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

Effects of gait training with body weight support on a treadmill vs. overground for individuals with stroke

Made available in DSpace on 2018-11-26T17:24:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-04-01Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Objective: To investigate the effects of gait training with body weight support (BWS) on a treadmill versus overground in individuals with chronic stroke. Design: Randomized controlled trial. Setting: University research laboratory. Participants: Individuals (N=28) with chronic stroke (>6mo from the stroke event). Interventions: Participants were randomly assigned to receive gait training with BWS on a treadmill (n=14) or overground (n=14) 3 times a week for 6 weeks. Main Outcome Measures: Gait speed measured using the 10-meter walk test, endurance measured using the 6-minute walk test, functional independence measured using the motor domain of the FIM, lower limb recovery measured using the lower extremity domain of the Fugl-Meyer assessment, step length, step length symmetry ratio, and single-limb support duration. Measurements were obtained at baseline, immediately after the training session, and 6 weeks after the training session. Results: At 1 week after the last training session, both groups improved in all outcome measures except paretic step length and step length symmetry ratio, which were improved only in the overground group (P=.01 and P=.01, respectively). At 6 weeks after the last training session, all improvements remained and the treadmill group also improved paretic step length (P.05). Conclusions: Individuals with chronic stroke equally improve gait speed and other gait parameters after 18 sessions of BWS gait training on either a treadmill or overground. Only the overground group improved step length symmetry ratio, suggesting a role of integrating overground walking into BWS interventions poststroke. (C) 2016 by the American Congress of Rehabilitation MedicineCruzeiro do Sul Univ, Inst Phys Act & Sport Sci, Rua Galvao Bueno 868, BR-01506000 Sao Paulo, SP, BrazilSao Paulo State Univ, Dept Phys Educ, Rio Claro, SP, BrazilVet Adm Maryland Hlth Care Syst, Maryland Exercise & Robot Ctr Excellence, Baltimore, MD USAUniv Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USAUniv Southampton, Fac Hlth Sci, Southampton, Hants, EnglandSao Paulo State Univ, Dept Phys Educ, Rio Claro, SP, Brazi

Ground reaction forces during level ground walking with body weight unloading

Background: Partial body weight support (BWS) systems have been broadly used with treadmills as a strategy for gait training of individuals with gait impairments. Considering that we usually walk on level ground and that BWS is achieved by altering the load on the plantar surface of the foot, it would be important to investigate some ground reaction force (GRF) parameters in healthy individuals walking on level ground with BWS to better implement rehabilitation protocols for individuals with gait impairments. Objective: To describe the effects of body weight unloading on GRF parameters as healthy young adults walked with BWS on level ground. Method: Eighteen healthy young adults (27 +/- 4 years old) walked on a walkway, with two force plates embedded in the middle of it, wearing a harness connected to a BWS system, with 0%, 15%, and 30% BWS. Vertical and horizontal peaks and vertical valley of GRF, weight acceptance and push-off rates, and impulse were calculated and compared across the three experimental conditions. Results: Overall, participants walked more slowly with the BWS system on level ground compared to their normal walking speed. As body weight unloading increased, the magnitude of the GRF forces decreased. Conversely, weight acceptance rate was similar among conditions. Conclusions: Different amounts of body weight unloading promote different outputs of GRF parameters, even with the same mean walk speed. The only parameter that was similar among the three experimental conditions was the weight acceptance rate.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

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