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

Some Criteria of the Knowledge Representation Method for an Intelligent Problem Solver in STEM Education

Nowadays, building intelligent systems for science, technology, engineering, and math (STEM) education is necessary to support the studying of learners. Intelligent problem solver (IPS) is a system that can be able to solve or tutor how to solve the problems automatically. Learners only declare hypothesis and goal of problems based on a sufficient specification language. They can request the program to solve it automatically or to give instructions that help them to solve it themselves. Knowledge representation plays a vital role in these kinds of intelligent systems. There are various methods for knowledge representation; however, they do not meet the requirements of an IPS in STEM education. In this paper, we propose the criteria of a knowledge model for an IPS in education. These criteria orient to develop a method for knowledge representation to meet actual requirements in practice, especially pedagogical requirements. For proving the effectiveness of these criteria, a knowledge model is also constructed. This model can satisfy these criteria and be applied to build IPS for courses, such as mathematics and physics

In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam.

BACKGROUND: By 2009, there were worrying signs from western Cambodia that parasitological responses to artesunate-containing treatment regimens for uncomplicated Plasmodium falciparum malaria were slower than elsewhere which suggested the emergence of artemisinin resistance. Vietnam shares a long land border with Cambodia with a large number of migrants crossing it on a daily basis. Therefore, there is an urgent need to investigate whether there is any evidence of a change in the parasitological response to the artemisinin derivatives in Vietnam. METHODS: From August 2010 to May 2011, a randomized controlled clinical trial in uncomplicated falciparum malaria was conducted to compare two doses of artesunate (AS) (2mg/kg/day versus 4 mg/kg/day for three days) followed by dihydroartemisinin-piperaquine (DHA-PPQ) and a control arm of DHA-PPQ. The goal was characterization of the current efficacy of artesunate in southern Vietnam. The primary endpoint of this study was the parasite clearance half-life; secondary endpoints included the parasite reduction ratios at 24 and 48 hours and the parasite clearance time. RESULTS: 166 patients were recruited into the study. The median parasite clearance half-lives were 3.54 (AS 2mg/kg), 2.72 (AS 4mg/kg), and 2.98 hours (DHA-PPQ) (p=0.19). The median parasite-reduction ratio at 24 hours was 48 in the AS 2mg/kg group compared with 212 and 113 in the other two groups, respectively (p=0.02). The proportions of patients with a parasite clearance time of &gt;72 hours for AS 2mg/kg, AS 4mg/kg and DHA-PPQ were 27%, 27%, and 22%, respectively. Early treatment failure occurred in two (4%) and late clinical failure occurred in one (2%) of the 55 patients in the AS 2mg/kg group, as compared with none in the other two study arms. The PCR-corrected adequate clinical and parasitological response (APCR) rates in the three groups were 94%, 100%, and 100% (p=0.04). CONCLUSIONS: This study demonstrated faster P. falciparum parasite clearance in southern Vietnam than in western Cambodia but slower clearance in comparison with historical data from Vietnam. Further studies to determine whether this represents the emergence of artemisinin resistance in this area are needed. Currently, the therapeutic response to DHA-PPQ remains satisfactory in southern Vietnam. TRIAL REGISTRATION: NTC01165372

Characteristics of the Vietnamese <i>Cryptococcus neoformans</i> var. <i>grubii</i> sequences unique to either ST5 or non-ST5 isolates.

<p>Lineage specific sequence was highly conserved within each lineage.</p

Population structure of Vietnamese clinical isolates (MLST).

<p>Minimum-spanning tree of the 14 detected STs and their relative distribution between HIV infected and HIV uninfected patients of 136 Vietnamese clinical isolates of <i>C</i>. <i>neoformans</i> var. <i>grubii</i>. Circle sizes are proportional to the number of isolates; red = isolate from HIV infected patient, grey—isolate from HIV uninfected patient. ST—multi locus sequence type.</p

Alignment of Vietnamese <i>Cryptococcus neoformans</i> var. <i>grubii</i> genome assemblies against the H99 reference genome.

<p>Alignment of Vietnamese <i>Cryptococcus neoformans</i> var. <i>grubii</i> genome assemblies against the H99 reference genome.</p

Genes containing genotype-specific SNPs and indels specific to the Vietnamese <i>Cryptococcus neoformans</i> var. <i>grubii</i> ST5 or non-ST5 organism.

<p>Genes containing genotype-specific SNPs and indels specific to the Vietnamese <i>Cryptococcus neoformans</i> var. <i>grubii</i> ST5 or non-ST5 organism.</p

BRIG plot showing the relatedness of an ST5 isolate (BMD700) and an ST4 isolate (BMD1415) to the H99 reference genome.

<p>On the inner two rings, the coloured regions represent high pairwise similarity with H99 (>70%) according to BLASTn; lighter regions show areas of difference with H99. The outer two rings plot the number of SNPs per 1000 base pairs. The bar scale is limited to a maximum frequency of 10 SNPs per 1000 bp; any window with greater than this frequency is coloured blue. The figure illustrates that SNP density varies widely across the genome between areas of high and low frequencies; some of these are common to both STs compared with H99, others are ST4 or ST5 specific.</p