Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036.
FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.
Neutron scattering has been used to investigate the crystal structure and lattice dynamics of superconducting Na 0.3 CoO 2 ·1.4(H/D) 2 O, and the "parent" Na 0.3 CoO 2 material. The structure of Na 0.3 CoO 2 consists of alternate layers of CoO 2 and Na and is the same as the structure at higher Na concentrations. For the superconductor, the water forms two additional layers between the Na and CoO 2 , increasing the c-axis lattice parameter of the hexagonal P6 3 /mmc space group from 11.16 Å to 19.5 Å. The Na ions are found to occupy a different configuration from the parent compound, while the water forms a structure that replicates the structure of ice. Both types of sites are only partially occupied. The CoO 2 layer in these structures is robust, on the other hand, and we find a strong inverse correlation between the CoO 2 layer thickness and the superconducting transition temperature (T C increases with decreasing thickness). The phonon density-ofstates for Na 0.3 CoO 2 exhibits distinct acoustic and optic bands, with a high-energy cutoff of ~100 meV. The lattice dynamical scattering for the superconductor is dominated by the hydrogen modes, with librational and bending modes that are quite similar to ice, supporting the structural model that the water intercalates and forms ice-like layers in the superconductor.
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