| 1. |
- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 2. |
- Bell, Jane C., et al.
(författare)
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Survival of infants born with esophageal atresia among 24 international birth defects surveillance programs
- 2021
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Ingår i: Birth Defects Research. - : Wiley. - 2472-1727. ; 113:12, s. 945-957
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Tidskriftsartikel (refereegranskat)abstract
- Background: Esophageal atresia (EA) affects around 2.3–2.6 per 10,000 births world-wide. Infants born with this condition require surgical correction soon after birth. Most survival studies of infants with EA are locally or regionally based. We aimed to describe survival across multiple world regions. Methods: We included infants diagnosed with EA between 1980 and 2015 from 24 birth defects surveillance programs that are members of the International Clearinghouse for Birth Defects Surveillance and Research. We calculated survival as the proportion of liveborn infants alive at 1 month, 1- and 5-years, among all infants with EA, those with isolated EA, those with EA and additional anomalies or EA and a chromosomal anomaly or genetic syndrome. We also investigated trends in survival over the decades, 1980s–2010s. Results: We included 6,466 liveborn infants with EA. Survival was 89.4% (95% CI 88.1–90.5) at 1-month, 84.5% (95% CI 83.0–85.9) at 1-year and 82.7% (95% CI 81.2–84.2) at 5-years. One-month survival for infants with isolated EA (97.1%) was higher than for infants with additional anomalies (89.7%) or infants with chromosomal or genetic syndrome diagnoses (57.3%) with little change at 1- and 5-years. Survival at 1 month improved from the 1980s to the 2010s, by 6.5% for infants with isolated EA and by 21.5% for infants with EA and additional anomalies. Conclusions: Almost all infants with isolated EA survived to 5 years. Mortality was higher for infants with EA and an additional anomaly, including chromosomal or genetic syndromes. Survival improved from the 1980s, particularly for those with additional anomalies.
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| 3. |
- de Boer, Anneloes, et al.
(författare)
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Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI
- 2022
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Ingår i: Journal of Magnetic Resonance Imaging. - : John Wiley & Sons. - 1053-1807 .- 1522-2586. ; 55:2, s. 323-335
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool.PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies.STUDY TYPE: Systematic consensus process using a modified Delphi method.POPULATION: Not applicable.SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI.ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated.STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts.RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting.DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI.LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.
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| 4. |
- Faltaous, Sarah, et al.
(författare)
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EMStriker: Potentials of Enhancing the Training Process of Racket-based Sports via Electrical Muscle Stimulation
- 2022
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Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : ACM.
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Konferensbidrag (refereegranskat)abstract
- Racket sports offer an enjoyable form of physical activity and are fertile ground for interactive technologies supporting new players. Yet, current research has neglected its potential to support not only active players but also coaches in their training methods. To investigate how interactive technologies can support skill acquisition in training, we designed an Electrical Muscle Stimulation (EMS) system that helps maintain the ready position in crossminton. We compared the system with a vibrotactile solution in a user study, interviewing novice players and experienced coaches about their perception of the system. The system allowed coaches to effectively and immediately guide players to the ready position. An EMS-based feedback system for coaches can potentially reduce delay (physical and cognitive) for trainees, as stated by coaches. Our work contributes insights into designing systems that facilitate learning sports techniques using interactive feedback.
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| 5. |
- Mc Goldrick, Niall, et al.
(författare)
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A multi-program analysis of cleft lip with cleft palate prevalence and mortality using data from 22 International Clearinghouse for Birth Defects Surveillance and Research programs, 1974–2014
- 2023
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Ingår i: Birth Defects Research. - 2472-1727. ; 115:10, s. 980-997
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cleft lip with cleft palate (CLP) is a congenital condition that affects both the oral cavity and the lips. This study estimated the prevalence and mortality of CLP using surveillance data collected from birth defect registries around the world. Methods: Data from 22 population- and hospital-based surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) in 18 countries on live births (LB), stillbirths (SB), and elective terminations of pregnancy for fetal anomaly (ETOPFA) for CLP from 1974 to 2014 were analyzed. Prevalence and survival (survival for LB only) estimates were calculated for total and subclassifications of CLP and by pregnancy outcome. Results: The pooled prevalence of total CLP cases was 6.4 CLP per 10,000 births. The prevalence of CLP and all of the pregnancy outcomes varied across programs. Higher ETOPFA rates were recorded in most European programs compared to programs in other continents. In programs reporting low ETOPFA rates or where there was no ascertainment of ETOPFA, the rate of CLP among LB and SB was higher compared to those where ETOPFA rates were ascertained. Overall survival for total CLP was 91%. For isolated CLP, the survival was 97.7%. CLP associated with multiple congenital anomalies had an overall survival of 77.1%, and for CLP associated with genetic/chromosomal syndromes, overall survival was 40.9%. Conclusions: Total CLP prevalence reported in this study is lower than estimates from prior studies, with variation by pregnancy outcomes between programs. Survival was lower when CLP was associated with other congenital anomalies or syndromes compared to isolated CLP.
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| 6. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 7. |
- Svensson, Maria K., et al.
(författare)
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Effects of lipid-lowering treatment intensity and adherence on cardiovascular outcomes in patients with a recent myocardial infarction : a Swedish register-based study
- 2022
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 127:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oral lipid-lowering treatment (LLT) is the standard of care for patients with cardiovascular disease (CVD). However, insufficient treatment intensity and poor adherence can lead to suboptimal treatment benefit, rendering patients at increased risk of CVD.Aims: The objective of this study was to evaluate trends in LLT intensity and adherence in Sweden over time, and their association with major adverse cardiovascular events (MACE) after recent myocardial infarction (MI), and also to assess the impact of transition from secondary to primary care on intensity and adherence.Methods and results: This retrospective observational cohort study used data from Swedish nationwide patient registers and included patients on LLT after an MI in the years 2010–2016 (n = 50,298; mean age, 68 years; 69% men). LLT intensity was evaluated over time (overall, for 2010–2013 and for 2014–2016) as the proportion of patients prescribed low-, moderate-, and high-intensity LLT. Adherence was assessed as the proportion of days covered. A combined measure of intensity and adherence was also considered. Differences in treatment patterns and MACE were assessed. Initiation of high-intensity LLT increased over the two time periods studied (2010–2013, 32%; 2014–2016, 91%). Adherence varied by LLT intensity and was highest in patients receiving high-intensity LLT (>80%), especially during the first time period. Little change in treatment intensity or the combined measure of intensity and adherence was observed after transition to primary care. There was a significant association between the combined measure of intensity and adherence and MACE reduction (hazard ratio [95% confidence interval] per 10% increase in the combined measure: 0.84 [0.82–0.86]; P < 0.01).Conclusion: The proportion of post-MI patients with high LLT intensity and adherence has increased in recent years, with little change after transfer from specialist to primary care. The combination of LLT intensity and adherence is important for preventing future cardiovascular events.
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