BackgroundTrials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to determine if daily fluoxetine for 6 months after stroke improves functional outcome in Australasian and Vietnamese patients. MethodsAFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial conducted in 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10). Eligible patients were adults with a clinical diagnosis of stroke in the previous 2-15 days and a persisting neurological deficit. Patients were randomised via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20mg or matching placebo for 6 months. Patients, investigators and outcome assessors were masked to the treatment allocation. The primary outcome was functional outcome, measured by the modified Rankin scale (mRS), at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Analyses were according to the patient's treatment allocation. The trial is registered with the ACTRN registry, number 12611000774921. FindingsPowered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation 1280 patients were recruited in Australia (n=532), New Zealand (n=42) and Vietnam (n=706) between 11 January 2013 and 30 June 2019; 642 were allocated fluoxetine and 638 placebo. Adherence to trial medication (mean 167 [SD 48] days) was similar between groups. At 6 months, mRS data were available in 624 (97.2%) patients allocated fluoxetine and 632 (99.1%) placebo. The distribution of mRS categories at 6 months was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0.936, 95% CI 0.762-1.150; p=0.53), and consistent among all pre-defined subgroups. Compared to placebo, patients allocated fluoxetine had more falls (20 [3.12%] vs 7 [1.10%]; p=0.02), bone fractures (19 [2•96%] vs 6 [0.94%]; p=0.01) and epileptic seizures (10 [1.56%] vs 2 [0.31%]; p=0.04) at 6 months. InterpretationFluoxetine 20mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. These results do not support the use of fluoxetine to improve outcome after stroke.

Nutritional epidemiological studies have frequently reported associations between higher (poly)phenol intake and a decrease in the risk or incidence of noncommunicable diseases. However, the assessment methods that have been used to quantify the intakes of these compounds in large-population samples are highly variable. This systematic review aims to characterize the methods used to assess dietary (poly)phenol intake in observational studies, report the validation status of the methods, and give recommendations on method selection and data reporting. Three databases were searched for publications that have used dietary assessment methods to measure (poly)phenol intake and 549 eligible full texts were identified. Food-frequency questionnaires were found to be the most commonly used tool to assess dietary (poly)phenol intake (73%). Published data from peer-reviewed journals were the major source of (poly)phenol content data (25%). An increasing number of studies used open-access databases such as Phenol-Explorer and USDA databases on flavonoid content since their inception, which accounted for 11% and 23% of the data sources, respectively. Only 16% of the studies reported a method that had been validated for measuring the target (poly)phenols. For future research we recommend: 1) selecting a validated dietary assessment tool according to the target compounds and target period of measurement; 2) applying and combining comprehensive (poly)phenol content databases such as USDA and Phenol-Explorer; 3) detailing the methods used to assess (poly)phenol intake, including dietary assessment method, (poly)phenol content data source; 4) follow the Strengthening the Reporting of Observational Studies in Epidemiology—Nutritional Epidemiology (STROBE-nut) framework; and 5) complementing dietary intake assessment based on questionnaires with measurement of (poly)phenols in biofluids using appropriate and validated analytical methods.

A tyrosine phosphatase-like protein, IA-2, is a major autoantigen in Type 1 diabetes but its role in islet function is unclear. Tyrosine phosphorylation mediates regulation of cellular processes such as exocytosis, cell growth, and cell differentiation. To investigate the potential involvement of IA-2 in islet differentiation and insulin secretion, we analyzed by immunohistochemistry expression of IA-2 during islet development in fetal rats and during the maturation of insulin secretory responses after birth. In the fetus, IA-2 immunoreactivity was detected in primitive islets positive for insulin and glucagon at 12 days' gestation. Subsequently, IA-2 was only weakly detectable in the fetal pancreas. In neonatal rat, a progressive increase in IA-2 immunoreactivity was observed in islets from very low levels at 1 day of age to moderate labeling at 10 days. In the adult, relatively high levels of IA-2 were detected in islets, with heterogeneous expression in individual cells within each islet. IA-2 marks a population of endocrine cells that transiently appear early in pancreatic ontogeny. Islet IA-2 expression reappears after birth concomitant with the development of mature insulin secretory responses, consistent with a role for this protein in regulated hormone secretion.

The primary aim was to systematically review the empirical evidence relating to models and guidance for providing effective feedback in clinical supervision occurring in postgraduate medical education contexts. A secondary aim was to identify the common and differentiating components of models and guidance for providing effective feedback in this context. A systematic review was conducted. Fifty-one records met the inclusion criteria, including 12 empirical studies. Empirical records meeting inclusion criteria were critically appraised. Qualitative content analysis was applied to the guidance on effective and ineffective feedback provision to identify key principles. A composite model was created synthesising the guidance identified for providing effective feedback. The evidence supporting specific models and guidance in postgraduate medical education was limited. However, there is evidence to support all of the commonly identified principles. In addition, a consensus about the principles of effective feedback in clinical supervision in postgraduate medical education was found.