Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial.

BACKGROUND: Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis. METHODS: Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the proportion of time covered (PTC) by screening. All patients were included in intention-to-screen analyses. RESULTS: All 2872 participants (median age 61.3 years; 32.3% women) were included in intention-to-screen analyses. Screening process completion was observed in 6.6% (95% CI: 5.3% to 7.9%) of patients randomised to outreach and 3.3% (95% CI: 2.4% to 4.3%) of those randomised to usual care (OR 2.05, 95% CI: 1.44 to 2.92). The intervention increased HCC screening process completion across most subgroups including age, sex, race and ethnicity, Child-Turcotte-Pugh class and health system. PTC was also significantly higher in the outreach arm than usual care (mean 37.5% vs 28.2%; RR 1.33, 95% CI: 1.31 to 1.35). Despite screening underuse, most HCC in both arms were detected at an early stage. CONCLUSION: Mailed outreach plus navigation significantly increased HCC screening process completion versus usual care in patients with cirrhosis, with a consistent effect across most examined subgroups. However, screening completion remained suboptimal in both arms, underscoring a need for more intensive interventions. TRIAL REGISTRATION NUMBER: NCT02582918.

Financial Burden of Hepatocellular Carcinoma Screening in Patients With Cirrhosis.

BACKGROUND: The overall value of hepatocellular carcinoma screening is defined by the balance of benefits and harms. Studies have only reported physical harms with none describing financial harms. METHODS: We conducted a multicenter pragmatic randomized clinical trial of hepatocellular carcinoma screening outreach among 2872 patients with cirrhosis from March 2018 to April 2021. Patients with positive or indeterminate results and matched patients with negative results completed surveys at baseline and at follow-up measuring financial harms via Cancer Self-Administered Questionnaire and financial burden via Comprehensive Score for Financial Toxicity Functional Assessment of Chronic Illness Therapy. Univariable and multivariable longitudinal regression analyses were performed to compare changes in financial harms across groups: true positive, true negative, false positive, and indeterminate. Semistructured interviews were conducted in a subset of patients, sampled by center and test result. RESULTS: Of 311 patients who completed at least 1 follow-up survey (75% response rate), 37 had true positive, 133 true negative, 64 false positive, and 77 indeterminate results. Financial harms increased in true positive and false positive patients with no significant changes noted among those with true negative or indeterminate results. At follow-up, 21.8% of patients reported moderate-severe financial burden, which was not significantly associated with test results. Semistructured interviews revealed variation in the frequency and severity of financial harms based on test results, with increased harm in those with false positive results. CONCLUSIONS: Financial harms of hepatocellular carcinoma screening vary by test result and can pose a barrier that must be considered when determining the optimal screening program.

Hepatocellular carcinoma surveillance may be associated with potential psychological harms in patients with cirrhosis.

BACKGROUND AND AIMS: The value of HCC surveillance is determined by the balance between benefits and harms; however, no studies have enumerated psychological harms. APPROACH AND RESULTS: We fielded surveys measuring psychological harms to patients with cirrhosis in a multicenter randomized trial of HCC surveillance outreach. All patients with positive or indeterminate surveillance results and matched patients with negative results were invited to complete surveys measuring (1) depression through the Patient Health Questionnaire-ninth version, (2) anxiety through State-Trait Anxiety Inventory, (3) HCC-specific worry through Psychological Consequences Questionnaire, and (4) decisional regret. Patients were classified into 4 groups: true positive (TP), false positive (FP), indeterminate, and true negative (TN). Multivariable longitudinal regression analysis using the generalized estimating equation method was performed to compare the means of measures across groups. We conducted 89 semistructured interviews in a subset of patients stratified by health system and test results. Of 2872 patients in the trial, 311 completed 1+ follow-up survey (63 FP, 77 indeterminate, 38 TP, and 133 TN). Moderate depression decreased in TN patients, increased in TP, and had intermittent but mild increases in those with FP and indeterminate results. High anxiety temporarily increased in patients with TP results but resolved over time and was stable in those with FP and indeterminate results. Decisional regret was low and did not differ across groups. In semistructured interviews, patients reported apprehension, anxiety, emotional distress, and coping related to HCC surveillance. CONCLUSIONS: Psychological harms of HCC surveillance appear mild but differ by test result. Future research should determine the impact of psychological harms on the value of HCC surveillance programs.

Bilingual problem size effect: an ERP study of multiplication verification and production in two languages.

The problem size effect (PSE) is defined by better performance solving small problems (e.g., 2x4) than large problems (e.g., 8x9). For monolinguals, the PSE is larger when problems are presented in unfamiliar formats (e.g., written words), reflecting increased processing difficulty. Bilinguals are typically faster and more accurate at retrieving multiplication facts in the language of learning (LA+) than in their other language (LA-). We hypothesized that the less familiar arithmetic language (i.e., LA-) would elicit larger PSEs than LA+. Here, fluent Spanish-English bilingual adults verified spoken multiplication problems presented in LA+ and LA- while event-related potentials (ERPs) were recorded (Experiment 1A). To further promote language differences, we increased task difficulty by presenting problems at a faster pace (Experiment 1B) and requiring bilinguals to verbally produce solutions (Experiment 2). Language differences in performance were only observed for Experiment 2, where solutions were produced more slowly in LA- than LA+. In the ERPs, a PSE was driven by larger P300s for small than large solutions. A language effect was only observed under time pressure where LA- elicited a PSE at the 2nd operand. Additionally, the PSE was smaller for LA- at the solution. This suggests that categorizing multiplication facts is more effortful in LA-. In sum, very subtle language differences arise in fluent bilinguals when problems are more difficult, such as larger problems presented under time pressure in a weaker language. Critically, the effect of LA+ is at the level of response production and not access to the facts from memory.

Unmet Needs and Receipt of Supportive Care Services in Head and Neck Cancer Patients Prior to Oncologic Treatment: A Prospective, Cross-Sectional Pilot Study.

OBJECTIVE: To characterize the supportive care (SC) needs and receipt of SC services among head and neck cancer (HNC) patients prior to oncologic treatment and to explore the influence of social determinants of health on these outcomes. MATERIALS AND METHODS: Newly diagnosed HNC patients were surveyed via telephone prior to oncologic treatment between 10/2019 and 1/2021 using a prospective, cross-sectional, bi-institutional, pilot study design. The primary study outcome was unmet SC needs (Supportive Care Needs Survey-Short Form34 [SCNS-SF34]). Hospital type (university- vs county safety-net) was explored as an exposure. Descriptive statistics were performed using STATA16 (College Station, TX). RESULTS: Among 158 potentially eligible patients, 129 were successfully contacted, 78 met the study criteria, and 50 completed the survey. The mean age was 61, 58% exhibited clinical stage III-IV disease, and 68% and 32% were treated at the university and county safety-net hospital, respectively. Patients were surveyed a median of 20 days after their first oncology visit and 17 days prior to initiation of oncology treatment. They had a median of 24 total needs (11 were met and 13 were unmet) and preferred to see a median of 4 SC services but received care from none. County safety-net patients had comparatively more unmet needs than university patients (14.5 vs 11.5, P = .04). CONCLUSION: Pretreatment HNC patients at a bi-institutional academic medical center report a high number of unmet SC needs with corollary poor receipt of available SC services. Novel interventions to address this significant gap in care are needed.

Reevaluating the Language of Learning Advantage in Bilingual Arithmetic: An ERP Study on Spoken Multiplication Verification.

Many studies of bilingual arithmetic report better performance when verifying arithmetic facts in the language of learning (LA+) over the other language (LA-). This could be due to language-specific memory representations, processes established during learning, or to language and task factors not related to math. The current study builds on a small number of event-related potential (ERP) studies to test this question while controlling language proficiency and eliminating potential task confounds. Adults proficient in two languages verified single-digit multiplications presented as spoken number words in LA+ and LA-, separately. ERPs and correctness judgments were measured from solution onset. Equivalent P300 effects, with larger positive amplitude for correct than incorrect solutions, were observed in both languages (Experiment 1A), even when stimuli presentation rate was shortened to increase difficulty (Experiment 1B). This effect paralleled the arithmetic correctness effect for trials presented as all digits (e.g., 2 4 8 versus 2 4 10), reflecting efficient categorization of the solutions, and was distinct from an N400 generated in a word-picture matching task, reflecting meaning processing (Experiment 2). The findings reveal that the language effects on arithmetic are likely driven by language and task factors rather than differences in memory representation in each language.

Multicenter Randomized Clinical Trial of a Mailed Outreach Strategy for Hepatocellular Carcinoma Surveillance.

BACKGROUND: The effectiveness of hepatocellular carcinoma (HCC) surveillance is mitigated by underuse in clinical practice, highlighting a need for interventions. We evaluated the effectiveness of mailed HCC surveillance outreach to promote HCC surveillance in patients with cirrhosis. METHODS: We conducted a multicenter pragmatic randomized clinical trial comparing mailed outreach for surveillance ultrasound (n = 1436) and usual care with visit-based surveillance (n = 1436) among patients with cirrhosis at 3 health systems (tertiary care referral center, safety net health system, and Veterans Affairs medical center) from April 2018 to December 2019. The primary outcome of this interim analysis was guideline concordant semiannual HCC surveillance over a 12-month period and a secondary outcome was proportion time covered by surveillance. All patients were included in intention-to-screen analyses. RESULTS: Compared with usual care, the outreach arm had significantly higher semiannual surveillance (35.1% vs 21.9%) and lower no-surveillance (29.8% vs 43.5%) (P < .001), resulting in significant increases in the proportion of time covered by surveillance (41.3% vs 31.0%; P < .001). The intervention increased HCC surveillance across most predefined subgroups; however, there were site-level differences in the intervention effect, with significant increases in semiannual surveillance at the Veterans Affairs and safety net health systems but not at the tertiary care referral center. CONCLUSIONS: Mailed outreach significantly increased semiannual HCC surveillance vs usual care in patients with cirrhosis, with a consistent intervention effect across most examined subgroups. Continued follow-up is ongoing to determine if these increases in surveillance translate into improved downstream outcomes includi.ng early HCC detection and curative treatment receipt. (ClinicalTrials.gov, Numbers: NCT02582918 and NCT03756051).

Differential effect of sleep deprivation on place cell representations, sleep architecture, and memory in young and old mice.

Poor sleep quality is associated with age-related cognitive decline, and whether reversal of these alterations is possible is unknown. In this study, we report how sleep deprivation (SD) affects hippocampal representations, sleep patterns, and memory in young and old mice. After training in a hippocampus-dependent object-place recognition (OPR) task, control animals sleep ad libitum, although experimental animals undergo 5 h of SD, followed by recovery sleep. Young controls and old SD mice exhibit successful OPR memory, whereas young SD and old control mice are impaired. Successful performance is associated with two cellular phenotypes: (1) "context" cells, which remain stable throughout training and testing, and (2) "object configuration" cells, which remap when objects are introduced to the context and during testing. Additionally, effective memory correlates with spindle counts during non-rapid eye movement (NREM)/rapid eye movement (REM) sigma transitions. These results suggest SD may serve to ameliorate age-related memory deficits and allow hippocampal representations to adapt to changing environments.

Bilingual children access multiplication facts from semantic memory equivalently across languages: Evidence from the N400.

Typically, bilinguals learn multiplication facts in only one instruction language. Consequently, these facts may be represented and/or accessed as language-specific memories, requiring a qualitatively different retrieval process in their other language. Indeed, behavioral studies reveal that bilinguals verify arithmetic facts faster and better in the language of learning. Here, event-related potentials (ERPs) were used as a window into the neurocognitive processes underlying this language bias in children. ERPs were recorded while bilingual children verified the correctness of multiplication solutions. Operands were presented as spoken number words in Spanish and English, separately. Although a language bias was revealed in behavior, both languages elicited the same ERP correctness effect, an N400, reflecting similar cognitive processes in both languages. This suggests that the source of the behavioral difference is not at the level of semantic access. Our findings highlight the flexibility of the bilingual brain, especially when both languages are learned early.

When 2 × 4 is meaningful: the N400 and P300 reveal operand format effects in multiplication verification.

Arithmetic problems share many surface-level features with typical sentences. They assert information about the world, and readers can evaluate this information for sensibility by consulting their memories as the statement unfolds. When people encounter the solution to the problem 3 × 4, the brain elicits a robust ERP effect as a function of answer expectancy (12 being the expected completion; 15 being unexpected). Initially, this was labeled an N400 effect, implying that semantic memory had been accessed. Subsequent work suggested instead that the effect was driven by a target P300 to the correct solutions. The current study manipulates operand format to differentially promote access to language-based semantic representations of arithmetic. Operands were presented either as spoken number words or as sequential Arabic numerals. The critical solution was always an Arabic numeral. In Experiment 1, the correctness of solutions preceded by spoken operands modulated N400 amplitude, whereas solutions preceded by Arabic numerals elicited a P300 for correct problems. In Experiment 2, using only spoken operands, the delay between the second operand and the Arabic numeral solution was manipulated to determine if additional processing time would result in a P300. With a longer delay, an earlier N400 and no distinct P300 were observed. In brief, highly familiar digit operands promoted target detection, whereas spoken numbers promoted semantic level processing-even when solution format itself was held constant. This provides evidence that the brain can process arithmetic fact information at different levels of representational meaningfulness as a function of symbolic format.