ORCID Profile
0000-0002-7472-3194
Current Organisations
American Heart Association
,
IT University of Copenhagen
,
Bispebjerg Hospital
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Elsevier BV
Date: 03-2014
Publisher: Elsevier BV
Date: 10-2017
Publisher: Elsevier BV
Date: 11-2018
Publisher: Massachusetts Medical Society
Date: 20-12-2018
Publisher: Elsevier BV
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 03-05-2014
Publisher: Elsevier BV
Date: 11-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2020
DOI: 10.1161/STROKEAHA.119.027390
Abstract: Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 ( P =0.169) and shift analysis ( P =0.086) but reached significance for mRS score of 0 to 2 ( P =0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.
Publisher: SAGE Publications
Date: 27-01-2020
Abstract: Approaches to economic evaluations of stroke therapies are varied and inconsistently described. An objective of the European Stroke Organisation (ESO) Health Economics Working Group is to standardise and improve the economic evaluations of interventions for stroke. The ESO Health Economics Working Group and additional experts were contacted to develop a protocol and a guidance document for data collection for economic evaluations of stroke therapies. A modified Delphi approach, including a survey and consensus processes, was used to agree on content. We also asked the participants about resources that could be shared to improve economic evaluations of interventions for stroke. Of 28 experts invited, 16 (57%) completed the initial survey, with representation from universities, government, and industry. More than half of the survey respondents endorsed 13 specific items to include in a standard resource use questionnaire. Preferred functional/quality of life outcome measures to use for economic evaluations were the modified Rankin Scale (14 respondents, 88%) and the EQ-5D instrument (11 respondents, 69%). Of the 12 respondents who had access to data used in economic evaluations, 10 (83%) indicated a willingness to share data. A protocol template and a guidance document for data collection were developed and are presented in this article. The protocol template and guidance document for data collection will support a more standardised and transparent approach for economic evaluations of stroke care.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-10-2022
DOI: 10.1212/WNL.0000000000201426
Abstract: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1–6.9] p 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1–4.6] p 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4–5.8] p 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6–0.9] p = 0.49). Stroke was diagnosed in 1.3% [1.31–1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82–2.97], 5,656/195,539) of all stroke hospitalizations. There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. This study is registered under NCT04934020 .
Publisher: American Medical Association (AMA)
Date: 05-05-2021
Publisher: SAGE Publications
Date: 24-08-2014
DOI: 10.1111/IJS.12309
Abstract: Intracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has updated its evidence-based guidelines for the management of ICH. A multidisciplinary writing committee of 24 researchers from 11 European countries identified 20 questions relating to ICH management and created recommendations based on the evidence in RCTs using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We found moderate- to high-quality evidence to support strong recommendations for managing patients with acute ICH on an acute stroke unit, avoiding hemostatic therapy for acute ICH not associated with antithrombotic drug use, avoiding graduated compression stockings, using intermittent pneumatic compression in immobile patients, and using blood pressure lowering for secondary prevention. We found moderate-quality evidence to support weak recommendations for intensive lowering of systolic blood pressure to mmHg within six-hours of ICH onset, early surgery for patients with a Glasgow Coma Scale score 9–12, and avoidance of corticosteroids. These guidelines inform the management of ICH based on evidence for the effects of treatments in RCTs. Outcome after ICH remains poor, prioritizing further RCTs of interventions to improve outcome.
Publisher: Springer Science and Business Media LLC
Date: 27-07-2017
Publisher: Elsevier BV
Date: 10-2020
Publisher: Springer Science and Business Media LLC
Date: 20-11-2020
DOI: 10.1186/S42466-020-00087-9
Abstract: One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial. WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0–1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase. Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years, p 0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%, p = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome ( p = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047–4.236). Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.
Publisher: American Association for Cancer Research (AACR)
Date: 12-2006
DOI: 10.1158/1055-9965.EPI-06-0368
Abstract: Background: Pancreatic cancer accounts for about 220,000 deaths each year. Known risk factors are smoking and type 2 diabetes. It remains to be seen whether these risk factors are equally important in Asia and whether other modifiable risk factors have important associations with pancreatic cancer. Methods: An in idual participant data analysis of 30 cohort studies was carried out, involving 420,310 Asian participants (33% female) and 99,333 from Australia/New Zealand (45% female). Cox proportional hazard models, stratified by study and sex and adjusted for age, were used to quantify risk factors for death from pancreatic cancer. Results: During 3,558,733 person-years of follow-up, there were 324 deaths from pancreatic cancer (54% Asia and 33% female). Mortality rates (per 100,000 person-years) from pancreatic cancer were 10 for men and 8 for women. The following are age-adjusted hazard ratios (95% confidence interval) for death from pancreatic cancer: for current smoking, 1.61 (1.12-2.32) for diabetes, 1.76 (1.15-2.69) for a 2-cm increase in waist circumference, 1.08 (1.02-1.14). All three relationships remained significant (P & 0.05) after adjustment for other risk factors. There was no evidence of heterogeneity in the strength of these associations between either cohorts from Asia and Australia/New Zealand or between the sexes. In men, the combination of cigarette smoking and diabetes more than doubled the likelihood of pancreatic cancer (2.47 95% confidence interval, 1.17-5.21) in both regions. Conclusions: Smoking, obesity, and diabetes are important and are potentially modifiable risk factors for pancreatic cancer in populations of the Asia-Pacific region. Activities to prevent them can be expected to lead to a major reduction in the number of deaths from this cancer, particularly in Asia with its enormous population. (Cancer Epidemiol Biomarkers Prev 2006 (12):2435–40)
Publisher: Elsevier BV
Date: 06-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-03-2021
Abstract: Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. This is an exploratory analysis of the TICH‐2 (Tranexamic Acid in Intracerebral Hemorrhage‐2) double‐blind, randomized, placebo‐controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre‐ICH antiplatelet therapy, and 24‐hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre‐ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no‐antiplatelet group. Pre‐ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28 95% CI, 1.01–1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58 95% CI, 1.32–1.91) and a higher risk of death at day 90 (adjusted OR, 1.63 95% CI, 1.25–2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76 95% CI, 0.62–0.93) and antiplatelet subgroup (adjusted OR, 0.61 95% CI, 0.41–0.91) with no significant interaction between pre‐ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use. URL: www.isrctn.com Unique identifier: ISRCTN93732214.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Frontiers Media SA
Date: 03-03-2022
DOI: 10.3389/FNEUR.2022.832903
Abstract: Data remain limited on sex-differences in patients with oral anticoagulant (OAC)-related intracerebral hemorrhage (ICH). We aim to explore similarities and differences in risk factors, acute presentation, treatments, and outcome in men and women admitted with OAC-related ICH. This study was a retrospective observational study based on 401 consecutive patients with OAC-related ICH admitted within 24 h of symptom onset. The study was registered on osf.io. We performed logarithmic regression and cox-regression adjusting for age, hematoma volume, Charlson Comorbidity Index (CCI), and pre-stroke modified Ranking Scale (mRS). Gender and age were excluded from CHA 2 DS 2 -VASc and CCI was not adjusted for age. A total of 226 men and 175 women were identified. More men were pre-treated with vitamin K-antagonists (73.5% men vs . 60.6% women) and more women with non-vitamin K-antagonist oral anticoagulants (26.5% men vs . 39.4% women), p = 0.009. Women were older (mean age 81.9 vs . 76.9 years, p & 0.001). CHA 2 DS 2 -VASc and CCI were similar in men and women. Hematoma volumes (22.1 ml in men and 19.1 ml in women) and National Institute of Health Stroke Scale (NIHSS) scores (13 vs . 13) were not statistically different, while median Glasgow Coma Scale (GCS) was lower in women, (14 [8 ] vs . 14 [10 ] p = 0.003). Women's probability of receiving reversal agents was significantly lower (adjusted odds ratio [ aOR ] = 0.52, p = 0.007) but not for surgical clot removal ( aOR = 0.56, p = 0.25). Women had higher odds of receiving do-not-resuscitate (DNR) orders within a week ( aOR = 1.67, p = 0.04). There were no sex-differences in neurological deterioration ( aOR = 1.48, p = 0.10), ability to walk at 3 months ( aOR = 0.69, p = 0.21) or 1-year mortality (adjusted hazard ratio = 1.18, p = 0.27). Significant sex-differences were observed in age, risk factors, access to treatment, and DNRs while no significant differences were observed in comorbidity burden, stroke severity, or hematoma volume. Outcomes, such as adjusted mortality, ability to walk, and neurological deterioration, were comparable. This study supports the presence of sex-differences in risk factors and care but not in presentation and outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2019
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000441098
Abstract: b i Background: /i /b Recent evidence suggests that stroke is increasing as a cause of morbidity and mortality in younger adults, where it carries particular significance for working in iduals. Accurate and up-to-date estimates of stroke burden are important for planning stroke prevention and management in younger adults. b i Objectives: /i /b This study aims to estimate prevalence, mortality and disability-adjusted life years (DALYs) and their trends for total, ischemic stroke (IS) and hemorrhagic stroke (HS) in the world for 1990-2013 in adults aged 20-64 years. b i Methodology: /i /b Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease (GBD) 2013 methods. All available data on rates of stroke incidence, excess mortality, prevalence and death were collected. Statistical models were used along with country-level covariates to estimate country-specific stroke burden. Stroke-specific disability weights were used to compute years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. b i Results: /i /b In 2013, in younger adults aged 20-64 years, the global prevalence of HS was 3,725,085 cases (95% UI 3,548,098-3,871,018) and IS was 7,258,216 cases (95% UI 6,996,272-7,569,403). Globally, between 1990 and 2013, there were significant increases in absolute numbers and prevalence rates of both HS and IS for younger adults. There were 1,483,707 (95% UI 1,340,579-1,658,929) stroke deaths globally among younger adults but the number of deaths from HS (1,047,735 (95% UI 945,087-1,184,192)) was significantly higher than the number of deaths from IS (435,972 (95% UI 354,018-504,656)). There was a 20.1% (95% UI -23.6 to -10.3) decline in the number of total stroke deaths among younger adults in developed countries but a 36.7% (95% UI 26.3-48.5) increase in developing countries. Death rates for all strokes among younger adults declined significantly in developing countries from 47 (95% UI 42.6-51.7) in 1990 to 39 (95% UI 35.0-43.8) in 2013. Death rates for all strokes among younger adults also declined significantly in developed countries from 33.3 (95% UI 29.8-37.0) in 1990 to 23.5 (95% UI 21.1-26.9) in 2013. A significant decrease in HS death rates for younger adults was seen only in developed countries between 1990 and 2013 (19.8 (95% UI 16.9-22.6) and 13.7 (95% UI 12.1-15.9)) per 100,000). No significant change was detected in IS death rates among younger adults. The total DALYs from all strokes in those aged 20-64 years was 51,429,440 (95% UI 46,561,382-57,320,085). Globally, there was a 24.4% (95% UI 16.6-33.8) increase in total DALY numbers for this age group, with a 20% (95% UI 11.7-31.1) and 37.3% (95% UI 23.4-52.2) increase in HS and IS numbers, respectively. b i Conclusions: /i /b Between 1990 and 2013, there were significant increases in prevalent cases, total deaths and DALYs due to HS and IS in younger adults aged 20-64 years. Death and DALY rates declined in both developed and developing countries but a significant increase in absolute numbers of stroke deaths among younger adults was detected in developing countries. Most of the burden of stroke was in developing countries. In 2013, the greatest burden of stroke among younger adults was due to HS. While the trends in declining death and DALY rates in developing countries are encouraging, these regions still fall far behind those of developed regions of the world. A more aggressive approach toward primary prevention and increased access to adequate healthcare services for stroke is required to substantially narrow these disparities.
Publisher: Elsevier BV
Date: 05-2018
Publisher: SAGE Publications
Date: 11-05-2021
DOI: 10.1177/23969873211012133
Abstract: The optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH) remains controversial. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions regarding BP management in acute stroke. The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. Despite several large randomised-controlled clinical trials, quality of evidence is generally low due to inconsistent results of the effect of blood pressure lowering in AIS. We recommend early and modest blood pressure control (avoiding blood pressure levels /105 mm Hg) in AIS patients undergoing reperfusion therapies. There is more high-quality randomised evidence for BP lowering in acute ICH, where intensive blood pressure lowering is recommended rapidly after hospital presentation with the intent to improve recovery by reducing haematoma expansion. These guidelines provide further recommendations on blood pressure thresholds and for specific patient subgroups. There is ongoing uncertainty regarding the most appropriate blood pressure management in AIS and ICH. Future randomised-controlled clinical trials are needed to inform decision making on thresholds, timing and strategy of blood pressure lowering in different acute stroke patient subgroups.
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000145331
Publisher: Elsevier BV
Date: 02-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2020
Publisher: Mary Ann Liebert Inc
Date: 11-2005
Abstract: There is much interest in promoting healthy heart awareness among women. However, little is known about the reasons behind the lower rates of heart disease among women compared with men, and why this risk difference diminishes with age. Previous comparative studies have generally had insufficient numbers of women to quantify such differences reliably. We carried out an in idual participant data meta-analysis of 39 cohort studies (32 from Asian countries and 7 from Australia and New Zealand). Cox models were used to estimate hazard ratios (HR) for coronary death, comparing men to women. Further adjustments were made for several proven coronary risk factors to quantify their contributions to the sex differential. Sex interactions were tested for the same risk factors. During 4 million person-years of follow-up, there were 1989 (926 female) deaths from coronary heart disease (CHD). The age-adjusted and study-adjusted male/female HR (95% confidence interval [95% CI]) was 2.05 (1.89-2.22). At baseline, 54% of men vs. 7% of women were current smokers hence, adjustment for smoking explained the largest component (20%) of this HR. A significant sex interaction was observed between systolic blood pressure (SBP) and CHD mortality such that a 10 mm Hg increase was associated with a 15% greater increase in the relative risk (RR) of coronary death in women compared with men (p = 0.002). Only a small amount of the sex differential in coronary death could be explained by differences in the prevalence of classic risk factors. Alternative explanations are required to explain the age-related attenuation of the sex difference in CHD risk.
Publisher: Elsevier BV
Date: 08-2015
Publisher: Springer Science and Business Media LLC
Date: 03-08-2020
DOI: 10.1186/S42466-020-00068-Y
Abstract: The anatomical distribution of acute lacunar infarcts has mainly been studied for supratentorial lesions. In addition, little is known about the association with distinct stroke symptoms, not summarized as classical lacunar syndromes. We aimed to describe the spatial lesion distribution of acute supra- and infratentorial lacunar infarcts and their association with stroke symptoms in patients eligible for thrombolysis. All patients enrolled in the WAKE-UP trial (efficacy and safety of magnetic resonance imaging [MRI]-based thrombolysis in wake-up stroke) were screened for lacunar infarcts on diffusion-weighted imaging (DWI). The relationship between the anatomical distribution of supra- and infratentorial lacunar infarcts, their demographic characteristics and acute stroke symptoms, defined by the National Institutes of Health Stroke Scale (NIHSS) score, were correlated and compared. Maps of lesion distribution from 224 lacunar infarct patients (76 [33.9%] females, mean age [standard deviation] of 63.4 [11.5] years) were generated using computational image mapping methods. Median infarct volume was 0.73 ml (interquartile range [IQR] 0.37–1.15 ml). Median NIHSS sum score on hospital arrival was 4 (IQR 3–6). 165 (73.7%) patients had lacunar infarcts in the supratentorial deep white or grey matter, while 59 (26.3%) patients had infratentorial lacunar infarcts. Patients with supratentorial lacunar infarcts presented with a significantly lower occurrence of deficits in the NIHSS items gaze ( p 0.001) and dysarthria ( p = 0.008), but had more often a paresis of the left arm ( p = 0.009) and left leg ( p = 0.068) compared to patients with infratentorial infarcts. The anatomical lesion distribution of lacunar infarcts reveals a distinct pattern and supports an association of localization with different stroke symptoms. NCT01525290 .
Publisher: BMJ
Date: 05-11-2020
Abstract: Nitrate-induced headache is common and may signify responsive cerebral vasculature. We assessed the relationship between nitrate headache and outcome in patients with acute stroke. Patients were those randomised to glyceryl trinitrate (GTN) versus no GTN in the efficacy of nitric oxide in stroke trial. Development of headache by end of treatment (day 7), and functional outcome (modified Rankin Scale, primary outcome) at day 90, were assessed. Analyses are adjusted for baseline prognostic factors and give OR and mean difference (MD) with 95% CI. In 4011 patients, headache was more common in GTN than control (360, 18.0% vs 170, 8.5% p .001). Nitrate-related headache was associated with: younger age, female sex, higher diastolic blood pressure, non-total anterior circulation syndrome, milder stroke and absence of dysphasia (p .05). Nitrate headache was not associated with improved functional outcome (OR 0.90, 95% CI 0.73 to 1.10, p=0.30) or death (day 90) (HR 0.64, 95% CI 0.40 to 1.02, p=0.062), but reduced death or deterioration (day 7) (OR 0.45, 95% CI 0.25 to 0.82), death in hospital (OR 0.44, 95% CI 0.22 to 0.88) and improved activities of daily living (Barthel index, MD 3.7, 95% CI 0.3 to 7.1) and cognition (telephone interview cognitive screen, MD 2.0, 95% CI 0.7 to 3.3) (day 90). Non-nitrate headache was not associated with death, disability or cognition. Development of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90, which was not seen with non-nitrate headache.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 10-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2016
DOI: 10.1161/STROKEAHA.115.010368
Abstract: The Efficacy of Nitric Oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset. In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days. Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference −7.5/−4.2 mm Hg both P ≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04 95% confidence interval, 0.78–1.37 P =0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22 95% confidence interval, 0.07–0.69 P =0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN. In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies. URL: www.isrctn.com/ISRCTN99414122 . Unique identifier: 99414122.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2019
DOI: 10.1161/STROKEAHA.118.023190
Abstract: Increased blood pressure (BP), heart rate, and their derivatives (variability, pulse pressure, rate-pressure product) are associated with poor clinical outcome in acute stroke. We assessed the effects of glyceryl trinitrate (GTN) on hemodynamic parameters and these on outcome in participants in the ENOS trial (Efficacy of Nitric Oxide in Stroke). Four thousand and eleven patients with acute stroke and raised BP were randomized within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral hemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as SD) was assessed in quintiles. Functional outcome was assessed as modified Rankin Scale and cognition as telephone mini-mental state examination at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference or odds ratios with 95% CI. Increased baseline BP (diastolic, variability), heart rate, and rate-pressure product were each associated with unfavorable functional outcome at day 90. Increased between-visit systolic BP variability was associated with an unfavourable shift in modified Rankin Scale (highest quintile adjusted odds ratio, 1.65 95% CI, 1.37–1.99), worse cognitive scores (telephone mini-mental state examination: highest quintile adjusted mean difference, −2.03 95% CI, −2.84 to −1.22), and increased odds of death at day 90 (highest quintile adjusted odds ratio, 1.57 95% CI, 1.12–2.19). GTN lowered BP and rate-pressure product and increased heart rate at day 1 and reduced between-visit systolic BP variability. Increased between-visit BP variability was associated with poor functional and cognitive outcomes and increased death 90 days after acute stroke. In addition to lowering BP and rate-pressure product, GTN reduced between-visit systolic BP variability. Agents that lower BP variability in acute stroke require further study.
Publisher: Oxford University Press (OUP)
Date: 06-03-2009
DOI: 10.1093/IJE/DYP150
Abstract: In Caucasian populations, adult height is inversely associated with cardiovascular disease (CVD) risk and positively related to some cancers. However, there are few data from Asian populations and from women. We sought to determine the sex- and region-specific associations between height and cardiovascular outcomes, and deaths due to cancer, respiratory and injury in populations from the Asia-Pacific region. Thirty-nine studies from the Asia Pacific Cohort Studies Collaboration database were included. We used Cox proportional hazard regression models to estimate the associations between height and pre-specified outcomes. A total of 510,800 participants with 21,623 deaths were included. Amongst men, inverse linear associations were observed between height and coronary heart disease (CHD), stroke, CVD, injury and total mortality. The hazard ratios [95% confidence intervals, (CI)] for a 1-SD (= 6 cm) increment in height ranged from 0.85 (0.80-0.91) for injury to 0.97 (0.95-0.98) for total mortality. Similar trends were found between height and CHD, haemorrhagic stroke and CVD in women. A positive linear association was observed between height and cancer mortality. For each standard deviation greater height, the risk of cancer was increased by 5% (2-8%) and 9% (5-14%) in men and women, respectively. No regional difference was observed between Asian and Australasian cohorts. Adjusting for markers of education did not alter the results. The opposing relationships of height with CVD and cancer suggest that care is required in setting national policies on childhood nutrition lest they have unintended consequences on the incidence of major non-communicable diseases.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2019
DOI: 10.1007/S00062-019-00800-5
Abstract: Lacunar infarcts are thought to result from occlusion of small penetrating arteries due to microatheroma and lipohyalinosis, pathognomonic for cerebral small vessel disease (CSVD). Concurrent embolic ischemic lesions indicate a different stroke mechanism. The purpose of this study was to examine the clinical characteristics and outcome of patients with lacunar infarcts and concurrent embolic infarcts on diffusion-weighted imaging (DWI). All patients screened for the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290) were reviewed for acute lacunar infarcts and concurrent embolic lesions on baseline DWI. Clinical characteristics and outcome were compared between lacunar infarct patients with and without concurrent embolic lesions. Of 244 patients with an acute lacunar infarct, 20 (8.2%) had concurrent acute embolic infarcts. Compared to patients with a lacunar infarct only, patients with concurrent embolic infarcts were older (mean age 69 years vs. 63 years p = 0.031), more severely affected (median National Institutes of Health Stroke Scale [NIHSS] score 5 vs. 4 p = 0.046), and-among those randomized-had worse functional outcome at 90 days (median modified Rankin Scale [mRS] 3 vs. 1 p = 0.011). Approximately 8% of lacunar infarct patients show concurrent embolic lesions suggesting a stroke etiology other than CSVD. These patients are more severely affected and have a worse functional outcome illustrating the need for a thorough diagnostic work-up of possible embolic sources even in patients with an imaging-defined diagnosis of lacunar infarcts.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-12-2019
DOI: 10.1212/WNL.0000000000008881
Abstract: To assess the association of baseline imaging markers of cerebral small vessel disease (SVD) and brain frailty with clinical outcome after acute stroke in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. ENOS randomized 4,011 patients with acute stroke ( hours of onset) to transdermal glyceryl trinitrate (GTN) or no GTN for 7 days. The primary outcome was functional outcome (modified Rankin Scale [mRS] score) at day 90. Cognition was assessed via telephone at day 90. Stroke syndrome was classified with the Oxfordshire Community Stroke Project classification. Brain imaging was adjudicated masked to clinical information and treatment and assessed SVD (leukoaraiosis, old lacunar infarcts/lacunes, atrophy) and brain frailty (leukoaraiosis, atrophy, old vascular lesions/infarcts). Analyses used ordinal logistic regression adjusted for prognostic variables. In all participants and those with lacunar syndrome (LACS 1,397, 34.8%), baseline CT imaging features of SVD and brain frailty were common and independently associated with unfavorable shifts in mRS score at day 90 (all participants: SVD score odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07–1.24 brain frailty score OR 1.25, 95% CI 1.17–1.34 those with LACS: SVD score OR 1.30, 95% CI 1.15–1.47, brain frailty score OR 1.28, 95% CI 1.14–1.44). Brain frailty was associated with worse cognitive scores at 90 days in all participants and in those with LACS. Baseline imaging features of SVD and brain frailty were common in lacunar stroke and all stroke, predicted worse prognosis after all acute stroke with a stronger effect in lacunar stroke, and may aid future clinical decision-making. ISRCTN99414122.
Publisher: BMJ
Date: 06-2023
Publisher: Informa UK Limited
Date: 03-2022
DOI: 10.2147/CLEP.S338149
Publisher: BMJ
Date: 03-2019
Abstract: There is concern that blood pressure (BP) lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis. We assessed the effect of glyceryl trinitrate (GTN) in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke (ENOS) Trial. ENOS randomised 4011 patients with acute stroke and raised systolic BP (140–220 mm Hg) to transdermal GTN or no GTN within 48 hours of onset. Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days. The primary outcome was the modified Rankin Scale (mRS) at day 90. Ipsilateral carotid stenosis was split: % 30– % 50– % ≥70%. Data are ORs with 95% CIs adjusted for baseline prognostic factors. 2023 (60.5%) ischaemic stroke participants had carotid imaging. As compared with %, ≥70% ipsilateral stenosis was associated with an unfavourable shift in mRS (worse outcome) at 90 days (OR 1.88, 95% CI 1.44 to 2.44, p .001). Those with ≥70% stenosis who received GTN versus no GTN had a favourable shift in mRS (OR 0.56, 95% CI 0.34 to 0.93, p=0.024). In those with 50– % stenosis, continuing versus stopping prestroke antihypertensives was associated with worse disability, mood, quality of life and cognition at 90 days. Clinical outcomes did not differ across bilateral stenosis groups. Following ischaemic stroke, severe ipsilateral carotid stenosis is associated with worse functional outcome at 90 days. GTN appears safe in ipsilateral or bilateral carotid stenosis, and might improve outcome in severe ipsilateral carotid stenosis.
Publisher: SAGE Publications
Date: 27-05-2021
DOI: 10.1177/17474930211019568
Abstract: Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization–World Health Organization– Lancet Neurology Commission on Stroke conducted a survey of the status of stroke services in low and middle-income countries (LMICs) compared to high-income countries. Using a validated World Stroke Organization comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across World Health Organization regions and economic strata. The World Health Organization also conducted a survey of non-communicable diseases in 194 countries in 2019. Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys, and participation in research) were reported in low-income countries than high-income countries. The overall global score for prevention was 40.2%. Stroke units were present in 91% of high-income countries in contrast to 18% of low-income countries (p 0.001). Acute stroke treatments were offered in ∼ 60% of high-income countries compared to 26% of low-income countries (p = 0.009). Compared to high-income countries, LMICs provided less rehabilitation services including in-patient rehabilitation, home assessment, community rehabilitation, education, early hospital discharge program, and presence of rehabilitation protocol. There is an urgent need to improve access to stroke units and services globally especially in LMICs. Countries with less stroke services can adapt strategies from those with better services. This could include establishment of a framework for regular monitoring of stroke burden and services, implementation of integrated prevention activities and essential acute stroke care services, and provision of interdisciplinary care for stroke rehabilitation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2022
DOI: 10.1161/STROKEAHA.121.035191
Abstract: Seeking consent rapidly in acute stroke trials is crucial as interventions are time sensitive. We explored the association between consent pathways and time to enrollment in the TICH-2 (Tranexamic Acid in Intracerebral Haemorrhage-2) randomized controlled trial. Consent was provided by patients or by a relative or an independent doctor in incapacitated patients, using a 1-stage (full written consent) or 2-stage (initial brief consent followed by full written consent post-randomization) approach. The computed tomography-to-randomization time according to consent pathways was compared using the Kruskal-Wallis test. Multivariable logistic regression was performed to identify variables associated with onset-to-randomization time of ≤3 hours. Of 2325 patients, 817 (35%) gave self-consent using 1-stage (557 68%) or 2-stage consent (260 32%). For 1507 (65%), consent was provided by a relative (1 stage, 996 [66%] 2 stage, 323 [21%]) or a doctor (all 2-stage, 188 [12%]). One patient did not record prerandomization consent, with written consent obtained subsequently. The median (interquartile range) computed tomography-to-randomization time was 55 (38–93) minutes for doctor consent, 55 (37–95) minutes for 2-stage patient, 69 (43–110) minutes for 2-stage relative, 75 (48–124) minutes for 1-stage patient, and 90 (56–155) minutes for 1-stage relative consents ( P .001). Two-stage consent was associated with onset-to-randomization time of ≤3 hours compared with 1-stage consent (adjusted odds ratio, 1.9 [95% CI, 1.5–2.4]). Doctor consent increased the odds (adjusted odds ratio, 2.3 [1.5–3.5]) while relative consent reduced the odds of randomization ≤3 hours (adjusted odds ratio, 0.10 [0.03–0.34]) compared with patient consent. Only 2 of 771 patients (0.3%) in the 2-stage pathways withdrew consent when full consent was sought later. Two-stage consent process did not result in higher withdrawal rates or loss to follow-up. The use of initial brief consent was associated with shorter times to enrollment, while maintaining good participant retention. Seeking written consent from relatives was associated with significant delays. URL: www.isrctn.com Unique identifier: ISRCTN93732214.
Publisher: SAGE Publications
Date: 06-2021
DOI: 10.1177/23969873211026998
Abstract: The optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH) remains controversial. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions regarding BP management in acute stroke. The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. Despite several large randomised-controlled clinical trials, quality of evidence is generally low due to inconsistent results of the effect of blood pressure lowering in AIS. We recommend early and modest blood pressure control (avoiding blood pressure levels /105 mm Hg) in AIS patients undergoing reperfusion therapies. There is more high-quality randomised evidence for BP lowering in acute ICH, where intensive blood pressure lowering is recommended rapidly after hospital presentation with the intent to improve recovery by reducing haematoma expansion. These guidelines provide further recommendations on blood pressure thresholds and for specific patient subgroups. There is ongoing uncertainty regarding the most appropriate blood pressure management in AIS and ICH. Future randomised-controlled clinical trials are needed to inform decision making on thresholds, timing and strategy of blood pressure lowering in different acute stroke patient subgroups.
Publisher: Elsevier BV
Date: 10-2020
Publisher: SAGE Publications
Date: 09-07-2016
Abstract: Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h of spontaneous intracerebral hemorrhage reduces death or dependency. Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8 h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1 g 10 min bolus followed by 1 g 8 h infusion, or placebo. A trial of 2000 participants (300 from start-up phase and 1700 from main phase) will have 90% power to detect an ordinal shift of the modified Rankin Scale with odds ratio 0.79. The primary outcome is death or dependency measured by ordinal shift analysis of the 7 level mRS at day 90. Secondary outcomes are neurological impairment at day 7 and disability, quality of life, cognition, and mood at day 90. Safety outcomes are death, serious adverse events, thromboembolic events, and seizures. Cost outcomes are length of stay in hospital, readmission, and institutionalization. This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013 as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial is registered as ISRCTN93732214.
Publisher: Oxford University Press (OUP)
Date: 28-07-2004
DOI: 10.1093/IJE/DYH163
Publisher: Wiley
Date: 20-04-2020
DOI: 10.1002/ANA.25730
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-03-2021
DOI: 10.1212/WNL.0000000000011885
Abstract: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] −11.7 to −11.3, p 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI −13.8 to −12.7, p 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI −13.7 to −10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2–9.8, p 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
Publisher: Wiley
Date: 22-03-2021
DOI: 10.1111/ENE.14797
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000330653
Abstract: Over 2 million people are affected by intracerebral haemorrhage (ICH) worldwide every year, one third of them dying within 1 month, and many survivors being left with permanent disability. Unlike most other stroke types, the incidence, morbidity and mortality of ICH have not declined over time. No standardised diagnostic workup for the detection of the various underlying causes of ICH currently exists, and the evidence for medical or surgical therapeutic interventions remains limited. A dedicated European research programme for ICH is needed to identify ways to reduce the burden of ICH-related death and disability. The European Research Network on Intracerebral Haemorrhage EURONICH is a multidisciplinary academic research collaboration that has been established to define current research priorities and to conduct large clinical studies on all aspects of ICH.
Publisher: Elsevier BV
Date: 05-2016
Publisher: Elsevier BV
Date: 07-2017
No related grants have been discovered for Hanne Christensen.