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.

Research in context panel: 445Identifying people at highest risk of ICH may facilitate timely and accurate prognostication to allow mitigation of reversible risk factors for bleeding (e.g. intensive blood pressure control), and selection of participants for clinical trials. While more complex combinations of clinical, biochemical, and radiological markers might further improve stroke risk prediction, balancing accuracy with simplicity will remain important.

Background and Purpose: Post-stroke pneumonia is a feared complication of stroke as it is associated with greater mortality and disability than in those without pneumonia. Patients are often kept “Nil By Mouth” (NBM) after stroke until after receiving a screen for dysphagia and declared safe to resume oral intake. We aimed to assess the proportional contribution of stroke severity and dysphagia screen to pneumonia by borrowing idea from coalition game theory on fair distribution of marginal profit (Shapley value).Method: Retrospective study of admissions to the stroke unit at Monash Medical Center in 2015. Seventy-five percent of data were partitioned into training set and the remainder (25%) into validation set. Variables associated with pneumonia (p < 0.1) were entered into Shapley value regression and conditional decision tree analysis.Results: In 2015, there were 797 admissions and 617 patients with ischemic and hemorrhagic stroke (age 69.9 ± 16.2, male = 55.0%, National Institute of Health Stroke Scale/NIHSS 8.1 ± 7.9). The frequency of pneumonia was 6.6% (41/617). In univariable analyses NIHSS, time to dysphagia screen, Charlson comorbidity index (CCI), and age were significantly associated with pneumonia but not weekend admission. Shapley value regression showed that the largest contributor to the model was stroke severity (72.8%) followed by CCI (16.2%), dysphagia screen (3.8%), and age (7.2%). Decision tree analysis yielded an NIHSS threshold of 14 for classifying people with (27% of 75 patients) and without pneumonia (2.5% of 308 patients). The area under the ROC curve for training data was 0.83 (95% CI 0.75–0.91) with no detectable difference between the training and test data (p = 0.4). Results were similar when dysphagia was exchanged for the variable dysphagia screen.Conclusion: Stroke severity status, and not dysphagia or dysphagia screening contributed to the decision tree model of post stroke pneumonia. We cannot exclude the chance that using dysphagia screen in this cohort had minimized the impact of dysphagia on development of pneumonia.

Nasogastric tube (NGT) is often used in stroke patients who are dysphagic (deglutition disorders) or have decreased conscious state. This method of feeding is assumed to have minimal complications. The aim of this study is to analyze complications associated with NGT and variables associated with mortality. Retrospective analysis of 250 acute stroke patients requiring NGT feeding between 2003 and 2020. There were 250 patients (median age 76 (IQR 68–83), 56.4% males, median time to NGT 1 day (IQR 0–3). Discussion with family prior to insertion of NGT recorded in 46 (18.4%). There were 123 cases (49.2%) of aspiration pneumonia. There were 188 (75.2%) NGT associated complications: 67 patients (26.8%) had failed insertion, 31 required multiple attempts, 129 patients (51.6%) pulled out NGT, 107 patients (42.8%) had NGT placed in wrong positions and require reinsertion, 20 cases in the lung, 5 pneumothorax cases, 97 in the gastro oesophageal junction or hiatus hernias, 1 case of oesophageal ulceration, 37 coiled, kinked or resistance. 78 cases the tips were not seen on chest X-ray (CXR), gastrointestinal bleeding in 9 cases, epistaxis in 6 cases), 96 patients (38.4%) required restrain. There were 91 death (36.4%) with 73 patients occurring during hospital admission and a further 18 died within 6 months. Death was more frequent in those age > 60 (72 of 216 patients versus 1 of 33 patients, p < 0.01). The median National Institute of Health Stroke Score/NIHSS of those with aspiration pneumonia was higher than those without (19.5 versus 15, p < 0.01). Decision tree analysis first split at age (≤ 59 versus > 59, p = 0.03), NIHSS (≤ 16 or > 16, p = 0.02), post-stroke pneumonia (p = 0.04) and multiple NGT insertion (p = 0.01). The area under the ROC curve was for this model was 0.75 (95% CI 0.69–0.80). Complications were common among patients with NGT complications. These findings may be used to inform discussions with families regarding NGT.