First- vs second-line CDK 4/6 inhibitor use for patients with hormone receptor positive, human epidermal growth-factor receptor-2 negative, metastatic breast cancer in the real world setting.

PURPOSE: To compare CDK4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) in the first- versus second-line setting for treatment of hormone receptor positive (HR+), HER2 negative, metastatic breast cancer (MBC) using real-world evidence. METHODS: Patients with HR+, HER2 negative MBC, diagnosed between 2/3/2015 and 11/2/2021 and having ≥ 3 months follow-up were identified from the nationwide electronic health record-derived Flatiron Health de-identified database. Treatment cohorts included: (1) first-line ET with a CDK 4/6i (1st-line CDK4/6i) versus (2) first-line ET alone followed by second-line ET with a CDK4/6i (2nd-line CDK4/6i). Differences in baseline characteristics were tested using chi-square tests and two-sample t-tests. Time to third-line therapy, time to start of chemotherapy, and overall survival were compared using Kaplan-Maier method. RESULTS: The analysis included 2771 patients (2170 1st-line CDK4/6i and 601 2nd-line CDK4/6i). Patients receiving 1st-line CDK4/6i were younger (75% vs 68% < 75 years old, p = 0.0001), less likely uninsured or not having insurance status documented (10% vs. 13%, p = 0.04), of better performance status (50% vs 43% with ECOG 0, p = 0.03), and more likely to have de novo MBC (36% vs. 24%, p < 0.001). Time to third-line therapy (49 vs 22 months, p < 0.001) and time to chemotherapy (68 vs 41 months, p < 0.001) were longer in those receiving first-line CDK4/6i. Overall survival (54 vs 49 months, p = 0.33) was similar between groups. CONCLUSION: Use of CDK4/6i with first-, vs second-, line ET was associated with longer time to receipt of 3rd-line therapy and longer time to receipt of chemotherapy.

Adult circadian behavior in Drosophila requires developmental expression of cycle, but not period.

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LN(v)s) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LN(v)s resulted in abnormal peptidergic small-LN(v) dorsal projections, and (2) PER expression rhythms in the adult LN(v)s appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex.

The Breast-Imaging Operations, Practices and Systems Inventory: A framework to examine mammography facility effects on screening in rural communities.

PURPOSE: Develop and test a measurement framework of mammogram facility resources, policies, and practices in Appalachia. METHODS: Survey items describing 7 domains of imaging facility qualities were developed and tested in the Appalachian regions of Kentucky, Ohio, Pennsylvania, Virginia, and West Virginia. Medicare claims data (2016-2018) were obtained on catchment area mammogram services. Construct validity was examined from associations with facility affiliation, community characteristics, mammogram screening uptake, and market reach. Analyses were performed with t-tests and ANOVA. RESULTS: A total of 192 (of 377) sites completed the survey. Five factors were initially selected in exploratory factor analysis (FA) and refined in confirmatory FA: capacity, outreach & marketing, operational support, radiology review (NNFI = .94, GFI = 0.93), and diagnostic services (NNFI = 1.00, GFI = 0.99). Imaging capacity and diagnostic services were associated with screening uptake, with capacity strongly associated with catchment area demographic and economic characteristics. Imaging facilities in economically affluent versus poorer areas belong to larger health systems and have significantly more resources (P < .001). Facilities in economically distressed locations in Appalachia rely more heavily on outreach activities (P < .001). Higher facility capacity was significantly associated (P < .05) with larger catchment area size (median split: 48.5 vs 51.6), mammogram market share (47.4 vs 52.7), and screening uptake (47.6 vs 52.4). CONCLUSIONS: A set of 18 items assessing breast imaging services and facility characteristics was obtained, representing policies and practices related to a facility's catchment area size, market share, and mammogram screening uptake.

Cancer Prevention from the Viewpoint of UVA Comprehensive Cancer Center.

Prevention is a cornerstone of the guiding mission of the University of Virginia Comprehensive Cancer Center, which is "to reduce the burden of cancer for the patients of today, through skilled, integrated, and compassionate care and to eliminate the threat of cancer for the patients of tomorrow, through research and education in an environment that promotes diversity, equity, and inclusion." We find it useful to conceptualize different opportunities for cancer prevention using NCI's Health Behaviors Research Branch's multilevel translational framework. The latter considers three intersecting continuums: cancer control-from prevention through survivorship; translation-from basic sciences to dissemination and implementation; and level of influence or impact-from genetics to policy. An advantage of this heuristic is that "prevention" is inherently defined as an inter-programmatic concept cutting across basic, clinical, and population science research rather than solely as a programmatic domain of Population Sciences. Through the UVA community outreach and engagement, we apply this multilevel framework to mitigate the social determinants of cancer risk and outcomes that drive cancer inequities in our catchment area. Below, we provide examples of our prevention research and translation along the model continuums and focus on equity.

Cancer Prevention from the Viewpoint of UVA Comprehensive Cancer Center.

Prevention is a cornerstone of the guiding mission of the University of Virginia Comprehensive Cancer Center, which is "to reduce the burden of cancer for the patients of today, through skilled, integrated, and compassionate care and to eliminate the threat of cancer for the patients of tomorrow, through research and education in an environment that promotes diversity, equity, and inclusion." We find it useful to conceptualize different opportunities for cancer prevention using NCI's Health Behaviors Research Branch's multilevel translational framework. The latter considers three intersecting continuums: cancer control-from prevention through survivorship; translation-from basic sciences to dissemination and implementation; and level of influence or impact-from genetics to policy. An advantage of this heuristic is that "prevention" is inherently defined as an inter-programmatic concept cutting across basic, clinical, and population science research rather than solely as a programmatic domain of Population Sciences. Through the UVA community outreach and engagement, we apply this multilevel framework to mitigate the social determinants of cancer risk and outcomes that drive cancer inequities in our catchment area. Below, we provide examples of our prevention research and translation along the model continuums and focus on equity.

Using the Socio-ecological Model to Explore Facilitators and Deterrents of Tobacco Use Among Airmen in Technical Training.

INTRODUCTION: Military personnel have some of the highest rates of tobacco use in the USA. Within the Air Force, a common point of Airmen's (re-)initiation of tobacco use is during technical training once the tobacco ban has been lifted. Unfortunately, little is known about what factors facilitate and deter tobacco use during technical training. The socio-ecological model, which emphasizes multiple levels of influence on behavior (e.g., personal, intrapersonal, and environmental), provides a strong and comprehensive basis for which to explore factors that may impact tobacco use during technical training. MATERIALS AND METHODS: Twenty-two focus groups were conducted among Airmen (n = 10), Military Training Leaders (MTLs, n = 7), and Technical Training Instructors (TTIs, n = 5). Semi-structured focus group protocols were developed based on the socio-ecological model and included questions intended to elicit factors that facilitated and deterred tobacco use during technical training. Focus groups were transcribed and then coded using a hybrid deductive-inductive process. RESULTS: At the personal level, five factors were identified that influenced tobacco use: choice, fit with lifestyle, associations with the tobacco experience, association with military job outcomes, and association with health outcomes. Three interpersonal level factors were identified: peer influence, leadership influence, and normative beliefs. There were two influential environmental level factors: pricing and promotion and access to tobacco. Except for normative beliefs, all personal, interpersonal, and environmental-level factors were discussed as having aspects that could either facilitate or deter tobacco use. Normative beliefs, an interpersonal-level factor, were only discussed as a facilitator of tobacco use. CONCLUSIONS: Taken together, study findings can be used to enhance the effectiveness of tobacco prevention and cessation programs for Air Force Technical Trainees. Specific strategies to support the reduction of tobacco use among Airmen are presented.

The Feasibility of Using Self-Generated Identification Codes in Longitudinal Research With Military Personnel.

Self-generated identification codes (SGICs) are strings of information based on stable participant characteristics. They are often used in longitudinal research to match data between time points while protecting participant anonymity. However, the use of SGICs with military personnel has been infrequent, even though military personnel do not have the same privacy protections as civilians. The current paper reports results from two studies that tested the feasibility, reliability, and validity of using a SGIC to collect sensitive longitudinal data among military personnel. In study one, a team of 105 participants was tracked three times over a period of 12 weeks. The 10-item SGIC produced optimal matching over the 12-weeks. In study two, 1,844 participants were randomly assigned to a SGIC group or an anonymous control group, and then were asked to provide information about their alcohol use. Although match rates declined over time, there were no observed differences between study groups in participants' beliefs about the use of a SGIC. However, differences were identified in reported alcohol use behaviors between the groups, with controls reporting significantly more drinks per week and higher AUDIT-10 scores. While these findings raise potential concerns about using SGICs for epidemiological assessments of highly sensitive problem behaviors, these codes may still be useful in determining group differences in behavior change in randomized studies.

Demographic and clinical characteristics of dominican adults admitted to a diabetic foot clinic in the Dominican Republic, 2015.

AIM: To identify the demographic and clinical characteristics of Dominican adults admitted to a diabetic foot clinic and compare these characteristics by sex to better characterize and understand the severity of diabetes in the Dominican Republic. METHODS: We conducted a retrospective medical chart review of Dominican adults admitted to the National Institute of Diabetes, Endocrinology, and Nutrition's (INDEN) diabetic foot clinic between January 1st, 2015 and December 31st, 2015. We generated descriptive statistics and compared results by sex. RESULTS: We assessed 447 medical charts of patients admitted in 2015. More men visited the clinic than women (65% vs. 35%). The average duration of diabetes was 14.4 ±â€¯8.9 years. Abscess was the most common foot problem (74% in men, 68% in women, p = 0.164). A slightly smaller proportion of men received amputations than women (46% vs. 51%, p = 0.390). Women were older (p < 0.001), less educated (p = 0.004), and less likely to be married (p < 0.001). Women also exhibited higher rates of obesity (p = 0.003), hypertension (p = 0.005), cardiovascular disease (p = 0.011), ischemic foot (p = 0.008), and above the knee amputations (p = 0.002). CONCLUSION: Implementation of diabetes education programs, introduction of proper foot care, and improved resources for lifestyle management are needed to increase awareness and subsequently decrease diabetes and its negative impact on the health and economy of the Dominican Republic. Our findings suggest that various risk factors and comorbidities important to the development of diabetes may be disproportionately affecting women. Interventions should focus on women and their behaviors that increase risk for diabetes.