Publications

2025

Morooka, Hikaru, Eirin B Haug, Vegard Malmo, Jan Pål Loennechen, Hanne Ellekjær, Abhijit Sen, Kenneth J Mukamal, Janet Rich-Edwards, Imre Janszky, and Julie Horn. (2025) 2025. “Adverse Pregnancy Outcomes and Risk of Atrial Fibrillation: Findings from the HUNT Study.”. European Journal of Preventive Cardiology. https://doi.org/10.1093/eurjpc/zwaf233.

BACKGROUND: Despite well-studied associations between hypertensive disorders of pregnancy (HDP) and atrial fibrillation (AF), the mechanisms of the excess risk of AF in women with history of HDP are not fully understood. Furthermore, little is known about associations between other adverse pregnancy outcomes (APOs) and AF, including preterm birth, small/large-for-gestational age (SGA/LGA) offspring.

METHODS: By linking the population-based HUNT study with the Medical Birth Registry of Norway (MBRN) and electronic patient administrative systems, 15,104 women ≥45 years with 34,674 births were followed and assessed for validated AF for a median of 12.9 years. Information on APOs was retrieved from the MBRN. We used Cox proportional hazards models to calculate hazard ratios (HR) for associations of APOs with risk of AF. By inverse odds ratio weighting, we assessed modifiable AF risk factors that could explain the associations.

RESULTS: Among women aged 45-65, those with HDP had a higher risk of AF [HR 2.03, 95% confidence interval (CI) 1.27-3.24] as women without HDP, but not among women >65 years [HR 0.95, 95% CI 0.57-1.60]. A history of LGA was associated with increased risk of AF [HR 1.38, 95% CI 1.03-1.84], but histories of preterm birth or SGA were not [HR 0.94, 95% CI 0.63-1.41, HR 0.90, 95% CI 0.66-1.23]. Postpregnancy body mass index (BMI) might possibly explain about 45% of the associations between HDP or LGA and AF.

CONCLUSIONS: Women with history of hypertensive disorders of pregnancy or large-for-gestational age offspring are at higher risk of atrial fibrillation.

Sasamoto, Naoko, Long H Ngo, Allison F Vitonis, Simon T Dillon, Maryam Aziz, Amy L Shafrir, Stacey A Missmer, Towia A Libermann, and Kathryn L Terry. (2025) 2025. “Prospective Evaluation of Plasma Proteins in Relation to Surgical Endometriosis Diagnosis in the Nurses’ Health Study II.”. EBioMedicine 115: 105688. https://doi.org/10.1016/j.ebiom.2025.105688.

BACKGROUND: Endometriosis is a chronic inflammatory condition characterised by pain and infertility. We conducted a prospective study to elucidate the pathophysiological mechanisms underlying endometriosis development.

METHODS: We examined the association between 1305 proteins measured by SomaScan proteomics and risk of endometriosis diagnosis in prospectively collected plasma from 200 laparoscopically-confirmed endometriosis cases and 200 risk-set sampling matched controls within the Nurses' Health Study II (NHSII) cohort. Using conditional logistic regression, we calculated odds ratios (OR) and 95% confidence intervals (CI) per one standard deviation increase in protein levels and area under the curve (AUC) to assess the multi-protein model in discriminating cases from controls. Analytical validation for three proteins was performed using immunoassays. Ingenuity Pathway Analysis and STRING analyses identified biological pathways and protein interactions.

FINDINGS: Blood samples from cases were collected up to 9 years before diagnosis (median = 4 years). Among 61 individual proteins nominally significantly associated with risk of endometriosis diagnosis compared to controls, endometriosis cases had higher plasma levels of S100A9 (OR = 1.52, 95%CI = 1.19-1.94), ICAM2 (OR = 1.47, 95%CI = 1.17-1.85), HIST1H3A (OR = 1.42, 95%CI = 1.31-1.78), TOP1 (OR = 1.95, 95%CI = 1.24-3.06), CD5L (OR = 1.23, 95%CI = 1.00-1.51) and lower levels of IGFBP1 (OR = 0.70, 95%CI = 0.52-0.94). We further evaluated three of the proteins in an independent set of 103 matched case-control pairs within the NHSII cohort. Pathway analyses revealed upregulation of multiple immune-related pathways in blood samples collected years before endometriosis diagnosis.

INTERPRETATION: In this prospective analysis using aptamer-based proteomics, we identified multiple proteins and biological pathways related to innate immune response upregulated years before endometriosis surgical diagnosis, suggesting the role of immune dysregulation in endometriosis development.

FUNDING: This study was supported by the Department of Defence, the 2017 Boston Center for Endometriosis Trainee Award. Investigators were supported by Aspira Women's Health and NIH which were not directly related to this project.

Salmi, Liz, Dana M Lewis, Jennifer L Clarke, Zhiyong Dong, Rudy Fischmann, Emily I McIntosh, Chethan R Sarabu, and Catherine M DesRoches. (2025) 2025. “A Proof-of-Concept Study for Patient Use of Open Notes With Large Language Models.”. JAMIA Open 8 (2): ooaf021. https://doi.org/10.1093/jamiaopen/ooaf021.

OBJECTIVES: The use of large language models (LLMs) is growing for both clinicians and patients. While researchers and clinicians have explored LLMs to manage patient portal messages and reduce burnout, there is less documentation about how patients use these tools to understand clinical notes and inform decision-making. This proof-of-concept study examined the reliability and accuracy of LLMs in responding to patient queries based on an open visit note.

MATERIALS AND METHODS: In a cross-sectional proof-of-concept study, 3 commercially available LLMs (ChatGPT 4o, Claude 3 Opus, Gemini 1.5) were evaluated using 4 distinct prompt series-Standard, Randomized, Persona, and Randomized Persona-with multiple questions, designed by patients, in response to a single neuro-oncology progress note. LLM responses were scored by the note author (neuro-oncologist) and a patient who receives care from the note author, using an 8-criterion rubric that assessed Accuracy, Relevance, Clarity, Actionability, Empathy/Tone, Completeness, Evidence, and Consistency. Descriptive statistics were used to summarize the performance of each LLM across all prompts.

RESULTS: Overall, the Standard and Persona-based prompt series yielded the best results across all criterion regardless of LLM. Chat-GPT 4o using Persona-based prompts scored highest in all categories. All LLMs scored low in the use of Evidence.

DISCUSSION: This proof-of-concept study highlighted the potential for LLMs to assist patients in interpreting open notes. The most effective LLM responses were achieved by applying Persona-style prompts to a patient's question.

CONCLUSION: Optimizing LLMs for patient-driven queries, and patient education and counseling around the use of LLMs, have potential to enhance patient use and understanding of their health information.

Steitz, Bryan D, Robert W Turer, Liz Salmi, Uday Suresh, Scott MacDonald, Catherine M DesRoches, Adam Wright, Jeremy Louissaint, and Trent Rosenbloom. (2025) 2025. “Repeated Access to Patient Portal While Awaiting Test Results and Patient-Initiated Messaging.”. JAMA Network Open 8 (4): e254019. https://doi.org/10.1001/jamanetworkopen.2025.4019.

IMPORTANCE: Patients have immediate access to test results in the patient portal, which can cause worry. Identifying behaviors associated with worry while awaiting results may allow health systems to support patients and reduce message volumes.

OBJECTIVE: To describe characteristics of patients who refresh their portal while awaiting test results and measure the association between refresh behavior and patient-initiated messaging.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study was performed at Vanderbilt University Medical Center, which uses a MyChart-based patient portal. All adult patients (aged ≥18 years) who received outpatient test results between January 1, 2022, and December 31, 2023, were included.

EXPOSURES: Use of the patient portal to review test results.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who refreshed the portal while awaiting test results. Tests were stratified into low-sensitivity (eg, basic metabolic panel) and high-sensitivity (eg, tissue biopsy) groups using validated categories based on each test's likelihood of being misinterpreted or causing distress. Portal access logs were used to identify refresh behaviors, in which patients accessed the portal seeking new results. Secondary outcomes included the association between patient characteristics and refresh behavior and between refresh behavior and messaging as measured using multivariable logistic regression.

RESULTS: A total of 968 774 results were reviewed by 290 349 patients (mean [SD] age, 47.8 [18.0] years; 66.3% female). Patients refreshed their portal for 25.9% of results. Patients more commonly refreshed for high-sensitivity results (25 280 of 64 356 [39.3%]) compared with low sensitivity results (225 516 of 904 418 [24.9%]) (P < .001). Patients who enabled notifications had higher odds of refreshing for high-sensitivity results (odds ratio, 1.11; 95% CI, 1.06-1.17) and low-sensitivity results (odds ratio, 1.54; 95% CI, 1.49-1.59). Each refresh for high-sensitivity results was associated with a lower increase in the probability of messaging within 24 hours (mean marginal effect, 0.41; 95% CI, 0.34-0.49) compared with refreshing for low-sensitivity results (mean marginal effect, 1.03; 95% CI, 0.96-1.11).

CONCLUSION AND RELEVANCE: This cross-sectional study found an association of patients' refresh activity for low-sensitivity results with patient-initiated messaging after review. These findings suggest that refresh behavior, a potential measure of worry, may be a characteristic of patient attitudes and preferences rather than the test.

Ghanbari, Fahime, Manuel A Morales, Jordan A Street, Jennifer Rodriguez, Scott Johnson, Patrick Pierce, Adele Carty, et al. (2025) 2025. “Free-Breathing, Highly Accelerated, Single-Beat, Multisection Cardiac Cine MRI With Generative Artificial Intelligence.”. Radiology. Cardiothoracic Imaging 7 (2): e240272. https://doi.org/10.1148/ryct.240272.

Purpose To develop and evaluate a free-breathing, highly accelerated, multisection, single-beat cine sequence for cardiac MRI. Materials and Methods This prospective study, conducted from July 2022 to December 2023, included participants with various cardiac conditions as well as healthy participants who were imaged using a 3-T MRI system. A single-beat sequence was implemented, collecting data for each section in one heartbeat. Images were acquired with an in-plane spatiotemporal resolution of 1.9 × 1.9 mm2 and 37 msec and reconstructed using resolution enhancement generative adversarial inline neural network (REGAIN), a deep learning model. Multibreath-hold k-space-segmented (4.2-fold acceleration) and free-breathing single-beat (14.8-fold acceleration) cine images were collected, both reconstructed with REGAIN. Left ventricular (LV) and right ventricular (RV) parameters between the two methods were evaluated with linear regression, Bland-Altman analysis, and Pearson correlation. Three expert cardiologists independently scored diagnostic and image quality. Scan and rescan reproducibility was evaluated in a subset of participants 1 year apart using the intraclass correlation coefficient (ICC). Results This study included 136 participants (mean age [SD], 54 years ± 15; 69 female, 67 male), 40 healthy and 96 with cardiac conditions. k-Space-segmented and single-beat scan times were 2.6 minutes ± 0.8 and 0.5 minute ± 0.1, respectively. Strong correlations (P < .001) were observed between k-space-segmented and single-beat cine parameters in both LV (r = 0.97-0.99) and RV (r = 0.89-0.98). Scan and rescan reproducibility of single-beat cine was excellent (ICC, 0.97-1.0). Agreement among readers was high, with 125 of 136 (92%) images consistently assessed as diagnostic and 133 of 136 (98%) consistently rated as having good image quality by all readers. Conclusion Free-breathing 30-second single-beat cardiac cine MRI yielded accurate biventricular measurements, reduced scan time, and maintained high diagnostic and image quality compared with conventional multibreath-hold k-space-segmented cine images. Keywords: MR-Imaging, Cardiac, Heart, Imaging Sequences, Comparative Studies, Technology Assessment Supplemental material is available for this article. © RSNA, 2025.

Zhang, Cancan, Elizabeth Mostofsky, Hui Zhang, Bo Zhang, Julia Lindenberg, Maelys J Amat, and Kenneth J Mukamal. (2025) 2025. “A Phenome-Wide Association Study of Marijuana Use and Circulating Biomarkers in the United States: National Health and Nutrition Examination Survey 2009-2018.”. Journal of Clinical Pharmacology. https://doi.org/10.1002/jcph.70022.

This study aimed to assess the associations between recent cannabis use and 49 biochemical biomarkers in a representative sample of American adults, using data from the 2009-2018 National Health and Nutrition Examination Survey. A phenotype-wide association study (PheWAS) was conducted to uncover new biomarkers linked to cannabis use. The analysis included 19,926 adults aged 18-59, with a mean age of 38.93 years (50.8% women), and 36.7% reporting recent cannabis use. Metabolic associations included higher high-density lipoprotein (HDL) cholesterol (3.51 mg/dL, 95% CI [2.50, 4.62]) and lower glycohemoglobin (-0.09%, 95% CI [-0.15, -0.04]) and glucose (-2.39 mg/dL, 95% CI [-4.07, -0.70]). Hematological findings included higher hemoglobin (0.09 g/dL, 95% CI [0.02, 0.16]), mean erythrocyte volume (1.46 fL, 95% CI [1.12, 1.80]), mean erythrocyte hemoglobin (0.46 pg, 95% CI [0.32, 0.60]), erythrocyte volume fraction (0.31%, 95% CI [0.11%, 0.50%]), and lower erythrocyte counts (-0.04 million cells/µL, 95% CI [-0.07, -0.02]). Serum chemistry associations included higher bicarbonate (0.20 mmol/L, 95% CI [0.06, 0.35]) and lower chloride (-0.47 mmol/L, 95% CI [-0.69, -0.24]). Associations were also observed with 25 hydroxyvitamin-3 (OHD3) (2.38 nmol/L, 95% CI [0.55, 4.22]) and epi-25OHD3 (0.40 nmol/L, 95% CI [0.15, 0.65]), and an inverse association with globulin (-0.03 g/dL, 95% CI [-0.06, -0.01]). Sensitivity analyses confirmed the robustness of these associations. Recent marijuana use is associated with diverse and complex phenotypes, several of which have not been previously evaluated. Further validation studies are warranted, this approach offers an opportunity to understand a comprehensive range of potential effects of marijuana use.

Wang, Yi-Xin, Orianne Dumas, Raphaëlle Varraso, Yang Sun, Janet W Rich-Edwards, JoAnn E Manson, Kenneth J Mukamal, Yu Zhang, Carlos A Camargo, and Carmen Messerlian. (2025) 2025. “Occupational Exposure to Disinfectants and Risk of Incident Cardiovascular Disease Among US Nurses: The Nurses’ Health Study II.”. Environmental Health Perspectives. https://doi.org/10.1289/EHP14945.

BACKGROUND: Exposure to certain chemicals in disinfectants has been associated with vascular dysfunction in toxicological studies, but the association between disinfectant exposure and clinical cardiovascular disease (CVD) remains unclear.

OBJECTIVE: To evaluate the association between occupational exposure to disinfectants and subsequent risk of CVD among United States (US) nurses.

METHODS: We included 75,675 participants from The Nurses' Health Study II who maintained a nursing job and reported data on occupational disinfectant exposure. We estimated hazard ratios (HR) and 95% confidence intervals (CIs) of incident CVD, including coronary heart disease (CHD) and stroke, using Cox proportional hazard models comparing job types and general disinfection tasks between participants. We also used a job-task-exposure matrix to evaluate the risk of CVD by frequency of cleaning/disinfection tasks and exposure levels of 7 specific disinfectants (formaldehyde, glutaraldehyde, hypochlorite bleach, hydrogen peroxide, alcohol, quaternary ammonium compounds, and enzymatic cleaners).

RESULTS: During 10 years of follow-up (2009-2019), we documented 726 incident cases of CVD. In fully adjusted models, the hazard ratio of CVD among nurses who worked in operating rooms was 1.72 (95% CI: 1.25 to 2.36), compared with those working as educators or administrators. A similar pattern of associations was found when we separately assessed the risk for CHD and stroke (HR= 1.69 [95% CI: 1.11 to 2.58] and 1.69 [95% CI: 1.05 to 2.74 ], respectively) among operating room nurses, compared with those working as educators or administrators. Those who used disinfectants weekly had modest elevations in CVD risk (HR=1.21 [95% CI: 1.04 to 1.40]), compared with women who never used disinfectants. The highest CVD risk was observed among nurses using disinfectants or spray or aerosol products 4-7 days/week and those exposed to the highest levels of the 7 specific disinfectants listed above.

CONCLUSION: Exposure to disinfectants in real-world healthcare settings was associated with a higher risk of CVD, including CHD and stroke, among US nurses. https://doi.org/10.1289/EHP14945.

Png, C Y Maximilian, Gloria Y Yeh, Anahita Dua, Abhisekh Mohapatra, Junaid Y Malek, Nikolaos Zacharias, James H Balcom, Sunita D Srivastava, and Matthew J Eagleton. (2025) 2025. “Pilot Study Protocol for a Novel Perioperative Mind-Body Intervention for Peripheral Vascular Interventions.”. JVS-Vascular Insights 3: 100199. https://doi.org/10.1016/j.jvsvi.2025.100199.

BACKGROUND: A novel mind-body intervention (MBI) targeting vascular surgery patients undergoing peripheral vascular interventions (PVIs) under procedural sedation and analgesia (PSA) was recently developed, but has yet to be clinically tested. An exploratory randomized controlled trial is planned to test the novel intervention in patients undergoing PVIs under PSA.

METHODS: Patients undergoing PVIs under PSA by vascular surgeons across four hospitals in Massachusetts and New Hampshire will be screened for enrollment. Exclusion criteria include urgent or emergent procedures, prior ipsilateral lower extremity amputations (including digit amputations) and non-English speakers. 30 patients will be enrolled and randomized 1:1 to either a perioperative MBI on the day of surgery (n = 15), or a standard of care control (n = 15). There would be no restriction on anesthesia practice, and collected data will include perioperative pain and sedation requirements and qualitative feedback from both the patients and perioperative staff.

CONCLUSIONS: This protocol delineates a pilot randomized controlled trial to test the feasibility and acceptability of a novel perioperative MBI for patients undergoing PVIs under PSA.