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

Optimization of Dressing Parameters for Minimum Surface Roughness and Maximum Material Removal Rate in Internal Grinding of SKD11 Tool Steel

This paper introduces a study on multi-objective optimization of dressing parameters in internal grinding of SKD 11 tool steel using Grey based Taguchi method. The L27 orthogonal array of the Taguchi method was selected to design the experiments. The input parameters of the dressing process are the depth of fine, the time of fine dressing, the depth of coarse dressing, the time of coarse dressing, non-feeding dressing, and dressing feed rate. The output factors are surface roughness (SR) and material removal rate (MRR). A grey relation grade was determined by using the signal-to-noise ratio. The ANOVA was applied to find out the effect of input factors on the grey relation grade. In conclusion, the fine dressing times is the parameter that has the strongest impact on multiple performance characteristics, followed by the coarse dressing times. Also, the optimum dressing parameters to get minimum SR and maximum MRR is the depth of coarse dressing of 0.03mm, the time of coarse dressing of 2 times, the depth of fine dressing of 0.01 mm, the time of fine dressing of 2 times, non-feeding dressing of 2 times, and dressing feed rate of 1.2mm/min

Optimization of Milling Process by Taguchi-PSI Method

060A4 steel (Chinese standard) is a steel with good machinability, which is very popularly used in mechanical engineering. Therefore, the study of solutions for improvement of quality and productivity when machining this steel type has great technical and economic significance. In this study, the multi-objective optimization process has been performed when milling this steel type on a vertical milling machine. The cutting tool is a face milling cutter made of High Speed Steel (HSS) material. The effect of spindle speed, feed rate, and cutting depth on surface roughness has been found. The combination of the Taguchi method and PSI method has been applied to determine the optimal value of three input parameters to simultaneously ensure the two criteria of the minimum surface roughness and the maximum Material Removal Rate (MRR). The works which will be done by the authors of this article in the near future has also been presented in the last part of this study

Optimization of Parameters for the Extraction of Phenolic Antioxidants from Boxberry Tree (Myrica Esculenta) Bark Using Response Surface Methodology

The boxberry tree (Myrica esculenta) bark has been known to have multiple health benefits and is used as a traditional medicine. A critical gap in knowledge exists on a simple but effective method to isolate the bioactive components from the bark. This study aimed to optimize the operating conditions, including temperature, ethanol concentration, and time, for the extraction of phenolic antioxidants from the boxberry bark sample using a response surface methodology. Results showed that the second-order polynomial regression models were statistically significant and sufficient to estimate the responses. Response surface optimization for all responses was successfully carried out to determine the optimum extraction conditions, which were a temperature, an ethanol concentration, and an extraction time of 75.8 °C, 48.3% (v/v), and 117 min, respectively. At these conditions, total phenolic and total flavonoid contents, 3-ethylbenzothiazoline-6-sulphonic acid diammonium salt (ABTS) scavenging capacity, and ferric-reducing antioxidant power were predicted to be 205.9 mg GAE/100 g, 37.8 mg CE/100 g, 271.3 mg AAE/100 g, and 111.4 mg AAE/100 g, respectively. The insignificant difference between the estimated and the experimental values suggested that the predictive models were valid to predict the process outcomes

Optimization of Oligomer Chitosan/Polyvinylpyrrolidone Coating for Enhancing Antibacterial, Hemostatic Effects and Biocompatibility of Nanofibrous Wound Dressing

A synergistic multilayer membrane design is necessary to satisfy a multitude of requirements of an ideal wound dressing. In this study, trilayer dressings with asymmetric wettability, composed of electrospun polycaprolactone (PCL) base membranes coated with oligomer chitosan (COS) in various concentrations of polyvinylpyrrolidone (PVP), are fabricated for wound dressing application. The membranes are expected to synergize the hygroscopic, antibacterial, hemostatic, and biocompatible properties of PCL and COS. The wound dressing was coated by spraying the solution of 3% COS and 6% PVP on the PCL base membrane (PVP6–3) three times, which shows good interaction with biological subjects, including bacterial strains and blood components. PVP6–3 samples confirm the diameter of inhibition zones of 20.0 ± 2.5 and 17.9 ± 2.5 mm against Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The membrane induces hemostasis with a blood clotting index of 74% after 5 min of contact. In the mice model, wounds treated with PVP6–3 closed 95% of the area after 10 days. Histological study determines the progression of skin regeneration with the construction of granulation tissue, new vascular systems, and hair follicles. Furthermore, the newly-growth skin shares structural resemblances to that of native tissue. This study suggests a simple approach to a multi-purpose wound dressing for clinical treatment

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that 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 seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. REGISTRATION: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921