Associations Between General Vaccine Hesitancy and Healthcare Access Among Arkansans.

BACKGROUND: Vaccines provide protection against numerous diseases that can cause serious illness and death. However, vaccine hesitancy threatens to undermine progress in reducing preventable diseases and illness. Vaccine hesitancy has been shown to vary by sociodemographic characteristics. However, studies examining associations between healthcare access and vaccine hesitancy are lacking. OBJECTIVE: Using a statewide random sample of Arkansas adults, we examined the relationship between general vaccine hesitancy and healthcare access. DESIGN: From July 12 to 30, 2021, participants were contacted by landlines and cellular phones using random digit dialing. PARTICIPANTS: A total of 1500 Arkansas adults were surveyed. Black/African American and Hispanic/Latinx adults were oversampled to ensure adequate representation. The survey had a cooperation rate of 20%. MAIN MEASURES: The dependent variable was an ordinal measure of general vaccine hesitancy. Age, gender, race, education, relationship status, and rural/urban residence were included in the model. Healthcare access was measured across four domains: (1) health insurance coverage; (2) having a primary care provider (PCP); (3) forgoing care due to cost; and (4) time since last routine checkup. The relationship between general vaccine hesitancy and healthcare access was modeled using ordinal logistic regression, controlling for sociodemographic characteristics. KEY RESULTS: Mean age was 48.5 years, 51.1% were women, 28% reported a race other than White, and 36.3% held a bachelor's degree or higher. Those with a PCP and those with health insurance had approximately two-thirds the odds of being more hesitant ([OR=0.63, CI=0.47, 0.84] and [OR=0.68; CI=0.49, 0.94]) than those without a PCP and those without health insurance. Participants reporting a routine checkup in the last 2 years were almost half as likely to be more hesitant than those reporting a checkup more than 2 years prior (OR=0.58; CI=0.43, 0.79). CONCLUSIONS: Results suggest improving access to health insurance, PCPs, and routine preventative care services may be critical to reducing vaccine hesitancy.

Associations between COVID-19 Death Exposure and COVID-19 Vaccine Hesitancy and Vaccine Uptake.

OBJECTIVES: The aim of the study was to determine the relation between coronavirus disease 2019 (COVID-19) death exposure and COVID-19 vaccine hesitancy and vaccine uptake among Arkansans, controlling for sociodemographic factors. METHODS: Data were collected from a telephone survey administered in Arkansas between July 12 and July 30, 2021 (N = 1500) via random digit dialing of telephone landlines and cellular telephones. Weighted data were used to estimate regressions. RESULTS: Controlling for sociodemographic variables, COVID-19 death exposure was not a significant predictor of COVID-19 vaccine hesitancy (P = 0.423) or COVID-19 vaccine uptake (P = 0.318). Younger individuals, those with lower levels of education, and those who live in rural counties were more likely to be COVID-19 vaccine hesitant. Older individuals, Hispanic/Latinx individuals, those who reported higher levels of education, and those who reported living in urban counties were more likely to have reported receiving the COVID-19 vaccine. CONCLUSIONS: Many efforts to promote COVID-19 vaccines have focused on prosocial norms, including encouraging vaccination to protect the community from COVID-19 infection and death; however, COVID-19 death exposure was not related to COVID-19 vaccine hesitancy or uptake in the present study. Future research should examine whether prosocial messaging is effective in decreasing hesitancy or motivating some individuals to receive the vaccine among those who have been exposed to COVID-19 deaths.

Four-Year Disease-Free Remission in a Patient With POLE Mutation-Associated Colorectal Cancer Treated Using Anti-PD-1 Therapy.

The stability of the human genome depends upon a delicate balance between replication by high- and low-fidelity DNA polymerases. Aberrant replication by error-prone polymerases or loss of function of high-fidelity polymerases predisposes to genetic instability and, in turn, cancer. DNA polymerase epsilon (Pol ε) is a high-fidelity, processive polymerase that is responsible for the majority of leading strand synthesis, and mutations in Pol ε have been increasingly associated with various human malignancies. The clinical significance of Pol ε mutations, including how and whether they should influence management decisions, remains poorly understood. In this report, we describe a 24-year-old man with an aggressive stage IV high-grade, poorly differentiated colon carcinoma who experienced a dramatic response to single-agent checkpoint inhibitor immunotherapy after rapidly progressing on standard chemotherapy. His response was complete and durable and has been maintained for more than 48 months. Genetic testing revealed a P286R mutation in the endonuclease domain of POLE and an elevated tumor mutational burden of 126 mutations per megabase, both of which have been previously associated with response to immunotherapy. Interestingly, tumor staining for PD-L1 was negative. This case study highlights the importance of genetic profiling of both early and late-stage cancers, the clinical significance of POLE mutations, and how the interplay between genetic instability and immune-checkpoint blockade can impact clinical decision-making.

COVID-19 Death Exposure among Adults in the United States.

As of May 17, 2022, more than a million deaths due to COVID-19 have been recorded in the US. For each COVID-19 death, there are an estimated nine bereaved family members and an unknown number of bereaved friends. This study aimed to assess the correlates of self-reported COVID-19 death exposure (i.e., loss of a close friend or family member) among US adults using online survey data (n = 1,869) collected between September 17, 2021 and October 3, 2021. One in four US adults in this national sample reported the loss of a close friend or family member due to COVID-19. The odds of losing a close friend or family member due to COVID-19 death were greater for those age 60 or older, all minoritized racial/ethnic groups except for Asian American respondents, married/coupled respondents, those who had foregone care due to cost in the past year, and those who reported a COVID-19 infection.

[CrIII8NiII6]n+ Heterometallic Coordination Cubes.

Three new heterometallic [CrIII8NiII6] coordination cubes of formulae [CrIII8NiII6L24(H2O)12](NO3)12 (1), [CrIII8NiII6L24(MeCN)7(H2O)5](ClO4)12 (2), and [CrIII8NiII6L24Cl12] (3) (where HL = 1-(4-pyridyl)butane-1,3-dione), were synthesised using the paramagnetic metalloligand [CrIIIL3] and the corresponding NiII salt. The magnetic skeleton of each capsule describes a face-centred cube in which the eight CrIII and six NiII ions occupy the eight vertices and six faces of the structure, respectively. Direct current magnetic susceptibility measurements on (1) reveal weak ferromagnetic interactions between the CrIII and NiII ions, with JCr-Ni = + 0.045 cm-1. EPR spectra are consistent with weak exchange, being dominated by the zero-field splitting of the CrIII ions. Excluding wheel-like structures, examples of large heterometallic clusters containing both CrIII and NiII ions are rather rare, and we demonstrate that the use of metalloligands with predictable bonding modes allows for a modular approach to building families of related polymetallic complexes. Compounds (1)-(3) join the previously published, structurally related family of [MIII8MII6] cubes, where MIII = Cr, Fe and MII = Cu, Co, Mn, Pd.

Undiagnosed Hypertension and Undiagnosed Type 2 Diabetes among Overweight and Obese Marshallese Participants in a Diabetes Prevention Program.

Hypertension and type 2 diabetes (T2D) are major public health issues that disproportionately affect minority communities, including Native Hawaiians and Pacific Islanders (NHPI). Minority communities are also more likely to have undiagnosed hypertension and T2D. Marshallese Pacific Islanders have been shown to have high proportions of diagnosed and undiagnosed hypertension and T2D. Using survey and biometric data collected from 378 overweight/obese Marshallese Pacific Islander adults, this study documents the prevalence of hypertension and T2D, as well as the prevalence of undiagnosed hypertension and T2D. The study also examines associations between undiagnosed hypertension and undiagnosed T2D and age group, sex, health care access (defined by foregone care due to cost and health insurance status), and body mass index (BMI). Among participants with blood pressure readings indicative of hypertension, 68.4% were undiagnosed, and among participants with HbA1c indicative of T2D, 31.6% were undiagnosed. A quarter of participants (24.5%) had blood pressure and HbA1c measures indicative of both undiagnosed hypertension and undiagnosed T2D. Undiagnosed hypertension was significantly associated with age group (p's<0.0001) and sex (p=0.028). Undiagnosed T2D was significantly associated with age group (p's<0.05), forgone care due to cost (p=0.018), health insurance status (p=0.035), and BMI (p=0.001). Participants in this study had high proportions of undiagnosed hypertension and undiagnosed T2D. These findings will be immediately useful for those working to address hypertension and T2D disparities among Marshallese and other NHPI populations.

Bemarituzumab with modified FOLFOX6 for advanced FGFR2-positive gastroesophageal cancer: FIGHT Phase III study design.

Bemarituzumab is an afucosylated monoclonal antibody against FGFR2b (a FGF receptor) with demonstrated monotherapy clinical activity in patients with late-line gastric cancer whose tumors overexpress FGFR2b (NCT02318329). We describe the rationale and design of the FIGHT trial (NCT03343301), a global, randomized, double-blind, placebo-controlled Phase III study evaluating the role of bemarituzumab in patients with previously untreated, FGFR2b-overexpressing advanced gastroesophageal cancer. Patients are randomized in a blinded fashion to the combination of mFOLFOX6 and bemarituzumab or mFOLFOX6 and placebo. Eligible patients are selected based on the presence of either FGFR2b protein overexpression determined by immunohistochemistry or FGFR2 gene amplification determined by circulating tumor DNA. The primary end point is overall survival, and secondary end points include progression-free survival, objective response rate and safety.

A single-arm, retrospective analysis of the incidence of febrile neutropenia using same-day versus next-day pegfilgrastim in patients with gastrointestinal cancers treated with FOLFOX or FOLFIRI.

BACKGROUND: Practice patterns of same-day versus next-day pegfilgrastim vary in numerous practice settings across the country. Current utilization with same-day pegfilgrastim reduced overall visits and reduced treatment time for chemotherapy administration. OBJECTIVE: To assess the efficacy and safety of same-day versus next-day pegfilgrastim in patients with colorectal cancer. METHODS: Patient data was extracted through electronic health records (EHR) search of ICD-9 codes that matched patients with CRC and treated with FOLFOX or FOLFIRI from November 2013 to January 2016. The incidence rates of primary and secondary endpoints were estimated for patients who received either FOLFOX or FOLFIRI and same-day pegfilgrastim with 2-sided 95% confidence intervals. Fisher's exact test for 2 × 2 contingency tables was used to compare the incidence of primary and secondary endpoints between the two study groups performed at the α = 0.05 significance level. A study by Hecht et al. served as a historical control for next-day pegfilgrastim. RESULTS: A total of 109 out of an initial 330 patients with appropriate ICD-9 criteria were eligible for study inclusion. The primary endpoint of incidence of FN recorded over 4 chemotherapy cycles with either FOLFOX6 or FOLFIRI occurred in 3.7% of patients (95% CI, 1.1-9.4%). Secondary endpoints also occurred with a relatively low incidence: 13 patients developed grades 3/4 neutropenia (11.9%; 95% CI, 7.0-19.5%); 11 patients required dose reductions because of neutropenia or FN (10.1%; 95% CI, 5.6-17.3%); and 5 patients were hospitalized due to neutropenia or FN (4.6%; 1.7-10.6%). There were 4 reported events of FN (3.2%; 95% CI, 1.0-8.3%) for those who received next-day pegfilgrastim compared to 11 events in the placebo group (9.4%; 95% CI, 5.1-16.4%). The incidence of dose delays or dose reductions due to neutropenia or FN were 5 (4.1%, 95% CI, 1.5-9.4%) in the next-day pegfilgrastim group versus 26 (22.1%, 95% CI, 15.5-30.4%) in the placebo group. LIMITATIONS: The study was retrospective in design and utilized a historical control for the comparator. CONCLUSIONS: Our study results suggest that same-day pegfilgrastim administration may be a safe and effective alternative to 24-h post-chemotherapy administration in patients with esophageal, gastric, appendiceal, or colorectal cancer undergoing treatment with FOLFOX or FOLFIRI.

Integrating STEADI for Falls Prevention in Outpatient Rehabilitation Clinics: An Outcomes Evaluation Using the RE-AIM Framework.

BACKGROUND AND OBJECTIVES: The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework was used to describe the implementation of the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) Initiative (2018-2021) for screening and assessing all older adults ≥65 years for falls risk across 34 outpatient rehabilitation clinics within a large health system. RESEARCH DESIGN AND METHODS: We described the Implementation process and strategies. Using Electronic Health Records (EHRs), we identified Reach, Adoption, and Maintenance of screenings and physical assessments to identify fall risk among older adults. RESULTS: STEADI Implementation strategies included health system mandates, EHR revisions, email instructions, educational sessions and resources, clinical leads and champions, and chart audits. Reach: 76.4% (50,023) had a completed screening, and 44.1% screened at risk for falls. Adoption: Clinic-level adoption varied, with most performing screenings. Profession-level adoption was highest for physical therapists (PTs; 94.2% initiated, 80.6% completed) and lowest for speech-language pathologists (SLPs; 79.8% initiated, 55.9% completed). Reach and Adoption of functional outcomes measures (FOM): PTs completed an FOM on 59.5% of at-risk patients, occupational therapists on 11.6%, and SLPs on 7.9%. Maintenance: All measures declined 1%-10% annually between 2018 and 2021. DISCUSSION AND IMPLICATIONS: STEADI screening and FOMs were implemented systemwide in 34 outpatient rehabilitation clinics, reaching over 50,000 older adults. Screening adoption rates varied by clinic. PTs had the highest adoption rate. All adoption rates declined over time. Future research should consider an implementation science approach with input from key partners before implementation to identify barriers and develop strategies to support STEADI in outpatient rehabilitation.

Racial Misclassification, Discrimination, Consciousness, and Self-Rated Health Among Native Hawaiian and Pacific Islander Adults in the USA.

BACKGROUND: Medical researchers have historically utilized the variable of race uncritically, rarely defining race, rarely acknowledging it as a social construct, and often omitting information about how it was measured. In this study, we use the following definition of race: "a system of structuring opportunity and assigning value based on the social interpretation of how one looks." We examine the influence of racial misclassification, racial discrimination, and racial consciousness on the self-rated health of Native Hawaiian and Pacific Islanders (NHPI) living in the United States of America (USA). METHODS: Our analysis used online survey data from a subgroup of NHPI adults living in the USA (n = 252) who were oversampled as part of a larger study of US adults (N = 2022). Respondents were recruited between September 7, 2021 and October 3, 2021, from an online opt-in panel of individuals across the USA. Statistical analyses include weighted and unweighted descriptive statistics for the sample, as well as a weighted logistic regression for poor/fair self-rated health. RESULTS: Odds of poor/fair self-rated health were greater for women (OR = 2.72; 95% CI [1.19, 6.21]) and those who experienced racial misclassification (OR = 2.90; 95% CI [1.20, 7.05]). No other sociodemographic, healthcare, or race-related variables were significantly associated with self-rated health in the fully adjusted results. CONCLUSIONS: Findings suggest that racial misclassification may be an important correlate of self-rated health among NHPI adults in the US context.

Hesitant adopters: COVID-19 vaccine hesitancy among diverse vaccinated adults in the United States.

Background: Despite the United States (US) having an abundant supply of COVID-19 vaccines, vaccination rates lag behind other high-income countries, suggesting that vaccine hesitancy and attitudes play a greater role in public health measures than pure supply and access. With the acknowledgment that vaccination attitudes and status may or may not be correlated, this study examined COVID-19 vaccine hesitancy among vaccinated US adults by asking: 1) What is the prevalence of COVID-19 vaccine hesitancy among the vaccinated? 2) Does COVID-19 vaccine hesitancy vary across sociodemographic characteristics? 3) Does COVID-19 vaccine hesitancy vary by healthcare access and influenza vaccination over the past 5 years? Methods: Data were collected through an online survey of 2022 US adults with a final analytic sample of 1383 vaccinated respondents. Results: Overall, 48.8% of vaccinated adults reported some level of hesitancy, while a slight majority reported they were "not at all hesitant". Younger respondents, women, and Black and American Indian or Alaska Native participants had greater adjusted odds of being more hesitant towards receiving the COVID-19 vaccine. Respondents who had a primary care physician had greater adjusted odds than those who did not have a primary care physician of being more hesitant towards receiving the COVID-19 vaccine. Conclusions: This is the first population-based national sample study examining COVID-19 vaccine hesitancy among vaccinated individuals from subgroups of distinctive backgrounds in order to inform targeted strategies for reducing vaccine hesitancy. Findings can assist in efforts to increase vaccination rates and also decrease vaccine hesitancy at the national level.

COVID-19 Vaccine Hesitancy and Experiences of Discrimination Among Black Adults.

Early in the COVID-19 vaccine rollout, Black adults consistently reported more hesitancy than White adults, but few studies have examined variation in hesitancy among Black adults or its associations with racial discrimination. Data were collected from Black Arkansas residents age 18 and older (n = 350) between July 12th and July 30th, 2021, as part of a larger survey of Arkansans (N = 1500). Participants were recruited through random digit dialing of both landline and cell phones, with oversampling of Black and Hispanic residents. Respondents reported COVID-19 vaccine hesitancy, sociodemographic information, influenza vaccination history, pandemic-related experiences, and experiences of racial discrimination. Almost half (48.9%) of Black adults in Arkansas were not hesitant towards COVID-19 vaccines, while the remainder reported some level of hesitancy. Nearly a quarter were very hesitant (22.4%), while fewer reported being somewhat (14.0%) and a little (14.7%) hesitant. Using an ordered logistic regression with partial proportional odds, we find odds of COVID-19 vaccine hesitancy decreased as age and influenza vaccination increased. Odds of COVID-19 vaccine hesitancy were 1.70 times greater for Black adults who experienced the death of a close friend/family member due to COVID-19 and 2.61 times greater for individuals reporting discrimination with police or in the courts. Within-group analysis revealed nearly half of Black adults did not report any COVID-19 vaccine hesitancy and heterogeneity among those who were hesitant. Findings suggest there may be an important link between racial discrimination in the criminal justice system and COVID-19 vaccine hesitancy among Black adults.

Lessons learned from the pilot family model of diabetes self-management intervention in the Republic of the Marshall Islands.

Background: The Republic of the Marshall Islands (RMI) has a high rate of type 2 diabetes mellitus (T2DM). To address the high rate of T2DM, we tested a culturally adapted family model of diabetes self-management education and support (F-DSMES). We report the results of the 12-month post-intervention data collection and describe the lessons learned from the delivery of the F-DSMES intervention. Methods: Recruitment took place in four churches in Majuro and included 10 h of content delivered over 8-10 weeks. Forty-one participants with T2DM were included. The primary study outcome was glycemic control measured by a change in HbA1c. We also conducted participant interviews to document the participant-reported barriers encountered during the F-DSMES intervention. Results: Participants did not show improvements in their biometric markers; however, participants did show improvement on multiple measures of diabetes knowledge and family support. We identified five areas to improve future interventions: 1) issues with recruitment, retention, and attendance; 2) needing help accessing information and additional healthcare provider counseling; 3) struggles with adhering to diet recommendations; 4) difficulty getting exercise, and 5) improving lessons within the intervention. Conclusion: Although the biomarker data did not show improvement, valuable information was gained to improve the development of larger-scale trials. The results provide evidence of the need for these trials and the desire of participants to continue pursuing this effort. Others doing similar work in other low-to-middle income countries will need to take into consideration the potential barriers and facilitators within participants' social and physical environments.

Precision Medicine in Biliary Tract Cancer.

Precision medicine has become a dominant theme in the treatment of biliary tract cancers (BTCs). Although prognosis remains poor, technologies for improved molecular characterization along with the US Food and Drug Administration approval of several targeted therapies have changed the therapeutic landscape of advanced BTC. The hallmark of BTC oncogenesis is chronic inflammation of the liver and biliary tract regardless of the anatomical subtype. Subtypes of BTC correspond to distinct molecular characteristics, making BTC a molecularly heterogenous collection of tumors. Collectively, up to 40% of BTCs harbor a potentially targetable molecular abnormality, and the National Comprehensive Cancer Network guidelines recommend molecular profiling for all patients with advanced BTC. Use of circulating tumor DNA, immunohistochemistry, and next-generation sequencing continues to expand the utility for biomarker-driven management and molecular monitoring of BTC. Improving outcomes using biomarker-agnostic treatment for nontargetable tumors also remains a priority, and combinational treatment strategies such as immune checkpoint inhibition plus chemotherapy hold promise for this subgroup of patients.

Experiences of Marshallese Food Processing Workers during the COVID-19 Pandemic.

The goal of this study was to conduct an exploratory assessment of COVID-19 mitigation steps and compare workplace experiences during the COVID-19 pandemic with Marshallese workers in other occupations. Marshallese adults residing in the continental United States (US) and Hawaii took part in an online survey. The sample was divided into two categories: food processing workers and workers in all other occupations. To examine differences between food processing workers and workers from all other occupations, we used Wilcoxon-Mann-Whitney U tests and Fisher's Exact tests. Of those employed at the time of the survey (n = 113), 31 were employed in food processing plants, and 82 were employed in another occupation. Food processing workers and workers in other occupations differed significantly on level of education, length of residence in the US, English-speaking ability, and health literacy. More food processing workers reported that their employers installed barriers or provided shields (45%), provided temperature screenings (71%), and tested for COVID-19 (61%) compared with those in other occupations. A larger proportion of food processing workers reported having no sick leave compared with workers in other occupations, although they reported COVID-19 testing and being insured at similar rates. This is the first study to examine Marshallese food processing workers' experiences during the COVID-19 pandemic. Our findings show that while some food processing employers implemented government-recommended guidelines to prevent the spread of COVID-19, preventative and protective measures were not comprehensively applied across the food processing industry, despite efforts by public health agencies and community partners.

Associations between 5-year influenza vaccination and sociodemographic factors and healthcare access among Arkansans.

Despite wide availability, only 50.2% of the United States (US) adult population and 50.3% of adult Arkansans were vaccinated for influenza during the 2020-2021 influenza season. The proportion of the population vaccinated for influenza varies by age, sex, race/ethnicity, education, rural/urban residence, and income. However, measures of healthcare access have not been adequately investigated as predictors of influenza vaccination. Using a large, statewide random sample, this study examined 5-year influenza vaccination among Arkansans by sociodemographic characteristics (age, sex, race/ethnicity, education, rural/urban residence), general vaccine hesitancy, and healthcare access (having a primary care provider, having health insurance, forgoing health care due to cost, and frequency of doctor checkups). Older age, being female, being Hispanic, having a bachelor's degree or higher, having a primary care provider, visiting a doctor for a checkup in the past two years, and lack of hesitancy towards vaccines were significant predictors of receiving influenza vaccination.

Examining the Relationship Between Physical Activity and Self-Efficacy for Exercise Among Overweight and Obese Marshallese Adults.

This study examined associations between physical activity frequency and self-efficacy for exercise (SEE) among Marshallese adults in the United States. Data were collected from overweight and obese Marshallese participants (N = 378) enrolled in a Diabetes Prevention Program trial. Logistic and ordinal logistic regressions were employed to examine associations between physical activity and SEE, adjusting for covariates. SEE was significantly associated with engaging in sufficient total physical activity [odds ratio (OR) = 1.70], moderate physical activity (OR = 2.23), and vigorous physical activity (OR = 2.13). Unemployment was associated with less frequent moderate physical activity (OR = 0.59). Younger age (OR = 0.98), being male (OR = 2.67), and reporting excellent health (OR = 3.14) or good health (OR = 2.06) were associated with more frequent vigorous physical activity. Physical activity is a modifiable lifestyle behavior associated with many chronic disease disparities faced by the Marshallese community, and the study results will be useful for practitioners and researchers working to address these disparities.

A Phase II Study Investigating Cabozantinib in Patients with Refractory Metastatic Colorectal Cancer (AGICC 17CRC01).

Purpose: Multi-tyrosine kinase inhibitors (TKI) have shown clinical activity in patients with metastatic colorectal cancer. Cabozantinib, a multi-TKI, exhibited potent antitumor activity superior to regorafenib in preclinical colorectal cancer patient-derived tumor xenograft models. This phase II study aimed to investigate cabozantinib, a multi-TKI, in patients with refractory, metastatic colorectal cancer (mCRC). Experimental Design: A nonrandomized, two-stage, phase II clinical trial evaluating 12-week progression-free survival (PFS) was conducted in eight cancer centers across the United States between May 2018 and July 2020. Results: A total of 44 patients were enrolled between May 2018 and May 2019, 40 of which were response evaluable. Of the total 769 reported adverse events (AE), 93 (12%) were ≥ grade 3. Five grade 5 AEs were reported of which four were unrelated to study drug and one was reported as possibly related due to bowel perforation. Eighteen patients (45%) achieved 12-week PFS with stable disease or better (confidence interval, 0.29-0.62; P < 0.001). One patient (3%) had a partial response, and 27 other patients achieved stable disease as best response per RECISTv1.1. Median PFS was 3.0 months, and median overall survival was 8.3 months. Of the 18 patients who achieved 12-week PFS, 12 had left-sided primary tumors, 11 were RAS wild type, 11 were PIK3CA wild type, and 6 had previous regorafenib therapy. The 12-week PFS rate was higher in RAS wild-type tumors compared with RAS mutant tumors (0.61 vs. 0.32; P = 0.11). Conclusions: This phase II study demonstrated clinical activity of cabozantinib in heavily pretreated, patients with refractory mCRC, and supports further investigation. Significance: Targeting angiogenesis through VEGF axis blockade provides incremental survival benefit in patients with mCRC. The hepatocyte growth factor/MET signal transduction pathway has been observed as a mechanism for acquired resistance. Dual inhibition of VEGF plus MET is an attractive therapeutic strategy. This phase II trial demonstrated clinical activity with cabozantinib, a multi-TKI targeting VEGFR2 and MET, in patients with refractory, mCRC.

Hesitant adopters: An examination of hesitancy among adults in Arkansas who have taken the COVID-19 vaccine.

Recent research suggests people who report vaccine hesitancy may still get vaccinated; however, little is known about hesitancy among those who chose to vaccinate. The current study focused on individuals who received the coronavirus disease 2019 (COVID-19) vaccine despite their hesitancy, whom we refer to as "hesitant adopters." With the understanding that vaccine attitudes and vaccine behaviors may or may not be correlated, we examined the prevalence of COVID-19 vaccine hesitancy among those who have been vaccinated, how COVID-19 vaccine hesitancy varies across sociodemographic groups, and how COVID-19 vaccine hesitancy relates to other factors (prior health care access and influenza vaccination behavior over the past 5 years). Random digit dialing of telephone landlines and cell phones was used to contact potential survey respondents, rendering a sample of 1500 Arkansan adults. Approximately one-third of those who received a COVID-19 vaccine also reported some level of hesitancy. Among hesitant adopters, 5.3% said they were "very hesitant," 8.8% said they were "somewhat hesitant," and 17.1% said they were "a little hesitant." Black/African American and Hispanic/Latinx respondents reported more hesitancy than White respondents, and female respondents reported greater hesitancy compared to male respondents. Greater hesitancy was associated with non-metro/rural residence, forgoing health care due to cost, and lower influenza vaccination rates over the past 5 years. Findings suggest those who are hesitant may get vaccinated despite their hesitancy, illustrating the complexity of vaccination behaviors. Prevalence of hesitancy among the vaccinated has implications for communication strategies in vaccine outreach programs and may help to reduce stigmatization of hesitant adopters.

Molecular characteristics and clinical outcomes of patients with Neurofibromin 1-altered metastatic colorectal cancer.

Loss-of-function alterations of Neurofibromin 1 (NF1) activate RAS, a driver of colorectal cancer. However, the clinical implications of NF1 alterations are largely unknown. We performed a comprehensive molecular profiling of NF1-mutant colorectal cancer using data from 8150 patients included in a dataset of commercial CLIA-certified laboratory (Caris Life Sciences). In addition, NF1 expression levels were tested for associations with clinical outcomes using data from 431 patients in the CALGB/SWOG 80405 trial. In the Caris dataset, 2.2% of patients had pathogenic or presumed pathogenic NF1 mutations. NF1-mutant tumors more frequently harbored PIK3CA (25.0% vs. 16.7%) and PTEN mutations (24.0% vs. 4.2%) than wild type tumors. Gene set enrichment analysis revealed that MAPK and PI3K pathway signatures were enriched in NF1-mutant tumors. In the CALGB/SWOG 80405 cohort, low NF1 expression was associated with poor prognosis, and high NF1 expression was associated with better efficacy of cetuximab than bevacizumab. Together, we revealed concurrent genetic alterations in the PI3K pathways in NF1-mutant tumors, suggesting the need to simultaneously block MAPK and PI3K pathways in treatment. The potential of NF1 alteration as a novel biomarker for targeted therapy was highlighted, warranting further investigations in clinical settings.