Citations

With most states lacking comprehensive legislation addressing overdose preparedness in schools, there is an urgent necessity for prompt and effective solutions that accommodate existing resource constraints. Arizona, the primary entry point for over 55% of US fentanyl trafficking, responded to this critical public health challenge by initiating the nation’s first unfunded grassroots collaboration between community and government sectors to enhance statewide school overdose prevention and preparedness. The School Training, Overdose Preparedness and Intelligence Task force (STOP-IT) included more than 60 volunteers from the health care, legal, education, local government and behavioral health fields and worked collaboratively with the Arizona Department of Education to develop a response. Within 6 months of inception, STOP-IT conducted a comprehensive school survey to identify barriers to naloxone accessibility, created evidence-based school policies, established a sustainable and complimentary naloxone supply chain for schools with an ordering platform, and implemented a statewide naloxone distribution plan. The amassed resources were organized into a Fentanyl and Overdose Response Toolkit, widely disseminated to more than 2000 public, private, and charter schools. Moreover, STOP-IT launched both a local and national public information campaign to effectively raise awareness about the opioid crisis in schools. Using various media channels such as webinars, podcasts, media broadcasts, newsletters, and peer-reviewed publications, the campaign successfully amplified its message and enhanced community engagement. The STOP-IT initiative emerged as an innovative collaboration between government and community leaders, united in their mission to combat the growing opioid crisis in schools.

Abstract Purpose: Chronic inflammation is integral to myeloproliferative neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among patients with MPN. Experimental Design: We randomly assigned patients with MPN to either a Mediterranean diet or standard U.S. Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four timepoints during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome. Results: The Mediterranean diet was as easy to follow for patients with MPN as the standard USDA diet. Approximately 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of ≥8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of ≥8 at any timepoint. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention. Conclusions: With dietician counseling and written education, patients with MPN can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially incorporated into the management of other hematologic conditions. Significance: Diet is a central tenant of management of chronic conditions characterized by subclinical inflammation, such as cardiovascular disease, but has not entered the treatment algorithm for clonal hematologic disorders. Here, we establish that a Mediterranean diet intervention is feasible in the MPN patient population and can improve symptom burden. These findings warrant large dietary interventions in patients with hematologic disorders to test the impact of diet on clinical outcomes.

Introduction Indolent systemic mastocytosis (ISM) is a rare clonal mast cell disease driven by the KIT D816V mutation in nearly all patients. Patients with ISM can present with debilitating acute and chronic cutaneous, gastrointestinal, neurocognitive, and systemic symptoms caused by the release of inflammatory mediators from abnormal mast cells. In some patients, symptoms are not adequately controlled with best supportive care (BSC) medications. Elenestinib (BLU-263) is a novel, investigational, oral, next-generation tyrosine kinase inhibitor that potently and selectively inhibits KIT D816V with limited central nervous system penetration and pharmacokinetics (PK) that support once daily dosing. HARBOR (NCT04910685) is a randomized, double-blind, placebo-controlled, phase 2/3 study assessing efficacy and safety of elenestinib in patients with ISM. Methods Eligible adult patients with ISM, confirmed following central review of bone marrow (BM) pathology, clinical, and laboratory findings per World Health Organization criteria and a moderate-to-severe symptom score based on minimum mean total symptom score (TSS) of the ISM-Symptom Assessment Form (ISM-SAF©2018), were stratified by baseline serum tryptase (<20 ng/mL vs ≥20 ng/mL) and randomly assigned 3:1 to elenestinib 25 mg, 50 mg, or 100 mg once daily + BSC (“elenestinib”) or placebo + BSC (“placebo”). The primary objective of Part 1 was to determine the recommended dose based on safety, PK, and pharmacodynamics. Secondary endpoints included changes in biomarkers of disease burden (serum tryptase, KIT D816V variant allele fraction [VAF], and BM mast cells) and ISM-SAF TSS. Three additional open-label PK groups enrolled patients at 50 mg, 75 mg, and 100 mg to further characterize PK and safety. Results As of data cutoff on July 3, 2023, a total of 122 patients with ISM have received their assigned treatment in Part 1 of the study; 39 were blinded and randomized to elenestinib or placebo, and 83 were treated with open-label elenestinib in the PK groups (21 patients at 50 mg, 34 patients at 75 mg, and 28 patients at 100 mg). Baseline demographics were similar to those reported for the general ISM population. After 12 weeks of therapy, symptom improvement was observed for all dose cohorts, and symptom reduction by TSS was greater for patients on elenestinib versus placebo in the blinded portion of Part 1. Patients receiving elenestinib at 25 mg, 50 mg, and 100 mg doses showed reduction (mean percent) from baseline for tryptase (-15.4%, -50.9%, and -68.4% vs 3.3%, respectively) and KIT D816VVAF (-37.5%, -70.3%, and -77.0% vs -2.5%, respectively) as compared to placebo. Similar reductions in TSS and disease-related biomarkers were observed in the open-label PK cohorts. After a median treatment duration of 35.3 weeks, elenestinib was well-tolerated at all dose levels. There were no treatment-related serious adverse events and no treatment-related adverse events that led to drug discontinuation. Conclusion Elenestinib at all tested doses demonstrated beneficial effects on disease-related symptoms and biomarkers of mast cell burden in this large and maturing cohort of patients with ISM with a moderate-to-severe symptom burden. Elenestinib was well tolerated across all dose levels with a promising early benefit-risk profile in ISM. These preliminary findings will inform dosing for the planned Part 2 of HARBOR, which will examine elenestinib versus placebo in a randomized, blinded, placebo-controlled setting.

Abstract Case reports of patients infected with COVID-19 and influenza virus (“flurona”) have raised questions around the prevalence and severity of coinfection. Using data from HHS Protect Public Data Hub, NCBI Virus, and CDC FluView, we analyzed trends in SARS-CoV-2 and influenza hospitalized coinfection cases and strain prevalences. We also characterized coinfection cases across the Mayo Clinic Enterprise from January 2020 to April 2022. We compared expected and observed coinfection case counts across different waves of the pandemic and assessed symptoms and outcomes of coinfection and COVID-19 monoinfection cases after propensity score matching on clinically relevant baseline characteristics. From both the Mayo Clinic and nationwide datasets, the observed coinfection rate for SARS-CoV-2 and influenza has been higher during the Omicron era (2021 December 14 to 2022 April 2) compared to previous waves, but no higher than expected assuming infection rates are independent. At the Mayo Clinic, only 120 coinfection cases were observed among 197,364 SARS-CoV-2 cases. Coinfected patients were relatively young (mean age: 26.7 years) and had fewer serious comorbidities compared to monoinfected patients. While there were no significant differences in 30-day hospitalization, ICU admission, or mortality rates between coinfected and matched COVID-19 monoinfection cases, coinfection cases reported higher rates of symptoms including congestion, cough, fever/chills, headache, myalgia/arthralgia, pharyngitis, and rhinitis. While most coinfection cases observed at the Mayo Clinic occurred among relatively healthy individuals, further observation is needed to assess outcomes among subpopulations with risk factors for severe COVID-19 such as older age, obesity, and immunocompromised status.

e19078 Background: Patients with myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), experience chronic disease-related symptoms. Surveying these patients while incorporating the MPN-Symptom Assessment Form (SAF) gains valuable insight. Independent surveys evaluating symptoms among MPN patients have seen disproportionate participation among females compared to males (upwards of 4:1). Though the general MPN patient population is roughly gender balanced, epidemiological studies show the occurrence of MPN types differ between men and women (MPN [%male]: PV [65%], ET [33%], MF [50%]. Mehta, et al. Leuk & Lymph 2014). In-clinic evaluations and international MPN surveys of disease-related symptoms suggest women report higher symptom burden on average compared to men, despite MPN type [Emanuel, et al. JCO 2012. Geyer, et al. Haematol 2017]. Further, a recent study across cancer trials showed women had a 34% increased risk of reporting severe symptoms [Unger, et al. JCO 2022]. This study aimed to evaluate gender imbalance in survey participation among MPN patient surveys and investigate its potential to overestimate symptom burden if gender is ignored. Methods: Five anonymous web-based surveys were used to assess the impact of disproportionate gender participation. The MPN-10 assessing the 10 most clinically meaningful SAF items was present in these surveys and generated the Total Symptom Score (TSS). Survey responses with no self-reported gender or ≥5 missing MPN-10 symptoms were excluded. Raking weights based on expected MPN population were applied at the survey- and MPN type-level. Relative bias of mean TSS was calculated to evaluate over- and underestimation due to this participation imbalance. Relative bias <5% is commonly acceptable. Results: There were 4962 survey participants total and 74% were female (Table). Epidemiologically expected gender frequency by MPN type was not seen (MPN [%male]: PV [31%], ET [15%], MF [37%]). The gender participation imbalance accounted for a 3.1% overestimation of overall TSS. This also resulted in a 6.8% underestimation of the mean difference in TSS between genders, across MPNs. Conclusions: Overall bias due to gender participation imbalance was relatively low. However, analyses considering gender differences were more impacted. Anonymous surveys should seek to reduce participation bias during the survey design phase. More research is needed to evaluate gender and other participation biases in surveys across cancer domains.[Table: see text]