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Background: Alzheimer's disease (AD) is the most prevalent form of dementia, exerting substantial personal and societal impacts. The apolipoprotein E (APOE) ε4 allele is a known genetic factor that increases the risk of AD, contributing to more severe brain atrophy and exacerbated symptoms. Purpose: We aim to provide a comprehensive review of the impacts of the APOE ε4 allele on brain atrophy in AD and mild cognitive impairment (MCI) as a transitional stage of AD. Methods: We performed a coordinate-based meta-analysis of voxel-based morphometry (VBM) studies to identify the patterns of grey matter atrophy in APOE ε4 carriers vs. non-carriers. We obtained coordinate-based structural magnetic resonance imaging (MRI) data for 1135 individuals from 12 studies on PubMed and Google Scholar that met our inclusion criteria. Results: We found significant atrophy in the hippocampus and parahippocampus of APOE ε4 carriers compared to non-carriers, especially within the AD and MCI groups, while healthy controls showed no significant atrophy in these regions. Conclusion: Our meta-analysis sheds light on the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, emphasizing the allele's critical influence on neurodegeneration, especially in the hippocampus. Our findings contribute to the understanding of the disease's pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals with the APOE ε4 allele who are at risk for Alzheimer's Disease.
RESUMO
BACKGROUND: Acetaminophen-opioid analgesics are among the most commonly prescribed pain medications in pediatric orthopedic patients. However, these combined opioid analgesics do not allow for individual medication titration, which can increase the risk of opioid misuse and hepatoxicity from acetaminophen. The primary aim of this quality improvement project was to alter the prescribing habits of pediatric orthopedic providers at our institution from postoperative acetaminophen-opioid analgesics to independent acetaminophen and opioids. METHODS: The study took place in a level 1 trauma center at a children's hospital. A multidisciplinary team of health professionals utilized lean methodology to develop a project plan. Guided by a key driver diagram, we removed acetaminophen-oxycodone products from hospital formulary, implemented a revised inpatient and outpatient electronic order set, and conducted multiple education efforts. Outcomes included inpatient and outpatient percent combined acetaminophen-opioid orders by surgical providers over 27 months. RESULTS: Before the intervention, inpatient acetaminophen-opioid products accounted for an average of 46% of all opioid prescriptions for orthopedic patients. After the intervention and multiple educational efforts, we reported a reduction in the acetaminophen-opioid products to 2.9%. For outpatient prescriptions, combined analgesics accounted for 88% before the intervention, and we reported a reduction to 15% after the intervention. CONCLUSIONS: By removing acetaminophen-oxycodone products from hospital formulary, educating the medical staff, and employing revised electronic order sets, the prescribing practice of pediatric orthopedic surgeons changed from the routine use of acetaminophen-opioid analgesics to independent medications.