EXTEND trial: Towards a more inclusive but complex thrombolysis

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Comparison of Cardiovascular Risk Factors for Coronary Heart Disease and Stroke Type in Women

Background Cardiovascular risk factors have differential effects on various manifestations of cardiovascular disease, but to date direct formal comparisons are scarce, have been conducted primarily in men, and include only traditional risk factors. Methods and Results Using data from the multi-ethnic Women's Health Initiative Observational Study, we used a case-cohort design to compare 1731 women with incident cardiovascular disease during follow-up to a cohort of 1914 women. The direction of effect of all 24 risk factors (including various apolipoproteins, hemoglobin A1c, high-sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, and tissue plasminogen activator antigen) was concordant for coronary heart disease (CHD, defined as myocardial infarction and CHD death) and ischemic stroke; however, associations were generally stronger with CHD. Significant differences for multiple risk factors, including blood pressure, lipid levels, and measures of inflammation, were observed when comparing the effects on hemorrhagic stroke with those on ischemic outcomes. For instance, multivariable adjusted hazard ratios per standard deviation increase in non-high-density lipoprotein cholesterol were 1.16 (95% confidence interval, 1.06-1.28) for CHD, 0.97 (0.88-1.07) for ischemic stroke, and 0.76 (0.63-0.91) for hemorrhagic stroke ( P<0.05 for equal association). Model discrimination was better for models predicting CHD or ischemic stroke than for models predicting hemorrhagic stroke or a combined end point. Conclusions Cardiovascular risk factors have largely similar effects on incidence of CHD and ischemic stroke in women, although the magnitude of association varies. Determinants of ischemic and hemorrhagic stroke substantially differ, underscoring their distinct biology. Cardiovascular disease risk may be more accurately reflected when combined cardiovascular disease or cerebrovascular outcomes are broken down into different first manifestations, or when restricted to ischemic outcomes

Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.Peer reviewe

Treating Patients With 'Wake-Up' Stroke The Experience of the AbESTT-II Trial

Background and Purpose-Approximately 10% to 20% of patients with a new stroke have symptoms present on awakening (wake-up stroke), but these persons are not treated with interventions to restore perfusion because the time of onset is not known. We elected to test the safety and possible efficacy of abciximab in treatment of enrolled subjects with wake-up stroke.Methods-Abciximab in Emergency Stroke Treatment Trial-II (AbESTT-II) tested the usefulness of abciximab in improving outcomes after acute ischemic stroke and it prospectively tested an intervention in subjects that awakened with their stroke. We compared the outcomes among the subjects in the wake-up group with the other subjects in the trial.Results-Of the 801 subjects randomized in the trial, 43 (22 abciximab and 21 placebo) had wake-up strokes. Those with wake-up strokes had similar baseline characteristics as the other subjects except for a higher rate of a new stroke found on CT. Recruitment of patients into the wake-up group was halted early because of the rate of bleeding with abciximab exceeded the prespecified safety margins (3 of 22 [13.6%]) within 5 days or at discharge versus 15 of 375 (4.0%) for the nonwake-up group (P=0.07). Favorable outcomes at 3 months, as defined by scores on the modified Rankin Scale, among the wake-up group (4 of 43 [9.3%]) were worse than the nonwake-up group (221 of 758 [ 29.2%]; P=0.005).Conclusions-Although the baseline characteristics of the wake- up group of subjects were similar to those of persons enrolled in the nonwake-up group, their outcomes were much poorer. Patients with wake- up stroke may not tolerate reperfusion therapies even when started within a short time of awakening. (Stroke. 2008;39:3277-3282.

Distance from Home to Research Center: A Barrier to In-Person Visits but Not Treatment Adherence in a Stroke Trial.

BACKGROUND AND PURPOSE: Clinical trials often seek to enroll patients from both urban and rural areas to safeguard the generalizability of results. However, maintaining contact with patients who live away from a recruitment site, including rural areas, can be challenging. In this research we examine the effect of distance between patient and study centers on treatment adherence and retention. METHODS: Secondary analysis of 2,466 participants in the Insulin Resistance Intervention after Stroke trial who were enrolled from research sites in the United States. Driving distance between the zipcodes of patient\u27s reported place of residence and the study center was calculated. Outcome measures were loss to follow-up, completion of annual in-person visits, adherence to preventive therapy, and adherence to study drug in the first 3 years of participation. Logistic regression models were used to adjust for confounders. RESULTS: Distance from residence to research center was not associated with loss to follow-up, adherence to study drug, or adherence to preventive therapy (p \u3e 0.05 for each). However, patients who lived farther from the research center (\u3e120 miles), compared to patients who lived closer (\u3c60 \u3emiles), were less likely to complete the second annual in-person visit (62 vs. 81%; adjusted OR 0.48; 95% CI 0.31-0.75) and third visit (53 vs. 75%; adjusted OR 0.44; 95% CI 0.29-0.67). CONCLUSIONS: Distance between patient and study center was an independent predictor of missed in-person visits but not with adherence to study treatment or preventive care

Brain Multimodality Monitoring: A New Tool in Neurocritical Care of Comatose Patients

Neurocritical care patients are at risk of developing secondary brain injury from inflammation, ischemia, and edema that follows the primary insult. Recognizing clinical deterioration due to secondary injury is frequently challenging in comatose patients. Multimodality monitoring (MMM) encompasses various tools to monitor cerebral metabolism, perfusion, and oxygenation aimed at detecting these changes to help modify therapies before irreversible injury sets in. These tools include intracranial pressure (ICP) monitors, transcranial Doppler (TCD), Hemedex6 (thermal diffusion probe used to measure regional cerebral blood flow), microdialysis catheter (used to measure cerebral metabolism), Licox6 (probe used to measure regional brain tissue oxygen tension), and continuous electroencephalography. Although further research is needed to demonstrate their impact on improving clinical outcomes, their contribution to illuminate the black box of the brain in comatose patients is indisputable. In this review, we further elaborate on commonly used MMM parameters, tools used to measure them, and the indications for monitoring per current consensus guidelines