| 1. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 2. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 3. |
- Ho, J. E., et al.
(författare)
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Clinical and genetic correlates of growth differentiation factor 15 in the community
- 2012
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 58:11, s. 1582-1591
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Growth differentiation factor 15(GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively. METHODS: Plasma GDF15 concentrations were measured in 2991 participants in the Framingham Offspring Study who were free of clinically overt CVD (mean age, 59 years; 56% women). Clinical correlates of GDF15 were examined in multivariable analyses. We then conducted a genomewide association study of the GDF15 concentration that included participants in the Framingham Offspring Study and participants in the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study. RESULTS: GDF15 was positively associated with age, smoking, antihypertensive treatment, diabetes, worse kidney function, and use of nonsteroidal antiinflammatory drugs (NSAIDs), but it was negatively associated with total cholesterol and HDL cholesterol. Clinical correlates accounted for 38% of interindividual variation in the circulating GDF15 concentration, whereas genetic factors accounted for up to 38% of the residual variability (h 2 = 0.38; P = 2.5 X 10 -11). We identified 1 locus of genomewide significance. This locus, which is on chromosome 19p13.11 and includes the GDF15 gene, is associated with GDF15 concentration (smallest P = 2.74 X 10 -32 for rs888663). Conditional analyses revealed 2 independent association signals at this locus (rs888663 and rs1054564), which were associated with altered cis gene expression in blood cell lines. CONCLUSIONS: In ambulatory individuals, both cardiometabolic risk factors and genetic factors play important roles in determining circulating GDF15 concentrations and contribute similarly to the overall variation.
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| 6. |
- Scirica, B. M., et al.
(författare)
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Patients with acute coronary syndromes and elevated levels of natriuretic peptides: the results of the AVANT GARDE-TIMI 43 Trial
- 2010
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Ingår i: European Heart Journal. - 0195-668X. ; 31:16, s. 1993-2005
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Tidskriftsartikel (refereegranskat)abstract
- Aims Elevated natriuretic peptides (NPs) are associated with an increased cardiovascular risk following acute coronary syndromes (ACSs). However, the therapeutic implications are still undefined. We hypothesized that early inhibition of renin-angiotensin-aldosterone system (RAAS) in patients with preserved left ventricular function but elevated NPs but following ACS would reduce haemodynamic stress as reflected by a greater reduction NP compared with placebo. Methods and results AVANT GARDE-TIMI 43 trial, a multinational, double-blind trial, randomized 1101 patients stabilized after ACS without clinical evidence of heart failure or left ventricular function
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| 7. |
- Swami, Viren, et al.
(författare)
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The Attractive Female Body Weight and Female Body Dissatisfaction in 26 Countries Across 10 World Regions : Results of the International Body Project I
- 2010
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Ingår i: Personality and Social Psychology Bulletin. - : Sage Publications. - 0146-1672 .- 1552-7433. ; 36:3, s. 309-325
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Tidskriftsartikel (refereegranskat)abstract
- This study reports results from the first International Body Project (IBP-I), which surveyed 7,434 individuals in 10 major world regions about body weight ideals and body dissatisfaction. Participants completed the female Contour Drawing Figure Rating Scale (CDFRS) and self-reported their exposure to Western and local media. Results indicated there were significant cross-regional differences in the ideal female figure and body dissatisfaction, but effect sizes were small across high-socioeconomic-status (SES) sites. Within cultures, heavier bodies were preferred in low-SES sites compared to high-SES sites in Malaysia and South Africa (ds = 1.94-2.49) but not in Austria. Participant age, body mass index (BMI), and Western media exposure predicted body weight ideals. BMI and Western media exposure predicted body dissatisfaction among women. Our results show that body dissatisfaction and desire for thinness is commonplace in high-SES settings across world regions, highlighting the need for international attention to this problem.
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| 8. |
- Cheng, Susan, et al.
(författare)
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Metabolite Profiling Identifies Pathways Associated With Metabolic Risk in Humans
- 2012
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Ingår i: Circulation. - 1524-4539. ; 125:18, s. 132-2222
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Tidskriftsartikel (refereegranskat)abstract
- Background-Although metabolic risk factors are known to cluster in individuals who are prone to developing diabetes mellitus and cardiovascular disease, the underlying biological mechanisms remain poorly understood. Methods and Results-To identify pathways associated with cardiometabolic risk, we used liquid chromatography/mass spectrometry to determine the plasma concentrations of 45 distinct metabolites and to examine their relation to cardiometabolic risk in the Framingham Heart Study (FHS; n=1015) and the Malmo Diet and Cancer Study (MDC; n=746). We then interrogated significant findings in experimental models of cardiovascular and metabolic disease. We observed that metabolic risk factors (obesity, insulin resistance, high blood pressure, and dyslipidemia) were associated with multiple metabolites, including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites. We observed strong associations of insulin resistance traits with glutamine (standardized regression coefficients, -0.04 to -0.22 per 1-SD change in log-glutamine; P<0.001), glutamate (0.05 to 0.14; P<0.001), and the glutamine-toglutamate ratio (-0.05 to -0.20; P<0.001) in the discovery sample (FHS); similar associations were observed in the replication sample (MDC). High glutamine-to-glutamate ratio was associated with lower risk of incident diabetes mellitus in FHS (odds ratio, 0.79; adjusted P=0.03) but not in MDC. In experimental models, administration of glutamine in mice led to both increased glucose tolerance (P=0.01) and decreased blood pressure (P=0.05). Conclusions-Biochemical profiling identified circulating metabolites not previously associated with metabolic traits. Experimentally interrogating one of these pathways demonstrated that excess glutamine relative to glutamate, resulting from exogenous administration, is associated with reduced metabolic risk in mice. (Circulation. 2012;125:2222-2231.)
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| 9. |
- Priebe, S, et al.
(författare)
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Good practice in emergency care: views from practitioners :
- 2011
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Ingår i: Migration and Health in the European Union. - : Open University Press. - 9780335245673
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Bokkapitel (refereegranskat)abstract
- Migrants make up a growing share of European populations. However, all too often their situation is compounded by problems with accessing health and other basic services. There is a need for tailored health policies, but robust data on the health needs of migrants and how best these needs can be met are scarce.Written by a collaboration of authors from three key international organisations (the European Observatory on Health Systems and Policies, the EUPHA Section on Migrant and Ethnic Minority Health, and the International Organization for Migration), as well as leading researchers from across Europe, the book thoroughly explores the different aspects of migration and health in the EU and how they can be addressed by health systems.Structured into five easy-to-follow sections, the volume includes:Contributions from experts from across EuropeKey topics such as: access to human rights and health care; health issues faced by migrants; and the national and European policy response so farConclusions drawn from the latest available evidenceComprehensive information on different aspects of health and migration and how they can best be addressed by health systems is still not easy to find. This book addresses this shortfall and will be of major value to researchers, students, policy-makers and practitioners concerned with migration and health in an increasingly diverse Europe.
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| 10. |
- von Sarnowski, Bettina, et al.
(författare)
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Prevalence of stenoses and occlusions of brain-supplying arteries in young stroke patients.
- 2013
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Ingår i: Neurology. - 1526-632X. ; 80:14, s. 1287-1294
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Atherosclerosis is believed to be a minor cause of TIA and stroke in younger and middle-aged patients. However, data from large cohorts are limited. This study investigates the prevalence of extracranial and intracranial atherosclerosis in stroke and TIA patients aged 18-55 years in the multinational sifap1 study. METHODS: From the sifap1 cohort (n = 5,023), we analyzed a subset of patients with complete data from carotid ultrasound studies. Patients with arterial dissections, vasculitis, and mobile thrombi were excluded. Among the remaining 2,187 patients (men: n = 1,319; 18-44 years: n = 744), intracranial arteries were additionally examined with ultrasonography in 1,612 patients (73.7%). Patients were stratified by sex and age groups (younger: 18-44 years; middle-aged: 45-55 years). RESULTS: In patients with ischemic stroke, the overall prevalence of carotid artery stenoses and occlusions was 8.9% (younger: 4.9%; middle-aged: 11.0%), of which 81% were symptomatic. Nonstenotic carotid plaques were more common in men than in women (15.8% vs 7.7%; p < 0.001), and in middle-aged than in younger patients (17.0% vs 4.9%; p < 0.001). Supratentorial intracranial artery stenoses and occlusions amounted to 11.8%. Supratentorial stenoses occurred more frequently in middle-aged patients (13.0% vs 7.8%; p < 0.001), whereas occlusions were equally common (both 3.2%; not significant). CONCLUSIONS: We observed a substantial proportion of atherosclerotic carotid artery stenoses and occlusions in younger stroke patients. Intracranial stenoses and occlusions were even more prevalent than extracranial carotid artery disease. Together with nonstenotic plaques, one-fifth of patients (21.2%) had symptomatic or asymptomatic large-artery atherosclerosis, which should encourage future stroke prevention campaigns to target risk factor modification in young people.
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