Behavioral Weight Loss Programs for Cancer Survivors Throughout Maryland: Protocol for a Pragmatic Trial and Participant Characteristics.

BACKGROUND: Clinical trials examining lifestyle interventions for weight loss in cancer survivors have been demonstrated to be safe, feasible, and effective. However, scalable weight loss programs are needed to support their widespread implementation. The ASPIRE trial was designed to evaluate real-world, lifestyle-based, weight loss programs for cancer survivors throughout Maryland. OBJECTIVE: The objectives of this protocol paper are to describe the design of a nonrandomized pragmatic trial, study recruitment, and baseline characteristics of participants. METHODS: Participants were aged ≥18 years, residing in Maryland, with a BMI ≥25 kg/m2, who reported a diagnosis of a malignant solid tumor, completed curative treatment, and had no ongoing or planned cancer treatment. Enrollment criteria were minimized to increase generalizability. The primary recruitment source was the Johns Hopkins Health System electronic health records (EHRs). Participants selected 1 of 3 remotely delivered weight loss programs: self-directed, app-supported, or coach-supported program. RESULTS: Participants were recruited across all 5 geographic regions of Maryland. Targeted invitations using EHRs accounted for 287 (84.4%) of the 340 participants enrolled. Of the 5644 patients invited through EHR, 5.1% (287/5644) enrolled. Participants had a mean age of 60.7 (SD 10.8) years, 74.7% (254/340) were female, 55.9% (190/340) identified as non-Hispanic Black, 58.5% (199/340) had a bachelor's degree, and the average BMI was 34.1 kg/m2 (SD 5.9 kg/m2). The most common types of cancers were breast (168/340, 49.4%), prostate (72/340, 21.2%), and thyroid (39/340, 8.5%). The self-directed weight loss program (n=91) included 25 participants who agreed to provide weights through a study scale; the app-supported program (n=142) included 108 individuals who agreed to provide their weight measurements; and the coach-supported weight loss program included 107 participants. We anticipate final analysis will take place in the fall of 2024. CONCLUSIONS: Using EHR-based recruitment efforts, this study took a pragmatic approach to reach and enroll cancer survivors into remotely delivered weight loss programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04534309; https://clinicaltrials.gov/study/NCT04534309. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54126.

Disparities in Cancer Stage Outcomes by Catchment Areas for a Comprehensive Cancer Center.

Importance: The National Cancer Institute comprehensive cancer centers (CCCs) lack spatial and temporal evaluation of their self-designated catchment areas. Objective: To identify disparities in cancer stage at diagnosis within and outside a CCC's catchment area across a 10-year period using spatial and statistical analyses. Design, Setting, and Participants: This cross-sectional, population-based study conducted between 2010 and 2019 utilized cancer registry data for the Johns Hopkins Sidney Kimmel CCC (SKCCC). Eligible participants included patients with cancer in the contiguous US who received treatment for cancer, a diagnosis of cancer, or both at SKCCC. Patients were geocoded to zip code tabulation areas (ZCTAs). Individual-level variables included sociodemographic characteristics, smoking and alcohol use, treatment type, cancer site, and insurance type. Data analysis was performed between March and July 2023. Exposures: Distance between SKCCC and ZCTAs were computed to generate a catchment area of the closest 75% of patients and outer zones in 5% increments for comparison. Main Outcomes and Measures: The primary outcome was cancer stage at diagnosis, defined as early-stage, late-stage, or unknown stage. Multinomial logistic regression was used to determine associations of catchment area with stage at diagnosis. Results: This study had a total of 94 007 participants (46 009 male [48.94%] and 47 998 female [51.06%]; 30 195 aged 22-45 years [32.12%]; 4209 Asian [4.48%]; 2408 Hispanic [2.56%]; 16 004 non-Hispanic Black [17.02%]; 69 052 non-Hispanic White [73.45%]; and 2334 with other or unknown race or ethnicity [2.48%]), including 47 245 patients (50.26%) who received a diagnosis of early-stage cancer, 19 491 (20.73%) who received a diagnosis of late-stage cancer , and 27 271 (29.01%) with unknown stage. Living outside the main catchment area was associated with higher odds of late-stage cancers for those who received only a diagnosis (odds ratio [OR], 1.50; 95% CI, 1.10-2.05) or only treatment (OR, 1.44; 95% CI, 1.28-1.61) at SKCCC. Non-Hispanic Black patients (OR, 1.16; 95% CI, 1.10-1.23) and those with Medicaid (OR, 1.65; 95% CI, 1.46-1.86) and no insurance at time of treatment (OR, 2.12; 95% CI, 1.79-2.51) also had higher odds of receiving a late-stage cancer diagnosis. Conclusions and Relevance: In this cross-sectional study of CCC data from 2010 to 2019, patients residing outside the main catchment area, non-Hispanic Black patients, and patients with Medicaid or no insurance had higher odds of late-stage diagnoses. These findings suggest that disadvantaged populations and those living outside of the main catchment area of a CCC may face barriers to screening and treatment. Care-sharing agreements among CCCs could address these issues.

Prevalence of Mental Health and Social Connection among Patients Seeking Tobacco Dependence Management: A Pilot Study.

INTRODUCTION: with regards to tobacco dependence management, there are certain barriers to successful smoking cessation for patients, such as untreated anxiety and depression. Complicating the impact of mental health morbidities on tobacco dependence may be the significant portion of patients whose mental health issues and limited social connections are undiagnosed and unaddressed. We hypothesize that patients with no prior mental health diagnoses who are treated for tobacco dependence have high rates of undiagnosed mental health morbidities. METHODS: patients were recruited from a tobacco treatment clinic in 2021. Every patient who came for an inaugural visit without a prior diagnosis of mental health disease was screened for depression, anxiety, social isolation and loneliness. Sociodemographic variables were collected. RESULTS: over a 12-month period, 114 patients were seen at the tobacco treatment clinic. Of these 114 patients, 77 (67.5%) did not have a prior diagnosis of a mental health disease. The mean age was 54.3 ± 11.2 years, 52 (67.5%) were females, and 64 (83.1%) were Black/African American. The mean age of starting smoking was 19.3 ± 5.2 years, and 43 (55.8%) had never attempted to quit smoking in the past. With regards to mental health screening, 32 (41.6%) patients had a score of 9 or greater on the Patient Health Questionnaire (PHQ) 9, 59 (76.6%) had a score of 7 or greater on the Generalized Anxiety Disorder (GAD) 7, 67 (87.0%) were identified with social isolation and 70 (90.1%) for loneliness on screening. CONCLUSION: there was a high prevalence of undiagnosed mental health morbidities and social disconnection in patients who were actively smoking and were struggling to achieve smoking cessation. While a larger scale study is necessary to reaffirm these results, screening for mental health morbidities and social disconnection may be warranted in order to provide effective tobacco dependence management.

Inclusion of the US Preventive Services Task Force Recommendation for Mammography in State Comprehensive Cancer Control Plans in the US.

Importance: The recommendations for the age and frequency that women at average risk for breast cancer should undergo breast cancer mammography screening have been a matter of emotional, political, and scientific debate over the past decades. Multiple national organizations provide recommendations for breast cancer screening age and frequency. US Centers for Disease Control and Prevention (CDC) funding for state comprehensive cancer control (CCC) planning requires compliance with stated objectives for attaining goals. US Preventive Services Task Force (USPSTF) recommendations on cancer prevention and control are currently used to require coverage of prevention services. Objectives: To evaluate the consistency of state CCC plan objectives compared with the most current (2016) USPSTF recommendations for the age and frequency that individuals should undergo mammography screening and to make recommendations for improvement of state CCC plans. Design, Setting, and Participants: This cross-sectional study used a descriptive, point-in-time evaluation and was conducted from November 1, 2019, to June 30, 2021. In November 2019, the most recent CCC plans from 50 US states and the District of Columbia were downloaded from the CDC website. The recommended ages at which to begin and end mammography examinations and the frequency of mammography examinations were extracted from plan objectives. Main Outcomes and Measures: The recommendations found in CCC plan objectives regarding the ages at which to begin and end mammography examinations and the frequency of mammography examinations for women with average risk for breast cancer were compared with USPSTF recommendations. Results: Of the 51 CCC plans, 16 (31%) were consistent with all USPSTF recommendations for age and frequency that women at average risk should undergo mammography. Twenty-six plans (51%) were partially consistent with recommendations, and 9 plans (18%) were not consistent with any of the 3 guideline components. Conclusions and Relevance: Compared with the USPSTF recommendation, state CCC plans are not homogenous regarding the age and frequency that women at average risk for breast cancer should undergo mammography. This variation is partially due to differences in state-specific planning considerations and discretion, variations in recommendations among national organizations, and publication of plans prior to the most current USPSTF recommendation (2016). Specifying the concept that high-risk populations need different age and frequency of screening recommendations than the general population may reduce heterogeneity among plans.

Progress in Cancer Control in Maryland: 1985-2015.

PURPOSE: Maryland historically had a high cancer burden, which prompted the implementation of aggressive cancer control strategies. We examined the status of cancer in Maryland and work under the current and previous editions of the MD Comprehensive Cancer Control Plan. METHODS: We examined the prevalence of cancer mortality, cancer incidence, and cancer-related behaviors in Maryland and the United States from 1985 to 2015 using publicly available data in the US Cancer Control PLANET, CDC WONDER, and Behavioral Risk Factor Surveillance System portals. We estimated the average annual cancer deaths avoided by triangulation. RESULTS: In 1983-1987, Maryland had the highest age-adjusted cancer mortality rate of all 50 states, second only to Washington, District of Columbia. Today (2011-2015), Maryland's age-adjusted cancer mortality rate ranks 31st. Overall cancer mortality rates have declined 1.9% annually from 1990 to 2015, avoiding nearly 60 000 deaths over 3 decades. While the prevalence of healthy cancer-related behaviors in Maryland was qualitatively similar or higher than that of the United States in 2015, Maryland's 5-year (2011-2015) cancer incidence rate was significantly greater than that of the United States. CONCLUSIONS: Maryland's 30-year cancer mortality declines have outpaced other states. However, a reduction in mortality while incidence rates remain high indicates a need for enhanced focus on primary prevention.

Rebuilding a US Federal Data Strategy After the End of the "Community Health Status Indicators".

For nearly 2 decades, the Community Health Status Indicators tool reliably supplied communities with standardized, local health data and the capacity for peer-community comparisons. At the same time, it created a large community of users who shared learning in addressing local health needs. The tool survived a transition from the Health Resources and Services Administration to the Centers for Disease Control and Prevention before being shuttered in 2017. While new community data tools have come online, nothing has replaced Community Health Status Indicators, and many stakeholders continue to clamor for something new that will enable local health needs assessments, peer comparisons, and creation of a community of solutions. The National Committee on Vital and Health Statistics heard from many stakeholders that they still need a replacement data source. (Am J Public Health. 2021;111(10):1865-1873. https://doi.org/10.2105/AJPH.2021.306437).

Tobacco treatment clinics in urban public housing: feasibility and outcomes of a hands-on tobacco dependence service in the community.

BACKGROUND: As a further extension of smoke-free laws in indoor public places and workplaces, the Department of Housing and Urban Development's declaration to propose a regulation that would make housing units smoke-free was inevitable. Of note is the challenge this regulation poses to current tenants of housing units who are active smokers. We aimed to assess the efficacy of a tobacco treatment clinic in public housing. The utilization of the clinic by tenants and tenants' respective outcomes regarding smoking status were used to determine the intervention's effectiveness. METHODS: Tobacco treatment clinics were held in two urban-based housing units for 1-year. The clinics provided on-site motivational interviewing and prescriptions for pharmacological agents if warranted. Outcomes collected include the tenants' clinic attendance and 3- and 6-month self-reported smoking status. RESULTS: Twenty-nine tobacco treatment clinic sessions were implemented, recruiting 47 tenants to participate in smoking cessation. The mean age of the cohort was 53 ± 12.3 years old. Of the 47 tenants who participated, 21 (44.7%) attended three or more clinic sessions. At the 3-month mark, five (10.6%) tenants were identified to have quit smoking; at 6-months, 13 (27.7%) tenants had quit smoking. All 13 of the tenants who quit smoking at the end of 6-months attended three or more sessions. CONCLUSION: An on-site tobacco treatment clinic to provide strategies on smoking cessation was feasible. Efforts are warranted to ensure more frequent follow-ups for tenants aiming to quit smoking. While further resources should be allocated to help tenants comply with smoke-free housing units' regulations, we believe an on-site tobacco treatment clinic is impactful.

Effects of Behavioral Weight Loss and Metformin on IGFs in Cancer Survivors: A Randomized Trial.

CONTEXT: Higher levels of insulin-like growth factor-1 (IGF-1) are associated with increased risk of cancers and higher mortality. Therapies that reduce IGF-1 have considerable appeal as means to prevent recurrence. DESIGN: Randomized, 3-parallel-arm controlled clinical trial. INTERVENTIONS AND OUTCOMES: Cancer survivors with overweight or obesity were randomized to (1) self-directed weight loss (comparison), (2) coach-directed weight loss, or (3) metformin treatment. Main outcomes were changes in IGF-1 and IGF-1:IGFBP3 molar ratio at 6 months. The trial duration was 12 months. RESULTS: Of the 121 randomized participants, 79% were women, 46% were African Americans, and the mean age was 60 years. At baseline, the average body mass index was 35 kg/m2; mean IGF-1 was 72.9 (SD, 21.7) ng/mL; and mean IGF1:IGFBP3 molar ratio was 0.17 (SD, 0.05). At 6 months, weight changes were -1.0% (P = 0.07), -4.2% (P < 0.0001), and -2.8% (P < 0.0001) in self-directed, coach-directed, and metformin groups, respectively. Compared with the self-directed group, participants in metformin had significant decreases on IGF-1 (mean difference in change: -5.50 ng/mL, P = 0.02) and IGF1:IGFBP3 molar ratio (mean difference in change: -0.0119, P = 0.011) at 3 months. The significant decrease of IGF-1 remained in participants with obesity at 6 months (mean difference in change: -7.2 ng/mL; 95% CI: -13.3 to -1.1), but not in participants with overweight (P for interaction = 0.045). There were no significant differences in changes between the coach-directed and self-directed groups. There were no differences in outcomes at 12 months. CONCLUSIONS: In cancer survivors with obesity, metformin may have a short-term effect on IGF-1 reduction that wanes over time.

The association of sex steroid hormone concentrations with non-alcoholic fatty liver disease and liver enzymes in US men.

BACKGROUND & AIMS: This study aimed to analyse the association of sex hormone levels with liver enzyme levels and non-alcoholic fatty liver disease (NAFLD) in a nationally representative sample of men. METHODS: A total of 919 men from the US National Health and Nutrition Examination Study (NHANES) III were included in this cross-sectional analysis of data from 1988 to 1991. We used existing data on serum total and free testosterone, total and free estradiol, androstanediol glucuronide (AAG) and sex steroid-binding globulin (SHBG), and estimated their associations with aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and NAFLD, as determined using ultrasound, after adjusting for possible confounders including age, race, smoking, alcohol, physical activity, waist circumference and steroid hormones. RESULTS: Lower total testosterone (TT) and higher free estradiol were associated with higher odds of NAFLD after adjusting for confounders including the other sex hormones. Lower TT was associated with higher odds of elevated AST, but not ALT. Free testosterone, total estradiol, SHBG and AAG were not associated with NAFLD or liver enzymes. CONCLUSIONS: This study supports an inverse association between TT concentration and NAFLD in men independent of other sex hormones (SHBG, AAG and estradiol) and known risk factors, such as obesity, age and lifestyle. Exploration of whether TT might be a non-invasive marker for NAFLD diagnosis is warranted.

Improving lung cancer screening: An equitable strategy through a tobacco treatment clinic.

Annual screening with low dose chest tomography has been adopted for those at high risk to aid in the early detection of lung cancer. In addition to screening, it is recommended that such persons receive evidence-based smoking-cessation. However, both lung cancer screening and evidence-based smoking-cessation strategies are underutilized in the US. We review the impact of a dedicated Tobacco Treatment Clinic (TTC), delivering evidence-based smoking cessation strategies, on lung cancer screening enrollment. Patients of the TTC, aged 50 years or older, having a minimum 20-pack-year smoking history were included. All patients had records reviewed to see if they had received lung cancer screening; if their lung cancer screening was achieved through the TTC, this was documented as "initial screening" versus "continued screening or surveillance". Sociodemographic variables were collected as well. As for results, between January 2019 to February 2020, 92 patients enrolled in the TTC and fulfilled criteria for lung cancer screening. The mean age was 65.7 ± 8.3 years old, with 58 (63.0%) of the patients being female. Seventy-five (81.5%) patients were African American. Of the 92, 68 (73.9%) patients had lung cancer screening, with 51 patients receiving their first lung cancer screening scan through the TTC. In conclusion, through enrollment in a dedicated TTC, a significant proportion of patients were able to access lung cancer screening for the first time. Further, many of these patients were of minority status. Having a dedicated TTC may improve current health equity gaps in lung cancer screenings in certain US populations.

Inclusion of Evidence-Based Breast Cancer Control Recommendations and Guidelines in State Comprehensive Cancer Control Plans.

INTRODUCTION: Each US state, territory, and tribe/tribal organization is supported by the Centers for Disease Control and Prevention to develop and implement a comprehensive cancer control (CCC) plan. The objective of this study was to inform areas for improvement of those plans. METHODS: To show how CCC plans can be improved, we used the example of breast cancer, which has a long public health history and an established, broad spectrum of prevention and control activities. We evaluated the inclusion of evidence-based breast cancer prevention topics as provided by guidelines from the Centers for Disease Control and Prevention (CDC) and recommendations of the US Preventive Services Task Force (USPSTF) in each state's CCC plan. From January through March 2019, we downloaded CCC plans from each state and the District of Columbia and abstracted and quantified the content of plans for 1) discussion of data on breast cancer mortality, breast cancer incidence, uptake of mammography; 2) statement of objective to reduce the burden of breast cancer; and 3) review of CDC guidelines and USPSTF recommendations. RESULTS: The discussion of breast cancer-relevant topics and specification of objectives was incomplete. Of 51 plans, data on breast cancer mortality and incidence and uptake of mammography were reported in 53% (n = 27) to 76% (n = 39) of plans. CDC and USPSTF recommendations for breast cancer-specific interventions were discussed in only 6% (n = 3) to 37% (n = 19) of plans. Discussion of general cancer prevention topics relevant to breast cancer ranged from 10% (n = 5) to 61% (n = 31) of plans. CONCLUSION: Our findings inform areas for quality improvement of state CCC plans and may contribute to other areas of public health planning.

Problem Solving to Enhance Clinical Trial Participation Utilizing a Framework-Driven Approach.

Health professionals agree that increasing diversity in clinical trial participants is an important way to improve cancer care and address disparities in outcomes. However, trial participation among minority populations has been low historically and continues to be low. Underrepresentation has resulted in majority groups reaping greater benefit from research findings, thus widening cancer health disparities. Addressing these disparities effectively has proven to be challenging. To maximize diversity among participants, it is necessary to understand the steps patients take to enroll in trials; the barriers patients face at each step; and the needs and preferences of the patient population overall and subgroups specified by age, race, ethnicity, or sex, in order to develop interventions to address barriers to participation. To improve clinical trial participation, and most importantly to eliminate disparities, cancer centers should examine reasons patients fail to enroll in trials and develop interventions designed to meet their patients' needs and preferences.

Applying an Innovative Model of Disaster Resilience at the Neighborhood Level : The COPEWELL New York City Experience.

Community resilience is a community's ability to maintain functioning (ie, delivery of services) during and after a disaster event. The Composite of Post-Event Well-Being (COPEWELL) is a system dynamics model of community resilience that predicts a community's disaster-specific functioning over time. We explored COPEWELL's usefulness as a practice-based tool for understanding community resilience and to engage partners in identifying resilience-strengthening strategies. In 2014, along with academic partners, the New York City Department of Health and Mental Hygiene organized an interdisciplinary work group that used COPEWELL to advance cross-sector engagement, design approaches to understand and strengthen community resilience, and identify local data to explore COPEWELL implementation at neighborhood levels. The authors conducted participant interviews and collected shared experiences to capture information on lessons learned. The COPEWELL model led to an improved understanding of community resilience among agency members and community partners. Integration and enhanced alignment of efforts among preparedness, disaster resilience, and community development emerged. The work group identified strategies to strengthen resilience. Searches of neighborhood-level data sets and mapping helped prioritize communities that are vulnerable to disasters (eg, medically vulnerable, socially isolated, low income). These actions increased understanding of available data, identified data gaps, and generated ideas for future data collection. The COPEWELL model can be used to drive an understanding of resilience, identify key geographic areas at risk during and after a disaster, spur efforts to build on local metrics, and result in innovative interventions that integrate and align efforts among emergency preparedness, community development, and broader public health initiatives.

Corrigendum to "Annexin 2 protein expression is associated with breast cancer subtypes in African American women" [Heliyon Volume 6, Issue 2, February 2020, e03241].

[This corrects the article DOI: 10.1016/j.heliyon.2020.e03241.].

Annexin 2 protein expression is associated with breast cancer subtypes in African American women.

BACKGROUND: A review of literature on the expression of Annexin 2 in cancer has shown that there is very limited research work on the association of this protein with breast cancer aggressiveness in African Americans. In the present study, TMA breast tissues from African American women were stained with Annexin 2 antibody to determine the association between the molecular subtypes and Annexin 2 protein expression. METHOD: An annotated case series of 135 breast cancer tissues archived from 2000 to 2010 was acquired from the Howard University Tumor Registry. The association between ANX2 expression and survival by molecular subtypes Luminal A, Luminal B, HER2, and Triple Negative (TN) was assessed using Multinomial regression, chi-square analysis, and Kaplan-Meir graphs (Stata 11). RESULTS: Our findings show a marked association between ANX2 protein expression in Luminal B and HER2 subtypes unadjusted and when adjusted for age. Borderline differences in tumor grade were found in TN only.Univariately, age (<50, 50 + years) and metastases were highly significant for overall survival, disease-free survival and recurrence-free survival. Stage, tumor size, and nodal involvement were of borderline or greater significance for overall and disease-free survival. ANX2 expression was not significant. Kaplan Meier tests of ANX2 showed significant separation of overall survival by ANX2 protein expression in all breast tumor subtypes. In multivariate analyses comparing TN to Luminal A, ANX2 was not important while controlling for age and grade. CONCLUSION: ANX2 might be a biomarker of aggressiveness and a relevant candidate biomarker in high risk African American women with Luminal B and HER2 breast cancer.

Nationally Representative Estimates of Serum Testosterone Concentration in Never-Smoking, Lean Men Without Aging-Associated Comorbidities.

CONTEXT: Testosterone deficiency prevalence increases with age, comorbidities, and obesity. OBJECTIVE: To inform clinical guidelines for testosterone deficiency management and development of targets for nonpharmacologic intervention trials for these men, we determined serum testosterone in never-smoking, lean men without select comorbidities in nationally representative surveys. DESIGN SETTING PARTICIPANTS: We used cross-sectional data for never-smoking, lean men ≥20 years without diabetes, myocardial infarction, congestive heart failure, stroke, or cancer, without use of hormone-influencing medications, and participated in morning sessions of National Health and Nutrition Examination Survey (NHANES) III (phase I 1988-1991) or continuous NHANES (1999-2004). By age, we determined median total testosterone (ng/mL) measured previously by a Food and Drug Administration-approved immunoassay and median estimated free testosterone concentration. RESULTS: In NHANES III, in never-smoking, lean men without comorbidities, median (25th, 75th percentile) testosterone was 4% to 9% higher than all men-20 to 39 years: 6.24 (5.16, 7.51), 40 to 59: 5.37 (3.83, 6.49), and ≥60: 4.61 (4.01, 5.18). In continuous NHANES, in never-smoking, lean men without comorbidities, levels were 13% to 24% higher than all men-20 to 39 years: 6.26 (5.32, 7.27), 40 to 59: 5.86 (4.91, 6.55), and ≥60: 4.22 (3.74, 5.73). In never-smoking, lean men without comorbidities, median estimated free testosterone was similar to (NHANES III) or slightly higher than (continuous NHANES) in all men. CONCLUSIONS: These nationally representative data document testosterone levels (immunoassay) in never-smoking, lean men without select comorbidities 30 and 15 to 20 years ago. This information can be incorporated into guidelines for testosterone deficiency management and used to develop targets for nonpharmacologic intervention trials for testosterone deficiency.

Age-Specific Serum Total and Free Estradiol Concentrations in Healthy Men in US Nationally Representative Samples.

PURPOSE: To report age-specific serum estradiol concentration in nonsmoking, lean US men without comorbidities. We provide concentrations from 30 and 15 to 20 years ago given previously described declines in serum estradiol in US men over time. METHODS: We used data from the Third National Health and Nutrition Examination Survey (NHANES III; 1988 to 1991) and continuous NHANES (1999 to 2004). Serum estradiol and SHBG were previously measured by competitive electrochemiluminescence immunoassays. Free estradiol was estimated from estradiol, SHBG, and albumin. By age, we calculated median concentrations overall and for nonsmoking, lean (body mass index <25 kg/m2 and waist <102 cm) men without diabetes, cardiovascular disease, or cancer. RESULTS: Overall, respective total estradiol medians for men ages 20 to 39, 40 to 59, and ≥60 years old were 37.0, 33.9, and 33.5 pg/mL in NHANES III and 31.3, 30.5, and 27.0 pg/mL in continuous NHANES. In nonsmoking, lean men without comorbidities, respective total estradiol medians were 32.0, 32.1, and 32.0 pg/mL in NHANES III and 29.1, 22.7, and 26.1 pg/mL in continuous NHANES. Overall, respective free estradiol medians were 0.82, 0.72, and 0.64 pg/mL in NHANES III and 0.67, 0.61, and 0.47 pg/mL in continuous NHANES. In nonsmoking, lean men without comorbidities, respective free estradiol medians were 0.64, 0.67, and 0.62 pg/mL in NHANES III and 0.58, 0.42, and 0.40 pg/mL continuous NHANES. CONCLUSION: We report US nationally representative serum estradiol concentrations in healthy men, which could be used for targeting estradiol during testosterone supplementation and for general good health.

Post-colposcopy Management of ASC-US and LSIL Pap Tests (PALS Trial): Pilot RCT.

OBJECTIVE: Evidence supporting optimal follow-up of women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion cytology found to have low-grade disease or normal findings at initial colposcopy is weak. Surveillance options include continued colposcopy, discharge with Pap testing, or HPV testing at 12 months. This study was a pilot RCT comparing these three follow-up policies. The objectives were to determine the feasibility of an RCT and to compare the incidence of greater than or equal to high-grade squamous intraepithelial lesion (≥HSIL) in each of the follow-up policies. METHODS: A total of 133 women referred with ASC-US or low-grade squamous intraepithelial lesion cytology between June and August 2012 underwent initial colposcopy where incident ≥HSIL histology was ruled out. Of these women, 125 were randomly assigned to colposcopic surveillance, Pap testing, or HPV testing. Patients with high-risk results at any point were treated according to standard of care. Patient recruitment and adherence to follow-up were calculated using descriptive statistics. Accuracy of the three follow-up arms was calculated (Canadian Task Force Classification: IC). RESULTS: Recruitment rates were 80%, and adherence to protocol was 85% to 100%. Nine of 125 (7.2%) patients overall were found to have ≥HSIL histology at exit: one of 43 in the reference colposcopy group, and six of 41 and three of 41 in Pap and HPV arms, respectively. One early cancer was detected in the HPV arm. Sensitivity and specificity (CI) for each arm, respectively, were as follows: colposcopy N/A, 100% (88.1%-100%); Pap, 100% (47.8%-100%) and 85.7% (63.7%-97%); and HPV, 66.7% (9.4%-99.2%) and 68% (46.5%-85.1%). CONCLUSION: This pilot study demonstrated the operational and safety feasibility of an RCT in this patient population. Validation of clinical findings is necessary.

Selenium and Sex Steroid Hormones in a U.S. Nationally Representative Sample of Men: A Role for the Link between Selenium and Estradiol in Prostate Carcinogenesis?

BACKGROUND: Given the recent findings from pooled studies about a potential inverse association between selenium levels and prostate cancer risk, this cross-sectional study aimed to investigate the association between serum selenium and serum concentrations of sex steroid hormones including estradiol in a nationally representative sample of U.S. men to investigate one mechanism by which selenium may influence prostate cancer risk. METHODS: The study included 1,420 men ages 20 years or older who participated in the Third National Health and Nutrition Examination Survey between 1988 and 1994. We calculated age/race-ethnicity-adjusted and multivariable-adjusted geometric mean serum concentrations of total and estimated free testosterone and estradiol, androstanediol glucuronide, and sex hormone binding globulin, and compared them across quartiles of serum selenium. RESULTS: Adjusting for age, race/ethnicity, smoking status, serum cotinine, household income, physical activity, alcohol consumption, and percent body fat, mean total estradiol [e.g., Q1, 38.00 pg/mL (95% confidence interval (CI), 36.03-40.08) vs. Q4, 35.29 pg/mL (95% CI, 33.53-37.14); P trend = 0.050] and free estradiol [e.g., Q1, 0.96 pg/mL (95% CI, 0.92-1.01) vs. Q4, 0.90 (95% CI, 0.85-0.95); P trend = 0.065] concentrations decreased over quartiles of selenium. Stratification by smoking and alcohol consumption, showed that the latter observation was stronger for never smokers (P interaction = 0.073) and those with limited alcohol intake (P interaction = 0.017). No associations were observed for the other sex steroid hormones studied. CONCLUSIONS: Our findings suggests that a possible mechanism by which selenium may be protective for prostate cancer is related to estrogen. IMPACT: Further studies of longitudinal measurements of serum and toenail selenium in relation to serum measurements of sex steroid hormones are needed.

Barriers to non-small cell lung cancer trial eligibility.

INTRODUCTION: Cancer clinical trial (CCT) enrollment is low potentially threatening the generalizability of trial results and expedited regulatory approvals. We assessed whether type of initial patient appointment for non-small cell lung cancer (NSCLC) is associated with CCT eligibility. METHODS: Using a patient-to-accrual framework, we conducted a quasi-retrospective cohort pilot study at Sidney Kimmel Comprehensive Cancer Center (SKCCC), Baltimore, Maryland. 153 NSCLC patients new to SKCCC were categorized based on type of initial appointment: patients diagnosed or treated and patients seen for a consultation. CCT eligibility was determined by comparing eligibility criteria for each open trial to the electronic medical record (EMR) of each patient at every office visit occurring within 6-months of initial visit. RESULTS: We found no association between type of initial appointment and CCT eligibility (OR, 1.15; 95% CI, 0.49-2.73). Analyses did suggest current smokers were less likely to be eligible for trials compared to never smokers (OR, 0.15; 95% CI, 0.03-0.64), and stage 4 patients with second line therapy or greater were more likely to be eligible than stage 1 or 2 patients (OR, 5.18; 95% CI, 1.08-24.75). Additional analyses suggested most current smokers and stage 1 or 2 patients had trials available but were still ineligible. CONCLUSIONS: SKCCC has a diverse portfolio of trials available for NSCLC patients and should consider research strategies to re-examine eligibility criteria for future trials to ensure increased enrollment of current smokers and stage 1 or 2 patients. We could not confirm whether type of initial visit was related to eligibility.