently in Phase 1 human clinical trials. Furthermore, we present high-resolution cryo-EM structures of the Leishmania tarentolae proteasome in complex with LXE408, which provides a compelling explanation for the noncompetitive mode of binding of this novel class of inhibitors of the kinetoplastid proteasome.
Background We aimed to estimate the risk of ischemic stroke after intracranial hemorrhage in patients with atrial fibrillation. Materials and Methods Using discharge data from all nonfederal acute ...care hospitals and emergency departments in California, Florida, and New York from 2005 to 2012, we identified patients at the time of a first-recorded encounter with a diagnosis of atrial fibrillation. Ischemic stroke and intracranial hemorrhage were identified using validated diagnosis codes. Kaplan-Meier survival statistics and Cox proportional hazard analyses were used to evaluate cumulative rates of ischemic stroke and the relationship between incident intracranial hemorrhage and subsequent stroke. Results Among 2,084,735 patients with atrial fibrillation, 50,468 (2.4%) developed intracranial hemorrhage and 89,594 (4.3%) developed ischemic stroke during a mean follow-up period of 3.2 years. The 1-year cumulative rate of stroke was 8.1% (95% CI, 7.5-8.7%) after intracerebral hemorrhage, 3.9% (95% CI, 3.5-4.3%) after subdural hemorrhage, and 2.0% (95% CI, 2.0-2.1%) in those without intracranial hemorrhage. After adjustment for the CHA2DS2-VASc score, stroke risk was elevated after both intracerebral hemorrhage (hazard ratio HR, 2.8; 95% CI, 2.6-2.9) and subdural hemorrhage (HR, 1.6; 95% CI, 1.5-1.7). Cumulative 1-year rates of stroke ranged from 0.9% in those with subdural hemorrhage and a CHA2DS2-VASc score of 0, to 33.3% in those with intracerebral hemorrhage and a CHA2DS2-VASc score of 9. Conclusions In a large, heterogeneous cohort, patients with atrial fibrillation faced a substantially heightened risk of ischemic stroke after intracranial hemorrhage. The risk was most marked in those with intracerebral hemorrhage and high CHA2DS2-VASc scores.
EXECUTIVE SUMMARY Stroke affects nearly 800,000 people annually in the United States and is the fifth most common cause of death and a leading cause of long-term disability. * Modifiable risk factors ...for stroke include hypertension, hypercholesterolemia, obstructive sleep apnea, and diabetes. * The ABCD2 score is a commonly used scale that can help stratify the risk of subsequent stroke in patients following TIA. * In the management of atrial fibrillation, novel oral anticoagulants have been shown to be at least noninferior to warfarin for ischemic stroke prevention and better tolerated in terms of intracranial bleeding risk. * Although symptomatic cervical carotid stenosis is amenable to revascularization, stenting of intracranial atherosclerosis has proven harmful in clinical trials.
Treatment of Acute Ischemic Stroke Lerario, Michael P; Segal, Alan Z
Primary care reports,
04/2016, Letnik:
22, Številka:
4
Journal Article
Executive Summary * The primary care physician’s role in stroke management involves prestroke education, prompt referral, and post-stroke care. * Office education of patients is important to identify ...symptoms of stroke and the need to seek medical attention immediately.Failure to report promptly to the emergency department leads to the loss of 1.9 million neurons per minute. * Public education efforts, such as the FAST campaign, contribute to increased awareness. * IV-tPA remains the mainstay of acute stroke treatment for patients presenting within 4.5 hours of symptom onset. * Endovascular therapies include intra-arterial tPA and mechanical clot extraction. * Profoundly positive results from five endovascular trials published in 2015 mark an extremely encouraging year in the history of stroke care.
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