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Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA. We used a computer-generated randomisation sequence and interactive voice and web response system to assign patients aged 18–83 years with moderately severe acute ischaemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 8–20 to treatment with intravenous multipotent adult progenitor cells (400 million or 1200 million cells) or placebo between 24 h and 48 h after symptom onset. Patients were ineligible if there was a change in NIHSS of four or more points during at least a 6 h period between screening and randomisation, had brainstem or lacunar infarct, a substantial comorbid disease, an inability to undergo an MRI scan, or had a history of splenectomy. In group 1, patients were enrolled and randomly assigned in a 3:1 ratio to receive 400 million cells or placebo and assessed for safety through 7 days. In group 2, patients were randomly assigned in a 3:1 ratio to receive 1200 million cells or placebo and assessed for safety through the first 7 days. In group 3, patients were enrolled, randomly assigned, and stratified by baseline NIHSS score to receive 1200 million cells or placebo in a 1:1 ratio within 24–48 h. Patients, investigators, and clinicians were masked to treatment assignment. The primary safety outcome was dose-limiting toxicity effects. The primary efficacy endpoint was global stroke recovery, which combines dichotomised results from the modified Rankin scale, change in NIHSS score from baseline, and Barthel index at day 90. Analysis was by intention to treat (ITT) including all patients in groups 2 and 3 who received the investigational agent or placebo. This study is registered with ClinicalTrials.gov, number NCT01436487. The study was done between Oct 24, 2011, and Dec 7, 2015. After safety assessments in eight patients in group 1, 129 patients were randomly assigned (67 to receive multipotent adult progenitor cells and 62 to receive placebo) in groups 2 and 3 (1200 million cells). The ITT populations consisted of 65 patients who received multipotent adult progenitor cells and 61 patients who received placebo. There were no dose-limiting toxicity events in either group. There were no infusional or allergic reactions and no difference in treatment-emergent adverse events between the groups (64 [99%] of 65 patients in the multipotent adult progenitor cell group vs 59 [97%] of 61 in the placebo group). There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90 (odds ratio 1·08 [95% CI 0·55–2·09], p=0·83). Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke. Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned. Athersys Inc.

Coronary artery disease remains the leading cause of death in developed countries despite significant progress in primary prevention and treatment strategies. Older patients are at particularly high risk of poor outcomes following acute coronary syndrome and impaired nutrition, including low vitamin D levels, may play a role. The extraskeletal effects of vitamin D, in particular, its role in maintaining a healthy cardiovascular system are receiving increased attention. Longitudinal studies have demonstrated increased cardiovascular mortality and morbidity associated with vitamin D deficiency. Low vitamin D levels have been linked to inflammation, higher coronary artery calcium scores, impaired endothelial function and increased vascular stiffness. However, so far, few randomized controlled trials have investigated the potential benefits of vitamin D supplementation in preventing cardiovascular events, and most available trials have tested low doses of supplementation in relatively low-risk populations. Whether vitamin D supplementation will be beneficial among patients with coronary artery disease, including high risk older patients presenting with acute coronary syndrome, is unknown and warrants further investigation.

\"Director Robert Luketic and screenwriters Jason Dean Hall and Barry Levy team up to adapt author Joseph Finder's novel centering on a tech-savvy twentysomething who becomes a corporate spy for a scheming businessman. Determined to make the most of his new job at Wyatt Telecom, Adam Cassidy (Liam Hemsworth) is horrified when a felonious mistake earns him the wrath of unforgiving CEO Nicholas Wyatt (Gary Oldman). Typically, Wyatt's first response would be to throw a lawbreaking employee under the bus. But this time he's willing to cut a deal: Should Adam agree to infiltrate Wyatt Telecom's chief rival, the CEO will turn a blind eye to his employee's error. In no time Adam is climbing the corporate ladder straight to the top. No one suspects a thing, and Wyatt is gaining a distinct advantage over the competition. Later, upon realizing that his success is a mere illusion and he's become a simple pawn in a much bigger game, Adam hatches an ingenious plan to get out of his situation before it's too late\"--Allmovie.com, viewed August 17, 2018.

Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments. Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470. 1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0–5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72–1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28–2·30, p<0·001; per-protocol population, 5-year cumulative risk 8·9% vs 5·8%, 1·53, 1·02–2·31, p=0·04), but were mainly non-disabling strokes. The distribution of modified Rankin scale scores at 1 year, 5 years, or final follow-up did not differ significantly between treatment groups. Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis. Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.

In February 2009, the Department of Health in England launched the Face, Arm, Speech, and Time (FAST) mass media campaign, to raise public awareness of stroke symptoms and the need for an emergency response. We aimed to evaluate the impact of three consecutive phases of FAST using population-level measures of behaviour in England. Interrupted time series (May 2007 to February 2011) assessed the impact of the campaign on: access to a national stroke charity's information resources (Stroke Association [SA]); emergency hospital admissions with a primary diagnosis of stroke (Hospital Episode Statistics for England); and thrombolysis activity from centres in England contributing data to the Safe Implementation of Thrombolysis in Stroke UK database. Before the campaign, emergency admissions (and patients admitted via accident and emergency [A&E]) and thrombolysis activity was increasing significantly over time, whereas emergency admissions via general practitioners (GPs) were decreasing significantly. SA webpage views, calls to their helpline and information materials dispatched increased significantly after phase one. Website hits/views, and information materials dispatched decreased after phase one; these outcomes increased significantly during phases two and three. After phase one there were significant increases in overall emergency admissions (505, 95% CI = 75 to 935) and patients admitted via A&E (451, 95% CI = 26 to 875). Significantly fewer monthly emergency admissions via GPs were reported after phase three (-19, 95% CI =  -29 to -9). Thrombolysis activity per month significantly increased after phases one (3, 95% CI = 1 to 6), and three (3, 95% CI = 1 to 4). Phase one had a statistically significant impact on information seeking behaviour and emergency admissions, with additional impact that may be attributable to subsequent phases on information seeking behaviour, emergency admissions via GPs, and thrombolysis activity. Future campaigns should be accompanied by evaluation of impact on clinical outcomes such as reduced stroke-related morbidity and mortality.

Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125-170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0-8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke's Cognitive Examination-Revised (ACE-R). We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1-48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference -10·6/-5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference -0·54/-0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison. In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. ISRCTN ISRCTN85562386.