Publications

Albuminuria reflects systemic endothelial dysfunction, but its relationships with subclinical brain abnormalities have not been comprehensively catalogued. The Cardiovascular Health Study recruited older adults from four US communities, beginning in 1989-1990. Systematic measurements of albuminuria were performed in 1996-1997; two brain MRIs, in 1992-1994 and 1997-1999; and serum neurofilament light chain (NfL) measurements from 1996-1997 stored samples. We examined the associations of albuminuria with longitudinal progression of white matter hyperintensities (WMH) and ventricular size, incident infarcts, and cross-sectional quantitative brain volumes and circulating biomarkers of neuronal injury (n = 834-1950). Albuminuria was positively associated with ventricular grade worsening (odds ratio per doubling 1.10, 95% confidence interval (CI) 1.01-1.19) and with circulating NfL levels (2% higher per doubling, 95% CI 1-4%), even after adjustment for vascular risk factors. Albuminuria was also associated with worsening of WMH, incident infarcts, and quantitative WMH and hippocampal volumes, but these latter associations appeared to reflect burden of cardiovascular risk factors. Albuminuria is independently associated with worsening ventricular size and circulating NfL, suggesting a specific role of microvascular dysfunction in brain atrophy. It also reflects cardiovascular risk factor burden on markers of vascular brain injury. These results highlight the diverse associations of albuminuria with common brain abnormalities of aging.

UNLABELLED: In 2023 the Centers for Medicare and Medicaid Services (CMS) expanded coverage for transfemoral carotid artery stenting (tfCAS) to include standard-risk patients. Given this shift, we sought to identify predictors of postoperative stroke in patients undergoing tfCAS.

METHODS: We analyzed VQI data from 2011-2024, identifying tfCAS patients treated for atherosclerosis or restenosis. We excluded patients with interventions outside the internal carotid artery (ICA) or bifurcation and procedures with concurrent intracranial treatment. We then stratified patients based on in-hospital postoperative stroke status. Baseline characteristics and outcomes were compared using X2 tests, and predictors of stroke risk were compared using logistic regression. Ten-fold cross-validation was used to identify predictors of stroke, and a point system was developed to predict the risk of in-hospital postoperative stroke.

RESULTS: In our cohort of 35,346 tfCAS cases, 693 (2%) patients had an in-hospital post-procedure stroke. Patients who had a post-procedure stroke were older, more likely to be female, non-white, and had a higher overall comorbidity burden. After 10-fold cross-validation using the original logistic regression model, the factors most strongly associated with increased odds of stroke included uncontrolled hypertension (23% vs. 14%, adjusted odds ratio (aOR) 2.66 [95% confidence interval (CI) 1.94-3.71] p<.001), emergent surgery (41% vs. 32%, aOR 2.39,[1.74-3.27] p<.001), severe distal tortuosity (13% vs. 8%, aOR 1.62 [1.25-2.27] p<.001), age greater than 75 (41% vs. 32%, aOR1.53[1.23-1.92] p<.001), preoperative stroke (44% vs. 29%, aOR 1.57[1.30-1.90] p<.001), prior CEA (14% vs. 12%, aOR 1.44 [1.14-1.81] p=.002 ), Type III arch (7.1% vs 5.5%, aOR 1.45 [1.02-2.03] p=.03) and circumferential or protruding calcification (3.3% vs 1.7%, aOR 1.43 [1.04-1.93] p=.02). Dual antiplatelet therapy (DAPT) and having a high-volume physician or center were associated with lower odds of stroke. Based on variable importance, a simplified point system was developed to predict postoperative stroke (ROC AUC = 0.68).

CONCLUSION: The identified mediators of stroke risk after tfCAS offer the opportunity to improve patient selection. These data highlight the importance of managing modifiable factors preoperatively, such as hypertension and antiplatelet therapy. The timing of surgery also emerged as a strong predictor of stroke, suggesting the need for careful consideration of the need for emergent or urgent surgery. Anatomic considerations such as vessel tortuosity, arch type and calcification should also prompt consideration for an alternate revascularization strategy.

BACKGROUND: In Haiphong, Vietnam, most hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). As part of multiple respondent-driven sampling (RDS) surveys among PWID in Haiphong, an intervention (DRIVE-C) provided HCV testing and treatment in 2019. Centres providing opiate agonist treatment (OAT) or antiretroviral therapy (ART) also provided HCV testing and linkage-to-treatment in 2021/22. We modelled the impact and cost-effectiveness of HCV testing and treatment for PWID in Haiphong.

METHODS: An HCV transmission model among PWID and former injectors was calibrated in a Bayesian framework using data from Haiphong. A status quo (SQ) scenario modelled past interventions, with no future HCV treatment. A future intervention scenario modelled the impact of providing HCV testing and linkage-to-treatment in OAT and ART centres, and annual RDS survey interventions over 2025-2030, each testing 1400 PWID. We estimated the incremental cost-effectiveness ratio (ICER) per disability adjusted life-year (DALY) averted for the future scenario compared to SQ over 2025-2054 (3 % annual discount rate).

RESULTS: For the SQ scenario, HCV incidence decreased from 8.1 (95 % credibility interval 5.1-13.6) per 100 person-years (/100pyrs) in 2015 to 5.3/100pyrs (3.0-9.6) in 2023 and increases to 6.2/100pyrs (3.5-10.7) in 2030. In the future intervention scenario, incidence decreases to 2.7/100pyrs (1.0-6.4) by 2030. The mean ICER is €884/DALY averted; cost-effective at a willingness-to-pay threshold of €2334 (57 % of Vietnam's 2023 GDP per capita).

CONCLUSIONS: Using RDS surveys and other care settings to scale-up HCV-testing and treatment are cost-effective strategies to reduce HCV incidence among PWID in Vietnam.

BACKGROUND: Treatment burden refers to the patient-perceived effort of managing health and health care, which impacts quality of life and engagement in care. International studies of treatment burden have found high rates of treatment burden among adults with chronic conditions. However, the scope of treatment burden among US older adults is unknown. We described the prevalence of and characteristics associated with treatment burden among US adults age ≥ 50 years.

METHODS: We performed a cross-sectional study of 1795 adult respondents to the 2022 Health and Retirement Study (HRS) Treatment Burden Questionnaire (TBQ), a random sub-sample from a nationally-representative panel study of community-dwelling US adults age ≥ 50 years. The primary outcome was total treatment burden score (15 items each scored 0-10, total 0-150; threshold ≥ 59 for high burden). We used multivariable linear regression to examine the association between log-transformed total treatment burden score and sociodemographic, health, and functional status characteristics.

RESULTS: The mean age of 1795 respondents was 68.5 (SD 8.5) years, 56% were female, and the median TBQ score was 12 (IQR 5-25). Overall, 87% (n = 1550) reported treatment burden (TBQ score ≥ 1); 5% reported high burden. The most common sources of treatment burden were reminders of health problems (61%) and administrative (53%) and financial burdens (46%). Adults age ≥ 65 years were both less likely to report treatment burden and reported lower burden than adults age 50-64 years. Factors associated with greater burden included a higher number of chronic conditions, vision or hearing impairment, ADL/IADL difficulty, and mobility difficulty.

CONCLUSIONS: Most US adults age ≥ 50 years report treatment burden, though there is wide variation in the degree of burden reported. Reducing treatment burden within the US may require reducing administrative and financial burdens of care and addressing factors that impair patient capacity to manage health and health care.

The vast majority of placebos are administered with concealment or deception. Most clinicians and researchers believe that either deception or concealment is necessary to achieve a placebo response; however, recent studies with open-label placebo (OLP), conditioning, and conditioning + OLP (COLP) have shown that placebos can be effective even when patients know they are receiving a placebo. To date, no studies have examined COLP in a pediatric surgical population, which is vulnerable to developing opioid dependence. COLP may assist in lowering opioid doses administered and quicker tapering off opioids. This study investigates the effectiveness of COLP on postoperative treatment of patients ages 10 through 17 undergoing posterior fusion for adolescent idiopathic scoliosis (AIS). It is a randomized controlled trial of 64 AIS patients assigned to one of the two arms: COLP + treatment as usual (TAU) and TAU control. Randomization and baseline assessments occur at the preoperative visit. Opioid consumption is recorded weekly after hospitalization until the first in-person postoperative visit at 6 weeks. The primary outcome measure is postoperative opioid consumption, both amount and duration. Secondary outcomes include pain, functional ability, and mental health scores.

IMPORTANCE: Conversations between seriously ill patients and clinicians about values and goals (ie, serious illness conversations [SICs]) can lead to patient-centered care toward the end of life. However, many patients have not had SICs when arriving in the emergency department (ED) and are at risk of receiving undesired care.

OBJECTIVE: To determine the effect of an ED-based, multimodal SIC intervention (known as ED GOAL) compared with usual care on patient-reported engagement in advance care planning (ACP) and clinician-documented SICs after leaving the ED.

DESIGN, SETTING, AND PARTICIPANTS: This 2-armed, 1:1, parallel-design randomized clinical trial was conducted at 3 participating EDs (2 academic medical centers and 1 community hospital) in Boston, Massachusetts, within a single health system between March 1, 2022, and July 1, 2024, with a follow-up duration of 6 months. Eligible participants were English-speaking adults 50 years or older with serious illnesses, including mild cognitive impairment or mild dementia, along with their caregivers. For patients with moderate to severe dementia, caregivers were the primary participants in the study. Patients with documented goals for medical care or physician orders in the last 3 months in medical records or deemed clinically inappropriate by the treating ED team were excluded.

INTERVENTION: SIC-trained research nurses conducted (1) a motivational interview about SICs, (2) a structured SIC, and (3) communication priming for the patients and their primary clinicians to reinitiate SICs on a tablet computer in the ED or within 1 week after leaving the ED.

MAIN OUTCOMES AND MEASURES: The primary outcome was a validated survey of patient-reported engagement in ACP at 1 month, with total possible scores ranging from 1 to 5, with higher scores indicating more engagement. Secondary outcomes included clinician documentation of end-of-life values and preferences in the medical record and completed advance directives.

RESULTS: A total of 141 patients (mean [SD] age, 66.7 [9.2] years; 73 [51.8%] female), predominantly diagnosed with metastatic cancer (85 [60.3%]), were enrolled and randomized to the intervention (n = 70) or usual care (n = 71). At 1 month, no difference was observed in patient-reported engagement in ACP (mean [SD] score, 3.32 [1.28] for control vs 3.37 [1.07] for intervention; maximum possible score, 5.00; P = .58), yet 12 patients in the intervention group (17.1%) discussed care preferences with their physicians compared with 5 (7.0%) control group patients (P = .07). Medical record documentation of end-of-life values and goals was significantly higher in the intervention group at 3 months (17 [24.3%] vs 7 [9.9%]; P = .03) and 6 months (22 [31.4%] vs 9 [12.7%]; P =  .008).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of seriously ill older adults in the ED, while a nurse-led SIC intervention did not significantly improve patient-reported engagement in ACP, it did increase clinician-documented SICs in the medical records. ED visits may serve as a critical access point to enhance SICs for seriously ill yet clinically stable older adults.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05209880.

This study examined changes in health-related quality of life (HRQOL) among people living with HIV in Vietnam over three years following antiretroviral therapy (ART) initiation. We analyzed data from a randomized trial of 639 ART-naïve patients in which HRQOL was measured using the SF-8 instrument. Mixed effects logistic regression was used to assess changes in HRQOL over time and identify associated factors. At baseline, 57.5% reported low HRQOL. HRQOL improved rapidly after ART initiation, with 89.0% reporting good HRQOL at 3 months and 96.4% at 36 months. Compared with men, women had slower improvement in HRQOL over time. Factors positively associated with HRQOL included higher BMI and alcohol use, while food insecurity, history of tuberculosis, advanced clinical stages, and TDF-based regimens were negatively associated. Older age was linked to poorer HRQOL outcomes. These findings highlight the effectiveness of ART in improving HRQOL while also revealing disparities in HRQOL improvements.

BACKGROUND: Prenatal per- and polyfluoroalkyl substance (PFAS) exposures may influence offspring blood pressure (BP), but long-term studies in diverse populations remain limited.

METHODS: Participants were from the Boston Birth Cohort. We measured PFAS in maternal plasma collected 24 to 72 hours after delivery and extracted children's BP from medical records. We calculated age-, sex-, and height-specific BP percentiles and defined elevated BP as systolic/diastolic BP ≥90th percentile (ages 3 to <13 years) or ≥120/80 mm Hg (ages 13 to <18 years). We used adjusted mixed-effects linear and modified Poisson models to examine associations of PFAS with BP percentiles and elevated BP. We used linear spline mixed-effects models to predict BP trajectories at ages 3 to 18 years by PFAS levels.

RESULTS: We included 13 404 BP measurements from 1094 children (median follow-up: 12 years [interquartile range, 9-15 years]; 61% Black and 22% Hispanic). Overall, higher perfluorodecanoic acid (PFDeA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnA) were associated with higher systolic BP percentile. The associations differed by child life stage, sex, race and ethnicity. For example, associations of PFDeA with systolic BP percentile were stronger in older (β3-5y=0.40; β6-12y=1.06; β13-18y=2.55), male (βmale=1.51; βfemale=0.52), and Black (βBlack=1.75; βHispanic=0.45) children. In male children, each doubling of perfluoroheptanesulfonic acid (PFHpS) was associated with a 9% higher risk of elevated BP at ages 6 to 12 years and a 17% higher risk at 13 to 18 years, with no increased risk at 3 to 5 years. PFHpS was associated with a dose-dependent divergence in BP trajectories beginning at age 13 years.

CONCLUSIONS: Prenatal exposures to certain PFAS were associated with offspring BP, with stronger associations in adolescents, male children, and Black children. Prenatal PFAS exposures may have intergenerational, long-term, and latent hypertensive effects.

BACKGROUND: We sought to determine the comparative effectiveness of two strategies for assigning care coordinators to people living with dementia (PLWD) and their caregivers.

METHODS: We conducted a pragmatic randomized clinical trial embedded in a Medicare accountable care organization (ACO) in New York, NY in 2022-2024. We included community-dwelling PLWD ≥ 65 years who were attributed to the ACO and had highly fragmented ambulatory care in the previous year (reversed Bice-Boxerman Index ≥ 0.86). The trial compared usual care (assigning care coordinators to PLWD after hospital discharge) to usual care plus proactive outreach, which assigned care coordinators to PLWD if they or their caregivers reported difficulty with care coordination on a telephone survey. Participants were followed for the combined outcome of emergency department (ED) visit or hospitalization.

RESULTS: Among the 385 PLWD in the trial, the mean age was 82.6 years (SD 6.9), and 56.4% were female. Overall, participants had had a mean of 14.9 ambulatory visits to 8.9 different providers the previous year. The acceptance rate of care management was higher in the control group (73.7%) than in the intervention group (38.0%). Care coordinators were ultimately assigned to 14 of 192 PLWD in the control group (7.3%) and 19 of 193 PLWD in the intervention group (9.8%). The intention-to-treat analysis (N = 385) found a trend toward fewer ED visits in the intervention group (0.14 ED visits per 100 person-days alive vs. 0.18 ED visits per 100 person-days alive, p = 0.07) but no difference in the combined outcome of ED visit or hospitalization (p = 0.71).

CONCLUSION: Although the particular intervention we tested was not more effective than usual care, this trial is novel in that it used highly fragmented care as an inclusion criterion and shows that more work is needed to address fragmented care among PLWD.