| 1. |
- Sacco, R. L., et al.
(författare)
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Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
- 2008
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Ingår i: New England Journal of Medicine. - Boston : Massachusetts medical society. - 1533-4406 .- 0028-4793. ; 359:12, s. 1238-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)
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| 2. |
- Yusuf, S., et al.
(författare)
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Telmisartan to prevent recurrent stroke and cardiovascular events
- 2008
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Ingår i: New England Journal of Medicine. - : Massachusetts medical society. - 1533-4406 .- 0028-4793. ; 359:12, s. 1225-37
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. METHODS: In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. RESULTS: The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10). CONCLUSIONS: Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)
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| 5. |
- Barocchi, M A, et al.
(författare)
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A pneumococcal pilus influences virulence and host inflammatory responses
- 2006
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 103:8, s. 2857-2862
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response.
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| 6. |
- von Euler, G., et al.
(författare)
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Coactivation of dopamine D1 and D2 receptors increases the affinity of cholecystokinin-8 receptors in membranes from post-mortem human caudate-putamen
- 1992
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Ingår i: Brain Research. - Amsterdam, Netherlands : Elsevier. - 0006-8993 .- 1872-6240. ; 584:1-2, s. 157-162
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Tidskriftsartikel (refereegranskat)abstract
- The effects of dopamine in vitro were investigated on the binding sites for cholecystokinin-8 (sulphated, CCK-8) and neurotensin in membrane preparations of the caudate-putamen and nucleus accumbens of post-mortem human brains. Dopamine reduced the IC50 value of competition curves with CCK-8 for [125I]CCK-8 binding in membranes from the caudate-putamen, but not the nucleus accumbens, with a maximal decrease of -25 +/- 9% at 300 nM of dopamine. This decrease could be antagonized by 100 nM of SCH 23390 or 100 nM of raclopride. Kinetic analysis of [125I]CCK-8 binding showed a decrease in the first order dissociation rate constant and in the kinetic Kd (-22 +/- 6% and -24 +/- 6%, respectively) at 300 nM of dopamine, without any significant effect on the apparent or actual association rate constant. Competition curves with neurotensin versus [125I]neurotensin were not affected by dopamine (10-1000 nM) in membranes from the caudate-putamen or the nucleus accumbens. These results suggest that dopamine, by synergistic stimulation of both D1 and D2 receptors, selectively increases the affinity of CCK-8 receptors in the human caudate-putamen, by a selective inhibition of ligand dissociation. This increase may reflect a positive feed-back mechanism, further enhancing the modulatory effects of CCK-8 on dopamine neurotransmission.
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| 7. |
- Åsberg, S., et al.
(författare)
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SEX DIFFERENCES IN STROKE CARE - OBSERVATIONS FROM THE SWEDISH STROKE REGISTER 2005-2018
- 2020
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Ingår i: International Journal of Stroke. - : Wiley-Blackwell Publishing Asia. - 1747-4930 .- 1747-4949. ; 15:Suppl. 1, s. 128-128
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and Aims: Previous studies of stroke management and outcome after stroke in Sweden reveal differences between men and women. Our aim was to analyze if these differences have altered over time.Methods: All stroke events registered in Riksstroke, the Swedish Stroke Register during 2005–2018 were included. We performed unadjusted and age-stratified analyzes.Results: We identified 335,183 events (161,939 women; 173,244 men). Women were older than men at stroke onset (mean age 78.1 vs. 73.3 years). In both sexes, there was an increase in the proportion of ischemic stroke patients receiving reperfusion therapy 2005–2018 (1.3–16.6% in women; 2.5–16.8% in men) and, among those with atrial fibrillation, oral anticoagulants at discharge (26.4–75.8% in women; 36.7–77.7% in men). There was an increased proportion of patients prescribed statins, but during the entire study period the proportion remained lower in women (31.7–75.3%) in comparison to men (42.6–83.5%). In addition, women were less likely to be treated at stroke or intensive care units (78.4–90.6%) than men (81.9–91.8%). In 2018, unadjusted 28-day case fatality was 14.9% in women and 10.8% in men. For patients under the age of 80, case fatality was 7.2% in both women and men.Conclusions: In this large nation-wide observational study, we report a more equal care between women and men. Still, women were less often prescribed statins and were less often treated at stroke units. One explanation to these differences could be women’s higher age at stroke onset, with a presumed frailty, but further analyzes are needed to investigate if the disparity is motivated.
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| 8. |
- Subic, A., et al.
(författare)
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Management of acute ischaemic stroke in patients with dementia
- 2017
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Ingår i: Journal of Internal Medicine. - : Blackwell Science Ltd.. - 0954-6820 .- 1365-2796. ; 281:4, s. 348-364
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Forskningsöversikt (refereegranskat)abstract
- An estimated 10% of stroke patients have an underlying dementia. As a consequence, health professionals often face the challenge of managing patients with dementia presenting with an acute stroke. Patients with dementia are less likely to receive thrombolysis (0.56-10% vs. 1-16% thrombolysis rates in the general population), be admitted to a stroke unit or receive some types of care. Anticoagulation for secondary stroke prevention is sometimes withheld, despite dementia not being listed as an exclusion criterion in current guidelines. Studies in this population are scarce, and results have been contradictory. Three observational studies have examined intravenous thrombolysis for treatment of acute ischaemic stroke in patients with dementia. In the two largest matched case-control studies, there were no significant differences between patients with and without dementia in the risks of intracerebral haemorrhage or mortality. The risk of intracerebral haemorrhage ranged between 14% and 19% for patients with dementia. Studies of other interventions for stroke are lacking for this population. Patients with dementia are less likely to be discharged home compared with controls (19% vs. 41%) and more likely to be disabled (64% vs. 59%) or die during hospitalization (22% vs. 11%). The aim of this review was to summarize current knowledge about the management of ischaemic stroke in patients with pre-existing dementia, including organizational aspects of stroke care, intravenous thrombolysis, access to stroke unit care and use of supportive treatment. Evidence to support anticoagulation for secondary prevention of stroke in patients with atrial fibrillation and antiplatelet therapy in nonembolic stroke will be discussed, as well as rehabilitation and how these factors influence patient outcomes. Finally, ethical issues, knowledge gaps and pathways for future research will be considered.
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| 9. |
- Evans, Colin E, et al.
(författare)
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Modelling pulmonary microthrombosis coupled to metastasis : Distinct effects of thrombogenesis on tumorigenesis
- 2017
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Ingår i: Biology Open. - : The Company of Biologists. - 2046-6390. ; 6:5, s. 688-697
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Tidskriftsartikel (refereegranskat)abstract
- Thrombosis can cause localized ischemia and tissue hypoxia, and both of these are linked to cancer metastasis. Vascular microocclusion can occur as a result of arrest of circulating tumour cells in small capillaries, giving rise to microthrombotic events that affect flow, creating localized hypoxic regions. To better understand the association between metastasis and thrombotic events, we generated an experimental strategy whereby we modelled the effect of microvascular occlusion in metastatic efficiency by using inert microbeads to obstruct lung microvasculature before, during and after intravenous tumour cell injection.We found that controlled induction of a specific number of these microthrombotic insults in the lungs caused an increase in expression of the hypoxia-inducible transcription factors (HIFs), a pro-Angiogenic and pro-Tumorigenic environment, as well as an increase in myeloid cell infiltration. Induction of pulmonary microthrombosis prior to introduction of tumour cells to the lungs had no effect on tumorigenic success, but thrombosis at the time of tumour cell seeding increased number and size of tumours in the lung, and this effect was strikingly more pronounced when the microocclusion occurred on the day following introduction of tumour cells. The tumorigenic effect of microbead treatment was seen even when thrombosis was induced five days after tumour cell injection. We also found positive correlations between thrombotic factors and expression of HIF2α in human tumours. The model system described here demonstrates the importance of thrombotic insult in metastatic success and can be used to improve understanding of thrombosis-Associated tumorigenesis and its treatment.
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| 10. |
- Kalar, I., et al.
(författare)
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Calcium channel blockers, survival and ischaemic stroke in patients with dementia : a Swedish registry study
- 2021
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Ingår i: Journal of Internal Medicine. - : Blackwell Science Ltd.. - 0954-6820 .- 1365-2796. ; 289:4, s. 508-522
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The effect of calcium channel blockers (CCB) on mortality and ischaemic stroke risk in dementia patients is understudied.OBJECTIVES: To calculate the risk of death and ischaemic stroke in dementia patients treated with CCBs, considering individual agents and dose response.METHODS: Longitudinal cohort study with 18 906 hypertensive dementia patients from the Swedish Dementia Registry (SveDem), 2008-2014. Other Swedish national registries contributed information on comorbidities, dispensed medication and outcomes. Individual CCB agents and cumulative defined daily doses (cDDD) were considered.RESULTS: In patients with hypertension and dementia, nifedipine was associated with increased mortality risk (aHR 1.32; CI 1.01-1.73; P < 0.05) compared to non-CCB users. Patients diagnosed with Alzheimer's dementia (AD) or dementia with Lewy bodies/Parkinson's disease dementia (DLB-PDD) taking amlodipine had lower mortality risk (aHR, 0.89; CI, 0.80-0.98; P < 0.05 and aHR 0.58; CI, 0.38-0.86; P < 0.01, respectively), than those taking other CCBs. Amlodipine was associated with lower stroke risk in patients with Alzheimer's dementia compared to other CCBs (aHR 0.63; CI, 0.44-0.89; P < 0.05). Sensitivity analyses with propensity score-matched cohorts repeated the results for nifedipine (aHR 1.35; 95% CI, 1.02-1.78; P < 0.05) and amlodipine in AD (aHR, 0.87; CI, 0.78-0.97; P < 0.05) and DLB-PDD (aHR, 0.56, 95%CI, 0.37-0.85; P < 0.05).CONCLUSION: Amlodipine was associated with reduced mortality risk in dementia patients diagnosed with AD and DLB-PDD. AD patients using amlodipine had a lower risk of ischaemic stroke compared to other CCB users.
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