Faculty Bibliography

BACKGROUND/UNASSIGNED:Traditional Chinese medicine (TCM) has guided generations of practice on disease treatment and health maintenance. The TCM principles include the framework of body constitution. However, no study has assessed the body constitution in US population. METHODS/UNASSIGNED:This is an ancillary study of the Personalized Prevention of Colorectal Cancer Trial which conducted in US in 2012-2016. 191 white participants were evaluated for body constitution type using a self-administered Traditional Chinese Medicine Questionnaire (English version). The body constitution subtypes and cardiovascular disease (CVD) risk were assessed. RESULTS/UNASSIGNED:Fifty-seven (29.8%) were identified as balanced constitution (BC), while Blood-stasis (17.3%), Qi-deficient (13.6%), and inherited-special constitutions (10.5%) were the pre-eminent pathologic subtypes. Additional analyses investigated the relationship between CVD risk and body constitution subtypes. No major types of TCM body constitution were associated with the GCRS and other CVD biomarkers. CONCLUSIONS/UNASSIGNED:It is important to understand the underlying mechanisms contributing to these differences, which may not only help to understand the underlying mechanism for TCM, but also help to identify novel factors or mechanisms for CVD risk, prevention and treatment.

INTRODUCTION/BACKGROUND:Long-term trajectories of plasma biomarkers in relation to incident traumatic brain injury (TBI) and whether TBI modifies associations of biomarkers with dementia risk are unknown. METHODS:), phosphorylated-tau181 (pTau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) measured from plasma collected in 1993 to 1995, 2011 to 2013, and 2016 to 2019. Linear mixed-effects models estimated biomarker trajectories associated with TBI and Cox proportional hazards models determined if TBI modified associations of biomarkers with incident dementia through December 31, 2020. RESULTS:NfL with incident dementia (p = 0.024). DISCUSSION/CONCLUSIONS:TBI alters trajectories of plasma biomarkers of neurodegeneration for approximately a decade after the injury and modifies associations of NfL with dementia risk. HIGHLIGHTS/CONCLUSIONS:Our findings provide evidence that TBI fundamentally alters trajectories of plasma biomarkers of AD-related pathology, neuronal degeneration, and astrogliosis for approximately a decade after the injury. Further, our findings also suggest that an incident TBI event adds to and interacts with ongoing neurodegenerative processes to increase the risk of later life dementia. These results suggest that the pathologic processes underlying post-TBI dementia are heterogeneous, that individuals with preclinical changes in neurodegenerative biomarkers may be more susceptible to TBI (i.e., that associations are bidirectional), or a combination thereof.

BACKGROUND:A majority of the 8.9 million Americans with opioid misuse have mild or no symptoms of opioid use disorder (OUD), but they may be at elevated risk of developing more severe OUD, overdose, or other health consequences of opioid use. The "Subthreshold Opioid Use Disorder Prevention"(STOP) Trial is evaluating a collaborative care intervention for risky opioid use in primary care. Here, we describe baseline characteristics of participants to understand their needs and assess the generalizability of the sample. METHODS:Recruitment at five primary care sites spanned March 2021-May 2023. Adult patients who screened positive for subthreshold OUD (current illicit or non-medical opioid use without meeting DSM-5 criteria for moderate-severe OUD) were eligible. Baseline assessments measured self-reported demographic characteristics, other substance use, pain, and physical and mental health symptoms. Descriptive statistics summarize characteristics of the enrolled sample across sites. RESULTS:Among the 202 participants, the majority identified as female (63.4%), white (70.8%), and non-Hispanic (96.5%), with mean age 55.7 (SD: 12.7) years. Nearly half (49.0%) had problem or high-risk use of prescription opioids, and most received a prescription for opioid medication in the past six months (74.8%). Many participants reported current problem use or high-risk use of alcohol (47.0%) or cannabis (31.2%). Approximately one-third endorsed mental health symptoms, including moderate-severe anxiety (35.6%), depression (31.2%), or sleep disturbance (29.7%), and 20.3% reported a past suicide attempt. In the prior six months, 14.7% had experienced a nonfatal overdose. Moderate-severe pain was reported by 63.4%, and 60.4% rated their general health as fair or poor. CONCLUSIONS:Patients with subthreshold OUD had high rates of polysubstance use and comorbidities that may present challenges to reducing risky opioid use. The STOP trial presents an opportunity to detect and address subthreshold OUD in a cohort with considerable medical and social needs, within primary care settings. CLINICAL TRIALS REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT04218201.

BACKGROUND:Our understanding of traditional atherosclerotic risk factors is based predominantly on one-time measurements and associations with adverse cardiovascular outcomes. OBJECTIVES/OBJECTIVE:The aim of this study was to evaluate the contribution of mid- to late-life cumulative risk factor exposure to healthy arterial aging, represented by a persistent coronary artery calcium (CAC) score of zero. METHODS:Among 2,044 community-dwelling, participants free of coronary heart disease from the ARIC (Atherosclerosis Risk in Communities) study, the associations of ∼30-year time-weighted average mid- to late-life (starting at a median age of 49 years in 1987-1989) traditional atherosclerotic risk factors (cholesterol, systolic blood pressure, fasting glucose, and smoking) with late-life (median age 80 years in 2018-2019) CAC 0 were evaluated. RESULTS:A total of 204 participants (10.0%) had CAC 0, and they tended to have more favorable mid- to late-life average risk factor profiles than those with CAC: lower total cholesterol, especially <160 mg/dL; lower systolic blood pressure, especially <125 mm Hg; and higher high-density lipoprotein cholesterol, especially >45 mg/dL. The association was less evident for fasting glucose, with no increased probability of CAC 0 at <95 mg/dL. Never smoking was associated with a 5.7 (95% CI: 2.3-16.7) times greater odds of CAC 0 vs smoking throughout mid- to late-life. Within sex-race groups, average modifiable risk factors predicted substantial differences in CAC 0 probability (eg, for a Black woman, 53% vs 0.4% for a low vs high risk factor profile, respectively). CONCLUSIONS:Favorable average risk factor profiles at mid- to late-life were associated with a greater probability of CAC 0 at older age. These results highlight the importance of maintaining a healthy risk factor profile from mid- to late-life, with implications for public health promotion and policy.

Factorial study designs can be important for understanding the effectiveness of interventions when multiple interventions are under investigation. In this design setting, a unit of randomization can be assigned to any combination of interventions. The rationale for taking this kind of approach can vary depending on the specific questions targeted by the research. These questions, in turn, have implications for the way in which the analyses will be conducted. The goal in this paper is to describe how we developed a factorial design along with a Bayesian analytic plan for a large cluster-randomized trial-the Emergency Departments LEading the transformation of Alzheimer's and Dementia care (ED-LEAD) study-focused on improving care for persons living with dementia.

BACKGROUND:Individuals with opioid use disorder have high rates of hospital admissions, which represent a critical opportunity to engage patients and initiate medications for opioid use disorder (MOUD). However, few patients receive MOUD and, even if MOUD is initiated in the hospital, patients may encounter barriers to continuing MOUD in the community. OBJECTIVE:Describe hospital providers' experiences and perspectives to inform initiatives and policies that support hospital-based MOUD initiation and continuation in community treatment programs. DESIGN/METHODS:As part of a broader implementation study focused on inpatient MOUD (NCT#04921787), we conducted semi-structured interviews with hospital providers. PARTICIPANTS/METHODS:Fifty-seven hospital providers from 12 community hospitals. APPROACH/METHODS:Thematic analysis examined an emergent topic on challenges transitioning patients to outpatient MOUD treatment and related impacts on MOUD initiation by inpatient providers. KEY RESULTS/RESULTS:Participants described structural barriers to transitioning hospitalized patients to continuing outpatient MOUD including (a) limited outpatient buprenorphine prescriber availability, (b) the siloed nature of addiction treatment, and (c) long wait times. As a result of observing these structural barriers, participants experienced a sense of futility that deterred them from initiating MOUD. Participants proposed strategies that could better support these patient transitions, including developing partnerships between hospitals and outpatient addiction treatment and supporting in-reach services from community providers. CONCLUSIONS:We identified concerns about inadequate and inaccessible community-based care and transition pathways that discouraged hospital providers from prescribing MOUD. As hospital-based opioid treatment models continue to expand, programmatic and policy strategies to support inpatient transitions to outpatient addiction treatment are needed. NCT TRIAL NUMBER/UNASSIGNED:04921787.

BACKGROUND:Unmet structural and social needs create barriers to breast cancer screening and treatment. The impact of the intersection of these barriers on screening participation and timeliness of breast cancer care remains poorly understood. METHODS:People identifying as women participating in a breast cancer navigation program for screening or treatment were included. Patient navigators administered survey questions that addressed potential barriers to care access using the Health Leads Screening Toolkit. Odds ratios were calculated for unadjusted bivariate associations, and Cox proportional hazards were used to examine the relationship between barriers and time to treatment. RESULTS:A total of 2804 women (mean age, 53 years) enrolled in navigation for screening or cancer treatment participated in the survey about barriers to care. Of those, 435 (16%) reported unstable housing, 610 (23%) reported poor health literacy, and 164 (6%) reported feeling depressed. Limited transportation was significantly associated with unstable housing (odds ratio [OR] = 26.5, 95% confidence interval [CI] 19.9-35.4, p < 0.00001), poor health literacy (OR = 11.5, 95% CI 9.3-14.2, p < 0.0001), and depression (OR = 2.9, 95% CI 2.1-4.0, p < 0.00001). Individual barriers were not associated with a longer time to treatment, but an increasing number of barriers was associated with a longer time to treatment (Coef = 0.9, p < 0.05). CONCLUSIONS:Compounding structural and social barriers limit participation in breast cancer screening, and women with increasing unmet social needs face delays in treatment for breast cancer. Navigation programs may help women overcome barriers to care; however, understanding and targeting the intersectionality of unmet needs is essential for targeted interventions through breast cancer care navigation programs to be effective.

PURPOSE/OBJECTIVE:Prostate cancer (PCA) germline testing (GT) informs precision therapy, cancer screening, and hereditary cancer risk for patients and families. To support patient-centered PCA GT, studying patient-reported outcomes (PROs) is essential. METHODS:PROGRESS was a national patient-driven registry (January 2021-April 2022) for English-speaking males older than 18 years with previous/current PCA GT and Internet access. Surveys collected demographics, PCA history, family cancer history, mode of genetics care delivery, satisfaction with genetic counseling, decisional conflict, cancer genetics knowledge, and attitudes toward GT. Multiple linear regression modeling was used to estimate and draw inferences (α = .05) on strength of relationships between participant characteristics and PROs. RESULTS:Analyses focused on 414 participants: White (88%), Black (3%), Asian (6%), and mixed/other (3%). Most participants were non-Hispanic (95.2%) and 46.9% had PCA. Genetic results were positive (pathogenic/likely pathogenic variants; mutations) in 27.9%. The three most common modes of genetics care were meeting with genetics professional (in-person or remotely; 30.9%), discussing with doctor (21.1%), and using website (20.8%). In covariate-adjusted models, satisfaction scores were highest with pretest counseling by phone (β = 1.31; 95% CI, 0.26 to 2.36) or discussion with doctor (β = 1.25; 95% CI, 0.38 to 2.12). Lower decisional conflict scores were reported for pretest counseling by phone (β = -3.76; 95% CI, -7.28 to -0.24). Males with mutations reported higher GT benefit scores (β = .30; 95% CI, 0.02 to 0.59) and importance of GT (β = .34; 95% CI, 0.08 to 0.61). Asian Americans reported lower GT satisfaction (β = -2.91; 95% CI, -4.34 to -1.48) and higher decisional conflict (β = 8.93; 95% CI, 4.36 to 13.51). CONCLUSION/CONCLUSIONS:PROGRESS Registry informs the first comprehensive report of PROs among males undergoing PCA GT, providing insights into opportunities to improve patient experience and leverage the benefit of GT.