Developing the IDCaRe team: an integrated and culturally-affirming approach to improving health engagement for HIV-positive veterans.

BACKGROUND: Veterans Health Administration (VHA) has been at the forefront of offering integrated and patient-centered care to address the complex needs of more than 30,000 Veterans with HIV in the United States of America. These Veterans present with diverse cultural identities, personal values, and goals pertinent to their care, and they are often managing multiple comorbid chronic conditions, mental health diagnoses, and psychosocial stressors alongside HIV. The quality of their care has often been affected by stigma, minority stress, and the quality of the patient-provider relationship and associated collaborations over treatment approaches and goals, which has a direct effect on outcomes. OBJECTIVE: At San Francisco VA Health Care System, the Infectious Disease Care and Resilience (IDCaRe) team was established to improve outcomes for Veterans with acute needs or persistent difficulties in care delivery and efficacy. METHOD: A five-step model to address complex needs in HIV care was adapted from existing literature and evidence base, combined with a culturally-aligned, interdisciplinary care orientation. This model was implemented with patients determined to be at high-risk for poor health engagement. A representative composite case study demonstrates the process. RESULTS: Three Veterans underwent the intervention with results presented. Lessons learned and future discussions are also discussed. CONCLUSION: The IDCaRe model has promise as an integrated, patient-centered, behaviorally-grounded intervention for improving HIV-related care outcomes for Veterans with complex needs.

Impact of Apolipoprotein E ε4 in Alzheimer's Disease: A Meta-Analysis of Voxel-Based Morphometry Studies.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is the most-prevalent form of dementia and imposes substantial burdens at the personal and societal levels. The apolipoprotein E (APOE) ε4 allele is a genetic factor known to increase AD risk and exacerbate brain atrophy and its symptoms. We aimed to provide a comprehensive review of the impacts of APOE ε4 on brain atrophy in AD as well as in mild cognitive impairment (MCI) as a transitional stage of AD. METHODS: We performed a coordinate-based meta-analysis of voxel-based morphometry studies to compare gray-matter atrophy patterns between carriers and noncarriers of APOE ε4. We obtained coordinate-based structural magnetic resonance imaging data from 1,135 individuals who met our inclusion criteria among 12 studies reported in PubMed and Google Scholar. RESULTS: We found that atrophy of the hippocampus and parahippocampus was significantly greater in APOE ε4 carriers than in noncarriers, especially among those with AD and MCI, while there was no significant atrophy in these regions in healthy controls who were also carriers. CONCLUSIONS: The present meta-analysis has highlighted the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, which emphasizes the critical influence of the allele on neurodegeneration, especially in the hippocampus. These findings improve the understanding of AD pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals at risk of AD who carry the APOE ε4 allele.

The impact of APOE ε4 in Alzheimer's disease: a meta-analysis of voxel-based morphometry studies.

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.

Chitinase 3-like-1 (CHI3L1) in the pathogenesis of epidermal growth factor receptor mutant non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for 85 % of all lung cancers. In NSCLC, 10-20 % of Caucasian patients and 30-50 % of Asian patients have tumors with activating mutations in the Epidermal Growth Factor Receptor (EGFR). A high percentage of these patients exhibit favorable responses to treatment with tyrosine kinase inhibitors (TKI). Unfortunately, a majority of these patients develop therapeutic resistance with progression free survival lasting 9-18 months. The mechanisms that underlie the tumorigenic effects of EGFR and the ability of NSCLC to develop resistance to TKI therapies, however, are poorly understood. Here we demonstrate that CHI3L1 is produced by EGFR activation of normal epithelial cells, transformed epithelial cells with wild type EGFR and cells with cancer-associated, activating EGFR mutations. We also demonstrate that CHI3L1 auto-induces itself and feeds back to stimulate EGFR and its ligands via a STAT3-dependent mechanism(s). Highly specific antibodies against CHI3L1 (anti-CHI3L1/FRG) and TKI, individually and in combination, abrogated the effects of EGFR activation on CHI3L1 and the ability of CHI3L1 to stimulate the EGFR axis. Anti-CHI3L1 also interacted with osimertinib to reverse TKI therapeutic resistance and induce tumor cell death and inhibit pulmonary metastasis while stimulating tumor suppressor genes including KEAP1. CHI3L1 is a downstream target of EGFR that feeds back to stimulate and activate the EGFR axis. Anti-CHI3L1 is an exciting potential therapeutic for EGFR mutant NSCLC, alone and in combination with osimertinib or other TKIs.

A Quality Improvement Project to Reduce Combination Acetaminophen-opioid Prescriptions to Pediatric Orthopedic Patients.

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.