Because of the different population allele frequencies of HLA-B*1502 among different ethnic groups, genotyping for HLA-B*1502 and providing alternate AEDs to those who test positive is cost-effective for Singaporean Chinese and Malays, but not for Singaporean Indians. Population frequency of HLA-B*1502, PPV, duration of treatment relative to life expectancy, and costs of alternative drugs are the key drivers influencing cost-effectiveness.
Clinical and preclinical applications of human hematopoietic stem cells (HSCs) are often limited by scarcity of cells. Expanding human HSCs to increase their numbers while maintaining their stem cell properties has therefore become an important area of research. Here, we report a robust HSC coculture system wherein cord blood CD34 þ CD133þ cells were cocultured with mesenchymal stem cells engineered to express angiopoietin-like-5 in a defined medium. After 11 days of culture, SCID repopulating cells were expanded *60-fold by limiting dilution assay in NOD-scid Il2rg À=À (NSG) mice. The cultured CD34 þ CD133 þ cells had similar engraftment potential to uncultured CD34 þ CD133 þ cells in competitive repopulation assays and were capable of efficient secondary reconstitution. Further, the expanded cells supported a robust multilineage reconstitution of human blood cells in NSG recipient mice, including a more efficient T-cell reconstitution. These results demonstrate that the expanded CD34 þ CD133 þ cells maintain both short-term and long-term HSC activities. To our knowledge, this *60-fold expansion of SCID repopulating cells is the best expansion of human HSCs reported to date. Further development of this coculture method for expanding human HSCs for clinical and preclinical applications is therefore warranted.
Efforts are under way to identify successful strategies to reduce long-term childhood obesity risk, such as ways to improve diet quality. To identify foods and beverages associated with excess weight gain, we used cohort data from the Avon Longitudinal Study of Parents and Children in the United Kingdom. We quantified the associations between changes in or levels of consumption of twenty-seven food and beverage groups and excess weight gain in three-year periods among youth ages 7-13. When we considered all dietary factors and physical activity levels simultaneously, we found that foods with the largest positive associations with three-year excess weight gain were fat spread (butter or margarine), coated (breaded or battered) poultry, potatoes cooked in oil (French fries, roasted potatoes, and potato chips), coated fish, processed meats, other meats, desserts and sweets, milk, and sugar-sweetened beverages. Foods associated with weight loss were whole grains and high-fiber cereals. These results provide evidence for targeting specific food and beverage groups in efforts to influence weight outcomes.
BackgroundThe Sustainable Development Goals (SDGs), adopted by all United Nations (UN) member states in 2015, established a set of bold and ambitious health-related targets to achieve by 2030. Understanding China’s progress toward these targets is critical to improving population health for its 1.4 billion people.Methods and findingsWe used estimates from the Global Burden of Disease (GBD) Study 2016, national surveys and surveillance data from China, and qualitative data. Twenty-eight of the 37 indicators included in the GBD Study 2016 were analyzed. We developed an attainment index of health-related SDGs, a scale of 0–100 based on the values of indicators. The projection model is adjusted based on the one developed by the GBD Study 2016 SDG collaborators.We found that China has achieved several health-related SDG targets, including decreasing neonatal and under-5 mortality rates and the maternal mortality ratios and reducing wasting and stunting for children. However, China may only achieve 12 out of the 28 health-related SDG targets by 2030. The number of target indicators achieved varies among provinces and municipalities. In 2016, among the seven measured health domains, China performed best in child nutrition and maternal and child health and reproductive health, with the attainment index scores of 93.0 and 91.8, respectively, followed by noncommunicable diseases (NCDs) (69.4), road injuries (63.6), infectious diseases (63.0), environmental health (62.9), and universal health coverage (UHC) (54.4). There are daunting challenges to achieve the targets for child overweight, infectious diseases, NCD risk factors, and environmental exposure factors. China will also have a formidable challenge in achieving UHC, particularly in ensuring access to essential healthcare for all and providing adequate financial protection. The attainment index of child nutrition is projected to drop to 80.5 by 2025 because of worsening child overweight. The index of NCD risk factors is projected to drop to 38.8 by 2025. Regional disparities are substantial, with eastern provinces generally performing better than central and western provinces. Sex disparities are clear, with men at higher risk of excess mortality than women. The primary limitations of this study are the limited data availability and quality for several indicators and the adoption of "business-as-usual" projection methods.ConclusionThe study found that China has made good progress in improving population health, but challenges lie ahead. China has substantially improved the health of children and women and will continue to make good progress, although geographic disparities remain a great challenge. Meanwhile, China faced challenges in NCDs, mental health, and some infectious diseases. Poor control of health risk factors and worsening environmental threats have posed difficulties in further health improvement. Meanwhile, an inefficient health system is a barrier to tackling these challenges among such a rapidly aging population. The eastern provinces are predicted to pe...
Aims: Allopurinol is an efficacious urate-lowering therapy (ULT), but is associated with rare serious adverse drug reactions of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with higher risk among HLA-B*5801 carriers. We assessed the cost–effectiveness of HLA-B*5801 testing, an enhanced safety program or strategies with both components. Methods: The analysis adopted a health systems perspective and considered Singaporean patients with chronic gout, over a lifetime horizon, using allopurinol or probenecid. The model incorporated SJS/TEN and gout treatment outcomes, allele frequencies, drug prices and other medical costs. Results: Based on cost–effectiveness threshold of US$50,000 per quality-adjusted life year, HLA-B*5801-guided ULT selection or enhanced safety program was not cost effective. Avoidance of ULTs was the least preferred strategy as uncontrolled gout leads to lower quality-adjusted life years and higher costs. Conclusion: The analysis underscores the need for biomarkers with higher positive predictive value for SJS/TEN, less expensive genetic tests or safety programs, or more effective gout drugs. .
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