Racial disparities in colorectal cancer outcomes and access to care: a multi-cohort analysis.

Introduction: Non-Hispanic Black (NHB) Americans have a higher incidence of colorectal cancer (CRC) and worse survival than non-Hispanic white (NHW) Americans, but the relative contributions of biological versus access to care remain poorly characterized. This study used two nationwide cohorts in different healthcare contexts to study health system effects on this disparity. Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) registry as well as the United States Veterans Health Administration (VA) to identify adults diagnosed with colorectal cancer between 2010 and 2020 who identified as non-Hispanic Black (NHB) or non-Hispanic white (NHW). Stratified survival analyses were performed using a primary endpoint of overall survival, and sensitivity analyses were performed using cancer-specific survival. Results: We identified 263,893 CRC patients in the SEER registry (36,662 (14%) NHB; 226,271 (86%) NHW) and 24,375 VA patients (4,860 (20%) NHB; 19,515 (80%) NHW). In the SEER registry, NHB patients had worse OS than NHW patients: median OS of 57 months (95% confidence interval (CI) 55-58) versus 72 months (95% CI 71-73) (hazard ratio (HR) 1.14, 95% CI 1.12-1.15, p = 0.001). In contrast, VA NHB median OS was 65 months (95% CI 62-69) versus NHW 69 months (95% CI 97-71) (HR 1.02, 95% CI 0.98-1.07, p = 0.375). There was significant interaction in the SEER registry between race and Medicare age eligibility (p < 0.001); NHB race had more effect in patients <65 years old (HR 1.44, 95% CI 1.39-1.49, p < 0.001) than in those ≥65 (HR 1.13, 95% CI 1.11-1.15, p < 0.001). In the VA, age stratification was not significant (p = 0.21). Discussion: Racial disparities in CRC survival in the general US population are significantly attenuated in Medicare-aged patients. This pattern is not present in the VA, suggesting that access to care may be an important component of racial disparities in this disease.

Correspondence between the alcohol-P3 event-related potential and alcohol reward phenotypes among young adults.

BACKGROUND: Behavioral economic theory suggests that the value of alcohol depends upon elements of the choice context, such that increasing constraints on alternatives (e.g., price) or increasing the benefits of alcohol (e.g., social context) may result in greater likelihood of heavy drinking. The P3 event-related potential elicited by alcohol-related cues, a proposed marker of incentive salience, may be an electrophysiological parallel for behavioral economic alcohol demand. However, these indices have not been connected in prior research, and studies typically do not disaggregate social influences in the context of alcohol cue reactivity. METHOD: The current study recruited heavy drinking young adults (N = 81) who completed measures of alcohol use and alcohol demand, in addition to a 2 (social/nonsocial) × 2 (alcohol/nonalcohol) visual oddball task to elicit the P3. RESULTS: In multilevel models controlling for demographic characteristics, P3 reactivity was greater to alcohol (p < 0.001) and social (p < 0.001) cues than to nonalcohol and nonsocial cues, but without a significant interaction. Higher alcohol consumption (p = 0.02) and lower elasticity of demand (p = 0.01) were associated with greater P3 response to alcohol than nonalcohol cues. CONCLUSIONS: The results highlight a brain-behavior connection that may be an important marker for alcohol reward across units of analysis and may be sensitive to changes in the economic choice contexts that influence the likelihood of alcohol use.

The association between PTSD symptom clusters and religion/spirituality with alcohol use among first responders.

Alcohol misuse and posttraumatic stress disorder (PTSD) co-occur at high rates among first responders (e.g., law enforcement, firefighters, paramedics), underscoring the need to better understand these relations to inform intervention efforts. Identifying malleable processes relevant to the association between PTSD and alcohol among first responders could inform tailored interventions. An example of such a malleable process is spirituality. As such, the current study examined the unique relationships between PTSD symptom clusters and alcohol misuse, while also accounting for the role of select demographics and religion/spirituality, in a sample of first responders. A national online sample of first responders (N = 320) completed measures of PTSD symptomology, alcohol misuse, religion/spirituality and demographics. Hierarchical linear regression analyses revealed that PTSD Intrusion (Cluster B) symptom severity was associated with greater alcohol misuse and PTSD Avoidance (Cluster C) was associated with lower alcohol misuse. Additionally, positive and negative spiritual coping were also associated with alcohol misuse. In the context of similar research among military samples, findings suggest potentially unique associations between PTSD symptom clusters and alcohol misuse among first responders. Additionally, findings highlight the potentially protective role of religion/spirituality in this population. Future research should explore nuanced relationships between PTSD symptom clusters and alcohol misuse as well as the salience of spirituality/religion in this unique population.

Associations Between Radiation Oncologist Demographic Factors and Segmentation Similarity Benchmarks: Insights From a Crowd-Sourced Challenge Using Bayesian Estimation.

PURPOSE: The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors. METHODS: Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used. Segmentations were derived from five disease sites: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and GI. Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus, which served as a reference standard benchmark. The Dice similarity coefficient (DSC) was primarily used as a metric for the comparisons. DSC was stratified into binary groups on the basis of structure-specific expert-derived interobserver variability (IOV) cutoffs. Generalized linear mixed-effects models using Bayesian estimation were used to investigate the association between demographic variables and the binarized DSC for each disease site. Variables with a highest density interval excluding zero were considered to substantially affect the outcome measure. RESULTS: Five hundred seventy-four, 110, 452, 112, and 48 segmentations were used for the breast, sarcoma, H&N, GYN, and GI cases, respectively. The median percentage of segmentations that crossed the expert DSC IOV cutoff when stratified by structure type was 55% and 31% for OARs and tumors, respectively. Regression analysis revealed that the structure being tumor-related had a substantial negative impact on binarized DSC for the breast, sarcoma, H&N, and GI cases. There were no recurring relationships between segmentation quality and demographic variables across the cases, with most variables demonstrating large standard deviations. CONCLUSION: Our study highlights substantial uncertainty surrounding conventionally presumed factors influencing segmentation quality relative to benchmarks.

Efficiently Quantifying Egocentric Social Network Cannabis Use: Initial Psychometric Validation of the Brief Cannabis Social Density Assessment.

OBJECTIVE: Social environment is a key determinant of substance use, but cannabis-related social network analysis is not common, in part due to the assessment burden of comprehensive egocentric social network analysis. METHOD: The current pre-registered secondary analysis assessed the psychometric properties (i.e., convergent, criterion-related, incremental validity) of the Brief Cannabis Social Density Assessment (B-CaSDA) in a cross-sectional sample of adults who use cannabis (N = 310) using a survey-based design. The B-CaSDA assesses the quantity and frequency of cannabis use for the respondent's four closest (non-parent) relationships. RESULTS: Cannabis use severity was elevated for each additional person who used cannabis at all or daily in the individual's social network. B-CaSDA indices (i.e., frequency, quantity, total score) were positively correlated with cannabis consumption, cannabis use severity indicators, and established risk factors for harmful cannabis use. B-CaSDA indices also discriminated between those above and below a clinical cutoff on the Cannabis Use Disorder Identification Test - Revised (CUDIT-R). Finally, in omnibus models that included common risk factors for cannabis use severity, the B-CaSDA quantity index contributed additional variance when predicting CUDIT-R total score, and B-CaSDA frequency contributed additional variance in predicting the CUDIT-R quantity-frequency subscale. CONCLUSIONS: The results suggest that the B-CaSDA has the potential to expand social network research on cannabis use and misuse by increasing its assessment feasibility in diverse designs.

An immunohistochemical atlas of necroptotic pathway expression.

Necroptosis is a lytic form of regulated cell death reported to contribute to inflammatory diseases of the gut, skin and lung, as well as ischemic-reperfusion injuries of the kidney, heart and brain. However, precise identification of the cells and tissues that undergo necroptotic cell death in vivo has proven challenging in the absence of robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry protocols to detect core necroptosis regulators - Caspase-8, RIPK1, RIPK3 and MLKL - in formalin-fixed mouse and human tissues. We observed surprising heterogeneity in protein expression within tissues, whereby short-lived immune barrier cells were replete with necroptotic effectors, whereas long-lived cells lacked RIPK3 or MLKL expression. Local changes in the expression of necroptotic effectors occurred in response to insults such as inflammation, dysbiosis or immune challenge, consistent with necroptosis being dysregulated in disease contexts. These methods will facilitate the precise localisation and evaluation of necroptotic signaling in vivo.

Molecular dissection of the pseudokinase ZED1 expands effector recognition to the tomato immune receptor ZAR1.

The highly conserved angiosperm immune receptor HOPZ-ACTIVATED RESISTANCE 1 (ZAR1) is a bacterial pathogen recognition hub that mediates resistance by guarding host kinases for modification by pathogen effectors. The pseudokinase HOPZ-ETI DEFICIENT 1 (ZED1) is the only known ZAR1-guarded protein that interacts directly with a pathogen effector, HopZ1a, from the bacterial pathogen Pseudomonas syringae, making it a promising system for rational design of effector recognition for plant immunity. Here, we conducted an in-depth molecular analysis of ZED1. We generated a library of 164 random ZED1 mutants and identified 50 mutants that could not recognize the effector HopZ1a when transiently expressed in Nicotiana benthamiana. Based on our random mutants, we generated a library of 27 point mutants and found evidence of minor functional divergence between Arabidopsis (Arabidopsis thaliana) and N. benthamiana ZAR1 orthologs. We leveraged our point mutant library to identify regions in ZED1 critical for ZAR1 and HopZ1a interactions and identified two likely ZED1-HopZ1a binding conformations. We explored ZED1 nucleotide and cation binding activity and showed that ZED1 is a catalytically dead pseudokinase, functioning solely as an allosteric regulator upon effector recognition. We used our library of ZED1 point mutants to identify the ZED1 activation loop regions as the most likely cause of interspecies ZAR1-ZED1 incompatibility. Finally, we identified a mutation that abolished ZAR1-ZED1 interspecies incompatibility while retaining the ability to mediate HopZ1a recognition, which enabled recognition of HopZ1a through tomato (Solanum lycopersicum) ZAR1. This provides an example of expanded effector recognition through a ZAR1 ortholog from a non-model species.

Relationships of State Alcohol Policy Environments With Homicides and Suicides.

INTRODUCTION: Alcohol use is involved in a large proportion of homicides and suicides each year in the U.S., but there is limited evidence on how policies targeting alcohol influence violence in the U.S. CONTEXT: Extant studies generally focus on individual policies in isolation of each other. This study examines the impacts of changes in states' alcohol policy restrictions on overall homicide and suicide rates and firearm-related homicide and suicide rates using a holistic measure of states' alcohol policy environments. METHODS: Using a composite measure of state-level alcohol policies (Alcohol Policy Scale) and data from the National Vital Statistics System from 2002 to 2018, this study applied a Bayesian time series model to estimate the impacts of alcohol policy changes on overall and firearm-involved homicide and suicide rates. The analysis was performed in 2023 and 2024. RESULTS: A 1 SD change in the Alcohol Policy Scale was associated with a 6% decline in homicide rates both overall (incident rate ratio=0.94; 95% credible interval = 0.89, 1.00) and for firearm homicides specifically (incident rate ratio=0.94, 95% CI=0.88, 1.01). There was no clear association of alcohol policy with suicides. The model predicts that a nationwide increase in alcohol restrictions equivalent to a shift from the 25th to 75th percentile of the scale's distribution would result in almost 1,200 fewer homicides annually. CONCLUSIONS: Increases in the restrictiveness of state-level alcohol policies are associated with reductions in homicides. More restrictive alcohol policy environments may offer an opportunity to reduce homicides.

Co-clustering of EphB6 and ephrinB1 in trans restrains cancer cell invasion.

EphB6 is an understudied ephrin receptor tyrosine pseudokinase that is downregulated in multiple types of metastatic cancers. Unlike its kinase-active counterparts which autophosphorylate and transmit signals upon intercellular interaction, little is known about how EphB6 functions in the absence of intrinsic kinase activity. Here, we unveil a molecular mechanism of cell-cell interaction driven by EphB6. We identify ephrinB1 as a cognate ligand of EphB6 and show that in trans interaction of EphB6 with ephrinB1 on neighboring cells leads to the formation of large co-clusters at the plasma membrane. These co-clusters exhibit a decreased propensity towards endocytosis, suggesting a unique characteristic for this type of cell-cell interaction. Using lattice light-sheet microscopy, 3D structured illumination microscopy and cryo-electron tomography techniques, we show that co-clustering of EphB6 and ephrinB1 promotes the formation of double-membrane tubular structures between cells. Importantly, we also demonstrate that these intercellular structures stabilize cell-cell adhesion, leading to a reduction in the invasive behavior of cancer cells. Our findings rationalize a role for EphB6 pseudokinase as a tumor suppressor when interacting with its ligands in trans.

Osteo-cutaneous microvascular free-flaps are a viable option for reconstructing the temporomandibular joint.

Background: There are multiple reconstructive options after mandibular resection and disarticulation of the condyle. The purpose of this study was to assess the clinical outcomes and functionality of osteocutaneous free flaps in the reconstruction of mandibular defects that involve the Temporo-Mandibular Joint (TMJ). Methods: Our study is a retrospective cohort study involving subjects who underwent mandibular resection and needed TMJ reconstruction with vascularized bony-free flaps from February 2016 to June 2018. Data gathered included patient demographics, post-operative function, maximum interincisal opening (MIO), occlusion status, deviation on opening, and TMJ symptoms. Data points collected from postoperative CT imaging included the following: position of the flap in relation to the glenoid fossa and articular eminence, and closest point of contact. Results: Eight out of the nine patients who underwent free flap reconstruction of mandibular defects involving the TMJ qualified for the study. The mean age was 39.7 years old. In all 8 cases, virtual surgical planning (VSP) was used. The mean follow-up time was 18.75 months. The flap success rate was 100%. The mean MIO was 37.37 mm. Six patients resumed their premorbid diet, and one patient developed dysphagia and was peg tube dependent. In seven cases the occlusion was intact and reproducible, one case was without sufficient teeth for occlusion. On imaging, the mean distance from the neo-condyle to the glenoid fossa was 14 mm and to the articular eminence 8.68 mm. The point of closest contact in all cases appeared to be the articular eminence. Conclusion: Vascularized Osteocutaneous-flaps such as FFFs and DCIA flaps provide a good option for the reconstruction of mandibular defects that involve the TMJ. Ipsilateral deviation on opening does not negatively affect clinical outcomes or function. Placing patients in Maxillomandibular fixation for 4-6 weeks may help to prevent condylar sag and provide stable post-operative occlusion.

Neural correlates of increased alcohol demand following alcohol cue exposure in adult heavy drinkers.

Alcohol use disorder is associated with overvaluation of alcohol relative to other rewards, in part due to dynamic increases in value in response to alcohol-related cues. In a neuroeconomic framework, alcohol cues increase behavioral economic demand for alcohol, but the neural correlates these cue effects are unknown. This functional magnetic resonance imaging study combined a neuroeconomic alcohol purchase task with an alcohol cue exposure in 72 heavy drinkers with established sensitivity to alcohol cues (51 % female; mean age=33.74). Participants reported how many drinks they would consume from $0-$80/drink following exposure to neutral and alcohol images in a fixed order. Participants purchased significantly more drinks in the alcohol compared to the neutral condition, which was also evident for demand indices (i.e., intensity, breakpoint, Omax, elasticity; ps<0.001; ds=0.46-0.92). Alcohol purchase decisions were associated with activation in rostral middle and medial frontal gyri, anterior insula, posterior parietal cortex, and dorsal striatum, among other regions. Activation was lower across regions in the alcohol relative to neutral cue condition, potentially due to greater automaticity of choices in the presence of alcohol cues or attenuation of responses due to fixed cue order. These results contribute to growing literature using neuroeconomics to understand alcohol misuse and provide a foundation for future research investigating decision-making effects of environmental alcohol triggers.

Behavioral economic and wellness-based approaches for reducing alcohol use and consequences among diverse non-student emerging adults: study protocol for Project BLUE, a randomized controlled trial.

BACKGROUND: Emerging adults (EAs) who are not 4-year college students nor graduates are at elevated risk for lifetime alcohol use disorder, comorbid drug use, and mental health symptoms, compared to college graduates. There is a need for tailored brief alcohol intervention (BAI) approaches to reduce alcohol risk and to facilitate healthy development in this high-risk population. Most BAIs include a single session focused on discussing risks associated with drinking and correcting normative beliefs about drinking rates. EAs may benefit from additional elements that enhance general wellness. The substance-free activity session (SFAS) aims to clarify life goals and values and increase goal-directed activities that provide alternatives to alcohol use, and the relaxation training (RT) session teaches relaxation and stress reduction skills. METHODS: The present study is a randomized 3-group (BAI + SFAS vs. RT + SFAS vs. education control) trial with 525 EAs (175 per group; estimated 50% women and 50% African American) who report recent risky drinking and who are not students or graduates of 4-year colleges. Participants will have the option of completing the intervention sessions in person or via a secure video teleconference. Levels of drinking and alcohol-related problems will be evaluated at baseline and 1, 3, 6, and 12 months post-intervention. The primary hypothesis is that both BAI + SFAS and RT + SFAS participants will report significantly greater reductions in alcohol use and problems relative to education control participants, with no differences in outcomes between the two active treatment conditions. DISCUSSION: The results of this study will inform alcohol prevention efforts for high-risk community dwelling emerging adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04776278.

Sleep, Alcohol and Cannabis Use in College Students With and Without Attention-Deficit/Hyperactivity Disorder.

Background: Relations among attention-deficit/hyperactivity disorder (ADHD), sleep, and substance-related negative consequences are largely unknown. In this cross-sectional study, we examined associations among ADHD diagnosis, sleep, and alcohol-related consequences. We also evaluated the independent and interactive effects of sleep and ADHD on alcohol-related negative consequences, above and beyond levels of alcohol use. Methods: College students who drink alcohol with (n = 51) and without (n = 50) ADHD completed an assessment that included a diagnostic interview assessing ADHD, and questionnaire measures of sleep quality, substance use, and associated consequences. Analyses utilized a series of hierarchical linear regression models and explored these aims for cannabis use in a subset of participants (n = 52 participants that used cannabis). Results: College students who drink alcohol with ADHD reported significantly worse sleep quality and more alcohol-related consequences, relative to those without ADHD. When ADHD and sleep quality were included in the model, ADHD-but not sleep quality-was independently associated with alcohol consequences, but not cannabis consequences. There were no moderating effects of ADHD on the associations between sleep and substance-related consequences. Conclusions: Students who drank alcohol with ADHD may be particularly vulnerable to experiencing poor sleep and consequences from their substance use, compared to their heavy drinking peers without ADHD. Future, larger scale studies should consider longitudinal effects as well as underlying mechanisms of risk.

Gasdermin and MLKL necrotic cell death effectors: Signaling and diseases.

Diverse inflammatory conditions, from infections to autoimmune disease, are often associated with cellular damage and death. Apoptotic cell death has evolved to minimize its inflammatory potential. By contrast, necrotic cell death via necroptosis and pyroptosis-driven by membrane-damaging MLKL and gasdermins, respectively-can both initiate and propagate inflammatory responses. In this review, we provide insights into the function and regulation of MLKL and gasdermin necrotic effector proteins and drivers of plasma membrane rupture. We evaluate genetic evidence that MLKL- and gasdermin-driven necrosis may either provide protection against, or contribute to, disease states in a context-dependent manner. These cumulative insights using gene-targeted mice underscore the necessity for future research examining pyroptotic and necroptotic cell death in human tissue, as a basis for developing specific necrotic inhibitors with the potential to benefit a spectrum of pathological conditions.

Behavioral Economic and Wellness-based Approaches for Reducing Alcohol Use and Consequences Among Diverse Non-Student Emerging Adults: Study Protocol for Project BLUE, a Randomized Controlled Trial.

Background: Emerging adults (EAs) who are not 4-year college students nor graduates are at elevated risk for lifetime alcohol use disorder, comorbid drug use, and mental health symptoms, compared to college graduates. There is a need for tailored brief alcohol intervention (BAI) approaches to reduce alcohol risk and to facilitate healthy development in this high-risk population. Most BAIs include a single session focused on discussing risks associated with drinking and correcting normative beliefs about drinking rates. EAs may benefit from additional elements that enhance general wellness. The Substance-Free Activity Session (SFAS) aims to clarify life goals and values and increase goal-directed activities that provide alternatives to alcohol use, and the Relaxation Training (RT) session teaches relaxation and stress reduction skills. Methods: The present study is a randomized 3-group (BAI+SFAS vs. RT+SFAS vs. education control) trial with 525 EAs (175 per group; estimated 50% women & 50% African American) who report recent risky drinking and who are not students or graduates of 4-year colleges. Participants will have the option of completing the intervention sessions in person or via a secure video teleconference. Levels of drinking and alcohol-related problems will be evaluated at baseline and 1, 3, 6, and 12-months post-intervention. The primary hypothesis is that both BAI+SFAS and RT+SFAS participants will report significantly greater reductions in alcohol use and problems relative to education control participants, with no differences in outcomes between the two active treatment conditions. Discussion: The results of this study will inform alcohol prevention efforts for high-risk community dwelling emerging adults. ClinicalTrialsgov Identifier: NCT04776278.

Longitudinal examination of alcohol demand and alcohol-related reinforcement as predictors of heavy drinking and adverse alcohol consequences in emerging adults.

BACKGROUND AND AIMS: Behavioral economic theory predicts that high alcohol demand and high proportionate alcohol-related reinforcement are important determinants of risky alcohol use in emerging adults, but the majority of research to date has been cross-sectional in nature. The present study investigated prospective and dynamic relationships between alcohol demand and proportionate alcohol-related reinforcement in relation to heavy drinking days and alcohol problems. DESIGN: Longitudinal cohort with assessments every 4 months for 20 months. SETTING: Ontario, Canada. PARTICIPANTS: Emerging adults reporting regular heavy episodic drinking (n = 636, Mage = 21.44; 55.8% female). MEASUREMENTS: Heavy drinking days (HDD; Daily Drinking Questionnaire), alcohol problems (Brief Young Adult Alcohol Consequences Questionnaire), alcohol demand (Alcohol Purchase Task) and proportionate alcohol-related reinforcement (Activity Level Questionnaire). FINDINGS: Linear mixed effects models revealed that behavioral economic indicators and alcohol-related outcomes significantly decreased over the study, consistent with 'aging out' of risky alcohol use. Random intercept cross-lagged panel models revealed significant between-person relationships, such that higher alcohol demand and alcohol-related reinforcement were positively associated with HDD and alcohol problems (random intercepts = 0.187-0.534, Ps < 0.01). Moreover, alcohol demand indicators (particularly the rate of change in elasticity of the demand curve, as measured by α, and the maximum expenditure, Omax) and proportionate alcohol-related reinforcement significantly forecasted changes in HDD at all time points (|ßs| = 0.063-0.103, Ps < 0.05) in cross-lagged relationships, with bidirectional associations noted for the rate of change in elasticity (ßs = -0.085 to -0.104, Ps < 0.01). Proportionate alcohol-related reinforcement also significantly forecasted changes in alcohol problems at all time points (ßs = 0.072-0.112, Ps < 0.01). CONCLUSIONS: Multiple behavioral economic indicators (demand elasticity, maximum expenditure and reinforcement ratio) forecast changes in heavy episodic drinking and alcohol problems over the course of emerging adulthood. These results further implicate alcohol demand and proportionate alcohol-related reinforcement as etiologically and developmentally important mechanisms in alcohol use trajectories.

Prostate Cancer Screening Uptake in Transgender Women.

Importance: There is no consensus in prostate-specific antigen (PSA) screening guidelines regarding transgender women despite their known prostate cancer risk. Objective: To identify factors associated with recent (within the last 2 years) PSA screening in transgender women compared with cisgender men. Design, Setting, and Participants: This case-control study used data from the 2018 and 2020 Behavioral Risk Factor Surveillance System (BRFSS) surveys to characterize rates of PSA screening for prostate cancer within the past 2 years and multivariable logistic regressions to characterize factors associated with recent screening among transgender women. The BRFSS program of the Centers for Disease Control and Prevention annually surveys over 400 000 US adults on behavioral risk factors, chronic illnesses, and use of preventive services. Respondents to the BRFSS who were cisgender men or transgender women 40 years or older and who had complete PSA testing responses and no prostate cancer history were included; 313 transgender women and 138 937 cisgender men met inclusion criteria. Matching was performed by age, race and ethnicity, educational level, employment, annual income, survey year, and cost barriers to care. Data were collected on November 2, 2022, and analyzed from November 2, 2022, to December 3, 2023. Main Outcomes and Measures: Rates of and factors associated with recent PSA screening in transgender women. Results: Among the 1275 participants included in the matched cohort (255 transgender women and 1020 cisgender men; 570 [44.7%] aged 55-69 years), recent PSA screening rates among transgender women and cisgender men aged 55 to 69 were 22.2% (n = 26) and 36.3% (n = 165), respectively; among those 70 years and older, these rates were 41.8% (n = 26) and 40.2% (n = 98), respectively. In the matched cohort, transgender women had lower univariable odds of recent screening than cisgender men (odds ratio [OR], 0.65 [95% CI, 0.46-0.92]; P = .02). In a hierarchical regression analysis adding time since the last primary care visit, effect size and significance were unchanged (OR, 0.61 [95% CI, 0.42-0.87]; P = .007). After adding whether a clinician recommended a PSA test, there was no statistically significant difference in odds of screening between transgender women and cisgender men (OR, 0.83 [95% CI, 0.45-1.27]; P = .21). The results were further attenuated when clinician-led discussions of PSA screening advantages and disadvantages were added (OR, 0.87 [95% CI, 0.47-1.31]; P = .32). In a multivariable logistic regression among transgender women, having a recommendation for PSA testing was the factor with the strongest association with recent screening (OR, 12.40 [95% CI, 4.47-37.80]; P < .001). Conclusions and Relevance: In this case-control study of one of the largest cohorts of transgender women studied regarding PSA screening, the findings suggest that access to care or sociodemographic factors were not principal drivers of the screening differences between transgender women and cisgender men; rather, these data underscore the clinician's role in influencing PSA screening among transgender women.

Association of platinum-based chemotherapy with live birth and infertility in female survivors of adolescent and young adult cancer.

OBJECTIVE: To estimate the effect of platinum-based chemotherapy on live birth (LB) and infertility after cancer, in order to address a lack of treatment-specific fertility risks for female survivors of adolescent and young adult cancer, which limits counseling on fertility preservation decisions. DESIGN: Retrospective cohort study. SETTING: US administrative database. PATIENTS: We identified incident breast, colorectal, and ovarian cancer cases in females aged 15-39 years who received platinum-based chemotherapy or no chemotherapy and matched them to females without cancer. INTERVENTION: Platinum-based chemotherapy. MAIN OUTCOME MEASURES: We estimated the effect of chemotherapy on the incidence of LB and infertility after cancer, overall, and after accounting for competing events (recurrence, death, and sterilizing surgeries). RESULTS: There were 1,287 survivors in the chemotherapy group, 3,192 in the no chemotherapy group, and 34,147 women in the no cancer group, with a mean age of 33 years. Accounting for competing events, the overall 5-year LB incidence was lower in the chemotherapy group (3.9%) vs. the no chemotherapy group (6.4%). Adjusted relative risks vs. no chemotherapy and no cancer groups were 0.61 (95% confidence interval [CI] 0.42-0.82) and 0.70 (95% CI 0.51-0.93), respectively. The overall 5-year infertility incidence was similar in the chemotherapy group (21.8%) compared with the no chemotherapy group (20.7%). The adjusted relative risks vs. no chemotherapy and no cancer groups were 1.05 (95% CI 0.97-1.15) and 1.42 (95% CI 1.31-1.53), respectively. CONCLUSIONS: Cancer survivors treated with platinum-based chemotherapy experienced modestly increased adverse fertility outcomes. The estimated effects of platinum-based chemotherapy were affected by competing events, suggesting the importance of this analytic approach for interpretations that ultimately inform clinical fertility preservation decisions.