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Sökning: WFRF:(Hamilton Steven P.)

  • Resultat 21-25 av 25
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21.
  • Traylor, Matthew, et al. (författare)
  • Genetic Variation at 16q24.2 is associated with small vessel stroke.
  • 2017
  • Ingår i: Annals of neurology. - : John Wiley and Sons Inc.. - 1531-8249 .- 0364-5134. ; 81:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises a quarter of all ischaemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown younger onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger onset SVS population, to identify novel associations with stroke.We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on mRNA expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain.We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (OR(95% CI)=1.16(1.10-1.22); p=3.2x10(-9) ). The lead SNP (rs12445022) was also associated with cerebral white matter hyperintensities (OR(95% CI)=1.10(1.05-1.16); p=5.3x10(-5) ; N=3,670), but not intracerebral haemorrhage (OR(95% CI)=0.97(0.84-1.12); p=0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p=9.4x10(-7) ), and DNA methylation at probe cg16596957 in whole blood (p=5.3x10(-6) ).16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements. This article is protected by copyright. All rights reserved.
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22.
  • Chow, Clara K., et al. (författare)
  • TEXT messages to improve MEDication adherence and Secondary prevention (TEXTMEDS) after acute coronary syndrome: a randomised clinical trial protocol
  • 2018
  • Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055 .- 2044-6055. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Identifying simple, low-cost and scalable means of supporting lifestyle change and medication adherence for patients following a cardiovascular (CV) event is important. Objective The TEXTMEDS (TEXT messages to improve MEDiGation adherence and Secondary prevention) study aims to investigate whether a cardiac education and support programme sent via mobile phone text message improves medication adherence and risk factor levels in patients following an acute coronary syndrome (ACS). Study design A single-blind, multicentre, randomised clinical trial of 1400 patients after an ACS with 12 months follow-up. The intervention group will receive multiple weekly text messages that provide information, motivation, support to adhere to medications, quit smoking (if relevant) and recommendations for healthy diet and exercise. The primary endpoint is the percentage of patients who are adherent to cardioprotective medications and the key secondary outcomes are mean systolic blood pressure (BP) and low density lipoprotein cholesterol. Secondary outcomes will also include total cholesterol, mean diastolic BP, the percentage of participants who are adherent to each cardioprotective medication class, the percentage of participants who achieve target levels of CV risk factors, major vascular events, hospital readmissions and all-cause mortality. The study will be augmented by formal economic and proGess evaluations to assess acceptability, utility and Gost-effectiveness. Summary The study will provide multicentre randomised trial evidence of the effects of a text message-based programme on cardioprotective medication adherence and levels of CV risk factors. Ethics and dissemination Primary ethics approval was received from Western Sydney Local Health District Human Research EthiGs Committee (HREC2012/12/4.1 (3648) AU RED HREC/13ANMEAD/15). Results will be disseminated via peer-reviewed publications and presentations at international conferences.
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23.
  • Im, Annie, et al. (författare)
  • Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
  • 2020
  • Ingår i: Biology of blood and marrow transplantation. - 1083-8791 .- 1523-6536. ; 26:8, s. 1459-1468
  • Tidskriftsartikel (refereegranskat)abstract
    • Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
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25.
  • Vlahos, Ross, et al. (författare)
  • Neutralizing granulocyte/macrophage colony-stimulating factor inhibits cigarette smoke-induced lung inflammation.
  • 2010
  • Ingår i: American journal of respiratory and critical care medicine. - 1535-4970. ; 182:1, s. 34-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Cigarette smoke is the major cause of chronic obstructive pulmonary disease (COPD), and there is currently no satisfactory therapy to treat people with COPD. We have previously shown that granulocyte/macrophage colony-stimulating factor (GM-CSF) regulates lung innate immunity to LPS through Akt/Erk activation of nuclear factor-kappaB and activator protein (AP)-1.
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  • Föregående 12[3]
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