421 research outputs found

    Mesoscopic motion of atomic ions in magnetic fields

    Get PDF
    We introduce a semiclassical model for moving highly excited atomic ions in a magnetic field which allows us to describe the mixing of the Landau orbitals of the center of mass in terms of the electronic excitation and magnetic field. The extent of quantum energy flow in the ion is investigated and a crossover from localization to delocalization with increasing center of mass energy is detected. It turns out that our model of the moving ion in a magnetic field is closely connected to models for transport in disordered finite-size wires.Comment: 4 pages, 2 figures, subm. to Phys.Rev.A, Rap.Co

    High Early Fluid Input After Aneurysmal Subarachnoid Hemorrhage: Combined Report of Association With Delayed Cerebral Ischemia and Feasibility of Cardiac Output–Guided Fluid Restriction

    Get PDF
    Background: Guidelines on the management of aneurysmal subarachnoid hemorrhage (aSAH) recommend euvolemia, whereas hypervolemia may cause harm. We investigated whether high early fluid input is associated with delayed cerebral ischemia (DCI), and if fluid input can be safely decreased using transpulmonary thermodilution (TPT). Methods: We retrospectively included aSAH patients treated at an academic intensive care unit (2007-2011; cohort 1) or managed with TPT (2011-2013; cohort 2). Local guidelines recommended fluid input of 3 L daily. More fluids were administered when daily fluid balance fell below +500 mL. In cohort 2, fluid input in high-risk patients was guided by cardiac output measured by TPT per a strict protocol. Associations of fluid input and balance with DCI were analyzed with multivariable logistic regression (cohort 1), and changes in hemodynamic indices after institution of TPT assessed with linear mixed models (cohort 2). Results: Cumulative fluid input 0 to 72 hours after admission was associated with DCI in cohort 1 (n=223; odds ratio [OR] 1.19/L; 95% confidence interval 1.07-1.32), whereas cumulative fluid balance was not. In cohort 2 (23 patients), using TPT fluid input could be decreased from 6.0 ± 1.0 L before to 3.4 ± 0.3 L; P =.012), while preload parameters and consciousness remained stable. Conclusion: High early fluid input was associated with DCI. Invasive hemodynamic monitoring was feasible to reduce fluid input while maintaining preload. These results indicate that fluid loading beyond a normal preload occurs, may increase DCI risk, and can be minimized with TPT

    Patients Enrolled in Large Randomized Clinical Trials of Antiplatelet Treatment for Prevention After Transient Ischemic Attack or Ischemic Stroke Are Not Representative of Patients in Clinical Practice: the Netherlands Stroke Survey

    Get PDF
    Background and Purpose—Many randomized clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of new vascular events in patients with a recent transient ischemic attack or ischemic stroke. Evidence from these trials forms the basis for national and international guidelines for the management of nearly all such patients in clinical practice. However, abundant and strict enrollment criteria may limit the validity and the applicability of results of randomized clinical trials to clinical practice. We estimated the eligibility for participation in landmark trials of antiplatelet drugs of an unselected group of patients with stroke or transient ischemic attack from a national stroke survey. Methods—Nine hundred seventy-two patients with transient ischemic at

    PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN 74418480]

    Get PDF
    BACKGROUND: In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1°C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3°C (95% CI: 0.1–0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic. METHODS/DESIGN: Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level. DISCUSSION: This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one

    Rapid alteplase administration improves functional outcomes in patients with stroke due to large vessel occlusions

    Get PDF
    Background and Purpose: We report the relation of onset-to-treatment time and door-to-needle time with functional outcomes and mortality among patients with ischemic stroke with imaging-proven large vessel occlusion treated with intravenous alteplase. Methods: Individual patient-level data from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration were pooled from 7 trials that randomized patients to mechanical thrombectomy added to best medical therapy versus best medical therapy alone. Analysis was restricted to patients who received alteplase directly at the endovascular hospital. The primary outcome was disability defined on the modified Rankin Scale at 3 months. Results: Among 601 patients, mean age was 66.0 years (SD, 13.9), 50% were women, and median National Institutes of Health Stroke Scale score was 17. Onset-to-treatment time was median 125 minutes (interquartile range, 90–170). Door-to-treatment time was median 38 minutes (interquartile range, 26–55). Each 60-minute onset-to-treatment time delay was associated with greater disability at 90 days; the odds of functional independence (modified Rankin Scale, 0–2) at 90 days was 0.82 (95% CI, 0.66–1.03). With each 60-minute delay in door-to-needle time; the odds of functional independence was 0.55 (95% CI, 0.37–0.81) at 90 days. The absolute decline in the rate of excellent outcome (modified Rankin Scale, 0–1 at 90 days) was 20.3 per 1000 patients treated per 15-minute delay in door-to-needle time. The adjusted absolute risk difference for a door-to-needle time <30 minutes versus 30 to 60 minutes was 19.3% for independent outcome (number-needed-to-treat ≈5 to gain 1 additional good outcome). Symptomatic intracranial hemorrhage occurred in 3.4% of patients, without a significant time dependency: odds ratio, 0.74 (95% CI, 0.43–1.28). Conclusions: Faster intravenous thrombolysis delivery is associated with less disability at 3 months among patients with large vessel occlusion

    National Institutes of Health Stroke Scale An Alternative Primary Outcome Measure for Trials of Acute Treatment for Ischemic Stroke

    Get PDF
    Background and Purpose- The modified Rankin Scale (mRS) at 3 months is the most commonly used primary outcome measure in stroke treatment trials, but it lacks specificity and requires long-term follow-up interviews, which consume time and resources. An alternative may be the National Institutes of Health Stroke Scale (NIHSS), early after stroke. Our aim was to evaluate whether the NIHSS assessed within 1 week after treatment could serve as a primary outcome measure for trials of acute treatment for ischemic stroke. Methods- We used data from 2 randomized controlled trials of endovascular treatment for ischemic stroke: the positive MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; N=500) and the neutral IMS (Interventional Management of Stroke) III trial (N=656). We used a causal mediation model, with linear and ordinal logistic regression adjusted for confounders, to evaluate the NIHSS 24 hours and 5 to 7 days after endovascular treatment as primary outcome measures (instead of the mRS at 3 months) in both trials. Patients who had died before the NIHSS was assessed received the maximum score of 42. NIHSS+1 was then log10-transformed. Results- In both trials, there was a significant correlation between the NIHSS at 24 hours and 5 to 7 days and the mRS. In MR CLEAN, we found a significant effect of endovascular treatment on the mRS and on the NIHSS at 24 hours and 5 to 7 days. After adjustment for NIHSS at 24 hours and 5 to 7 days, the effect of endovascular treatment on the mRS decreased from common odds ratio 1.68 (95% CI, 1.22-2.32) to respectively 1.36 (95% CI, 0.97-1.91) and 1.24 (95% CI, 0.87-1.79), indicating that treatment effect on the mRS is in large part mediated by the NIHSS. In the IMS III trial there was no treatment effect on the NIHSS at 24 hours and 5 to 7 days, corresponding with the absence of a treatment effect on the mRS. Conclusions- The NIHSS within 1 week satisfies the requirements for a surrogate end point and may be used as a primary outcome measure in trials of acute treatment for ischemic stroke, particularly in phase II(b) trials. This could reduce stroke-outcome assessment to its essentials (ie, neurological deficit), and reduce trial duration and costs. Whether and under which conditions it could be used in phase III trials requires a debate in the field with all parties. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758; https://www.clinicaltrials.gov. Unique identifier: NCT00359424.</p

    Does sex modify the effect of endovascular treatment for ischemic stroke? A subgroup analysis of seven randomized trials

    Get PDF
    Background and Purpose: Previous studies have reported less favorable outcome and less effect of endovascular treatment (EVT) after ischemic stroke in women than in men. Our aim was to study the influence of sex on outcome and on the effect of EVT for ischemic stroke in recent randomized trials on EVT. Methods: We used data from 7 randomized controlled trials on EVT within the HERMES collaboration. The primary outcome was 90-day functional outcome (modified Rankin Scale). We compared baseline characteristics and outcomes between men and women. With ordinal logistic regression, we evaluated the association between EVT and 90-day functional outcome for men and women separately, adjusted for potential confounders. We tested for interaction between sex and EVT. Results: We included 1762 patients in the analyses, of whom 833 (47%) were women. Women were older (median, 70 versus 66 years; P&lt;0.001), were smoking less often (30% versus 44%; P&lt;0.001), and had higher collateral grades (grade 3: 46% versus 35%; P&lt;0.001) than men. Functional independence (modified Rankin Scale score, 0–2) at 90 days was reached by 318 women (39%) and 364 men (39%). The effect of EVT on the ordinal modified Rankin Scale was similar in women (adjusted common odds ratio [acOR], 2.13; 95% CI, 1.47–3.07) and men (acOR, 2.16; 95% CI, 1.59–2.96), with a P for interaction of 0.926. Conclusions: Sex does not influence clinical outcome after EVT and does not modify treatment effect of EVT. Therefore, sex should not be a consideration in the selection of patients for EVT

    Prediction of Outcome and Endovascular Treatment Benefit:Validation and Update of the MR PREDICTS Decision Tool

    Get PDF
    Background and Purpose: Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice. Methods: We used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0–2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C) statistic. Results: We included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C-statistic for functional independence was 0.74 (95% CI, 0.72–0.77) in HERMES and, after model updating, 0.80 (0.78–0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%–14.4%). Patients with low (&lt;1%) predicted treatment benefit (n=135/3156 [4.3%]) had low rates of functional independence, irrespective of reperfusion status, suggesting potential absence of treatment benefit. The updated model was made available online for clinicians and researchers at www.mrpredicts.com. Conclusions: Because of the substantial treatment effect and small potential harm of EVT, most patients arriving within 6 hours at an endovascular-capable center should be treated regardless of their clinical characteristics. MR PREDICTS can be used to support clinical judgement when there is uncertainty about the treatment indication, when resources are limited, or before a patient is to be transferred to an endovascular-capable center
    corecore