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- Turro, Ernest, et al.
(författare)
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Whole-genome sequencing of patients with rare diseases in a national health system.
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 583:7814, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065extensively phenotypedparticipants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data ofUK Biobankparticipants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
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- Kotanidis, Christos P, et al.
(författare)
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Invasive vs. conservative management of older patients with non-ST-elevation acute coronary syndrome: individual patient data meta-analysis.
- 2024
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Ingår i: European heart journal. - 1522-9645.
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Tidskriftsartikel (refereegranskat)abstract
- Older patients with non-ST-elevation acute coronary syndrome (NSTEACS) are less likely to receive guideline-recommended care including coronary angiography and revascularization. Evidence-based recommendations regarding interventional management strategies in this patient cohort are scarce. This meta-analysis aimed to assess the impact of routine invasive vs. conservative management of NSTEACS by using individual patient data (IPD) from all available randomized controlled trials (RCTs) including older patients.MEDLINE, Web of Science and Scopus were searched between 1 January 2010 and 11 September 2023. RCTs investigating routine invasive and conservative strategies in persons >70 years old with NSTEACS were included. Observational studies or trials involving populations outside the target range were excluded. The primary endpoint was a composite of all-cause mortality and myocardial infarction (MI) at 1 year. One-stage IPD meta-analyses were adopted by use of random-effects and fixed-effect Cox models. This meta-analysis is registered with PROSPERO (CRD42023379819).Six eligible studies were identified including 1479 participants. The primary endpoint occurred in 181 of 736 (24.5%) participants in the invasive management group compared with 215 of 743 (28.9%) participants in the conservative management group with a hazard ratio (HR) from random-effects model of 0.87 (95% CI 0.63-1.22; P = .43). The hazard for MI at 1 year was significantly lower in the invasive group compared with the conservative group (HR from random-effects model 0.62, 95% CI 0.44-0.87; P = .006). Similar results were seen for urgent revascularization (HR from random-effects model 0.41, 95% CI 0.18-0.95; P = .037). There was no significant difference in mortality.No evidence was found that routine invasive treatment for NSTEACS in older patients reduces the risk of a composite of all-cause mortality and MI within 1 year compared with conservative management. However, there is convincing evidence that invasive treatment significantly lowers the risk of repeat MI or urgent revascularisation. Further evidence is needed from ongoing larger clinical trials.
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