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Lundström, E, DocentORCID iD iconorcid.org/0000-0002-5313-9052
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Publications (10 of 36) Show all publications
Ahmed, N., Audebert, H., Turc, G., Cordonnier, C., Christensen, H., Sacco, S., . . . Steiner, T. (2019). Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018.. European Stroke Journal, 4(4), 307-317
Open this publication in new window or tab >>Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018.
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2019 (English)In: European Stroke Journal, ISSN 2396-9873, E-ISSN 2396-9881, Vol. 4, no 4, p. 307-317Article in journal (Refereed) Published
Abstract [en]

The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at www.eso-karolinska.org and http://eso-stroke.org) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.

Keywords
Stroke, intracerebral haemorrhage, ischaemic stroke, oral anticoagulation, patent foramen ovale, prehospital, thrombectomy, thrombolysis
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-401409 (URN)10.1177/2396987319863606 (DOI)31903429 (PubMedID)
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-02-07Bibliographically approved
Dennis, M., Forbes, J., Graham, C., Hackett, M., Hankey, G. J., House, A., . . . Rodgers, H. (2019). Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. The Lancet, 393(10168), 265-274
Open this publication in new window or tab >>Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial
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2019 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 393, no 10168, p. 265-274Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-375812 (URN)10.1016/S0140-6736(18)32823-X (DOI)000456000000029 ()30528472 (PubMedID)
Available from: 2019-02-05 Created: 2019-02-05 Last updated: 2019-02-05Bibliographically approved
Dennis, M., Forbes, J., Graham, C., Hackett, M. L., Hankey, G. J., House, A., . . . Mead, G. (2019). Fluoxetine and Fractures After Stroke: Exploratory Analyses From the FOCUS Trial. Stroke, 50(11), 3280-3282
Open this publication in new window or tab >>Fluoxetine and Fractures After Stroke: Exploratory Analyses From the FOCUS Trial
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2019 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 50, no 11, p. 3280-3282Article in journal (Refereed) Published
Abstract [en]

Background and Purpose- The FOCUS trial (Fluoxetine or Control Under Supervision) showed that fluoxetine did not improve modified Rankin Scale scores (mRS) but increased the risk of fractures. We aimed to describe the fractures, their impact on mRS and factors associated with fracture risk. Methods- A United Kingdom, multicenter, parallel-group, randomized, placebo-controlled trial. Patients ≥18 years with a clinical stroke and persisting deficit assessed 2 to 15 days after onset were eligible. Consenting patients were allocated fluoxetine 20 mg or matching placebo for 6 months. The primary outcome was the mRS at 6 months and secondary outcomes included fractures. Results- Sixty-five of 3127 (2.1%) patients had 67 fractures within 6 months of randomization; 43 assigned fluoxetine and 22 placebo. Fifty-nine (90.8%) had fallen and 26 (40%) had fractured their neck of femur. The effect of fluoxetine on mRS (common odds ratio =0.951) was not significantly altered by excluding fracture patients (common odds ratio =0.961). Cox proportional hazards modeling showed that only age >70 year (hazard ratio =1.97; 95% CI, 1.13-3.45; P=0.017), female sex (hazard ratio =2.13; 95% CI, 1.29-3.51; P=0.003), and fluoxetine (hazard ratio =2.00; 95% CI, 1.20-3.34; P=0.008) were independently associated with fractures. Conclusions- Most fractures resulted from falls. Although many fractures were serious, and likely to impair patients' function, the increased fracture risk did not explain the lack of observed effect of fluoxetine on mRS. Only increasing age, female sex, and fluoxetine were independent predictors of fractures. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN83290762.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
Keywords
fluoxetine, fractures, odds ratio, randomized controlled trial, risk
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-394921 (URN)10.1161/STROKEAHA.119.026639 (DOI)000492999300069 ()31426731 (PubMedID)
Available from: 2019-10-10 Created: 2019-10-10 Last updated: 2019-11-18Bibliographically approved
Mead, G. E., Legg, L., Tilney, R., Hsieh, C. F., Wu, S., Lundström, E., . . . Hankey, G. J. (2019). Fluoxetine for stroke recovery: Meta-analysis of randomized controlled trials.. International Journal of Stroke, Article ID 1747493019879655.
Open this publication in new window or tab >>Fluoxetine for stroke recovery: Meta-analysis of randomized controlled trials.
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2019 (English)In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, article id 1747493019879655Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: To determine whether fluoxetine, at any dose, given within the first year after stroke to patients who did not have to have mood disorders at randomization reduced disability, dependency, neurological deficits and fatigue; improved motor function, mood, and cognition at the end of treatment and follow-up, with the same number or fewer adverse effects.

METHODS: Searches (from 2012) in July 2018 included databases, trials registers, reference lists, and contact with experts. Co-primary outcomes were dependence and disability. Dichotomous data were synthesized using risk ratios (RR) and continuous data using standardized mean differences (SMD). Quality was appraised using Cochrane risk of bias methods. Sensitivity analyses explored influence of study quality.

RESULTS: The searches identified 3414 references of which 499 full texts were assessed for eligibility. Six new completed RCTs (n = 3710) were eligible, and were added to the seven trials identified in a 2012 Cochrane review (total: 13 trials, n = 4145). There was no difference in the proportion independent (3 trials, n = 3249, 36.6% fluoxetine vs. 36.7% control; RR 1.00, 95% confidence interval 0.91 to 1.09, p = 0.99, I2 = 78%) nor in disability (7 trials n = 3404, SMD 0.05, -0.02 to 0.12 p = 0.15, I2 = 81%) at end of treatment. Fluoxetine was associated with better neurological scores and less depression. Among the four (n = 3283) high-quality RCTs, the only difference between groups was lower depression scores with fluoxetine.

CONCLUSION: This class I evidence demonstrates that fluoxetine does not reduce disability and dependency after stroke but improves depression.

Keywords
Stroke, fluoxetine, recovery, rehabilitation
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-401403 (URN)10.1177/1747493019879655 (DOI)31619137 (PubMedID)
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-02-06Bibliographically approved
Lundström, E. (2019). Hur ska alla i Sverige få tillgång till trombektomi vid stroke?. Neurologi i Sverige (2), 46-49
Open this publication in new window or tab >>Hur ska alla i Sverige få tillgång till trombektomi vid stroke?
2019 (Swedish)In: Neurologi i Sverige, ISSN 2000-8538, no 2, p. 46-49Article in journal (Other (popular science, discussion, etc.)) Published
Keywords
stroke, trombektomi, akut neurologi
National Category
Neurosciences
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-383287 (URN)
Available from: 2019-05-13 Created: 2019-05-13 Last updated: 2019-05-24Bibliographically approved
Isaksson, E., Wester, P., Laska, A. C., Nasman, P. & Lundström, E. (2019). Identifying important barriers to recruitment of patients in randomised clinical studies using a questionnaire for study personnel. Trials, 20(1), Article ID 618.
Open this publication in new window or tab >>Identifying important barriers to recruitment of patients in randomised clinical studies using a questionnaire for study personnel
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2019 (English)In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 20, no 1, article id 618Article in journal (Refereed) Published
Abstract [en]

Background:

Many randomised controlled trials (RCT) fail to meet their recruitment goals. Study personnel play a key role in recruitment. The aim of this study was to identify successful strategies that study personnel consider to be important in patient recruitment to RCT.

Methods:

We constructed a questionnaire based on the literature, discussions with colleagues and our own experience as trialists. The survey was named "What is Important for Making a Study Successful questionnaire" (WIMSS-q). Our target group was the study personnel in the ongoing EFFECTS study. The questionnaire was sent out electronically to all physicians and nurses (n = 148). Success factors and barriers were divided according to patient, centre and study level, respectively.

Results:

Responses were received from 94% of the study personnel (139/148). The five most important factors at centre level for enhancing recruitment were that the research question was important (97%), a simple procedure for providing information and gaining consent (92%), a highly engaged local principal investigator and research nurse (both 87%), and that study-related follow-ups are practically feasible and possible to coordinate with the clinical follow-up (87%). The most significant barrier at the local centre was lack of time and resources devoted to research (72%). Important patient-related barriers were fear of side effects (35%) and language problems (30%).

Conclusions:

For recruitment in an RCT to be successful, the research question must be relevant, and the protocol must be simple and easy to implement in the daily routine.

Keywords
Recruitment, Survey, Questionnaire, Randomised controlled trials, RCT
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-400767 (URN)10.1186/s13063-019-3737-1 (DOI)000502747500001 ()31666093 (PubMedID)
Funder
Swedish Research CouncilSwedish Heart Lung Foundation
Available from: 2020-01-03 Created: 2020-01-03 Last updated: 2020-01-03Bibliographically approved
Legg, L. A., Tilney, R., Hsieh, C.-F., Wu, S., Lundström, E., Rudberg, A.-S., . . . Mead, G. E. (2019). Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database of Systematic Reviews, 2019(11), Article ID CD009286.
Open this publication in new window or tab >>Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery
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2019 (English)In: Cochrane Database of Systematic Reviews, ISSN 1469-493X, E-ISSN 1469-493X, Vol. 2019, no 11, article id CD009286Article, review/survey (Refereed) Published
Abstract [en]

BACKGROUND: Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence.

OBJECTIVES: To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects.

SEARCH METHODS: For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early).

DATA COLLECTION AND ANALYSIS: We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria.

MAIN RESULTS: We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow-up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta-analysis of these three trials found little or no effect of SSRI on either disability score: SMD -0.01 (95% CI -0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate-quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate-quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate-quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate-quality evidence), with no evidence of heterogeneity (I2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants.

AUTHORS' CONCLUSIONS: We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta-analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta-analysis of large ongoing trials will be required to determine the generalisability of these findings.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
National Category
Clinical Medicine Neurology
Identifiers
urn:nbn:se:uu:diva-401395 (URN)10.1002/14651858.CD009286.pub3 (DOI)000504427100035 ()31769878 (PubMedID)
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-02-19Bibliographically approved
Lundström, E., Dennis, M. & Mead, G. (2019). The Effects Of Fluoxetine On Fracture Risk After Stroke: Further Analyses From The Focus Trial. In: : . Paper presented at European Stroke Conference ESOC 2019, May 22-24 2019, Milan, italy (pp. 714-714). , S1
Open this publication in new window or tab >>The Effects Of Fluoxetine On Fracture Risk After Stroke: Further Analyses From The Focus Trial
2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

Background and Aims: The FOCUS trial showed that 20mg of fluoxetine daily, for six months, started 2–15 days post stroke had no effect on the modified Rankin scale (mRS), reduced the risk of new depression (Risk difference 3.8%) but increased the risk of bone fractures (Risk difference 1.4%). Further analyses aimed to explore the factors associated with bone fractures.

Methods: Sixty five of the 3127 (2.1%) patients enrolled had a fracture within six months of randomisation. Of these 59 (90.8%) resulted from a fall and 26 (40%) affected the neck of femur. Cox proportional hazards modelling of the risk of fracture showed that only age ≤70yr (Hazard Ratio = 0.51 (95%CI 0.29-0.89; p = 0.017), female sex (HR = 2.13 (1.29-3.51; p = 0.003) and fluoxetine treatment (HR = 2.00 (1.20-3.34; p = 0.008) were independent predictors. Stroke pathology, severity, type of deficit, prior fractures, other medication affecting blood pressure, bone density and balance had no significant effect. Furthermore, removing patients with a fracture from the primary analysis did not significantly alter the effect on mRS (Common odds ratio 0.951 with fractures, 0.961 without).

Results: Only increasing age, female sex and fluoxetine were independent predictors of fracture risk. Most fractures resulted from falls. Although many of the fractures were serious, and are likely to have impaired patients’ function, the increased fracture risk did not explain the lack of observed effect of fluoxetine on mRS.

Conclusions: A future individual patient data meta-analysis including the patients from the ongoing AFFINITY and EFFECTS trials may clarify the mechanism of fractures due to fluoxetine.

Trial registration number: ISRCTN registry, number ISRCTN83290762.

Keywords
stroke, fluoxetine, SSRI, fracture
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-389566 (URN)10.1177/2396987319845581 (DOI)
Conference
European Stroke Conference ESOC 2019, May 22-24 2019, Milan, italy
Note

FOCUS trial collaboration

Available from: 2019-07-18 Created: 2019-07-18 Last updated: 2019-08-27Bibliographically approved
Hedlund, F., Leighs, A., Barber, P. A., Lundström, E., Wu, T. Y. & Ranta, A. (2019). Trends in stroke reperfusion treatment and outcomes in New Zealand.. Internal medicine journal (Print)
Open this publication in new window or tab >>Trends in stroke reperfusion treatment and outcomes in New Zealand.
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2019 (English)In: Internal medicine journal (Print), ISSN 1444-0903, E-ISSN 1445-5994Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: Intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) can help reverse stroke symptoms in selected patients but are both time sensitive interventions.

AIMS: To report current stroke reperfusion rates and quality measures as well as trends over time in New Zealand.

METHOD: Since 2015 New Zealand treatment centers have been mandated to prospectively enter all IVT and EVT patients into a low cost National Stroke Register. Data was cleaned and missing data added where possible through contact with individual hospitals. Main outcomes include treatment delays, vital status at day seven and complications.

RESULTS: In 2018, there were 719 of 7173 (10.0%) patients with ischemic stroke or stroke unspecified treated with intravenous IVT, up from 389 of 5963 (6.5%) patients in 2015 (p < 0.001), with no change in day seven mortality (p = 0.63) or sICH rate (p = 0.22). Median (interquartile range (IQR)) door-to-needle times decreased from 65 (47-89) minutes in 2017 to 59 (40-84) minutes in 2018 (p = 0.022), and patients treated within 60 min increased from 40% to 51% (p < 0.001). In 2018, there were 243 (3.4%) patients treated with EVT up from 134/6859 (1.9%) in 2017 (p < 0.0001), with no change in seven mortality (p = 0.39) or sICH (p = 0.78). There was no significant change in onset-to-needle (p = 0.21), arrival-to-groin (p = 0.28) or onset-to-reperfusion time (p = 0.32).

CONCLUSION: Stroke reperfusion rates in New Zealand are continuously rising with no associated increase in complications. More patients are being treated faster upon hospital arrival but there remains room for further improvement in reducing onset to treatment delays. This article is protected by copyright. All rights reserved.

Keywords
Endovascular Clot Retrieval, Ischaemic Stroke, Mechanical Thrombectomy, Reperfusion, Stroke, Thrombolysis
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-401400 (URN)10.1111/imj.14682 (DOI)31707750 (PubMedID)
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-02-06Bibliographically approved
Roaldsen, M. B., Soyland, M.-H. -., Jusufovic, M., Tveiten, A., Lundström, E., Petersson, J., . . . Berge, E. (2019). TWIST tenecteplase in wake-up ischaemic stroke trial. European Journal of Neurology, 26(1, SI)
Open this publication in new window or tab >>TWIST tenecteplase in wake-up ischaemic stroke trial
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2019 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 26, no 1, SIArticle in journal (Refereed) Published
Place, publisher, year, edition, pages
WILEY, 2019
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-401410 (URN)
Note

5th Congress of the European-Academy-of-Neurology (EAN), Oslo, NORWAY, JUN 29-JUL 02, 2019

Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-02-04Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-5313-9052

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