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

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Abstract P305: Post-Stroke Aphasia as a Predictor of 30-Day Readmission Associated With Infection: A Retrospective Chart Review

Introduction: Studies have demonstrated that aphasia may negatively impact morbidity and mortality among ischemic stroke (IS) patients. However, the association between post-stroke aphasia and readmission with infection (RI) is poorly understood. We sought to assess the impact of aphasia on post-stroke RI. We hypothesized that aphasic patients are at increased risk of infection in the 30-day post-stroke period. Methods: We performed retrospective chart review of the Mount Sinai Hospital IS patients with 30-day all cause readmission from January 2016 - December 2019. All variables were abstracted from the index admission (IA) electronic medical records except for aspects related to the readmission (RA). Aphasia was present if a neurologist diagnosed the patient with acquired language dysfunction during IA. We performed chi square and logistic regression analyses to compare readmitted patients with and without aphasia at IA. Our fully adjusted model controlled for age, sex, medical comorbidities, NIHSS ≥ 8, IA LOS &gt; 7, IA infection, discharge to facility. We completed all analyses with SPSS. Results: During IA, 36% (n=42) were diagnosed with aphasia. At IA, there were no significant differences in age (dichotomized at 65), sex, or medical comorbidities between aphasic and non-aphasic cohorts. However, more aphasic patients had admission NIHSS ≥ 8 (89% vs 35%, p&lt;0.0001), LOS &gt; 7 (76% vs 42%, p=0.0004), discharge to facility (79% vs 49%, p=0.0016), and RI (52% vs 19%, p=0.002). The presence of aphasia predicted RI in both unadjusted (OR=4.6, p&lt;0.001) and adjusted (OR= 3.3, p=0.014) multivariate analyses. The Kappa inter-reliability ranged from 0.7-1.0 for the key variables included in our adjusted model. Conclusions: The adjusted odds of 30-day readmission with infection were significantly greater in those with diagnosis of aphasia at the time of index admission compared to those without. Our study provides preliminary evidence that the presence of aphasia may have negative consequences on a patient’s health beyond the language disturbance. Further study is needed to better understand the reasons and risk reduction strategies in this vulnerable population. </jats:p

High Risk Features Contributing to 30-Day Readmission After Acute Ischemic Stroke: A Single Center Retrospective Case-Control Study

Background and Purpose: Risk of 30-day stroke readmission has been attributed to medical comorbidities, stroke severity, and hospitalization metrics. The leading etiologies appear to vary across institutions and remain a moving target. We hypothesized that patients with increased medical complexity have higher odds of 30-day readmission and the immediate time after discharge may be most vulnerable. We aimed to characterize patients with 30-day readmission after acute ischemic stroke (IS) and identify predictors of post-IS readmission. Methods: We performed a retrospective case-control study analyzing post-IS 30-day readmission between January 2016-December 2019 using data from Mount Sinai Hospital’s Get With The Guidelines database. We performed chi square analyses and multivariate adjusted logistic regression model including age, sex, coronary artery disease (CAD), renal insufficiency (RI), history of prior stroke or TIA, length of stay (LOS) &gt; 7, and NIHSS ≥ 5. Results: 6.7% (n = 115) of 1,706 IS encounters had 30-day readmission. The 115 cases were compared to 1,591 controls without 30-day readmission. In our adjusted model, CAD (OR = 1.7, p = 0.01), history of prior stroke or TIA (OR = 1.6, p = 0.01), LOS &gt;7 (OR = 1.7, p = 0.02), and NIHSS ≥ 5 (OR = 4.5, p &lt; 0.001) predicted 30-day readmission. 65% (n = 75) of readmitted patients had readmission within 14 days post-discharge. Conclusions: Patients with post-IS 30-day readmission were more likely to have complex medical comorbidities and history of stroke or TIA compared to controls. Patients with more severe stroke and longer LOS may benefit from individualized transition of care plans and closer follow up during the vulnerable 30-day post-stroke period. </jats:sec

Surface Cooling System for Fever Control in Neurocritical Care Patients: A Pilot Study

OBJECTIVES: Fever occurs in up to 50% of critically-ill patients with acute neurological injury. Small temperature elevations have been correlated with increased morbidity and mortality in this patient population. We sought to evaluate a novel single-use surface cooling system for the treatment of fever in patients with acute brain injury. PATIENTS AND METHODS: We conducted a retrospective analysis of a prospective product evaluation using the EMCOOLS Flex.Pad™ system for acute fever (≥38.3 °C) in our 16-bed neuro-ICU. Four refrigerated pads (-18 °C) were applied to the chest, back, and anterior thighs. Core temperature (bladder) was continuously recorded over 4 h, and the highest Bedside Shivering Assessment Scale (BSAS) score was recorded hourly. RESULTS: Twelve subjects were included in the analysis. Mean age was 55 ± 9 years, 9 patients were men, and mean weight was 85 ± 12 kg. The most common primary diagnoses were subarachnoid (N = 5) and intracerebral (N = 4) hemorrhage. Application of the EMCOOLS system resulted in a linear 1.3 ± 0.6 °C drop (T0avg=38.9 (0)C, T90avg=37.6 (0)C, P=0.0032) in mean temperature over 90min, followed by a plateau with only one subject rebounding to \u3e38 degrees C within 4h. Normothermia (\u3c38.0 (0)C) was achieved in all but one patient (92%) in an average of 65min. Comatose patients displayed a non-significantly higher degree of cooling at 90min than did awake subjects (DeltaTcoma=1.74 degrees C vs DeltaTawake=0.74 degrees C hr(-1), P=0.067). There was no observed skin irritation upon removal of the device for any patients. CONCLUSION: The EMCOOLs system is a well-tolerated, safe and effective short-term intervention for control of fever in neurological patients. Future studies are needed to compare efficacy of the EMCOOLs to other devices and interventions

Abstract 95: The Mobile Interventional Stroke Team (MIST) Model Improves Early Outcomes in Elvo Stroke: The NYC Mist Trial

Introduction: Endovascular therapy (EVT) has become the standard of care for treatment of emergent large vessel occlusion (ELVO) in ischemic stroke. It is a time sensitive procedure that has previously only been performed at comprehensive stroke centers (CSC). Transfer was required for patients presenting at a primary stroke center (PSC). PSCs with interventional capacity (PSCI) have emerged to increase access to EVT. We have developed a Mobile Interventional Stroke Team (MIST) model, in which a MIST transfers from a CSC to PSCI to perform EVT. Hypothesis: The delivery of care by the MIST at PSCIs is more time efficient and leads to improved clinical outcomes in comparison to transferring patients from a PSC to PSCI or CSC and comparable to direct presentation to a CSC. Methods: Analysis of prospectively collected data from 228 patients who received EVT for ELVO at a CSC or 4 PSCIs between June 2016 - December 2018 was performed. The cohorts include: Mothership with patient presentation to CSC (n=20), Drip-and-Ship with patient transfer from PSC or PSCI to CSC (DS) (n=114), MIST and patient presentation to PSCI (n=64), and DS with patient transfer from PSC to PSCI and MIST (DS/MIST) (n=30). The primary outcome was initial door-to-recanalization. Secondary outcomes measured other time intervals and clinical outcomes at discharge and 3 months. Results: MIST had a faster mean initial door-to-recanalization time than DS by 83 minutes (p &lt; 0.05). MIST and Mothership had similar median times of 192 minutes and 181 minutes, respectively (p = 0.84). A greater proportion of patients reached a discharge NIHSS of 0 or 1 in MIST compared to DS (34% vs. 17%; p &lt; 0.01). MIST led to 53% with a mRS of ≤ 2 at 3 months compared to 39% in DS, although not statistically significant (p = 0.10). Conclusions: MIST has led to significantly faster initial door-to-recanalization times compared to DS. This decrease in time has translated into improved short-term outcomes and a trend towards improved long-term outcomes. </jats:p