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

Etude de la dynamique atmosphérique de la région grenobloise en vue de l'application à la diffusion des Polluants

Zusammenfassung. — Die Studien uber die Verunreinigung der unteren Luftschichten in Verbindung mit der Umgebung des Gebiets von Grenoble stellen ein Problem von grosser Vielfalt auf. Um das Problem, bezogen auf die Verwaltungsamt Direktion Isère anzugehen, hat man ein hydraulische Model ins Auge gefasst, das aile mdglichen atmosphárischen Erscheinungen enthált. Die Ergebnisse in Laboratorien wiirden, wáhrend der ganzen Arbeit, den Vorkommnissen in der Nátur gegeniiber gestellt. Die Studie hat vollkommen auf das Problem geantwortet. Sie lieferte daher im einzelnen aile Auskiinfte bezogen auf die Stellen die entweder fur Státeplanung oder fur die verschmutzende Industrie geeignet waren. Weiterhin allé die Stellen die entweder « sáubere » oder « halbsâubere » Industrie aufnehmen kdnnen wurden festgestellt.Abstract. — The pollution studies associated with low level atmospheric dynamics, in connection with the surroundings in the Grenoble region create a very complex problem. In order to tackle this problem, a scale model was built reproducing the atmospheric phenomena in similitude so as to compare, throughout the study, the features of characteristic situations observed in a laboratory, with those observed in real life. The study was a success as it mainly gave information concerning sites suitable for urban or polluting industrial development, by indicating those areas which can only accommodate « clean » or « semi- clean » industries.Résumé. — Les études de pollution associées à la dynamique atmosphérique des basses couches, en liaison avec l'environnement de la région de Grenoble, posent un problème de grande complexité. Pour aborder ce problème on a envisagé la reproduction en similitude des phénomènes atmosphériques sur modèle réduit en confrontant, tout au long de l'étude, les aspects observés en laboratoire avec les aspects observés dans la nature, pour des situations caractéristiques. L'étude a parfaitement répondu au problème en fournissant en particulier tous les renseignements concernant les sites préférentiels d'aménagement urbain ou d'industries polluantes, et en indiquant les zones qui ne peuvent accueillir que des industries « propres » ou « semi-propres ».Vadot L., Belle P., Milhe M. Etude de la dynamique atmosphérique de la région grenobloise en vue de l'application à la diffusion des Polluants. In: Revue de géographie alpine, tome 59, n°3, 1971. pp. 283-324

Clinical and economic impact of drug eluting beads in transarterial chemoembolization for hepatocellular carcinoma

International audienceWHAT IS KNOWN AND OBJECTIVE:Drug eluting beads (DEBs) theoretically improve the efficacy and safety of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). Nonetheless, their economic profile has not been assessed. Our retrospective before/after study aimed to compare efficacy, safety and economic profile of two strategies of TACE without (Period 1) or with the possibility of using DEBs (Period 2).METHODS:All HCC patients treated by TACE in our hospital between March 2006 and May 2013 were included. Economic analyses were performed from the French Public Health Insurance point of view according to the French Diagnosis-Related Group prospective payment system and from the analytic accountability.RESULTS AND DISCUSSION:One hundred and sixty-one patients were included. Median time to treatment failure and overall survival were 13.1 and 23.8 months in Period 1 vs. 14.1 and 30.2 months in Period 2 (P = 0.45 and P = 0.40). Mean hospital durations and tariffs were 14.9 ± 7.7 days and € 11 472 ± 5901 in Period 1 vs. 12.4 ± 8.4 days and € 7654 ± 4625 in Period 2 (P = 0.03 and P < 10(-4) ).WHAT IS NEW AND CONCLUSION:The possibility of using DEBs did not improve the prognosis in HCC patients treated by TACE. Nonetheless, it had a better medico-economic profile

Medical students' skills and needs for training in breaking bad news.

This study assessed medical students' perception of individual vs. group training in breaking bad news (BBN) and explored training needs in BBN. Master-level students (N = 124) were randomised to group training (GT)-where only one or two students per group conducted a simulated patient (SP) interview, which was discussed collectively with the faculty-or individual training (IT)-where each student conducted an SP interview, which was discussed during individual supervision. Training evaluation was based on questionnaires, and the videotaped interviews were rated using the Roter Interaction Analysis System. Students were globally satisfied with the training. Still, there were noticeable differences between students performing an interview (GT/IT) and students observing interviews (GT). The analysis of the interviews showed significant differences according to scenarios and to gender. Active involvement through SP interviews seems required for students to feel able to reach training objectives. The evaluation of communication skills, revealing a baseline heterogeneity, supports individualised training

The donders model of the circulation in normo- and pathophysiology.

Item does not contain fulltextThe solution of some recent as well as of long standing problems, unanswerable due to experimental inaccessibility or moral objections are addressed. In this report, a model of the closed human cardiovascular loop is developed. This model, using one set of 88 equations, allows variations from normal resting conditions to exercise, as well as to the ultimate condition of a circulation following cardiac arrest. The principal purpose of the model is to evaluate the continuum of physiological conditions to cardiopulmonary resuscitation (CPR) effects within the circulation.Within the model, Harvey's view of the circulation has been broadened to include impedance-defined flow as a unifying concept, and as a mechanism in CPR. The model shows that depth of respiration, sympathetic stimulation of cardiac contractile properties and baroreceptor activity can exert powerful influences on the increase in cardiac output, while heart and respiratory rate increases tend to exert an inhibiting influence, with the pressure and flow curves compatible with accepted references. Impedance-defined flow encompasses both positive and negative effects.The model also demonstrates the limitations to cardiopulmonary resuscitation caused by external force applied to intrathoracic structures, with effective cardiac output being limited by collapse and sloshing. Stroke volumes from 6 to 51 ml are demonstrated. It shows that the clinical inclination to apply high pressures to intrathoracic structures may not be rewarded with improved net flow