Publications

BACKGROUND: Alcohol intake is associated with a higher risk of estrogen receptor-positive (ER+) breast cancer (BC), presumably through its confirmed ability to increase sex hormone levels. Whether consuming alcohol within the recommended limit of one serving per day increases sex hormone levels among postmenopausal women taking aromatase inhibitors (AI) to inhibit estrogen production remains unknown. Therefore, we compared sex hormone levels following white wine to levels following white grape juice among ER + BC survivors taking AIs.

METHODS: In this 10-week randomized controlled two-period crossover trial conducted from September 2022 to July 2023 among 20 postmenopausal women on AIs, we examined within-person changes in sex hormone levels following 3 weeks of 5 ounces of white wine daily versus 3 weeks of 6 ounces of white grape juice daily, with each drinking period preceded by two-week washouts and drinking period sequence allocated by randomization.

RESULTS: All 20 participants completed the trial. Compared to daily grape juice, daily wine led to decreases in total estradiol (11.1%, 95%confidence interval[CI] -49.8%,57.2%), free estradiol index (0.7%, 95%CI -2%,0.7%), and free estradiol concentration (7.7%, 95%CI -48%, 63.9%) but increases in estrone (13.8%, 95%CI -9.5%,43.1%), dehydroepiandrosterone sulfate (DHEAS; 11.4%, 95%CI -3.3%,28.4%), and testosterone (12.6%, 95%CI -0.8%,27.7%) and decreased sex hormone-binding globulin (SHBG; -2.7%, 95%CI -21.9%,21.2%).

CONCLUSIONS: Five ounces of white wine daily did not lead to statistically significant increases in estradiol, but it led to changes in other sex hormones suggesting higher BC risk. Whether this level of alcohol intake diminishes AI effectiveness warrants further investigation.

TRIALS REGISTRATION: Clinicaltrials.gov NCT05423730 registered June 14, 2022.

BACKGROUND: Delirium after cardiac surgery is common, morbid, and costly, but may be prevented with risk stratification and targeted intervention. In this study, we aimed to identify protein biomarkers and develop a predictive model for postoperative delirium in older patients undergoing cardiac surgery.

METHODS: SomaScan analysis of 1305 proteins in the plasma from 57 older adults undergoing cardiac surgery requiring cardiopulmonary bypass was conducted to define delirium-specific protein signatures at baseline (preoperative baseline timepoint [PREOP]) and postoperative day 2 (POD2). Selected proteins were validated in 115 patients using the Enzyme-Linked Lectin Assay (ELLA) multiplex immunoassay platform. Proteins were combined with clinical and demographic variables to build multivariable models that estimate the risk of postoperative delirium and bring light to the underlying pathophysiology.

RESULTS: Of the 115 patients, 21 (18.3%) developed delirium after surgery. The SomaScan proteome screening evidenced differential expression of 115 and 85 proteins in delirious patients compared to nondelirious preoperatively and at POD2, respectively ( P < .05). Following biological and methodological criteria, 12 biomarker candidates (Tukey's fold change [|tFC|] >1.4, Benjamini-Hochberg [BH]- P < .01) were selected for ELLA multiplex validation. Statistical analyses of model fit resulted in the combination of age, sex, and 3 proteins (angiopoietin-2; C-C motif chemokine 5; and metalloproteinase inhibitor 1; area under the curve [AUC] = 0.829) as the best performing predictive model for delirium. Analyses of pathways showed that delirium-associated proteins are involved in inflammation, glial dysfunction, vascularization, and hemostasis.

CONCLUSIONS: Our results support the identification of patients at higher risk of developing delirium after cardiac surgery using a multivariable model that combines demographic and physiological features, also bringing light to the role of immune and vascular dysregulation as underlying mechanisms.

OBJECTIVES: Endovascular aneurysm repair (EVAR) for large infrarenal abdominal aortic aneurysms (AAAs) has been associated with worse outcomes compared with EVAR for smaller AAAs. Whether these findings apply to complex AAAs (cAAA) remains uncertain.

METHODS: We identified all intact complex EVAR (cEVAR) from 2012 to 2024 in the Vascular Quality Initiative. cEVAR was defined as having a proximal extent between zones 6 and 9 and at least one side branch/fenestration/chimney/parallel grafting. Aneurysm size was defined as follows: large: >65 mm (males), >60 mm (females); medium: 55 to 65 mm (males), 50 to 60 mm (females); and small: <55 mm (males), <50 mm (females). We assessed perioperative death, any complication, and in-hospital reintervention using logistic regression and midterm mortality using adjusted Kaplan-Meier methods and Cox regression analyses. Medium-sized aneurysms were compared with large and small aneurysms.

RESULTS: Of the 3426 patients, 22.6% had large, 60.4% medium, and 17.0% had small aneurysms. As compared with medium and small aneurysms, large aneurysms demonstrated higher rates of perioperative death (4.8% vs 2.6% vs 0.5%), any complication (33.3% vs 23.6% vs 19.4%), and in-hospital reintervention (6.2% vs 4.0% vs 2.6%) (all P < .05). The median follow-up was 445 days. One-year mortality rates were higher in large aneurysms (12.3% vs 7.8% vs 3.8%; P < .001). After adjustment, when compared with medium-sized aneurysms, large aneurysms were associated with a significantly higher risk of perioperative death (adjusted odds ratio [aOR], 1.73; 95% confidence interval [CI], 1.09-2.72), any complication (aOR, 1.44; 95% CI, 1.18-1.76), and midterm mortality (adjusted hazard ratio, 1.50; 95% CI, 1.19-1.88), but not in-hospital reintervention (aOR, 1.46; 95% CI, 0.99-2.13). Although small aneurysms, as compared with medium-sized aneurysms, did not demonstrate a difference in any complication (aOR, 0.87; 95% CI, 0.68-1.10), in-hospital reintervention (aOR, 0.77; 95% CI, 0.42-1.33), and midterm mortality (adjusted hazard ratio, 0.78; 95% CI, 0.57-1.08], they did demonstrate a lower risk of perioperative death (aOR, 0.26; 95% CI, 0.06-0.71).

CONCLUSIONS: In cEVAR for cAAA, large aneurysms, compared with medium-sized aneurysms, were associated with higher rates of perioperative death, any complication, and midterm mortality, with in-hospital reinterventions trending toward a statistically significant higher risk. Although these results align with expectations, they emphasize the importance of effectively managing patients with large cAAAs and highlight the need for future research to determine whether patients might benefit more from medical therapy or open repair.

BACKGROUND: Patients in the United States have recently gained federally mandated, free, and ready electronic access to clinicians' computerized notes in their medical records ("open notes"). This change from longstanding practice can benefit patients in clinically important ways, but studies show some patients feel judged or stigmatized by words or phrases embedded in their records. Therefore, it is imperative that clinicians adopt documentation techniques that help both to empower patients and minimize potential harms.

OBJECTIVE: At a time when open and transparent communication among patients, families, and clinicians can spread more easily throughout medical practice, this inquiry aims to develop informed guidelines for documentation in medical records.

METHODS: Through a series of focus groups, preliminary guidelines for documentation language in medical records were developed by health professionals and patients. Using a structured focus group decision guide, we conducted 4 group meetings with different sets of 27 participants: physicians experienced with writing open notes (n=5), patients accustomed to reviewing their notes (n=8), medical student educators (n=7), and resident physicians (n=7). To generate themes, we used an iterative coding process. First-order codes were grouped into second-order themes based on the commonality of meanings.

RESULTS: The participants identified 10 important guidelines as a preliminary framework for developing notes sensitive to patients' needs.

CONCLUSIONS: The process identified 10 discrete themes that can help clinicians use and spread patient-centered documentation.

IMPORTANCE: Nocturnal hypertension while asleep is associated with substantial increases in risk of cardiovascular disease (CVD) and death. Whether hypertension while supine is a risk factor associated with CVD independent of seated hypertension remains unknown.

OBJECTIVE: To investigate the association between supine hypertension and CVD outcomes and by hypertension treatment status.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the Atherosclerosis Risk in Communities (ARIC) study, which was established in 1987 to examine cardiovascular risk factors among middle-aged adults from 4 communities in the US. Supine and seated blood pressure were measured in more than 13 000 middle-aged adults with longitudinal surveillance for CVD over 27 years. Participants with a history of coronary heart disease (CHD), heart failure, or stroke were excluded. Data were analyzed from May 2023 through December 2024.

EXPOSURES: Supine hypertension (supine systolic blood pressure ≥130 or diastolic blood pressure ≥80 mm Hg) with and without seated hypertension (seated systolic blood pressure ≥130 or diastolic blood pressure ≥80 mm Hg).

MAIN OUTCOMES AND MEASURES: Cox proportional hazard models with adjustment for CVD risk factors were performed to investigate the association of supine hypertension with and without seated hypertension with incident CHD, heart failure, stroke, fatal CHD, and all-cause mortality.

RESULTS: Of 11 369 participants without known CVD (6332 female [55.7%] and 5037 male [44.3%]; 2858 Black [25.1%] and 8511 White [74.9%]; mean [SD] age 53.9 [5.7] years]), 16.4% (95% CI, 15.5%-17.2%) of those without seated hypertension had supine hypertension and 73.5% (95% CI, 72.2%-74.8%) of those with seated hypertension had supine hypertension. Supine hypertension was associated with incident CHD (hazard ratio [HR], 1.60; 95% CI, 1.45-1.76), heart failure (HR, 1.83; 95% CI, 1.68-2.01), stroke (HR, 1.86; 95% CI, 1.63-2.13), fatal CHD (HR, 2.18; 95% CI, 1.84-2.59), and all-cause mortality (HR, 1.43; 95% CI, 1.35-1.52) during a median (25th, 75th percentile) follow-up of 25.7 (15.4, 30.4) years, 26.9 (17.6, 30.5) years, 27.6 (18.5, 30.6 years), 28.3 (20.5, 30.7) years, and 28.3 (20.5 years, 30.7) years, respectively. There were no meaningful differences by seated hypertension status. Results were similar by hypertension medication use. Participants with supine hypertension alone had risk associations similar to those of participants with hypertension in both positions and significantly greater than those of participants with seated hypertension alone with the exception of fatal CHD; seated vs supine HRs were 0.72 (95% CI, 0.61-0.85) for CHD, 0.72 (95% CI, 0.60-0.85) for heart failure, 0.66 (95% CI, 0.51-0.86) for stroke, and 0.83 (95% CI, 0.74-0.92) for all-cause mortality.

CONCLUSIONS AND RELEVANCE: Supine hypertension regardless of seated hypertension had a higher HR for CVD risk than seated hypertension alone. Future research should evaluate supine hypertension in the setting of nocturnal hypertension and as an independent target of blood pressure treatment.

BACKGROUND: Hypotensive episodes detected by 24-hour ambulatory blood pressure (BP) monitoring capture daily cumulative hypotensive stress and could be clinically relevant to cognitive impairment, but this relationship remains unclear.

METHODS: We included participants from the Systolic Blood Pressure Intervention Trial (receiving intensive or standard BP treatment) who had 24-hour ambulatory BP monitoring measured near the 27-month visit and subsequent biannual cognitive assessments. We evaluated the associations of hypotensive episodes (defined as systolic BP drops of ≥20 mm Hg between 2 consecutive measurements that reached <100 mm Hg) and hypotensive duration (cumulative time of systolic BP <100 mm Hg) with subsequent cognitive function using adjusted linear mixed models. We further assessed 24-hour average BP and variability.

RESULTS: Among 842 participants with treated hypertension (mean age, 71±9 years; 29% women), the presence (versus absence) of recurrent hypotensive episodes (11%) was associated with lower digit symbol coding scores (difference in Z scores, -0.249 [95% CI, -0.380 to -0.119]) and faster declines (difference in Z score changes, -0.128 [95% CI, -0.231 to -0.026]). A consistent dose-response association was also observed for longer hypotensive duration with worse Montreal Cognitive Assessment and digit symbol coding scores. The association with digit symbol coding scores remained significant after further adjusting for 24-hour average BP and variability and was not observed for hypotension defined by clinic, orthostatic, or 24-hour average BP. Intensive BP treatment increased 24-hour hypotensive episodes and modified its association with the decline in digit symbol coding score.

CONCLUSION: Twenty-four-hour hypotensive episodes were associated with worse cognitive function, especially in processing speed, and could be a novel marker for optimal BP control and dementia prevention.

AIMS: The purpose of this integrative review was to identify effective diabetes self-management education and support for increasing adult primary care referrals, participation rates and improving health outcomes for persons with diabetes.

DESIGN: Integrative review.

METHODS: A systematic literature search of PubMed/MEDLINE, Embase and CINAHL was performed by applying the PRISMA guidelines. Following Whittemore and Knafl's method, 11 papers were included for review.

RESULTS: Integration of diabetes self-management education and support in primary care clinics and a multifaceted approach resulted in improved referral and participation rates, ameliorated glycated haemoglobin A1C and boosted patient, provider and staff satisfaction.

CONCLUSION: Patient-centred multifaceted interventions can boost current diabetes self-management education referrals and participation rates and enhance health outcomes for persons with diabetes. Nurses in their role as primary care providers, diabetes educators and clinic staff are well-positioned to undertake this intervention. Further investigation is needed to explore the impact of these interventions among individuals with type 1 diabetes, gestational diabetes and those living across various global regions.

IMPLICATIONS FOR PATIENT CARE: Along with other healthcare providers, nurses are qualified to advocate for, and lead programmes that increase referrals for persons with diabetes to improve health outcomes. Additionally, as primary care providers, nurse practitioners are well placed to positively impact the outcomes of individuals with diabetes by referring them to diabetes self-management education. Nurses, as diabetes educators, are well positioned to implement diabetes self-management education which can improve patient outcomes.

IMPACT: Improved referral of persons with diabetes to diabetes self-management education and increased participation have the propensity to contribute to the achievement of positive health outcomes for individuals living with Type 2 Diabetes.

PATIENT OR PUBLIC CONTRIBUTION: There is no patient or public contribution for this review.

RATIONALE: The chronic kidney disease (CKD) burden in the US varies by race/ethnicity. It was unclear whether nativity status influences these disparities. This study compared CKD prevalence by nativity status, race and ethnicity, and length of US residence.

STUDY DESIGN: Cross-sectional analysis.

SETTING/PARTICIPANTS: We drew a weighted sample of 13,636 adults representing 155,147,141 Hispanic, White, Black, and Asian adults from the pooled 2011-March 2020 National Health and Nutrition Examination Survey (NHANES), which included 155,147,141 US- and foreign-born adults.

EXPOSURES: Nativity (US- or foreign-born), race/ethnicity, and length of US residence.

OUTCOME: We defined CKD as eGFR <60mL/min/1.73m2 or a urinary albumin-to-creatinine ratio ≥30 mg/g.

ANALYTICAL APPROACH: Survey-weighted multivariable Poisson models estimated associations among nativity status, race, and ethnicity, length of US residence, and CKD, adjusting for covariates.

RESULTS: The prevalence of CKD among US-born adults was 14.0%, vs. 11.5% of foreign-born. Foreign-born adults were less likely to have CKD (prevalence rate ratio [PRR]: 0.75, 95% CI 0.60-0.93) than US-born adults, adjusting for age, sex, and socioeconomic factors. Black adults were more likely to have CKD than White adults (PRR: 1.44, 95% CI 1.23-1.68); this difference was greater among US-born adults (PRR: 1.48, 95% CI 1.25-1.76). Among Hispanic and Asian adults, age- and sex-adjusted prevalence of CKD increased with longer length of residence in the US.

CONCLUSIONS: There are clear CKD disparities related to nativity location and length of US residence, and these vary by race/ethnicity. Interventions addressing the unique challenges faced by populations most at risk for CKD, such as access to healthcare barriers and socioeconomic disparities, may help mitigate the burden of CKD and promote health equity.

BACKGROUND AND OBJECTIVES: Care partners are critical for making treatment decisions in persons living with dementia. However, identifying them is challenging, hindering the broader use of interventions, such as those using digital technologies. We aimed to (i) assess the feasibility of identifying and contacting care partners using electronic health record (EHR) systems, and (ii) elicit their perspectives on electronic interventions for deprescribing.

RESEARCH DESIGN AND METHODS: We systematically identified care partners of persons living with dementia ≥65 years of age via structured EHR data in a large healthcare system. Eligible care partners were contacted by patient portal (if they were an established proxy), mail, and phone to complete a survey.

RESULTS: Of 4,138 eligible persons living with dementia identified, 1,084 (26%) had a care partner name recorded in the EHR. Out of 259 (6%) with sufficient care partner contact information for outreach, 74 (29%) completed the survey. Among care partners, 62 (84%) reported being confident in managing dementia medications, 59 (80%) were willing to stop ≥1 medications, and 43 (58%) were very/extremely interested in using digital tools for decision-making.

DISCUSSION AND IMPLICATIONS: Despite the low percentage of care partners with sufficient contact information, reach rates were high for contacted care partners, suggesting feasibility for pragmatic system-level interventions. Most care partners showed great interest in using digital health tools for decision-making and managing medications. Therefore, electronic tools could help with identifying care partners and engaging them. However, scaling up interventions requires better care partner documentation or extracting information from free text.