Faculty Bibliography

OBJECTIVES/OBJECTIVE:In mild traumatic brain injury, imaging biomarkers are needed to support clinical management. In four antecedent publications, we used two new (sodium and fingerprinting) and two established (spectroscopy and diffusion) MR techniques in a longitudinally followed patient cohort. Here we report final results and combine all data to determine which marker(s) from the four modalities offer the greatest utility for detecting injury and predicting outcomes. We also leverage the independent specificities offered by each modality to explore injury mechanisms. MATERIALS AND METHODS/METHODS:The longitudinal spectroscopy data were analysed to complete a full data set of proton (spectroscopy, fingerprinting, diffusion) and sodium MRI, acquired alongside symptomatic, cognitive, and functional assessments in 27 patients at 1, 3, and 12 months following injury. Twenty-three matched controls were scanned once. Testing for associations between nine MR markers and three outcome measures was standardized across the entire data set, and performed using Spearman correlations and logistic regression. RESULTS:from fingerprinting (marker of the cellular microenvironment). CONCLUSIONS:We identified independent, dynamic, metabolic and ionic changes, with choline and creatine from spectroscopy fulfilling the most criteria for a clinical biomarker.

BACKGROUND:Hypertension (HTN) is the leading cause of cardiovascular morbidity and mortality among people living with HIV (PLWH) in Africa, yet integration of hypertension treatment in HIV clinics is sub-optimal. Cost-effective strategies to implement evidence-based hypertension care for this population are urgently needed to preserve the life-expectancy gains of antiretroviral therapy. METHODS:Building on insights gained from a comprehensive mixed-methods formative assessment, we used a human-centered design approach to develop a multi-component HIV-HTN integration (HTN-PLUS) strategy. In a stepped-wedge cluster randomized trial, we are assessing the effectiveness, costs, and implementation of HTN-PLUS as well as a less resource intensive strategy of providing HTN medication and blood pressure cuffs (HTN-BASIC) free of charge to clinics. The trial is being conducted in 16 public and private not-for-profit HIV clinics in Kampala and Wakiso districts in Uganda. The co-primary effectiveness outcomes are population BP control (screened and documented BP < 140/90 mmHg) and HTN patient BP control [BP < 140/90 mmHg among PLWH with HTN]. The trial is designed to have > 80% power to detect a 12%-point increase in both outcomes compared to the pre-implementation control period across a range of scenarios of baseline hypertension prevalence and temporal improvements in the control period. At two pre-specified time points, we are conducting a Learn-As-You-Go optimization analysis and will adapt the HTN-PLUS strategy accordingly. To assess implementation outcomes, we have enrolled a prospective longitudinal mixed-methods cohort study of clinic health workers and PLWH with HTN. An extensive economic evaluation will include time and motion studies, facility-based costing, and out-of-pocket cost surveys to determine costs and cost-effectiveness from a societal perspective. DISCUSSION/CONCLUSIONS:Innovative implementation strategies to integrate evidence-based hypertension care for PLWH in Africa must be informed by the health workers and PLWH who are cared for across diverse HIV clinics. These clinics currently provide high quality HIV care as evidenced by high rates of HIV viral suppression but often lack the knowledge, skills and resources to provide HTN care. Funders and policymakers critically need to know both the effectiveness and costs to scale these strategies and potentially expand them to include other non-AIDS comorbidities. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT05609513. Registered on November 11, 2022.

While approximately one in five Americans with substance use disorder (SUD) receives treatment in addiction treatment programs, a majority have seen a primary care medical provider in the past year. Recognizing the critical role of primary care in addressing prevention and treatment of unhealthy substance use, for over a decade the National Drug Abuse Treatment Clinical Trials Network (CTN) has supported research to build the tools and evidence needed to support the integration of SUD care, while remaining realistic about the barriers to doing so. Authored by primary care and addiction medicine physician researchers, this commentary provides an overview of CTN primary care-focused research, from developing and implementing substance use screening tools to advancing evidence-based SUD treatment delivery in primary care settings. We identify three priority areas for research and practice innovations: 1) identifying effective treatment interventions to address polysubstance use; 2) improved screening and treatment for cannabis use; and 3) building the evidence base for substance use interventions among non-treatment seeking patients who have unhealthy drug use identified through screening. Addressing these areas can help primary care fulfill its potential as a key component of the substance use services continuum of care.

BACKGROUND:Hispanic/Latinx males and those who are non-English proficient are significantly less likely to receive germline genetic evaluation for prostate cancer. Undertesting can impact downstream outcomes, including reduced access to approved targeted therapies, barriers to precision medicine trials, and hereditary cancer assessment for patients and family members. The goal of our study was to explore the knowledge and perceptions of genetic testing among U.S. Hispanic males, with the ultimate goal to identify potentially actionable targets to increase guideline-concordant genetic evaluation. METHODS:We conducted a nationwide online survey including U.S. Hispanic males aged ≥ 40 in English and Spanish using the 9-item Knowledge of Hereditary Prostate Cancer Scale and adapted questions about desire for more information from the Behavioral Beliefs about BRCA Genetic Counseling scale. RESULTS:Among 807 participants, the mean score for genetic knowledge was 5.8 out of 9, with gaps in understanding of incomplete penetrance of genes and maternal genetic inheritance. Medical mistrust and lower health literacy were associated with significantly lower knowledge of prostate cancer genetics. Overall, attitudes toward genetic counseling were favorable, with the majority of participants endorsing that it would help with decision-making, is concordant with cultural beliefs, and that they were interested in more information. Concerns about genetic evaluation included cost and impact for insurance. CONCLUSIONS:Despite generally favorable attitudes toward genetic evaluation among Hispanic males, there are important knowledge gaps, including the importance of both maternal and paternal family history, as well as logistical concerns. Addressing these gaps through culturally targeted outreach may help to promote equitable uptake of germline genetic evaluation.

BACKGROUND:Advances in antiretroviral therapy have enabled people living with HIV (PLHIV) to live longer and healthier lives. However, aging with HIV infection is accompanied by an increased risk of non-communicable diseases (NCDs), highlighting the need to integrate care services. The Academic Model Providing Access to Healthcare (AMPATH) in Eldoret, Kenyahas, which has been providing care for PLHIV for over 30 years, is seeing an increase in NCDs, particularly hypertension and diabetes, especially among older patients. It is unclear how healthcare providers manage the complex healthcare needs of older adults living with HIV (OALWH) and comorbid NCDs, or how they perceive the integration of hypertension and diabetes care within the HIV care platform. METHODS:We conducted in-depth interviews at an AMPATH facility in Eldoret, Kenya. Ten healthcare providers (three nurses and seven clinical officers) were interviewed to explore the facilitators and barriers to integrating HIV and NCD care services for OALWH. Audio records were transcribed verbatim, content analysis was performed, and the capabilities (C), opportunities (O), and motivation (M) models for behavior change (COM-B model) were used to comprehensively map the drivers and barriers that shape healthcare providers' acceptance, adoption, and implementation of integrated HIV and NCD care services. RESULTS:The majority of participants had worked for more than five years, offering care for people living with HIV. All participants had experience managing older adults living with HIV and expressed challenges with the lack of coordinated care delivery for HIV and NCDs. The participants highlighted the potential challenges of optimal adherence to antiretroviral therapy (ART) among OALWH in the presence of multiple chronic conditions. Based on these challenges, participants perceived the integration of hypertension and diabetes care into the HIV care platform as beneficial to clients and the overall healthcare system. Factors such as the availability of physical resources and infrastructure (C), availability of training opportunities for NCD care (O), leadership support (M), and motivation to provide person-centered care (M) were perceived as facilitators of HIV/NCD integrated care delivery. Impeding factors such as lack of guidelines for integration (O), siloed healthcare service delivery (O), inadequate resource allocation for NCDs (O), and perceived increased workload (M) were also highlighted by healthcare providers. CONCLUSION/CONCLUSIONS:The findings of this study highlight healthcare providers' perceived facilitators and barriers to the integration of NCD care into HIV care platforms. The insights gained from this study hold the potential to inform tailored interventions, policy decisions, and capacity-building initiatives aimed at fostering successful integration and improving overall health care delivery to meet the needs of OALWH in resource-constrained settings.

Recreational cannabis outlets may influence rates of interpersonal violence, but research has yielded inconsistent findings. Modification by alcohol outlet density may help explain inconsistencies. We estimated the impacts of recreational cannabis outlets on neighborhood-level assault injury rates in California and evaluated whether alcohol outlet density moderated these associations. We applied Bayesian spatiotemporal analyses to ZIP code-level statewide data on alcohol outlets, recreational cannabis outlets, and injuries and deaths due to firearm and nonfirearm assault, 2017-2019, accounting for confounders and spatial autocorrelation. Using the model posteriors, we estimated parameters corresponding to hypothetical shifts in outlet densities, overall and by age, sex, and race/ethnicity. If recreational cannabis outlets were never introduced, we estimated that nonfirearm assault injuries would have been 1.63 per 100,000 lower (95%CI: -3.08, 0.01) but we observed no association with firearm assault injuries (RD per 100,000: -0.07; 95%CI: -0.34, 0.21). These associations did not depend on alcohol outlet density, but a hypothetical 20% reduction in alcohol outlet densities was associated with fewer firearm (RD per 100,000: -1.89; 95%CI: -0.46, 0.09) and nonfirearm (RD per 100,000: -5.67; 95%CI: -7.44, -3.95) assault injuries. The introduction of recreational cannabis outlets may have contributed to a small increase in nonfirearm assault injuries.

Frailty is an age-related syndrome characterized by an increased vulnerability to adverse health outcomes in the face of stressors. By deriving a blood-based proteomic signature for frailty, the current study aimed to enhance the understanding of frailty biology and created a person-specific predictor for the risk of frailty and other adverse age-related health outcomes. A 25-protein signature (proteomic frailty index [pFI]) predictive of the cumulative frailty index (FI) in the LonGenity cohort was derived using a penalized regression method. The pFI was significantly correlated with the FI at baseline (Pearson r = 0.58) and showed significant associations with age-related chronic conditions, incident mortality, and clinical measures. In an independent cohort of 5195 participants in the Atherosclerosis Risk in Communities study, pFI was successfully validated with measured FI (r = 0.61, p < 0.001) and was associated with physical frailty at baseline (p < 0.001). The pFI was significantly associated with physical, clinical, and cognitive measures, as well as incident mortality (HR [95% CI] = 1.13 [1.12-1.14]) and dementia (HR [95% CI] = 1.07 [1.05-1.09]) after accounting for demographic factors. The pFI was further validated against FI (r = 0.45, p < 0.001) in a second independent study in 654 participants from the Baltimore Longitudinal Study of Aging. In conclusion, we identified and validated a 25-protein signature as an index of frailty that also captures overall well-being, health, and risk for key age-related diseases.

INTRODUCTION/BACKGROUND:The impact of remote patient monitoring (RPM) for hypertension (HTN) on cardiovascular health (CVH) remains ill-defined. This study characterized the association between a RPM, team-based HTN intervention and CVH markers. METHODS:This retrospective, single-arm cohort study included patients with uncontrolled HTN enrolled February 2022-July 2024 in the ALTA trial (clinicaltrials.gov NCT03713515) at five safety-net practices. The ALTA intervention involves RPM supported by a virtual clinic including a nurse practitioner (NP), registered nurse, and community health worker. Demographics, ALTA utilization, and CVH markers (blood pressure [BP], lipids, glycemic indicators, body mass index [BMI], and smoking) at baseline and 12 months were collected. Five markers were scored (0=poor, 1=intermediate, 2=ideal) and summed into a CVH score. The primary endpoint was the 12-month CVH score change in patients with baseline score ≤7. Secondary endpoints included individual non-BP marker changes in patients with baseline derangements. RESULTS:Among 568 patients (mean age: 56 years), most were female, non-Hispanic Black, and English-speaking. NP visits were more common among females (p=0.04); no other demographics predicted ALTA utilization. The CVH score improved from 4.5 to 5.2 (n=196, p<0.001), independent of ALTA utilization. Total cholesterol (n=86, p<0.001), LDL (n=128, p<0.001), and triglycerides (n=51, p=0.004) improved. Hemoglobin A1c (n=195) dropped among patients with ≥1 NP visit (p=0.02). Fasting glucose (n=135) and BMI (n=289) decreased in the highest tertile of NP visits (p=0.03) and RPM (p=0.02), respectively. 4 of 27 patients quit smoking. CONCLUSIONS:RPM with team-based support was associated with CVH improvements. Benefits may depend on intervention utilization.

The Chatbot Assessment Reporting Tool (CHART) is a reporting guideline developed to provide reporting recommendations for studies evaluating the performance of generative artificial intelligence (AI)-driven chatbots when summarizing clinical evidence and providing health advice, referred to as Chatbot Health Advice (CHA) studies. CHART was developed in several phases after performing a comprehensive systematic review to identify variation in the conduct, reporting and methodology in CHA studies. Findings from the review were used to develop a draft checklist that was revised through an international, multidisciplinary modified asynchronous Delphi consensus process of 531 stakeholders, three synchronous panel consensus meetings of 48 stakeholders, and subsequent pilot testing of the checklist. CHART includes 12 items and 39 subitems to promote transparent and comprehensive reporting of CHA studies. These include Title (subitem 1a), Abstract/Summary (subitem 1b), Background (subitems 2ab), Model Identifiers (subitem 3ab), Model Details (subitems 4abc), Prompt Engineering (subitems 5ab), Query Strategy (subitems 6abcd), Performance Evaluation (subitems 7ab), Sample Size (subitem 8), Data Analysis (subitem 9a), Results (subitems 10abc), Discussion (subitems 11abc), Disclosures (subitem 12a), Funding (subitem 12b), Ethics (subitem 12c), Protocol (subitem 12d), and Data Availability (subitem 12e). The CHART checklist and corresponding methodological diagram were designed to support key stakeholders including clinicians, researchers, editors, peer reviewers, and readers in reporting, understanding, and interpreting the findings of CHA studies.