US Men Research Articles

Abstract 7116: Targeting the CBP/p300 axis in lethal prostate cancer impacts DNA repair

Abstract Prostate cancer (PCa) is the 2nd leading cause of cancer related deaths in US men. PCa is an androgen dependent disease driven by the androgen receptor (AR). Currently, androgen-deprivation therapy (ADT) is the standard of care first-line therapy for metastatic PCa. Resistance to ADT uniformly leads to lethal disease, termed castration-resistant prostate cancer (CRPC). Thus, there is an unmet clinical need to identify and develop novel strategies to treat CRPC. CBP/p300 are potent co-activators for AR. High expression of CBP/p300 is associated with locally advanced disease and castration resistant function of AR, resulting in poor patient outcomes and further highlighting the need to discern the role of CBP/p300 to potentially develop therapeutic targets for precision medicine. Previous studies have relied on non-specific compounds and genetic silencing to target CBP/p300. In this study, CBP/p300 mediated bromodomain activity is targeted by CCS1477 (inobrodib), a first-in-class bromodomain inhibitor developed by Cell Centric. CCS1477 treatment demonstrated effective inhibition in growth and clonogenicity assays. Inhibition of the CBP/p300 bromodomain with CCS1477 resulted in significant downregulation of AR-FL, AR-V7, and its targets’ mRNA expression in addition to inhibition of associated factors such as c-MYC and its downstream targets in PCa cell lines as well as patient derived xenograft (PDX) models. This study shows that CBP and p300 are highly expressed and correlate closely with AR gene expression and AR activity score in primary PCa and CRPC patient samples. The clinical significance of CBP/p300 expression in PCa has been investigated via elucidation of CBP/p300 transcriptional reprogramming and its role in DNA damage response (DDR) pathways. Specifically, findings revealed that CBP/p300 bromodomain suppression sensitizes to AR-dependent DNA-repair. Transcriptional mapping identified CBP/p300 as regulators of cell proliferation and DNA repair processes, which were functionally confirmed across several PCa model systems. To assess relevance, exogenous challenge with radiation revealed that CBP/p300 are required for AR-mediated DNA repair, and CBP/p300 expression is linked to DNA repair capacity in the clinical setting. Molecular analyses revealed that CBP/p300 facilitate double-strand break (DSB) repair efficiency via homologous recombination (HR) mediated DDR. Congruently, CBP/p300 strongly correlated with HR gene expression in PCa patient tissue. These collective findings reveal that CBP/p300 govern repair of DNA DSBs by regulating HR, thus modulating genome integrity and promoting CRPC growth. These studies identify CBP/p300 as a driver of PCa tumorigenesis through coordinated control of critical transcriptional events and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed therapies. Citation Format: Sumaira Sardar, Lakshmi Ravindranath, Christopher McNair, Saswati N. Chand, Wei Yuan, Denisa Bogdan, Jonathan Welti, Adam Sharp, Matthew Schiewer, Lisa Butler, Johann de Bono, Kris Frese, Nigel Brooks, Neil Pegg, Karen Knudsen, Ayesha A. Shafi. Targeting the CBP/p300 axis in lethal prostate cancer impacts DNA repair [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7116.

Abstract 4858: Examining state- and race-specific five-year prostate cancer mortality rates (2016-2020) and their association with prostate-specific antigen screening

Abstract Background: In 2023, 34,000 US men will die from prostate cancer. The impact of prostate cancer mortality varies greatly across states. Racial differences in state populations may explain some but not all of this variability. This study examined prostate cancer mortality rates by state and race and their associations with state-level prostate-specific antigen (PSA) screening prevalence. Methods: We obtained race-specific, state level five-year average age-standardized prostate cancer mortality rates from 2016-2020 from the NCI State Cancer Profiles. Data on race-specific, state level PSA screening prevalence in 2010 were obtained from the Behavioral Risk Factor Surveillance System. We compared mortality rate ratios (RR, 95% confidence intervals [CI]) of state level prostate cancer mortality rates of Black, Hispanic, Asian/Pacific Islander, and American Indian/Alaskan Native men to White men. We generated descriptive statistics (median and range) on state level mortality rates to quantify the variability within racial/ethnic groups. We fit univariable Poisson regression models to explore associations between prostate cancer mortality rates and PSA screening prevalence, for White, Black, and Hispanic men, but omitted Asian and American Indian men due to sparse data. Results: Mortality data were available for 50 states and the District of Columbia (D.C.) for White, 40 states and D.C. for Black, 36 states for Hispanic, 24 states for Asian, and 11 states for American Indian men. The US average prostate cancer mortality rate was 18.8 deaths per 100,000 per year. As expected, rates were higher among Black than White men (RR 2.07; 1.90, 2.24), while rates among Hispanic (RR 0.75; 0.68, 0.84) and Asian (RR 0.48; 0.41, 0.56) men were lower. Rates among American Indian men were slightly higher than White men (RR 1.12; 0.96, 1.29). Variability of state-level mortality rates within each race was quite high, with largest ranges for Black and American Indian men. Black men had a median (range) state-level prostate cancer mortality rate of 37.9 (23.9 to 49.2), and American Indian men had a median rate of 20.4 (7.7 to 28.9). Median (range) rates were 17.7 (11.3 to 22.3) for White, 8.3 (4.3 to 17.4) for Asian, and 13.5 (8.9 to 22.5) for Hispanic men. Associations between a 5-percentage point increase in PSA screening prevalence and prostate cancer mortality rates were RR 0.92 (95% CI: 0.84, 0.99) in White, RR 0.96 (0.88, 1.05) in Black, and 0.98 (0.90, 1.07) in Hispanic men. Conclusion: There is considerable variability in prostate cancer mortality rates across states, both between and within racial/ethnic groups, highlighting complexity of racial disparities. PSA screening may weakly contribute to this variability, but other factors such as health care access, social determinants, and lifestyle factors that vary between states should be considered in future studies. Citation Format: Hannah E. Guard, Jane B. Vaselkiv, Ethan Ecsedy, Florian Kuechen, Nareg Minassian, James Dun Rappaport, Zhiyu Qian, Michelle O. Sodipo, Kathryn L. Penney, Konrad H. Stopsack, Lorelei A. Mucci. Examining state- and race-specific five-year prostate cancer mortality rates (2016-2020) and their association with prostate-specific antigen screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4858.

Abstract P476: Changes in Olive Oil Consumption and Weight Changes in US Men and Women

Background: Olive oil intake is inversely associated with the risk of chronic diseases and mortality. However, it is unclear whether there is an association between olive oil intake and weight changes; because it is an energy-dense food concerns have been raised that high intake may contribute to weight gain. Therefore, we aimed to determine the associations between long-term changes in olive oil consumption and changes in weight. Methods: We examined data from 116,243 women and men from the Nurses’ Health Study (NHS, 1990-2010), NHSII (1991-2015), and Health Professional Follow-up Study (HPFS, 1990-2014), who were free from chronic diseases at baseline. We applied multivariable linear regression models with robust variance estimators to assess the association of changes in olive oil intake within each 4-year interval with concurrent weight changes. Results across the three cohorts were pooled using inverse-variance weights. Results: At baseline, mean ± SD age was 54.8 ± 6.6 years in the NHS, 45.3 ± 8.0 years in the NHS2, and 53.9 ± 7.2 years in the HPFS. Mean body mass index was 25 kg/m2 at baseline across the three cohorts. The mean weight gain over each 4-year follow-up cycle was highest in the NHS2 (1.8; 95%CI -6.8 to 11.3 kg), followed by the NHS (1.0; 95%CI -6.8 to 9.1 kg), and lastly the HPFS (0.6; 95%CI -5.4 to 6.8 kg). Pooling across the cohorts after adjustment for sociodemographic, lifestyle, and set of dietary factors (fruits, vegetables, red and processed meat, sugar sweetened beverages, coffee, refined grains), each ½ Tablespoon (7 grams) serving per day increment in olive oil was associated with a slightly lower 4-year weight gain of -0.06 kg (95%CI -0.08 to -0.04 kg; p<0.0001). This inverse association was observed in the three cohorts, with a greater magnitude of association in the NHS2 (-0.08; 95%CI -0.10 to -0.05 kg; p<0.0001), followed by the HPFS (-0.07; 95%CI -0.12 to -0.02 kg; p=0.003) and lastly the NHS (-0.05; 95%CI -0.07 to -0.01 kg; p=0.02). Results were attenuated after adjustment for the Alternative Healthy Eating index (pooled -0.03; 95%CI -0.05 to -0.02; p=0.0003). Conclusions: Long-term habitual increase in olive oil consumption was not associated with increased weight gain in middle-aged and older adults.

Access to inflatable penile prosthesis surgery as indicated by distances traveled among US men with Medicare.

The significance of geographic barriers to receiving inflatable penile prosthesis (IPP) treatment is uncertain according to the existing medical literature. To describe the travel patterns of men with erectile dysfunction (ED) in the United States who underwent IPP surgery. This retrospective cohort study utilized data from the 100% Medicare Standard Analytical Files. Men aged ≥65 years with an ED diagnosis who underwent IPP surgery between January 2016 and December 2021 were identified from the database. Federal Information Processing Series codes from the National Bureau of Economic Research's County Distance Database were used to determine geographic distances from patients' homes to the facilities at which surgery was performed. Evaluations included the proportions of men who traveled outside their county of residence or state for IPP treatment and the average distances in miles traveled. Among 15 954 men with ED undergoing IPP treatment, 56.4% received care out of their county for IPP, at a mean distance of 125.6miles (range, 3.8-4935.0). Although patients aged ≥80 years were less likely to travel outside their county as compared with men aged 65 to 69 years (48.1% vs 57.1%, P < .001), if they traveled, they were likely to travel farther (mean, 171.8 vs 117.7miles; P < .001). South Dakota had the highest proportion of men traveling outside their county for IPP treatment (91.3%; mean, 514.2miles), while Vermont had the highest proportion traveling outside their home state (73.7%). By unveiling disparities in access, this study will potentially lead to tailored interventions that enhance patient care and health outcomes. Strengths include the uniqueness in (1) evaluating the proportions of patients who travel out of their county of residence or home state for IPP treatment and (2) quantifying the average distances that patients traveled. An additional strength is the large sample size due to the retrospective design and database used. The analysis did not capture all Medicare enrollees; however, it did encompass all traditional Medicare enrollees, representing approximately half of all men in the US aged ≥65years. Limitations include not being generalizable to entire population of the US, as the study examined only Medicare enrollees. In addition, the study period includes the pandemic, which could have affected travel patterns. Furthermore, the coding and accuracy of the data are limitations of using administrative claims data for research. Study findings showed that many men with Medicare and ED traveled from their home geographic location for IPP treatment.

Comparison of the cost-effectiveness of sequential treatment with abaloparatide in US men and women at very high risk of fractures

BackgroundOsteoporotic-related fractures represent an increasing burden to patients, health care systems and society.AimsThis study estimated cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) compared to relevant alternative strategies in US men and women aged 50 to 80 years at very high fracture risk (bone mineral density T-score ≤ − 2.5 and a recent fracture).MethodsA lifetime Markov-based microsimulation model was used to estimate healthcare costs and quality-adjusted life years (QALYs). Comparators were sequential treatment with unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Analyses were conducted based on initial fracture site (hip, vertebral, or any fracture) and treatment efficacy data (derived from clinical trials or a recent network meta-analysis).ResultsFrom all analyses completed, sequential ABL/ALN demonstrated more QALYs for lower healthcare costs versus unbranded TPTD/ALN. No treatment was dominated (higher costs for less QALYs) versus ALN monotherapy. Sequential ABL/ALN resulted in favorable cost-effectiveness (at US threshold of $150,000/QALY) versus generic ALN monotherapy in men aged ≥ 50 years with any fracture type, women aged ≥ 65 years with any fracture type, and women aged ≥ 55 years having a hip or vertebral fracture.DiscussionSimilar cost-effectiveness of sequential ABL/ALN versus unbranded TPTD/ALN, ALN monotherapy, and no treatment was observed in both US men and women at very high fracture risk, with a moderate improvement in cost-effectiveness in men versus women and in patients with a hip or vertebral fracture.ConclusionsSequential therapy with ABL/ALN was cost-effective in US men and women at very high risk of fractures.

Associations between Urinary Concentrations of Polycyclic Aromatic Hydrocarbons and Overactive Bladder in US Adults: Data from the National Health and Nutrition Examination Survey 2005–2016

Introduction: Polycyclic aromatic hydrocarbons (PAHs) are a group of chemicals that can induce oxidative stress and related cytotoxicity. Whether urinary concentrations of PAHs have effects on overactive bladder (OAB) in the general population is still unclear. This study investigated the associations between urinary PAHs and OAB. Methods: 7,146 adults aged over 20 who participated in the US National Health and Nutrition Examination Survey 2005–2016 were studied. The impact of the six PAHs on OAB was evaluated by multivariate logistic regression, and percent changes related to different quartiles of those six PAH levels were calculated. Confounders including age, logarithmic urinary creatinine, gender, race, body mass index, educational level, marriage, poverty income ratio, diabetes, hypertension, and metabolic syndrome were controlled. Results: There is a significant positive correlation between urinary concentrations of the six PAHs we include in the study and the occurrence of OAB. Furthermore, individuals with higher PAH levels also reported a more severe OAB symptom score (OABSS). Conclusions: Our findings revealed that adult men in the USA with higher urinary PAHs had a higher risk of OAB incidence. These findings suggest the importance of strong environmental regulation of PAHs to protect population health. However, the underlying mechanisms still need further exploration.

Abstract B009: Targeting the AR co-activator CBP/p300 axis in castration resistant prostate cancer Impacts DNA damage repair function

Abstract Prostate cancer (PCa) is the second leading cause of cancer related deaths in US men. PCa is an androgen dependent disease and the transcription factor, androgen receptor (AR), is crucial for the overall outcome. Currently, androgen-deprivation therapy (ADT) is the standard of care first-line therapy for metastatic PCa. Resistance to ADT almost uniformly leads to lethal disease, termed castration-resistant prostate cancer (CRPC). Thus, there is a significant unmet clinical need to identify and develop novel strategies to treat CRPC. CBP/p300 are potent co-activators for AR. High expression of CBP/p300 are associated with locally advanced disease and castration resistant function of AR; thus, resulting in poor patient outcome and further highlighting the need to discern the role of CBP/p300 to potentially develop novel therapeutic targets for precision medicine. Previous studies have relied on non-specific compounds and genetic silencing to target CBP/p300 and its associated transcriptional machinery. In this study, CBP/p300 mediated bromodomain activity is targeted by CCS1477 (Inobrodib), a first-in-class bromodomain inhibitor developed by Cell Centric. CCS1477 was shown to demonstrate effective inhibition in growth and clonogenicity assays. Inhibition of the CBP/p300 bromodomain with CCS1477 resulted in significant downregulation of AR-FL, AR-V7, and its targets’ mRNA expression in addition to inhibition of associated factors such as c-MYC and its downstream targets in PCa cell lines as well as patient derived xenograft (PDX) models. This study shows that CBP and p300 are highly expressed and correlate closely with AR gene expression and AR activity score in primary PCa and CRPC patient samples. The clinical significance of CBP/p300 expression in PCa has been investigated via elucidation of CBP/p300 transcriptional reprogramming and role in DNA damage response (DDR) pathways. Specifically, findings revealed that CBP/p300 bromodomain suppression sensitizes to AR-dependent DNA-repair. Transcriptional mapping identified CBP/p300 as regulators of cell proliferation and DNA repair processes, which were functionally confirmed across several PCa model systems. To assess relevance, exogenous challenge with radiation revealed that CBP/p300 bromodomain is required for AR-mediated DNA repair, and CBP/p300 expression is linked to DNA repair capacity in the clinical setting. Molecular analyses revealed that CBP/p300 facilitate double-strand break (DSB) repair efficiency via homologous recombination (HR) mediated DDR. Congruently, CBP/p300 strongly correlated with HR gene expression in PCa patient tissue. These collective findings reveal that CBP/p300 govern repair of DNA DSBs by regulating HR, thus modulating genome integrity, and promoting CRPC growth. In conclusion, these studies identify CBP/p300 as a driver of PCa tumorigenesis through coordinated control of critical transcriptional events and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed therapies. Citation Format: Sumaira Sardar. Targeting the AR co-activator CBP/p300 axis in castration resistant prostate cancer Impacts DNA damage repair function [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B009.

How Work Hour Variability Matters for Work-to-Family Conflict

Variable work hours are an understudied source of work-to-family conflict (WFC). We examine the relationships between the magnitude and direction of work hour variability and WFC and whether work hour control and schedule predictability moderate these relationships. We estimate a series of linear regressions using the 2016 US General Social Survey, examining women and men workers separately and together. Findings indicate that as the magnitude of work hour variability increases, so does WFC, controlling for the usual number of hours worked. Work hour control helps to protect workers, especially women, from WFC when work hour variability is high and hours surge. Although schedule predictability tempers the relationship between work hour variability and WFC, its potency diminishes as variability increases. Our study emphasizes the potential benefit to workers and families of government policies and employer practices that promote work hour stability, schedule predictability, and equity in employee work hour control.

A protocol for the prospective study of urinary cadmium with risk of fracture, bone loss, and muscle loss.

Cadmium (Cd) is a heavy metal and natural element found in soil and crops with increasing concentrations linked to phosphate fertilizers and sewage sludge applied to crop lands. A large fraction of older US men and woman have documented Cd exposure. Cd exposure has proven health concerns such as risk of lung cancer from inhalation and impaired renal function; however, growing evidence suggests it also influences bone and muscle health. Given that low levels of Cd could affect bone and muscle, we have designed prospective studies using the two largest and most detailed US studies of bone health in older men and women: the Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures. We are investigating the association of urinary cadmium (U-Cd), as a surrogate for long-term Cd exposure, with bone and muscle health. Building off suggestive evidence from mechanistic and cross-sectional studies, this will be the first well-powered prospective study of incident fracture outcomes, bone loss, and muscle loss in relation to U-Cd, an established biomarker of long-term Cd exposure. The following is a proposed protocol for the intended study; if successful, the proposed studies could be influential in directing future US policy to decrease Cd exposure in the US population similar to recent policies adopted by the European Union to limit Cd in fertilizers.

Preconception health indicators among adult US men: Race/ethnicity variations and temporal trends.

Preconception health is important for men as it is for women. However, optimizing preconception health is understudied among men. To examine the time trends and temporal shifts in preconception health risk indicators among 20-44-year-old adult US men in need of preconception care and their racial/ethnic variations. Data from the 2011-2019 National Survey of Family Growth male file was used to estimate the prevalence of nine preconception health indicators among men (20-44 years) intending to have a future pregnancy (n=6813), stratifying by race/ethnicity, and assessing temporal changes across the study period. Binary logit and linear regression models estimated temporal trends from 2011-2013 to 2017-2019. Absolute and relative changes were estimated to detect temporal shifts in men's preconception health comparing 2011-2013 to 2017-2019. Men in all groups exhibited substantial preconception health needs, with unique trends across race/ethnicity groups. Between 2011 and 2019, the prevalence of marijuana use (28.6%-39.4%, p=0.001), overweight/obese status (60.7%-65.1%, p≤0.001), and the mean number of preconception health indicators (M=2.69-2.84, p=0.018) increased. Among non-Hispanic White men, the prevalence of marijuana use (30.1%-41.4%, p=0.028), overweight/obese status (60.6%-63.7%, p=0.002), and mean number of preconception health risk indicators (M=2.74-2.90, p=0.033) increased. Among Hispanic men, the prevalence of inconsistent/no condom use (68.9%-81.4%, p=0.022), marijuana use (18.9%-40.4%, p=0.001), and the mean number preconception health risk indicators (M=2.50-2.96, p=0.014) increased. Among non-Hispanic Black men, sexually transmitted infections declined (5.4%-3.6%, p=0.002). Significant temporal shifts, which varied by race/ethnicity, were also observed. Our study, which provides initial insight into men's preconception health development in the last decade, highlights a tremendous need for preconception health care among men. Their increasing preconception health needs, and their racial/ethnic variations, suggest additional contributors to racial/ethnic differences in men's reproductive outcomes and their long-term health.

Abstract B145: Validation of a colorectal cancer risk prediction model in US Black women

Abstract Background: The National Cancer Institute’s Colorectal Cancer Risk Assessment Tool (NCI-CCRAT) estimates an individual's five-year risk of developing colorectal cancer. It was developed by estimating relative risks from a population of US White women and men and incorporating race, gender, and age-specific incidence data from population-based cancer registries. However, the model performance has not been assessed for Black Americans, who have the highest colorectal cancer incidence and mortality rates of any US racial/ethnic group. Methods: The NCI-CCRAT estimates the absolute risk of colorectal cancer based on an individual’s age, sex, family history of colorectal cancer, sigmoidoscopy/colonoscopy, polyps, smoking, physical activity, regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use, vegetable intake, body mass index, and hormone replacement therapy use. Validation of the NCI-CCRAT was performed using prospective data from 57,558 participants ages 40 to 84 years in the Black Women's Health Study (BWHS). We predicted 5-year absolute risk using data from 2001 through 2015 in three 5-year prediction periods: 2001-2005, 2006-2010, and 2011-2015. To assess model performance, we computed calibration by comparing the expected number of colorectal cancer cases predicted by the model to the observed number of cases (E/O) in the BWHS overall and in subgroups of the population. We assessed discriminatory accuracy by calculating the area under the curve (AUC). Results: During follow-up from 2001 through 2015 (634,512 person-years), 433 BWHS participants developed invasive colorectal cancer. Based on the NCI-CCRAT, 543 cases were expected. The NCI-CCRAT was well-calibrated in the first 5-year prediction period (2001-2005 E/O=1.03, 95% CI: 0.88–1.21), but the model overestimated risk in the subsequent 5-year prediction periods, with E/O=1.30 for 2006-2010 and E/O=1.44 for 2011-2015. The overall E/O ratio was 1.25 (95% confidence interval: 1.14–1.38), indicating that NCI-CCRAT overestimated the number of cases in this population of Black women. Of note, associations with colorectal cancer were weaker in the BWHS than in the development cohort for vigorous physical activity, aspirin/NSAID use, vegetable intake, and body mass index. We estimated discriminatory accuracy only for the first 5-year prediction period (2001-2005, N cases=151) for which the model was well calibrated, and obtained an age-adjusted AUC of 0.61 (95% CI: 0.57–0.66). Conclusions: The NCI-CCRAT overestimated the overall number of colorectal cancer cases by 25% in this prospective cohort of Black women, possibly due to population-specific differences in the relative risks of key factors driving colorectal cancer incidence. Discriminatory accuracy was similar to measures from the original validation cohort of White women and men. Impact: This study suggests that further research is needed to determine the most important predictors of colorectal cancer etiology in Black women and to develop and test a colorectal cancer risk prediction model for Black Americans. Citation Format: Jessica L. Petrick, Nelsy Castro-Webb, Gary R. Zirpoli, Kerrie P. Nelson, Julie R. Palmer, Ruth M. Pfeiffer. Validation of a colorectal cancer risk prediction model in US Black women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B145.

Inflammatory Tongue Conditions and Risk of Oral Tongue Cancer Among the US Elderly Individuals.

The incidence of oral tongue cancers has increased since the 1980s among US men and women for unknown reasons. We investigated associations of inflammatory tongue conditions with risk of cancers of the oral tongue, other oral cavity, and oropharynx among the US elderly individuals (age 65 years or older). We conducted a case-control study (2,534 oral tongue cancers, 6,832 other oral cavity cancers, 9,373 oropharyngeal cancers, and 200,000 controls) within the SEER-Medicare data set (1992-2013). Medicare records were used to identify patients with clinically diagnosed inflammatory tongue conditions (glossitis, benign migratory glossitis, median rhomboid glossitis, atrophic glossitis, glossodynia, other specified conditions [eg, atrophy and hypertrophy], and other unspecified conditions) and oral precancer (leukoplakia/erythroplakia). Only conditions preceding cancer/control selection by >12 months were included. The prevalence of inflammatory tongue conditions was significantly higher in patients with tongue cancer than controls (6.0% v 0.6%; odds ratios [ORs], adjusted for age, sex, race, Medicare utilization, and precancer, 5.8 [95% CI, 4.7 to 7.2]). This overall association primarily arose from glossitis, 5.6 (95% CI, 4.4 to 7.2); other specified conditions, 9.1 (95% CI, 5.5 to 15.2); and other unspecified conditions, 13.7 (95% CI, 8.0 to 23.7). These associations remained strongly elevated >5 years preceding tongue cancer (arguing against reverse causation), for conditions diagnosed by a specialist (arguing against misclassification), and among patients who received an oral biopsy (arguing against missed cancer). During 2013, an estimated 1 in 11 patients with oral tongue cancer had a preceding diagnosis of inflammatory tongue conditions. Associations of inflammatory tongue conditions were relatively weak for other oral cavity cancers (ORs, 1.8 [95% CI, 1.5 to 2.3]) and oropharyngeal cancer (OR, 1.3 [95% CI, 1.0 to 1.6]) and were observed only closest to cancer diagnosis. Inflammatory tongue conditions were associated with strongly increased risks of oral tongue cancers and preceded cancer diagnosis by several years, underscoring the need for increased clinical surveillance among patients with such apparently benign diagnoses.

Screening for lung cancer: 2023 guideline update from the American Cancer Society.

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.

The association between several serum micronutrients and benign prostatic hyperplasia: Results from NHANES 2003-2006.

Benign prostatic hyperplasia (BPH) is a common condition that affects the quality of life of older men. Specific micronutrients, including retinol, retinyl esters, carotenoids, vitamin E, and vitamin C, have antioxidant and anti-inflammatory properties. However, the correlation between serum concentrations of these micronutrients and BPH is unclear. We used data from the National Health and Nutrition Examination Survey (NHANES), which included 2067 representative US men. BPH was assessed using the self-reported questionnaire. This association was explored by adjusting for confounders using multivariate logistic regression. After fully adjusting for confounders, for every 0.01 μmol/L increase in serum retinyl esters, the risk of BPH increased by 2% (OR = 1.02; 95% CI: 1.01-1.03; p = 0.006). Based on the Bonferroni-corrected p-value, we found this correlation to be significant. One μmol/L increase in total carotenoids was associated with a 22% increase in BPH risk (OR = 1.22; 95% CI: 1.03-1.46; p = 0.025). By analyzing the correlation between different types of carotenoids and BPH, we also found that β-carotenoids (OR = 1.43; 95% CI: 1.03-1.99; p = 0.036) was also positively correlated with BPH. The subgroup analysis revealed a positive correlation between serum vitamin E (OR = 1.02; 95% CI: 1.00-1.04; p = 0.018) and BPH in men under 60 years of age. Serum retinyl ester (OR = 1.02; 95% CI: 1.01-1.04; p = 0.008) and carotenoid (OR = 1.52; 95% CI: 1.22-1.87; p < 0.001) concentrations were positively correlated with BPH in men over 60 years of age. Our study suggests that excessive serum retinyl esters, total carotenoids, and especially β-carotenoids are potential risk factors for BPH, and this association should be further investigated.

Association of serum uric acid levels with benign prostatic hyperplasia in US men: results from NHANES 2005–2008

Background The relationship between uric acid (UA) and benign prostatic hyperplasia (BPH) is controversial and has rarely been studied in American populations. Methods Data from two cycles of the National Health and Nutrition Examination Surveys, comprising data from 2005 to 2008, were used. The majority of BPH were identified by self-report. We investigated the relationship between UA and BPH using univariate and multivariate logistic regression analyses. Results 2,845 participants were enrolled in the study, including 531 participants with BPH and 2,314 controls. After fully adjusting for all confounders, the risk of developing BPH was reduced by 18% for every 100 μmol/L increase in UA (OR = 0.82, 95% CI: 0.69–0.97, p = 0.023). Participants in the highest quartile of UA were found to have a reduced likelihood of developing BPH (ORQ4vs1 = 0.61, 95% CI: 0.41–0.91) in comparison to those in the lowest quartile of UA. Subgroup analyses found that among those younger than 60 years, non-Hispanic whites, former smokers, heavy drinkers, those without diabetes, or those with hypertension, high UA remained negatively associated with BPH. Conclusions The above results suggest that UA may be a potential protective factor for BPH, but the mechanism needs to be further explored.

Effect of transurethral resection of prostate on Uroflowmetry parameters on patients having benign prostatic hyperplasia

Objective: To determine improvement in uroflowmetry after Transurethral resection ofprostateStudy design: A prospective observational Study Place and Duration of the Study: January 2014 to June 2016 Department at urology POF HospitalWah Cantt, Pakistan INTRODUCTION:Lower urinary tract problems affect 15%–60% of men over 40. Complex symptoms include frequency, urgency, nocturia, problems commencing urination, insufficient bladder emptying, low steam force, and steam stoppage. BPH frequently causes male LUTS. Benign prostatic enlargement Chronic BOO may induce urine retention, renal insufficiency, recurrent UTIs, extensive hematuria, and bladder calculi. It involves prostate histopathological cellular element proliferation. BPH and LUTS rise considerably with age. BPH affects 70% of US men aged 60–69 and 80% over 70. Autopsy examinations indicated 8%, 50%, and 80% histological frequency in the 4". and 9*decades. LUTS risk factors and larger prostates cause benign prostatic enlargement. Formerly, TURP was the best BPH procedure. Higher disease pathophysiology knowledge and digital rectal examination, transabdominal, and transrectal ultrasounds are the second most prevalent interventions in adult male patients worldwide. Urodynamic and serum PSA tests may misdiagnose the condition and require surgery. Uroflowmetry records voiding time from urinal pee. It would assess average flow and obstruction severity. For boys 14–45, the average flow rate is 21 mL/s, 46–65 mL/s, and 66–80 mL/s. Uroflowmetry in post-TURP benign hypertrophic hyperplasia patients will be examined after transurethral prostate removal. keywords: transurethral resection , prostate Uroflowmetry parameters, prostatic hyperplasia

FRI682 Cost Effectiveness Of Four Treatment Approaches For US Women And Men At Very High Risk Of Osteoporotic Fractures

Abstract Disclosure: M. Hiligsmann: Grant Recipient; Self; Radius Health, Inc. S. Silverman: Consulting Fee; Self; Amgen Inc, Radius Health, Inc. Grant Recipient; Self; Amgen Inc, Radius Health, Inc. A.J. Singer: Consulting Fee; Self; Agnovos, Amgen Inc, Radius Health, Inc, UCB. Speaker; Self; Amgen Inc, Radius Health, Inc. L. Pearman: Employee; Self; Radius Health, Inc. Stock Owner; Self; Radius Health, Inc. Y. Wang: Employee; Self; Radius Health, Inc. Stock Owner; Self; Radius Health, Inc. J.N. Caminis: Employee; Self; Radius Health, Inc. Stock Owner; Self; Radius Health, Inc. J. Reginster: Advisory Board Member; Self; Pierre Fabre. Consulting Fee; Self; IBSA-Genevrier, Mylan, Teva Pharmaceutical Industries Ltd. Speaker; Self; IBSA-Genevrier, Mylan, CNIEL, Dairy Research Council, Teva Pharmaceutical Industries Ltd. Background: Cost-effectiveness analyses are becoming increasingly important for efficiency in healthcare resource allocation. This study aims to assess the cost-effectiveness of four common treatment approaches of US men and women at very high risk of fracture: bisphosphonate (alendronate [ALN]) monotherapy, sequential treatment with an anabolic first (either abaloparatide [ABL] or teriparatide [TPTD]) followed by a bisphosphonate, and no treatment, as many patients at very high fracture risk do not receive an osteoporosis medication. Methods: A microsimulation-based Markov model was used to assess the cost-effectiveness of four treatment approaches in US women and men aged 50 to 80 years who had a recent fracture and had densitometry-confirmed osteoporosis (bone mineral density T-score ≤−2.5): ALN monotherapy, sequential ABL/ALN, sequential unbranded TPTD/ALN, and no treatment. Analyses were conducted from the US healthcare decision-maker perspective using $2022 costs, and health outcomes were expressed in quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were performed to characterize uncertainty. Results: In both sexes and over the full age range, no treatment and sequential unbranded TPTD/ALN were dominated (ie, they had lower QALYs for more costs than a comparator treatment), and should be excluded. Sequential ABL/ALN was associated with more QALYs and more costs than ALN monotherapy. At the US threshold of $150,000 per QALY gained, sequential ABL/ALN was cost-effective compared to ALN monotherapy in men aged ≥50 years and in women aged ≥65 years. Sensitivity analyses suggested that sequential ABL/ALN was also cost-effective in women with a recent hip or vertebral fracture aged ≥55 years. Conslusion: In both US men (aged ≥50 years) and women (aged ≥65 years) at very high risk of fracture, sequential ABL/ALN is the most cost-effective intervention among the four treatment approaches. Sequential unbranded TPTD/ALN and no treatment were dominated, and are thus not efficient treatment approaches. Treating US men and women at very high fracture risk with sequential ABL/ALN leads to an efficient resource allocation. Presentation: Friday, June 16, 2023

Physical Activity Among Rural Men: Barriers and Preferences.

Physical activity positively affects health. Although 94% of Americans know the health benefits of regular physical activity, more than 75% do not achieve recommended levels. The objective of our study was to identify and define the key components of a physical activity intervention tailored to rural American men. We recruited rural men (N = 447) via Amazon's Mechanical Turk online platform to complete a needs assessment survey focused on their interest in a physical activity intervention, preferred intervention features, and potential intervention objectives. Data were summarized by using descriptive statistics. A cumulative logistic regression model examined associations between the men's perceived importance of physical activity to health and their interest in a physical activity intervention. Almost all participants (97.7%) rated physical activity as "at least somewhat important" to their health, and 83.9% indicated they would be "at least somewhat interested" in participating in a physical activity intervention. On a scale of 1 (not at all a barrier) to 5 (very much a barrier), motivation (mean 3.4; 95% CI, 3.3-3.5), cold weather (mean, 3.4; 95% CI, 3.3-3.5), and tiredness (mean, 3.3; 95% CI, 3.2-3.4) were rated the biggest barriers to physical activity. Becoming fitter (54.1%) was the top reason for joining a physical activity program. Preferred delivery channels for receiving an intervention were mobile application (ranked from 1 being the most preferred and 9 being the least preferred: mean, 2.8; 95% CI, 2.70-3.09) and e-mail (mean, 4.2; 95% CI, 3.92-4.36). Rural men preferred interventions that taught them how to exercise and that could be done from home. Our findings suggest US men in rural areas are receptive to physical activity programs. A systematic approach and a clear model of development are needed to tailor future physical activity interventions to the special needs of rural men.

Probable Parasomnias and Mortality: A Prospective Study in US Men

ObjectiveTo examine the association between parasomnias, including rapid eye movement sleep behavior disorder (RBD) and sleep walking (SW), and mortality risk in a large-scale population-based cohort. MethodsThis prospective cohort study was based on 25,695 participants from the Health Professionals Follow-up Study, a population-based cohort of male health professionals in the United States. Probable SW (pSW) and probable RBD (pRBD) were measured by questions adapted from the Mayo Sleep Questionnaire in 2012. All-cause mortality and cause-specific mortality were ascertained through the national registry, reports by the families, and the postal system from January 1, 2012, through June 30, 2018. ResultsOf the studied population, 223 reported pSW and 2720 reported pRBD. During 6 years of follow-up (2012 to 2018), 4743 mortality cases were documented. The co-occurrence of both probable parasomnias was associated with higher all-cause mortality risk (Ptrend=.008), and the adjusted hazard ratio (HR) of mortality was 1.65 (95% CI, 1.20 to 2.28) compared with participants without either probable parasomnia after adjustment for major lifestyle, sleep, and metabolic risk factors, and chronic diseases. Significant associations were found for mortality attributed to neurodegenerative diseases (adjusted HR for both parasomnias vs none, 4.57; 95% CI, 2.62 to 7.97) and accidents (adjusted HR for both parasomnias vs none, 7.36; 95% CI, 2.95 to 18.4). Having pSW alone was associated with all-cause mortality, and pSW and pRBD were individually associated with mortality attributed to neurodegenerative diseases and accidents too (P<.05 for all). ConclusionProbable parasomnia was associated with a higher risk of all-cause mortality and mortality attributed to neurodegenerative diseases and accidents.

Variation in Preferences for Long-Acting Injectable Pre-Exposure Prophylaxis Among US Men Who Have Sex with Men: A Latent Class Analysis.

Cabotegravir long-acting injectable HIV pre-exposure prophylaxis (LA PrEP) is efficacious, with a good safety profile, and was approved by the US Food and Drug Administration in December 2021. Understanding variations in potential user preferences for LA PrEP may inform implementation and subsequently improve uptake and community-level effectiveness. HIV-negative, sexually active men who have sex with men (MSM) aged ≥15 years were recruited online for the 2019 American Men's Internet Survey, before LA PrEP approval. Respondents completed a discrete-choice experiment (DCE) with hypothetical LA PrEP attributes (out-of-pocket cost, perceived side effects, injection frequency, perceived stigma, service location). Latent class analysis segmented respondents into groups based on their preferences for the attributes presented, and relative importance of preference weights and willingness-to-pay were calculated. While the majority had never used daily oral PrEP, 73% of the 2489 respondents were very or somewhat likely to use LA PrEP. Three latent classes were identified from 2241 respondents in the DCE. The "side effects-averse" class was the largest group (64% of respondents) and placed 61% relative importance on side effects. The "ambivalent" class (20% of respondents) placed higher importance on stigma (17% of relative importance) than other classes. The "cost-conscious" class (16% of respondents) placed higher relative importance (62%) on cost compared with other attributes and classes. Perceived side effects were an important hypothetical barrier for LA PrEP uptake among a large proportion of potential MSM users. Minimizing out-of-pocket costs is likely to increase uptake and may be important to equitable access. Tailored communication strategies are recommended for the different groups of potential LA PrEP users.