Thrombolysis in very elderly people: controlled comparison of SITS international stroke thrombolysis registry and virtual international stroke trials archive

<p>Objective To assess effect of age on response to alteplase in acute ischaemic stroke.</p> <p>Design Adjusted controlled comparison of outcomes between non-randomised patients who did or did not undergo thrombolysis. Analysis used Cochran-Mantel-Haenszel test and proportional odds logistic regression analysis.</p> <p>Setting Collaboration between International Stroke Thrombolysis Registry (SITS-ISTR) and Virtual International Stroke Trials Archive (VISTA).</p> <p>Participants 23 334 patients from SITS-ISTR (December 2002 to November 2009) who underwent thrombolysis and 6166 from VISTA neuroprotection trials (1998-2007) who did not undergo thrombolysis (as controls). Of the 29 500 patients (3472 aged >80 (“elderly,” mean 84.6), data on 272 patients were missing for baseline National Institutes of Health stroke severity score, leaving 29 228 patients for analysis adjusted for age and baseline severity.</p> <p>Main outcome measures Functional outcomes at 90 days measured by score on modified Rankin scale.</p> <p>Results Median severity at baseline was the same for patients who underwent thrombolysis and controls (median baseline stroke scale score: 12 for each group, P=0.14; n=29 228). The distribution of scores on the modified Rankin scale was better among all thrombolysis patients than controls (odds ratio 1.6, 95% confidence interval 1.5 to 1.7; Cochran-Mantel-Haenszel P<0.001). The association occurred independently among patients aged ≤80 (1.6, 1.5 to 1.7; P<0.001; n=25 789) and in those aged >80 (1.4, 1.3 to 1.6; P0.001; n=3439). Odds ratios were consistent across all 10 year age ranges above 30, and benefit was significant from age 41 to 90; dichotomised outcomes (score on modified Rankin scale 0-1 v 2-6; 0-2 v 3-6; and 6 (death) v rest) were consistent with the results of the ordinal analysis.</p> <p>Conclusions Outcome in patients with acute ischaemic stroke is significantly better in those who undergo thrombolysis compared with those who do not. Increasing age is associated with poorer outcome but the association between thrombolysis treatment and improved outcome is maintained in very elderly people. Age alone should not be a barrier to treatment.</p&gt

The long-term spectroscopic misadventures of AG Dra with a nod toward V407 Cyg: Degenerates behaving badly

We present some results of an ongoing study of the long-term spectroscopic variations of AG Dra, a prototypical eruptive symbiotic system. We discuss the effects of the environment and orbital modulation in this system and some of the physical processes revealed by a comparison with the nova outburst of the symbiotic-like recurrent nova V407 Cyg 2010.Comment: 11 pages, invited review to appear in the proceedings of the 2011 Asiago Workshop on Symbiotic Stars, A. Siviero and U. Munari eds., Baltic Astronomy special issue. See also http://etd.adm.unipi.it/theses/available/etd-05052010-002805

Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset

<p><b>Background and Purpose:</b> Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke.</p> <p><b>Methods:</b> We assessed the safety of thrombolysis under APs in 11 865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale >= 4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale >= 4 plus any ICH]), functional outcome at 3 months and mortality.</p> <p><b>Results:</b> A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogrel, 175 (1.5%) ASA and dipyridamole, 151 (1.3%) ASA and clopidogrel, and 197 (1.7%) others. Patients receiving APs were 5 years older and had more risk factors than AP nave patients. Incidences of SICH per SITS-MOST (ECASS II respectively) were as follows: 1.1% (4.1%) AP naive, 2.5% (6.2%) any AP, 2.5% (5.9%) ASA, 1.7% (4.2%) clopidogrel, 2.3% (5.9%) ASA and dipyridamole, and 4.1% (13.4%) ASA and clopidogrel. In multivariable analyses, the combination of ASA and clopidogrel was associated with increased risk for SICH per ECASS II (odds ratio, 2.11; 95% CI, 1.29 to 3.45; P = 0.003). However, we found no significant increase in the risk for mortality or poor functional outcome, irrespective of the AP subgroup or SICH definition.</p> <p><b>Conclusion:</b> The absolute excess of SICH of 1.4% (2.1%) in the pooled AP group is small compared with the benefit of thrombolysis seen in randomized trials. Although caution is warranted in patients receiving the combination of ASA and clopidogrel, AP treatment should not be considered a contraindication to thrombolysis.</p&gt

The spectroscopic evolution of the symbiotic star AG Draconis. I.The O VI Raman, Balmer, and helium emission line variations during the outburst of 2006-2008

AG Dra is one of a small group of low metallicity S-type symbiotic binaries with K-type giants that undergoes occasional short-term outbursts of unknown origin. Our aim is to study the behavior of the white dwarf during an outburst using the optical Raman lines and other emission features in the red giant wind. The goal is to determine changes in the envelope and the wind of the gainer in this system during a major outburst event and to study the coupling between the UV and optical during a major outburst. Using medium and high resolution groundbased optical spectra and comparisons with archival $FUSE$ and $HST/STIS$ spectra, we study the evolution of the Raman O VI features and the Balmer, He I, and He II lines during the outburst from 2006 Sept. through 2007 May and include more recent observations (2009) to study the subsequent evolution of the source. The O VI Raman features disappeared completely at the peak of the major outburst and the subsequent variation differs substantially from that reported during the previous decade. The He I and He II lines, and the Balmer lines, vary in phase with the Raman features but there is a double-valuedness to the He I 6678, 7065 relative to the O VI Raman 6825\AA\ variations in the period between 2006-2008 that has not been previously reported. The variations in the Raman feature ratio through the outburst interval are consistent with the disappearance of the O VI FUV resonance wind lines from the white dwarf and of the surrounding O$^{+5}$ ionized region within the red giant wind provoked by the expansion and cooling of the white dwarf photosphere.Comment: 10 pages, 15 figs. A&A (in press, accepted for publication 23/11/2009

High Mass Triple Systems: The Classical Cepheid Y Car

We have obtained an HST STIS ultraviolet high dispersion Echelle mode spectrum the binary companion of the double mode classical Cepheid Y Car. The velocity measured for the hot companion from this spectrum is very different from reasonable predictions for binary motion, implying that the companion is itself a short period binary. The measured velocity changed by 7 km/ s during the 4 days between two segments of the observation confirming this interpretation. We summarize "binary" Cepheids which are in fact members of triple system and find at least 44% are triples. The summary of information on Cepheids with orbits makes it likely that the fraction is under-estimated.Comment: accepted by A

The O I] 1641A line as a probe of symbiotic star winds

The neutral oxygen resonance 1302A line can, if the optical depth is sufficiently high, de-excite by an intercombination transition at 1641A to a metastable state. This has been noted in a number of previous studies but never systematically investigated as a diagnostic of the neutral red giant wind in symbiotic stars and symbiotic-like recurrent novae. We used archival $IUE$ high resolution, and GHRS and STIS medium and high resolution, spectra to study a sample of symbiotic stars. The integrated fluxes were measured, where possible, for the O I 1302A and O I] 1641A lines. The intercombination 1641A line is detected in a substantial number of symbiotic stars with optical depths that give column densities comparable with direct eclipse measures (EG And) and the evolution of the recurrent nova RS Oph 1985 in outburst. In four systems (EG And, Z And, V1016 Cyg, and RR Tel), we find that the O I] variations are strongly correlated with the optical light curve and outburst activity. This transition can also be important for the study of a wide variety of sources in which an ionization-bounded H II region is imbedded in an extensive neutral medium, including active galactic nuclei, and not only for evaluations of extinction.Comment: accepted for publication in Astronomy and Astrophysics (2010 Feb. 23), in press, NASA-GSFC-Code 66

The Virtual International Stroke Trials Archive

BACKGROUND AND PURPOSE: Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. METHODS: Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. RESULTS: Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on \u3e15,000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 69+/-12 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. CONCLUSIONS: This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning

Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis

BackgroundImatinib, a tyrosine kinase inhibitor, has been shown to restore bloodâ brain barrier integrity and reduce infarct size, haemorrhagic transformation and cerebral oedema in stroke models treated with tissue plasminogen activator. We evaluated the safety of imatinib, based on clinical and neuroradiological data, and its potential influence on neurological and functional outcomes.MethodsA phase II randomized trial was performed in patients with acute ischaemic stroke treated with intravenous thrombolysis. A total of 60 patients were randomly assigned to four groups [3 (active): 1 (control)]; the active treatment groups received oral imatinib for 6 days at three dose levels (400, 600 and 800 mg). Primary outcome was any adverse event; secondary outcomes were haemorrhagic transformation, cerebral oedema, neurological severity on the National Institutes of Health Stroke Scale (NIHSS) at 7 days and at 3 months and functional outcomes on the modified Rankin scale (mRS).ResultsFour serious adverse events were reported, which resulted in three deaths (one in the control group and two in the 400â mg dose group; one patient in the latter group did not receive active treatment and the other received two doses). Nonserious adverse events were mostly mild, resulting in full recovery. Imatinib ameliorated neurological outcomes with an improvement of 0.6 NIHSS points per 100 mg imatinib (P = 0.02). For the 800â mg group, the mean unadjusted and adjusted NIHSS improvements were 4 (P = 0.037) and 5 points (P = 0.012), respectively, versus controls. Functional independence (mRS 0â 2) increased by 18% versus controls (61 vs. 79; P = 0.296).ConclusionThis phase II study showed that imatinib is safe and tolerable and may reduce neurological disability in patients treated with intravenous thrombolysis after ischaemic stroke. A confirmatory randomized trial is currently underway.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136298/1/joim12576_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136298/2/joim12576.pd

Evolution of the Thrombolytic Treatment Window for Acute Ischemic Stroke

Ischemic stroke is a major cause of morbidity and mortality for which the only approved treatment in the acute setting is intravenous thrombolysis. The efficacy and safety of recombinant tissue plasminogen activator (rt-PA) have been firmly established within 3 h of symptom onset; however, few patients are eligible for treatment in this time window. Expanding the time for treatment has been challenging, but new evidence has demonstrated a modest statistical improvement in selected patients when rt-PA is administered within 4.5 h. This important finding hopefully will enable more patients to receive treatment and simultaneously provides an opportunity to reaffirm that the benefits of rt-PA diminish with time