Faculty Bibliography

Randomized controlled trials (RCTs) often include subgroup analyses to assess whether treatment effects vary across prespecified patient populations. However, these analyses frequently suffer from small sample sizes, which limit the power to detect heterogeneous effects. Power can be improved by leveraging predictors of the outcome-that is, through covariate adjustment-as well as by borrowing external data from similar RCTs or observational studies. The benefits of covariate adjustment may be limited when the trial sample is small. Borrowing external data can increase the effective sample size and improve power, but it introduces two key challenges: (i) integrating data across sources can lead to model misspecification, and (ii) practical violations of the positivity assumption-where the probability of receiving the target treatment is near zero for some covariate profiles in the external data-can lead to extreme inverse-probability weights and unstable inferences, ultimately negating potential power gains. To account for these shortcomings, we present an approach to improving power in preplanned subgroup analyses of small RCTs that leverages both baseline predictors and external data. We propose de-biased estimators that accommodate parametric, machine learning (ML), and nonparametric Bayesian methods. To address practical positivity violations (PPVs), we introduce three estimators: A covariate-balancing approach, an automated de-biased machine learning (DML) estimator, and a calibrated-DML estimator. We show improved power in various simulations and offer practical recommendations for the application of the proposed methods. Finally, we apply them to evaluate the effectiveness of citalopram for negative symptoms in first-episode schizophrenia (FES) patients across subgroups defined by duration of untreated psychosis (DUP), using data from two small RCTs.

BACKGROUND/UNASSIGNED:Advances in endoscopic endonasal approaches in ventral skull base surgery have led to increasingly complex resections and reconstructions. This study investigates differences in postoperative outcomes, including postoperative cerebrospinal fluid (CSF) leak and infection, following anterior skull base surgery and reconstruction, as a function of the type of nasal packing (absorbable vs. nonabsorbable) used to bolster the skull base reconstruction. METHODS/UNASSIGNED:A retrospective chart review was performed at a single tertiary care institution. Patients who underwent ventral skull base surgery with placement of nasal packing between January 1, 2020, and December 1, 2023, were included. We included only patients of a single rhinologist (S.L.) involved. Outcome measures included postoperative CSF leaks and postoperative infection. RESULTS/UNASSIGNED: = 0.309) between these two cohorts of patients. CONCLUSION/UNASSIGNED:While no significant differences were found in the rate of postoperative CSF leak or infection, additional patient factors should be taken into consideration when choosing between absorbable and nonabsorbable nasal packing for ventral skull base reconstruction. LEVEL OF EVIDENCE/UNASSIGNED:4.

OBJECTIVE/UNASSIGNED:Signaling was introduced to the otolaryngology match in 2021, with 5 signals allotted to applicants in 2021, 4 in 2022, 7 in 2023, and 25 in 2024. This study investigated the modifying effect of signaling volume on the relationship between away rotations and matching in otolaryngology from 2018 to 2024. STUDY DESIGN/UNASSIGNED:Cross-sectional. SETTING/UNASSIGNED:National survey of US medical students. METHODS/UNASSIGNED:We used the Texas Seeking Transparency in Application to Residency (STAR) survey responses of otolaryngology applicants from 2018 to 2024. Using multivariate logistic regression, we determined the odds of matching where away rotations were performed and how these odds varied across the pre-volume (2018-2020), low-volume (2021-2023), and high-volume (2024) signaling eras. RESULTS/UNASSIGNED: < .001). CONCLUSION/UNASSIGNED:The introduction of signaling and the recent increase in signal number are associated with decreased likelihood of matching at a program where an away rotation was performed compared to the pre-signaling era. LEVEL OF EVIDENCE/UNASSIGNED:V.

PURPOSE/UNASSIGNED:Underutilization of genetic testing among Hispanic males results in higher rates of variants of uncertain significance (VUS). We examined the impact of VUS on decision making and behavioral intentions. METHODS/UNASSIGNED:We conducted a nationwide survey of 807 US Hispanic males aged ≥40 in English and Spanish on perspectives about genetic testing results. Logistic regression was used to examine predictors of worry and behavior change with a hypothetical VUS result. RESULTS/UNASSIGNED:Over half of Hispanic male participants would still participate in genetic testing with a 1 in 5 chance of VUS. However, 36% were at least somewhat likely to regret testing and 49.9% would worry about cancer risk with VUS results. In addition, 56.3% were somewhat or very likely to change behavior due to a VUS, such as getting checked by the doctor more often or telling family members to get checked. Younger age and college education were associated with more worry and intended behavior change. CONCLUSION/UNASSIGNED:Although many Hispanic males are interested in genetic testing despite the higher likelihood of VUS, potential consequences include decisional regret, anxiety, and even changes in behavior. Effective counseling and support are important for minoritized groups undergoing genetic evaluation to avoid the potential to exacerbate health disparities.

BACKGROUND:Hispanic/Latinx males and those who are non-English proficient are significantly less likely to receive germline genetic evaluation for prostate cancer. Undertesting can impact downstream outcomes, including reduced access to approved targeted therapies, barriers to precision medicine trials, and hereditary cancer assessment for patients and family members. The goal of our study was to explore the knowledge and perceptions of genetic testing among U.S. Hispanic males, with the ultimate goal to identify potentially actionable targets to increase guideline-concordant genetic evaluation. METHODS:We conducted a nationwide online survey including U.S. Hispanic males aged ≥ 40 in English and Spanish using the 9-item Knowledge of Hereditary Prostate Cancer Scale and adapted questions about desire for more information from the Behavioral Beliefs about BRCA Genetic Counseling scale. RESULTS:Among 807 participants, the mean score for genetic knowledge was 5.8 out of 9, with gaps in understanding of incomplete penetrance of genes and maternal genetic inheritance. Medical mistrust and lower health literacy were associated with significantly lower knowledge of prostate cancer genetics. Overall, attitudes toward genetic counseling were favorable, with the majority of participants endorsing that it would help with decision-making, is concordant with cultural beliefs, and that they were interested in more information. Concerns about genetic evaluation included cost and impact for insurance. CONCLUSIONS:Despite generally favorable attitudes toward genetic evaluation among Hispanic males, there are important knowledge gaps, including the importance of both maternal and paternal family history, as well as logistical concerns. Addressing these gaps through culturally targeted outreach may help to promote equitable uptake of germline genetic evaluation.

More than one million people have died from drug overdose in the United States in the past 20 years. The overdose crisis started in the late 1990s with the proliferation of overdoses involving prescription opioids, transitioned to heroin-involved overdoses in 2010, and is currently driven by illegally manufactured synthetic opioids such as fentanyl. In response to this crisis, New York City implemented two publicly recognized overdose prevention centers (OPCs) in the nation in November 2021. Rhode Island became the first US state to authorize OPCs through state legislation and will open a site in Fall 2024. We are conducting a rigorous, multi-site, multi-component evaluation of OPCs in New York City and Rhode Island. At the individual level, we assess whether a cohort of 500 persons utilizing OPCs experience lower rates of overdose, other health problems (e.g., hepatitis C, skin infections), and emergency department use, and a higher rate of substance use treatment initiation, compared to a cohort of 500 persons who use drugs but do not utilize OPCs. At the community level, we examine whether neighborhoods surrounding the OPCs experience a greater change in overdose, measures of drug-related public disorder, and acute economic conditions following the opening of OPCs, compared to neighborhoods with no OPCs. Third, we delve into the role that the operational context, including neighborhood location, program models, and operating procedures, plays in shaping the effectiveness of OPCs using qualitative and ethnographic approaches. Fourth, we estimate the costs and cost savings associated with starting up and operating OPCs. In this paper, we: (1) present the study design and harm reduction framework which is used to evaluate the impact of OPCs in New York City and Rhode Island; (2) share the types of assessment instruments and data sources used to measure changes at the individual and community level; and (3) discuss the strengths and limitations associated with the planned approach to evaluate the health and community effects of OPCs.

OBJECTIVE:This study aims to describe current practices among otolaryngology-trained microtia surgeons in the United States. STUDY DESIGN/METHODS:Survey. SETTING/METHODS:A tertiary care center. METHODS:A 22-question anonymous digital survey of practice patterns and surgical methods was distributed to all members of the American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS) and the American Society of Pediatric Otolaryngology (ASPO). Responses were analyzed using descriptive statistics and linear regression models. RESULTS:Of 1730 eligible members, 83 (4.8%) responses were collected. Forty-three (51.8%) were AAFPRS members, 39 (47.0%) were ASPO members, and 1 (1.2%) reported dual membership. Respondents had multiple practice settings, were at different stages in their experience, and were well-distributed geographically. Forty (48.2%) don't perform microtia repair and half (52.5%) refer to an FPRS-trained colleague. Among microtia surgeons, most (N = 30, 69.8%) received fellowship training. Autologous reconstruction was the most popular method for training and practice; however, most perform multiple methods (N = 33, 76.7%). Autologous rib training was positively correlated with experience of >20 years. Those with combined autologous/alloplastic practice were more frequently trained by PO fellowship. Surgical site infection was the most frequent complication and was seen more often by those trained via residency alone (OR 12.8, P < .05). Those who trained in autologous rib alone were less likely to encounter postoperative graft exposure (OR 5.0, P < .05); however, they were more likely to encounter skin and soft tissue infection (OR 0.07, P < .05). CONCLUSION/CONCLUSIONS:Otolaryngology-trained microtia surgeons come from a variety of academic backgrounds and progress to varied practices. They are trained and practice both alloplastic and autologous repair methods, although autologous methods remain the most common.

Platform trials are multi-arm designs that simultaneously evaluate multiple treatments for a single disease within the same overall trial structure. Unlike traditional randomized controlled trials, they allow treatment arms to enter and exit the trial at distinct times while maintaining a control arm throughout. This control arm comprises both concurrent controls, where participants are randomized concurrently to either the treatment or control arm, and non-concurrent controls, who enter the trial when the treatment arm under study is unavailable. While flexible, platform trials introduce the challenge of using non-concurrent controls, raising questions about estimating treatment effects. Specifically, which estimands should be targeted? Under what assumptions can these estimands be identified and estimated? Are there any efficiency gains? In this article, we discuss issues related to the identification and estimation assumptions of common choices of estimand. We conclude that the most robust strategy to increase efficiency without imposing unwarranted assumptions is to target the concurrent average treatment effect (cATE), the ATE among only concurrent units, using a covariate-adjusted doubly robust estimator. Our studies suggest that, for the purpose of obtaining efficiency gains, collecting important prognostic variables is more important than relying on non-concurrent controls. We also discuss the perils of targeting ATE due to an untestable extrapolation assumption that will often be invalid. We provide simulations illustrating our points and an application to the ACTT platform trial, resulting in a 20% improvement in precision compared to the naive estimator that ignores non-concurrent controls and prognostic variables.