Over 20% of patients with cirrhosis are nonadherent with hepatocellular carcinoma (HCC) surveillance recommendations; however, few studies have evaluated the impact of patient-level factors on surveillance receipt. We characterized the association between HCC surveillance receipt and patient knowledge, attitudes, and perceived barriers in a racially diverse and socioeconomically disadvantaged cohort of patients with cirrhosis. Patients with cirrhosis followed at a large urban hospital were invited to complete a survey about HCC surveillance between August 2014 and December 2015. Multivariable logistic regression was performed to identify factors associated with HCC surveillance receipt during the 12-month period preceding and 6-month period after survey administration. We achieved a response rate of 71.8% (n = 541 of 753). Patients demonstrated high levels of HCC-related knowledge (summary score, 77.7%); however, 48.6% believed that eating a healthy diet precluded the need for HCC surveillance, and 34.0% believed that HCC surveillance was not necessary if they had a normal physical exam and/or lacked clinical symptoms. Patients expressed worry about developing and dying from HCC, but nearly half (49.9%) of patients reported barriers to receiving HCC surveillance, including difficulty with the scheduling process (30.5%), costs of surveillance testing (25.3%), and transportation difficulties (17.3%). HCC surveillance receipt was significantly higher in patients who knew cirrhosis is a risk factor for developing HCC (odds ratio [OR], 3.09; 95% confidence ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO: Amit G. Singal, M.D., M.S., Division of Digestive and Liver Diseases, UT Southwestern Medical Center, 5959 Harry Hines Boulevard, POB 1, Suite 420, amit.singal@utsouthwestern.edu,. * These authors contributed equally to this work and are co-first authors.Potential conflict of interest: Dr. Singal consults for and is on the speakers' bureau for Bayer. Dr. Yopp is on the speakers' bureau for Bayer and received grants from Novartis and Peregrine.Author names in bold designate shared co-first Although provider recommendation is reported to be a strong predictor for HCC surveillance, (9) patient-level factors may also play an important role in surveillance underuse. In prospective cohort studies, nearly 1 in 5 patients were nonadherent with provider recommendations for HCC surveillance. (10,11) The cancer-screening literature has applied theoretical models of behavior change and demonstrated that patients' poor knowledge, negative attitudes, or perceived barriers to cancer screening may be associated with lower screening rates. (12,13) However, most studies evaluating HCC surveillance correlates have primarily focused on patient sociodemographic and clinical characteristics. (7,14) The effect of theory-based, patient-reported psychosocial factors on HCC surveillance completion has not been quantified. A better understanding of patient knowledge, attitudes, and barriers, particularly among low-income minorities, i...

Background Prior studies assessing quality of life (QOL) in patients with hepatocellular carcinoma (HCC) primarily included patients with preserved liver function and/or early HCC, leading to overestimation of QOL. Our study's aim was to evaluate the association of QOL with survival among a cohort of cirrhotic patients with HCC that was diverse with respect to liver function and tumor stage. Methods We conducted a prospective cohort study among cirrhotic patients with HCC from a large urban safety-net hospital between April 2011 and September 2013. Patients completed two self-administered surveys, the EORTC QLQ-C30, and QLQ-HCC18, prior to treatment. We used generalized linear models to identify correlates of QOL. Survival curves were generated using Kaplan–Meier analysis and compared using log rank test to determine whether QOL is associated with survival. Results A total of 130 treatment-naïve patients completed both surveys. Patients reported high cognitive and social function (median scores 67) but poor global QOL (median score 50) and poor role function (median score 50). QOL was associated with cirrhosis-related (p = 0.02) and tumor-related (p = 0.02) components of Barcelona Clinic Liver Cancer (BCLC) tumor stage. QOL was associated with survival on univariate analysis (HR 0.37, 95 % CI 0.16–0.85) but became nonsignificant (HR 0.82, 95 % CI 0.37–1.80) after adjusting for BCLC stage and treatment. Role functioning was significantly associated with survival (HR 0.40, 95 % CI 0.20–0.81), after adjusting for Caucasian race (HR 0.31, 95 % CI 0.16–0.59), BCLC stage (HR 1.51, 95 % CI 0.21– 1.89), and treatment (HR 0.57, 95 % CI 0.33–0.97). Conclusions Role function has prognostic significance and is important to assess in patients with HCC.

BACKGROUND Circadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness. METHODS We retrospectively analyzed a large Israeli cohort with timestamped COVID-19 vaccinations ( n = 1,515,754 patients over 12 years old, 99.2% receiving BNT162b2). Endpoints included COVID-19 breakthrough infection and COVID-19–associated emergency department visits and hospitalizations. Our main comparison was among patients vaccinated during morning (800–1159 hours), afternoon (1200–1559 hours), or evening hours (1600–1959 hours). We employed Cox regression to adjust for differences in age, sex, and comorbidities. RESULTS Breakthrough infections differed based on vaccination time, with lowest the rates associated with late morning to early afternoon and highest rates associated with evening vaccination. Vaccination timing remained significant after adjustment for patient age, sex, and comorbidities. Results were consistent in patients who received the basic 2-dose series and who received booster doses. The relationship between COVID-19 immunization time and breakthrough infections was sinusoidal, consistent with a biological rhythm that modifies vaccine effectiveness by 8.6%–25%. The benefits of daytime vaccination were concentrated in younger (<20 years old) and older patients (>50 years old). COVID-19–related hospitalizations varied significantly with the timing of the second booster dose, an intervention reserved for older and immunosuppressed patients (HR = 0.64, morning vs. evening; 95% CI, 0.43–0.97; P = 0.038). CONCLUSION We report a significant association between the time of COVID-19 vaccination and its effectiveness. This has implications for mass vaccination programs. FUNDING NIH.

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Importance Circadian rhythms affect fundamental immune processes, but how this translates to clinical outcomes like real-world vaccine effectiveness is unclear. Objective To examine associations between Coronavirus Infectious Disease 2019 (COVID-19) vaccination timing and effectiveness. Design, Setting, and Participants Retrospective cohort study of database records from Maccabi Healthcare Services (MHS), a major Israeli Health Maintenance Organization (HMO). We included all individuals over 12 with at least one timestamped vaccine dose and no documented COVID-19 infection prior to completing the initial 2-dose immunization series (n=1,515,754, 99.2% receiving BNT162b2). Database records spanned December 19, 2020, to April 25, 2022, encompassing two spikes in COVID infection dominated by the delta (B.1.617.2) and omicron (B.1.1.529) SARS-CoV-2 variants. Main Outcomes and Measures Outcomes included COVID-19 breakthrough infection and COVID-19 associated emergency department (ED) visits. Our main comparison was between patients vaccinated exclusively during morning hours (8:00-11:59), afternoon (12:00-15:59), or evening hours (16:00-19:59). We employed Cox multivariate regression to adjust for differences in age, sex, and co-morbidities. Results. Breakthrough infections differed based on vaccination time, with lowest rates associated with late morning to early afternoon, and highest rates with evening vaccination. Vaccination timing remained significant after adjustment for patient age, sex, and co-morbidities (HR=0.88 afternoon vs. evening, [95% CI 0.87-0.90]). Results were consistent in patients who received the basic two-dose vaccine series and who received booster doses. The association between COVID immunization time and infection risk followed a sinusoidal pattern, consistent with a biological rhythm in vaccine effectiveness that modifies clinical effectiveness by 8.6-25% depending on the vaccine dose (initial vaccine series, first booster, or second booster). The benefits of daytime vaccination were concentrated in younger and elderly patients. In contrast to breakthrough infections, COVID-19 related ED visits correlated with age and medical comorbidities but not with time of vaccination. Conclusions and Relevance We report a significant association between the time of COVID-19 vaccination and its clinical effectiveness in terms of breakthrough infection. These data have implications for mass vaccination programs.