Methods and Results—This retrospective cohort study of 695 patients enrolled at a university hospital-based anticoagulation clinic includes patients who received anticoagulation with warfarin or warfarin and aspirin between June 1, 2007 and September 30, 2008. All patients were ≥45 years old, had AF as the indication for anticoagulation, and did not have mechanical heart valves. Hemorrhages were classified as major if they caused death, involved critical sites, or required hospitalization with transfusion of ≥2 units of blood. All other bleeds were classified as minor. Of the 695 patients 307(44.2%) received combination therapy. Hemorrhage rates in the warfarin and the combination cohorts were 5.2% and 7.0% per 100-people years (p=0.29), respectively. There were 17 (3.4%) patients with major hemorrhages in the warfarin only group and 9 (2.8%) in the combination group (p=0.62). On average, patients on combination therapy had lower international normalized ratio (INR) values circa presentation (4.27 vs 3.13 p=0.049). In either group, any history of hemorrhage was associated with a 3.8 (95% CI, 1.79-8.13) times higher risk of hemorrhaging compared to patients without such a history.

Conclusions—This study highlights the high incidence of combination therapy and suggests that patients on combination therapy may bleed at lower INR levels. However, hemorrhagic outcomes did not differ significantly.

METHODS: An Internet-based survey was sent to 400 US vascular neurologists affiliated with a university to assess whether there are consensus opinions on how they treat patients beyond 3 hours from symptom onset and which patients they are willing to enroll into clinical trials of fibrinolysis for acute ischemic stroke.

RESULTS: We received 161 responses; 81% were male. Ninety-three percent of respondents treat patients with intravenous tissue plasminogen activator beyond 3 hours. More than 80% were treated beyond 3 hours with intra-arterial therapy (IAT). When asked if IAT improves stroke outcome, >50% selected the choice of "yes for middle cerebral artery and basilar occlusions" and only 2% selected the choice that "IAT does not improve outcome." Over half believe that imaging could be used to approximate the penumbra but with improvements to better identify salvageable tissue. Eighty-seven percent were willing to enroll patients into a placebo-controlled intravenous thrombolysis beyond 3 hours. For IAT trials, >80% would randomize beyond 3 hours with or without prior intravenous treatment.

CONCLUSIONS: Vascular neurologists have been treating acute ischemic stroke beyond 3 hours with intravenous tissue plasminogen activator even before the American Heart Association guidelines supported extending the therapeutic window. There is a paradox among the respondents willing to enroll patients into trials involving IAT given that a majority is offering IAT as part of their practice. These results suggest that clinical practice may impair enrollment into trials testing reperfusion therapies for acute ischemic stroke.

METHODS: We reviewed the literature focusing on case-control studies of the 5 most commonly inherited disorders of coagulation: protein C deficiency, protein S deficiency, antithrombin deficiency, and the factor V Leiden and prothrombin gene mutations in patients with stroke. We also analyzed the available data on stroke patients with inherited thrombophilia and patent foramen ovale.

RESULTS: Multiple case-control studies have not convincingly shown an association of the inherited thrombophilias with ischemic stroke, even in young patients and patients with patent foramen ovale.

CONCLUSIONS: If there is an association between the inherited thrombophilias and arterial stroke, then it is a weak one, likely enhanced by other prothrombotic risk factors. The consequences of ordering these tests and attributing causality to an arterial event can result in significant costs to the health care system and pose a potential risk to patients, because this may lead to inappropriate use of long-term oral anticoagulants, exposing patients to harm without a clearly defined benefit.

METHODS: Preliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium.

RESULTS: Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures.

CONCLUSIONS: To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.

METHODS: Four intravenous dose regimens (total cumulative doses of 30-180 mug/kg over the course of 3 days) of G-CSF were tested in 44 patients in a national, multicenter, randomized, placebo-controlled dose escalation study (NCT00132470; www.clinicaltrial.gov). Main inclusion criteria were a 12-hour time window after stroke onset, infarct localization to the middle cerebral artery territory, a baseline National Institutes of Health Stroke Scale range of 4 to 22, and presence of diffusion-weighted imaging/perfusion-weighted imaging mismatch.

RESULTS: Concerning the primary safety end points, we observed no increase of thromboembolic events in the active treatment groups, and no increase in related serious adverse events. G-CSF led to expected increases in neutrophils and monocytes that resolved rapidly after end of treatment. We observed a clinically insignificant drug-related decrease of platelets. As expected from the low number of patients, we did not observe significant differences in clinical outcome in treatment vs. placebo. In exploratory analyses, we observed an interesting dose-dependent beneficial effect of treatment in patients with DWI lesions > 14-17 cm(3).

CONCLUSIONS: We conclude that G-CSF was well-tolerated even at high dosages in patients with acute ischemic stroke, and that a substantial increase in leukocytes appears not problematic in stroke patients. In addition, exploratory analyses suggest treatment effects in patients with larger baseline diffusion-weighted imaging lesions. The obtained data provide the basis for a second trial aimed to demonstrate safety and efficacy of G-CSF on clinical end points.

CONCLUSIONS: Here, we set out a series of measures to reduce bias in the design, conduct and reporting of animal experiments modeling human stroke.

Limited preview available via Google Book Search.

METHODS: A review of the literature concerning the utility of cardiac rhythm monitoring (ECG, telemetry, Holter monitors, and event recorders) and structural imaging (transthoracic and transesophageal echocardiography) was performed.

RESULTS: Data supporting a definitive, optimal, and cost-effective approach are lacking, though some data suggest that appropriate patient selection can improve the diagnostic and therapeutic yield of rhythm monitoring and echocardiography in the evaluation of stroke etiology.

CONCLUSIONS: Based on available data, an algorithmic approach for the evaluation of patients with acute ischemic cerebrovascular events that takes into account therapeutic and diagnostic yield as well as cost-efficiency is proposed.