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

Evaluating the impact of improvements in urban green space on older adults' physical activity and wellbeing: Protocol for a natural experimental study

Abstract Background Creating or improving urban green space has the potential to be an effective, sustainable and far-reaching way to increase physical activity and improve other aspects of wellbeing in the population. However, there is a dearth of well-conducted natural experimental studies examining the causal effect of changing urban green space on physical activity and wellbeing. This is especially true in older adults and in the United Kingdom. This paper describes a natural experimental study to evaluate the effect of four small-scale urban street greening interventions on older adults’ physical activity and wellbeing over a 1-year period, relative to eight matched comparison sites. All sites are located in deprived urban neighbourhoods in Greater Manchester, United Kingdom. Methods Components of the interventions include tree and flower planting, and artificial tree decorations. Eight unimproved comparison sites were selected based on a systematic process of matching using several known objective and subjective environmental correlates of physical activity in older adults. The outcome measures are physical activity and two other behavioural indicators of wellbeing (Connect: connecting with other people; and Take Notice: taking notice of the environment), collected using a newly developed observation tool. The primary outcome is Take Notice behaviour due to largest effects on this behaviour being anticipated from improvements in the aesthetic quality of green space at the intervention sites. Baseline data collection occurred in September 2017 before the interventions were installed in November 2017. Follow-up data collection will be repeated in February/ March 2018 (6 months) and September 2018 (12 months). Discussion The present study permits a rare opportunity to evaluate the causal effects of small-scale changes in urban green space in an understudied population and setting. Although the interventions are expected to have small effects on the outcomes, the present study contributes to developing natural experiment methodology in this field by addressing key methodological weaknesses causing high risk of bias in previous natural experimental studies. Key improvements to reduce risk of bias in the present study are rigorous matching of multiple comparison sites and appropriate statistical control of key confounders. Trial registration Retrospectively registered with study ID NCT03575923. Date of registration: 3 July 2018

Coherent combination of experts' opinions

Expert Opinions, Coherence, Compatibility, Combining Opinions, Linear Opinion Pool, Logarithmic Opinion Pool, Harmonic Opinion Pool,

Security implications of Turkey's March towards EU membership

[No abstract available

Several Bayesians: A review

Amalgamation of Opinion, Expert Opinion, Game Theory (Bayesian), Sequential Decision Processes,