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.

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Background Acute gastric variceal hemorrhage (AGVH) is a serious complication of portal hypertension. Endoscopic cyanoacrylate glue injection is standard therapy for acute hemostasis; however, it may be associated with serious complications. The role of thrombin injection has not been confirmed. This study compared endoscopic thrombin and glue injections in the hemostasis of AGVH. Methods 68 eligible patients with AGVH were randomized to receive thrombin injection (33 patients) or glue injection (35 patients). The primary end point was injection-induced gastric ulcers. Secondary end points were acute hemostasis, rebleeding, and mortality within 42 days. Results Both groups had comparable baseline data. Hemostasis of active bleeding at endoscopy was 90.0 % (9/10) in the thrombin group and 90.9 % (10/11) in the glue group (P = 0.58), and 48-hour hemostasis was achieved in 93.9 % (31/33) and 97.1 % (34/35), respectively (P = 0.60). Treatment failure at 5 days occurred in two patients (6.1 %) in the thrombin group and two patients (5.7 %) in the glue group (P > 0.99). Gastric ulcers occurred in none of the thrombin group and 11/30 (36.7 %) of the glue group (P < 0.001, 95 % confidence interval [CI] 8 % – 27 %). Complications occurred in 4 (12.1 %) and 18 (51.4 %) patients in the thrombin and glue groups, respectively (P < 0.001, 95 %CI 22 % – 45 %). Two patients who received glue had post-treatment gastric ulcer bleeding. One patient in each group died. Conclusions Endoscopic thrombin injection was similar to glue injection in achieving successful hemostasis of AGVH. However, a higher incidence of complications may be associated with glue injection.

Background and Aim Simethicone is an anti‐foaming agent commonly used during colonoscopy. Although several randomized trials have shown that oral simethicone in the bowel preparation regimen may improve bowel cleanness, whether it improves adenoma detection rate (ADR) or polyp detection rate remains undetermined. The aim of this study was to determine if oral simethicone in bowel preparation regimen before colonoscopy improves the ADR. Methods A comprehensive literature review was conducted using PubMed, SDOL, Cochrane Library, and ProQuest databases through December 2017. Randomized controlled trials that compared bowel preparation regimens with simethicone versus those without it were included. Effect estimates from each study were extracted and underwent meta‐analysis using appropriate models. The primary outcomes were ADR and polyp detection rate, and secondary outcomes included bowel preparation, bubble score, and withdrawal time. Results Twelve published randomized controlled studies with 6003 participants were included for meta‐analysis. There was no difference in the overall ADR (pooled risk ratio = 1.06, 95% confidence interval = 0.91–1.24) and right‐side ADR (risk ratio = 1.50, 95% confidence interval = 0.82–2.75) between the groups with or without simethicone. However, the addition of simethicone improved adenoma detected per patient (2.20 ± 1.36 vs 1.63 ± 0.89) according to one of the included studies. Meta‐regression revealed that the baseline ADR < 25% of the included studies was associated with significant benefit of oral simethicone; the number needed to treat was 15. Conclusions The adjunction of oral simethicone significantly improved bowel preparation quality and might benefit adenoma detection in specific settings with low baseline ADR.