| 1. |
- Birnefeld, Johan, 1989-
(författare)
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Cerebral hemodynamics in stroke, cerebral small vessel disease and pharmacological interventions : a 4D flow MRI study
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aim: Current cerebrovascular imaging techniques provide important information on arterial anatomy and structural pathologies, such as stenoses and occlusions, but physicians are left to infer how the blood flow is affected. In addition, the relationship between blood pressure and cerebral blood flow is complex and poorly understood. Increased transmission of cardiac pulsatility to the cerebral microvasculature has been suggested as a causative factor of cerebral small vessel disease (CSVD) but previous research have yielded conflicting results regarding this relationship. 4D flow magnetic resonance imaging (MRI) is a novel and promising technique enabling time-resolved blood flow quantification with whole-brain coverage and relatively short scan times. However, despite its obvious potential, there is not yet an evidence-based application for the use of 4D flow MRI within stroke or CSVD. This dissertation aimed to apply 4D flow MRI to describe blood flow patterns in posterior circulation stroke and cerebral blood flow responses to common pharmacological agents used to alter arterial blood pressure as well as to examine the relationship between cerebral arterial pulsatility and CSVD.Methods and Results: This doctoral dissertation consisted of four papers, referred to by roman numerals. 4D flow MRI and computed tomography angiography (CTA) were applied in 25 patients with acute ischemic stroke in the posterior circulation and a reference population of 15 healthy elderly (paper I). Individual flow profiles were created for each stroke patient and hemodynamic disturbances as well as collateral compensation were described. We show that hemodynamic findings were related to structural findings from CTA.The cross-sectional relationship between cerebral arterial pulsatility (quantified using 4D flow MRI as pulsatility index [PI] and flow volume pulsatility [FVP]) and features of CSVD were examined using regression analysis in 89 patients with acute ischemic stroke (paper II) and a population-based sample of 862 elderly (paper III). Internal carotid artery FVP was associated with increasing white matter hyperintensity (WMH) volume in patients with stroke and TIA (paper II). In addition, increasing middle cerebral artery FVP and PI were associated with worse cognitive function. In the population sample, high FVP and PI were associated with increasing WMH volume, lower brain volume and the presence of lacunes, but not the composite MRI-CSVD (paper III). Among subjects with MRI-CSVD, displaying symptoms consistent with cerebral small vessel disease was associated with higher WMH volume, lower brain volume and active smoking, but not any measure of pulsatility.Eighteen healthy volunteers were administered noradrenaline to increase mean arterial pressure by 20% above baseline, and labetalol to decrease mean arterial pressure to 15% below baseline (paper IV). Cerebral blood flow was measured using phase-contrast MRI at each blood pressure level and compared to baseline. Despite a marked increase in blood pressure, noradrenaline administration caused a reduction in cerebral blood flow and cardiac output. Meanwhile, labetalol administration caused no change in cerebral blood flow but an increased cardiac output.Conclusions: 4D flow MRI can detect hemodynamic disturbances and discriminate between hemodynamic disturbances and normal flow in patients with structural vascular pathologies. This additional information compared to structural imaging alone could potentially be used for prognosis and selection for procedures in clinical care. Cerebral arterial pulsatility is modestly associated with several MRI and clinical features of CSVD but not all. Cerebral arterial pulsatility as the main risk factor of CSVD seems unlikely but its involvement in the pathophysiology cannot be ruled out. Raising the blood pressure with noradrenaline decreases cerebral blood flow and cardiac output without any redistribution from peripheral to cerebral flow. This highlights the pitfalls of using blood pressure as a surrogate for cerebral blood flow and questions the validity of our understanding of cerebral autoregulation. Lowering the blood pressure with labetalol does not affect cerebral blood flow, reassuring its use in clinical routine. 4D flow MRI can be integrated into an in-patient work-up in selected cases of acute ischemic stroke and into the workflow of large epidemiological studies.
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| 2. |
- Darehed, David, 1986-
(författare)
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The impact of organizational and temporal factors on acute stroke care in Sweden
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Acute stroke carries a high risk of morbidity and death, but early treatment can improve outcomes. Intravenous stroke thrombolysis (IVT) is one such treatment, it is however time-sensitive and show better outcomes the sooner it is given. Most studies on time to IVT so far have looked at fixed time-intervals, and studies of short delays in clinical practice are relatively scarce. Another well-established treatment is managing acute stroke patients in stroke units (SU). Admission rates to a SU as first destination of hospital care have improved over time in Sweden. In the past decade however, the rates have leveled out at around 75-80% without further improvement. A hypothesis is that in-hospital overcrowding contributes. Previous studies have shown that outcomes after stroke differ between hospital types, and also vary depending on time of admission, with higher mortality seen for off-hours, weekend and winter admissions. The reasons behind temporal variations are not fully understood, but it has been proposed that environmental, patient-related and organizational factors contribute. The overall aim of this thesis was to study the effect of organizational factors on quality of care and outcomes after stroke, primarily focusing on the role of in-hospital overcrowding, in-hospital time to IVT and time of admission, while also studying differences between hospitals.Methods: All papers in this thesis were based on data from the Swedish stroke register (Riksstroke), a national quality register that holds data on patient related factors, acute care and outcomes. Paper I included 13,955 patient admissions from 14 hospitals in Region Norrbotten and Region Skåne from 2011-2014, enriched with data on in-hospital bed occupancy. Papers II-IV included all 72 Swedish hospitals caring for patients with acute stroke. Paper II included data from 2011-2015 (N=113,862), paper III from 2011-2016 (N=132,744) and paper IV from 2010-2017 (N=14,132). Analyses included descriptive statistics, unadjusted analyses and multivariable adjusted analyses.Results: We found that each percent increase in in-hospital bed occupancy above 85% decreased admission rates to a SU as first destination of hospital care by 1.5% (odds ratio (OR) 0.985, 95% confidence interval (CI) 0.978-0.992), with significant differences between hospitals. Admission rates were also lower off-hours, compared to on-hours (OR 0.73, 95% CI 0.70-0.75). Over time, admission rates to a SU as first destination of hospital care decreased in university hospitals, while they increased in specialized non-university hospitals and community hospitals. Each minute delay in door-to-needle time (DNT) decreased the odds of 90-day survival by 0.6% (OR 0.994, 95% CI 0.992-0.996), increased the odds of ICH within 36 hours by 0.3% (OR 1.003, 95% CI 1.000-1.006), and led to significantly higher odds of a worsening in functional outcomes at 3 months by 0.3-0.4%. DNT within 30 minutes was most likely daytime, and varied between hospital types. 90-day survival was lowest for patients admitted in January (81.5%), and highest for those admitted in May (84.1%) (OR 1.28, 95% CI 1.17-1.40).Conclusion: We found that in-hospital overcrowding decrease admission rates to a SU as first destination of hospital care, and that even short delays in DNT decreases survival, increases ICH complications and leads to a worsening in functional outcomes in routine clinical practice. We also found that quality of care varied depending on time of admission and between hospitals, indicating unequal care. Organizational differences should be accessible through quality improvement efforts aiming to implement robust local guidelines for in-hospital stroke treatment.
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| 3. |
- Eriksson, Marie, 1970-
(författare)
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Aspects on stroke outcome : survival, functional status, depression and sex differences in Riks-Stroke, the National Quality Register for Stroke Care
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stroke is a major cause of death and disability worldwide. In Sweden, about 30 000 strokes occur each year. The aim of this thesis was to analyse survival, functional outcome and self-reported depression after stroke, and to explore possible differences between men and women in stroke care and outcome. These studies were based on Riks-Stroke, the Swedish national quality register for stroke care. Information on background variables and treatment were collected during the hospital stay. The patient’s situation and outcome after stroke were followed-up after 3 months. Long term survival was retrieved from the Swedish Population Register (Folkbokföringen). Possible sex-differences in stroke care and outcome 3 months after stroke were explored in 24 633 strokes, registered during 2006. In conscious patients, the proportions treated at stroke units were similar for men and women. Men and women had equal chance to receive thrombolytic therapy or secondary prevention with oral anticoagulants. Compared to men, women were less likely to develop pneumonia, but more likely to experience deep venous thromboses and fractures during hospital stay. Women had worse 3-month survival and functional outcome, differences that were explained by their higher age and impaired level of consciousness on admission. Women felt more depressed and perceived their health as worse than men did. Women were also less satisfied with the care they had received in the hospital. The agreement between self-reported functional outcome 3 months after stroke and the commonly used modified Rankin Scale (mRS) was explored in 555 stroke survivors from 4 hospitals during May-September 2005. Riks-Stroke’s self-reported questions classified 76% of the patients into correct mRS grade. The association between functional outcome 3 months after stroke and 3-year survival was assessed in 15 959 men and women who had had a stroke during 2001-2002. Patients with estimated mRS grades 3, 4 and 5 had hazard ratios for death of 1.7, 2.5 and 3.8, respectively, as compared with patients with lower grades, 0-2. Depressed mood, male sex, high age, diabetes, smoking, antihypertensive therapy at onset and atrial fibrillation were also identified as predictors of poor survival. Self-reported depression 3 months after stroke and use of antidepressants were analysed in 15 747 stroke survivors from 2002. Fourteen percent felt depressed 3 months after stroke. Female sex, age <65, previous stroke, living alone or in institution, or being dependent in activities of daily living (ADL) were factors associated with self-reported depression. At the follow-up, 22% of the men and 28% of the women were using antidepressant medication, which were approximately twice as many as in the general population. Still, 8% of all patients in Riks-Stroke reported depressive mood but no treatment with antidepressants. In conclusion, men and women with stroke in Sweden experience similar treatment and outcome in most aspects. Patient-reported functional outcome can be reliably transformed to a standard disability scale. Impaired functional outcome three months after stroke is an independent predictor of poor long-term survival. Depressive mood is common after stroke and is associated with poor survival and impaired functional outcome.
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| 4. |
- Hörnsten, Carl, 1985-
(författare)
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Stroke and depression in very old age
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background The prevalence and incidence of stroke are known to increase with age, which, combined with demographic change, means that very old patients with stroke are a growing patient group. Risk factors for incident stroke among very old people have not been widely investigated. The impact of depression on mortality in very old people who have had a stroke also remains unclear. The aim of this thesis was to investigate the risk factors for incident stroke, the epidemiology of stroke and depression, and the consequences of having had a stroke regarding the risk of depression and mortality among very old people.Methods A randomly selected half of 85-, all 90-, and all ≥95-year-olds in certain municipalities in Västerbotten County, Sweden, and Pohjanmaa County, Finland were targeted in a population-based cohort study from 2000-2012. The 65-, 70-, 75-, and 80-year-olds in all the rural and random samples from the urban municipalities in the same counties were furthermore targeted in a survey in 2010.In the cohort study patients were assessed in their homes, by means of the 15-item Geriatric Depression Scale (GDS-15) and other assessment scales, as well as blood pressure measurements, several physical tests, and a review of medical diagnoses appearing in the medical charts. Incident stroke data were collected from medical charts guided by hospital registry records, cause of death records, and reassessments after 5 years. Depression was defined as a GDS-15 score ≥5. A clinical definition of all depressive disorders, based on assessment scale scores and review of medical charts was also used. A specialist in geriatric medicine evaluated the diagnoses. The survey included yes/no questions about stroke and depression status, and the 4-item Geriatric Depression Scale. Associations with mortality and incident stroke were tested using Cox proportional-hazard models. Results In the ≥85-year-olds examined in 2005-2007 (n=601), the stroke prevalence was 21.5%, the prevalence of all depressive disorders was 37.8% and stroke was independently associated with depressive disorders (odds ratio 1.644, p=0.038). The prevalence of depression according to GDS-15 scores was 43.2% in people with stroke compared with 25.0% in people without stroke (p=0.001). However, in ≥85-year-olds examined in Sweden from 2000-2012 (n=955), from all past data collections in the study, depression was not independently associated with incident stroke. In ≥65-year-olds who responded to a survey in 2010 (n=6098), the stroke prevalence rose with age from 4.7% among the 65- to 11.6% among the 80-year-olds (p<0.001). The prevalence of depression rose from 11.0% among the 65- to 18.1% among the 80-year-olds (p<0.001). In the group with stroke, depression was independently associated with dependence in personal activities of daily living and having a life crisis the preceding year, while in the non-stroke group, depression was independently associated with several additional demographic, social and health factors.In ≥85-year-olds examined in 2005-2007 with valid GDS-15 tests (n=452), having had a stroke was associated with increased 5-year mortality [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.15-2.03]. Having had a stroke and depression was associated with increased 5-year mortality compared with having only stroke (HR 1.90, 95% CI 1.15-3.13), having only depression (HR 1.59, 95% CI 1.03-2.45), and compared with having neither stroke nor depression (HR 2.50, 95% CI 1.69-3.69). Having only stroke without a depression did not increase mortality compared with having neither stroke nor depression.In ≥85-year-olds examined in Sweden from 2000-2012 (n=955), from all past data collections in the study, the stroke incidence was 33.8/1000 person-years during a mean follow-up period of about three years. In a comprehensive multivariate model, atrial fibrillation (HR 1.85, 95% CI 1.07–3.19) and higher systolic blood pressure (SBP; HR 1.19, 95% CI 1.08–1.30 per 10-mmHg increase) were associated with incident stroke overall. In additional multivariate models, diastolic blood pressure (DBP) ≥90 mmHg (HR 2.45, 95% CI 1.47–4.08) and SBP ≥160 mmHg (v. <140 mmHg; HR 2.80, 95% CI 1.53–5.14) were associated with incident stroke.Conclusion The prevalence of both stroke and depression increased with age, and rates were especially high among very old people. Having had a stroke was independently associated with a higher prevalence of depression among very old people, however, depression was not independently associated with a higher incidence of stroke. Having had a stroke was associated with increased all-cause mortality among very old people, but only among those who were also depressed. High SBP (≥160 mmHg), DBP (≥90 mmHg) and atrial fibrillation were the only consistent independent risk factors for incident stroke among very old people.
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| 5. |
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| 6. |
- Darehed, David, et al.
(författare)
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Diurnal variations in the quality of stroke care in Sweden
- 2019
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 140:2, s. 123-130
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: A recent study of acute stroke patients in England and Wales revealed several patterns of temporal variation in quality of care. We hypothesized that similar patterns would be present in Sweden and aimed to describe these patterns. Additionally, we aimed to investigate whether hospital type conferred resilience against temporal variation. Materials and Methods: We conducted this nationwide registry-based study using data from the Swedish Stroke Register (Riksstroke) including all adult patients registered with acute stroke between 2011 and 2015. Outcomes included process measures and survival. We modeled time of presentation as on/off-hours, shifts, day of week, 4-hour, and 12-hour time blocks. We studied hospital resilience by comparing outcomes across hospital types. Results: A total of 113 862 stroke events in 72 hospitals were included. The process indicators and survival all showed significant temporal variation. Door-to-needle (DTN) time within 30 minutes was less likely during nighttime than daytime (OR 0.50; 95% CI 0.41-0.60). Patients admitted during off-hours had lower odds of direct stroke unit (SU) admission (OR 0.72; 95% CI 0.70-0.75). 30-day survival was lower in nighttime vs daytime presentations (OR 0.90, 95% CI 0.84-0.96). The effects of temporal variation differed significantly between hospital types for DTN time within 30 minutes and direct SU admission where university hospitals were more resilient than specialized non-university hospitals. Conclusions: Our study shows that variation in quality of care and survival is present throughout the whole week. We also found that university hospitals were more resilient to temporal variation than specialized non-university hospitals.
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| 7. |
- Darehed, David, 1986-, et al.
(författare)
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In-hospital delays in stroke thrombolysis : every minute counts
- 2020
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Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 51:8, s. 2536-2539
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Intravenous thrombolysis is a well-established treatment for acute ischemic stroke. Our aim was to quantify the effect of each minute delay in door-to-needle time (DNT) on 90-day survival, intracerebral hemorrhagic complication <36 hours, and functional outcomes at 3 months, in routine clinical practice.Methods: Our nationwide registry-based study included 14 132 adult patient admissions with ischemic stroke receiving intravenous thrombolysis from 2010 to 2017. Outcomes were analyzed using multivariable logistic regression, adjusting for potential confounders.Results: Median DNT was 47 minutes, with an improvement from 65 to 38 minutes during the study. Median age was 74 years, and median National Institutes of Health Stroke Scale 8 points. We found a significant impact of each minute delay in DNT with reduced odds of survival by 0.6%, increased odds of intracerebral hemorrhagic and worse activities of daily living by 0.3%, and worse living conditions and mobility by 0.4%.Conclusions: Improving DNT is a key factor in achieving good outcomes after stroke. We estimate that in Sweden alone in 2017, compared with 2010, the shorter DNT achieved have saved 38 lives, avoided 8 intracerebral hemorrhagic transformations, and spared, respectively, 36, 51, and 52 patients from a worsening in activities of daily living, living conditions, and mobility. DNT is sensitive for interventions and should be targeted in quality improvement efforts.
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| 8. |
- Darehed, David, et al.
(författare)
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Time Trends and Monthly Variation in Swedish Acute Stroke Care
- 2019
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Studies of monthly variation in acute stroke care have led to conflicting results. Our objective was to study monthly variation and longitudinal trends in quality of care and patient survival following acute stroke.Methods: Our nationwide study included all adult patients (≥18 years) with acute stroke (ischemic or hemorrhagic), admitted to Swedish hospitals from 2011 to 2016, and that were registered in The Swedish Stroke Register (Riksstroke). We studied how month of admission and longitudinal trends affected acute stroke care and survival. We also studied resilience to this variation among hospitals with different levels of specialization. Results: We included 132,744 stroke admissions. The 90-day survival was highest in May and lowest in January (84.1 vs. 81.5%). Thrombolysis rates and door-to-needle time within 30 min increased from 2011 to 2016 (respectively, 7.3 vs. 12.8% and 7.7 vs. 28.7%). Admission to a stroke unit as first destination of hospital care was lowest in January and highest in June (78.3 vs. 80.5%). Stroke unit admission rates decreased in university hospitals from 2011 to 2016 (83.4 vs. 73.9%), while no such trend were observed in less specialized hospitals. All the differences above remained significant (p < 0.05) after adjustment for possible confounding factors. Conclusion: We found that month of admission and longitudinal trends both affect quality of care and survival of stroke patients in Sweden, and that the effects differ between hospital types. The observed variation suggests an opportunity to improve stroke care in Sweden. Future studies ought to focus on identifying the specific factors driving this variation, for subsequent targeting by quality improvement efforts.
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| 9. |
- Engdahl, Johan, et al.
(författare)
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Multicentre, national, investigator-initiated, randomised, parallel-group, register-based superiority trial to compare extended ECG monitoring versus standard ECG monitoring in elderly patients with ischaemic stroke or transient ischaemic attack and the effect on stroke, death and intracerebral bleeding : the AF SPICE protocol
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring after ischaemic stroke or TIA is recommended by all major societies in cardiology and cerebrovascular medicine as a secondary prophylactic measure. However, data on stroke reduction are lacking, and the recommendations show significant diversity.Methods and analysis: AF SPICE is a multicentre, national, investigator-initiated, randomised, parallel-group, register-based trial comparing extended ECG monitoring versus standard ECG monitoring in patients admitted with ischaemic stroke or TIA, with a composite endpoint of stroke, all-cause-mortality and intracerebral bleeding. Patients aged ≥ 70 years without previous AF will be randomised 1:1 to control (standard ECG monitoring) or intervention (extended ECG monitoring). In the control arm, patients will undergo 48±24 hours (ie, a range of 24-72hours) of continuous ECG monitoring according to national recommendations. In the intervention arm, patients will undergo 14+14 days of continuous ECG monitoring 3months apart using an ECG patch device, which will provide an easy-accessed, well-tolerated 14-day continuous ECG recording. All ECG patch recordings will be read in a core facility. In cases of AF detection, oral anticoagulation will be recommended if not contraindicated. A pilot phase has been concluded in 2022, which will transcend into the main trial during 2023-2026, including approximately 30 stroke units. The sample size was calculated to be 3262 patients. The primary outcome will be collected from register data during a 36-month follow-up.Ethics and dissemination: Ethical approval has been provided by the Swedish Ethical Review Authority, reference 2021-02770. The trial will be conducted according to the ethical principles of the Declaration of Helsinki and national regulatory standards. Positive results from the study have the potential for rapid dissemination in clinical practice. Trial registration number NCT05134454.
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| 10. |
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