Granulocyte-colony-stimulating factor mobilizes bone marrow stem cells in patients with subacute ischemic stroke: the Stem Cell Trial of Recovery EnhanceMent After Stroke (STEMS) Pilot Randomized, Controlled Trial (ISRCTN 16784092)

Background and Purpose - Loss of motor function is common after stroke and leads to significant chronic disability. Stem cells are capable of self-renewal and of differentiating into multiple cell types, including neurones, glia, and vascular cells. We assessed the safety of granulocyte-colony-stimulating factor (G-CSF) after stroke and its effect on circulating CD34 stem cells. Methods - We performed a 2-center, dose-escalation, double-blind, randomized, placebo-controlled pilot trial (ISRCTN 16784092) of G-CSF (6 blocks of 1 to 10 g/kg SC, 1 or 5 daily doses) in 36 patients with recent ischemic stroke. Circulating CD34 stem cells were measured by flow cytometry; blood counts and measures of safety and functional outcome were also monitored. All measures were made blinded to treatment. Results - Thirty-six patients, whose mean SD age was 768 years and of whom 50% were male, were recruited. G-CSF (5 days of 10 g/kg) increased CD34 count in a dose-dependent manner, from 2.5 to 37.7 at day 5 (area under curve, P0.005). A dose-dependent rise in white cell count (P0.001) was also seen. There was no difference between treatment groups in the number of patients with serious adverse events: G-CSF, 7/24 (29%) versus placebo 3/12 (25%), or in their dependence (modified Rankin Scale, median 4, interquartile range, 3 to 5) at 90 days. Conclusions - ”G-CSF is effective at mobilizing bone marrow CD34 stem cells in patients with recent ischemic stroke. Administration is feasible and appears to be safe and well tolerated. The fate of mobilized cells and their effect on functional outcome remain to be determined. (Stroke. 2006;37:2979-2983.)

The Warwick-Edinburgh Mental Well-Being Scale

Background There is increasing international interest in the concept of mental well-being and its contribution to all aspects of human life. Demand for instruments to monitor mental well-being at a population level and evaluate mental health promotion initiatives is growing. This article describes the development and validation of a new scale, comprised only of positively worded items relating to different aspects of positive mental health: the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS). Methods WEMWBS was developed by an expert panel drawing on current academic literature, qualitative research with focus groups, and psychometric testing of an existing scale. It was validated on a student and representative population sample. Content validity was assessed by reviewing the frequency of complete responses and the distribution of responses to each item. Confirmatory factor analysis was used to test the hypothesis that the scale measured a single construct. Internal consistency was assessed using Cronbach’s alpha. Criterion validity was explored in terms of correlations between WEMWBS and other scales and by testing whether the scale discriminated between population groups in line with pre-specified hypotheses. Test-retest reliability was assessed at one week using intra-class correlation coefficients. Susceptibility to bias was measured using the Balanced Inventory of Desired Responding. Results WEMWBS showed good content validity. Confirmatory factor analysis supported the single factor hypothesis. A Cronbach’s alpha score of 0.89 (student sample) and 0.91 (population sample) suggests some item redundancy in the scale. WEMWBS showed high correlations with other mental health and well-being scales and lower correlations with scales measuring overall health. Its distribution was near normal and the scale did not show ceiling effects in a population sample. It discriminated between population groups in a way that is largely consistent with the results of other population surveys. Test–retest reliability at one week was high (0.83). Social desirability bias was lower or similar to that of other comparable scales. Conclusions WEMWBS is a measure of mental well-being focusing entirely on positive aspects of mental health. As a short and psychometrically robust scale, with no ceiling effects in a population sample, it offers promise as a tool for monitoring mental well-being at a population level. Whilst WEMWBS should appeal to those evaluating mental health promotion initiatives, it is important that the scale’s sensitivity to change is established before it is recommended in this context.