Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Age-hardening characteristics of δ-alumina fibre reinforced aluminium-silicon LM-13 alloy metal matrix composites

Metal Matrix Composites (MMCs) with an aluminium-silicon based LM-13 alloy and short-staple Saffil (δ-alumina) fibres with volume fractions of 0.10, 0.15, 0.20, 0.25 and 0.30 have been produced using a pressure liquid infiltration process. The standard T6 heat treatment procedure was applied to both the unreinforced matrix alloy and the composites, and the effect of the fibres on the age-hardening characteristics of the composites has been investigated by means of hardness measurements

Comparison of uncertainty sources for climate change impacts: flood frequency in England

This paper investigates the uncertainty in the impact of climate change on flood frequency in England, through the use of continuous simulation of river flows. Six different sources of uncertainty are discussed: future greenhouse gas emissions; Global Climate Model (GCM) structure; downscaling from GCMs (including Regional Climate Model structure); hydrological model structure; hydrological model parameters and the internal variability of the climate system (sampled by applying different GCM initial conditions). These sources of uncertainty are demonstrated (separately) for two example catchments in England, by propagation through to flood frequency impact. The results suggest that uncertainty from GCM structure is by far the largest source of uncertainty. However, this is due to the extremely large increases in winter rainfall predicted by one of the five GCMs used. Other sources of uncertainty become more significant if the results from this GCM are omitted, although uncertainty from sources relating to modelling of the future climate is generally still larger than that relating to emissions or hydrological modelling. It is also shown that understanding current and future natural variability is critical in assessing the importance of climate change impacts on hydrology