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

Prise en compte économique du long terme dans les choix énergétiques relatifs à la gestion des déchets radioactifs

Nowadays, the deep geological repository is generally considered as the reference solution for the definitive management of spent nuclear fuel/high-level waste, but different countries have decided different disposal deployment schedules. Via the economic calculation, we hope to offer some answers to the following question: In terms of disposal time management, how should the present generations, benefiting from the nuclear power generation, bear the costs of radioactive waste management, while taking into account future generations? This thesis proposes to analyze specifically the French decision in its context. We propose a set of tools to evaluate the Utility of the deep geological repository project according to the deployment schedule choices. Our thesis also studies the influence of disposal choices on the nuclear fuel cycle. Beyond, we also take into account the interactions between the deep geological repository, nuclear fleet and cycle choices which constitute a "complete system".Actuellement, bien que la plupart des pays nucléaires converge vers la même solution technique: le stockage profond pour la gestion des déchets radioactifs de haute activité et à vie longue, les objectifs calendaires divergent d'un pays à l'autre. Grâce au calcul économique, nous souhaitons apporter des éléments de réponse à la question suivante : En termes de temporalité, comment les générations présentes, qui bénéficient de la production d'électricité nucléaire, doivent-elles supporter les charges de la gestion des déchets radioactifs en tenant compte des générations futures ? Cette thèse se propose d'analyser spécifiquement la décision française en tenant compte de son contexte. Nous proposons un ensemble d'outils qui permet d'évaluer l'Utilité du projet de stockage profond en fonction des choix de temporalité. Notre thèse étudie également l'influence en retour des choix de stockage sur le cycle du combustible nucléaire. Au-delà, nous prenons en compte les interactions entre le stockage profond et les choix de parc nucléaire et de cycle du combustible qui constituent un « système complet »

Economic analysis of long-term energy choices related to the radioactive waste management

Actuellement, bien que la plupart des pays nucléaires converge vers la même solution technique: le stockage profond pour la gestion des déchets radioactifs de haute activité et à vie longue, les objectifs calendaires divergent d'un pays à l'autre. Grâce au calcul économique, nous souhaitons apporter des éléments de réponse à la question suivante : En termes de temporalité, comment les générations présentes, qui bénéficient de la production d'électricité nucléaire, doivent-elles supporter les charges de la gestion des déchets radioactifs en tenant compte des générations futures ? Cette thèse se propose d'analyser spécifiquement la décision française en tenant compte de son contexte. Nous proposons un ensemble d'outils qui permet d'évaluer l'Utilité du projet de stockage profond en fonction des choix de temporalité. Notre thèse étudie également l'influence en retour des choix de stockage sur le cycle du combustible nucléaire. Au-delà, nous prenons en compte les interactions entre le stockage profond et les choix de parc nucléaire et de cycle du combustible qui constituent un « système complet ».Nowadays, the deep geological repository is generally considered as the reference solution for the definitive management of spent nuclear fuel/high-level waste, but different countries have decided different disposal deployment schedules. Via the economic calculation, we hope to offer some answers to the following question: In terms of disposal time management, how should the present generations, benefiting from the nuclear power generation, bear the costs of radioactive waste management, while taking into account future generations? This thesis proposes to analyze specifically the French decision in its context. We propose a set of tools to evaluate the Utility of the deep geological repository project according to the deployment schedule choices. Our thesis also studies the influence of disposal choices on the nuclear fuel cycle. Beyond, we also take into account the interactions between the deep geological repository, nuclear fleet and cycle choices which constitute a "complete system"

Economic assessment of the political and technical management of large-scale public projects. The deployment schedule of France’s deep geological repository of radioactive waste

In France, the 2006 act on radioactive waste management stipulated the rapid deployment of a deep geological repository (DGR) for high-level waste (HLW) management. This paper analyzes the impact of different DGR deployment schedules on project costs in order to discern an optimal schedule for the disposal of radioactive waste. It appears more economically favorable to extend the duration of storage rather than to dispose of the waste immediately. However, the French parliament has decided to act quickly, accepting a 1.5% excess cost every year, to avoid leaving the burden to future generations and to continue nuclear development. Secondly, the analysis reveals the economic benefits of shortening the duration of the disposal process.JEL classification: Q01, Q58, Q48.En France, la loi 2006 de programme relative à la gestion durable des matières et déchets radioactifs a insisté sur la mise en service rapide d’un stockage profond des déchets radioactifs de haute activité et à vie longue. Cet article analyse les coûts des différents calendriers envisageables dans le but de rechercher s’il existe une date optimale pour la mise en stockage des déchets radioactifs. Il apparaît plus préférable de prolonger l’entreposage que de stocker immédiatement des déchets radioactifs. Pourtant, le Parlement a décidé à agir rapidement en acceptant 1.5% de surcoût chaque année, afin d’éviter les charges sur les générations futures et de maintenir l’option nucléaire. Deuxièmement, l’analyse relève également l’intérêt économique du raccourcissement de la durée d’opération du stockage profond.Classification JEL : Q01, Q58, Q48

Economic appraisal of deployment schedules for high-level radioactive waste repositories

The deep geological repository (DGR) is considered as the definitive management solution for high-level waste (HLW). Countries defined different DGR implementation schedules, depending on their national context and political choices. We raise the question of the economic grounds of such political decisions by providing an economic analysis of different DGR schedules. We investigate the optimal timing for DGR commissioning based on available Nuclear Energy Agency (NEA) data (2013). Two scenarios are considered: (1) rescheduling the deployment of a DGR with the same initial operational period, and (2) rescheduling the deployment of a DGR with a shorter operational period, i.e. initial closure date. Given the long timescales of such projects, we also take into account the discounting effect. The first finding is that it appears more economically favorable to extend the interim storage than to dispose of the HLW immediately. Countries which chose “immediate” disposal are willing to accept higher costs to quickly solve the problem. Another interesting result is that there is an optimal solution with respect to the length of DGR operational period and the waste flow for disposal. Based on data provided by the Organisation for Economic Cooperation and Development (OECD)/Nuclear Energy Agency (NEA), we find an optimal operating period of about 15 years with a flow of 2000 tHM/year

Synthesis of Silver Nanoparticles: From Conventional to ‘Modern’ Methods—A Review

Silver nanoparticles, also known as AgNPs, have been extensively researched due to their one-of-a-kind characteristics, including their optical, antibacterial, and electrical capabilities. In the era of the antibiotics crisis, with an increase in antimicrobial resistance (AMR) and a decrease in newly developed drugs, AgNPs are potential candidates because of their substantial antimicrobial activity, limited resistance development, and extensive synergistic effect when combined with other drugs. The effect of AgNPs depends on the delivery system, compound combination, and their own properties, such as shape and size, which are heavily influenced by the synthesis process. Reduction using chemicals or light, irradiation using gamma ray, laser, electron beams or microwave and biological synthesis or a combination of these techniques are notable examples of AgNP synthesis methods. In this work, updated AgNP synthesis methods together with their strength and shortcomings are reviewed. Further, factors affecting the synthesis process are discussed. Finally, recent advances and challenges are considered

Chronic Pain and Associated Factors Related to Depression among Older Patients in Hanoi, Vietnam

The interaction of chronic pain and depression among older people has been studied for many years. This study aimed to investigate the frequency of chronic pain and depression among older patients and correlated factors. A cross-sectional study was conducted in 921 older patients at the National Geriatric Hospital from November 2019 to March 2020. We used the Charlson Comorbidity Index (CCI) to assess the comorbid condition, a numerical rating scale (NRS) to examine pain severity, and Geriatric Depression Scale—15 items (GDS-15) to measure depression among participants. A chi-square test and Tobit regression were used to analyze the relationships. A total of 921 older patients participated in the study. The proportion of depression accounted for 55.8%. The mean Charlson score and number of diseases were 1.2 and 4.7, respectively. A positive correlation was found between comorbidity and chronic pain and depression. Moreover, socio-demographic variables such as occupation, education, and income were associated with pain and depressive symptoms. This study highlights the issue of mental health in older people with chronic pain. The results indicate the necessity of frequent depression screening, pain management, and social activity programs for older people to enhance their health

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