SummaryBackgroundResults of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.MethodsFOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.FindingsBetween Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.InterpretationFluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.FundingUK Stroke Association and NIHR Health Technology Assessment Programme.

Summary Background Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. Funding British Heart Foundation.

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy. Methods RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627.

Circadian variation of onset of transient ischaemic attack (TIA) or stroke during four 6-hourly periods starting from midnight was studied in Hong Kong Chinese patients admitted to a regional hospital between October 1996 and July 1999. The onset was classifiable into one of the 6-hourly periods in 832 of 905 patients; patients with unclassifiable onset were more likely to have lacunar infarct and less likely to have intracerebral haemorrhage (ICH). There was a significant circadian variation of onset in all strokes and TIA, TIA alone, ischaemic stroke (IS), ICH and different IS subtypes. The risk of onset was greatest between 6 a.m. and noon for IS or TIA, but between noon and 6 p.m. for ICH. There was no difference in the circadian variation between patients with and without prior TIA or stroke. This hospital-based study revealed a significant circadian variation of onset in different types and subtypes of stroke.

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Context and Objective: Hamstring strain is a common injury in football and it causes a significant amount of time lost from competition and training. Since poor flexibility is thought to predispose to muscle strain, stretching is routinely recommended during warm-up routines by coaches to prevent injuries. However, available evidence suggests that pre-exercise stretching (PES), especially static stretching, has no benefit on injury rates and may even reduce performance in explosive type activities. We designed this study to assess the attitudes, beliefs and practices of football coaches regarding stretching in the prevention of hamstring strains. Design: A cross-sectional survey. Setting: Mauritius Football Association (MFA). Participants: 26 football coaches registered with the MFA. Intervention: Questionnaires were distributed to football coaches of the MFA via sports officers. Questionnaires were then collected two weeks after distribution. Main Outcome Measures: Attitudes, beliefs and practices of football coaches regarding stretching in the prevention of hamstring strains. Results: MFA coaches held generally positive attitudes and beliefs towards stretching. 88% of coaches felt that PES is beneficial and 93% believed that PES prevents hamstring strains. The majority of coaches recommended stretching after warming up (81%) and after the training session (93%). 76% of coaches also advised stretching outside the training sessions. 96% of coaches used static stretching to stretch the hamstrings. The hamstrings were stretched on average for 4 times at each training session and the mean duration of a static stretch was 12 seconds. Conclusions: Nearly all coaches believed that PES prevents hamstring strains although evidence is limited. Some of the coaches' beliefs and practices were not in line with current recommendations. Coaches reported that their stretching practices would be most likely influenced by scientific research. Thus there is an urgent need to devise awareness and training programmes in this area.

Venous thromboembolism (VTE) impacts an estimated one in every three patients with malignant glioma (MG), resulting in increased morbidity and mortality. Despite the high prevalence and serious consequences of VTE, there is no outpatient standard of care prevention strategy. There have been three prospective clinical trials of VTE prophylaxis in patients with newly diagnosed MG, all of which used an injectable low molecular weight heparin (LMWH) product. We performed an open-label safety study of apixaban, a direct oral anticoagulant (DOAC), for VTE prevention in patients with newly diagnosed MG. All patients had surgery or biopsy two to twenty-one days prior to enrollment in the study. Patients were treated with apixaban 2.5 mg twice daily for up to 6 months. Peak and trough apixaban concentrations were measured at the beginning and end of treatment. Thirteen patients consented to the study and ten enrolled (2 screen-fail, 1 withdrawal). The patients have completed a mean of 4.5 cycles of apixaban (range 2 to 6, with 2 patients still undergoing treatment). There were no bleeding events while receiving apixaban. There were no hematologic or non-hematologic treatment-related adverse events. There were no VTE events observed in patients receiving apixaban. Two patients who came off treatment early due to disease progression developed VTEs after stopping prophylactic apixaban. Quality of life analysis is ongoing. In this pilot study we found that prophylactic dosing of 2.5 mg twice daily of apixaban was safe in the post-operative period for patients with newly diagnosed MG. Our preliminary results suggest that this may be a safe and effective prevention strategy for VTE prophylaxis in this high risk group of patients.