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: The ABCD

Background: It is important to establish the validity of diagnostic coding in administrative datasets used in stroke and transient ischemic attack (TIA) research. This study examines the accuracy of emergency department (ED) TIA diagnosis and final diagnostic coding after hospital admission. Methods: Using administrative datasets, we identified all patients with an ED TIA diagnosis (435.9; ICD-9) admitted to Liverpool Hospital from January 2003 to December 2007. ED and hospital admission records were matched and final diagnosis codes (ICD-10-AM) recorded. All records were expertly reviewed to determine coding validity. Results: 570 patients were admitted with an ED TIA diagnosis. According to ICD-10-AM coding, 46% had TIA, 29% stroke and 25% TIA mimic diagnoses. Expert review determined final diagnoses of TIA in 51.4%, stroke in 26.1% and TIA mimic in 22.5% of the patients. The positive predictive value of a final TIA diagnosis (ICD-10-AM) was 88.2% when subjected to expert review. TIA mimic disorders diagnosed after admission included serious conditions. Conclusions: Half of the emergency diagnoses retained a TIA diagnosis after hospital admission. In the setting of neurological admission there were small percentage differences between coded final diagnosis for TIA, stroke and mimic and diagnoses at expert review. Admission of ED TIA cases permitted identification of TIA mimics with serious conditions requiring non-TIA management.

Background and Purpose Paroxysmal atrial fibrillation (PAF) underlying acute stroke frequently evades detection by standard practice, considered to be a combination of routine electrocardiogram (ECG) monitoring, and 24-hour Holter recordings. We hypothesized that nurse-led in-hospital intermittent monitoring approach would increase PAF detection rate.Methods We recruited patients hospitalised for stroke/transient ischemic attack, without history of atrial fibrillation (AF), in a prospective multi-centre observational study. Patients were monitored using a smartphone-enabled handheld ECG (iECG) during routine nursing observations, and underwent 24-hour Holter monitoring according to local practice. The primary outcome was comparison of AF detection by nurse-led iECG versus Holter monitoring in patients who received both tests: secondary outcome was oral anticoagulant commencement at 3-month following PAF detection.Results One thousand and seventy-nine patients underwent iECG monitoring: 294 had iECG and Holter monitoring. AF was detected in 25/294 (8.5%) by iECG, and 8/294 (2.8%) by 24-hour Holter recordings (<i>P</i>&lt;0.001). Median duration from stroke onset to AF detection for iECG was 3 days (interquartile range [IQR], 2 to 6) compared with 7 days (IQR, 6 to 10) for Holter recordings (<i>P</i>=0.02). Of 25 patients with AF detected by iECG, 11 were commenced on oral anticoagulant, compared to 5/8 for Holter. AF was detected in 8.8% (69/785 patients) who underwent iECG recordings only (<i>P</i>=0.8 vs. those who had both iECG and 24-hour Holter).Conclusions Nurse-led in-hospital iECG surveillance after stroke is feasible and effective and detects more PAF earlier and more frequently than routine 24-hour Holter recordings. Screening with iECG could be incorporated into routine post-stroke nursing observations to increase diagnosis of PAF, and facilitate institution of guideline-recommended anticoagulation.

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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.

No abstract

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive, generally late-onset, neurological disorder associated with biallelic pentanucleotide expansions in intron 2 of the RFC1 gene. The locus exhibits substantial genetic variability, with multiple pathogenic and benign pentanucleotide repeat alleles previously identified. To determine the contribution of pathogenic RFC1 expansions to neurological disease within an Australasian cohort and further investigate the heterogeneity exhibited at the locus, a combination of flanking and repeat-primed PCR was used to screen a cohort of 242 Australasian neurological disease patients. Patients whose data indicated large gaps within expanded alleles following repeat-primed PCR, underwent targeted long-read sequencing to identify novel repeat motifs at the locus. To increase diagnostic yield, additional probes at the RFC1 repeat region were incorporated into the PathWest diagnostic laboratory targeted neurological disease gene panel to enable first pass screening of the locus for all samples tested on the panel. Within the Australasian cohort, we detected known pathogenic biallelic expansions in 15.3% (n = 37) of cases. Thirty indicated biallelic AAGGG expansions, two had biallelic Māori alleles [(AAAGG)exp(AAGGG)exp], two samples were compound heterozygous for the Māori allele and a AAGGG expansion, two samples had biallelic ACAGG expansions and one sample was compound heterozygous for the ACAGG expansion and the AAGGG expansion. Forty-five samples tested indicated the presence of biallelic expansions not known to be pathogenic. A large proportion (84%) showed complex interrupted patterns following repeat-primed PCR, suggesting that these expansions are likely to be comprised of more than one repeat motif including previously unknown repeats. Using targeted long-read sequencing we identified three novel repeat motifs in expanded alleles. Here we also show that short read sequencing can be used to reliably screen for the presence or absence of biallelic RFC1 expansions in all samples tested using the PathWest targeted neurological disease gene panel. Our results show that RFC1 pathogenic expansions make a substantial contribution to neurological disease in the Australasian population and further extend the heterogeneity of the locus. To accommodate the increased complexity, we outline a multi-step workflow utilising both targeted short- and long-read sequencing to achieve a definitive genotype and provide accurate diagnoses for patients.