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

Rapport II.2. Modifications climatiques dues à la pollution atmosphérique

Evaluation of climatic changes risks due to the effects of : — dusts, according to their dimensions and nature ; — gases : C02 — CO and SO2; — heat, produced by different industries.Estimation des risques de modifications climatiques dues aux effets : — des poussières suivant leurs dimensions et leur nature, — des gaz CO2 , CO, S02, — de la chaleur produite par les diverses industries.Vadot L. Rapport II.2. Modifications climatiques dues à la pollution atmosphérique. In: Influence des activités de l'homme sur le cycle hydrométéorologique. Compte rendu des treizièmes journées de l'hydraulique. Paris, 16-18 septembre 1974. Tome 1, 1975

Rapport V.11. Les transferts liquides dans l’organisme

A review of the behaviour of fluid circuits in metabolic organic transport processes is followed by an examination of the most important special features of the circuits and fluids at the exchange zones (passive and active membrane transfers ). A method of analysis based on a hydraulic analogy is suggested, and its application to the following complex problems is considered : — Heat transfer in extreme cases ; — Extra-corporal dialysis and purification by artificial kidney ; — Dissolved gas transfer under transient conditions associated with major pressure variations.Après un rappel du comportement des circuits fluides intervenant dans les transports métaboliques organiques, un examen est fait des principales particularités de ces circuits et de ces fluides au niveau des zones d’échange (transferts membranaires passifs et actifs). Une méthode d’analyse s’appuyant sur l’emploi d’une analogie hydraulique est proposée. L’application de cette méthode est envisagée pour la résolution de problèmes complexes : — Transfert thermique dans des cas extrêmes ; — Dialyse extracorporelle et épuration par rein artificiel ; — Transfert des gaz dissous dans les régimes transitoires accompagnant les fortes variations de pression.Vadot L. Rapport V.11. Les transferts liquides dans l’organisme. In: Hydrotechnique des liquides industriels. Compte rendu des douzièmes journées de l'hydraulique. Paris, 6-8 juin 1972. Tome 2, 1973