Clinical and sociodemographic characteristics as predictors for quality of life in transmasculine and transfeminine individuals receiving gender-affirming hormone therapy.

Healthcare systems and providers have increasingly acknowledged the role and impact of social determinants in overall health. However, gender-diverse individuals face persistent health disparities due to their identities. There is limited research on the impact of clinical and sociodemographic characteristics on mood and quality of life (QoL) for transgender (TG) individuals. Our study aims to understand and better elucidate social and clinical characteristics of transmasculine (TM) and transfeminine (TF) individuals and their impact on quality of life and depressive symptoms. In this cross-sectional study, 298 TF and TM individuals on gender-affirming hormone therapy (GAHT) were surveyed about their demographic characteristics (age, gender identity, body mass index (BMI), and education), social needs, mood, and quality of life. Multivariable regression modelling was performed to assess the effect of each variable listed above on three domains of QoL (psychological, environmental, and physical) as well as depressive symptoms. We find that QoL scores are similar between TM and TF individuals, with scores in the psychological domain particularly low in both cohorts. TM individuals report higher rates of stress and restroom avoidance than TF individuals. In particular, psychological well-being (measured by the psychological domain of QoL and depressive symptoms) is significantly associated with increased BMI, financial instability, and stress in TM individuals while for TF individuals, psychological well-being is associated with stress and social integration. These data suggest that social circumstances are key drivers of QoL and psychological well-being among gender-diverse individuals receiving GAHT with specific differences between TF and TM individuals. This information may be utilized by healthcare providers and policymakers to address and improve clinical care and social policies to improve health equity for gender-diverse individuals.

Primary Care and Health Care of Transgender and Gender-Diverse Older Adults.

Clinicians working with older transgender and gender-diverse (TGD) individuals need to acquire the necessary knowledge and skills to provide care that is high quality and culturally appropriate. This includes supporting patients in their exploration of gender and attainment of gender-affirming medical interventions. Clinicians should strive to create environments that are inclusive and safe, and that will facilitate health care access and build constructive provider-patient relationships. Clinicians should be aware of best practices, including that age-appropriate health screenings should be anatomy based, and ensure that TGD older adults on gender-affirming hormone therapy (GAHT) receive ongoing laboratory monitoring and physical assessments, including serum hormone levels and biomarkers. Older TGD adults underutilize advance care planning, and need individualized assessments that consider their unique family structures, social support, and financial situation. End-of-life care services should ensure that TGD individuals are treated with dignity and respect.

Assessment of the role of gut health in childhood stunting in a multisite, longitudinal study in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol.

INTRODUCTION: Childhood stunting has a complex aetiology, with poor gut health being an important contributor. This study will assess inter-relationships between maternal and infant gut health indices and infant linear growth. Inter-relationships between gut health indices, systemic inflammation and growth hormones in early childhood will also be assessed. METHODS AND ANALYSIS: A longitudinal observational study of cohorts of 600 newborns and their mothers in India, Indonesia and Senegal will be conducted. Women will be recruited during pregnancy and their children followed up to age 24 months. Stool, urine and blood samples will be collected from the women and children for assessments of helminthic and protozoal parasites, bacterial pathogens, faecal microbiota taxa, biomarkers of environmental enteric dysfunction, systemic inflammation and growth hormones. Child anthropometric measurements will be collected at birth and at ages 3, 6, 9, 12, 18 and 24 months. The gut health indices will be integrated with cohort data from other Action Against Stunting Hub (AASH) workstreams for interdisciplinary analyses of childhood stunting and the development of a new typology of stunting. DISCUSSION: This study will advance scientific understanding of the role of gut health in childhood stunting and will contribute to a broader knowledge of the complex aetiology of this condition as part of the interdisciplinary AASH research to reduce the global burden of childhood stunting. ETHICS AND DISSEMINATION: This study has been approved by the relevant Ethics Committees in Senegal, India, and Indonesia and LSHTM. The results will be submitted for publication in peer-reviewed journals.

A UK prospective multicentre decision impact, decision conflict and economic evaluation of the 21-gene assay in women with node+ve, hormone receptor+ve, HER2-ve breast cancer.

BACKGROUND: For a tumour profiling test to be of value, it needs to demonstrate that it is changing clinical decisions, improving clinical confidence, and of economic benefit. This trial evaluated the use of the Oncotype DX Breast Recurrence Score® assay against these criteria in 680 women with hormone receptor-positive (HR+), HER2-negative early breast cancer with 1-3 lymph nodes positive (LN+) in the UK National Health Service (NHS). METHODS: Prior to receipt of the Recurrence Score (RS) result, both the physician and the patient were asked to state their preference for or against chemotherapy and their level of confidence on a scale of 1-5. Following receipt of the RS result, the physician and patient were asked to make a final decision regarding chemotherapy and record their post-test level of confidence. RESULTS: Receipt of the RS result led to a 51.5% (95% CI, 47.2-55.8%) reduction in chemotherapy, significantly increased the relative and absolute confidence for both physicians and patients and led to an estimated saving to the NHS of £787 per patient. CONCLUSION: The use of the Oncotype DX assay fulfils the criteria of changing clinical decisions, improving confidence and saving money.

Cost-Effectiveness Analysis of Systemic Therapy for Intensification of Treatment in Metastatic Hormone-Sensitive Prostate Cancer in India.

BACKGROUND AND OBJECTIVE: Androgen-deprivation therapy is the mainstay of treatment for patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). However, the intensification of treatment with either docetaxel or novel anti-androgens (abiraterone-acetate plus prednisone [AAP], enzalutamide, and apalutamide) is being recommended based on the improved clinical outcomes and quality of life among patients. This study aimed to determine the most cost-effective drug for treatment intensification for patients with mHSPC in India. METHODS: A Markov model was developed with four health states: progression-free survival, progressive disease, best supportive care, and death. Lifetime costs and consequences were estimated for four treatment sequences: AAP-first, enzalutamide-first, apalutamide-first, and docetaxel-first. Incremental cost per quality-adjusted life-year (QALY) gained with a given treatment option was compared against the next best alternative and assessed for cost effectiveness using a willingness to pay threshold of 1 × per capita gross domestic product in India. RESULTS: We estimated that the total lifetime cost per patient was ₹1,367,454 (US$17,487), ₹2,168,885 (US$27,735), ₹7,678,501 (US$98,190), and ₹1,358,746 (US$17,375) in the AAP-first, enzalutamide-first, apalutamide-first, and docetaxel-first treatment sequence, respectively. The mean quality-adjusted life-years lived per patient were 4.78, 5.03, 3.22, and 2.61, respectively. The AAP-first sequence incurs an incremental cost of ₹4014 (US$51) per quality-adjusted life-year gained as compared with the docetaxel-first sequence, with a 87% probability of being cost effective at the willingness-to-pay threshold of 1 × per-capita gross domestic product of India. The use of AAP-first also incurs an incremental net monetary benefit of ₹396,491 (US$5070) as compared with the docetaxel-first treatment sequence. Nearly a 48% reduction in the price of enzalutamide is required to make it a cost-effective treatment sequence as compared with AAP-first in India. CONCLUSIONS: We concur with the inclusion of standard-dose AAP in India's publicly financed health insurance scheme for the intensification of treatment in mHSPC as it is the only cost-effective sequence among the various novel anti-androgens when compared with the docetaxel-first treatment sequence. Furthermore, a systematic reduction in the price of enzalutamide would further help to improve clinical outcomes among patients with mHSPC.

Environmental bisphenol A disrupts methylation of steroidogenic genes in the ovary of Paradise threadfin Polynemus paradiseus via abnormal DNA methylation: Implications for human exposure and health risk assessment.

Bisphenol A, endocrine-disrupting chemicals (EDCs) impacting disease development via epigenetic modifications, is crucial in transcriptional regulation. However, ecotoxicology's limited exploration of epigenetics prompted our study's objective: examining the extended exposure of riverine Bisphenol A (BPA), a potent EDC, on DNA methylation during female paradise threadfin (Polynemus paradiseus) reproductive maturation. Assessing BPA contamination in riverine water, we collected fish samples from two locations with distinct contamination levels. In the highly contaminated region (Hc), we observed elevated DNA methylation in aromatase (7.5-fold), 20ß-HSD (3-fold), and FSHR (2-fold) genes. Hormone receptor investigation highlighted an escalating connection between transcriptional hyper-methylation and contamination levels. Additionally, our study revealed a positive correlation between oocyte growth and global DNA methylation, suggesting BPA's potential to modify DNA methylation in female paradise threadfins. This effect likely occurs through changes in hormone receptor expression, persisting throughout oocyte maturation. Notably, our research, the first of its kind in estuarine areas, confirmed BPA contamination in paradise threadfins, raising concerns about potential health risks for humans.

Nonprescription Hormone Use Among Transgender Women - National HIV Behavioral Surveillance Among Transgender Women, Seven Urban Areas, United States, 2019-2020.

Certain transgender women who seek gender-affirming hormone treatment (GAHT) face economic and social barriers that limit or prevent access to medically supervised GAHT. Transgender women facing such barriers might acquire GAHT without prescription, potentially without proper dosage, administration, and health monitoring in the absence of medical supervision. For this report, survey data were analyzed from 1,165 transgender women in seven urban areas in the United States to examine associations between self-reported use of nonprescription GAHT and known correlates of nonprescription GAHT, including cost, insurance coverage for GAHT, homelessness, receiving money or drugs in exchange for sex during the past 12 months (exchange sex), lack of comfort discussing gender with provider, and lack of health care use. After controlling for complex sampling design, transgender women who reported recent health care use or insurance coverage for GAHT were less likely to report nonprescription GAHT, and those reporting recent exchange sex or recent homelessness were more likely to report nonprescription GAHT. Findings suggest that transgender women were more likely to use GAHT without a prescription in situations of economic and social marginalization (e.g., disengagement from health care, lack of insurance or trans-specific health care, homelessness, or engagement in sex work). Public health professionals can use these results to design effective interventions to facilitate prescribed hormone use among transgender women in the United States, although access to housing, trans-affirming health care, and insurance coverage might be needed to prevent nonprescription use.

Understanding Their Experiences: Psychosocial Functioning of Nonbinary and Binary Youth at the Time of Hormone Readiness Assessment.

Purpose: The unique psychosocial experiences of nonbinary individuals across the lifespan are understudied compared with those of binary transgender individuals. This study examined the psychosocial stressors faced by nonbinary youth compared with their binary transgender counterparts at the time of gender-affirming hormone (GAH) readiness assessment. Methods: This study compared the psychosocial functioning of nonbinary youth with their binary transgender peers, ages 14-18, utilizing the Youth Self Report (YSR) at the time of GAH readiness assessment. Clinically relevant subscale scores of the YSR were analyzed. Results: Data from 479 binary and 55 nonbinary individuals were analyzed for this study. Analysis found that nonbinary youth reported substantially more psychosocial distress in the form of total problems (ß = 2.86, 95% confidence interval [CI] [0.15-5.56]), internalizing problems (ß = 4.57, 95% CI [1.55-7.59]), depression (ß = 4.52, 95% CI [1.70-7.33]), and self-harm (odds ratio 2.65, 95% CI [1.26-5.56]) than their binary transgender peers. Conclusion: Nonbinary youth experienced higher psychosocial distress compared with their binary transgender counterparts. Future research is needed to better understand the possible health disparities experienced by nonbinary people across their lifespan so that their psychosocial needs can be better met.

Latent pathway-based Bayesian models to identify intervenable factors of racial disparities in breast cancer stage at diagnosis.

PURPOSE: We built Bayesian Network (BN) models to explain roles of different patient-specific factors affecting racial differences in breast cancer stage at diagnosis, and to identify healthcare related factors that can be intervened to reduce racial health disparities. METHODS: We studied women age 67-74 with initial diagnosis of breast cancer during 2006-2014 in the National Cancer Institute's SEER-Medicare dataset. Our models included four measured variables (tumor grade, hormone receptor status, screening utilization and biopsy delay) expressed through two latent pathways-a tumor biology path, and health-care access/utilization path. We used various Bayesian model assessment tools to evaluate these two latent pathways as well as each of the four measured variables in explaining racial disparities in stage-at-diagnosis. RESULTS: Among 3,010 Black non-Hispanic (NH) and 30,310 White NH breast cancer patients, respectively 70.2% vs 76.9% were initially diagnosed at local stage, 25.3% vs 20.3% with regional stage, and 4.56% vs 2.80% with distant stage-at-diagnosis. Overall, BN performed approximately 4.7 times better than Classification And Regression Tree (CART) (Breiman L, Friedman JH, Stone CJ, Olshen RA. Classification and regression trees. CRC press; 1984) in predicting stage-at-diagnosis. The utilization of screening mammography is the most prominent contributor to the accuracy of the BN model. Hormone receptor (HR) status and tumor grade are useful for explaining racial disparity in stage-at diagnosis, while log-delay in biopsy impeded good prediction. CONCLUSIONS: Mammography utilization had a significant effect on racial differences in breast cancer stage-at-diagnosis, while tumor biology factors had less impact. Biopsy delay also aided in predicting local and regional stages-at-diagnosis for Black NH women but not for white NH women.

Association of Pubertal Blockade at Tanner 2/3 With Psychosocial Benefits in Transgender and Gender Diverse Youth at Hormone Readiness Assessment.

PURPOSE: Compare psychosocial function at the time of hormone readiness assessment for transgender and gender diverse (TGD) youth who received pubertal blockade to prevent a nonaffirming puberty with those who did not. METHODS: Retrospective cohort study of psychological assessment data from hormone readiness evaluations conducted at a multispecialty gender clinic. Participants include all TGD youth between the ages of 13 and 17 assessed for hormone readiness between 2017 and 2021. RESULTS: Our cohort consisted of 438 TGD youth, 40 who were prescribed pubertal blockade at Tanner stage 2 or 3, and 398 who had not. The blocker population was younger, more likely to be assigned male and affirming a female identity, and had a different racial/ethnic identity distribution. Having puberty blocked was associated with significantly lower T-scores on the Youth Self Report for internalizing problems (ß = -7.4, p < .001), anxiety problems (ß = -4.6, p = .003), depressive problems (ß = -6.5, p < .001), stress problems (ß = -4.0, p = .01), and total problems (ß = -4.9, p = .003). The blocker population was also significantly less likely to report any suicidal thoughts (odds ratio = 0.38, p = .05). With the exception of increased risk of suicidal thoughts, these associations remained significant when adjusted for gender. DISCUSSION: At the time of hormone readiness evaluation, TGD youth who received pubertal blockade at Tanner 2 or 3 were found to have less anxiety, depression, stress, total problems, internalizing difficulties, and suicidal ideation than TGD peers who had been through more of a nonaffirming puberty.

Racial and Ethnic Disparities in Use of Novel Hormonal Therapy Agents in Patients With Prostate Cancer.

Importance: Novel hormonal therapy (NHT) agents have been shown to prolong overall survival in numerous randomized clinical trials for patients with advanced prostate cancer (PCa). There is a paucity of data regarding the pattern of use of these agents in patients from different racial and ethnic groups. Objective: To assess racial and ethnic disparities in the use of NHT in patients with advanced PCa. Design, Setting, and Participants: This cohort study comprised all men diagnosed with de novo advanced PCa (distant metastatic [M1], regional [N1M0], and high-risk localized [N0M0] per Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy [STAMPEDE] trial criteria) with Medicare Part A, B, and D coverage between January 1, 2011, and December 31, 2017, in a Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database including prescription drug records. Data analysis took place from January through May 2023. Exposures: Race and ethnicity (Black [non-Hispanic], Hispanic, White, or other [Alaska Native, American Indian, Asian, Pacific Islander, or not otherwise specified and unknown]) abstracted from the SEER data fields. Main Outcomes and Measures: The primary outcome was receipt of an NHT agent (abiraterone, enzalutamide, apalutamide, or darolutamide) using a time-to-event approach. Results: The study included 3748 men (median age, 75 years [IQR, 70-81 years]). A total of 312 (8%) were Black; 263 (7%), Hispanic; 2923 (78%), White; and 250 (7%) other race and ethnicity. The majority of patients had M1 disease (2135 [57%]) followed by high-risk N0M0 (1095 [29%]) and N1M0 (518 [14%]) disease. Overall, 1358 patients (36%) received at least 1 administration of NHT. White patients had the highest 2-year NHT utilization rate (27%; 95% CI, 25%-28%) followed by Hispanic patients (25%; 95% CI, 20%-31%) and patients with other race or ethnicity (23%; 95% CI, 18%-29%), with Black patients having the lowest rate (20%; 95% CI, 16%-25%). Black patients had significantly lower use of NHT compared with White patients, which persisted at 5 years (37% [95% CI, 31%-43%] vs 44% [95% CI, 42%-46%]; P = .02) and beyond. However, there was no significant difference between White patients and Hispanic patients or patients with other race or ethnicity in NHT utilization (eg, 5 years: Hispanic patients, 38% [95% CI, 32%-46%]; patients with other race and ethnicity: 41% [95% CI, 35%-49%]). Trends of lower utilization among Black patients persisted in the patients with M1 disease (eg, vs White patients at 5 years: 51% [95% CI, 44%-59%] vs 55% [95% CI, 53%-58%]). After adjusting for patient, disease, and sociodemographic factors in multivariable analysis, Black patients continued to have a significantly lower likelihood of NHT initiation (adjusted subdistribution hazard ratio, 0.76; 95% CI, 0.61-0.94, P = .01). Conclusions and Relevance: In this cohort study of Medicare beneficiaries with advanced PCa, receipt of NHT agents was not uniform by race, with decreased use observed in Black patients compared with the other racial and ethnic groups, likely due to multifactorial obstacles. Future studies are needed to identify strategies to address the disparities in the use of these survival-prolonging therapies in Black patients.

Assessing Patient Goals for Gender-Affirming Hormone Therapy: A Standardized Patient Case for Medical Students.

Introduction: Inadequate coverage of transgender and gender-diverse (TGD) health in the UME curriculum contributes to the scarcity of competent physicians to care for TGD patients. Increasing TGD health skills-based curricula in UME can help address TGD health disparities. We developed a standardized patient (SP) case to assess TGD health skills-based competencies and attitudes among medical students. Methods: An interdisciplinary team, including individuals with lived TGD experience, developed the SP case that was completed by second-year medical students at the University of Pittsburgh School of Medicine in January 2020. After the TGD SP session, students and faculty completed a postsession survey to assess the degree to which the case met the learning objectives. Students were assessed via self-reports, faculty reports, and SP video evaluations. Results: Seventy second-year medical students, 30 faculty facilitators, and eight SPs participated in 2020. Students reported being significantly more prepared to care for TGD patients (Z = -5.68, p < .001) and to obtain a gender history (Z = -5.82, p < .001). Both faculty and students felt that skills for caring for TGD patients were important in medical education and agreed the case should remain in the curriculum. Discussion: The case effectively honed and assessed students' ability to collect a gender history and discuss goals for hormone therapy with TGD patients. It should complement ongoing curricula to effectively train medical students in TGD health care. Developing these skills in students directly addresses the barriers that many TGD patients experience in health care settings.

Quality of life assessment of breast cancer survivors in Northern Morocco: Rural-urban disparity.

This article is a cross-sectional study of 216 women undergoing adjuvant hormone therapy for breast cancer in two oncology centers in northern Morocco. Quality of life (QoL) was assessed using the Functional Assessment of Cancer Therapy (FACT) questionnaire and its endocrine subscale (ES). The relationship between rural-urban status in our sample and QoL was assessed by linear regression analysis using sociodemographic and clinical variables as covariates. Our results show that physical and functional well-being are significantly (p < 0.001) higher in rural areas (24 and 29, respectively) than in urban areas (16 and 19, respectively), while social and emotional well-being are significantly (p < 0.001) higher in urban areas (22 and 21, respectively) than in rural areas (15 and 16, respectively). However, there was no significant difference (p = 0.097) between rural and urban breast cancer survivors regarding endocrine symptom burden. Regarding the effect of sociodemographic and clinical factors on overall HRQOL of breast cancer survivors, hormone type was shown to have a significant effect on overall HRQOL (FACT-ES) of rural and urban breast cancer survivors (𝛽 = +0.849 and 𝛽 = +0.678, respectively). A similar effect was observed for ES (𝛽 = +0.896 and 𝛽 = +0.180, respectively).In contrast, other factors (age, marital status, economic status, menopausal status, type of surgery) did not have a significant effect on HRQOL (FACT-ES) or ES.The study highlighted the need for increased psychosocial supportive care efforts for rural breast cancer survivors to improve their QoL.

Gender-affirming pharmacotherapy and additional health considerations: A contemporary review.

BACKGROUND: Transgender and gender-diverse (TGD) individuals in the United States face health care disparities compounded with discrimination and limited access to necessary medical services. Gender-affirming interventions have been shown to mitigate gender dysphoria and psychiatric comorbidities, yet United States legislation limiting such interventions has increased. As medication experts, pharmacists can facilitate access to care and appropriate use of gender-affirming hormone therapy (GAHT) and educate other health care providers on best practices for caring for TGD individuals in a variety of settings. OBJECTIVES: To provide pharmacists with a contemporary review of GAHT and associated medication-related concerns. METHODS: We searched PubMed for articles published until December 2022. MeSH terms such as transgender, transsexual, gender diverse, gender variant, or gender nonconforming in combination with phrases like gender-affirming care, treatment, pharmacotherapy, or hormone therapy were used to capture desired articles. RESULTS: Feminizing hormone therapy (FHT), such as estrogen and antiandrogen agents, increases female secondary sex characteristics while suppressing male secondary sex characteristics. Masculinizing hormone therapy (MHT) achieves male secondary sex characteristics and minimizes female secondary sex characteristics using testosterone. For both FHT and MHT, the choice of therapy and formulation ultimately involves the patient's treatment goals, preferences, and tolerability. GAHT has additional health considerations pertaining to renal drug dosing, fertility, cardiovascular, and cancer risks. Pharmacists may provide crucial guidance and education to both patients and health care providers regarding risks associated with GAHT. CONCLUSION: Many pharmacists feel unprepared to help provide, manage, and optimize GAHT. For many TGD individuals, GAHT is medically necessary and a life-saving treatment. Therefore, pharmacists should be provided tools to close knowledge gaps and improve their ability to care for these patients. By offering a thorough updated overview of GAHT, pharmacists can gain confidence to provide appropriate care for this increasingly visible population.

Cost-effectiveness of Trastuzumab Deruxtecan for HER2-low Advanced Breast Cancer in the United States.

PURPOSE: Trastuzumab deruxtecan has been shown to be effective for advanced breast cancer with low levels of human epidermal growth factor receptor 2. To optimize the allocation of limited health care resources, this study evaluated the cost-effectiveness of trastuzumab deruxtecan from the US payer perspective. METHODS: A partitioned survival model was developed to project the disease course of advanced breast cancer. Clinical efficacy, treatment utilization, safety, and cost data were gathered from the DESTINY-Breast04 (Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer) trial and the Centers for Medicare & Medicaid Services. Transition probabilities were obtained from the reported survival probabilities per DESTINY-Breast04 group. The incremental cost-effectiveness ratio (ICER), the incremental monetary benefit, and the incremental net health benefit were measured. One-way sensitivity analysis, probabilistic sensitivity analysis, and subgroup analysis were performed to explore the uncertainty of the model. FINDINGS: Trastuzumab deruxtecan had an ICER of $307,751 per quality-adjusted life-year (QALY) gained, with an incremental net health benefit of -0.317 QALY and an incremental monetary benefit of -$63,313 compared with the physician's choice of alternative chemotherapy agents. Subgroup analysis indicated that trastuzumab deruxtecan had an ICER of $383,776 per QALY gained for the hormone receptor-positive subgroup and an ICER of $194,424 per QALY for the hormone receptor-negative subgroup. One-way sensitivity analysis showed that the cost of trastuzumab deruxtecan had the most impact on model outcomes. The cost-effectiveness acceptability curve projected that the probability of trastuzumab deruxtecan being cost-effective was 5% in the overall population, 2% in the hormone receptor-positive subgroup, and 56% in the hormone receptor-negative subgroup at the willingness-to-pay threshold of $200,000 per QALY. IMPLICATIONS: Trastuzumab deruxtecan may be a cost-effective option for hormone receptor-negative patients with advanced breast cancer with low levels of human epidermal growth factor receptor 2.

Adherence to and persistence with adjuvant hormone therapy, healthcare utilization, and healthcare costs among older women with breast cancer: A population-based longitudinal cohort study.

INTRODUCTION: To assess associations between adherence to and persistence with adjuvant hormone therapy, healthcare utilization, and healthcare costs among older women with breast cancer. MATERIALS AND METHODS: This study was a population-based longitudinal cohort study using the Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare claims. This study included older women diagnosed with stage I-III hormone receptor-positive breast cancer from 2009 through 2017. Participants were considered adherent with a proportion of days covered (PDC) of 0.80 or more and persistent if they had no hormone therapy discontinuation, i.e., a break of at least 180 continuous days. Length of persistence was calculated as time from therapy initiation to discontinuation. All participants were followed for up to five years after hormone therapy initiation. Generalized linear mixed models with repeated measures or hurdle generalized linear mixed models in the event of excess zeroes were used to assess associations between adherence to and persistence with annual healthcare utilization and costs. RESULTS: This study included 25,796 women. Being adherent was associated with lower annual healthcare utilization, i.e., hospitalizations, hospital days, emergency room visits, and hospital outpatient visits. Persistence was associated with fewer annual hospitalizations, hospital days, emergency room visits, and hospital outpatient visits. Adherent participants had lower annual inpatient costs, outpatient costs, medical costs, and total healthcare costs despite higher prescription drug costs. Both being persistent and longer persistence were associated with lower inpatient costs, outpatient costs, medical costs, and total healthcare costs despite higher prescription drug costs. DISCUSSION: This study underscores the economic benefits associated with adherence to and persistence with adjuvant hormone therapy based on comprehensive measures for healthcare utilization and costs. To our best knowledge, this was the first study that reported total healthcare cost savings associated with adherence to and persistence with adjuvant hormone therapy.

TripleAiM1: a nationwide registry of de novo metastatic hormone-sensitive prostate cancer with prospective quality-of-life assessment.

INTRODUCTION: The treatment landscape for de novo metastatic hormone sensitive prostate cancer (mHSPC) is rapidly evolving. With an abundance of available treatment strategies, selecting the optimal strategy for an individual patient is becoming increasingly challenging. TripleAiM1 aims to evaluate the impact of mHSPC treatments on health-related quality of life (HRQoL) and to provide real-world data insights on diagnostics, treatment strategies, patient subgroups and related healthcare expenditure for mHSPC. The aspirational target of TripleAiM1 is that in the near future, a more tailored therapy can be offered based on the individual patient's wishes and needs in accordance with the overarching principle of value-based healthcare. METHODS AND ANALYSIS: We describe the TripleAiM1 study design; a nationwide registry comprising a retrospective and prospective cohort of patients with de novo mHSPC. Starting in May 2020, eligible patients are identified, selected and recruited in 14 participating hospitals in the Netherlands. Our hypothesis is that, in a real-world setting, differences in clinically meaningful HRQoL deterioration will be observed for treatment strategies over time. HRQoL data, assessed with patient-reported outcome measures, costs and clinical data will be collected for 24 months.For the retrospective cohort, all patients diagnosed with de novo mHSPC from January 2017 onwards are eligible for inclusion. Patient and tumour characteristics, imaging modalities and treatment patterns will be analysed descriptively to provide a real-world overview.Time-to-event endpoints will be assessed using the Kaplan-Meier method and regression models will be employed to analyse baseline characteristics associated with an increased likelihood of death, progression and HRQoL deterioration. Longitudinal mixed-effects models will be employed to assess change of patient-reported outcome scores from baseline until the end of follow-up. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Research Ethics Committee, Twente. Study results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NL9719.

Patterns of Evidence-Based Care for the Diagnosis, Staging, and First-line Treatment of Breast Cancer by Race-Ethnicity: A SEER-Medicare Study.

BACKGROUND: Racial and ethnic disparities in guideline-recommended breast cancer treatment are well documented, however studies including diagnostic and staging procedures necessary to determine treatment indications are lacking. The purpose of this study was to characterize patterns in delivery of evidence-based services for the diagnosis, clinical workup, and first-line treatment of breast cancer by race-ethnicity. METHODS: SEER-Medicare data were used to identify women diagnosed with invasive breast cancer between 2000 and 2017 at age 66 or older (n = 2,15,605). Evidence-based services included diagnostic procedures (diagnostic mammography and breast biopsy), clinical workup (stage and grade determination, lymph node biopsy, and HR and HER2 status determination), and treatment initiation (surgery, radiation, chemotherapy, hormone therapy, and HER2-targeted therapy). Poisson regression was used to estimate rate ratios (RR) and 95% confidence intervals (CI) for each service. RESULTS: Black and American Indian/Alaska Native (AIAN) women had significantly lower rates of evidence-based care across the continuum from diagnostics through first-line treatment compared to non-Hispanic White (NHW) women. AIAN women had the lowest rates of HER2-targeted therapy and hormone therapy initiation. While Black women also had lower initiation of HER2-targeted therapy than NHW, differences in hormone therapy were not observed. CONCLUSIONS: Our findings suggest patterns along the continuum of care from diagnostic procedures to treatment initiation may differ across race-ethnicity groups. IMPACT: Efforts to improve delivery of guideline-concordant treatment and mitigate racial-ethnic disparities in healthcare and survival should include procedures performed as part of the diagnosis, clinical workup, and staging processes.

Barriers and Facilitators to Gender-affirming Hormone Therapy in the Veterans Health Administration.

BACKGROUND: In 2011, the Veterans Health Administration (VHA) established a policy for the delivery of transition-related services, including gender-affirming hormone therapy (GAHT), for transgender and gender diverse (TGD) patients. In the decade since this policy's implementation, limited research has investigated barriers and facilitators of VHA's provision of this evidence-based therapy that can improve life satisfaction among TGD patients. PURPOSE: This study provides a qualitative summary of barriers and facilitators to GAHT at the individual (e.g., knowledge, coping mechanisms), interpersonal (e.g., interactions with other individuals or groups), and structural (e.g., gender norms, policies) levels. METHODS: Transgender and gender diverse patients (n = 30) and VHA healthcare providers (n = 22) completed semi-structured, in-depth interviews in 2019 regarding barriers and facilitators to GAHT access and recommendations for overcoming perceived barriers. Two analysts used content analysis to code and analyze transcribed interview data and employed the Sexual and Gender Minority Health Disparities Research Framework to organize themes into multiple levels. RESULTS: Facilitators included having GAHT offered through primary care or TGD specialty clinics and knowledgeable providers, with patients adding supportive social networks and self-advocacy. Several barriers were identified, including a lack of providers trained or willing to prescribe GAHT, patient dissatisfaction with prescribing practices, and anticipated or enacted stigma. To overcome barriers, participants recommended increasing provider capacity, providing opportunities for continual education, and enhancing communication around VHA policy and training. CONCLUSIONS: Multi-level system improvements within and outside the VHA are needed to ensure equitable and efficient access to GAHT.

Veterans Health Administration (VHA) policy mandates the provision of several gender-affirming health services, including gender-affirming hormone therapy (GAHT). GAHT can improve quality of life among transgender and gender diverse (TGD) patients by more closely aligning their physical self with their internal sense of self. We conducted interviews with 30 TGD patients and 22 VHA healthcare providers to gather their perspectives on barriers and facilitators to GAHT in the VHA. Findings revealed that facilitators of GAHT access included information sharing through social networks and relying on providers in primary care or specialized TGD health clinics for prescribing, while barriers included a shortage of trained providers and patient dissatisfaction with prescribing practices. Anticipating or experiencing stigma from providers and other patients was also identified as a barrier to GAHT. To overcome barriers, participants recommended increasing provider capacity, offering continuous education on GAHT prescribing, and improving communication about VHA policies and training. Comprehensive improvements at various levels, both within and outside the VHA, are necessary to improve access to this important evidence-based treatment for TGD patients.

Survival benefits associated with being adherent and having longer persistence to adjuvant hormone therapy across up to five years among U.S. Medicare population with breast cancer.

PURPOSE: To assess associations between adherence to and persistence with adjuvant hormone therapy and mortality among older women with breast cancer. METHODS: The surveillance, epidemiology, and end results data linked with U.S. Medicare claims was used. This study included older women diagnosed with stage I-III hormone receptor-positive breast cancer from 2009 through 2017. Adherence was defined as having proportion of days covered (PDC) ≥ 0.80. Persistence was defined as having no discontinuation, i.e., no break of ≥ 180 continuous days. Length of persistence was calculated as time from therapy initiation to discontinuation. Cox models with time-dependent covariates were used to assess associations between adherence and persistence with mortality. RESULTS: This study included 25,796 women. Adherence rates were 78.1 percent, 75.2 percent, 72.4 percent, 70.0 percent, and 61.5 percent from year 1 to year 5 after hormone therapy initiation. Persistence rates were 87.5 percent, 81.7 percent, 77.1 percent, 72.9 percent, and 68.9 percent through cumulative intervals of 1 year up to 5 years. Adherence was associated with all-cause mortality but not associated with breast cancer-specific mortality. Persistent women had lower risk of all-cause mortality and breast cancer-specific mortality. Each additional year of persistence had additional contributions to survival benefits (11% decreased risk of all-cause mortality and 37% decreased risk of breast cancer-specific mortality). CONCLUSION: This study confirms the detrimental effect of nonadherence to adjuvant hormone therapy across up to 5 years on all-cause survival in older U.S. women. It also reveals the survival benefits associated with having longer persistence across up to 5 years.