Faculty Bibliography

BACKGROUND:Young adult cancer survivors face medical financial hardships that may lead to delaying or forgoing medical care. This study describes the medical financial difficulties experienced by young adult cancer survivors in the United States in the post Affordable Care Act (ACA) period. METHOD/METHODS:We identified 1,009 cancer survivors aged 18-39 years from the National Health Interview Survey 2015-2022 and matched 963 (95%) cancer survivors to 2,733 controls using nearest neighbor matching. We used conditional logistic regression to examine the association between cancer history and medical financial hardship and assess whether this association varied by age, sex, race/ethnicity, and region of residence. RESULTS:Compared to those without a cancer history, young adult cancer survivors were more likely to report material financial hardship (22.8% vs 15.2%; odds ratio (OR) 1.65, 95% confidence interval (CI):1.50-1.81) and behavioral medical financial hardship (34.3% vs 24.4%; OR 1.62, 95% CI: 1.49-1.76), but not psychological financial hardship (526% vs 50.9%; OR 1.07, 95% CI: 0.99-1.16). Young adult cancer survivors who were Hispanic, or lived in the Midwest and South were more likely to report psychological financial hardship than their counterparts. CONCLUSIONS:We found that young adult cancer survivors were more likely to experience material and behavioral medical financial hardship than young adults without a cancer history. We also identified specific subgroups of young adult cancer survivors that may benefit from targeted policies and interventions to alleviate medical financial hardship.

With the advent of Large Language Models (LLMs) like ChatGPT, the integration of Generative Artificial Intelligence (GAI) into clinical medicine is becoming increasingly feasible. This study aimed to evaluate the ability of the freely available ChatGPT-3.5 to generate complex differential diagnoses, comparing its output to case records of the Massachusetts General Hospital published in the New England Journal of Medicine (NEJM). Forty case records were presented to ChatGPT-3.5, prompting it to provide a differential diagnosis and then narrow it down to the most likely diagnosis. The results indicated that the final diagnosis was included in ChatGPT-3.5's original differential list in 42.5% of the cases. After narrowing, ChatGPT correctly determined the final diagnosis in 27.5% of the cases, demonstrating a decrease in accuracy compared to previous studies using common chief complaints. These findings emphasize the necessity for further investigation into the capabilities and limitations of LLMs in clinical scenarios while highlighting the potential role of GAI as an augmented clinical opinion. Anticipating the growth and enhancement of GAI tools like ChatGPT, physicians and other healthcare workers will likely find increasing support in generating differential diagnoses. However, continued exploration and regulation are essential to ensure the safe and effective integration of GAI into healthcare practice. Future studies may seek to compare newer versions of ChatGPT or investigate patient outcomes with physicians integrating this GAI technology. Understanding and expanding GAI's capabilities, particularly in differential diagnosis, may foster innovation and provide additional resources, especially in underserved areas in the medical field.

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily¹, producing a growing public health concern¹ that disproportionately affects minority groups². The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear³. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant (P < 2.6 × 10^-6) gene-level associations (HNF1A, MC4R, ATXN2L). Furthermore, we report rare variant association enrichments within 25 gene sets related to obesity, monogenic diabetes and β-cell function. Many youth-onset T2D associations are shared with adult-onset T2D, but genetic risk factors of all frequencies-and rare variants in particular-are enriched within youth-onset T2D cases (5.0-fold increase in the rare variant and 3.4-fold increase in common variant genetic liability relative to adult-onset cases). The clinical presentation of participants with youth-onset T2D is influenced in part by the frequency of genetic risk factors within each individual. These findings portray youth-onset T2D as a heterogeneous disease situated on a spectrum between monogenic diabetes and adult-onset T2D.

INTRODUCTION:Traditional survey-based surveillance is costly, limited in its ability to distinguish diabetes types and time-consuming, resulting in reporting delays. The Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network seeks to advance diabetes surveillance efforts in youth and young adults through the use of large-volume electronic health record (EHR) data. The network has two primary aims, namely: (1) to refine and validate EHR-based computable phenotype algorithms for accurate identification of type 1 and type 2 diabetes among youth and young adults and (2) to estimate the incidence and prevalence of type 1 and type 2 diabetes among youth and young adults and trends therein. The network aims to augment diabetes surveillance capacity in the USA and assess performance of EHR-based surveillance. This paper describes the DiCAYA Network and how these aims will be achieved. METHODS AND ANALYSIS:The DiCAYA Network is spread across eight geographically diverse US-based centres and a coordinating centre. Three centres conduct diabetes surveillance in youth aged 0-17 years only (component A), three centres conduct surveillance in young adults aged 18-44 years only (component B) and two centres conduct surveillance in components A and B. The network will assess the validity of computable phenotype definitions to determine diabetes status and type based on sensitivity, specificity, positive predictive value and negative predictive value of the phenotypes against the gold standard of manually abstracted medical charts. Prevalence and incidence rates will be presented as unadjusted estimates and as race/ethnicity, sex and age-adjusted estimates using Poisson regression. ETHICS AND DISSEMINATION:The DiCAYA Network is well positioned to advance diabetes surveillance methods. The network will disseminate EHR-based surveillance methodology that can be broadly adopted and will report diabetes prevalence and incidence for key demographic subgroups of youth and young adults in a large set of regions across the USA.

BACKGROUND:Previous studies have demonstrated the association between food security and cardiometabolic diseases (CMDs), yet none have investigated trends in prevalence of CMDs by food security status in the United States (US). METHODS:Serial cross-sectional analysis of the US nationally representative data from National Health and Nutrition Examination Survey (1999-2018) was conducted among adults aged 20 years or older. Food security status was defined by the US Household Food Security Survey Module (full, marginal, low, and very low food security). We estimated the age-adjusted prevalence of CMDs including obesity, hypertension, diabetes, and coronary heart disease by food security status. Racial and ethnic disparities in age-adjusted prevalence of CMDs by food security status were also assessed. RESULTS:A total of 49,738 participants were included in this analysis (weighted mean age 47.3 years; 51.3% women). From 1999 to 2018, the age-adjusted prevalence of CMDs was lower in full food secure group as compared with other groups. For example, trends in hypertension decreased from 49.7% (47.5-51.8%) to 45.9% (43.8-48.0%) (P-trend = 0.002) among the full and from 54.2% (49.9-58.5%) to 49.7% (46.8-52.6%) (P-trend = 0.02) among the marginal but remained stable among the low at 49.7% (47.9-51.6%) and among the very low at 51.1% (48.9-53.3%) (P-interaction = 0.02). Prevalence of diabetes increased from 8.85% (8.15-9.60%) to 12.2% (11.1-13.5%) among the full (P-trend < 0.001), from 16.5% (13.2-20.4%) to 20.9% (18.6-23.5%) (P-trend = 0.045) among the marginal and from 14.6% (11.1-19.0%) to 20.9% (18.8-23.3%) (P-trend = 0.001) among the low but remained stable at 18.8% (17.0-20.9) among the very low (P-trend = 0.35) (P-interaction = 0.03). Racial and ethnic differences in prevalence of CMD by food security status were observed. For example, among individuals with full food secure status, the prevalence of diabetes was 9.08% (95% CI, 8.60-9.59%) for non-Hispanic whites, 17.3% (95% CI, 16.4-18.2%) for non-Hispanic blacks, 16.1% (95% CI, 15.0-17.4%) for Hispanics and 14.9% (95% CI, 13.3-16.7%) for others. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Prevalence of CMDs was greatest among those experiencing food insecurity, and food insecurity disproportionately affected racial/ethnic minorities. Disparities in CMD prevalence by food security status persisted or worsened, especially among racial/ethnic minorities.

Objective: Irritability, typically defined as a proneness to anger, particularly in response to frustration, falls at the intersection of emotion and disruptive behavior. Despite well-defined translational models, there are few convergent findings regarding the pathophysiology of irritability. Most studies utilize computer-based tasks to examine neural responses to frustration, with little work examining stress-related responding to frustration in social contexts. The present study is the first to utilize the novel Frustration Social Stressor for Adolescents (FSS-A) to examine associations between adolescent irritability and psychological and physiological responses to frustration. Method: The FSS-A was completed by a predominantly male, racially, ethnically, and socioeconomically diverse sample of 64 12- to 17-year-olds, who were originally recruited as children with varying levels of irritability. Current irritability was assessed using the Multidimensional Assessment Profiles-Temper Loss scale (MAP-TL-Youth). Adolescents rated state anger and anxiety before and after the FSS-A, and usable salivary cortisol data were collected from 43 participants. Results: Higher MAP-TL-Youth scores were associated with greater increases in anger during the FSS-A, but not increases in anxiety, or alterations in cortisol. Pre-task state anger negatively predicted the slope of the rise in cortisol observed in anticipation of the FSS-A. Conclusions: Results provide support for unique associations between adolescent irritability and anger during, and in anticipation of, frustrating social interactions. Such findings lay a foundation for future work aimed at informing physiological models and intervention targets.

PURPOSE/OBJECTIVE:Curative-intent radiotherapy for locally advanced and select early stage cervical cancer in the US includes external beam radiotherapy (EBRT) with brachytherapy. Although there are guidelines for brachytherapy dose and fractionation regimens, there are limited data on practice patterns. This study aims to evaluate the contemporary utilization of cervical cancer brachytherapy in the US and its association with patient demographics and facility characteristics. METHODS:We retrospectively analyzed clinical covariates of cervical cancer patients diagnosed and treated in 2018-2020 with curative-intent radiotherapy from the 2020 National Cancer Database. Associations between patient and institutional factors with the number of brachytherapy fractions were identified with logistic regression. Factors with association (p < 0.10) were then included in a multivariable logistic regression model. All tests were two-sided with significance <0.05 unless specified otherwise. RESULTS:Among the eligible 2517 patients, 97.3% received HDR or LDR and is further analyzed. More patients received HDR than LDR brachytherapy (98.9% vs 1.1%) and intracavitary than interstitial brachytherapy (86.4% vs 13.6%). The most common number of HDR fractions prescribed were 5 (51.0%), 4 (32.9%), and 3 (8.6%). After adjusting for the other variables in the model, ethnicity, private insurance status, overall insurance status, and facility type were the only factors that were significantly associated with the number of brachytherapy factions (p < 0.0001, p = 0.028, p = 0.001, and p < 0.0001, respectively, n = 2184). CONCLUSIONS:In the US, various HDR brachytherapy regimens are utilized depending on patient and institutional factors. Future research may optimize cervical cancer brachytherapy by correlating specific dose and fractionation regimens with patient outcomes.

OBJECTIVES/OBJECTIVE:This study explores racial and ethnic differences in 1) receiving tissue plasminogen activator (tPA) and endovascular thrombectomy (EVT) as treatment for ischemic stroke and 2) outcomes and quality of care after use of tPA or EVT in the US. MATERIALS AND METHODS/METHODS:An observational analysis of 89,035 ischemic stroke patients from the 2019 National Inpatient Sample was conducted. We performed weighted logistic regressions between race and ethnicity and 1) tPA and EVT utilization and 2) in-hospital mortality. We also performed a weighted Poisson regression between race and ethnicity and length of stay (LOS) after tPA or EVT. RESULTS:Non-Hispanic (NH) Black patients had significantly lower odds of receiving tPA (Adjusted odds ratio [AOR] = 0.85, 95 % Confidence Internal [C.I.]: 0.80-0.91) and EVT (AOR = 0.75, 95 % CI: 0.70-0.82) than NH White patients. Minority populations (including but not limited to NH Black, Hispanic, Pacific Islander, Native American, and Asian) had significantly longer hospital LOS after treatment with tPA or EVT. We did not find a significant difference between race/ethnicity and in-hospital mortality post-tPA or EVT. CONCLUSIONS:While we failed to find a difference in in-hospital mortality, racial and ethnic disparities are still evident in the decreased usage of tPA and EVT and longer LOSs for racial and ethnic minority patients. This study calls for interventions to expand the utilization of tPA and EVT and advance quality of care post-tPA or EVT in order to improve stroke care for minority patients.

OBJECTIVES/OBJECTIVE:To examine the predictors and outcomes associated with the development of acute pancreatitis (AP) in patients hospitalized with Coronavirus Disease 2019 (COVID-19). METHODS:This is an observational analysis of the 2020 National Inpatient Sample Database. The study includes adult patients who were admitted with a confirmed diagnosis of COVID-19 and stratifies them based on the presence or absence of AP during their hospitalization. Predictors of AP development between the two groups and differences in outcomes are examined. Multivariate logistic regression analysis using Stata/BE 17.0 is conducted, with adjustments made for age, sex, race, and Charlson Comorbidity Index (CCI). Statistical significance is determined at a p-value of <0.05. RESULTS:Significant factors associated with an increased risk of AP in COVID-19 patients include Hispanic ethnicity, higher Charlson Comorbidity Index (CCI) score, residence in states located in the southern region, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use. COVID-19 patients who developed AP were also found to be at higher risk of adverse outcomes, including mortality, acute coronary syndrome, acute kidney injury, sepsis, septic shock, in-hospital cardiac arrest, invasive mechanical ventilation, upper gastrointestinal bleeding, prolonged length of stay, and increased healthcare cost. CONCLUSIONS:In hospitalized patients with COVID-19, the presence of AP is associated with increased mortality and morbidity. Risk factors for developing AP in this population include Hispanic ethnicity, residence in the southern region, higher Charlson Comorbidity Index (CCI) score, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use.

PURPOSE/OBJECTIVE:Historically, toxicity concerns have existed in patients with large prostate glands treated with radiation therapy, particularly brachytherapy. There are questions whether this risk extends to stereotactic body radiation therapy (SBRT). In this retrospective review, we examine clinical outcomes of patients with prostate glands ≥100 cc treated curatively with SBRT. METHODS AND MATERIALS/METHODS:We retrospectively analyzed a large institutional database to identify patients with histologically confirmed localized prostate cancer in glands ≥100 cc, who were treated with definitive-robotic SBRT. Prostate volume (PV) was determined by treatment planning magnetic resonance imaging. Toxicity was measured using Common Terminology Criteria for Adverse Events, version 5.0. Many patients received the Expanded Prostate Cancer Index Composite Quality of Life questionnaires. Minimum follow-up (FU) was 2 years. RESULTS:Seventy-one patients were identified with PV ≥100 cc. Most had grade group (GG) 1 or 2 (41% and 37%, respectively) disease. All patients received a total dose of 3500 to 3625 cGy in 5 fractions. A minority (27%) received androgen deprivation therapy (ADT), which was used for gland size downsizing in only 10% of cases. Nearly half (45%) were taking GU medications for urinary dysfunction before RT. Median toxicity FU was 4.0 years. Two-year rates of grade 1+ genitourinary (GU), grade 1+ gastrointestinal (GI), and grade 2+ GU toxicity were 43.5%, 15.9%, and 30.4%, respectively. Total grade 3 GU toxicities were very limited (2.8%). There were no grade 3 GI toxicities. On logistic regression analysis, pretreatment use of GU medications was significantly associated with increased rate of grade 2+ GU toxicity (odds ratio, 3.19; P = .024). Furthermore, PV (analyzed as a continuous variable) did not have an effect on toxicity, quality of life, or oncologic outcomes. CONCLUSIONS:With early FU, ultra large prostate glands do not portend increased risk of high-grade toxicity after SBRT but likely carry an elevated risk of low-grade GU toxicity.