Stroke Mortality Outcomes in Uganda.

BACKGROUND AND PURPOSE: Stroke outcome data in Uganda is lacking. The objective of this study was to capture 30-day mortality outcomes in patients presenting with acute and subacute stroke to Mbarara Regional Referral Hospital (MRRH) in Uganda. METHODS: A prospective study enrolling consecutive adults presenting to MRRH with abrupt onset of focal neurologic deficits suspicious for stroke, from August 2014 to March 2015. All patients had head computed tomography (CT) confirmation of ischemic or hemorrhagic stroke. Data was collected on mortality, morbidity, risk factors, and imaging characteristics. RESULTS: Investigators screened 134 potential subjects and enrolled 108 patients. Sixty-two percent had ischemic and 38% hemorrhagic stroke. The mean age of all patients was 62.5 (SD 17.4), and 52% were female. More patients had hypertension in the hemorrhagic stroke group than in the ischemic stroke group (53% vs. 32%, p = 0.0376). Thirty-day mortality was 38.1% (p = 0.0472), and significant risk factors were National Institutes of Health Stroke Scale (NIHSS) score, female sex, anemia, and HIV infection. A one unit increase of the NIHSS on admission increased the risk of death at 30 days by 6%. Patients with hemorrhagic stroke had statistically higher NIHSS scores (p = 0.0408) on admission compared to patients with ischemic stroke, and also had statistically higher Modified Rankin Scale (mRS) scores at discharge (p = 0.0063), and mRS score change from baseline (p = 0.04). CONCLUSIONS: Our study highlights an overall 30-day stroke mortality of 38.1% in southwestern Uganda, and identifies NIHSS at admission, female sex, anemia, and HIV infection as predictors of mortality.

Retinal Microvascular Abnormalities as Surrogate Markers of Cerebrovascular Ischemic Disease: A Meta-Analysis.

BACKGROUND: To determine the predictive value of retinal microvascular abnormalities for cerebrovascular ischemic diseases (CVDs), we aimed to investigate the quantitative association between retinal microvascular changes and CVD subcategories: white matter hyperintensities (WMHIs), lacunar infarcts (LIs), and cerebral infarctions (CIs). METHODS: Using Meta-analyses Of Observational Studies in Epidemiology guidelines, we searched 6 databases through September 2016 for studies evaluating the linkage between retinal microvascular abnormalities and WMHI, and LI and CI. Studies were included if they reported odds ratios (ORs) and 95% confidence intervals or raw patient level data (that were computed into ORs). Unadjusted and vascular risk-factor adjusted ORs were pooled into meta-analysis using DerSimonian Laird random effects model. Study quality and dissemination biases were assessed and integrated. RESULTS: From 24,444 search-identified records, 28 prospective studies encompassing 56,379 patients were eligible for the meta-analysis. After vascular risk-factor adjustment, focal arteriolar narrowing was associated with WMHI (OR, 1.24 [1.01-1.79]), LI (OR, 1.77 [1.14-2.74]), and CI (OR, 1.75 [1.14-2.69]). Venular dilation was associated with LI (OR, 1.46 [1.10-1.93]), and retinal hemorrhages with WMHI (OR, 2.23 [1.34-3.70]). Any retinopathy exhibited significant association with CI (OR, 1.96 [1.65-2.50]). Heterogeneity was significant (I2>50%) for all syntheses except retinal hemorrhages and WMHI, and retinopathy and CI (I2=0 ⋅ 0%). Associations remained significant after adjustments for quality and publication bias. CONCLUSIONS: We found the most significant association between retinal hemorrhages and WMHI. Focal arteriolar narrowing and retinopathy predicted CVD subtypes after risk-factor adjustment, suggesting that features different than traditional vascular risk factors, are involved in CVD pathophysiology.

Robotic telepresence versus standardly supervised stroke alert team assessments.

BACKGROUND: Telemedicine has created access to emergency stroke care for patients in all communities, regardless of geography. We hypothesized that there is no difference in speed of assessment between vascular neurologist (VN) robotic telepresence and standard VN-supervised stroke alert patients in a metropolitan primary stroke center. MATERIALS AND METHODS: A retrospective stroke alert database was used to identify all robotic telepresence and standardly supervised stroke alert patient assessments at a primary stroke center emergency department from 2009 to 2012. The primary outcome measure was the duration of assessment from stroke alert activation to treatment or downgrade. RESULTS: The sample size was 196 subjects. The mean duration of time from stroke alert activation to initiation of intravenous (IV) thrombolytic treatment or downgrade was 8.6 min longer in the robotic group than in the standard group (p=0.03). Among the subgroup of acute ischemic stroke patients treated with IV thrombolysis, the mean duration of time from activation to treatment was 18 min longer in the robotic group than in the standard group (p=0.01). Safety outcomes including thrombolysis protocol violations (0% versus 1%), post-thrombolysis symptomatic intracranial hemorrhagic complications (3% versus 1%), and death during hospitalization (8% versus 6%) were low in the robotic group and not significantly different from that in the standard group. CONCLUSIONS: Standard VN-supervised acute stroke team assessments were swifter than those supervised by robotic telepresence. Safety outcomes of robotic telepresence-supervised stroke alerts were excellent, and this modality may be preferred in circumstances when a VN is not immediately available on-site.

Statins and intracerebral hemorrhage: collaborative systematic review and meta-analysis.

BACKGROUND: A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. METHODS AND RESULTS: We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86-1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81-1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41-0.88). Substantial statistical heterogeneity was evident for the case-control studies (I(2)=66%, P=0.01), but not for the cohort studies (I(2)=0%, P=0.48) or randomized trials (I(2)=30%, P=0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. CONCLUSIONS: We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.

Smartphone teleradiology application is successfully incorporated into a telestroke network environment.

BACKGROUND AND PURPOSE: ResolutionMD mobile application runs on a Smartphone and affords vascular neurologists access to radiological images of patients with stroke from remote sites in the context of a telemedicine evaluation. Although reliability studies using this technology have been conducted in a controlled environment, this study is the first to incorporate it into a real-world hub and spoke telestroke network. The study objective was to assess the level of agreement of brain CT scan interpretation in a telestroke network between hub vascular neurologists using ResolutionMD, spoke radiologists using a Picture Archiving and Communications System, and independent adjudicators. METHODS: Fifty-three patients with stroke at the spoke hospital consented to receive a telemedicine consultation and participate in a registry. Each CT was evaluated by a hub vascular neurologist, a spoke radiologist, and by blinded telestroke adjudicators, and agreement over clinically important radiological features was calculated. RESULTS: Agreement (κ and 95% CI) between hub vascular neurologists using ResolutionMD and (1) the spoke radiologist; and (2) independent adjudicators, respectively, were: identification of intracranial hemorrhage 1.0 (0.92-1.0), 1.0 (0.93-1.0), neoplasm 1.0 (0.92-1.0), 1.0 (0.93-1.0), any radiological contraindication to thrombolysis 1.0 (0.92-1.0), 0.85 (0.65-1.0), early ischemic changes 0.62 (0.28-0.96), 0.58 (0.30-0.86), and hyperdense artery sign 0.40 (0.01-0.80), 0.44 (0.06-0.81). CONCLUSIONS: CT head interpretations of telestroke network patients by vascular neurologists using ResolutionMD on Smartphones were in excellent agreement with interpretations by spoke radiologists using a Picture Archiving and Communications System and those of independent telestroke adjudicators using a desktop viewer. CLINICAL TRIAL REGISTRATION INFORMATION: www.clinicaltrials.gov unique identifier NCT00829361.

CT interpretation in a telestroke network: agreement among a spoke radiologist, hub vascular neurologist, and hub neuroradiologist.

BACKGROUND AND PURPOSE: The American Stroke Association guidelines emphasized the need for further high-quality studies that assess agreement by radiologists and nonradiologists engaged in emergency telestroke assessments and decision-making. Therefore, the objective of this study was to determine the level of agreement of baseline brain CT scan interpretations of patients with acute stroke presenting to telestroke spoke hospitals between central reading committee neuroradiologists and each of 2 groups, spoke hospital radiologists and hub hospital vascular neurologists (telestrokologists). METHODS: The Stroke Team Remote Evaluation Using a Digital Observation Camera Arizona trial was a prospective, urban single-hub, rural 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine and teleradiology system designed for remote evaluation of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. In the telemedicine arm, the subjects' CT scans were interpreted by the hub telestrokologist and in the telephone arm by the spoke radiologist. All subjects' CT scans were subsequently interpreted centrally, independently, and blindly by 2 hub neuroradiologists. The primary CT outcome was determination of a CT-based contraindication to thrombolytic treatment. Kappa statistics and exact agreement rates were used to analyze interobserver agreement. RESULTS: Fifty-four subjects underwent random assignment. The overall agreement for the presence of radiological contraindications to thrombolysis was excellent (0.91) and did not differ substantially between the hub telestrokologist to neuroradiologist and spoke radiologist to neuroradiologist (0.92 and 0.89, respectively). CONCLUSIONS: In the context of a telestroke network designed to assess patients with acute stroke syndromes, agreement over the presence or absence of radiological contraindications to thrombolysis was excellent whether the comparisons were between a telestrokologist and neuroradiologist or between spoke radiologist and neuroradiologist. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00623350.

Stroke Telemedicine for Arizona Rural Residents, the Legacy Telestroke Study.

Background: Efficacy of telemedicine for stroke was first established by the Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC) trials in California and Arizona. Following these randomized controlled trials, the Stroke Telemedicine for Arizona Rural Residents (STARR) network was the first telestroke network to be established in Arizona. It consisted of a 7 spoke 1 hub telestroke system, and it was designed to serve rural, remote, or neurologically underserved communities. Objective: The objective of STARR was to establish a multicenter state-wide telestroke research network to determine the feasibility of prospective collection, recording, and regularly analysis of telestroke patient consultations and care data for the purposes of establishing quality measures, improvement, and benchmarking against other national and international telestroke programs. Methods: The STARR trial was open to enrollment for 29 months from 2008 to 2011. Mayo Clinic Hospital, Phoenix, Arizona served as the hub primary stroke center and its vascular neurologists provided emergency telestroke consultations to seven participating rural, remote, or underserved spoke community hospitals in Arizona. Eligibility criteria for activation of a telestroke alert and study enrollment were established. Consecutive patients exhibiting symptoms and signs of acute stroke within a 12 h window were enrolled, assessed, and treated by telemedicine. The state government sponsor, Arizona Department of Health Services' research grant covered the cost of acquisition, maintenance, and service of the selected telemedicine equipment as well as the professional telestroke services provided. The study deployed multiple telemedicine video cart systems, picture archive and communications systems software, and call management solutions. The STARR protocol was reviewed and approved by Mayo Clinic IRB, which served as the central IRB of record for all the participating hospitals, and the trial was registered at ClinicalTrials.gov. Results: The telestroke hotline was activated 537 times, and ultimately 443 subjects met criteria and consented to participate. The STARR successfully established a multicenter state-wide telestroke research network. The STARR developed a feasible and pragmatic approach to the prospective collection, storage, and analysis of telestroke patient consultations and care data for the purposes of establishing quality measures and tracking improvement. STARR benchmarked well against other national and international telestroke programs. STARR helped set the foundation for multiple regional and state telestroke networks and ultimately evolved into a national telestroke network. Conclusions: Multiple small and rurally located community hospitals and health systems can successfully collaborate with a more centrally located larger hospital center through telemedicine technologies to develop a coordinated approach to the assessment, diagnosis, and emergency treatment of patients manifesting symptoms and signs of an acute stroke syndrome. This model may serve well the needs of patients presenting with other time-sensitive medical emergencies.Clinical Trial Registration number: NCT00829361.

Intracranial hemorrhage following neuroendovascular procedures with abciximab is associated with high mortality: a multicenter series.

BACKGROUND: Abciximab is being used as an adjunct to neuroendovascular procedures both to prevent and treat ischemic sequelae. Experience with abciximab in this setting is limited; major bleeding complications, including fatal intracranial hemorrhage (ICH), are of particular concern. We report our multicenter experience with ICH following the administration of abciximab during neuroendovascular procedures. METHODS: We identified neuroendovascular procedures (including cerebral angiograms, aneurysm coiling procedures, angioplasty/vascular stenting procedures, and emergent revascularization procedures) that used abciximab at Mayo Clinic Hospitals in Rochester, Jacksonville, and Phoenix between November 2000 and April 2009. Cases of periprocedural ICH were identified and pertinent demographic, historical, procedural, radiographic, and laboratory data were collected. Clinical outcome was measured either at death or discharge by the Glasgow Outcome Scale (GOS). RESULTS: Abciximab was used in 51 neuroendovascular procedures; 9 cases of ICH were identified. Procedures performed and indications for abciximab use varied. Route of abciximab administration included IV bolus only (n = 4), IA bolus followed by IV infusion (n = 3), IV bolus followed by IV infusion (n = 1), and IV infusion without preceding bolus (n = 1). All but 1 of the patients received concomitant periprocedural antiplatelet, anticoagulant, or thrombolytic agents. Eight of the 9 cases of ICH were detected within 7 h of abciximab administration. ICH pattern varied. Four patients died following ICH. CONCLUSIONS: Adjunctive use of abciximab to prevent or treat ischemic sequelae during neuroendovascular procedures is associated with a high risk of ICH (18%). We report 9 cases of ICH associated with abciximab administration during neuroendovascular procedures with 44% mortality.

Anti-inflammatory activities, triterpenoids, and diarylheptanoids of Alnus acuminata ssp. arguta.

CONTEXT: The main use of stem bark infusions of Alnus acuminata ssp. arguta (Schlecht.) Furlow (Betulaceae) includes treatments for acute inflammation in Mexican traditional medicine. OBJECTIVE: n-Hexane (CHE), chloroform (CCE), and methanol (CME) extracts of the stem bark were investigated for anti-inflammatory activity and its safety. MATERIALS AND METHODS: The anti-inflammatory effects of the orally administered CME, CCE, and CHE extracts, using carrageenan-induced rat hind paw edema model, and acute oral toxicity in mice, using Lorke's method, were determined. RESULTS AND DISCUSSION: The column chromatographic fraction (CME-3) showed a higher anti-inflammatory activity (92.2%) (IC(50): 60.8 mg/mL) as compared with CME (76.9%); both were in the same order of magnitude as that of indomethacin, the positive control drug. Safety parameters for acute oral toxicity test showed that CME was not toxic (LD(50): >5000). Several triterpenoids (1-7) from hexane extracts and diarylheptanoids (10-14) from methanol extracts of A. acuminata ssp. arguta were isolated and characterized. CONCLUSIONS: These results confirm the traditional uses of A. acuminata in acute inflammatory conditions and its safety for consumption.

Stroke team remote evaluation using a digital observation camera in Arizona: the initial mayo clinic experience trial.

BACKGROUND AND PURPOSE: Telemedicine techniques can be used to address the rural-metropolitan disparity in acute stroke care. The Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC) trial reported more accurate decision making for telemedicine consultations compared with telephone-only and that the California-based research network facilitated a high rate of thrombolysis use, improved data collection, low risk of complications, low technical complications, and favorable assessment times. The main objective of the STRokE DOC Arizona TIME (The Initial Mayo Clinic Experience) trial was to determine the feasibility of establishing, de novo, a single-hub, multirural spoke hospital telestroke research network across a large geographical area in Arizona by replicating the STRokE DOC protocol. METHODS: Methods included prospective, single-hub, 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine system designed for remote examination of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. The primary outcome measure was whether the decision to give thrombolysis was correct. Secondary outcomes were rate of thrombolytic use, 90-day functional outcomes, incidence of intracerebral hemorrhages, and technical observations. RESULTS: From December 2007 to October 2008, 54 patients were assessed, 27 of whom were randomized to each arm. Mean National Institutes of Health Stroke Scale score at presentation was 7.3 (SD 6.2) points. No consultations were aborted; however, technical problems (74%) were prevalent in the telemedicine arm. Overall, the correct treatment decision was established in 87% of the consultations. Both modalities, telephone (89% correct) and telemedicine (85% correct), performed well. Intravenous thrombolytic treatment was used in 30% of the telemedicine and telephone consultations. Good functional outcomes at 90 days were not significantly different. There were no statistically significant differences in mortality (4% in telemedicine and 11% in telephone) or rates of intracerebral hemorrhage (4% in telemedicine and 0% in telephone). CONCLUSIONS: It is feasible to extend the original STRokE DOC trial protocol to a new state and establish an operational single-hub, multispoke rural hospital telestroke research network in Arizona. The trial was not designed to have sufficient power to detect a difference between the 2 consultative modes: telemedicine and telephone-only. Whether by telemedicine or telephone consultative modalities, there were appropriate treatment decisions, high rates of thrombolysis use, improved data collection, low rates of intracerebral hemorrhage, and equally favorable time requirements. The learning curve was steep for the hub and spoke personnel of the new telestroke network, as reflected by frequent technical problems. Overall, the results support the effectiveness of highly organized and structured stroke telemedicine networks for extending expert stroke care into rural remote communities lacking sufficient neurological expertise.

Spontaneous intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (sICH) is defined as bleeding within the brain parenchyma, and occurs twice as commonly as subarachnoid hemorrhage, but is equally as deadly. Risk factors for sICH include hypertension, advanced age, leukoaraiosis, prior ICH, renal failure, use of anticoagulant drugs, and cerebral amyloid angiopathy. When a patient is clinically suspected of having sICH, head computed tomography scan is the standard diagnostic tool. However, newer magnetic resonance neuroimaging techniques may aid in determining the underlying pathology and aid in prognosis. Supportive care and blood pressure management are important in the care of patients with sICH. Ongoing research is aimed at determining a safe blood pressure goal that may also prevent expansion of hemorrhage. Hemostatic medications and neuroprotectants have thus far not shown clinical improvement. Although several neurosurgical trials have failed to demonstrate benefit for surgical evacuation of sICH, multiple research trials are ongoing investigating acute blood pressure control, deep or basal ganglionic hemorrhage evacuation via minimally invasive approach (MISTIE; http://mistietrial.com/default.aspx), lobar ICH evacuation (STICH; II http://research.ncl.ac.uk/stich/), and intraventricular thrombolysis with tissue plasminogen activator (tPA) (CLEAR III; http://biosgroup-johnshopkinsmedicine.health.officelive.com/default.aspx).

Treatment of coagulopathy in intracranial hemorrhage.

OPINION STATEMENT: Intracranial hemorrhage (ICH) complicated by coagulopathy is a medical emergency, which can delay neurosurgical intervention, lead to larger hematoma size, and increase mortality until the coagulopathy is corrected. Prompt recognition of coagulopathy during ICH is essential for correct, rapid treatment to reduce ongoing bleeding and improve survival. The proper treatment of a coagulopathic ICH patient is centered on rapid identification of the coagulopathic defect and correction of the underlying coagulopathy to stop acute bleeding. Patients with coagulopathic ICH require admission to a neuro-intensive unit care with management of airway, oxygenation, and systemic arterial and cerebral perfusion pressure; optimization of serum glucose; aggressive treatment of fever; and rehabilitation. Once the coagulopathic defect is reversed, some patients benefit from emergent neurosurgical intervention to prevent secondary brain injury from raised intracranial pressure, hydrocephalus, or mass effect. The management of ICH patients prescribed common antithrombotics such as aspirin, clopidogrel, warfarin, or heparin, as well as thrombolytic agents such as tissue plasminogen activator, is the focus of this review.

Does prophylactic postoperative hypervolemic therapy prevent cerebral vasospasm and improve clinical outcome after aneurysmal subarachnoid hemorrhage?

BACKGROUND: Delayed cerebral vasospasm is a common cause of morbidity and mortality after acute aneurysmal subarachnoid hemorrhage. Hypovolemia and fluid restriction are risk factors for delayed vasospasm; hypervolemic therapeutic approaches are commonly used in patients with subarachnoid hemorrhage to prevent and to treat cerebral vasospasm. OBJECTIVE: To determine if postoperative prophylactic hypervolemic therapy prevents cerebral vasospasm and improves clinical outcome in patients with aneurysmal subarachnoid hemorrhage. METHODS: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular neurology. RESULTS: One randomized controlled trial addressed the questions. There was no difference in the incidence of symptomatic cerebral vasospasm (20% each) or clinical outcome at 14 days and 3 months between the hypervolemic and normovolemic groups. Hypervolemic therapy also had no effect on measures of cerebral blood flow. A second quasi-randomized trial reached the same conclusions. CONCLUSION: Available evidence is insufficient to support use of prophylactic hypervolemic therapy after surgery in patients with aneurysmal subarachnoid hemorrhage. Although completed studies may be insufficiently sensitive (underpowered) to detect a treatment effect, the magnitude of any as yet undetected benefit of prophylactic hypervolemic therapy is likely modest and its risks have not been systematically evaluated.

Stroke prevention in atrial fibrillation and other major cardiac sources of embolism.

The frequency of cardioembolic stroke is expected to rise as the general population ages. Much of the increase may be attributed to atrial fibrillation, the most common cause of cardioembolic stroke and one that plays a substantial role in aging adults. Other sources of cardioembolic stroke may include ventricular thrombus from myocardial infarction, heart failure, structural heart defects such as patent foramen ovale (PFO), atrial septal aneurysm, proximal aortic atheroma, valvular heart disease, and endocarditis. Diagnostic studies, such as neuroimaging, ECG, and echocardiography, are helpful in uncovering cardioembolic sources of stroke. Medical therapy is predicated on the underlying mechanism. For example, warfarin may be indicated in certain patients who have atrial fibrillation, atrial, or ventricular thrombi, and PFO with atrial septal aneurysm and cryptogenic stroke in select young patients to prevent stroke. Newer diagnostic technologies, including multidetector CT and cardiac MRI, may be useful to diagnose cardiac causes of stroke when transesophageal echocardiography is indeterminate or cryptogenic stroke is present.

Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.

BACKGROUND: Atrial fibrillation is a strong independent risk factor for stroke. PURPOSE: To characterize the efficacy and safety of antithrombotic agents for stroke prevention in patients who have atrial fibrillation, adding 13 recent randomized trials to a previous meta-analysis. DATA SOURCES: Randomized trials identified by using the Cochrane Stroke Group search strategy, 1966 to March 2007, unrestricted by language. STUDY SELECTION: All published randomized trials with a mean follow-up of 3 months or longer that tested antithrombotic agents in patients who have nonvalvular atrial fibrillation. DATA EXTRACTION: Two coauthors independently extracted information regarding interventions; participants; and occurrences of ischemic and hemorrhagic stroke, major extracranial bleeding, and death. DATA SYNTHESIS: Twenty-nine trials included 28,044 participants (mean age, 71 years; mean follow-up, 1.5 years). Compared with the control, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% CI, 49% to 74%) and 22% (CI, 6% to 35%), respectively. Adjusted-dose warfarin was substantially more efficacious than antiplatelet therapy (relative risk reduction, 39% [CI, 22% to 52%]) (12 trials, 12 963 participants). Other randomized comparisons were inconclusive. Absolute increases in major extracranial hemorrhage were small (< or =0.3% per year) on the basis of meta-analysis. LIMITATION: Methodological features and quality varied substantially and often were incompletely reported. CONCLUSIONS: Adjusted-dose warfarin and antiplatelet agents reduce stroke by approximately 60% and by approximately 20%, respectively, in patients who have atrial fibrillation. Warfarin is substantially more efficacious (by approximately 40%) than antiplatelet therapy. Absolute increases in major extracranial hemorrhage associated with antithrombotic therapy in participants from the trials included in this meta-analysis were less than the absolute reductions in stroke. Judicious use of antithrombotic therapy importantly reduces stroke for most patients who have atrial fibrillation.

Aqueous extract of Sedum oxypetalum induces mineralization and osteogenic differentiation by human Periodontal Ligament-Derived cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant Sedum oxypetalum Kunth (Crassulaceae), locally known as Jiote or in general Siempreviva (always alive) has been traditionally used by people of the Mexican community of Tenango del Valle as a home remedy to treat periodontal diseases, inducing teeth strengthening. Consequently, the aim of this work was to investigate its capacity directed to mineralized tissues regeneration. MATERIALS AND METHODS: The aerial parts of the plant were processed and its aqueous extract (AE) was chemically characterized. The AE and its components sedoheptulose and syngenite were tested for either osteogenic differentiation or mineral-nucleation induction respectively. RESULTS: The AE and one of its components (sedoheptulose) were shown to promote the proliferation and/or osteogenic differentiation by Human Periodontal Ligament-Derived Cells (hPDLs), while inducing the mineralization process. The AE also promoted the nucleation of octacalcium phosphate and its component syngenite, the hydroxyapatite crystals formation in vitro. CONCLUSION: The findings reported herein support the traditional use of S. oxypetalum due to its potential capacity to promote the regeneration of mineralized tissues.

Treatment of warfarin-associated intracerebral hemorrhage: literature review and expert opinion.

Wider use of oral anticoagulants has led to an increasing frequency of warfarin-related intracerebral hemorrhage (ICH). The high early mortality of approximately 50% has remained stable in recent decades. In contrast to spontaneous ICH, the duration of bleeding is 12 to 24 hours in many patients, offering a longer opportunity for intervention. Treatment varies widely, and optimal therapy has yet to be defined. An OVID search was conducted from January 1996 to January 2006, combining the terms warfarin or anticoagulation with intracranial hemorrhage or intracerebral hemorrhage. Seven experts on clinical stroke, neurologic intensive care, and hematology were provided with the available information and were asked to independently address 3 clinical scenarios about acute reversal and resumption of anticoagulation in the setting of warfarin-associated ICH. No randomized trials assessing clinical outcomes were found on management of warfarin-associated ICH. All experts agreed that anticoagulation should be urgently reversed, but how to achieve it varied from use of prothrombin complex concentrates only (3 experts) to recombinant factor VIIa only (2 experts) to recombinant factor VIIa along with fresh frozen plasma (1 expert) and prothrombin complex concentrates or fresh frozen plasma (1 expert). All experts favored resumption of warfarin therapy within 3 to 10 days of ICH in stable patients in whom subsequent anticoagulation is mandatory. No general agreement occurred regarding subsequent anticoagulation of patients with atrial fibrillation who survived warfarin-associated ICH. For warfarin-associated ICH, discontinuing warfarin therapy with administration of vitamin K does not reverse the hemostatic defect for many hours and is inadequate. Reasonable management based on expert opinion includes a wide range of additional measures to reverse anticoagulation in the absence of solid evidence.

Improving Blood Pressure Management and Disease Severity Documentation in Patients With Acute Intracerebral Hemorrhage.

OBJECTIVE: To ensure prime blood pressure management and intracerebral hemorrhage (ICH) score documentation within 6 hours of arrival and/or before any intervention in patients admitted to Mayo Clinic Hospital with acute ICH. PATIENTS AND METHODS: A quality improvement initiative was conducted between September 29, 2015, and May 30, 2017, following the Define-Measure-Analyze-Improve-Control methodology. Our prespecified goals for the first 8 months postintervention were that at least 80% of patients with ICH will have systolic blood pressure (SBP) control as per guideline-based recommendations (SBP ≤140 mm Hg) and at least 80% will have ICH score documented within 6 hours postadmission. Neurovascular stakeholders' feedback was included in the process development. Practice gaps and their leading causes were identified and served rational interventions' planning. Education and admission order-set modifications were chosen as intervention methods. RESULTS: At 4 (first measurement, n=13) and 8 months (second measurement, n=15) postintervention, 92.3% and 100% of patients with ICH, respectively, reached the target SBP, compared with 50% in the preintervention group (comparison group, n=26); 84.6% and 85.7% of the patient population had the ICH score documented at the first and second outcome measurement, respectively, compared with 42.3% in the preintervention group. Stakeholders reported good satisfaction with the novel applications. Sustainability plans and future directions were established. CONCLUSION: Effective education methods enhance the introduction of guideline-based clinical practices. This quality improvement project has the potential to impact patient outcomes, staff efficiency, and stroke centers' maintenance of certification and quality care recognition. This initiative warrants implementation at hospitals across all Mayo Clinic campuses and nationwide.

CHA2DS2-VASc Score: A Predictor of Thromboembolic Events and Mortality in Patients With an Implantable Monitoring Device Without Atrial Fibrillation.

OBJECTIVE: To determine if the CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, sex category) predicts thromboembolism and death in patients without atrial fibrillation in a population with implantable cardiac monitoring devices. PATIENTS AND METHODS: A retrospective review utilizing the Rochester Epidemiology Project research infrastructure was conducted to evaluate the CHA2DS2-VASc tool as a predictor of mortality and ischemic stroke, transient ischemic attack, or systemic embolism in patients without atrial fibrillation. An implantable device was required in the inclusion criteria to discern the absence of atrial fibrillation. The study period was January 1, 2004, through March 7, 2016. RESULTS: The study population (N=1606) had a mean (SD) age of 69.8 (12.6) years and median follow-up of 4.8 years (range, 0-12 years; quartile 1, 2.6 years and quartile 3, 8.1 years). The number of thromboembolic and mortality events stratified by CHA2DS2-VASc score groupings of 0 to 2 (399 patients), 3 to 5 (756 patients), and 6 to 9 (451 patients) were 12 (3.0%), 109 (14.4%), and 123 (27.3%) and 22 (5.5%), 205 (27.1%), and 214 (47.4%), respectively. The CHA2DS2-VASc score predicted thromboembolism and death. The hazard ratios (HRs) for thromboembolic events for CHA2DS2-VASc scores 3 to 5 and 6 to 9 were 4.84 (95% CI, 2.66-8.80) and 10.53 (95% CI, 5.77-19.21) (reference group, scores 0-2). The HRs for death for the corresponding score categories were 4.45 (95% CI, 2.86-6.91) and 8.18 (95% CI, 5.23-12.78). The CHA2DS2-VASc score also predicted development of atrial fibrillation, for which the HRs for scores 3 to 5 and 6 to 9 were 1.51 (95% CI, 1.13-2.00) and 2.17 (95% CI, 1.60-2.95). CONCLUSION: The CHA2DS2-VASc tool predicts thromboembolic events and overall mortality in patients without atrial fibrillation who have implantable devices.