Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None

L'absorption hertzienne de quelques alcools

The dielectric absorption in 14 different alcohols (aliphatic, mono-, di-, trihydric, alicyclic, having double bond) in supercooled state, has been studied as a function of temperature at low frequency (0,5 kHz-300 kHz). From these results it has been proposed that the dielectric absorption of alcohol is due to the OH group.L'absorption hertzienne de 14 alcools différents (aliphatiques, mono-, di-, trialcools, alicyclique, à double liaison), a été étudiée à l'état surrefroidi, en fonction de la température, en basse fréquence (0,5 kHz à 300 kHz). Ces résultats conduisent à admettre que l'absorption hertzienne des alcools provient du groupement OH

L'absorption hertzienne du mélange de deux liquides polaires

The dielectric behaviour was studied on a number of mixtures of two polar liquids as a function of concentration. The results show that in the mixture of two associated liquids the dielectric absorption of each liquid joints to be one common absorption at any concentration (n-propanol + cyclohexanol, ethanol + cyclohexanol), but in the mixture of associated and non-associated liquids the absorption only approach more or less (isoamyl bromide + geraniol, isoamyl bromide + cyclohexanol). Results contrary to this rule were observed on the mixture of glycerol and n-propanol (two absorptions). It is suggested that the magnitude of the displacement of dielectric absorption in the mixture may be the indication of degree of mixture.On a étudié le comportement diélectrique de quelques mélanges de deux liquides polaires, en fonction de la concentration. Les résultats montrent que dans le mélange de deux liquides autoassociés les absorptions hertziennes de chaque liquide s'unissent en une absorption commune, quelle que soit la concentration (n-propanol + cyclohexanol, éthanol + cyclohexanol) ; mais dans le mélange de deux liquides, l'un autoassocié et l'autre non-autoassocié, les absorptions se rapprochent seulement plus ou moins (bromure isoamylique + géraniol, bromure isoamylique + cyclohexanol). Des résultats contraires à cette règle ont toutefois été observés pour le mélange glycérol + n-propanol (deux absorptions). On a suggéré que la grandeur du déplacement des absorptions hertziennes dans le mélange peut être l'indication du degré de perfection du mélange