| 1. |
- Dennis, Martin, et al.
(author)
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Effects of fluoxetine on functional outcomes after acute stroke (FOCUS) : a pragmatic, double-blind, randomised, controlled trial
- 2019
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 393:10168, s. 265-274
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Journal article (peer-reviewed)abstract
- Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.Methods FOCUS 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.Findings Between 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.Interpretation Fluoxetine 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.
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| 2. |
- Eeg-Olofsson, Måns, 1967, et al.
(author)
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TTCOV19: timing of tracheotomy in SARS-CoV-2-infected patients: a multicentre, single-blinded, randomized, controlled trial
- 2022
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 26:1
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Journal article (peer-reviewed)abstract
- Background: Critically ill COVID-19 patients may develop acute respiratory distress syndrome and the need for respiratory support, including mechanical ventilation in the intensive care unit. Previous observational studies have suggested early tracheotomy to be advantageous. The aim of this parallel, multicentre, single-blinded, randomized controlled trial was to evaluate the optimal timing of tracheotomy. Methods: SARS-CoV-2-infected patients within the Region Vastra Gotaland of Sweden who needed intubation and mechanical respiratory support were included and randomly assigned to early tracheotomy (<= 7 days after intubation) or late tracheotomy (>= 10 days after intubation). The primary objective was to compare the total number of mechanical ventilation days between the groups. Results: One hundred fifty patients (mean age 65 years, 79% males) were included. Seventy-two patients were assigned to early tracheotomy, and 78 were assigned to late tracheotomy. One hundred two patients (68%) underwent tracheotomy of whom sixty-one underwent tracheotomy according to the protocol. The overall median number of days in mechanical ventilation was 18 (IQR 9; 28), but no significant difference was found between the two treatment regimens in the intention-to-treat analysis (between-group difference:- 1.5 days (95% CI -5.7 to 2.8); p= 0.5). A significantly reduced number of mechanical ventilation days was found in the early tracheotomy group during the per-protocol analysis (between-group difference: - 8.0 days (95% CI - 13.8 to - 2.27); p= 0.0064). The overall correlation between the timing of tracheotomy and days of mechanical ventilation was significant (Spearman's correlation: 0.39, p < 0.0001). The total death rate during intensive care was 32.7%, but no significant differences were found between the groups regarding survival, complications or adverse events. Conclusions: The potential superiority of early tracheotomy when compared to late tracheotomy in critically ill patients with COVID-19 was not confirmed by the present randomized controlled trial but is a strategy that should be considered in selected cases where the need for MV for more than 14 days cannot be ruled out.
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| 3. |
- Järvelä, Sally, et al.
(author)
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Antioxidant enzymes in oligodendroglial brain tumors : association with proliferation, apoptotic activity and survival
- 2006
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In: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 77:2, s. 131-40
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Journal article (peer-reviewed)abstract
- Purpose of the study was to investigate the relationship between antioxidant enzyme expression and clinicopathological features in oligodendroglial tumors. The expression of antioxidant enzymes and related proteins (AOEs), manganese superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin reductase (TrxR) and gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and GLCL-R), was studied in 85 oligodendroglial tumors. The material included 71 primary (43 grade II and 28 grade III) and 14 recurrent (6 grade II and 8 grade III) tumors. Fifty-seven cases were pure oligodendrogliomas and 28 were mixed oligoastrocytomas. Immunoreactivity for MnSOD was found in 89%, Trx in 29%, TrxR in 76%, GLCL-C in 70% and GLCL-R in 68% of cases. Increased Trx expression was associated with higher tumor grade, cell proliferation and apoptosis (P=0.006, P=0.001 and P=0.003, Mann-Whitney test). Pure oligodendrogliomas showed more intense staining than oligoastrocytomas, especially for MnSOD (P=0.002, Mann-Whitney test). In the total series Trx was associated with poor prognosis in univariate survival analysis (P=0.0343, log-rank test) and furthermore in Cox multivariate analysis (P=0.009) along with age (P=0.002). The results suggest that the expression of Trx has a correlation to patient outcome and that there may be some association between AOEs, like MnSOD and Trx, and clinicopathological features of oligodendrogliomas.
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| 4. |
- Järvelä, Sally, et al.
(author)
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Decreased expression of antioxidant enzymes is associated with aggressive features in ependymomas
- 2008
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In: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 90:3, s. 283-291
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Journal article (peer-reviewed)abstract
- The purpose of this study was to investigate the relationship between antioxidant enzyme expression and clinicopathological features in 67 ependymal tumors. We included into the analysis antioxidant enzymes (AOEs) and related proteins, such as, manganese superoxide dismutase (MnSOD), gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and GLCL-R), thioredoxin (Trx) and thioredoxin reductase (TrxR). Their expression was studied in 46 primary (10 grade I, 30 grade II and 6 grade III) and 21 recurrent (3 grade I, 12 grade II and 6 grade III) tumors. Immunoreactivity for MnSOD was found in 87%, GLCL-C in 74%, GLCL-R in 89%, Trx in 72%, TrxR in 54%, of primary tumors. Lower GLCL-C and GLCL-R expression was associated with higher tumor grade (P = 0.047 and 0.049, respectively). MnSOD, GLCL-C and TrxR expressions were significantly higher in tumors located in the spinal cord compared to those in the brain (P = 0.044, 0.046 and 0.004, respectively). In the primary tumors Trx-positivity was found to correlate significantly with patient survival. In univariate survival analysis patients whose tumors did not express Trx had shorter survival (P = 0.045) and there was even more significant association (P = 0.011) when only adults were included in the analysis (in the total material median follow-up time of Trx-positive tumors was 9.7 years and of Trx-negative 5.4 years). The results indicate that AOEs have several biological functions in ependymal tumors. Trx had important prognostic value: all adults with Trx-positive tumors were alive at follow-up (median 7.8 years).
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