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.

Despite evidence of a relationship among obstructive sleep apnea (OSA), metabolic dysregulation, and diabetes, it is uncertain whether OSA treatment can improve metabolic parameters. We sought to determine effects of long-term continuous positive airway pressure (CPAP) treatment on glycemic control and diabetes risk in patients with cardiovascular disease (CVD) and OSA. RESEARCH DESIGN AND METHODSBlood, medical history, and personal data were collected in a substudy of 888 participants in the Sleep Apnea cardioVascular Endpoints (SAVE) trial in which patients with OSA and stable CVD were randomized to receive CPAP plus usual care, or usual care alone. Serum glucose and glycated hemoglobin A 1c (HbA 1c ) were measured at baseline, 6 months, and 2 and 4 years and incident diabetes diagnoses recorded. RESULTSMedian follow-up was 4.3 years. In those with preexisting diabetes (n 5 274), there was no significant difference between the CPAP and usual care groups in serum glucose, HbA 1c , or antidiabetic medications during follow-up. There were also no significant between-group differences in participants with prediabetes (n 5 452) or new diagnoses of diabetes. Interaction testing suggested that women with diabetes did poorly in the usual care group, while their counterparts on CPAP therapy remained stable. CONCLUSIONSAmong patients with established CVD and OSA, we found no evidence that CPAP therapy over several years affects glycemic control in those with diabetes or prediabetes or diabetes risk over standard-of-care treatment. The potential differential effect according to sex deserves further investigation.Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper-airway collapse during sleep that causes intermittent hypoxemia, sleep fragmentation, and daytime sleepiness. The standard therapy for OSA is continuous positive airway pressure (CPAP) to prevent airway obstruction (1).OSA is common in the population and strongly associated with obesity (2). Prospective cohort studies have found associations between moderate to severe OSA and

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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.

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.