Okafor, Philip N.

Importance: Chronic liver disease requires sustained engagement with the health system, which co-occurring social and functional risks may disrupt. Whether these risks form reproducible patterns with different mortality associations is uncertain. Objective: To identify social and functional risk patterns among US adults with chronic liver disease and evaluate their associations with all-cause mortality. Design, Setting, and Participants: Nationally representative cohort study of National Health Interview Survey sample adults interviewed from 2011 through 2018 and linked to the National Death Index through 31 December 2019. Participants were aged 18 years or older, eligible for mortality linkage, reported a chronic liver condition, and had no baseline liver cancer. Exposures: Latent class membership derived from 7 binary indicators: poverty, food insecurity, uninsurance, cost-related delayed care, no usual place of care, single-adult household status, and activity limitation. A complete 0- to 7-item count was a secondary exposure. Main Outcomes and Measures: All-cause mortality. Survey-weighted Cox models estimated hazard ratios (HRs) with sequential demographic, clinical, and liver-specific adjustment. Prespecified sensitivity analyses used 20 multiple imputed data sets, sampling-weighted pseudo-likelihood latent class models, complete-case re-estimation, a fixed 5-year horizon, and class-by-age interaction testing. Results: Among 3407 adults (weighted mean age, 54.0 years; 49.4% female), 529 deaths occurred over 17,297.6 person-years (median follow-up, 5.0 years [IQR, 3.0–7.0]). Four classes were retained: low social and access burden (weighted prevalence, 63.1%); functional limitation with financial strain (13.2%); poverty, single-adult household, and functional limitation (15.0%); and uninsurance with major access barriers (8.7%). Compared with the low-burden class, the functional-limitation/financial-strain class had higher adjusted mortality (HR, 1.95; 95% CI, 1.34–2.82; p < 0.001); the other 2 classes did not differ significantly. Sampling-weighted latent class analysis after multiple imputation reproduced 97.2% of modal assignments, and the association persisted with attenuation (HR, 1.55; 95% CI, 1.08–2.22; p = 0.02). Each additional risk was associated with higher mortality (exact count: HR, 1.24 [95% CI, 1.13–1.36]; imputed count: HR, 1.19 [95% CI, 1.10–1.29]). The class-by-age interaction was not significant (p = 0.41). Conclusions and Relevance: Among US adults with self-reported chronic liver disease, social and functional adversity was both cumulative and patterned. A profile combining functional limitation, food insecurity, and cost-related delayed care had the clearest independent mortality association despite largely retained insurance coverage. These profiles are not a validated clinical score, but the findings argue against reliance on any single indicator, particularly insurance status, as a marker of vulnerability.

Objectives: Diabetes mellitus and chronic pancreatitis are established risk factors for pancreatic ductal adenocarcinoma (PDAC). The co-occurrence of exocrine and endocrine pancreatic dysfunction may increase the risk of progression to PDAC and could play a role in early detection. We sought to explore this hypothesis by comparing PDAC risk among patients with diabetes mellitus (DM) and low fecal elastase (FE) in a real-world cohort of patients. Materials and Methods: A retrospective cohort study was conducted using the TriNetX research network including adults with continuous follow-up from 2016 to 2023. The cohort was stratified into 4 groups based on the presence or absence of DM, and normal FE (>200 µg/g) or low FE (<200 µg/g). The 4 groups included: (1) low FE and DM, (2) low FE without DM, (3) normal FE and DM, (4) normal FE without DM. Propensity score matching was performed to balance covariates including age, sex, race, comorbidities to allow for a 6-way comparison of PDAC risk between groups. Time-to-event analyses were conducted with Kaplan-Meier curves and Cox proportional hazards models to estimate hazard ratios (HR) and 95% CIs for the primary outcome of PDAC incidence. Results: Of the study cohort, 29,207 had fecal elastase levels. Low FE (<200 µg/g) was observed in 33% (n = 9585) of these patients. After 6-way comparisons, we observed a higher PDAC risk among individuals with both DM and low FE compared with other groups. The highest PDAC risk was observed in patients with both a low FE (<200 µg/g) and DM compared with those with a normal FE and without a history of DM (HR: 3.68; 95% CI, 2.07–6.53; P < 0.001). Sensitivity analysis using a stricter fecal elastase cutoff of <100 µg/g showed a similar finding, with the highest hazard ratio for PDAC among patients with both DM and very low FE levels (HR: 3.07, 95% CI, 1.37–6.91; P = 0.004). Conclusions: The coexistence of low fecal elastase and DM amplifies the risk of pancreatic ductal adenocarcinoma in our cohort of patients. These results suggest that fecal elastase values may be used to enrich the diabetic population for future PDAC risk stratification, though more studies are needed to validate these findings.

Significance: Hepatic encephalopathy (HE) occurs in 20–80% of patients with liver cirrhosis, impacting attention, memory, processing speed, and visuospatial skills. HE standard-of-care psychometric assessments are time-consuming and require staff training. Oculometrics may provide a fast, non-invasive brain health assessment that can be self-administered in a medical environment. Purpose: We investigated whether an oculometric assessment could measure the severity of HE as accurately as standard-of-care psychometric methods. Methods: Forty-eight participants (19 with decompensated cirrhosis, 10 with compensated cirrhosis, 19 controls) completed a previously validated five-minute oculometric test and the standard-of-care psychometric hepatic encephalopathy (PHE) battery. The oculometric test consists of following a dot as it moves across a computer screen and generates 10 metrics including a summary score called nFit. The PHE battery entails five standard cognitive tests, generating seven metrics including a PHE composite score (PHES). Results: The oculometric summary score, nFit, correlated with the current diagnostic standard, the PHES (r = 0.51, p < 0.001), the presence or absence of HE as determined by PHES composite (r = −0.44, p < 0.001), as well as the severity of cirrhosis (r = −0.59, p < 0.001). Additionally, performance on both nFit and PHES distinguished compensated (ROC: nFit: 0.71, PHES: 0.68) and decompensated (ROC: nFit: 0.88, PHES: 0.85) patient groups from control participants comparably. Finally, compared to participants with decompensated cirrhosis, control participants had better scores for almost all oculometrics: acceleration, catch-up saccade amplitude, proportion smooth, direction noise, and speed noise. Conclusions: Patients with liver disease showed impairment on multiple aspects of visual processing compared to a control group. These functional visual processing impairments correlate with the presence or absence of HE, showing significant sensitivity in distinguishing people with HE from controls. Oculometric tests provide a quick, non-invasive functional assessment of brain health in patients with liver disease, with sensitivity indistinguishable from standard-of-case psychometric tests.

Objectives The aim of this study was to study the prevalence of exocrine pancreas insufficiency (EPI) at a population level and the subsequent risk of pancreatic ductal adenocarcinoma (PDAC). Materials and Methods Using TriNetX (a database of over 79 million US residents), we included patients ≥18 years with EPI (identified via ICD-10 codes) and continuous follow-up from 2016–2022. Patients with prior pancreas resection and PDAC before an EPI diagnosis were excluded. The primary outcome was EPI prevalence. Secondary outcomes included imaging utilization, PDAC risk, and pancreatic enzyme replacement therapy (PERT) utilization. We performed 1:1 propensity score matching (PSM) of patients with EPI versus patients without an EPI diagnosis. Results The population prevalence of EPI was 0.8% (n = 24,080) with a mean age of 55.6 years. After PSM, PDAC risk among patients with EPI was twice as high compared with patients without EPI (aHR, 1.97; 95% CI, 1.66–2.36). This risk persisted even after excluding patients with a history of acute or chronic pancreatitis (adjusted odds ratio, 4.25; 95% CI, 2.99–6.04). Only 58% (n = 13, 390) of patients with EPI received PERT. No difference was observed in PDAC risk between patients with EPI on PERT and those not on PERT (aHR, 1.10; 95% CI, 0.95–1.26; P = 0.17). Conclusions Despite a low prevalence, patients with EPI may have a higher risk of PDAC, and majority with EPI were not on PERT. PERT did not impact incident PDAC risk after an EPI diagnosis.

Objective: Patients with inflammatory bowel disease (IBD) are at increased risk of vaccine-preventable diseases (VPDs). Despite the increasing prevalence of IBD in non-white populations, little is known regarding racial disparities in VPD burden. Methods: Retrospectively analyzing the 2016 to 2020 National Inpatient Sample, we identified adults with IBD hospitalized for a principal diagnosis of VPD. The primary outcome investigated was hospitalization for VPD stratified by patient-reported race. Secondary outcomes were in-hospital morbidity, mortality, length of stay, and health care utilization. Multivariable regression analysis was performed to adjust for patient and hospital characteristics. Results: The search identified 554,114 hospitalizations for VPD, including 4170 hospitalizations in patients with IBD. Patients with IBD had significantly greater odds of hospitalization from herpes zoster virus (adjusted odds ratio [aOR]: 1.73) and varicella zoster virus (aOR: 2.31). Comparing white and non-white patients with IBD, significant racial disparities were noted. Non-white patients were at greater odds of hospitalization from influenza (aOR: 1.74), herpes zoster virus (aOR: 1.77), and varicella zoster virus (aOR: 1.62). In-hospital morbidity was greater in non-white patients, including greater odds of requiring intensive care unit stay (aOR: 1.18). Morbidity was elevated in African Americans, with greater odds of acute kidney injury (aOR: 1.25), venous thromboembolism (aOR: 1.17), respiratory failure (aOR: 1.16), and intensive care unit stay (aOR: 1.18). No differences were found in mortality, length of stay, and health care utilization. Conclusions: Significant racial disparities in VPD hospitalization and in-hospital morbidity were found among adults with IBD in the United States. With the increasing prevalence of IBD in non-white populations, targeted efforts are needed to improve health equity.

Abstract Background Homelessness is an important public health issue with a prevalence around 4.2% in the United States. Homelessness has been associated with lack of access to healthcare services, poor quality of care, and negative health outcomes. However, there is limited data on clinical outcomes among homeless individuals with Crohn’s disease (CD). Aims In this study, we examine inpatient outcomes including endoscopy utilization, surgical treatment, and post-operative complications among homeless patients with CD. Methods The Healthcare Utilization Project (HCUP) State Inpatient Databases from New York, Arizona, Massachusetts and Florida for 2013 and 2014 were used to identify adults ≥18 years admitted with CD identified by International Classification of Diseases, Ninth Revision codes. Homeless patients were then identified, and propensity score matched using a one-to-ten greedy nearest-neighbor approach to non-homeless patients to balance the distribution of baseline covariates. Differences in outcomes including endoscopy utilization, surgical treatment and post-operative complications were reported as odds ratios (ORs) and 95% confidence intervals (CI). Results A total of 70,457 CD hospitalizations were identified, of which 469 (0.6%) were associated with homelessness. We matched 440 homeless patients with 4,400 housed patients with CD. Homeless individuals had a higher proportion of males (p=0.002), tended to be older (p=0.035), and had more comorbidities than non-homeless individuals. There was no difference in mortality between non-homeless and homeless patients (OR 1.6, 95% CI 0.72-3.57). Endoscopy utilization was comparable between non-homeless and homeless patients with CD including gastroscopy (OR 0.71, 95% CI 0.40-1.18), colonoscopy (OR 0.80, 95% CI 0.31-1.69), and sigmoidoscopy (OR 0.37, 95% CI 0.02-1.74) [Figure 1]. Surgical treatment was also comparable, except for lower rates of bowel resection among homeless patients (OR 0.55, 95% CI: 0.29-0.93). The two groups also had similar rates of post-operative complications including pulmonary, cardiovascular, gastrointestinal, and infectious complications (Figure 1). Conclusions Homeless patients with CD have comparable endoscopy utilization and surgical treatment as non-homeless patients, except for lower bowel resection rates. Postoperative complications are also similar between the two groups. Future studies are needed to better understand the impact of homelessness on health outcomes and healthcare service utilization among patients with CD. Figure 1. Endoscopy utilization, surgical treatment, and post-operative complications among homeless and non-homeless individuals using 1:10 propensity matching Funding Agencies None