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- Taddei, C, et al.
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Journal article (peer-reviewed)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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- Mercuri, E., et al.
(author)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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In: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Journal article (peer-reviewed)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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- Kristensen, A., et al.
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Simple cardiovascular risk stratification using anthropometric measures instead of serum cholesterol. The MORGAM Prospective Cohort Project
- 2020
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:Suppl 2, s. 2913-2913
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Journal article (other academic/artistic)abstract
- Background: Body composition predicts cardiovascular outcomes, but it is uncertain whether anthropometric measures can replace the more expensive serum total cholesterol for cardiovascular risk stratification in low resource settings.Purpose: The purpose of the study was to compare the additive prognostic ability of serum total cholesterol with that of body mass index (BMI), waist/hip ratio (WHR), and estimated fat mass (EFM, calculated using a validated prediction equation), individually and combined.Methods: We used data from the MORGAM (MONICA, Risk, Genetics, Archiving, and Monograph) Prospective Cohort Project, an international pooling of cardiovascular cohorts, to determine the relationship between anthropometric measures, serum cholesterol, and cardiovascular events, using multivariable Cox proportional-hazards regression analysis. We further investigated the ability of these measures to enhance prognostication beyond a simpler prediction model, consisting of age, sex, smoking status, systolic blood pressures, and country, using comparison of area under the receiver operating characteristics curve (AUCROC) derived from binary logistic regression models. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of death from coronary heart disease, myocardial infarction, or stroke.Results: The study population consisted of 52,188 apparently healthy subjects (56.3% men) aged 47±12 years ranging from 20 to 84, derived from 37 European cohorts, with baseline between 1982–2002 all followed for 10 years during which MACE occurred in 2465 (4.7%) subjects. All anthropometric measures (BMI: hazard ratio (HR) 1.04 [95% confidence interval (CI): 1.03–1.05] per kg/m2; WHR: HR 7.5 [4.0–14.0] per unit; EFM: HR 1.02 [1.01–1.02] per kg) as well as serum total cholesterol (HR 1.20 [1.16–1.24] per mmol/l) were significantly associated with MACE (P<0.001 for all), independently of age, sex, smoking status, systolic blood pressures, and country. The addition of serum cholesterol significantly improved the predictive ability of the simple model (AUCROC 0.818 vs. 0.814, P<0.001), as did the combination of WHR, BMI, and EFM (AUCROC 0.817 vs. 0.814, P=0.004). When assessed individually, BMI (AUCROC 0.816 vs. 0.814, P=0.004) and WHR (AUCROC 0.815 vs. 0.814, P=0.02) improved model performance, while EFM narrowly missed significance (AUCROC 0.815 vs. 0.814, P=0.06). There was no significant difference in the predictive ability of a model including serum cholesterol versus that including all three anthropometric measures (AUCROC 0.818 vs. 0.817, P=0.13). The figure shows the pertinent areas under the ROC curve in predicting MACE.Conclusion: In this large population-based cohort study, the addition of a combination of anthropometric measures, i.e. BMI, WHR, and EFM, raised the predictive ability of a simple prognostic model comparable to that obtained by the addition of serum total cholesterol.
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- Liu, JJ, et al.
(author)
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Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 9688-
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Journal article (peer-reviewed)abstract
- In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859–1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482–1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
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