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

On the inclusion of dissipation on top of mean-field approaches

International audienc

Collective Electron Dynamics in Metallic and Semiconductor nanostructures

International audienceWe review different approaches to the modeling and numerical simulation of the nonlinear electron dynamics in metallic and semiconductor nanostructures. Depending on the required degree of sophistication, such models go from the full N-body dynamics (configuration interaction), to mean-field approaches such as the time-dependent Hartree equations, down to macroscopic models based on hydrodynamic equations. The time-dependent density functional theory and the localdensity approximation - which have become immensely popular during the last two decades - can be understood as an upgrade of the Hartree approach allowing one to include, at least approximately, some effects that go beyond the mean-field. Alternative methods, based onWigner's phase-space representation of quantum mechanics, are also described. Wigner's approach has the advantage of permitting a more straightforward comparison between semiclassical and fully quantum results. As an illustrative example, the many-electron dynamics in a semiconductor quantum well is studied numerically, using both a mean-field approach (Wigner-Poisson system) and a quantum hydrodynamical model. Finally, the above methods are extended to include the spin degrees of freedom of the electrons. The local-spin-density approximation is used to investigate the linear electron response in metallic nanostructures. The modeling of nonlinear spin effects is sketched within the framework of Wigner's phase-space dynamics