Publications

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.

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.

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.

OBJECTIVE: In October 2023, CMS approved transfemoral carotid artery stenting (tfCAS) for standard-risk patients. Thus, we sought to compare outcomes among tfCAS, TCAR, and CEA in standard-risk and high-risk patients.

METHODS: All carotid revascularization procedures in the VQI following the CMS decision (October 2023-March 2025) were analyzed. Patients were classified as standard or high-risk per CMS criteria and stratified by symptom status. The primary outcome was perioperative stroke/death. Inverse probability of treatment weighting (IPTW) was performed to mitigate selection bias in high-risk patients and included demographics, comorbidities, physician volume, and operative characteristics. IPTW was also applied to symptomatic standard-risk patients to account for the large proportion of tfCAS cases performed outside of SVS guidelines.

RESULTS: Overall, 57,843 patients underwent revascularization (9,123 tfCAS, 21,814 TCAR, and 26,906 CEA). Before weighting, tfCAS patients were more often symptomatic (standard-risk: tfCAS: 45% vs. TCAR: 25% vs. CEA: 31%, P<.01; high-risk: 35% vs. 24% vs. 28%, P<.01), more frequently had a modified Rankin score of 4 or 5 (standard-risk: 7.7% vs. 2.4% vs. 1.7%; high-risk: 6.6% vs. 2.6% vs. 2.4%, P<.01) and more frequently underwent urgent or emergent surgery (standard-risk: 33% vs. 11% vs. 16%, high-risk: 28% vs. 12% vs. 17%, P<.01). Standard-risk asymptomatic patients undergoing tfCAS had the highest rates of perioperative stroke/death (1.6% vs. 1.2% vs. 1.0%, P=.01), as did symptomatic patients (2.9% vs. 1.9% vs. 1.7%, P=.01). tfCAS was associated with higher overall odds of stroke/death compared to CEA (OR 1.89 [1.43, 2.48] P<.01) and TCAR (OR 1.59 [1.15,2.18] P<.01). Compared to CEA tfCAS was associated with higher odds of stroke/death in both asymptomatic (OR 1.71 [1.12, 2.55] P=.01) and symptomatic patients (aOR 1.78 [1.21, 2.56] P<.01). After weighting, there were no significant differences in perioperative stroke/death overall for either tfCAS or TCAR compared to CEA in standard-risk symptomatic patients. In high-risk patients, TCAR was associated with lower odds of perioperative stroke/death overall compared to CEA (1.5% vs. 2.1%, aOR 0.75[0.59, 0.94] P=.01) while tfCAS had higher odds of stroke/death compared to TCAR. (1.5% vs. 2.4%, aOR 1.57 [1.25, 1.98] P<.01).

CONCLUSION: In this retrospective analysis, there were higher odds of perioperative stroke/death when comparing tfCAS to CEA overall and among asymptomatic and symptomatic standard-risk patients, as well as overall compared to TCAR. In high-risk patients, TCAR performed better with lower odds of stroke/death compared to both CEA and tfCAS.

BACKGROUND: Trial recruitment is a major determinant of study success, and participants' non-arrival at study visits represents a significant barrier to study completion. Little is known about the participant and study process characteristics associated with visit non-arrival.

OBJECTIVE: To investigate factors associated with non-arrival at initial in-person screening visits in two ongoing randomized controlled trials.

METHODS: The Groceries for Black Residents of Boston to Stop Hypertension trials (GoFresh and GoFreshRx) studied whether home-delivered, DASH-patterned groceries can reduce blood pressure among Black adults living in urban food priority areas. In this analysis, we examined sociodemographic and study-related factors associated with participant non-arrival at their initial study visit (defined as rescheduling or not showing up at all). Associations were determined using logistic regression with adjustment for age, estimated gender, and hypertension treatment status.

RESULTS: Among 2224 participants (mean age = 44.0 years, 72.5 % women), the non-arrival rate at screening visit 1 was 29.5 %. Older participants were more likely to arrive, while those with larger families and a longer duration between initial contact and visit were less likely to arrive. Participants' method of contacting the study, visit time, and season of visit were not associated with visit non-arrival.

CONCLUSION: In this large trial recruitment drive, older age, larger family size, and a longer time between initial contact and scheduled visit were associated with non-arrival at initial study visits. These factors represent potential targets for future interventions that either accommodate patient factors or intervene upon study process barriers to achieve timely recruitment goals.

OBJECTIVE: To examine the prospective associations of metal mixtures during pregnancy with midlife adiposity and explore metal-folate interactions.

METHODS: In 500 participants from Project Viva, we measured six non-essential metals (arsenic, barium, cadmium, cesium, mercury, and lead) and five essential metals (copper, magnesium, manganese, selenium, and zinc) in red blood cells and folate in plasma collected during early pregnancy (mean gestational age: 10.0 weeks; mean age: 32.9 years). We assessed midlife (mean age: 51.2 years) adiposity using BMI and dual-energy X-ray absorptiometry (DXA) measures. We used multivariable-adjusted linear and multinomial logistic regression models to analyze individual exposures and Bayesian kernel machine regression to examine exposure mixtures.

RESULTS: Higher arsenic, cesium, and mercury levels were associated with lower midlife DXA percentage fat, total fat mass index, and/or trunk fat mass index, even after adjustments for diet in pregnancy. We observed an antagonistic interaction between folate and arsenic: arsenic was associated with higher obesity risk at lower folate levels but lower obesity risk at higher folate levels. The essential metal mixture tended to be associated with lower midlife BMI and obesity risk.

CONCLUSIONS: Higher pregnancy levels of arsenic, cesium, mercury, and the mixture of essential metals were associated with lower midlife adiposity.

Orthostatic hypotension (OH) is a common inpatient condition associated with falls, syncope, and mortality. However, standardized approaches for inpatient management of OH are lacking and may vary across clinical specialties. In this retrospective observational cohort study, we reviewed the electronic medical records of patients admitted to Beth Israel Deaconess Medical Center between April 1, 2015 and June 1, 2021 with a diagnosis of OH or medication-related hypotension. Variables of interest included admitting service, presenting symptoms, suspected etiology, and management. Among the 400 inpatients with OH, one-third had OH documented on admission. Dizziness and lightheadedness were the most common symptoms; medical patients experienced dizziness, falls, and other symptoms more frequently than surgical patients. Volume depletion and medications were the leading suspected causes of OH. Surgical patients were less likely to have medication-related OH and were more likely to lack an identified etiology. Cardiovascular disease was more frequently implicated in cardiology patients. Volume depletion, neurodegenerative disease, and other conditions were more often suspected among medical patients. Management commonly involved volume resuscitation and medication adjustment, though medication changes were less frequent in surgical patients. Nonpharmacologic interventions were more common among medical patients. By discharge, OH had resolved in only one-third of patients. In summary, inpatient OH was most often identified after admission, attributed to hypovolemia, treated with fluids, and unresolved at discharge, with differences in symptoms, etiology, and management between specialties. Prospective studies are needed to formalize diagnostic and treatment strategies for OH in the hospital setting.

BACKGROUND: Chronic hepatitis B is a leading cause of cirrhosis and hepatocellular carcinoma globally. In 2022, only 13% of the 254 million people with chronic hepatitis B were diagnosed and 3% were treated, highlighting a major gap in care provision. We aimed to comprehensively review service delivery models and their outcomes across the hepatitis B care cascade.

METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, and Scopus for observational and interventional studies of chronic hepatitis B service delivery models that reported care outcomes, published between May 1, 2013, and July 15, 2024, with no language restrictions. Care cascade outcomes were the proportion of people diagnosed with hepatitis B who were assessed for treatment eligibility; the proportion of eligible people who started antiviral therapy; the proportion retained in care; and the proportion on therapy who had HBV DNA viral suppression. We evaluated pooled outcomes across hospital-based specialist care; co-managed care between primary and specialist care; community screening with linkage to specialist care; community screening with passive linkage to care; community test and treat clinics; primary care; and integrated care with antenatal, non-communicable disease, HIV, prison health, and substance misuse services and clinics, using a generalised linear mixed model with logit link and study random effects. For within-study comparisons of different models, we used inverse variance weighting to estimate the pooled risk ratio (RR). Heterogeneity was assessed with I2. This study is registered with PROSPERO (CRD42023410009).

FINDINGS: Of 4883 studies identified in the search, we included 106 studies comprising 110 cohorts from 50 countries in our meta-analysis. 45 (41%) of 110 cohorts were from low-income and middle-income countries and 65 (59%) were from high-income countries. 76 (72%) of 106 studies were observational, 23 (22%) were non-randomised interventional studies, and seven (7%) were randomised trials. Treatment eligibility assessment occurred in 73·9% (95% CI 65·8-80·6; I2=98·5%) of patients for hospital-based specialist care (20 cohorts), 63·1% (53·0-72·2; I2=99·9%) for co-managed care (23 cohorts), 50·4% (25·9-74·8; I2=99·7%) for primary care (four cohorts), 82·3% (58·7-93·8; I2=96·1%) for community screening with linkage to specialist care (ten cohorts), 33·2% (23·1-45·1; I2=98·6%) for community screening with passive linkage to care (three cohorts), 56·9% (40·2-72·1; I2=98·8%) for diagnosis in antenatal clinics and post-delivery linkage to specialist care (five cohorts), 75·0% (37·7-93·7; I2=0·0%) for integrated care with harm reduction services (two cohorts), and 85·4% (78·0-90·6; I2=0·0%) for integrated care with prison health services (two cohorts). Initiation of antiviral therapy when eligible was 78·1% (95% CI 68·1-85·7; I2=99·2%) in hospital-based specialist care (25 cohorts), 67·2% (55·5-77·1; I2=95·8%) in co-managed care (11 cohorts), 49·3% (32·4-66·4; I2=87·9%) in primary care (four cohorts), 97·7% (80·6-99·8; I2=39·2%) in community screening with linkage to specialist care (seven cohorts), and 49·4% (22·1-77·0; I2=84·0%) for integrated care with non-communicable disease clinics (two cohorts). Higher rates of treatment eligibility assessment (RR 2·07 [95% CI 1·65-2·59], p<0·0001; I2=97·1%; three cohorts) and initiation of antiviral therapy (1·45 [1·13-1·85], p=0·0031; I2=0·0%; three cohorts) were observed in hospital-based specialist versus primary care models. Retention in care, assessed between 12 and 48 months, was 87·7% (95% CI 79·9-92·8, I2 =96·7%) in patients on antiviral therapy in hospital-based specialist care (13 cohorts) and 47·2% (95% CI 22·2-73·6, I2=99·5%) in patients not receiving antiviral therapy (two cohorts). Overall, retention was higher in patients with versus without antiviral therapy (RR 1·72 [95% CI 1·16-2·54]; p=0·019). HBV DNA viral suppression for patients on antiviral therapy in specialist care (nine cohorts) was 73·1% (95% CI 64·3-80·4; I2=92·0%) after a median of 12 months on antiviral therapy (IQR 12-33).

INTERPRETATION: Considerable attrition was seen across the chronic hepatitis B care cascade, with low rates of retention especially in patients not on antiviral therapy. Assessment for treatment eligibility and initiation of antiviral therapy were lower in primary versus hospital-based specialist care models. Chronic hepatitis B services need to adopt strategies to optimise linkage to care after diagnosis, initiation of antiviral therapy if eligible, adherence to antiviral therapy and retention in care, as promoted in 2024 WHO hepatitis B guidelines. Further research is also needed to explore simplified care models integrated with existing services to promote access.

FUNDING: World Health Organization.