The Insulin Resistance Intervention after Stroke trial: a perspective on future practice and research

The prevention of recurrent events after ischaemic stroke and transient ischaemic attack is well established and based on lifestyle changes, antithrombotics, statins, antihypertensives and carotid surgery. The international IRIS trial assessed whether pioglitazone, a glucose-lowering insulin-sensitizing drug, would reduce recurrent vascular events in patients with ischaemic stroke or transient ischaemic attack. After 4.8 years, pioglitazone therapy was associated with reduced vascular events and new diabetes, and an increase in weight, oedema and bone fractures. Pioglitazone may add to the strategies for preventing further events in patients with stroke or transient ischaemic attack

Real-world Independent Testing of e-ASPECTS Software (RITeS): statistical analysis plan

Background: Artificial intelligence-based software may automatically detect ischaemic stroke lesions and provide an Alberta Stroke Program Early CT score (ASPECTS) on CT, and identify arterial occlusion and provide a collateral score on CTA. Large-scale independent testing will inform clinical use, but is lacking. We aim to test e-ASPECTS and e-CTA (Brainomix, Oxford UK) using CT scans obtained from a range of clinical studies.Methods: Using prospectively collected baseline CT and CTA scans from 10 national/international clinical stroke trials or registries (total >6600 patients), we will select a large clinically representative sample for testing e-ASPECTS and e-CTA compared to previously acquired independent expert human interpretation (reference standard). Our primary aims are to test agreement between software-derived and masked human expert ASPECTS, and the diagnostic accuracy of e-ASPECTS for identifying all causes of stroke symptoms using follow-up imaging and final clinical opinion as diagnostic ground truth. Our secondary aims are to test when and why e-ASPECTS is more or less accurate, or succeeds/fails to produce results, agreement between e-CTA and human expert CTA interpretation, and repeatability of e-ASPECTS/e-CTA results. All testing will be conducted on an intention-to-analyse basis. We will assess agreement between software and expert-human ratings and test the diagnostic accuracy of software. Conclusions: RITeS will provide comprehensive, robust and representative testing of e-ASPECTS and e-CTA against the current gold-standard, expert-human interpretation

Platelet and haemoglobin levels in patients on isosorbide mononitrate and/or cilostazol with lacunar ischaemic stroke: data from the LACI-1 trial

Background: Cilostazol and isosorbide mononitrate (ISMN) have properties that may be of benefit in the context of cerebral small vessel disease and lacunar ischaemic stroke. As both drugs may influence platelet and haemoglobin levels, we sought to assess their effects using data from the lacunar intervention trial-1 (LACI-1). Methods: LACI-1 recruited 57 patients with lacunar ischaemic stroke and randomised them to ISMN or cilostazol in isolation, or combined for 9 weeks. One group received both drugs but with a delayed start. Full blood counts were taken at baseline, and weeks 3 and 8. Platelet function was assessed with remote measurement of surface expression of P-selectin (CD62P) using kits sensitive to aspirin or clopidogrel at the same timepoints. Differences in haemoglobin and platelet levels and platelet function were assessed by multiple linear regression with adjustment for baseline value. Results: Haemoglobin levels did not differ between the treatment groups at week 8 (Table), whilst platelet levels were slightly higher in those who received cilostazol compared with no cilostazol. No differences were noted in platelet function in unstimulated, aspirin or clopidogrel testing between groups. Conclusions: Cilostazol and isosorbide mononitrate have no clinically concerning effects on haemoglobin and platelet levels and function in the short to medium term. Further assessment of the safety and efficacy of these medications following lacunar ischaemic stroke is warranted

Second Annual Seminar on Estate Planning

Schedule and materials from the Second Annual Seminar on Estate Planning held by UK/CLE on July 18-19, 1975

PRECIOUS: PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke: rationale and design of a randomised, open, phase III, clinical trial with blinded outcome assessment

Background: Elderly patients are at high risk of complications after stroke, such as infections and fever. The occurrence of these complications has been associated with an increased risk of death or dependency. Hypothesis: Prevention of aspiration, infections, or fever with metoclopramide, ceftriaxone, paracetamol, or any combination of these in the first four days after stroke onset will improve functional outcome at 90 days in elderly patients with acute stroke. Design: International, 3 × 2-factorial, randomised-controlled, open-label clinical trial with blinded outcome assessment (PROBE) in 3800 patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and an NIHSS score ≥ 6. Patients will be randomly allocated to any combination of oral, rectal, or intravenous metoclopramide (10 mg thrice daily); intravenous ceftriaxone (2000 mg once daily); oral, rectal, or intravenous paracetamol (1000 mg four times daily); or usual care, started within 24 h after symptom onset and continued for four days or until complete recovery or discharge from hospital, if earlier. Outcome: The primary outcome measure is the score on the modified Rankin Scale at 90 days (± 14 days), as analysed with multiple regression. Summary: This trial will provide evidence for a simple, safe and generally available treatment strategy that may reduce the burden of death or disability in patients with stroke at very low costs. Planning: First patient included in May 2016; final follow-up of the last patient by April 202

Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy

Publication bias confounds attempts to use systematic reviews to assess the efficacy of various interventions tested in experiments modelling acute ischaemic stroke, leading to a 30% overstatement of efficacy of interventions tested in animals