Ascertaining Whether an Intelligent Voice Assistant Can Meet Older Adults' Health-Related Needs in the Context of a Geriatrics 5Ms Framework.

The Geriatrics 5Ms: Medications, Mind, Mobility, what Matters most and Multicomplexity is a framework to address the complex needs of older adults. Intelligent Voice Assistants (IVAs) are increasingly popular and have potential to support health-related needs of older adults. We utilized previously collected qualitative data on older adults' views of how an IVA may address their health-related needs and ascertained their fit into the Geriatrics 5Ms framework. The codes describing health challenges and potential IVA solutions fit the framework: (1) Medications: difficulty remembering medications. SOLUTION: reminders. (2) Mind: isolation, anxiety, memory loss. SOLUTION: companionship, memory aids. (3) Mobility: barriers to exercise. SOLUTION: incentives, exercise ideas. (4) Matters most: eating healthy foods. SOLUTION: suggest and order nutritious foods, (5) Multicomplexity; managing multimorbidity. SOLUTION: symptom tracking and communicating with health care professionals. Incorporating the 5Ms framework into IVA design can aid in addressing health care priorities of older adults.

Cannabis use for Sleep Disturbance Among Older Patients in a Geriatrics Clinic.

Cannabis use is growing among older adults to manage medical concerns including poor sleep. In this study, we characterized how patients seen at a geriatrics clinic use cannabis to address sleep disturbance. Specifically, we conducted an anonymous survey of 568 adults, including 83 who reported cannabis use within the past 3 years, to inquire about such use. We compared cannabis use characteristics between those using it for sleep disturbance versus all other conditions. We considered a p-value <.10 to be statistically significant. Among the cannabis users in our sample, 29% reported using cannabis for sleep disturbance (N = 24). They were more likely than other users to be female (p = .07), consume cannabis more frequently (p = .01), use products containing tetrahydrocannabinol (THC) (vs. cannabidiol [CBD]-only; p < .01), and use cannabis to target more symptoms (p < .01). As cannabis use continues to grow in older populations, it is essential to delineate better how cannabis may be used safely and effectively to improve older adults' sleep health.

Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor.

Recent progress in targeting KRASG12C has provided both insight and inspiration for targeting alternative KRAS mutants. In this study, we evaluated the mechanism of action and anti-tumor efficacy of MRTX1133, a potent, selective and non-covalent KRASG12D inhibitor. MRTX1133 demonstrated a high-affinity interaction with GDP-loaded KRASG12D with KD and IC50 values of ~0.2 pM and <2 nM, respectively, and ~700-fold selectivity for binding to KRASG12D as compared to KRASWT. MRTX1133 also demonstrated potent inhibition of activated KRASG12D based on biochemical and co-crystal structural analyses. MRTX1133 inhibited ERK1/2 phosphorylation and cell viability in KRASG12D-mutant cell lines, with median IC50 values of ~5 nM, and demonstrated >1,000-fold selectivity compared to KRASWT cell lines. MRTX1133 exhibited dose-dependent inhibition of KRAS-mediated signal transduction and marked tumor regression (≥30%) in a subset of KRASG12D-mutant cell-line-derived and patient-derived xenograft models, including eight of 11 (73%) pancreatic ductal adenocarcinoma (PDAC) models. Pharmacological and CRISPR-based screens demonstrated that co-targeting KRASG12D with putative feedback or bypass pathways, including EGFR or PI3Kα, led to enhanced anti-tumor activity. Together, these data indicate the feasibility of selectively targeting KRAS mutants with non-covalent, high-affinity small molecules and illustrate the therapeutic susceptibility and broad dependence of KRASG12D mutation-positive tumors on mutant KRAS for tumor cell growth and survival.

Cannabis: An Emerging Treatment for Common Symptoms in Older Adults.

BACKGROUND/OBJECTIVES: Use of cannabis is increasing in a variety of populations in the United States; however, few investigations about how and for what reasons cannabis is used in older populations exist. DESIGN: Anonymous survey. SETTING: Geriatrics clinic. PARTICIPANTS: A total of 568 adults 65 years and older. INTERVENTION: Not applicable. MEASUREMENTS: Survey assessing characteristics of cannabis use. RESULTS: Approximately 15% (N = 83) of survey responders reported using cannabis within the past 3 years. Half (53%) reported using cannabis regularly on a daily or weekly basis, and reported using cannabidiol-only products (46%). The majority (78%) used cannabis for medical purposes only, with the most common targeted conditions/symptoms being pain/arthritis (73%), sleep disturbance (29%), anxiety (24%), and depression (17%). Just over three-quarters reported cannabis "somewhat" or "extremely" helpful in managing one of these conditions, with few adverse effects. Just over half obtained cannabis via a dispensary, and lotions (35%), tinctures (35%), and smoking (30%) were the most common administration forms. Most indicated family members (94%) knew about their cannabis use, about half reported their friends knew, and 41% reported their healthcare provider knowing. Sixty-one percent used cannabis for the first time as older adults (aged ≥61 years), and these users overall engaged in less risky use patterns (e.g., more likely to use for medical purposes, less likely to consume via smoking). CONCLUSION: Most older adults in the sample initiated cannabis use after the age of 60 years and used it primarily for medical purposes to treat pain, sleep disturbance, anxiety, and/or depression. Cannabis use by older adults is likely to increase due to medical need, favorable legalization, and attitudes.