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.
www.dissection.co.uk, ISRNCTN44555237.
Background and Purpose-Studies suggest that women with stroke are investigated less aggressively and receive tissue plasminogen activator less frequently than men. We tested whether gender differences in the investigation, treatment, and outcome of stroke are due to confounding factors. Methods-Gender differences in the use of investigations, trial enrollment, treatment with intravenous tissue plasminogen activator, and in-hospital outcomes were examined in data from our prospective registry using multivariate analysis to adjust for age, prestroke functional status, stroke subtype and severity, and atrial fibrillation. Results-Of 2725 consecutive hospitalized patients (1996 to 2006), 88% had ischemic stroke and 48% were women.Women were older (median age, 77 versus 70 years), had more severe strokes, and were less likely to be independent prestroke (78% versus 87%) compared with men (all PϽ0.001). There was no gender difference in adjusted use of investigations. Conclusion-The majority of the gender differences in stroke were explained by confounding. More research is required to understand gender differences in stroke pathophysiology and the utilization of thrombolytic therapy.
this study demonstrates an externally validated stroke outcome prediction model using simple clinical variables. Outcome prediction was not significantly improved with CT-derived radiological variables or more complex clinical variables.
Age and size of aneurysm were the only 2 independent predictors of surgical outcome.
A blinded RCT investigating the role of epidural and WIC administration for postoperative analgesia following LCR is feasible. Rigorous standard operating procedures for data collection are required.
Sulfonylureas reduce cerebral blood flow (CBF) during hypoxia but not during hypercapnia, whereas blockers of nitric oxide (NO) synthesis reduce hypercapnic CBF. However, the effect of NO blockers on hypoxic CBF is uncertain. CBF was measured in the cortex of 51 enflurane-anesthetized rats by the hydrogen clearance technique during eucapnia, hypercapnia (arterial PCO2 65 Torr), and hypoxia (arterial PO2 40 Torr). CBF increased twofold in both hypercapnia and hypoxia from eucapnia. Intracortical (ic) NG-monomethyl-L-arginine (L-NMMA, 100 microM-5 mM) attenuated both the hypercapnic and hypoxic dilations by 60-70%, and L-arginine (300 mg/kg iv) partially reversed these effects. Glibenclamide (10 microM ic) and L-NMMA gave no further attenuation of the hypoxic dilation than L-NMMA alone. Cromakalim (10 microM, ic) increased CBF in eucapnia, but this was not seen in the presence of glibenclamide. The adenosine antagonist 8-phenyl-theophylline did not attenuate the hypoxic dilation. This suggests that NO synthesis plays a major role in the regulation of CBF in hypercapnia and hypoxia. But the combined effects of glibenclamide and L-NMMA do not further attenuate CBF in hypoxia.
SummaryLittle is known about orthostatic blood pressure regulation in acute stroke. We determined postural haemodynamic responses in 40 patients with acute stroke (mild or moderate severity) and 40 nonstroke control in-patients, at two days ('Day 1') and one week ('Week 1') postadmission. Following a 10-minute supine rest and baseline readings, subjects sat up and blood pressure and heart rate were taken for 5 minutes. The procedure was repeated with subjects moving from supine to the standing posture. Haemodynamic changes from supine data were analysed. On standing up, the control group had a transient significant fall in mean arterial blood pressure on Day 1 but not Week 1. No significant changes were seen on either day when sitting up. In contrast to controls, the stroke group showed increases in mean arterial blood pressure on moving from supine to the sitting and standing positions on both days. Persistent postural hypotension defined as >20 mmHg systolic fall occurred in <10% of either of the study groups on both days. Sitting and standing heart rates in both groups were significantly faster than supine heart rate on both days. The orthostatic blood pressure elevation is consistent with sympathetic nervous system overactivity which has been reported in acute stroke. Upright positioning as part of early rehabilitation and mobilisation following mild-to-moderate stroke would, therefore, not predispose to detrimental postural reductions in blood pressure.
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