Publications

STUDY OBJECTIVES: Time-restricted eating (TRE) is a novel dietary intervention targeting weight loss and cardiometabolic risk factors. The impact of TRE on sleep patterns remains under-explored.

METHODS: This was a post-hoc analysis of a parallel-arm, controlled feeding trial in 41 adults with obesity and prediabetes/diabetes, randomized to TRE (8am-6pm) or usual eating pattern (UEP; 8am-12am) for 12 weeks. We objectively determined sleep/wake patterns from 7-day wrist actigraphy data obtained at baseline and week-12. From this data, we derived total sleep time (TST) and sleep midpoint over a 24-hour period, sleep onset/offset, and sleep continuity measures. We used paired t-tests or Wilcoxon signed rank tests to compare data between baseline and week-12 within intervention arms and Mann-Whitney U tests or Wilcoxon signed rank tests to compare changes between intervention arms.

RESULTS: 38 participants (20 UEP; 18 TRE; 93% of those randomized in the parent trial) with adequate actigraphy data (mean age 59.6 ± 7.3 years, 92% female, 92% Black, mean BMI 36.3 ± 4.7 kg/m2) were analyzed. Compared to UEP, TRE increased TST by 55 minutes (p=0.03). TRE shifted sleep midpoint to 44 minutes earlier, from 3:24am to 2:40am (p=0.01), while UEP maintained the same sleep midpoint at 3:15am. Sleep onset shifted from a median of 12:22am to 11:52pm in TRE (p=0.03) while it remained stable in UEP (p=0.97). There were no differences in sleep offset and sleep continuity within and between intervention arms.

CONCLUSIONS: TRE increased sleep time and caused earlier sleep onset compared to UEP, revealing how timing of eating may affect sleep timing and duration.

BACKGROUND: Guidelines recommend primary care practitioners ("PCPs") engage women ≥ 75 years in shared decision-making (SDM) around mammography screening. Therefore, we aimed to develop a web-based conversation aid about mammography screening for women ≥ 75 using output from established simulation models to provide screening outcomes based on > 23,000 combinations of individual women's health and breast cancer risk factors.

METHODS: We used an end-user centered design approach to develop a prototype web-based conversation aid incorporating feedback. From July 2023 to April 2024, 10 PCPs from a Boston-area health system and a safety-net hospital used the prototype aid during encounters with women ≥ 75 without breast cancer or dementia (n = 30; 1-5 patients per PCP). We observed aid use and assessed clinician effort to involve patients in SDM using OPTION5 (assesses five components of SDM, scores range 0-100). We surveyed PCPs and patients about the aid's acceptability. Patients completed the SDM-process scale (scores range 0-4) to rate the SDM quality experienced. Participants' comments were subject to thematic analysis.

RESULTS: Of 10 PCP-participants, seven were female and four were community-based. Of 30 patient-participants, 22 (73%) were non-Hispanic White, 9 (30%) had ≥ 2 Charlson comorbidities and mean age was 78.5 years (SD 2.8). Nine PCPs agreed that the aid helped them with SDM and was easy-to-use; six felt it had too much information; and seven planned to continue using the aid. Patients rated the SDM-process highly (scores = 3.0 [SD 0.9]) and we observed high SDM (mean OPTION5 = 77.9 [SD 20.6]). Participants felt the aid was "empowering" and "helpful for decision-making." After SDM discussions, seven patients intended to stop screening, nine to screen less frequently, and 14 to continue screening regularly.

CONCLUSIONS: We developed a novel conversation aid that supports SDM about mammography screening with women ≥ 75 years. Lessons learned will guide revisions of a final tool for testing in a clinical trial.

STUDY OBJECTIVES: Hyperarousal is common in patients with insomnia. Autonomic stress may reflect hyperarousal and distinguish participants with insomnia vs good sleepers. Slope analysis of heart rate reduction during sleep onset might be a promising measure of such autonomic modulation. We aim to explore the potential utility of this measure with data collected from home settings from the Sleep Heart Health Study.

METHODS: In this secondary analysis with 743 participants, we applied two approaches to compute slopes for heart rate reduction during sleep onset. We compared slopes among participants with and without insomnia symptoms, with short versus long sleep onset latency, with or without difficulty falling asleep during the study night, and with sleep-onset insomnia versus other insomnia subtypes. We also explored correlations between heart rate reduction and sleep outcome measures.

RESULTS: We found that the slopes of heart rate reduction during sleep onset were most significantly associated with objectively measured sleep onset latency, followed by subjectively reported sleep onset latency, regardless of the approach used to compute the slopes. Participants with self-reported difficulty falling asleep during the study night had significantly blunted heart rate reduction. The slopes were significantly blunted in participants with self-reported sleep-onset insomnia compared to other types of insomnia.

CONCLUSIONS: As measures of autonomic activity, the slopes of heart rate reduction may serve as a physiological biomarker to indicate hyperarousal during wakefulness before sleep onset. Tracking changes of heart rate reduction during sleep onset may have potential value in the evaluation of insomnia treatments, especially those targeting sleep onset difficulties.

Background: The emerging paradigm of whole person health shares many core principles with traditional complementary and integrative health frameworks, including Tai Chi and Qigong (TCQ). Methods: In the fall of 2023, the Harvard Medical School Osher Center for Integrative Health hosted the inaugural international conference on The Science of Tai Chi & Qigong for Whole Person Health: Advancing the Integration of Mind-Body Practices into Contemporary Healthcare at Harvard Medical School. A two-part white paper was written to summarize key conference topics, findings, and issues. Results and Discussion: Part II presented here summarizes evidence gaps and future research opportunities, including: understudied clinical conditions and populations, impact of long-term TCQ training, understanding the impact of specific TCQ styles, training regimens, dosage, and contextual effects; implementation, cost-effectiveness, and medical utilization research; individual data meta-analysis, and teaching competencies, credentialing, and licensure. Part I of this white paper discusses the rationale for the conference, synthesizes the state of evidence for TCQ as rehabilitative and preventive tools for a range of clinical conditions, and summarizes the translational research informing therapeutic mechanisms associated with TCQ training.

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.

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.

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.

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.

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.