| 1. |
- Deming, Yuetiva, et al.
(författare)
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Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers
- 2017
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 133:5, s. 839-856
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Tidskriftsartikel (refereegranskat)abstract
- More than 20 genetic loci have been associated with risk for Alzheimer’s disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case–control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = −0.059, P = 2.08 × 10−8) and within SERPINB1 on 6p25 (β = −0.025, P = 1.72 × 10−8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10−2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10−2), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10−3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform future AD studies.
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| 2. |
- Fourie, Anika, et al.
(författare)
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Development of prone positioning and skin damage prevention digital education : the PRONEtect project
- 2023
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Ingår i: Journal of Wound Care. - : MA Healthcare Ltd.. - 0969-0700 .- 2052-2916. ; 32:9, s. 570-578
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The incidence of skin/tissue damage, such as pressure ulcers, remains high in mechanically ventilated patients in the prone position. According to guidelines, critically ill patients with acute respiratory distress syndrome (ARDS) should be prone for at least 12-16 hours to improve oxygenation and decrease mortality. Therefore, educating clinicians on how to reposition and manage the patient safely in a prone position plays a vital role in preventing adverse events. This project aimed to develop accessible online educational content to assist clinicians in safely executing the prone manoeuvre and minimise skin/tissue damage.METHOD: The development of the educational content was based on: a gap analysis and comprehensive review of available educational resources; evidence-based scientific literature; advice from international experts; and a qualitative study exploring the learning needs of 20 clinicians in Belgium and Sweden between February-August 2022.RESULTS: Volunteer clinicians assisted with the creation of eight simulation videos which were professionally filmed and edited. The interactive videos included the supine-to-prone and prone-to-supine manoeuvres, endotracheal and nasogastric tube securement, eye care, stoma care, protecting high-risk areas from pressure damage, and incontinence-associated dermatitis prevention. A prone positioning protocol, a checklist summarising the key aspects of the protocol, and teaching aids (slide deck for didactic lecturing) were developed and validated by a review of the relevant evidence-based literature and the international expert panel. A website was designed to host the content, with free user access, at www.pronetection.com.CONCLUSION: Education is one strategy towards prevention of complications of prone positioning. Accessible education could assist clinicians unfamiliar with prone positioning or current clinicians requiring refresher training to safely manage patients in this position.
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| 3. |
- Fourie, Anika, et al.
(författare)
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Enhancing prone positioning and skin damage prevention education : A randomized controlled non-inferiority trial comparing a digital education hub (PRONEtect) and a traditional lecture on final-year nursing participants' confidence and knowledge
- 2024
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Ingår i: Journal of tissue viability. - 0965-206X .- 1876-4746.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The incidence of pressure ulcers remains high in patients with moderate to severe acute respiratory distress syndrome, ventilated in the prone position. A digital platform, dedicated to prone positioning and skin/tissue damage education was developed.OBJECTIVE: To evaluate the impact of the PRONEtect Education Hub versus a traditional lecture on final-year nursing students' confidence levels and knowledge in a non-inferiority study.DESIGN: A multicenter, non-blinded, parallel-group, non-inferiority study with equal randomization (1:1 allocation) was conducted at two nursing schools in Belgium. CLINICALTRIALS: gov (NCT05575869).METHODS: Following baseline assessments, the control group received a 1-h classroom lecture, and the experimental group gained access to the PRONEtect website. Three weeks later, participants completed the knowledge, confidence, and visual knowledge assessment.RESULTS: At baseline, 67 of the 80 participants completed the assessments and post-intervention, 28 and 27 participants respectively completed the confidence, knowledge, and visual knowledge assessments (dropout rate of 66.25%). Confidence levels: a mean ratio of relative change from baseline = 0.96 (Control (C)/Experimental (E)); 97.5% confidence interval (CI): 0.74 to 1.26; p = 0.74. Knowledge assessment: a mean difference in change from baseline = 1.58 (C-E); 97.5% CI: -0.58 to 3.75; p = 0.1. Although confidence and knowledge scores increased in both groups, the study cannot conclude non-inferiority.CONCLUSIONS: The trade-off between the inability to conclude efficacy of the impact of the website and the benefit of having an accessible educational platform on prone positioning and skin damage prevention makes the PRONEtect Education Hub an acceptable adjunct to traditional lecturing.
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| 4. |
- Fourie, Anika, et al.
(författare)
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Skin damage prevention in the prone ventilated critically ill patient : A comprehensive review and gap analysis (PRONEtect study)
- 2021
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Ingår i: Journal of tissue viability. - : Elsevier. - 0965-206X. ; 30:4, s. 466-477
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Ventilating critically ill patients with acute respiratory distress syndrome in the prone position is a life-saving strategy, but it is associated with adverse consequences such as skin damage.AIM: To identify, review and evaluate international proning and skin care guidelines and make an inventory of commonly used equipment and training resources.DESIGN: A gap analysis methodology was applied.METHODS: 1) Comprehensive search and evaluation of proning and skin care guidelines, 2) extensive search and listing equipment and educational resources, and 3) international consultation with 11 experts (8 countries).DATA SOURCES: A variety of sources researched through July 2021 were used to identify relevant literature: (1) scientific literature databases and clinical trials registries, (2) intensive care and wound care associations, (3) healthcare organisations, (4) guideline development organisations, and (5) the Google search engine. Eleven international experts reviewed the literature and provided insights in two, 2-h online sessions.FINDINGS: The search yielded 24 guidelines. One clinical practice guideline had high methodological quality. Twenty-five devices/equipment and sixteen teaching materials were identified and discussed with the expert panel. The gap analysis identified a lack of concise, accessible, evidence-based guidelines and educational materials of short duration.CONCLUSION: This analysis forms the basis for designing a competency-based education and training intervention for an interdisciplinary team caring for the skin of critically ill patients in the prone position.IMPACT: The results can assist the multidisciplinary team to review their current protocol for prone positioning. This is a first step in developing a training package for clinicians.
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| 5. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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