Bmc Med
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Homozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies. ⋯ Our findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.
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China has one of the highest numbers of liver disease cases in the world, including 6.4 million cirrhosis associated with alcohol-related liver disease (ALD) cases. However, there is still a lack of urgent awareness about the growth of alcohol consumption and the increased burden of ALD in China. Therefore, we aimed to project the potential impact of changes in alcohol consumption on the burden of ALD in China up to 2040 under different scenarios. ⋯ Without any substantial change in alcohol attitudes and policies to regulate excessive drinking, the disease burden of ALD in China will increase enormously. Strengthening the implementation of alcohol restriction interventions is critical and urgent to reduce the impact of ALD on the Chinese population.
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Meat-free diets may be associated with a higher risk of hip fracture, but prospective evidence is limited. We aimed to investigate the risk of hip fracture in occasional meat-eaters, pescatarians, and vegetarians compared to regular meat-eaters in the UK Biobank, and to explore the role of potential mediators of any observed risk differences. ⋯ Vegetarian men and women had a higher risk of hip fracture than regular meat-eaters, and this was partly explained by their lower BMI. Ensuring adequate nutrient intake and weight management are therefore particularly important in vegetarians in the context of hip fracture prevention.
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The estimand for a clinical trial is a precise definition of the treatment effect to be estimated. Traditionally, estimates of treatment effects are based on either an ITT analysis or a per-protocol analysis. However, there are important clinical questions which are not addressed by either of these analyses. For example, consider a trial where patients take a rescue medication. The ITT analysis includes data after use of rescue, while the per-protocol analysis excludes these patients altogether. Neither of these analyses addresses the important question of what the treatment effect would have been if patients did not take rescue medication. ⋯ The estimand framework is an important step forward in improving the clarity and transparency of clinical trials. The centrality of estimands to clinical trials is currently not reflected in methods recommended by the Cochrane group or the CONSORT statement, the current standard for reporting clinical trials in medical journals. We encourage revisions to these guidelines.
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Persistent infection by oncogenic human papillomavirus (HPV) is necessary although not sufficient for development of cervical cancer. Behavioural, environmental, or comorbid exposures may promote or protect against malignant transformation. Randomised evidence is limited and the validity of observational studies describing these associations remains unclear. ⋯ Our main analysis supported the association of systemic (HIV infection, immunosuppressive medications) and local immunosuppression (altered vaginal microbiota) with increased risk for worse HPV and cervical disease outcomes. Mendelian randomisation confirmed the link for genetically predicted lifetime smoking index, and young age at first pregnancy with cervical cancer, highlighting also that observational evidence can hide different inherent biases. This evidence strengthens the need for more frequent HPV screening in people with immunosuppression, further investigation of the vaginal microbiome and access to sexual health services.