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- Hart, R. G., et al.
(författare)
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Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source
- 2018
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 378:23, s. 2191-2201
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding.
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- Schild, R., et al.
(författare)
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Disparities in treatment and outcome of kidney replacement therapy in children with comorbidities: an ESPN/ERA Registry study
- 2023
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 16:4, s. 745-755
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Tidskriftsartikel (refereegranskat)abstract
- Background Data on comorbidities in children on kidney replacement therapy (KRT) are scarce. Considering their high relevance for prognosis and treatment, this study aims to analyse the prevalence and implications of comorbidities in European children on KRT. Methods We included data from patients <20 years of age when commencing KRT from 2007 to 2017 from 22 European countries within the European Society of Paediatric Nephrology/European Renal Association Registry. Differences between patients with and without comorbidities in access to kidney transplantation (KT) and patient and graft survival were estimated using Cox regression. Results Comorbidities were present in 33% of the 4127 children commencing KRT and the prevalence has steadily increased by 5% annually since 2007. Comorbidities were most frequent in high-income countries (43% versus 24% in low-income countries and 33% in middle-income countries). Patients with comorbidities had a lower access to transplantation {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61-0.74]} and a higher risk of death [aHR 1.79 (95% CI 1.38-2.32)]. The increased mortality was only seen in dialysis patients [aHR 1.60 (95% CI 1.21-2.13)], and not after KT. For both outcomes, the impact of comorbidities was stronger in low-income countries. Graft survival was not affected by the presence of comorbidities [aHR for 5-year graft failure 1.18 (95% CI 0.84-1.65)]. Conclusions Comorbidities have become more frequent in children on KRT and reduce their access to transplantation and survival, especially when remaining on dialysis. KT should be considered as an option in all paediatric KRT patients and efforts should be made to identify modifiable barriers to KT for children with comorbidities. Lay Summary Kidney transplantation (KT) is considered the optimal treatment for children who suffer from permanent kidney failure, because it leads to a lower mortality and higher quality of life compared with dialysis. Children on dialysis frequently suffer from diseases of other organs (comorbidities) that can directly lower their life expectancy and could potentially represent a barrier for transplantation, posing an additional disease burden for these children. In this study we looked at data from a large multinational registry for children with kidney failure who require kidney replacement. Using these data, we studied whether these children suffered from comorbidities and whether these impact their life expectancy or their access to KT. We found that more and more children with kidney failure suffer from comorbidities when starting kidney replacement therapy. We also found that these children have a lower access to KT and a higher mortality on dialysis compared with children without comorbidities, especially in low-income countries. After KT, children with comorbidities have a similar mortality and graft survival compared with children without comorbidities. We concluded that reduced access to a kidney transplant might represent a modifiable barrier to KT in children with comorbidities, especially in low-resource countries. We suggest that children with comorbidities in need for kidney replacement therapy should be rapidly evaluated for eligibility for KT.
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- Bereczki, E, et al.
(författare)
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Corrigendum
- 2019
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 142:6, s. e24-
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Tidskriftsartikel (refereegranskat)
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- Bereczki, E., et al.
(författare)
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Synaptic proteins in CSF relate to Parkinson's disease stage markers
- 2017
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Ingår i: Npj Parkinsons Disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings of morphological and functional changes in Parkinson's disease brains have shown altered synapse formation, but their role in cognitive decline is still an area under exploration. Here we measured the concentration of three key synaptic proteins, Rab3A, SNAP25 and neurogranin by enzyme-linked immunosorbent assay, in cerebrospinal fluid from a total of 139 participants (87 controls and 52 Parkinson's disease patients out of which 30 were drug-naive) and explored their associations with motor and cognitive symptoms. Associations with motor disease stage (assessed by Hoehn and Yahr scale) and cognitive performance (assessed by the Montreal Cognitive Assessment scores) were explored. An overall increase in the concentration of SNAP25 was found in Parkinson's disease patients (p = 0.032). Increased neurogranin levels were found in the drug naive patients subgroup (p = 0.023). Significant associations were observed between increased concentration of neurogranin and cognitive impairment in total Parkinson's disease group (p = 0.017), as well as in the drug naive (p = 0.021) and with motor disease stage (p = 0.041). There were no significant disease-driven changes observed in the concentration of Rab3a. Concentrations SNAP25 and neurogranin were increased in cerebrospinal fluid of Parkinson's disease patients in a disease specific manner and related to cognitive and motor symptom severity. Future longitudinal studies should explore whether cerebrospinal fluid synaptic proteins can predict cognitive decline in Parkinson's disease.
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- Bereczki, E., et al.
(författare)
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Synaptic proteins predict cognitive decline in Alzheimer's disease andLewy body dementia
- 2016
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 12:11, s. 1149-1158
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Our objective was to compare the levels of three synaptic proteins involved in different steps of the synaptic transmission: Rab3A, SNAP25, and neurogranin, in three common forms of dementia: Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia. Methods A total of 129 postmortem human brain samples were analyzed in brain regional specific manner exploring their associations with morphologic changes and cognitive decline. Results We have observed robust changes reflecting synaptic dysfunction in all studied dementia groups. There were significant associations between the rate of cognitive decline and decreased levels of Rab3 in DLB in the inferior parietal lobe and SNAP25 in AD in the prefrontal cortex. Of particular note, synaptic proteins significantly discriminated between dementia cases and controls with over 90% sensitivity and specificity. Discussion Our findings suggest that the proposition that synaptic markers can predict cognitive decline in AD, should be extended to Lewy body diseases. © 2016 The Alzheimer's Association
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