Publications by Year: 2025

INTRODUCTION: Transgender and gender-diverse adults have worse mental health than cisgender adults, yet few studies assess unmet mental health needs. This study compares frequent mental distress, access to care, and barriers among transgender and gender-diverse and cisgender adults.

METHODS: Using the 2022 KFF/The Washington Post Trans Survey of U.S. adults (n=1,338), unadjusted prevalence differences in frequent mental distress, unmet mental health need, and reasons for unmet mental health need were described. Logistic regression models assessed unmet mental health need likelihood, adjusting for sociodemographic characteristics and distress. Data were analyzed in 2024.

RESULTS: Among transgender and gender-diverse adults, 64% were nonbinary or gender nonconforming, 22% were transgender women, 12% were transgender men, and 2% were of another gender. Transgender and gender-diverse adults were more likely to have Medicaid (21% vs 14%, p=0.01) or be uninsured (15% vs 10%, p=0.04) and less likely to have Medicare (6% vs 25%, p<0.001) than cisgender adults. Transgender and gender-diverse adults reported more frequent mental distress (47% vs 21%, p<0.001) and unmet mental health need (48% vs 26%, p<0.001) than cisgender adults. In multivariable models, transgender and gender-diverse adults had higher unmet mental health need than cisgender adults (OR=1.62, 95% CI=1.08, 2.43). Transgender and gender-diverse adults were more likely to report cost as the main care barrier than cisgender adults (30% vs 15%, p=0.01).

CONCLUSIONS: Transgender and gender-diverse adults reported higher rates of frequent mental distress, unmet mental health need, and cost-related barriers to mental health care than cisgender adults. Efforts to improve the affordability and availability of mental health treatment could reduce high levels of unmet need among transgender and gender-diverse adults.

OBJECTIVE: Although complex endovascular repairs are becoming increasingly common, complication rates are less well studied, and published rates of technical success vary widely. In addition, whether high volume surgeons are more able to rescue intra-operative complications has not been well studied.

METHODS: This study analysed all complex abdominal aortic aneurysm (AAA) repairs in the Vascular Quality Initiative from 2014 to 2023. Multilevel logistic regression with inverse probability weighting was used to identify factors associated with lack of technical success (defined as successful introduction of the main graft, incorporation of all target vessels without occlusion or stenosis > 50%, and no type I or III endoleaks). Secondary analyses assessed the differential impact of type I and III endoleaks compared with graft and target vessel complications.

RESULTS: There were 6 556 repairs (3 246 para- or juxtarenal AAAs and 3 310 thoraco-abdominal aortic aneurysms) with an overall technical success rate of 82.7%; technical failures were due to type I or III endoleak in 9.6%, target vessel complications in 5.6%, and complications with the main body in 4.0%. Technical success increased in concert with volume in crude and adjusted analyses. Technical failure was associated with a markedly higher adjusted odds of peri-operative death, thoraco-abdominal life altering events, acute kidney injury, dialysis, spinal cord ischaemia, and re-operation. Repairs with technical failure at the hands of higher volume surgeons were less likely to experience death than cases of technical failure in the hands of lower volume surgeons (p < .006 for interaction). Technical success was similarly associated with higher 5 year survival (86% vs. 65%; p < .001). Both type I and III endoleaks, and target vessel and main body complications were associated with worse peri-operative outcomes and lower 5 year survival. However, although type I and III endoleaks had less impact than target vessel and main body complications in elective repairs, in symptomatic and ruptured settings these endoleaks had simlarly poor outcomes to target vessel and main body complications.

CONCLUSION: Technical success had a strong association with outcomes of endovascular complex AAA repair, especially in non-elective settings. Higher volume surgeons had higher rates of technical success, and their outcomes were less negatively impacted by technical failures, suggesting a potential benefit to centralising more urgent and complex cases.

OBJECTIVE: Child sexual abuse is associated with mental health (MH) challenges across the lifespan. Black and Latino children are less likely to receive MH services than children of other backgrounds. We aimed to identify facilitators and barriers to MH services for Black and Latino children after sexual abuse.

METHODS: We conducted semistructured interviews with 30 Black and Latino, English- and Spanish-speaking caregivers of children who have experienced sexual abuse. Interviews were completed in caregivers' preferred language and modality (phone, video conferencing, or in person). Caregivers were asked about their opinions and experiences with initiating child MH services after sexual abuse. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis.

RESULTS: Caregivers (27% Black, 47% Latino, 27% Black and Latino) were mostly biological mothers (87%). Half were born outside the United States. Caregivers reported 3 facilitators to MH services after sexual abuse: 1) perceived benefits of MH services; 2) trust in MH providers; and 3) support from frontline professionals and systems. Caregivers reported timely support when there was cross-system care coordination. Caregivers described 5 barriers to MH services after sexual abuse: 1) perceived harms of MH services; 2) concerns about misjudgment and discrimination by MH providers; 3) stigma of sexual abuse; 4) youth's lack of engagement in MH services; and 5) structural obstacles to MH services.

CONCLUSIONS: Black and Latino caregivers identified multiple facilitators and barriers to MH services after sexual abuse. Our findings can inform the development and testing of evidence-based strategies to improve MH engagement and outcomes after sexual abuse.

BACKGROUND: People who smoke are at increased risk of unfavourable tuberculosis treatment outcomes compared with those who do not, but the pathways that explain this disparity are unclear.

OBJECTIVE: To estimate the difference in a successful end-of-treatment outcome by smoking status among people with multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) and to examine if this difference changes if people who smoked had the same retention in treatment as those who did not smoke.

DESIGN AND METHODS: Using data from the prospective endTB Observational Study, we estimated the difference in treatment success by cigarette smoking status, adjusting for baseline confounders including demographics, social history and comorbidities. To examine how this difference changed if everyone was retained in treatment, we censored participants who were lost to follow-up and applied inverse probability of censoring weights to simulate this scenario.

RESULTS: Among 1786 participants in 12 countries, 539 (30.2%) reported smoking at least one cigarette daily. People who smoked were more frequently found in post-Soviet countries and had a complex social history (eg, incarceration and substance use) and infectious comorbidities (eg, hepatitis C). At the end of treatment, 73.5% of people who smoked and 80.3% of people who did not smoke had treatment success (risk difference in percentage points: -6.8, 95% CI -11.1 to -2.6). After adjusting for baseline confounders, the risk difference was similar (-5.2 percentage points), but the 95% CI was less precise (-14.1 to 3.2). When simulating a scenario in which everyone was retained in treatment, the risk difference was attenuated (-1.9 percentage points; 95% CI -11.1 to 4.7).

CONCLUSION: People who smoked had a lower frequency of MDR/RR-TB treatment success than those who did not smoke. Eliminating loss to follow-up reduced this difference by smoking status, suggesting that pathways related to retention in treatment were a major driver of this disparity.

BACKGROUND: Human immunodeficiency virus (HIV) cases among people who inject drugs increased during the US overdose crisis. Although HIV pre-exposure prophylaxis (PrEP) decreases HIV acquisition, and medications for opioid use disorder (MOUD) reduce overdose deaths, uptake remains suboptimal. The CHORUS + study will test the efficacy of a comprehensive peer recovery coaching intervention to increase PrEP and MOUD initiation and adherence.

METHODS: This two-arm RCT will enroll 284 people who inject opioids (PWIO) and are negative for HIV from two sites. Participants randomized to the CHORUS + intervention will receive a study smartphone, motivational interviewing sessions, assistance connecting to PrEP and/or MOUD, and support to access resources addressing social needs such as employment and housing. We will also incorporate adapted 'Life-Steps for PrEP' modules to increase adherence. The control arm will receive information on local organizations with access to PrEP and MOUD. Participants will complete assessments at baseline, 1-, 3-, 6-, and 12-month visits. The primary outcome is adherence to HIV PrEP, assessed by tenofovir-diphosphate drug levels at 6-months post enrollment. Secondary outcomes include PrEP adherence assessed at 3- and 12-months, measured by drug levels (3-months), prescription refills, and self-report; and MOUD receipt at 3-, 6-, and 12-months, measured by prescription refills, self-report, and urine toxicology. The primary analysis will employ intent-to-treat logistic regression to assess differences in adherence between treatment arms, adjusting for stratification factors including site, race and sex assigned at birth. We will analyze secondary outcomes using similar methods. We will use multilevel growth curve modeling to evaluate changes in adherence over time by treatment group, incorporating random intercepts and slopes to account for individual trajectories. We will use exploratory multilevel structural equation modeling to assess mediators including HIV risk perception and PrEP/MOUD knowledge to understand pathways that may influence adherence.

DISCUSSION: The CHORUS + intervention integrates a novel, theory-based, peer-delivered, smartphone-supported approach to address HIV prevention and opioid use disorder, while tackling social and structural barriers to care. Findings will inform strategies for linking PWIO to rapid HIV prevention and substance use treatment.

TRIAL REGISTRATION: ClinicalTrials.gov number: NCT05769218.

Organoids, an emerging bioengineering approach, can replicate the structure and function of human organs in vitro, providing valuable tools for biomedical research. Patient-derived organoids (PDOs) retain the histological and genetic characteristics of the original tumor, playing a crucial role in precision oncology. Ultrasound-assisted technology, particularly multimodal ultrasound imaging, facilitates the establishment of PDOs for inoperable or rare tumors by enabling precise tumor localization, minimally invasive tissue sampling, and high-purity cell extraction.This review explores the application of multimodal ultrasound techniques in PDO development across various tumor types, highlighting their advantages in obtaining high-purity tumor cells, improving PDO culture success rates, and advancing personalized cancer treatment. Additionally, we discuss factors influencing PDO establishment, such as tumor type, sampling methods, and bioengineering advancements. By summarizing current progress and challenges, this review provides insights into optimizing ultrasound-assisted PDO construction for clinical and research applications.

Retrospective cohort study evaluating the association between time to antibiotic administration and clinical outcomes in pediatric sepsis using data from 6153 patients treated at 19 pediatric emergency departments between 2013 and 2016. Time to antibiotics was analyzed both as a continuous variable and as a dichotomized variable (≤60 vs >60 minutes from sepsis time zero). The primary outcome was 3- and 30-day all-cause mortality; secondary outcomes included use of vasoactive agents and intensive care unit and hospital length of stay. In adjusted analyses, longer time to antibiotics was associated with lower 30-day mortality but not with 3-day mortality or other secondary outcomes. Patients receiving antibiotics more than 60 minutes from recognition had a significantly lower risk of 30-day mortality. These findings suggest that rigid time-based antibiotic thresholds may not align with improved outcomes in pediatric sepsis and underscore the need for prospective studies to inform future guidelines.

OBJECTIVE: Semicircular canal dehiscence (SCD) and vestibular aqueduct (VA) hypoplasia are developmental anomalies associated with distinct inner ear syndromes-SCD syndrome and Meniere's disease (MD). Our previous work found frequent SCD in MD patients with VA hypoplasia, suggesting a shared developmental origin. To further explore this association, we adopted a reciprocal approach by assessing VA hypoplasia prevalence in patients diagnosed with SCD.

STUDY DESIGN: Retrospective cohort study.

SETTING: Tertiary referral center.

PATIENTS: A total of 219 ears from 173 patients (mean age 53.5 years, standard deviation 16.6 years; 54.3% females) were evaluated for suspected SCD, confirmed by temporal bone computed tomography (CT).

INTERVENTIONS: Radiological analysis of temporal bone CT scans using the angular trajectory of the vestibular aqueduct (ATVA) marker; review of clinical records for diagnosis of MD.

MAIN OUTCOME MEASURES: Prevalence of VA hypoplasia among SCD patients; association of radiological findings with clinical diagnosis of MD.

RESULTS: VA hypoplasia was identified in 4 of 173 patients (2.3%), representing a 46-fold increase compared with the estimated 0.05% prevalence of MD patients with VA hypoplasia in the general population. These cases showed an atypical SCD localization in the posterior limb of the superior semicircular canal. All 4 patients were diagnosed with MD ipsilateral to the SCD/VA hypoplasia.

CONCLUSIONS: SCD and VA hypoplasia are associated in a distinct patient group, suggesting a shared developmental etiology. These patients may be predisposed to an early overlap of SCD syndrome and MD, with their clinical course eventually dominated by the progressive nature of MD.

OBJECTIVE: To determine the test performance of cutaneous phosphorylated alpha-synuclein (P-SYN) in dementia with Lewy bodies (DLB), individuals with reduced Montreal Cognitive Assessment (MoCA) and healthy controls.

METHODS: This is the first subgroup analysis of the Synuclein-One study, a prospective, blinded study evaluating P-SYN detection from skin biopsies in 218 subjects with a referral diagnosis of control (N = 151) and DLB (N = 67). All subjects completed detailed examinations, questionnaires, and had skin biopsies for detection of P-SYN. DLB patients were included if meeting the 4th DLB consensus probable criteria. Control subjects, aged 40-99, had no history, examination findings, or symptoms suggestive of a synucleinopathy or neurodegenerative disease. An expert review panel, blinded to pathological data, determined the final diagnosis. Controls with reduced MoCA (MoCA < 26, N = 26) at screening were analyzed separately.

RESULTS: After expert panel review, only 50/67 patients met consensus criteria for DLB, 26/151 controls had a reduced MoCA, and 120/151 controls had a normal MoCA. The proportions of subjects with cutaneous P-SYN detected by skin biopsy were 96.0% (48 of 50) of the DLB group, 31% (8 of 26) of the controls with reduced MoCA, and 3.3% (4 of 120) of the controls with normal MoCA.

INTERPRETATION: In this prospective, blinded, cross-sectional study, a high proportion of subjects meeting clinical consensus criteria for DLB had P-SYN detected in skin biopsies. Almost 1/3 of subjects with reduced MoCA testing also had P-SYN detected. These results support a role for skin biopsy detection of P-SYN in patients with DLB.

TRIAL REGISTRATION: NCT04700722.

The Glasgow Outcome Scale-Extended (GOSE) is the most frequently used outcome measure for traumatic brain injury (TBI) clinical trials. The GOSE may be administered several ways, the choice depending on the purpose of the research. For example, the GOSE can be administered to reflect functional limitations attributed to the overall injury, including extracranial injuries (GOSE-All), or to discount limitations attributed to extracranial injuries (GOSE-TBI). In this investigation, we assessed the effect of using GOSE-All versus GOSE-TBI in clinical trial design. We estimated the impact of the differences in assessment strategy on sample size and power for a clinical trial of an intervention that affects only TBI-related limitations. Inclusion criteria based on TBI severity and extracranial injury severity were examined, as were primary assessments at 2 weeks or 3, 6, or 12 months after injury. Data from 2,288 participants in the prospective observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study were used to simulate the effects. If the trial were analyzed by a Mann-Whitney test comparing GOSE-All scores between treatment groups, sample size would need to increase 8-158% to account for the apparent decreased effect of a treatment that affects only the brain injury. If the sample size were not adjusted, power to detect a treatment effect would decrease from 80% to as low as 41%. If the outcome were dichotomized (favorable=GOSE 8 if including only patients with Glasgow Coma Scale [GCS]=13-15, GOSE 5-8 if GCS = 3-12), the sample size would need to increase 6-165%. The ratios of sample size are largest when the trial population consists of people with milder brain injuries and decrease with time since injury in those with GCS 13-15. It is crucial for researchers, given the aims of their studies, to decide in advance whether the classification of the GOSE should be based on effects attributed to the brain injury, despite the fact that extracranial injuries may not have allowed one to experience the extent of limitation due to the TBI, or all injuries, including extracranial injuries, and to power their studies accordingly. Instructions to the respondent and outcomes examiner need to be clear about what causes of disability are to be included. The assessment method should be accounted for in the power and sample size calculations, clearly indicated in the protocol and publications and documentation accompanying shared data, and emphasized in the training of the outcome examiners so all are collecting the desired information.