Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88–1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74–2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53–8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67–1·94; p=0·64). Interpretation: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Funding: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health

Quadrupole Relaxation of 79\text{}^{79}Br Nuclei in Ferroelectric (CH3\text{}_{3})4\text{}_{4}NCdBr3\text{}_{3} (TMCB)

Investigations of temperature dependence of a nuclear quadrupole spin-lattice relaxation time of $\text{}^{79}$Br nuclei in ferroelectric (CH$\text{}_{3}$)$\text{}_{4}$NCdBr$\text{}_{3}$ are presented. It is shown that in paraelectric phase in the vicinity of phase transition temperature relaxation process is determined by critical fluctuations of electric field gradient. In ferroelectric phase relaxation is related to three different mechanisms, namely: lattice vibrations, CH$\text{}_{3¯}$ group reorientations and TMA cation motions. According to the results of measurements it is concluded that the phase transition is connected with ordering of TMA cations

Nuclear Quadrupole Resonance Investigation of Phase Transition in Tetramethylammonium Cadmium Tribromide

The critical temperature dependence of the nuclear quadrupole- resonance $\text{}^{79}$Br frequencies at the phase transition (T$\text{}_{c}$ = 163 K) was found in (CH$\text{}_{3}$)$\text{}_{4}$NCdBr$\text{}_{3}$. It was concluded that bromine nuclei take part in the phase transition not directly but via the interaction with the crystal polarization

Low-temperature crystal structure, specific heat, and dielectric properties of lithium tetraborate Li2B4O7Li_{2}B_{4}O_{7}

Coherent neutron powder diffraction experiments were carried out together with specific heat, dilatometry, and dielectric spectroscopy studies on Li2B4O7 enriched with B-11 isotope to 99.3% at low temperatures. Neither traces of phase transformations nor discontinuous changes in physical properties were observed. Negative thermal expansion, anomalous thermal behavior of selected interatomic distances/angles, isotropic displacement parameters on specific sites as well as dielectric constant were discussed in terms of dynamic lithium disorder. (C) 2010 American Institute of Physics. [doi:10.1063/1.3504244