Publications by Year: 2026

IMPORTANCE: Alcohol use disorder (AUD) is a major public health concern; medications for AUD (MAUD) are an effective form of treatment but remain underused. Identifying MAUD access trends and the characteristics of counties with limited availability can inform targeted efforts to expand treatment capacity.

OBJECTIVE: To examine trends in geographic availability of MAUD at US substance use disorder treatment facilities (SUDTFs) from 2017 to 2023 and assess county characteristics associated with SUDTFs offering MAUD.

DESIGN, SETTING, AND PARTICIPANTS: This nationwide cross-sectional study used data from the Mental Health and Addiction Treatment Tracking Repository, which includes longitudinal data on licensed SUDTFs and whether they offer MAUD (acamprosate, disulfiram, or naltrexone), to quantify trends in MAUD availability at SUDTFs from January 2017 to December 2023.

MAIN OUTCOMES AND MEASURES: The primary outcome was a county-year indicator for whether at least 1 SUDTF in the county offered MAUD. Explanatory county variables included rurality, percentage of traffic fatalities involving alcohol, percentage of the population that drank excessively, percentage of uninsured individuals, poverty rate, percentage of individuals over age 65 years, and percentage of non-Hispanic White individuals. Univariate logistic regressions with state and year fixed effects were used to explore associations between county characteristics and the probability that a county had any SUDTFs offering MAUD.

RESULTS: Across 22 000 county-years in a total of 3153 counties, the mean (SD) percentage of counties with at least 1 SUDTF offering MAUD increased from 34.12% (47.42%) in 2017 to 43.88% (49.63%) in 2021, but growth plateaued after 2021. Lower MAUD presence in a county was associated with rural-adjacent (difference, -22.40 percentage points [pp]; 95% CI, -24.43 to -20.38 pp) and rural-remote (-23.64 pp; 95% CI, -25.72 to -21.56 pp) relative to metropolitan county status as well as with a higher poverty rate (-0.66 pp; 95% CI, -0.93 to -0.38 pp), greater percentage of individuals aged 65 years or older (-2.33 pp; 95% CI, -3.02 to -1.65 pp), and higher proportion of non-Hispanic White individuals (-0.58 pp; 95% CI, -0.71 to -0.46 pp), whereas greater prevalence of binge drinking (difference, 1.90 pp; 95% CI, 1.26-2.54 pp) and a higher percentage of college-educated individuals (1.28 pp; 95% CI, 1.13-1.43) were associated with higher MAUD presence.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the proportion of SUDTFs offering MAUD increased from 2017 to 2021, but growth then plateaued. Policies supporting the expansion of MAUD-providing facilities, particularly in underserved counties, may be needed to address persistent gaps in access.

IMPORTANCE: Influenza infection poses a substantial risk of severe complications, particularly in older adults and high-risk populations, such as individuals with diabetes. The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior efficacy against influenza infection compared with the standard-dose inactivated influenza vaccine (SD-IIV) among adults 65 years or older. However, there is limited evidence on its effectiveness in preventing severe respiratory and cardiovascular outcomes in individuals with diabetes.

OBJECTIVE: To investigate the relative vaccine effectiveness (rVE) of HD-IIV vs SD-IIV against severe respiratory and cardiovascular outcomes according to diabetes status and across diabetes subgroups.

DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of DANFLU-2, a pragmatic, open-label, individually randomized clinical trial conducted in Denmark during the 2022/2023 to 2024/2025 influenza seasons. Adults 65 years or older were eligible for inclusion regardless of comorbidities. Data were obtained from nationwide health registries and analyzed from June to October 2025.

INTERVENTIONS: Participants were randomly allocated 1:1 to receive HD-IIV or SD-IIV.

MAIN OUTCOMES AND MEASURES: Outcomes included respiratory and cardiovascular hospitalizations. The potential effect modification by diabetes status and across diabetes subgroups was tested.

RESULTS: Among 332 438 participants (mean [SD] age, 73.7 [5.8] years; 161 538 female individuals [48.6%]), 43 881 (13.2%) had diabetes. Overall, HD-IIV compared with SD-IIV was associated with reduced cardiorespiratory hospitalization, cardiovascular hospitalization, and influenza hospitalization. Effect estimates were similar for participants with and without diabetes for cardiorespiratory hospitalization (diabetes: rVE, 7.4%; 95% CI, -2.5% to 16.3%; no diabetes: rVE, 5.3%; 95% CI, 0.4%-10.0%; interaction P = .69), cardiovascular hospitalization (diabetes: rVE, 12.0%; 95% CI, -0.9% to 23.3%; no diabetes: rVE, 6.0%; 95% CI, -0.4% to 12.0%; interaction P = .38), and influenza hospitalization (diabetes: rVE, 41.6%; 95% CI, 5.0%-64.7%, vs no diabetes: rVE, 44.3%; 95% CI, 25.3%-58.7%; interaction P = .87). Duration of diabetes appeared to modify the effect of HD-IIV vs SD-IIV for cardiorespiratory hospitalization, with suggested benefit of HD-IIV in participants with diabetes duration longer than 5 years (rVE, 20.4%; 95% CI, 5.3%-33.1%), but not in those with shorter duration (rVE, -0.4%; 95% CI, -13.8% to 11.5%; interaction P = .03).

CONCLUSIONS AND RELEVANCE: The trial results suggest that, among adults 65 years or older, HD-IIV provided consistent benefit for cardiorespiratory, cardiovascular, and influenza hospitalizations compared with SD-IIV, regardless of diabetes status.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05517174.

BACKGROUND: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is a surrogate for long-term outcomes in breast cancer, yet response rates vary widely. Biomarkers are needed to predict efficacy. Vitamin D, through its receptor-mediated diverse biological effects on tumor biology and immune regulation, has been suggested as a potential predictor of pCR.

METHODS: We retrospectively evaluated breast cancer patients who received NACT between December 2022 and December 2024. Baseline serum vitamin D and inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), and atherogenic index of plasma (AIP), were assessed. Pathological response was defined as pCR or Miller-Payne grades 4-5. ROC analysis identified optimal cut-offs, and logistic regression was applied to explore factors associated with pathological response.

RESULTS: Among 223 patients, pCR occurred in 39.0%. ROC analysis identified 14.5 ng/mL as the optimal vitamin D threshold (AUC 0.705, p < 0.001). Vitamin D ≥ 14.5 ng/mL was independently associated with higher response, particularly in HR + /HER2 - and HER2 + subtypes; multivariable analyses also supported significance in TNBC. Recent vitamin D supplementation before NACT was significantly correlated with improved outcomes. Elevated CAR and AIP were inversely associated with response.

CONCLUSIONS: Vitamin D levels above 14.5 ng/mL independently predicted superior pathological response to NACT, with subtype-specific effects. Both baseline status and supplementation may enhance chemosensitivity, supporting vitamin D as a clinically relevant predictive biomarker.

OBJECTIVES:: To develop and validate a logistic regression model and point-based scoring system for predicting ≥Grade Group 3 clinically significant prostate cancer using a combination of multiparametric MRI findings and patient risk factors.

METHODS:: This Institutional Review Board-approved, retrospective cohort study was conducted1/1/2022–12/31/2022 with data analysis 7/1/2023–6/30/2025. Males undergoing prostate multiparametric MRI during the study period at a multi-institutional health system with prostate-specific antigen ≥4ng/mL and prostate biopsy and/or radical prostatectomy within 6 months post-multiparametric MRI were included in the study. A separate derivation cohort included 960 men who underwent multiparametric MRI from 2015–2019. A logistic regression and point-based scoring system for predicting high-grade clinically significant prostate cancer (≥Grade Group 3) was developed using predictors including prostate-specific antigen density (PSAD), highest PI-RADS score from multiparametric MRI, extraprostatic extension, and age groups (e.g., 65-<70). Discrimination was assessed using area under the curve.

RESULTS:: 1245 patients met inclusion criteria; 83% were White; 86% were ≥60 years of age. 83% had a focal lesion with PI-RADS score of ≥3. Based on the new point-based scoring system for predicting high-grade (≥Grade Group 3) prostate cancer,  28% of patients had a cumulative score of 0–7, with an estimated clinically significant prostate cancer risk of 9%. The area under the curve was 0.77 for both the logistic regression model and the point-based system.

CONCLUSIONS:: In a multi-institutional health system, age, as well as prostate-specific antigen density, highest PI-RADS score from multiparametric MRI, and extraprostatic extension significantly predicted high-grade clinically significant prostate cancer in a logistic regression and point-based scoring system.

PURPOSE: To evaluate the diagnostic contribution of MRI-based morphological and signal features-particularly T2-weighted signal intensity-for differentiating the etiology of pituitary stalk thickening (PST), and to develop imaging-based models for predicting inflammatory and neoplastic pathologies.

METHODS: This retrospective study included 41 adult (51.2%) and pediatric (48.8%) patients with confirmed PST who underwent contrast-enhanced pituitary MRI between 2012 and 2021. Etiologies were classified as congenital/idiopathic, inflammatory/infectious, or neoplastic based on clinical, radiological, or histopathological criteria. Imaging findings including enhancement pattern and T2 signal intensity were assessed in consensus by two neuroradiologists blinded to clinical data. Statistical analyses included univariate and multivariate logistic regression and receiver operating characteristic (ROC) curve analysis.

RESULTS: Neoplastic lesions were associated with significantly greater stalk thickness (median: 5.9 mm) compared to non-neoplastic lesions (median: 3.83 mm; p = 0.012). T2-weighted hyperintensity was present in 70% of neoplastic lesions, while hypointensity was more frequent in inflammatory/infectious lesions (p = 0.017). A multivariable model incorporating stalk thickness, non-T2 hypointensity and V-shaped enhancement patterns yielded excellent diagnostic performance for neoplastic pathologies (AUC: 0.848; 95% CI: 0.713-0.982). A second model using stalk thickness and T2 hypointensity predicted inflammatory lesions with an AUC of 0.836 (95% CI: 0.715-0.957).

CONCLUSION: To our knowledge, this is the first study to propose MRI-based models using stalk morphology and signal features to predict PST etiology. These non-invasive models, developed without clinical input, demonstrate promising diagnostic accuracy and may aid in differential diagnosis. Further validation in larger cohorts is needed.

Patients with cerebellar ataxia experience fatigue, impaired executive function, and psychosocial deficits. Personal social networks affect physical and mental well-being but there are no data on their effect on quality of life (QOL) and function in ataxia. We examined social network metrics in patients with cerebellar ataxia to test the hypothesis that supportive relationships enhance quality of life and physical function. We used a cross-sectional, survey-interview design with the Personal Network Survey for Clinical Research, World Health Organization QOL-BREF (WHOQOL), Functional Staging Scale for Ataxia, Friedreich's Ataxia Rating Scale-Activities of Daily Living (FARS-ADL), and Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia). We used univariate and bivariate descriptive statistics and bivariate correlations to explore relationships between social network characteristics and QOL, and multivariable linear regression for associations between them. In 106 ataxia patients (56 ± 15.3 years), social network size averaged 7.6 ± 2.8 people, mostly friends (52%) and family (33%). Social networks were dense (0.7 ± 0.3) and constrained (0.5 ± 0.1). Omnibus test showed that positive relationships, camaraderie, weekly communication, and high levels of emotional support correlated with PROM-Ataxia Total (p = 0.03), PROM-Ataxia Mental health (p = 0.05), WHOQOL (p = 0.03), FARS-ADL and Functional Staging. Those with constrained social networks and fewer positive relationships reported low QOL, as did those with frequent therapy/counseling and organizational involvement. Positive relationships within social networks of cerebellar ataxia patients positively influence QOL and functional measures. Counterintuitive negative associations with external sources of support need further study to explore causality. Network interventions to enhance emotional support and camaraderie may improve quality of life.

Epicardial and hepatic fat are suspected to play a role in cardiac remodeling. The primary objective of this study was to identify the cardiac MRI (CMR) parameters that are associated with indexed epicardial fat mass (EFMi) and hepatic steatosis in patients after the Fontan operation. This was a single-center, retrospective analysis of Fontan patients. Epicardial and subcutaneous fat were analyzed with CMR post-processing software, cvi42 (Circle Cardiovascular Imaging, Calgary, Alberta, Canada). Hepatic steatosis was measured with controlled attenuation parameter (CAP) scores via vibration controlled transient elastography. The cohort included 82 patients (65% male, median age 16 years). On univariate analysis, EFMi correlated with BMI (ρ = 0.52, p < 0.001), age (ρ = 0.48, p < 0.001), ESVi (ρ = 0.44, p < 0.001), EDVi (ρ = 0.42, p < 0.001), ventricular massi (ρ = 0.41, p < 0.01), subcutaneous fat thickness (ρ = 0.32, p < 0.01), ejection fraction (ρ=-0.37, p < 0.001), and inferior vena cava (IVC) flowi (ρ=-0.26, p < 0.05). On multivariable regression analysis, BMI (β 2.21, p < 0.001) and EDVi (β 0.33, p < 0.001) were independently associated with EFMi (R2 = 0.51). On univariate analysis, CAP scores correlated with BMI (ρ = 0.54, p < 0.001), subcutaneous fat thickness (ρ = 0.49, p < 0.001), subcutaneous fat massi (ρ = 0.44, p < 0.001), age (ρ = 0.36, p < 0.01), EFMi (ρ = 0.36, p < 0.001), and ventricular massi (ρ = 0.24, p < 0.05). On linear regression analysis, BMI (β 6.6, p < 0.001) was independently associated with CAP scores (R2 = 0.27). Neither EFMi nor CAP was significantly associated with adverse clinical events. BMI is strongly associated with epicardial and hepatic fat distribution. Epicardial fat mass is also associated with ventricular dilation.