Statewide Survey of Primary Care and Subspecialty Providers on Hepatocellular Carcinoma Risk-Stratification and Surveillance Practices.

BACKGROUND: Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is associated with improved survival. Provision of HCC surveillance is low in the US, particularly in primary care settings. AIMS: To evaluate current hepatitis C virus (HCV) and HCC surveillance practices and physician attitudes regarding HCC risk-stratification among primary care and subspecialty providers. METHODS: Using the Tailored Design Method, we delivered a 34-item online survey to 7654 North Carolina-licensed internal/family medicine or gastroenterology/hepatology physicians and advanced practice providers in 2022. We included the domains of HCV treatment, cirrhosis diagnosis, HCC surveillance practices, barriers to surveillance, and interest in risk-stratification tools. We performed descriptive analyses to summarize responses. Tabulations were weighted based on sampling weights accounting for non-response and inter-specialty comparisons were made using chi-squared or t test statistics. RESULTS: After exclusions, 266 responses were included in the final sample (response rate 3.8%). Most respondents (78%) diagnosed cirrhosis using imaging and a minority used non-invasive tests that were blood-based (~ 15%) or transient elastography (31%). Compared to primary care providers, subspecialists were more likely to perform HCC surveillance every 6-months (vs annual) (98% vs 35%, p < 0.0001). Most respondents (80%) believed there were strong data to support HCC surveillance, but primary care providers did not know which liver disease patients needed surveillance. Most providers (> 70%) expressed interest in potential solutions to improve HCC risk-stratification. CONCLUSIONS: In this statewide survey, there were great knowledge gaps in HCC surveillance among PCPs and most respondents expressed interest in strategies to increase appropriate HCC surveillance.

Comparing characteristics of individuals screened for lung cancer with 2021 versus 2013 USPSTF recommendations.

We conducted a cross-sectional multi-center study to compare the demographics, clinical characteristics, and lung cancer screening (LCS) results among those eligible for LCS per 2013 vs 2021 US Preventive Services Task Force (USPSTF) recommendations. Statistical tests are two-sided, with p < .05 considered statistically significant. Among 17,702 screened individuals (85.2% 2013 Eligible, 14.8% 2021 Newly Eligible), a higher proportion of those screened per 2021 vs 2013 criteria were female (56.1% vs 48.1%, p < .0001) and non-Hispanic Black (19.3% vs 13.4%, p < .0001). The risk of developing and dying from lung cancer per 1000 was statistically significantly higher among those eligible per 2013 vs 2021 criteria. A higher proportion of LCS exams had an increased suspicion of lung cancer in the 2013 vs 2021 criteria groups. Our data suggest that, as intended, updated 2021 USPSTF recommendations are leading to a higher proportion of LCS exams among non-Hispanic Black individuals and women.

Trust In US Federal, State, And Local Public Health Agencies During COVID-19: Responses And Policy Implications.

Public health agencies' ability to protect health in the wake of COVID-19 largely depends on public trust. In February 2022 we conducted a first-of-its-kind nationally representative survey of 4,208 US adults to learn the public's reported reasons for trust in federal, state, and local public health agencies. Among respondents who expressed a "great deal" of trust, that trust was not related primarily to agencies' ability to control the spread of COVID-19 but, rather, to beliefs that those agencies made clear, science-based recommendations and provided protective resources. Scientific expertise was a more commonly reported reason for "a great deal" of trust at the federal level, whereas perceptions of hard work, compassionate policy, and direct services were emphasized more at the state and local levels. Although trust in public health agencies was not especially high, few respondents indicated that they had no trust. Lower trust was related primarily to respondents' beliefs that health recommendations were politically influenced and inconsistent. The least trusting respondents also endorsed concerns about private-sector influence and excessive restrictions and had low trust in government overall. Our findings suggest the need to support a robust federal, state, and local public health communications infrastructure; ensure agencies' authority to make science-based recommendations; and develop strategies for engaging different segments of the public.

Randomized control trial of unconditional versus conditional incentives to increase study enrollment rates in participants at increased risk of lung cancer.

INTRODUCTION: Understanding how incentives and their timing influence study enrollment rates is important to efficient study design and increasing the generalizability of findings. This 2-arm, parallel randomized trial evaluated how conditional vs. unconditional mailed incentives of a $20 gift card affected study enrollment in a sample of participants screened for lung cancer screening. METHODS: Eligible participants included Black and White adults who underwent lung cancer screening with low-dose CT and had negative screening results at two North Carolina imaging facilities in 2018. We used a stratified randomization scheme, by sex and race, to assign incentive type (conditional vs. unconditional). We used the Tailored Design Method with six points of mailed contact to engage participants. We compared study enrollment rates using chi-square tests and logistic regression analyses. RESULTS: After adjusting for sex, race, age, smoking status, participant residence, and screening site, participants who received unconditional incentives were 74% more likely to enroll than those who received conditional incentives (adjusted OR = 1.74 (95% CI: 1.01, 3.00). CONCLUSIONS: Type of incentive can play a role in increasing study enrollment, especially mailed surveys that target individuals who currently or previously smoked. Unconditional incentives may be worth the initial cost to engage study participants.

Prospective Multisite Cohort Study to Evaluate Shared Decision-Making Utilization Among Individuals Screened for Lung Cancer.

PURPOSE: The aim of this study was to determine the frequency, components of, and factors associated with shared decision-making (SDM) discussions according to electronic health record (EHR) documentation among individuals undergoing lung cancer screening (LCS). METHODS: A prospective observational cohort study was conducted of individuals undergoing LCS between February 2015 and June 2020 at four LCS centers. The primary outcome was EHR-documented SDM, defined using Medicare-designated components. A multivariable logistic regression model was used to examine predictors of EHR-documented SDM. A secondary outcome was agreement of individual's self-report of SDM and EHR-documented SDM, evaluated using Cohen's κ statistic. RESULTS: Among screened individuals, 41.9% (243 of 580) had EHR-documented SDM, and 71.1% (295 of 415) had self-reported SDM. Decision aids were used in 55.6% of EHR-documented SDM encounters (135 of 243), and 21.8% of documented SDM encounters (53 of 243) included all Medicare-designated components. SDM was documented more frequently in individuals with body mass index ≥ 25 versus <25 kg/m2 (adjusted odds ratio [aOR], 1.63; 95% confidence interval [CI], 1.05-2.52) and in currently versus formerly smoking individuals (aOR, 1.53; 95% CI, 1.02-2.32). Nonpulmonary referring clinicians were less likely to document SDM than pulmonary clinicians (internal medicine: aOR, 0.32; 95% CI, 0.18-0.53; family medicine: aOR, 0.08; 95% CI, 0.04-0.14; other specialties: aOR, 0.08; 95% CI, 0.03-0.21). In a subset of 415 individuals, there was little agreement between individual self-report of SDM and EHR-documented SDM (κ = 0.184), with variation in agreement on the basis of referring clinician specialty. CONCLUSIONS: Although EHR-documented SDM occurred in fewer than half of individuals undergoing LCS, self-reported SDM rates were higher, suggesting that SDM may be underdocumented in the EHR. In addition, EHR-documented SDM was more likely in individuals with higher body mass index and those referred for LCS by pulmonary clinicians. These findings indicate areas for improvement in the implementation and documentation of SDM.

Receipt of Recommended Follow-up Care After a Positive Lung Cancer Screening Examination.

Importance: Maximizing benefits of lung cancer screening requires timely follow-up after a positive screening test. The American College of Radiology (ACR) Lung CT Screening Reporting and Data System (Lung-RADS) recommends testing and follow-up timing based on the screening result. Objective: To determine rates of and factors associated with recommended follow-up after a positive lung cancer screening examination by Lung-RADS category. Design, Setting, and Participants: This prospective cohort study of lung cancer screening examinations performed from January 1, 2015, through July 31, 2020, with follow-up through July 31, 2021, was conducted at 5 academic and community lung cancer screening sites in North Carolina. Participants included 685 adults with a positive screening examination, Lung-RADS categories 3, 4A, 4B, or 4X. Statistical analysis was performed from December 2020 to March 2022. Exposures: Individual age, race, sex, smoking exposure, year of lung cancer screening examination, chronic obstructive pulmonary disease, body mass index, referring clinician specialty, rural or urban residence. Main Outcomes and Measures: Adherence, defined as receipt of recommended follow-up test or procedure after the positive screen per ACR Lung-RADS timeframes: 6 months for Lung-RADS 3 and 3 months for Lung-RADS 4A. For Lung-RADS 4B or 4X, adherence was defined as follow-up care within 4 weeks, as ACR Lung-RADS does not specify a timeframe. Results: Among the 685 individuals included in this study who underwent lung cancer screening with low-dose computed tomography, 416 (60.7%) were aged at least 65 years, 123 (18.0%) were Black, 562 (82.0%) were White, and 352 (51.4%) were male. Overall adherence to recommended follow-up was 42.6% (292 of 685) and varied by Lung-RADS category: Lung-RADS 3 = 30.0% (109 of 363), Lung-RADS 4A = 49.5% (96 of 194), Lung-RADS 4B or 4X = 68.0% (87 of 128). Extending the follow-up time increased adherence: Lung-RADS 3 = 68.6% (249 of 363) within 9 months, Lung-RADS 4A = 77.3% (150 of 194) within 5 months, and Lung-RADS 4B or 4X = 80.5% (103 of 128) within 62 days. For Lung-RADS 3, recommended follow-up was less likely among those currently smoking vs those who quit (adjusted odds ratio [aOR], 0.48; 95% CI, 0.29-0.78). In Lung-RADS 4A, recommended follow-up was less likely in Black individuals vs White individuals (aOR, 0.35; 95% CI, 0.15-0.86). For Lung-RADS 4B or 4X, recommended follow-up was more likely in female individuals vs male individuals (aOR, 2.82; 95% CI, 1.09-7.28) and less likely in those currently smoking vs those who quit (aOR, 0.31; 95% CI, 0.12-0.80). Conclusions and Relevance: In this cohort study, adherence to recommended follow-up after a positive screening examination was low but improved among nodules with a higher suspicion of cancer and after extending the follow-up timeline. However, the association of extending the follow-up time of screen-detected nodules with outcomes at the population level, outside of a clinical trial, is unknown. These findings suggest that studies to understand why recommended follow-up is lower in Black individuals, male individuals, and individuals currently smoking are needed to develop strategies to improve adherence.

Lung Cancer Screening in Individuals With and Without Lung-Related Comorbidities.

Importance: Comorbidities characterize the underlying health status of individuals. In the context of lung cancer screening (LCS), lung-related comorbidities may influence the observed benefits and harms. Objective: To compare the characteristics of individuals undergoing LCS, the LCS examination result, the cancer detection rate (CDR), and the false-positive rate (FPR) in those with and without lung-related comorbidities. Design, Setting, and Participants: A prospective cohort study was conducted in 5 academic and community screening sites across North Carolina from January 1, 2014, to November 7, 2020. Participants included 611 individuals screened for lung cancer who completed a 1-page health history questionnaire. Exposures: Presence of at least 1 self-reported lung-related comorbidity, including chronic obstructive pulmonary disease, chronic bronchitis, emphysema, asthma, bronchiectasis, pulmonary fibrosis, silicosis, asbestosis, sarcoidosis, and tuberculosis. Main Outcomes and Measures: The LCS examination result was determined from the radiologist's Lung Imaging Reporting and Data System assessment (negative, 1 or 2; positive, 3 or 4). The age-adjusted CDR and FPR were calculated per 100 LCS examinations, using binary logistic regression. Results: Among the 611 individuals screened for lung cancer (308 men [50.4%]; mean [SD] age, 64 [6.2] years), 335 (54.8%) had at least 1 lung-related comorbidity. Individuals with vs without lung-related comorbidities were more likely to be female than male (180 of 335 [53.7%] vs 123 of 276 [44.6%]; P = .02), White vs non-White race (275 of 326 [84.4%] vs 193 of 272 [71.0%]; P < .001), and have high school or less education vs greater than a high school education (108 of 231 [46.7%] vs 64 of 208 [30.8%]; P = .001). There were no significant differences in the proportion of positive LCS examinations in those with vs without a lung-related comorbidity at baseline (37 [16.0%] vs 22 [11.1%]; P = .14) or subsequent (40 [12.3%] vs 23 [10.6%]; P = .54) LCS examination. Comparing individuals with vs without lung-related comorbidities, there was no statistically significant difference in the CDR (1.6 vs 1.9 per 100; P = .73) or FPR (13.0 vs 9.3 per 100; P = .16). Of the 17 individuals with lung cancer, 13 patients (76.5%) were diagnosed with stage I lung cancer. Conclusions and Relevance: The findings of this study suggest that individuals with self-reported lung-related comorbidities undergoing LCS were more likely to be female, of White race, and have less education than those without lung-related comorbidity. Although no statistically significant differences in the proportion of positive examinations, CDR, or FPR by self-reported lung comorbidities were noted, additional studies with larger numbers of individuals undergoing screening are needed to understand LCS outcomes in those with lung-related comorbidities.

Getting Critical Information During the COVID-19 Pandemic: Experiences of Spanish and Chinese Speakers With Limited English Proficiency.

People with limited English proficiency in the United States have suffered disproportionate negative health outcomes during the COVID-19 pandemic. Effective communications are critical tools in addressing inequities insofar as they can motivate adoption of protective behaviors and reduce incidence of disease; however, little is known about experiences of communities with limited English proficiency receiving relevant information during COVID-19 or other outbreaks. To address this gap and provide inputs for communication strategies, we completed a study based on 2 novel and nationally representative surveys conducted between June and August 2020 among Spanish and Chinese speakers with limited English proficiency (n = 764 and n = 355, respectively). Results first showed that Spanish and Chinese speakers did not consistently receive information about protective behaviors from key public health and government institutions early in the pandemic. Second, for such information, Spanish and Chinese speakers used a diverse set of information resources that included family and friends, social media, and traditional media from both inside and outside the United States. Third, Spanish and Chinese speakers faced challenges getting COVID-19 information, including receiving media messages that felt discriminatory toward Latinx or Chinese people. Together, these findings suggest gaps in effectively reaching Spanish and Chinese speakers. Data highlight the important role of bilingual materials to support sharing of information between Spanish or Chinese speakers and English speakers within their social networks, and the need for digital news content for traditional and social media. Finally, efforts are needed to address discriminatory messaging in media and to actively counter it in public health communications.

Niemann-Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking.

Niemann-Pick C1 (NPC1) is a key participant in cellular cholesterol trafficking. Loss of NPC1 function leads to defective suppression of SREBP-dependent gene expression and failure to appropriately activate liver X receptor-mediated (LXR-mediated) pathways, ultimately resulting in intracellular cholesterol accumulation. To determine whether NPC1 contributes to regulation of macrophage sterol homeostasis in vivo, we examined the effect of NPC1 deletion in BM-derived cells on atherosclerotic lesion development in the Ldlr-/- mouse model of atherosclerosis. High-fat diet-fed chimeric Npc1-/- mice reconstituted with Ldlr-/-Npc1-/- macrophages exhibited accelerated atherosclerosis despite lower serum cholesterol compared with mice reconstituted with wild-type macrophages. The discordance between the low serum lipoprotein levels and the presence of aortic atherosclerosis suggested that intrinsic alterations in macrophage sterol metabolism in the chimeric Npc1-/- mice played a greater role in atherosclerotic lesion formation than did serum lipoprotein levels. Macrophages from chimeric Npc1-/- mice showed decreased synthesis of 27-hydroxycholesterol (27-HC), an endogenous LXR ligand; decreased expression of LXR-regulated cholesterol transporters; and impaired cholesterol efflux. Lower 27-HC levels were associated with elevated cholesterol oxidation products in macrophages and plasma of chimeric Npc1-/- mice and with increased oxidative stress. Our results demonstrate that NPC1 serves an atheroprotective role in mice through regulation of LXR-dependent cholesterol efflux and mitigation of cholesterol-induced oxidative stress in macrophages.

Molecular Biomarker and Programmed Death-Ligand 1 Expression Testing in Patients With Advanced Stage Non-small Cell Lung Cancer Across North Carolina Community Hospitals.

BACKGROUND: Precision medicine in advanced non-small cell lung cancer (NSCLC) requires molecular biomarker testing in patients with nonsquamous and select patients with squamous histologies, and programmed death-ligand 1 (PD-L1) testing in both. RESEARCH QUESTION: What are rates of molecular and PD-L1 biomarker testing in patients with advanced NSCLC in community practices, and do rates vary by sociodemographic factors? What is the prevalence of molecular biomarker mutations and PD-L1 expression levels? STUDY DESIGN AND METHODS: From 389 stage IV NSCLC pathology reports obtained through the University of North Carolina Lineberger Comprehensive Cancer Center's Rapid Case Ascertainment Program from 38 community hospitals across North Carolina, we abstracted demographics, histology, molecular biomarker testing and results, and PD-L1 testing and expression. We geocoded patient and hospital addresses to determine travel time, distance to care, and census block level contextual variables. We compared molecular biomarker and PD-L1 testing rates, the prevalence of molecular biomarkers, and PD-L1 expression levels by race and sex, using χ2 tests. We determined predictors of testing, using multivariable logistic regression and report adjusted ORs and 95%CI. RESULTS: Among patients with nonsquamous NSCLC, 64.4% were tested for molecular biomarkers, and among all NSCLC patients 53.2% were tested for PD-L1 expression. Differences in biomarker testing rates by sociodemographic factors were not statistically significant in univariate or adjusted analyses. Adjusted analyses showed that patients living in areas with higher household internet access were more likely to undergo PD-L1 testing (adjusted OR = 1.66, 95% CI, 1.02-2.71). Sociodemographic differences in molecular biomarker prevalence and PD-L1 expression levels were not statistically significant, except for human epidermal growth factor receptor 2 (HER2) mutations, which occurred in 16.7% of males vs 0% in females, P = .05. INTERPRETATION: Biomarker testing remains underused in NSCLC. Future work should include larger populations and evaluate hospital-specific testing protocols to identify and address barriers to guideline-recommended testing.

Patterns and Factors Associated With Adherence to Lung Cancer Screening in Diverse Practice Settings.

Importance: For lung cancer screening to confer mortality benefit, adherence to annual screening with low-dose computed tomography scans is essential. Although the National Lung Screening Trial had an adherence rate of 95%, current data are limited on screening adherence across diverse practice settings in the United States. Objective: To evaluate patterns and factors associated with adherence to annual screening for lung cancer after negative results of a baseline examination, particularly in centralized vs decentralized screening programs. Design, Setting, and Participants: This observational cohort study was conducted at 5 academic and community-based sites in North Carolina and California among 2283 individuals screened for lung cancer between July 1, 2014, and March 31, 2018, who met US Preventive Services Task Force eligibility criteria, had negative results of a baseline screening examination (American College of Radiology Lung Imaging Reporting and Data System category 1 or 2), and were eligible to return for a screening examination in 12 months. Exposures: To identify factors associated with adherence, the association of adherence with selected baseline demographic and clinical characteristics, including type of screening program, was estimated using multivariable logistic regression. Screening program type was classified as centralized if individuals were referred through a lung cancer screening clinic or program and as decentralized if individuals had a direct clinician referral for the baseline low-dose computed tomography scan. Main Outcomes and Measures: Adherence to annual lung cancer screening, defined as a second low-dose computed tomography scan within 11 to 15 months after baseline screening. Results: Among the 2283 eligible individuals (1294 men [56.7%]; mean [SD] age, 64.9 [5.8] years; 1160 [50.8%] aged ≥65 years) who had negative screening results at baseline, overall adherence was 40.2% (n = 917), with higher adherence among those who underwent screening through centralized (46.0% [478 of 1039]) vs decentralized (35.3% [439 of 1244]) programs. The independent factor most strongly associated with adherence was type of screening program, with a 2.8-fold increased likelihood of adherence associated with centralized screening (adjusted odds ratio [aOR], 2.78; 95% CI, 1.99-3.88). Another associated factor was age (65-69 vs 55-59 years: aOR, 1.38; 95% CI, 1.07-1.77; 70-74 vs 55-59 years: aOR, 1.47; 95% CI, 1.10-1.96). Conclusions and Relevance: After negative results of a baseline examination, adherence to annual lung cancer screening was suboptimal, although adherence was higher among individuals who were screened through a centralized program. These results support the value of centralized screening programs and the need to further implement strategies that improve adherence to annual screening for lung cancer.

Cardiovascular Risk in the Lung Cancer Screening Population: A Multicenter Study Evaluating the Association Between Coronary Artery Calcification and Preventive Statin Prescription.

OBJECTIVE: Coronary artery calcification (CAC) is a marker of atherosclerotic cardiovascular disease (ASCVD), the leading cause of death in individuals receiving lung cancer screening (LCS) with low-dose CT. Our purpose was to determine the proportion of the LCS population eligible for primary ASCVD preventive statin therapy by American College of Cardiology/American Heart Association guidelines, assess statin prescription rates among statin-eligible individuals, and determine associations of CAC on downstream statin prescribing within 90 days of LCS. METHODS: Individuals receiving LCS between January 1, 2016, and December 31, 2018, across three centers were retrospectively enrolled. Statin eligibility in individuals without pre-existing ASCVD was determined by 2013 American College of Cardiology/American Heart Association guidelines: (1) low-density lipoprotein ≥190 mg/dL, (2) diabetes, or (3) ASCVD risk score ≥7.5%. CAC presence and severity (mild, moderate, heavy) were extracted from LCS reports. Variation in statin prescription rates and associations between CAC and statin prescription were determined using mixed-effects logistic regression. RESULTS: Of 5,495 individuals receiving LCS, 31.4% (1,724 of 5,495) had pre-existing ASCVD. Of the remaining 3,771 individuals, 73.6% were statin eligible (2,777 of 3,771). However, most lacked statin prescription (60.5%, 1,681 of 2,777). CAC was associated with downstream statin prescribing (adjusted odds ratio = 2.60, 95% confidence interval: 1.12-6.02), with a higher likelihood of statin prescribing with increasing CAC severity (adjusted odds ratio = 2.21, 95% confidence interval: 1.35-3.60). CONCLUSION: Although most of the LCS population is eligible for guideline-directed statin therapy, statins are underprescribed in this group. Radiologist reporting of CAC at LCS reflects a potential opportunity to raise awareness of ASCVD risk and improve preventive statin prescribing.

Communication of Positive Lung Cancer Screening Findings and Receipt of Recommended Follow-up Care.

This cohort study evaluates associations of communication methods and content of positive lung cancer screening findings with receipt of recommended follow-up care.