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- 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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| 2. |
- Lundström, Erik, 1964-
(författare)
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Spasticity after first-ever stroke
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prevalence of spasticity after first-ever stroke is approximately 20%, but there are no data on the prevalence of disabling spasticity.The reported prevalence of pain after stroke varies between 19% and 74%, whether pain is associated with spasticity is not known. Until now, there is no health economic analysis of patients with spasticity after stroke. Methods: Two groups of patients were studied. Cohort I was a cross-sectional survey. A representative sample of 140 patients was investigated 1 year after their first-ever stroke. Spasticity was defined as ≥ 1 score on the modified Ashworth scale, disabling spasticity was defined as spasticity having such an impact that intervention, e.g. intensive physiotherapy, orthoses or pharmacological treatment, should be offered. Pain was assesed with the Visual Analogue Scale. All direct costs during one year were identified and converted into Purchasing Power Parities US dollar (PPP$). Cohort II was a prospective cohort study. Forty-nine patients were examined at day 2–10, at one month, and at six months after their first-ever stroke. Assessment and definitions were similar as for cohort I. Results: Spasticity occurs within 1 month and disabling spasticity occur within 6 months. After one year, the prevalence of spasticity was 17% and that of disabling spasticity 4%. Disabling spasticity was more frequent in the upper extremity. There was an independent effect of severe upper extremity paresis (OR 22, CI 3.9–125) and age below 65 years (OR 9.5, CI 1.5–60). The prevalence of stroke-related pain was 21% after one year. Stroke-related pain was associated with paresis (OR 3.1, 95% CI 1.2–7.7), sensory disturbance (OR 3.1, 95% CI 1.1–8.9) and depression (OR 4.1, 95% CI 1.4–13), but not with spasticity as an independent variable. The majority of the direct costs for one year (78%) were associated with hospitalization, whereas 20% was associated with municipality services. Only 1% of all direct costs were related to primary health care and 1% to medication. The mean (median, inter-quartile range) direct cost for stroke patients with spasticity was PPP$ 84 195 (72 116, 53 707) compared to PPP$ 21 842 (12 385, 17 484) for stroke patients without spasticity (P < 0.001).
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| 3. |
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| 4. |
- Farrokhnia, Nasim, 1972-
(författare)
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Hyperglycemia and Focal Brain Ischemia : Clinical and Experimental Studies
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetes is a major risk factor for ischemic stroke and is associated with increased mortality. Additionally, hyperglycemia, a common complication in acute stroke, is associated with poor outcome.In order to identify the correlation between blood glucose and early mortality, multiple logistic regression analyses were used and odds ratios calculated in a retrospective study of 447 stroke patients. Eighty-one patients (18%) had diabetes. The odds ratios for 30-day case-fatality and blood glucose were 1.9 and 1.6 in diabetic and non-diabetic patients respectively. Optimal blood glucose concentrations in respective group were 10.3 and 6.3 mmol/L, as determined by receiver operator characteristic (ROC) curves.Cerebral ischemia triggers different signaling pathways including mitogen-activated protein kinases (MAPK) which regulate fundamental cell functions. In an experimental rat model of combined hyperglycemia and transient middle cerebral artery occlusion (MCAO), the activation pattern of one such MAPK, extracellular signal-regulated kinase (ERK) was studied along with infarct volumes and neurological function. Hyperglycemia resulted in markedly increased ERK activation and approximately three-fold increase of infarcts compared with controls. Based on the increased ERK activation, further experiments were conducted to limit the hyperglycemic-ischemic damage by interfering with ERK and supposedly related mechanisms. Consequently, rats were given U0126 (inhibiting ERK activation), PBN (anti-oxidative), PP2 (inhibiting src-family kinases), or vehicle. PBN reduced infarcts and improved neurological function compared with controls while no statistically significant effects were observed for U0126 or PP2. However, when the dose was doubled, U0126 significantly reduced infarcts and improved neurological function after 1 day in hyperglycemic rats. Post-ischemic ERK activation was completely inhibited by U0126 as demonstrated with Western immunoblotting. The findings suggest that ERK is an important mediator of hyperglycemic-ischemic brain injury and possible target for future interventions.
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| 5. |
- Lennmyr, Fredrik, 1971-
(författare)
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Signal Transduction in Focal Cerebral Ischemia : Experimental Studies on VEGF, MAPK and Src family kinases
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cerebral ischemia elicits a wide range of events, including complex activation of various intracellular signaling pathways. This study aims to investigate the expression of vascular endothelial growth factor (VEGF) and the activation pattern of mitogen-activated protein kinases (MAPK) in reponse to focal cerebral ischemia. Furtermore, the functional roles of the p38 MAPK and the Src family kinases (SFKs) are investigated with specific signal transduction inhibitors in the rat in vivo.VEGF was found upregulated in several cell types including neurons, glia and vascular cells after both permanent and transient cerebral ischemia. VEGF-receptor 1 (VEGFR1) was expressed in a similar manner, while VEGFR2 expression was more restricted and confined to endothelial cells and glia.The main MAPK pathways, including extracellular-regulated kinase (ERK), c-jun N-terminal kinase (JNK) and p38, were differentially activated by cerebral ischemia. ERK activation was present in blood vessels, suggesting a potential role in neovascularization. JNK was also activated in blood vessels in the infarcted hemisphere, possibly reflecting an interaction with ERK, whereas p38 activity was absent in vessels. In neurons, ERK was activated in cortical cells up to days of survival, while no substantial JNK or p38 activation was seen in ischemic neurons. Invading macrophages showed distinct activation of p38 and to some extent also JNK but not ERK. Glia showed activation of all MAPK to a variable extent.Pretreatment with the p38-inhibitor SB203580 before transient cerebral ischemia (ischemia-reperfusion) was investigated with magnetic resonance imaging (MRI). The experiment group suffered worse infarcts and blood-brain barrier (BBB) damage than controls, which contrasts to previous studies. The results might be attributed to interference with protective effects of the vehicle or with preconditioning mechanisms. The SFK-inhibitor PP2 significantly reduced infarct size after cerebral ischemia-reperfusion, which is consistent with previously reported effects in permanent ischemia. Due to the multifunctional role of SFKs, it cannot be easily concluded in exactly what cellular context(s) SFKs are of importance to cerebral ischemia.In conclusion, the VEGF and MAPK systems of extra- and intracellular signaling are activated in focal cerebral ischemia. Manipulation of p38 as well as SFK in vivo can influence the course of transient cerebral ischemia, which may be of significance to the understanding of the pathology of cerebral ischemia and to the development of therapeutic strategies.
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| 6. |
- Stenborg, Anna, 1967-
(författare)
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Vascular Dysfunction in Stroke and CADASIL
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cerebrovascular disease (CVD) is strongly linked to hypertension and generally occurs later in life than coronary artery disease (CAD). Three quarters of the patients with symptomatic CVD are above 65 years of age. The risk factors are the same for CVD and CAD, but the relative importance of the vascular risk factors differs greatly.Genetic causes of stroke are relatively rare. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary disease which causes CVD in young adults and middle-aged people, with migraine, stroke, psychiatric illness and dementia as clinical manifestations.The subject of this thesis is vascular function in stroke and CADASIL. Endothelium-dependent vasodilation (EDV) and arterial stiffness were investigated by different methods in stroke patients and CADASIL patients compared with healthy controls. Venous occlusion plethysmography with intra-arterial acetylcholine was used to evaluate EDV in the forearm resistance vessels. Flow-mediated vasodilation of the brachial artery was used to evaluate EDV in a conduit artery. Stroke patients displayed reduced EDV in resistance vessels compared with a healthy control group, but this reduction was not significant when, in a larger group of stroke patients, adjustments were made for blood pressure, antihypertensive treatment and other risk factors. Flow mediated vasodilation of the brachial artery was reduced in the stroke patients even after adjustment for risk factors. Compared with controls, the CADASIL patients showed similar EDV in the conduit artery, but reduced EDV in resistance vessels.Arterial compliance was evaluated by augmentation index from pulse wave analysis, by a ratio of cardiac stroke volume and pulse pressure, and by the distensibility of the carotid artery in relation to pulse pressure. Stroke patients and CADASIL patients did not display any significant increase in arterial stiffness when evaluated by these methods.
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| 7. |
- Säfwenberg, Urban, 1960-
(författare)
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Presenting complaint and mortality in non-surgical emergency medicine patients
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In 1995 and 2000 a total of 29 886 non surgical ED visits at Uppsala University Hospital were registered. Presenting complaint, admittance to a ward, length of stay, in-hospital mortality, discharge diagnoses, 30-day and long-term mortality were registered. The presenting complaints were sorted into 33 presenting complaint groups (PCGs). For different PCGs there was different in-hospital fatality rate. Compared to the largest PCG, chest pain, the gender and age adjusted OR was 2.12 (95% CI 1.01 – 4.44) for the miscellaneous complaint group and 2.04 (95 % CI 1.35 – 3.08) for the stroke–like symptom group. Within a given PCG the in-hospital mortality could vary depending on discharge diagnoses. By relating PCG and long term mortality to the expected mortality in the population, the Standardized Mortality Ratio (SMR) could be calculated. The SMR was found to be highest in seizure 2.62 (95 % CI 2.13 – 3.22), intoxication 2.51 (95% CI 2.11-2.98) and symptoms of asthma 1.8 (1.65 – 2.06). For the same discharge diagnoses the long term mortality could differ considerably depending on PCG at ED arrival (p<0.001). Between 1995 and 2000 there was a 30 % increase in ED visits at the non surgical ED. PCGs representing lesser severe conditions had increased. Demographic changes could account for 45 % of the increment and the remaining increase could be ascribed to change in visiting pattern. In the 2000 cohort 41.0 % of all visits were performed by re-visitors. The number of revisits and five-year mortality had an inversed u-shaped relationship were patients with three re-visits within the same year had an increased mortality compared to patients with more or less visits. Conclusion: It is possible to define presenting complaint groups (PCGs) that are robust and consistent over time and useful as a tool for epidemiological studies in the ED.
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| 8. |
- Åsberg, Signild, 1972-
(författare)
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Outcome of Stroke Prevention : Analyses Based on Data from Riks-Stroke and Other Swedish National Registers
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to explore variations in stroke prevention and the effect of prevention on outcome. The studies were based on patients registered in the Swedish Stroke Register between 2001 and 2009 and although used to different extents in each paper, additional information was retrieved through linkage to The National Patient Register, the Cause of Death Register, the Prescribed Drug Register and the Total Population Register.Cardiovascular risk factors were prevalent among ischemic stroke (IS) patients; however, they were not always prescribed the drugs recommended, and increasing age was an important negative predictor (Paper I).After IS, the rate of hemorrhage in patients prescribed antiplatelet agents (2.4 per 100 person-years) was double to results from randomized controlled trails, but was similar for patients prescribed warfarin (2.5 per 100 person-years). Age ≥75 years and previous hemorrhage were associated with a moderately increased risk of future hemorrhage (Paper II).Among IS patients with atrial fibrillation, one-third was prescribed warfarin and two-thirds were prescribed antiplatelets. After adjustment for a propensity score (used to adjust for the non-randomized design), warfarin was associated with a reduced risk of death (0.67; 95% CI, 0.63-0.71) (Paper III). The rate of subsequent hemorrhagic stroke was 0.4 per 100 person-years and the risk did not change (HR 1.04; 95% CI, 0.73-1.48) when later years of the 2000s (inclusion period 2005-8: follow-up until 2009) was compared with earlier years (inclusion period 2001-4: follow-up until 2005) (Paper IV, cohort).Although the risk of first-ever hemorrhagic stroke more than doubled with warfarin than without, the risk did not change between 2006 and 2009 (Paper IV, case-control).In summary, the prescription of secondary preventive drugs varies with age, even though cardiovascular risk factors are prevalent in all ages. The risk of death and hemorrhage are affected by the type of antithrombotic prescribed. Therefore, it is important individual’s stroke and bleeding risks in stroke prevention are assessed.
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