Variation in Time-to-Gender-Affirming Hormone Therapy in US Active Duty Service Members.

BACKGROUND: Beginning in July 2016, transgender service members in the US military were allowed to receive gender-affirming medical care, if so desired. OBJECTIVE: This study aimed to evaluate variation in time-to-hormone therapy initiation in active duty Service members after the receipt of a diagnosis indicative of gender dysphoria in the Military Health System. RESEARCH DESIGN: This retrospective cohort study included data from those enrolled in TRICARE Prime between July 2016 and December 2021 and extracted from the Military Health System Data Repository. PARTICIPANTS: A population-based sample of US Service members who had an encounter with a relevant International Classification of Diseases 9/10 diagnosis code. MEASURES: Time-to-gender-affirming hormone initiation after diagnosis receipt. RESULTS: A total of 2439 Service members were included (M age 24 y; 62% white, 16% Black; 12% Latine; 65% Junior Enlisted; 37% Army, 29% Navy, 25% Air Force, 7% Marine Corps; 46% first recorded administrative assigned gender marker female). Overall, 41% and 52% initiated gender-affirming hormone therapy within 1 and 3 years of diagnosis, respectively. In the generalized additive model, time-to-gender-affirming hormone initiation was longer for Service members with a first administrative assigned gender marker of male relative to female ( P <0.001), and Asian and Pacific Islander ( P =0.02) and Black ( P =0.047) relative to white Service members. In time-varying interactions, junior enlisted members had longer time-to-initiation, relative to senior enlisted members and junior officers, until about 2-years postinitial diagnosis. CONCLUSION: The significant variation and documented inequities indicate that institutional data-driven policy modifications are needed to ensure timely access for those desiring care.

Incidence and prevalence of eating disorders among U.S. military service members, 2016-2021.

OBJECTIVE: Despite unique experiences that may increase eating disorder risk, U.S. military service members are an understudied population. The current study examined incidence and prevalence of eating disorder diagnoses in U.S. military personnel. METHOD: This retrospective cohort study utilized Military Health System Data Repository (MDR) data on eating disorder diagnoses (2016-2021). Active duty, Reserve, and National Guard U.S. military service members who received care via TRICARE Prime insurance were identified by ICD-10 eating disorder diagnostic codes. RESULTS: During the 6-year surveillance period, 5189 Service members received incident eating disorders diagnoses, with a crude overall incidence rate of 6.2 cases per 10,000 person-years. The most common diagnosis was other/unspecified specified eating disorders, followed by binge-eating disorder, bulimia nervosa, and anorexia nervosa. There was an 18.5% overall rise in total incident cases across the surveillance period, but this trend was not statistically significant (p = 0.09). Point prevalence significantly increased across the 6-year timeframe for total eating disorders (p < 0.001). Period prevalence for 6-year surveillance period was 0.244% for total eating disorders, 0.149% for other/unspecified eating disorder, 0.043% for bulimia nervosa, 0.038% for binge-eating disorder, and 0.013% for anorexia nervosa. DISCUSSION: Overall crude incidence estimates for total eating disorders were higher than reported in prior research that included only active duty Service members and required an eating disorder diagnosis code in the first or second diagnostic position of the medical record. Comprehensive and confidential studies are needed to more thoroughly characterize the nature and scope of eating disorder symptomatology within U.S. military personnel. PUBLIC SIGNIFICANCE: U.S. military service members are a vulnerable population with regard to eating disorder symptoms. Previously reported incidence and prevalence estimates using data from the Military Health System may have been underestimated due to overly stringent case definitions. Given personal and occupational barriers (e.g., career consequences), confidential studies of military personnel may provide more complete data on the scope of eating disorders to inform screening and clinical practice guidelines for military populations.

Incidence and prevalence of eating disorders among active duty US military-dependent youth from 2016 to 2021.

OBJECTIVE: The offspring of US military service members may be at increased risk for eating disorders. However, no epidemiological studies to date have evaluated eating disorder incidence rates and prevalence estimates among military-dependent youth. METHOD: This retrospective cohort study examined eating disorder diagnoses in the military healthcare system (MHS) from 2016 through 2021. Active duty and national guard military-dependent youth, aged 10-17 years, who received care in the MHS via TRICARE Prime insurance, were identified by one or more ICD-10 codes indicative of an eating disorder diagnosis (anorexia nervosa, bulimia nervosa, binge-eating disorder, and other-specified eating disorders). RESULTS: During the 6-year surveillance period, 2534 dependents received incident diagnoses of eating disorders, with a crude overall incidence rate of 1.75 cases per 10,000 person-years. The most common diagnosis was other-specified eating disorder, followed by anorexia nervosa, bulimia nervosa, and binge-eating disorder. The crude annual incidence rate of all eating disorder diagnoses increased by nearly 65% from 2016 to 2021. Rates for all diagnoses were highest in 2020 and 2021. Period prevalence estimates were .08% for any eating disorder diagnosis, .01% for anorexia nervosa, .004% for bulimia nervosa, .004% for binge-eating disorder, and .06% for other-specified eating disorders. DISCUSSION: The observed increase in eating disorder diagnoses during the surveillance period appeared to be driven by female dependents. More military dependents experienced a new-onset diagnosis during the COVID-19 pandemic compared to previous years. These findings highlight the need for eating disorder screening, identification, and treatment for dependents within the MHS. PUBLIC SIGNIFICANCE STATEMENT: Children of US military service members may be at increased risk for eating disorders. Results indicate new-onset eating disorder cases increased 65% from 2016 to 2021, primarily among girls compared to boys. The most diagnosed and fastest growing diagnosis was other-specified eating disorder. Rates of anorexia nervosa increased following the COVID-19 pandemic. Findings highlight the need for eating disorder screening, identification, and treatment within the military healthcare system.

Disturbed flow's impact on cellular changes indicative of vascular aneurysm initiation, expansion, and rupture: A pathological and methodological review.

Aneurysms are malformations within the arterial vasculature brought on by the structural breakdown of the microarchitecture of the vessel wall, with aneurysms posing serious health risks in the event of their rupture. Blood flow within vessels is generally laminar with high, unidirectional wall shear stressors that modulate vascular endothelial cell functionality and regulate vascular smooth muscle cells. However, altered vascular geometry induced by bifurcations, significant curvature, stenosis, or clinical interventions can alter the flow, generating low stressor disturbed flow patterns. Disturbed flow is associated with altered cellular morphology, upregulated expression of proteins modulating inflammation, decreased regulation of vascular permeability, degraded extracellular matrix, and heightened cellular apoptosis. The understanding of the effects disturbed flow has on the cellular cascades which initiate aneurysms and promote their subsequent growth can further elucidate the nature of this complex pathology. This review summarizes the current knowledge about the disturbed flow and its relation to aneurysm pathology, the methods used to investigate these relations, as well as how such knowledge has impacted clinical treatment methodologies. This information can contribute to the understanding of the development, growth, and rupture of aneurysms and help develop novel research and aneurysmal treatment techniques.

Two Closely Spaced Aneurysms of the Supraclinoid Internal Carotid Artery: How Does One Influence the Other?

The objective of this study was to use image-based computational fluid dynamics (CFD) techniques to analyze the impact that multiple closely spaced intracranial aneurysm (IAs) of the supra-clinoid segment of the internal carotid artery (ICA) have on each other's hemodynamic characteristics. The vascular geometry of fifteen (15) subjects with 2 IAs was gathered using a 3D digital subtraction angiography clinical system. Two groups of computer models were created for each subject's vascular geometry: both IAs present (model A) and after removal of one IA (model B). Models were separated into two groups based on IA separation: tandem (one proximal and one distal) and adjacent (aneurysms directly opposite on a vessel). Simulations using a pulsatile velocity waveform were solved by a commercial CFD solver. Proximal IAs altered flow into distal IAs (5 of 7), increasing flow energy and spatial-temporally averaged wall shear stress (STA-WSS: 3-50% comparing models A to B) while decreasing flow stability within distal IAs. Thus, proximal IAs may "protect" a distal aneurysm from destructive remodeling due to flow stagnation. Among adjacent IAs, the presence of both IAs decreased each other's flow characteristics, lowering WSS (models A to B) and increasing flow stability: all changes statistically significant (p < 0.05). A negative relationship exists between the mean percent change in flow stability in relation to adjacent IA volume and ostium area. Closely spaced IAs impact hemodynamic alterations onto each other concerning flow energy, stressors, and stability. Understanding these alterations (especially after surgical repair of one IA) may help uncover risk factor(s) pertaining to the growth of (remaining) IAs.

Health Care Utilization During the First 5½ Years of Authorized Service by Transgender U.S. Service Members (2016-2021).

Purpose: This study examined the utilization of gender-affirming health care by active-duty service members during the initial 5½ years that transgender and gender-diverse (TGD) individuals were authorized to serve in the U.S. military. The aim of this study was to inform policy discussions regarding inclusion of TGD individuals in the military. Methods: We conducted a retrospective cohort study using administrative health care data from the Military Data Repository (MDR). We assessed the association of demographic factors with the utilization of gender-affirming medical and surgical care. We calculated the incidence rate of initial TGD-related encounters and new prescriptions for gender-affirming hormones among Defense Department Service members between July 2016 and December 2021. Results: We identified 2481 service members with an initial health care encounter with an associated TGD-related diagnosis. More than half (53%) of these service members started gender-affirming hormones, and 14% underwent gender-affirming surgery. Mastectomies and hysterectomies accounted for more than 70% of surgeries. Service members made 3.22 initial encounters with a TGD-related diagnosis per 10,000 service members per year, with an overrepresentation of service members who were designated female in the MDR (8.62), junior enlisted (4.98), and young (4.64). Individuals designated female in the MDR comprised 17% of all service members but accounted for 46% of initial encounters, 51% of new prescriptions, and 73% of surgeries. Conclusion: The study revealed a higher-than-expected number of service members seeking gender-affirming care, particularly among service members designated female in the MDR. Military Health System clinicians provided most of this care, which may mitigate the cost of delivering this essential medical care.

Time to Gender-Affirming Hormone Therapy Among US Military-Affiliated Adolescents and Young Adults.

Importance: Use of exogenous sex steroid hormones, when indicated, may improve outcomes in adolescents and young adults with gender incongruence. Little is known about factors associated with the time from diagnosis of gender dysphoria to initiation of gender-affirming hormone therapy. Identification of inequities in time to treatment may have clinical, policy, and research implications. Objective: To evaluate factors associated with time to initiation of gender-affirming hormone therapy after a diagnosis of gender dysphoria in adolescents and young adults receiving care within the US Military Health System. Design, Setting, and Participants: This retrospective cohort study used TRICARE Prime billing and pharmacy data contained in the Military Health System Data Repository. Patients aged 14 to 22 years, excluding service members and their spouses, who received a diagnosis of gender dysphoria between September 1, 2016, and December 31, 2021, were included. The data were analyzed between August 30 and October 12, 2023. Exposures: Included patient characteristics were race and ethnicity, age group, first sex assigned in the medical record, and TRICARE Prime sponsor military rank and service at the time of diagnosis. Health care and contextual characteristics included the year of diagnosis and the primary system in which the patient received health care. Main Outcomes and Measures: The primary outcome was the time between initial diagnosis of gender dysphoria to the first prescription for gender-affirming hormone medication within a 2-year period. A Poisson generalized additive model was used to evaluate this primary outcome. Adjusted probability estimates were calculated per specified reference categories. Results: Of the 3066 patients included (median [IQR] age, 17 [15-19] years; 2259 with first assigned gender marker of female [74%]), an unadjusted survival model accounting for censoring indicated that 37% (95% CI, 35%-39%) initiated therapy by 2 years. Age-adjusted curves indicated that the proportion initiating therapy by 2 years increased by age category (aged 14-16 years, 25%; aged 17-18 years, 39%; aged 19-22 years, 55%). Incidence rate ratios (IRRs) and 2-year adjusted probabilities indicated that longer times to hormone initiation were experienced by adolescents aged 14 to 16 years (IRR, 0.36; 95% CI, 0.30-0.44) and 17 to 18 years (IRR, 0.66; 95% CI, 0.54-0.79) compared with young adults aged 19 to 22 years and Black compared with White adolescents (IRR, 0.73; 95% CI, 0.54-0.99). Senior officer compared with junior enlisted insurance sponsor rank (IRR, 1.93; 95% CI, 1.04-3.55) and civilian compared with military health care setting (IRR, 1.21; 95% CI, 1.02-1.43) was associated with shorter time to hormone initiation. Conclusions and Relevance: In this cohort study, most adolescents and young adults with a diagnosis of gender dysphoria receiving health care through the US military did not initiate exogenous sex steroid hormone therapy within 2 years of diagnosis. Inequities in time to treatment indicate the need to identify and reduce barriers to care.

Impact of spatial and temporal stability of flow vortices on vascular endothelial cells.

PURPOSE: Intracranial aneurysms (IAs) are pathological dilations of cerebrovascular vessels due to degeneration of the mechanical strength of the arterial wall, precluded by altered cellular functionality. The presence of swirling hemodynamic flow (vortices) is known to alter vascular endothelial cell (EC) morphology and protein expression indicative of IAs. Unfortunately, less is known if vortices with varied spatial and temporal stability lead to differing levels of EC change. The aim of this work is to investigate vortices of varying spatial and temporal stability impact on ECs. METHODS: Vortex and EC interplay was investigated by a novel combination of parallel plate flow chamber (PPFC) design and computational analysis. ECs were exposed to laminar (7.5 dynes/[Formula: see text] wall shear stress) or low (<1 dynes/[Formula: see text]) stress vortical flow using PPFCs. Immunofluorescent imaging analyzed EC morphology, while ELISA tests quantified VE-cadherin (cell-cell adhesion), VCAM-1 (macrophage-EC adhesion), and cleaved caspase-3 (apoptotic signal) expression. PPFC flow was simulated, and vortex stability was calculated via the temporally averaged degree of (volume) overlap (TA-DVO) of vortices within a given area. RESULTS: EC morphological changes were independent of vortex stability. Increased stability promoted VE-cadherin degradation (correlation coefficient r = [Formula: see text]0.84) and 5-fold increased cleaved caspase-3 post 24 h in stable (TA-DVO 0.736 ± 0.05) vs unstable (TA-DVO 0.606 [Formula: see text]0.2) vortices. ECs in stable vortices displayed a 4.5-fold VCAM-1 increase than unstable counterparts after 12 h. CONCLUSION: This work demonstrates highly stable disturbed flow imparts increased inflammatory signaling, degraded cell-cell adhesion, and increased cellular apoptosis than unstable vortices. Such knowledge offers novel insight toward understanding IA development and rupture.

Multiple Myeloma in Adolescent and Young Adults: An ASCO CancerLinQ and SEER Analysis.

BACKGROUND: Multiple myeloma (MM) is exceedingly rare in adolescents and young adults (AYAs) < 45 years of age. METHODS: Real-world data from ASCO's CancerLinQ DiscoveryⓇ (CLQD) MM dataset and SEER were utilized to characterize demographics and outcomes of AYA MM patients in the United States in the modern treatment era. Frequencies of SPMs, VTEs, and infections were assessed, as were OS and cause of death. RESULTS: A total of 1946 AYA MM patients from SEER and 1334 from CancerLinQ were included. In terms of SPMs, AYAs were more likely to develop ALL (RR 2.6, P = .003) and AML (RR 1.7, P = .034), and less likely to develop nonmelanoma skin cancer (RR 0.2, P = .001) and prostate cancer (RR 0.1, P = .013) than MM patients ≥ 45. AYAs were at lower risk of VTE (RR 0.75, P = .002) and slightly higher risk of infections (RR 1.11, P = .002). Median OS among AYA MM patients was significantly longer than MM patients ≥ 45 in both datasets. In the SEER cohort, female sex (HR 0.74, P = .003), non-Hispanic ethnicity (HR 0.73, P = .005), and annual household income ≥ $65,000 per year (HR 0.67, P = .001) were associated with lower hazards of mortality. In the CLQD cohort, OS was significantly influenced by female sex (HR 0.6, P = .048). Race did not have a statistically significant impact OS in either cohort. Most AYAs died of MM (68.3%), other primary malignancy (7.5%, mostly leukemia), and cardiovascular events (5.2%). Infections accounted for 3.2% of deaths. CONCLUSION: This analysis highlights some unique characteristics of AYA MM patients in the United States in the modern era.

Real-World Pitfalls of Analyzing Real-World Data: A Cautionary Note and Path Forward.

PURPOSE: Real-world data (RWD) are pervasive in oncology research and offer insights into clinical trends and patient outcomes. However, RWD have shortcomings, making them prone to pitfalls during survival analyses. The American Society of Clinical Oncology (ASCO) CancerLinQ Discovery (CLQD) multiple myeloma (MM) data set was used to demonstrate some common pitfalls when analyzing survival from RWD: using incorrect surrogate markers for missing data and/or classification errors, ignoring deaths at time zero, and failing to account for guarantee-time bias. METHODS: The ASCO CLQD MM data set (July 19, 2021, release) was used to compare overall survival (OS) in patients with a known versus presumed date of MM diagnosis, in patients with secondary AML (sAML) with early deaths (ie, 0 months) included versus dropped, and in patients with second primary malignancies (SPMs) matched versus unmatched to control for time-related confounding factors (ie, guarantee-time bias). Analyses were conducted using STATA Version 17.0 (College Station, TX). RESULTS: In the CLQD MM data set, 28% of patients were missing a diagnosis date. Attempts to use the presumed diagnosis date (ie, first bortezomib or lenalidomide administration) as a surrogate marker for missing diagnosis dates were not successful as median OS was significantly different in patients with a recorded versus presumed diagnosis date (107 v 40 months, hazard ratio [HR], 2.5; 95% CI, 2.39 to 2.64; P < .001). Dropping deaths within 1 month of sAML diagnosis resulted in an exaggerated median OS (46 v 39 months). OS in patients with MM with SPMs differed substantially before and after incorporation of matching methods to account for guarantee-time bias (HR, 0.73; 95% CI, 0.67 to 0.78; P < .001 before matching, HR, 1.30; 95% CI, 1.18 to 1.43; P < .001 after matching). CONCLUSION: To fully maximize the benefits of RWD in oncology research, clinicians must be aware of analytic methods that can overcome pitfalls in survival analyses.

Computerized Differentiation of Growth Status for Abdominal Aortic Aneurysms: A Feasibility Study.

Fast-growing abdominal aortic aneurysms (AAA) have a high rupture risk and poor outcomes if not promptly identified and treated. Our primary objective is to improve the differentiation of small AAAs' growth status (fast versus slow-growing) through a combination of patient health information, computational hemodynamics, geometric analysis, and artificial intelligence. 3D computed tomography angiography (CTA) data available for 70 patients diagnosed with AAAs with known growth status were used to conduct geometric and hemodynamic analyses. Differences among ten metrics (out of ninety metrics) were statistically significant discriminators between fast and slow-growing groups. Using a support vector machine (SVM) classifier, the area under receiving operating curve (AUROC) and total accuracy of our best predictive model for differentiation of AAAs' growth status were 0.86 and 77.50%, respectively. In summary, the proposed analytics has the potential to differentiate fast from slow-growing AAAs, helping guide resource allocation for the management of patients with AAAs.

Computational Assessment of Hemodynamics Vortices Within the Cerebral Vasculature Using Informational Entropy.

Propper assessment of hemodynamic swirling flow patterns, vortices, may help understand the influence of disturbed flow on arterial wall pathophysiology and remodeling. Studies have shown that vortices trigger pathologic cellular changes within the vasculature such as increased inflammation and cellular apoptosis, leading to weakening of the vessel wall indicative of aneurysm development and rupture. Yet many studies qualitatively assess the presence of vortices within the vasculature or assess only their centermost region (critical point analysis) which overlooks the broader characteristics of flow, leading to a narrow view of vortices. This chapter provides a protocol for utilizing commercially available computational fluid dynamic software (ANSYS-FLUENT) to simulate realistic hemodynamic flow patterns, fluid velocity, and wall shear stress in the complex geometry of the cerebral vasculature, as well as an innovative method for assessing flow vortices. This innovative analytic methodology can identify areas of flow vortices and quantify how the broader bulk-flow (opposed to critical point) characteristics change in space and time over the cardiac cycle. Analysis of such flow structures can be used to identify specific characteristics such as vortex stability and the portion of an aneurysmal sac that is dominated by swirling flow, which may be indicative of vascular pathologies.

Vortex Analysis of Intra-Aneurismal Flow in Cerebral Aneurysms.

This study aims to develop an alternative vortex analysis method by measuring structure ofIntracranial aneurysm (IA) flow vortexes across the cardiac cycle, to quantify temporal stability of aneurismal flow. Hemodynamics were modeled in "patient-specific" geometries, using computational fluid dynamics (CFD) simulations. Modified versions of known λ2 and Q-criterion methods identified vortex regions; then regions were segmented out using the classical marching cube algorithm. Temporal stability was measured by the degree of vortex overlap (DVO) at each step of a cardiac cycle against a cycle-averaged vortex and by the change in number of cores over the cycle. No statistical differences exist in DVO or number of vortex cores between 5 terminal IAs and 5 sidewall IAs. No strong correlation exists between vortex core characteristics and geometric or hemodynamic characteristics of IAs. Statistical independence suggests this proposed method may provide novel IA information. However, threshold values used to determine the vortex core regions and resolution of velocity data influenced analysis outcomes and have to be addressed in future studies. In conclusions, preliminary results show that the proposed methodology may help give novel insight toward aneurismal flow characteristic and help in future risk assessment given more developments.