Introduction The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily, contributes to acute and chronic disease processes, including sepsis.

SummaryBackgroundResults of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.MethodsFOCUS 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.FindingsBetween 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.InterpretationFluoxetine 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.FundingUK Stroke Association and NIHR Health Technology Assessment Programme.

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The idea that physical activity differentially impacts upon performance of various cognitive tasks has recently gained increased interest. However, our current knowledge about how cognition is altered by acute physical activity is incomplete. To measure how different intensity levels of physical activity affect cognition during and after 1 bout of physical activity, 30 healthy, young participants were randomized to perform a not-X continuous performance test (CPT) during low (LI)- and moderate intensity (MI) running. The same participants were subsequently randomized to perform the not-X CPT post LI, MI, and high intensity (HI) running. In addition, exercise related mood changes were assessed through a self-report measure pre and post running at LI, MI, and HI. Results showed worsening of performance accuracy on the not-X CPT during one bout of moderate compared to low intensity running. Post running, there was a linear decrease in reaction time with increasing running intensity and no change in accuracy or mood. The decreased reaction times post HI running recovered back to baseline within 20 min. We conclude that accuracy is acutely deteriorated during the most straining physical activity while a transient intensity-dependent enhancement of cognitive control function is present following physical activity.

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