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.

Background: Failure to recognise acute stroke may result in worse outcomes due to missed opportunity for acute stroke therapies. Our study examines factors associated with stroke misdiagnosis in patients admitted to a large comprehensive stroke centre. Methods: Retrospective review comparing 156 consecutive stroke patients misdiagnosed in emergency department (ED) with 156 randomly selected stroke controls matched for age, gender, language spoken and stroke subtype for the period 2014–2016. Results: There were 141 ischemic and 15 hemorrhagic misdiagnosed strokes (median age: 77 years, male:female = 1.3: 1). Symptom resolution, altered mental status, nausea/vomiting, dizziness and vertigo favored misdiagnosis (p < 0.05). Hemiparesis and dysarthria favored an accurate diagnosis (p < 0.05). Misdiagnosed patients were more commonly triaged into a lower ED category (62 vs. 42%, p = 0.001), clinically assessed as Face, Arm, Speech and Time (FAST) – negative (78 vs. 22%, p < 0.001) and underwent delayed CT imaging (median 4.1 vs. 1.5 h, p < 0.001). Misdiagnosed patients were more likely to have posterior circulation stroke (PCS; 39 vs. 22%, p = 0.01) and be admitted under non-neurological services (35 vs. 11%, p < 0.001) with worse discharge outcomes including increased mortality. Conclusions: Patients with stroke misdiagnosis were commonly FAST-negative with nonspecific symptoms including altered mental status, dizziness and nausea/vomiting often associated with PCS. Improved diagnostic accuracy may increase access to acute therapies.

Background Epidemiological studies demonstrate associations between obstructive sleep apnea (OSA) and cancer incidence and mortality. The aim of this study was to measure OSA in women with breast (BC) or endometrial cancer (EC) and associations with clinico-pathological tumor variables. Methods and findings In a cross sectional study, women with BC (12 months) or EC (3 months) post-diagnosis were recruited from cancer clinics. We collected demographic, anthropometric data, cancer stage, grade, histopathology and history of cancer treatment and all subjects had in-laboratory polysomnography. Sleepiness was assessed with the Epworth Sleepiness Scale (ESS). We compared anthropometric and polysomnographic data between cancer groups (unpaired t-tests), and assessed relationships between cancer characteristics and OSA variables (Fishers exact test). There were no significant differences between average age (BC:59.6±8.7 years(n = 50); EC:60.3±7.7 years(n = 37)), or ESS score (BC:6.4±4.4; EC 6.8±4.7; mean±SD; all p>0.2), however, BMI was higher in EC (BC: 29.7±7.9kgm-2; EC: 34.2±8.0 kgm-2; p<0.05). BC had longer sleep latency (BC:31.8±32minutes; EC:19.3±17.9 minutes), less Stage 3 sleep (BC:20.0±5.2%; EC:23.6±8.2%) and more REM sleep (BC:21.1±6.9%; EC: 16.6±5.7%), all p<0.05. EC had lower average awake and asleep oxygen saturation levels (BC: 95.6±1.3%; EC: 94.6±1.9% [awake]: BC: 94.8±2.1%; EC: 93.3±2.4% [asleep]; both p<0.05). Apnea-Hypopnea Index (AHI) (BC: 21.2(7.3–36.9) events/hr; EC: 15.7 (10–33.5) events/hour (median (interquartile range)) was not different p = 0.7), however, 58% and 57% of women with BC and EC respectively, had an AHI>15 events/hour. In this small sample size group, no significant associations (all p>0.1) were detected between OSA metrics and clinico-pathological tumor variables. Conclusion In postmenopausal women with breast or endometrial cancer there is high prevalence of OSA, with no association with specific tumor characteristics detected. Recognition of the high prevalence of OSA in women with cancer is important to recognise as it may impact on surgical risk and quality of life.

CollaborationIMPORTANCE One in 3 adults experiences clinically significant symptoms of depression during the first year after a stroke, but evidence to support the use of antidepressants in this population remains scant.OBJECTIVE To investigate whether daily treatment with 20 mg of fluoxetine hydrochloride reduces the proportion of people affected by clinically significant symptoms of depression after stroke. DESIGN, SETTING, AND PARTICIPANTSIn this secondary analysis of the Assessment of Fluoxetine in Stroke Recovery parallel-group, randomized (1:1 assignment), double-blind, placebo-controlled clinical trial, 1221 participants in Australia, New Zealand, and Vietnam were recruited between January 11, 2013, and June 30, 2019, and were followed up for 6 months. Adults aged 18 years or older were recruited 2 to 15 days after experiencing a stroke associated with modified Rankin Scale score of 1 or higher.INTERVENTIONS Fluoxetine hydrochloride, 20 mg, or matched placebo daily for 26 weeks. MAIN OUTCOMES AND MEASURESA 9-item Patient Health Questionnaire (PHQ-9) score of 9 or lower was a prespecified secondary outcome of the trial. Assessments were completed at baseline and at 4, 12, and 26 weeks. Other outcomes of interest included participant-reported clinician diagnosis of depression, prescription of a nontrial antidepressant, or nonpharmacologic treatment of depression. Analysis was on an intention-to-treat basis.RESULTS A total of 607 participants (378 men [62.3%]; mean [SD] age, 64.3 [12.2] years) were randomly assigned treatment with placebo, and 614 participants (397 men [64.7%]; mean [SD] age, 63.4 [12.4] years) were randomly assigned treatment with 20 mg of fluoxetine hydrochloride daily. The groups were balanced for demographic and clinical measures. At baseline, 112 patients (18.5%) in the placebo group and 116 patients (18.9%) in the fluoxetine group had PHQ-9 scores of 9 or higher. During follow-up, 126 of 596 participants (21.1%) treated with placebo and 121 of 598 participants (20.2%) treated with fluoxetine had PHQ-9 scores of 9 or higher (P = .70). A similar proportion of participants with PHQ-9 scores less than 9 at baseline who were treated with fluoxetine hydrochloride and placebo developed PHQ-9 scores of 9 or higher during the trial (placebo, 72 of 488 [14.8%]; and fluoxetine, 63 of 485 [13.0%]; P = .43). A slightly higher number of participants in the placebo group than in the fluoxetine group had a participant-reported clinician diagnosis of depression (42 of 602 [7.0%] vs 26 of 601 [4.3%]; P = .05). By week 26, 14 participants (2.3%) in the placebo group and 12 participants (1.9%) in the fluoxetine group had died (P = .67). CONCLUSIONS AND RELEVANCERoutine daily treatment with 20 mg of fluoxetine did not decrease the proportion of people affected by clinically significant symptoms of depression after a stroke, nor did it affect the proportion of people prescribed an antidepressant or receiving nonpharmacologic treatments compared with placebo.