Faculty Bibliography

Rates of cognitive decline in Alzheimer's disease (AD) are extremely heterogeneous. Although biomarkers for amyloid-beta (Aβ) and tau proteins, the hallmark AD pathologies, have improved pathology-based diagnosis, they explain only 20-40% of the variance in AD-related cognitive impairment (CI). To discover novel biomarkers of CI in AD, we performed cerebrospinal fluid (CSF) proteomics on 3,397 individuals from six major prospective AD case-control cohorts. Synapse proteins emerged as the strongest correlates of CI, independent of Aβ and tau. Using machine learning, we derived the CSF YWHAG:NPTX2 synapse protein ratio, which explained 27% of the variance in CI beyond CSF pTau₁₈₁:Aβ₄₂, 11% beyond tau positron emission tomography, and 28% beyond CSF neurofilament, growth-associated protein 43 and neurogranin in Aβ⁺ and phosphorylated tau⁺ (A+T₁+) individuals. CSF YWHAG:NPTX2 also increased with normal aging and 20 years before estimated symptom onset in carriers of autosomal dominant AD mutations. Regarding cognitive prognosis, CSF YWHAG:NPTX2 predicted conversion from A+T₁+ cognitively normal to mild cognitive impairment (standard deviation increase hazard ratio = 3.0, P = 7.0 × 10^-4) and A+T₁+ mild cognitive impairment to dementia (standard deviation increase hazard ratio = 2.2, P = 8.2 × 10^-16) over a 15-year follow-up, adjusting for CSF pTau₁₈₁:Aβ₄₂, CSF neurofilament, CSF neurogranin, CSF growth-associated protein 43, age, APOE4 and sex. We also developed a plasma proteomic signature of CI, which we evaluated in 13,401 samples, which partly recapitulated CSF YWHAG:NPTX2. Overall, our findings underscore CSF YWHAG:NPTX2 as a robust prognostic biomarker for cognitive resilience versus AD onset and progression, highlight the potential of plasma proteomics in replacing CSF measurement and further implicate synapse dysfunction as a core driver of AD dementia.

BACKGROUND/UNASSIGNED:Ecological momentary assessment (EMA) provides insight into the effectiveness and feasibility of smoking-related interventions. OBJECTIVE/UNASSIGNED:The objective of this paper was to assess adherence to an EMA protocol and compare EMA-derived responses with measures collected through multiple surveys. METHODS/UNASSIGNED:A subanalysis was conducted using data from a 12-week, open-label, and 2-arm pilot randomized clinical trial among adult smokers with chronic obstructive pulmonary disease, coronary artery disease, peripheral vascular disease, or asthma in the last 12 months (n=109). Participants were randomized to either electronic cigarette (EC) or nicotine replacement therapy (NRT) treatment arms. We compared EMA data collected through automated SMS text message prompts sent to participants 4 times daily for 12 weeks, including cigarettes smoked per day (CPD), craving, and satisfaction, to survey data collected at 12 weeks. Convergent validity between survey- and EMA-reported measures was evaluated using Pearson correlation and paired t tests. CPD was modeled using negative binomial regression. Relative rates (RRs) of reaching at least 50%, 75%, and 100% CPD reduction between two arms were calculated using both EMA and survey data. RESULTS/UNASSIGNED:The majority of participants were non-Hispanic White (63/109, 58%) and female (60/109, 55%), and had a median age of 60 (IQR 54-65) years. Among the 109 participants, 59.6% (n=65) were consistently adherent to the EMA protocol over the 12-week period. Median weekly EMA response rate remained high over the 12-week study period even though a modest decline was observed (week 1, 97.8% and week 12, 89.4%). The mean CPD declined significantly (week 1, mean 14.2, SD 9.9 and week 12, mean 4.6, SD 6.7; P<.001). EMA-derived and survey-based CPD measurements were positively correlated (r=0.73, 95% CI 0.6-0.82) as were measures of craving (r=0.38, 95% CI 0.17-0.56). No significant paired difference in CPD was observed between EMA measurements and surveys. A significant effect of time on CPD EMA data (incidence rate ratio [IRR] 1-week change 0.93; P<.01) and survey data was found (IRR 12-week change 0.36; P<.01). However, the treatment effect was not significant, which aligned with the RR results. An increase in the EC consumption was observed over time in the EC arm, with 12.1% (7/58) fully switched to EC (defined as CPD=0 and EC use>0) and 20.7% (12/58) mostly switched (defined as a reduction in CPD>75% and EC use>0) in week 12. CONCLUSIONS/UNASSIGNED:EMA is a suitable method to collect recall-based smoking-related data. Though results from mixed effect modeling and RR comparisons were similar using EMA or survey data, EMA provides unique advantages, namely greater granularity in the time and the capability to detect switching patterns in near real time. These findings provide the feasibility of using EMA in developing smoking cessation interventions in future tobacco harm reduction research.

INTRODUCTION/BACKGROUND:E-cigarettes (ECs) may be an effective harm reduction strategy for individuals with conditions like chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease (CAD), and peripheral arterial disease (PAD) who smoke combustible cigarettes (CCs). Our aim was to examine how individuals with chronic conditions transition from CCs to ECs and its impact on health outcomes. METHODS:In a pilot randomized controlled trial (RCT), patients with COPD, asthma, CAD/PAD who currently smoke CCs and have not used nicotine replacement therapy (NRT) or ECs in the past 14 days were randomized to receive ECs or combination NRT with behavioral counselling. Disease symptoms, acceptability/satisfaction (TSQM-9) and feasibility, and cigarettes per day (CPD), and/or EC use were collected at baseline, 3-, and 6-months. Descriptive statistics and a linear regression were conducted to explore changes in CPD and chronic condition-specific assessments (CAT, SAQ-7, ACT) that assess COPD, asthma, and CAD/PAD symptom change. RESULTS:At 3-months, the EC group (n=63, mean CPD=9±11) reduced their CPD by 54% vs. 60% in the NRT group (n=58, mean CPD=7±6), p=0.56. At 6-months, 17.5% had switched completely to ECs while 23% quit smoking in the NRT arm. CAT scores showed a significant 6-point reduction in the EC arm (p=0.03). Participants scored an average of 69±27 for EC effectiveness, 87±23 for convenience, and 75±27 for overall satisfaction. CONCLUSIONS:This pilot study suggests that ECs may be a safer alternative for chronic condition patients using CCs and warrants further research on expected smoking cessation/reduction among individuals who use ECs. IMPLICATIONS/CONCLUSIONS:The findings from this pilot RCT hold significant implications with chronic conditions such as COPD, asthma, CAD and PAD who smoke CCs. The observed reduction in cigarettes per day and improvement in respiratory symptoms suggest that switching to ECs appears feasible and acceptable among those with chronic diseases. These results suggest that ECs may offer an alternative for individuals struggling to quit CC smoking through existing pharmacotherapies. This study supports further exploration of switching to ECs as a harm reduction strategy among CC users who have been unsuccessful at quitting by other means.

INTRODUCTION/BACKGROUND:Early lung cancer screening (LCS) through low-dose CT (LDCT) is crucial but underused due to various barriers, including incomplete or inaccurate patient smoking data in the electronic health record and limited time for shared decision-making. The objective of this trial is to investigate a patient-centred intervention, MyLungHealth, delivered through the patient portal. The intervention is designed to improve LCS rates through increased identification of eligible patients and informed decision-making. METHODS AND ANALYSIS/METHODS:MyLungHealth is a multisite pragmatic trial, involving University of Utah Health and New York University Langone Health primary care clinics. The MyLungHealth intervention was developed using a user-centred design process, informed by patient and provider focus groups and interviews. The intervention's effectiveness will be evaluated through a patient-randomised trial, comparing the combined use of MyLungHealth and DecisionPrecision+ (a provider-focused shared decision-making intervention) against DecisionPrecision+ alone. The first study hypothesis is that among patients aged 50-79 with uncertain LCS eligibility (eg, 10-19 pack-years or unknown pack-years or unknown quit date for individuals who used to smoke), MyLungHealth eligibility questionnaires will result in increased identification of LCS-eligible patients (n~26 729 patients). The second study hypothesis is that among patients aged 50-79 with documented LCS eligibility (20+ pack-years, quit within the last 15 years if individuals who used to smoke, and no recent screening or screening discussion), MyLungHealth education will result in increased LDCT ordering (n~4574 patients). Primary outcomes will be identification of LCS-eligible patients among individuals with uncertain LCS eligibility and LDCT ordering rates among individuals with documented LCS eligibility. ETHICS AND DISSEMINATION/BACKGROUND:The protocol was approved by the University of Utah Institutional Review Board (# 00153806). The patient data collected for this study will not be shared publicly due to the sensitive nature of the patient health information and the fact that we will not be obtaining written informed consent to allow public sharing of their data. Results will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER/BACKGROUND:Clinicaltrials.gov, NCT06338592.

INTRODUCTION/BACKGROUND:Failure to document colonoscopy follow-up needs postpolypectomy can lead to delayed detection of colorectal cancer (CRC). Automating the update of a unified follow-up date in the electronic health record (EHR) may increase the number of patients with guideline-concordant CRC follow-up screening. METHODS:Prospective pre-post design study of an automated rules engine-based tool using colonoscopy pathology results to automate updates to documented CRC screening due dates was performed as an operational initiative, deployed enterprise-wide May 2023. Participants were aged 45-75 years who received a colonoscopy November 2022 to November 2023. Primary outcome measure is rate of updates to screening due dates and proportion with recommended follow-up < 10 years. Multivariable log-binomial regression was performed (relative risk, 95% confidence intervals). RESULTS:Study population included 9,824 standard care and 19,340 intervention patients. Patients had a mean age of 58.6 ± 8.6 years and were 53.4% female, 69.6% non-Hispanic White, 13.5% non-Hispanic Black, 6.5% Asian, and 4.6% Hispanic. Postintervention, 46.7% of follow-up recommendations were updated by the rules engine. The proportion of patients with a 10-year default follow-up frequency significantly decreased (88.7%-42.8%, P < 0.001). The mean follow-up frequency decreased by 1.9 years (9.3-7.4 years, P < 0.001). Overall likelihood of an updated follow-up date significantly increased (relative risk 5.62, 95% confidence intervals: 5.30-5.95, P < 0.001). DISCUSSION/CONCLUSIONS:An automated rules engine-based tool has the potential to increase the accuracy of colonoscopy follow-up dates recorded in patient EHR. The results emphasize the opportunity for more automated and integrated solutions for updating and maintaining EHR health maintenance activities.

Highly effective antiobesity and diabetes medications such as glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide/GLP-1 (dual) receptor agonists (RAs) have ushered in a new era of treatment of these highly prevalent, morbid conditions that have increased across the globe. However, the rapidly escalating use of GLP-1/dual RA medications is poised to overwhelm an already overburdened health care provider workforce and health care delivery system, stifling its potentially dramatic benefits. Relying on existing systems and resources to address the oncoming rise in GLP-1/dual RA use will be insufficient. Generative artificial intelligence (GenAI) has the potential to offset the clinical and administrative demands associated with the management of patients on these medication types. Early adoption of GenAI to facilitate the management of these GLP-1/dual RAs has the potential to improve health outcomes while decreasing its concomitant workload. Research and development efforts are urgently needed to develop GenAI obesity medication management tools, as well as to ensure their accessibility and use by encouraging their integration into health care delivery systems.

Prostate-specific antigen (PSA)-based prostate cancer screening is a preference-sensitive decision for which experts recommend a shared decision making (SDM) approach. This study aimed to examine PSA screening SDM in primary care. Methods included qualitative analysis of audio-recorded patient-provider interactions supplemented by quantitative description. Participants included 5 clinic providers and 13 patients who were: (1) 40-69 years old, (2) Black, (3) male, and (4) attending clinic for routine primary care. Main measures were SDM element themes and "observing patient involvement in decision making" (OPTION) scoring. Some discussions addressed advantages, disadvantages, and/or scientific uncertainty of screening, however, few patients received all SDM elements. Nearly all providers recommended screening, however, only 3 patients were directly asked about screening preferences. Few patients were asked about prostate cancer knowledge (2), urological symptoms (3), or family history (6). Most providers discussed disadvantages (80%) and advantages (80%) of PSA screening. Average OPTION score was 25/100 (range 0-67) per provider. Our study found limited SDM during PSA screening consultations. The counseling that did take place utilized components of SDM but inconsistently and incompletely. We must improve SDM for PSA screening for diverse patient populations to promote health equity. This study highlights the need to improve SDM for PSA screening.

OBJECTIVE:Both diabetes and smoking significantly increase the risk of cardiovascular disease (CVD). Understanding whether a diagnosis of diabetes can be leveraged to promote smoking cessation is a gap in the literature. METHODS:We used data from the US National Health Interview Survey, 2006 to 2018, to investigate the relationship between self-report of diagnosis of diabetes and subsequent smoking abstinence among 142,884 respondents who reported regular smoking at baseline. Effect sizes were presented as hazard ratios (HRs) derived from multivariable Cox regression models adjusted for potential confounders using diabetes as a time-dependent covariate. Subgroup-specific estimates were obtained using interaction terms between diabetes and variables of interest. RESULTS:A self-reported diagnosis of diabetes was associated with smoking abstinence (HR: 1.21; 95% CI: 1.16 to 1.27). The strength of the association varied based on race (P for interaction: 0.004), where it was strongest in African Americans (HR: 1.44; 95% CI: 1.29 to 1.60); income (P for interaction <0.001), where it was strongest in those with a yearly income less than $35,000 (HR: 1.45; 95% CI: 1.36 to 1.53); and educational attainment (P for interaction <0.001), where it was strongest in those who did not attend college (HR: 1.48; 95% CI: 1.40 to 1.57). CONCLUSION/CONCLUSIONS:Among adults who smoke, a diagnosis of diabetes is significantly associated with subsequent smoking abstinence. The association is strongest in socially disadvantaged demographics, including African Americans, low-income individuals, and those who did not attend college.

INTRODUCTION/BACKGROUND:Six hospitals within the New York City public hospital system implemented the Consult for Addiction Treatment and Care in Hospitals (CATCH) program, an interprofessional addiction consult service. A stepped-wedge cluster randomized controlled trial tested the effectiveness of CATCH for increasing initiation and engagement in post-discharge medication for opioid use disorder (MOUD) treatment among hospital patients with opioid use disorder (OUD). The objective of this study was to identify facility characteristics that were associated with stronger performance of CATCH. METHODS:This study used a mixed methods multiple-case study design. The six hospitals in the CATCH evaluation were each assigned a case rating according to intervention reach. Reach was considered high if ≥50 % of hospitalized OUD patients received an MOUD order. Cross-case rating comparison identified attributes of high-performing hospitals and inductive and deductive approaches were used to identify themes. RESULTS:Higher-performing hospitals exhibited attributes that were generally absent in lower-performing hospitals, including (1) complete medical provider staffing; (2) designated office space and resources for CATCH; (3) existing integrated OUD treatment resources; and (4) limited overlap between the implementation period and COVID-19 pandemic. CONCLUSIONS:Hospitals with attributes indicative of awareness and integration of OUD services into general care were generally higher performing than hospitals that had siloed OUD treatment programs. Future implementations of addiction consult services may benefit from an increased focus on hospital- and community-level buy-in and efforts to integrate MOUD treatment into general care.

OBJECTIVES/OBJECTIVE:To evaluate demographic biases in diagnostic accuracy and health advice between generative artificial intelligence (AI) (ChatGPT GPT-4) and traditional symptom checkers like WebMD. MATERIALS AND METHODS/METHODS:Combination symptom and demographic vignettes were developed for 27 most common symptom complaints. Standardized prompts, written from a patient perspective, with varying demographic permutations of age, sex, and race/ethnicity were entered into ChatGPT (GPT-4) between July and August 2023. In total, 3 runs of 540 ChatGPT prompts were compared to the corresponding WebMD Symptom Checker output using a mixed-methods approach. In addition to diagnostic correctness, the associated text generated by ChatGPT was analyzed for readability (using Flesch-Kincaid Grade Level) and qualitative aspects like disclaimers and demographic tailoring. RESULTS:ChatGPT matched WebMD in 91% of diagnoses, with a 24% top diagnosis match rate. Diagnostic accuracy was not significantly different across demographic groups, including age, race/ethnicity, and sex. ChatGPT's urgent care recommendations and demographic tailoring were presented significantly more to 75-year-olds versus 25-year-olds (P < .01) but were not statistically different among race/ethnicity and sex groups. The GPT text was suitable for college students, with no significant demographic variability. DISCUSSION/CONCLUSIONS:The use of non-health-tailored generative AI, like ChatGPT, for simple symptom-checking functions provides comparable diagnostic accuracy to commercially available symptom checkers and does not demonstrate significant demographic bias in this setting. The text accompanying differential diagnoses, however, suggests demographic tailoring that could potentially introduce bias. CONCLUSION/CONCLUSIONS:These results highlight the need for continued rigorous evaluation of AI-driven medical platforms, focusing on demographic biases to ensure equitable care.