Publications

We investigated the associations of pregnancy levels of heavy metals and trace elements with the risk of gestational diabetes mellitus (GDM). Participating pregnant women were from the Boston Birth Cohort. We measured levels of mercury, lead, cadmium, selenium, and manganese in maternal red blood cells collected after delivery. We verified the GDM diagnosis using ICD codes, medication history, and plasma glucose profile abstracted from medical records. We used modified Poisson regression and Bayesian kernel machine regression models to examine associations of metals and elements, individually and as a mixture, with GDM. We stratified the analyses by race and ethnicity. Among 1256 pregnant women, 58% were non-Hispanic Black and 22% were Hispanic. Overall, each doubling of mercury and manganese levels was associated with 1.14 (95% CI: 1.01-1.28) and 0.65 (95% CI: 0.50-0.84) times the risk of GDM, respectively. In the race- and ethnicity-stratified analyses, the mercury-GDM association was stronger among Black women, and higher selenium levels were associated with higher GDM risk only among Hispanic women (Pinteraction = 0.01). In conclusion, women with higher mercury or lower manganese levels during pregnancy were more likely to develop GDM. An increased GDM risk associated with higher selenium levels was observed only in Hispanic women.

INTRODUCTION: The present study examined the dimensional structure of the neuropsychological test batteries from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) versions 2.0 and 3.0 and measurement equivalence across UDS versions and race/ethnicity groups.

METHODS: There were 49,895 participants included in the present study. The best-fitting model was developed and tested in separate samples. Multiple group confirmatory factor analysis (CFA) evaluated measurement equivalence across UDS versions and race/ethnicity groups.

RESULTS: Results identified a best-fitting four-factor model with residual structure. Multiple group CFA supported partial scalar invariance by UDS version and race/ethnicity group. Regarding race/ethnicity groups, the Language and Attention domains had more non-invariant intercepts, which most affected the White group.

DISCUSSION: A four-factor model effectively summarizes the UDS neuropsychological test batteries across UDS versions and race/ethnicity groups. Crucial differences in measurement parameters must be accounted for in studies using these neuropsychological tests as outcomes.

HIGHLIGHTS: A four-factor model summarizes cognition across Uniform Data Set (UDS) versions and race/ethnicity groups. Measurement invariance exists across race/ethnicity groups. Model fit differs between cognitively impaired and unimpaired samples. Accounting for differences in measurement parameters across groups is essential. Tailored normative data are crucial for certain UDS tests, including category fluency.

STUDY OBJECTIVES: Circulating non-esterified fatty acids (NEFAs) have been associated with impaired glucose metabolism but their modifiable determinants remain uncertain. We sought to determine the association between objectively-measured sleep disordered breathing (SDB), which is also associated with dysglycemia, and NEFA levels among community-dwelling older adults.

METHODS: We analyzed 787 older adults who had total fasting and post-load NEFAs measured in 1996-1997 in the Cardiovascular Health Study and underwent polysomnography between 1995 and 1997 in the Sleep Heart Health Study. We used multivariable linear regression to model NEFAs as a function of four SDB parameters: apnea-hypopnea index, arousal index, hypoxemia, and slow-wave sleep, and tested formal mediating effects by insulin sensitivity estimated with the Gutt index.

RESULTS: The mean age of study participants was 77.5 ± 4.3 years. The proportion of females and non-Hispanic whites was 58.7 per cent and 84.2 per cent, respectively. We did not find statistically significant associations between any of the SDB parameters and fasting NEFAs, but higher amounts of slow-wave sleep were significantly associated in a linear fashion with lower total post-load NEFAs in unadjusted and adjusted models [adjusted: β = -0.004, SE = 0.001, p = .02]. In mediation analyzes, 10 per cent of the slow wave sleep-NEFA association was mediated by Gutt-estimated insulin sensitivity (p = .45 for the indirect effect).

CONCLUSIONS: Among the SDB measures studied, only higher levels of objectively measured slow-wave sleep were significantly associated with lower levels of post-load NEFAs, although the underlying mechanism is uncertain. Establishing a causal link would make SDB interventions a promising target for NEFA regulation.

BACKGROUND: Advanced glycation end-products result from chemical modification of proteins under conditions of hyperglycemia or oxidative stress common with advancing age. Advanced glycation end-product (AGE) formation alters vascular and cardiac structure and function, yet the prospective associations of circulating AGEs with heart failure (HF) and atrial fibrillation (AF) have not been studied.

METHODS: We evaluated the associations of serum Nε-carboxymethyl-lysine (CML), a major AGE in tissue proteins, and incident HF and AF in the CHS (Cardiovascular Health Study), a population-based cohort of older adults. HF subtypes were examined secondarily, as were prevalent echocardiographic phenotypes. CML was measured by immunoassay.

RESULTS: Among 2685 eligible participants (age 77±5; 63% women; 17% with diabetes), 832 HF and 1016 AF events occurred over a median follow-up of 9 years. After adjustment for potential confounders, serum CML was associated with a higher risk of incident HF and AF (hazard ratio per SD, 1.10 and 1.09 [95% CI, 1.02-1.17 and 1.02-1.16], respectively). The association with AF was attenuated and nonsignificant after adjusting for estimated glomerular filtration rate and urine albumin-creatinine ratio. The CML-HF relation was similarly attenuated after adjusting for time-updated myocardial infarction. Both associations were nonsignificant after adjusting for natriuretic peptides or excluding those with elevated levels at baseline. Secondary analyses of incident HF subtypes or baseline cardiac mechanics showed no significant associations.

CONCLUSIONS: In older adults, serum CML was prospectively associated with higher risk of HF and AF independent of potential confounders, with evidence of attenuation by certain putative mediators. AGEs and AGE-countering therapies merit additional evaluation in this high-risk population.

BACKGROUND: Heart rate variability (HRV) is a measure of autonomic function that has been associated with worse lung function and worse respiratory health. Using data from a community-based cohort, we aimed to test if HRV is associated with lung function and self-reported chronic lung disease (CLD).

METHODS: The Atherosclerosis Risk in Communities (ARIC) study is a community-based cohort that collected HRV measurements from 14-day continuous ECG patches and self-reported CLD at visit 6 (2016-2017). Pulmonary function testing was performed a prior visit (visit 5; 2011-2013). We used multivariate linear regression to test cross-sectional associations between HRV and lung function, and logistic regression to test associations between HRV and self-reported CLD. All analyses were adjusted for important confounders including smoking, demographics, and medications.

RESULTS: HRV and lung function measurements were available for 1456 participants. Included participants had a mean ± standard deviation (SD) age of 78.7 ± 4.5 years, 59.6 % were female, and 30.1 % were African American. Higher HRV reflective of overall HRV (standard deviation of normal RR intervals) and sympathetic activity [low frequency (LF) to high frequency (HF) ratio (LF/HF)] were associated with better lung function and lower odds of self-reported CLD. Higher HRV reflective of parasympathetic function (HF) was associated with worse lung function and higher odds of self-reported CLD.

CONCLUSIONS: We confirmed associations between HRV and respiratory health outcomes. Our data from a community-based cohort demonstrate the importance of utilizing several HRV measurements to capture multiple components of autonomic function when analyzing respiratory health outcomes.

Widespread misuse of prescription opioids has resulted in large numbers of opioid-related overdose deaths. It is critical to have a better understanding of the temporal patterns of opioid prescribing practices and associated clinical scenarios. We examined opioid prescription trends over 7 years in a large medical system using electronic health record data. Between 2017 and 2023, we identified 1,019,706 patients from 13 hospitals within a large health system in the northeastern United States, who had at least 1 opioid prescription. In total, there were 3,877,281 associated encounters with 18,225 prescribers. We examined the overall monthly opioid prescription rates and observed an average decrease during the 84 months of study period and discovered 4 distinct stages. A decrease was seen between January 2017 and January 2020 (monthly rate change: -0.70%, 95% CI: -0.89% to -0.41%), followed by a sharp decrease and a fast rebound between February 2020, April 2020, and July 2020 (monthly rate change: -10.60%, 95% CI: -14.73% to -2.52%; 13.06%, 95% CI: 3.42%-18.47%), then back to a gradual decrease from August 2020 to December 2023 (monthly rate change: -0.46%, 95% CI: -0.67% to -0.29%). When prescriptions were further classified by prescribing setting, patient demographics, and patient visit encounter types, we observed variations among these subgroups. We also identified significant associations between patient characteristics and provider specialty with high morphine milligram equivalent dose prescriptions. These results highlight the complexity of opioid prescription practice trends indicating that all these issues need to be considered in developing prescription guidance.

PURPOSE: After a cancer diagnosis, uncertainty is common. IN FOCUS is a pilot randomized controlled trial that evaluated the feasibility and acceptability of a virtual mind-body group resiliency intervention on fear of cancer recurrence (FCR). The current study examines secondary outcomes of this trial, specifically exploring changes in related mental health constructs, which will contribute to our understanding of symptom relief as well as diagnostic overlap and discrepancies.

METHODS: A single-blinded, 2-arm, randomized controlled trial was conducted from July 2021 to March 2022 comparing IN FOCUS (8 weekly, 90-min, synchronous virtual group classes teaching cognitive behavioral techniques, relaxation training, meditation, adaptive health behaviors, and positive psychology skills) to usual care (synchronous virtual community group support referral) among cancer survivors with non-metastatic disease and clinically elevated FCR (FCR Inventory severity ≥ 16). Secondary outcomes assessed included anxiety (PHQ-4), depression (PHQ-4), worry (Penn State Worry Questionnaire), health anxiety (Short Health Anxiety Inventory), intolerance of uncertainty (Intolerance of Uncertainty Scale), and cancer-related uncertainty (Mishel Uncertainty in Illness Scale-Survivor version). Intent-to-treat analyses with separate general linear mixed models were used to identify group-by-time effects (Cohen's d; 0.5 a medium effect, 0.8 a large effect) from baseline through 2 months and 5 months.

RESULTS: Sixty-four survivors enrolled (25-73 years old, M = 7 years since diagnosis, 83% female). By 5 months, IN FOCUS produced large effect size reductions in anxiety (d = - 0.83), medium effect size reductions in depression (d = - 0.45), health anxiety (d = - 0.54), and prospective intolerance of uncertainty (d = - 0.54), and small effect size reductions in inhibitory intolerance of uncertainty (d = - 0.39) and worry (d = - 0.38). Notably, cancer-related uncertainty did not change in either study arm (d = - 0.14).

CONCLUSIONS: Although in the parent trial IN FOCUS did not have a sustained effect on FCR, secondary analyses showed that IN FOCUS produced improvements in anxiety, depression, worry, and health anxiety 3 months post-treatment.

GOV ID: NCT04876599, Mind-body Resiliency Intervention for Fear of Cancer Recurrence.

TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04876599 IMPLICATIONS FOR CANCER SURVIVORS: While cancer survivors' uncertainties remained steady over time, their capacity to tolerate uncertainty seemed to improve after engaging in a novel virtual mind-body intervention.

Elevated blood pressure is one of the most important risk factors for cardiovascular disease (CVD). Despite blood pressure being historically measured in the supine position prior to the 20th century, current clinical guidelines are primarily based on seated measurements. Emerging evidence suggests that hypertension in the supine position may be equally or more strongly associated with cardiovascular risk and mortality than seated hypertension. However, there is no standardized protocol or diagnostic criteria to evaluate supine hypertension (SH) in the general population. Moreover, if SH is detected, clinical recommendations for its treatment remain unclear. In this review, we synthesized the literature on SH by conducting a MEDLINE search of publications from 2024 to 2025 and offer recommendations for the assessment, interpretation, and treatment of SH in the outpatient setting. In addition, we identify gaps in evidence and opportunities for future research to advance our understanding of this underappreciated and yet potent risk factor for cardiovascular disease.