A systematic review of economic evidence for community-based obesity prevention interventions in children

Multicomponent community-based obesity prevention interventions that engage multiple sectors have shown promise in preventing obesity in childhood; however, economic evaluations of such interventions are limited. This systematic review explores the methods used and summarizes current evidence of costs and cost-effectiveness of complex obesity prevention interventions. A systematic search was conducted using 12 academic databases and grey literature from 2006 to April 2022. Studies were included if they reported methods of costing and/or economic evaluation of multicomponent, multisectoral, and community-wide obesity prevention interventions. Results were reported narratively based on the Consolidated Health Economic Evaluation Reporting Standards. Seventeen studies were included, reporting costing or economic evaluation of 13 different interventions. Five interventions reported full economic evaluations, five interventions reported economic evaluation protocols, two interventions reported cost analysis, and one intervention reported a costing protocol. Five studies conducted cost-utility analysis, three of which were cost-effective. One study reported a cost-saving return-on-investment ratio. The economic evidence for complex obesity prevention interventions is limited and therefore inconclusive. Challenges include accurate tracking of costs for interventions with multiple actors, and the limited incorporation of broader benefits into economic evaluation. Further methodological development is needed to find appropriate pragmatic methods to evaluate complex obesity prevention interventions.     

Frequent PIK3CA mutation in normal endometrial gland drives spheroid formation and may be involved in stem cell propagation

Recent studies reported the presence of oncogenic mutations in normal endometrial glands, but the biological significance remains unclear. The present study investigated the status of KRAS/PIK3CA driver mutations in normal endometrial glands as well as spheroids derived from single glands. The normal endometria of surgically removed uteri (n = 3) were divided into nine regions, and 40 endometrial single glands were isolated from each region. The DNAs of 10 glands in each region were extracted and subjected to Sanger sequencing for KRAS or PIK3CA driver mutations, while the remaining 30 glands were conferred to a long-term spheroid culture, followed by Sanger sequencing. Immunohistochemical analyses of stem cell (Axin2, ALDH1A1, SOX9) markers were undertaken for spheroids. Sanger sequencing successfully detected oncogenic mutations of KRAS or PIK3CA in a single gland. Twenty-five of the 270 glands (9.3%) had mutations in either KRAS or PIK3CA, and the mutation frequency in each endometrial region varied from 0% to 50%. The droplet digital PCR showed high mutation allele frequency (MAF) of PIK3CA mutation, suggestive of clonal expansion of mutated cells within a gland. Over 60% of the collected spheroids had PIK3CA mutations, but no KRAS mutations were detected. Immunohistochemically, spheroids were mainly composed of cells with stem cell marker expressions. High MAF of PIK3CA mutation in a single gland as well as frequent PIK3CA mutation in stem cell-rich spheroids that originated from a single gland suggest the role of PIK3CA mutation in stem cell propagation. This information could improve our understanding of endometrial physiology as well as stem cell-oriented endometrial regeneration and carcinogenesis.     

Aducanumab for the treatment of Alzheimer's disease: a systematic review

Aducanumab is a novel disease-modifying anti-amyloid-beta (Aβ) human monoclonal antibody specifically targeted to the pathophysiology of Alzheimer's disease (AD). It was granted for treating AD in June 2021 by the United States Food and Drug Administration. We systematically analyzed available trials to evaluate the efficacy and safety of aducanumab treating AD. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. We conducted an extensive literature search using the electronic databases MEDLINE through PubMed, EMBASE, Cochrane, Web of Science, and Scopus for suitable studies on aducanumab. We considered human clinical trials of aducanumab, assessing its efficacy and adverse effects in treating AD, excluding any experimental animal studies. We included three randomised controlled trials. Studies reported that aducanumab reduced brain amyloid-beta plaques in a time- and dose-dependent manner (dose–response, P < 0.05) and a slowed decline in cognition (22% reduction) in the high-dose treated group, difference of −0.39 versus placebo in Clinical Dementia Rating Scale Sum Boxes (95% CI, −0.69 to −0.09; P = 0.012) along with a reduced amyloid positron emission tomography standard uptake value ratio score (P < 0.001) and plasma p181-tau (phosphorylated tau) level. Amyloid-related imaging abnormality was reported as a serious adverse event and was profound in high-dose treated group (425/1029 in 10 mg/kg). Aducanumab has been reported to affect two main pathophysiologic hallmarks (Aβ and tau) of AD. We suggest future studies addressing aducanumab's efficacy and safety to confirm that the benefit of this drug outweighs the risk.