Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Behaviour of the food spoilage yeast Zygosaccharomyces bailii in acidified products: a modelling and cellular approach

Zygosaccharomyces bailii is a well-known food spoilage yeast with an exceptional acid resistance. The yeast often causes spoilage in shelf-stable acidified products (such as mayonnaises, ketchups, dressings), leading to substantial economic losses to the food industry. In the first part of this PhD study, effects of acetic and lactic acids on this yeast at 7 and 30°C were investigated. It was observed that these acids at low concentrations (in high-sugar media) can cause stimulations on yeast growth and metabolism. A caution in the use of the acids at low doses for preservation purpose was suggested. In the second part of the research, growth/no growth models predicting growth probability of Z. bailii in different environmental conditions were developed, and one of the models was validated in a real food product (i.e. ketchup). These models can be used as a convenient tool to evaluate the stability of acidified foods and to assist in the formulation of new products without chemical preservatives. Besides, the importance of expressing antimicrobial concentrations on water basis in predictive models was demonstrated, which is necessary for the successful applications of the models in practice. The last part of this study deals with the use of pH-sensitive green fluorescent protein (GFP) for intracellular pH (pHi) measurement in Z. bailii. The yeast was transformed into a GFP-carrying strain; thereby its pHi can be determined quickly and accurately based on the cellular fluorescent signals. This was the first time that a GFP-based approach was applied to measure pHi in this yeast. It can be expected that more understandings about the physiological characteristics of Z. bailii will be obtained from the use of this new yeast strain