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To evaluate recovery of platelet count after transjugular intrahepatic portosystemic shunt (TIPS) creation and patient factors predicting platelet recovery after TIPS creation. Adults with cirrhosis who underwent TIPS creation at 9 U.S. hospitals from 2010 to 2015 were included in this retrospective analysis. Change in platelets from before TIPS to 4 months after TIPS creation was characterized. Logistic regression was used to assess factors associated with top quartile percentage platelet increase after TIPS. Subgroup analyses were performed among patients with a pre-TIPS platelet count of ≤50 ×109/L. A total of 601 patients were included. The median absolute change in platelets was 1 × 109/L (−26 × 109/L to 25 × 109/L). Patients with top quartile percent platelet increase experienced ≥32% platelet increase. In multivariable analysis, pre-TIPS platelet counts (odds ratio [OR], 0.97 per 109/L; 95% CI, 0.97–0.98), age (OR, 1.24 per 5 years; 95% CI, 1.10–1.39), and pre-TIPS model for end-stage liver disease (MELD) scores (OR, 1.06 per point; 95% CI, 1.02–1.09) were associated with top quartile (≥32%) platelet increase. Ninety-four (16%) patients had a platelet count of ≤50 × 109/L before TIPS. The median absolute platelet change was 14 × 109/L (2 × 109/L to 34 × 109/L). Fifty-four percent of patients in this subgroup were in the top quartile for platelet increase. In multivariable logistic regression, age (OR, 1.50 per 5 years; 95% CI, 1.11–2.02) was the only factor associated with top quartile platelet increase in this subgroup. TIPS creation did not result in significant platelet increase, except among patients with a platelet count of ≤50 × 109/L before TIPS. Lower pre-TIPS platelet counts, older age, and higher pre-TIPS MELD scores were associated with top quartile (≥32%) platelet increase in the entire cohort, whereas only older age was associated with this outcome in the patient subset with a pre-TIPS platelet count of ≤50 × 109/L. [Display omitted] [ABSTRACT FROM AUTHOR]

There are well-described racial and ethnic disparities in the burden of chronic liver diseases. Hispanic persons are at highest risk for developing nonalcoholic fatty liver disease, the fastest growing cause of liver disease. Hepatitis B disproportionately affects persons of Asian or African descent. The highest rates of hepatitis C occur in American Indian and Alaskan Native populations. In addition to disparities in disease burden, there are also marked racial and ethnic disparities in access to treatments, including liver transplantation. Disparities also exist by gender and geography, especially in alcohol-related liver disease. To achieve health equity, we must address the root causes that drive these inequities. Understanding the role that social determinants of health play in the disparate health outcomes that are currently observed is critically important. We must forge and/or strengthen collaborations between patients, community members, other key stakeholders, health care providers, health care institutions, professional societies, and legislative bodies. Herein, we provide a high-level review of current disparities in chronic liver disease and describe actionable strategies that have potential to bridge gaps, improve quality, and promote equity in liver care. [ABSTRACT FROM AUTHOR]

Shorter duration therapy for hepatitis C virus (HCV) infection might reduce treatment costs and increase the number of patients treated and cured. We determined factors associated with treatment response after an 8-week sofosbuvir-based therapy and developed a simple model to predict an individual's likelihood of treatment success. Among 2907 patients who received ledipasvir/sofosbuvir for 8 weeks, we determined failure rates by demographic and clinical characteristics, and IFNL4 -∆G/TT genotype. We estimated the average IFNL4 genotype-related treatment failure rate in major ancestry groups by applying our IFNL4 genotype results to genotype distributions from reference populations. We created a treatment response model based on three personal characteristics. Overall, 4.4% of the patients failed treatment. We observed significantly lower failure rates for persons <50 years (1.6%), females (2.6%), those carrying the IFNL4 -TT/TT genotype (1.8%), those with HCV RNA <5.8 log 10 copies/mL (2.0%) or HCV genotype-1B infection (2.6%). In a model based on ancestry, age and sex, the predicted probability of treatment failure ranged from 0.5% among females of East Asian ancestry <50 years of age to 8.5% among males of African ancestry age ≥65 years. Applying this algorithm at the point-of-care might facilitate HCV elimination, especially in low- and middle-income countries. [Display omitted] • Shorter therapy for HCV could increase the number of patients treated and cured. • We examined response to 8 weeks of ledipasvir/sofosbuvir in a large cohort. • Predictive factors included IFNL4 genotype, which varies markedly by ancestry. • A model based on ancestry, age and sex predicted treatment response. • This model might enhance efforts to eliminate hepatitis C virus. [ABSTRACT FROM AUTHOR]

Guidelines recommend hospitalization for severe immune checkpoint inhibitor (ICI) hepatitis. We compared patient outcomes in the inpatient versus outpatient settings. We conducted a multicenter, retrospective cohort study of 294 ICI-treated patients who developed grade 3-4 ICI hepatitis. The primary outcome was time to alanine aminotransferase (ALT) normalization (≤40); secondary outcomes included time to ALT ≤100 U/L and time to death. To account for confounding by indication, inverse probability of treatment weighting was applied to perform Cox regression. A sensitivity analysis was performed excluding patients with grade 4 hepatitis. One hundred and sixty-six patients (56.5%) were hospitalized for a median of 6 (interquartile range, 3–11) days. On inverse probability of treatment weighting Cox regression, hospitalization was not associated with time to ALT normalization (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.86–1.43; P =.436) or time to ALT ≤100 U/L (HR, 1.11; 95% CI, 0.86–1.43; P =.420). In the sensitivity analysis limited to patients with grade 3 hepatitis, hospitalization was also not associated with time to ALT normalization (HR, 1.11; 95% CI, 0.83–1.50; P =.474) or time to ALT ≤100 U/L (HR, 1.19; 95% CI, 0.90–1.58; P =.225). In a subgroup analysis of 152 patients with melanoma, hospitalization was not associated with reduced risk of all-cause death (HR, 0.93; 95% CI, 0.53–1.64; P =.798). Notably, despite their Common Terminology Criteria for Adverse Events classification of high-grade hepatitis, 94% of patients had "mild" liver injury based on International Drug-Induced Liver Injury Criteria. Hospitalization of patients with high-grade ICI hepatitis was not associated with faster hepatitis resolution and did not affect mortality. Routine hospitalization may not be necessary in all patients with high-grade ICI hepatitis and Common Terminology Criteria for Adverse Events criteria may overestimate severity of liver injury. [ABSTRACT FROM AUTHOR]

To date, studies evaluating the association between frailty and mortality in patients with cirrhosis have been limited to assessments of frailty at a single time point. We aimed to evaluate changes in frailty over time and their association with death/delisting in patients too sick for liver transplantation. Adults with cirrhosis, listed for liver transplantation at 8 US centers, underwent ambulatory longitudinal frailty testing using the liver frailty index (LFI). We used multilevel linear mixed-effects regression to model and predict changes in LFI (ΔLFI) per 3 months, based on age, gender, model for end-stage liver disease (MELD)-Na, ascites, and hepatic encephalopathy, categorizing patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk. We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe worsening of frailty had worse baseline LFI and were more likely to have non-alcoholic fatty liver disease, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted because of sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELD-Na, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI 1.35–3.09). Worsening frailty was significantly associated with death/delisting independent of baseline frailty and MELD-Na. Notably, patients who experienced improvements in frailty had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty. Frailty, as measured at a single time point, is predictive of death in patients with cirrhosis, but whether changes in frailty over time are associated with death is unknown. In a study of over 1,000 patients with cirrhosis who underwent frailty testing, we demonstrate that worsening frailty is strongly linked with mortality, regardless of baseline frailty and liver disease severity. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty. • In patients with cirrhosis, changes in frailty were significantly associated with death/delisting. • Patients with cirrhosis who experienced improvements in frailty over time had a lower risk of death/delisting. • Our data support the longitudinal measurement of frailty in patients with cirrhosis. • This study lays the foundation for interventional work aimed at reversing frailty. [ABSTRACT FROM AUTHOR]

• K155M stabilizes V1V2 β-strand conformation relevant to broad antibody recognition. • β-strand stabilized V1V2 immunogens elicit antibody responses with greater cross-reactivity. • Fine-tuning immunogen conformation modulates immunogenicity. Antibodies against the HIV-1 V1V2 loops were the only correlate of reduced infection risk in the RV144 vaccine trial, highlighting the V1V2 loops as promising targets for vaccine design. The V1V2 loops are structurally plastic, exhibiting either an α-helix-coil or β-strand conformation. V1V2-specific antibodies may thus recognize distinct conformations, and an antibody's conformational specificity can be an important determinant of breadth and function. Restricting V1V2 conformational plasticity in an immunogen may thus provide control over the conformational specificity and quality of a vaccine-elicited antibody response. Previously, we identified a V1V2 sequence variant (K155M) that results in enhanced recognition by cross-reactive antibodies recognizing the β-strand conformation. Here, we relate V1V2 antigenicity to immunogenicity by comparing the immunogenicity profiles of wildtype and K155M immunogens in two mouse models. In one model, immunization with gp70 V1V2 K155M but not wildtype elicited antibody responses that were cross-reactive to a panel of heterologous gp120 and gp140 antigens. In a second model, we compared the effect of K155M on immunogenicity in the context of gp70 V1V2, gD V1V2 and gp120, examining the effects of scaffold, epitope-focusing and immunization regimen. K155M variants, especially in the context of a gp120 immunogen, resulted in more robust, durable and cross-reactive antibody responses than wildtype immunogens. Restriction of the β-stranded V1V2 conformation in K155M immunogens may thus be associated with the induction of cross-reactive antibody responses thought to be required of a protective HIV-1 vaccine. [ABSTRACT FROM AUTHOR]

Renal dysfunction increases risk of death for patients with cirrhosis. We investigated whether mortality differs significantly among patients with acute kidney injury (AKI), chronic kidney disease (CKD), and both. We performed a retrospective analysis of all non-status 1 adults on the waitlist for liver transplantation for at least 90 days, collected from the Organ Procurement and Transplantation Network registry from July 1, 2007 through July 1, 2014. We assigned patients to groups of AKI (an increase of ≥0.3 mg/dL or ≥50% in serum creatinine in the last 7 days or fewer than 72 days of hemodialysis), CKD (an estimated glomerular filtration rate <60 ml/min/1.73 m2 for 90 days with a final rate ≥30 ml/min/1.73 m2 or ≥72 days of hemodialysis), AKI and CKD (meet both definitions), or normal (meet neither definition). We performed competing risk analyses to associate patterns of renal dysfunction with waitlist mortality, accounting for liver transplantation, with renal pattern as a time-dependent covariate. Logistic regression for 6-month mortality determined the added benefit of including renal function pattern in the assessment. There were 22,680 patients in the cohort; they spent a median 1.6 years (range, 0.7–3.1 years) on the waitlist and a median 5 years (range, 2–9 years) undergoing assessments of renal function. In competing risk analysis, even after adjusting for confounders including final model for end-stage liver disease sodium (MELD-Na) scores, the pattern of renal function was significantly associated with waitlist mortality: AKI and CKD (subhazard ratio [SHR], 2.86; 95% CI, 2.65–3.10), AKI (SHR, 2.42; 95% CI 2.22–2.64), CKD (SHR, 1.56; 95% CI, 1.45–1.67) compared with normal. The area under the curve values, based on MELD-Na score at time of placement on the waitlist, were 0.80 with renal function pattern and 0.71 without (P <.001). In competing risk analysis, even after adjusting for confounders including final MELD-Na score, we found the pattern of renal dysfunction to associate with mortality in patients with cirrhosis. Including information on type of renal dysfunction could improve risk analysis. [ABSTRACT FROM AUTHOR]

• Hospitality service employees can react positively toward uncivil service encounters. • Hospitality service employees offer extra-role customer service under high supervisor support. • Work engagement mediates the conditional effect of customer incivility. This study investigates the conditions under which service employees can react positively after encountering customer incivility. Building on the work engagement theory, we hypothesize that customer incivility interacts with workplace social support (i.e., perceived supervisor and co-worker support) to influence work engagement, which in turn leads to extra-role customer service. We test our model within the context of hotels. The results of a two-wave survey with a sample of 198 frontline service employees provide support for most of the hypotheses. In particular, the findings show that employees encountering uncivil customer interactions provide extra-role customer service only when they have high (vs. low) supervisor support. Work engagement mediates the conditional effect of customer incivility on extra-role customer service. The results thus suggest that supervisors play a vital role in encouraging employees' positive reaction toward customer incivility. This work has notable implications for hospitality management research. [ABSTRACT FROM AUTHOR]

Abstract There are a large variety of methodologies, contexts and perspectives that have been used to evaluate the use of technology in education. The vast array of literature involving learning technology evaluation makes it challenging to acquire an accurate sense of the different aspects of learning that are evaluated, and the possible approaches that can be used to evaluate them. This study conducted a systematic review of how technology use in education has been evaluated, based on 365 papers published in Computers and Education between 2015 and 2017. The papers analyzed encompassed a diverse range of education levels, disciplines and technologies, that were broadly commensurate with characterizations of the learning technology field from other studies. The analysis found that the evaluation of learning technology use tended to focus on eight themes: learning outcomes, affective elements, behaviors, design, technology elements, pedagogy, presence, and institutional environment. In the majority of studies (66.6%) at least one established instrument was used to evaluate the effectiveness of learning technology usage, however, a wide variety of instruments were observed within sub-themes of evaluation. The 22 instruments used to evaluate an aspect of learning technology usage in more than one study are identified. Evaluation trends for different disciplines, technologies and educational levels are also established. The findings provide an analytical framework that educators and researchers can utilize when evaluating the use of technology in education, and could potentially inform the development of new, more holistic and more robust evaluation methods. Highlights • Eight foci of learning technology evaluations emerged from a systematic review. • The main foci were learning outcomes, affective elements, behaviors and design. • Of the 365 papers analyzed, 66.6% used at least one instrument from a prior study. • The 22 instruments used in multiple studies to evaluate sub-categories are reported. • The results assist learning technology evaluation and characterize the field. [ABSTRACT FROM AUTHOR]

Background & Aims Frailty is associated with mortality in patients with cirrhosis. We measured frailty using 3 simple tests and calculated Liver Frailty Index (LFI) scores for patients at multiple ambulatory centers. We investigated associations between LFI scores, ascites, and hepatic encephalopathy (HE) and mortality. Methods Adults without hepatocellular carcinoma who were on the liver transplantation waitlist at 9 centers in the United States (N = 1044) were evaluated using the LFI; LFI scores of at least 4.5 indicated that patients were frail. We performed logistic regression analyses to assess associations between frailty and ascites or HE and competing risk regression analyses (with liver transplantation as the competing risk) to estimate sub-hazard ratios (sHRs) of waitlist mortality (death or removal from the waitlist). Results Of study subjects, 36% had ascites, 41% had HE, and 25% were frail. The odds of frailty were higher for patients with ascites (adjusted odd ratio 1.56, 95% confidence interval [CI] 1.15–2.14) or HE (odd ratio 2.45, 95% CI 1.80–3.33) than for those without these features. Larger proportions of frail patients with ascites (29%) or HE (30%) died while on the waitlist compared with patients who were not frail (17% of patients with ascites and 20% with HE). In univariable analysis, ascites (sHR 1.52, 95% CI 1.14–2.05), HE (sHR 1.84, 95% CI 1.38–2.45), and frailty (sHR 2.38, 95% CI 1.77–3.20) were associated with waitlist mortality. In adjusted models, only frailty remained significantly associated with waitlist mortality (sHR 1.82, 95% CI 1.31–2.52); ascites and HE were not. Conclusions Frailty is a prevalent complication of cirrhosis that is observed more frequently in patients with ascites or HE and independently associated with waitlist mortality. LFI scores can be used to objectively quantify risk of death related to frailty—in excess of liver disease severity—in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Gender differences in the natural history of chronic liver disease have been well-described. Women have lower rates of chronic liver disease and slower fibrosis progression, yet higher rates of waitlist mortality.1,2 Although previous studies have identified several clinical factors including height and creatinine that explain some of this transplant disparity, most have used data from administrative records, which are limited in their ability to identify clinically relevant differences and opportunities for intervention to reduce disparities.3-5 Additionally, most studies have focused on the period between waitlist and transplant, failing to capture gender differences in access to transplant.3,6 In the present study, we took advantage of a multicenter inpatient cohort with granular clinical data to characterize how women and men with cirrhosis differ, to stimulate future research aimed at reducing the well-established gender disparity in liver transplantation. [ABSTRACT FROM AUTHOR]

Strategic planning for hepatitis C virus (HCV) screening and treatment requires up-to-date information on the prevalence of HCV spontaneous clearance. Published estimates of HCV spontaneous clearance range from 15% to 60%.1–3 We conducted an observational study over 20 years to evaluate trends in the prevalence of HCV spontaneous clearance. Our goals were to estimate the proportion of HCV-antibody–positive patients who were viremic, and to identify factors associated with viremia, thus facilitating prediction of the number of patients needing treatment. [ABSTRACT FROM AUTHOR]

Background & Aims Treatment with the combination of ledipasvir and sofosbuvir for 12 weeks has been approved by the Food and Drug Administration for patients with genotype 1 hepatitis C virus (HCV) infection; some patients can be treated with an 8-week course. Guidelines recommend a 12-week treatment course for black patients, but studies have not compared the effectiveness of 8 vs 12 weeks in black patients who are otherwise eligible for an 8-week treatment regimen. Methods We conducted an observational study of Kaiser Permanente Northern California members with HCV genotype 1 infection who were eligible for 8 weeks of treatment with ledipasvir and sofosbuvir (treatment-naïve, no cirrhosis, no HIV infection, level of HCV RNA <6 million IU/mL) and were treated for 8 or 12 weeks from October 2014 through December 2016. We used χ 2 analyses to compare sustained virologic response 12 weeks after the end of treatment (SVR12) among patients treated for 8 vs 12 weeks, and adjusted Poisson models to identify factors associated with receipt of 12 weeks of therapy among patients eligible for 8 weeks. Results Of 2653 patients eligible for 8 weeks of treatment with ledipasvir and sofosbuvir, 1958 (73.8%) received 8 weeks of treatment and 695 (26.2%) received 12 weeks; the proportions of patients with SVR12 were 96.3% and 96.3%, respectively ( P = .94). Among 435 black patients eligible for the 8-week treatment regimen, there was no difference in the proportions who achieved an SVR12 following 8 vs 12 weeks’ treatment (95.6% vs 95.8%; P = .90). Male sex, higher transient elastography or FIB-4 scores, higher INR and level of bilirubin, lower level of albumin, obesity, diabetes, and ≥15 alcohol drinks consumed/week were independently associated with receiving 12 weeks of treatment among patients eligible for the 8-week treatment regimen, but were not associated with reduced SVR12 after 8 weeks of treatment. Conclusion In an observational study of patients who received ledipasvir and sofosbuvir treatment for HCV genotype 1 infection, we found that contrary to guidelines, 8-week and 12-week treatment regimens do not result in statistically significant differences in SVR12 in black patients. Patient characteristics were associated with receipt of 12-week regimens among patients eligible for 8 weeks, but were not associated with reduced SVR12 after 8 weeks. Shorter treatment courses might therefore be more widely used without compromising treatment effectiveness. [ABSTRACT FROM AUTHOR]

Background & Aims Approximately 10% of children on the liver transplant wait-list in the United States die every year. We examined deceased donor liver offer acceptance patterns and their contribution to pediatric wait-list mortality. Methods We performed a retrospective cohort study of children on the US liver transplant wait-list from 2007 through 2014 using national transplant registry databases. We determined the frequency, patterns of acceptance, and donor and recipient characteristics associated with deceased donor liver organ offers for children who died or were delisted compared with those who underwent transplantation. Children who died or were delisted were classified by the number of donor liver offers (0 vs 1 or more), limiting analyses to offers of livers that were ultimately transplanted into pediatric recipients. The primary outcome was death or delisting on the wait-list. Results Among 3852 pediatric liver transplant candidates, children who died or were delisted received a median 1 pediatric liver offer (inter-quartile range, 0–2) and waited a median 33 days before removal from the wait-list. Of 11,328 donor livers offered to children, 2533 (12%) were transplanted into children; 1179 of these (47%) were immediately accepted and 1354 (53%) were initially refused and eventually accepted for another child. Of 27,831 adults, 1667 (6.0%; median, 55 years) received livers from donors younger than 18 years (median, 15 years), most (97%) allocated locally or regionally. Of children who died or were delisted, 173 (55%) received an offer of 1 or more liver that was subsequently transplanted into another pediatric recipient, and 143 (45%) died or were delisted with no offers. Conclusions Among pediatric liver transplant candidates in the US, children who died or were delisted received a median 1 pediatric liver offer and waited a median of 33 days. Of livers transplanted into children, 47% were immediately accepted and 53% were initially refused and eventually accepted for another child. Of children who died or were delisted, 55% received an offer of 1 or more liver that was subsequently transplanted into another pediatric recipient, and 45% died or were delisted with no offers. Pediatric prioritization in the allocation and development of improved risk stratification systems is required to reduce wait-list mortality among children. [ABSTRACT FROM AUTHOR]

Grades 3 to 4 hepatic encephalopathy (advanced HE), also termed brain failure, is an organ failure that defines acute-on-chronic liver failure. It is associated with poor outcomes in cirrhosis but cannot be predicted accurately. We aimed to determine the admission metabolomic biomarkers able to predict the development of advanced HE with subsequent validation. Prospective inpatient cirrhosis cohorts (multicenter and 2-center validation) without brain failure underwent admission serum collection and inpatient follow-up evaluation. Serum metabolomics were analyzed to predict brain failure on random forest analysis and logistic regression. A separate validation cohort also was recruited. The multicenter cohort included 602 patients, of whom 144 developed brain failure (105 only brain failure) 3 days after admission. Unadjusted random forest analysis showed that higher admission microbially derived metabolites and lower isoleucine, thyroxine, and lysophospholipids were associated with brain failure development (area under the curve, 0.87 all; 0.90 brain failure only). Logistic regression area under the curve with only clinical variables significantly improved with metabolites (95% CI 0.65-0.75; P =.005). Four metabolites that significantly added to brain failure prediction were low thyroxine and maltose and high methyl-4-hydroxybenzoate sulfate and 3-4 dihydroxy butyrate. Thyroxine alone also significantly added to the model (P =.05). The validation cohort including 81 prospectively enrolled patients, of whom 11 developed brain failure. Admission hospital laboratory thyroxine levels predicted brain failure development despite controlling for clinical variables with high specificity. In a multicenter inpatient cohort, admission serum metabolites, including thyroxine, predicted advanced HE development independent of clinical factors. Admission low local laboratory thyroxine levels were validated as a predictor of advanced HE development in a separate cohort. [Display omitted] [ABSTRACT FROM AUTHOR]

Transplant-ineligible patients with advanced liver disease rarely receive timely advance care planning (ACP). Tools are needed to educate these patients about medical interventions available at the end of life to promote ACP. This single-site pilot randomized controlled trial assessed the feasibility, acceptability, and preliminary efficacy of an ACP video decision support tool for improving transplant-ineligible advanced liver disease patients' knowledge about and preferences for end-of-life care. Intervention participants watched a 5-minute video depicting 3 levels of goals of care: life-prolonging care (cardiopulmonary resuscitation [CPR] and intubation), life-limiting care (hospitalization, no CPR/intubation), and comfort care. Control subjects received only a verbal narrative of these 3 levels of goals of care. The primary outcome was feasibility (≥60% enrollment rate). Secondary outcomes included acceptability of the video, patients' knowledge of end-of-life care options (6-item test; range, 0–6), and postintervention goals-of-care and CPR or intubation preferences. We enrolled 85% (n = 50 of 59) of eligible patients randomized to the video (n = 26) or verbal (n = 24) arm. In the video arm, 81% of patients reported being very comfortable watching the video. Patients in the video arm had higher mean knowledge scores (5.7 vs 4.8; P <.001) and were less likely to prefer to receive CPR compared with patients in the verbal arm (35% vs 63%; P =.09). An ACP video decision support tool to improve knowledge about and preferences for end-of-life care is both feasible and highly acceptable to transplant-ineligible patients with advanced liver disease with a high enrollment rate and promising preliminary efficacy. Future studies should examine the efficacy of the ACP video for enhancing the quality of their end-of-life care. (ClinicalTrials.gov , Number: NCT03557086). [ABSTRACT FROM AUTHOR]

Travel agents' customer service behavior (CSB) and organizational citizenship behavior (OCB) are pivotal to the success of a retail travel agency. According to social exchange theory, these behaviors can be motivated by leader–member exchange (LMX, exchange between travel agents and their supervisors) and internal marketing orientation (IMO, exchange between travel agents and their organizations). In addition, the two exchange relationships are interdependent. Data from a two-phase survey of 288 travel agents working in Hong Kong were analyzed through hierarchical linear modeling. The findings indicate that leader-member exchange is positively associated with travel agents' organizational citizenship behavior, whereas internal marketing orientation is positively associated with travel agents' customer service behavior only when leader-member exchange is low. Moreover, the quality of one exchange relationship affects the salience of the other relationship. The manuscript concludes with implications for theory and practice. [ABSTRACT FROM AUTHOR]

Objective: To characterize associations between living in primary care shortage areas and graft failure/death for children after liver transplantation.Study Design: This was an observational study of all pediatric patients (aged <19 years) who received a liver transplant between January 1, 2005, and December 31, 2015 in the US, with follow-up through January 2019 (N = 5964). One hundred ninety-five patients whose home ZIP code could not be matched to primary care shortage area status were excluded. The primary outcome was a composite endpoint of graft failure or death. We used Cox proportional hazards to model the associations between health professional shortage area (HPSA) and graft failure/death.Results: Children living in HPSAs had lower estimated graft survival rates at 10 years compared with those not in HPSAs (76% vs 80%; P < .001). In univariable analysis, residence in an HPSA was associated with a 22% higher hazard of graft failure/death than non-residence in an HPSA (hazard ratio [HR], 1.22; 95% CI, 1.09-1.36; P < .001). Black children from HPSAs had a 67% higher hazard of graft failure/death compared with those not in HPSAs (HR, 1.67; 95% CI, 1.29 to 2.16; P = .006); the effect of HPSA status was less pronounced for White children (HR, 1.11; 95% CI, 0.98-1.27; P = .10).Conclusions: Children living in primary care shortage areas are at increased risk of graft failure and death after liver transplant, and this risk is particularly salient for Black children. Future work to understand how living in these regions contributes to adverse outcomes may enable teams to mitigate this risk for all children with chronic illness. [ABSTRACT FROM AUTHOR]

Background & Aims: We aimed to characterize offers of organs to candidates awaiting liver transplantation (LT). Methods: We analyzed data from the United Network for Organ Sharing registry on all US LT candidates with nonfulminant disease who were offered livers from February 1, 2005, to January 31, 2010, and ultimately received transplants. We excluded candidates with a final Model for End-stage Liver Disease score of less than 15. Livers were classified as high quality if they were from donors 18–50 years of age who were ≥170 cm tall, of non-black race, suffered brain death secondary to trauma, hepatitis C antibody-negative, not categorized as high risk by the Centers for Disease Control, and locally or regionally located. Results: Of 33,389 candidates for LT, 20% died or were removed from the list and 64% received LT; the median (interquartile range) number of liver offers for all candidates was 5 (range, 2–12). Of those who died or were removed from the list, 84% received 1 or more liver offers. Overall, 55% of those who died or were removed from the list, and 57% of those who received LT, received 1 or more offers of a high-quality liver when they had Model for End-stage Liver Disease scores of 15 or greater (P = .005). However, the proportion of last liver offers of high quality to patients who underwent LT was twice that of patients who died or were removed from the list (28% vs 14%; P < .001). Most liver offers (68%) were refused for reasons related to donor quality. Conclusions: Most candidates for LT who died or were removed from the list received 1 or more offers of a liver beforehand, and 55% received 1 or more offers of a high-quality liver. These findings indicate that a substantial proportion of wait-list mortality results in part from declined livers, rather than lack of opportunity, for transplantation. Understanding the real-time factors involved in the complex decision to accept a liver offer is vital to reducing wait-list mortality for LT candidates. [Copyright &y& Elsevier]

Abstract: Equol (EQ) is produced by intestinal bacteria from the soy isoflavone daidzein (DE) in 30%–60% of the population and is believed to provide benefits from soy intake. A robust EQ status definition is lacking, and it is uncertain whether EQ is formed consistently within an individual and ceases upon oral antibiotic treatment. In a randomized, double-blind, placebo-controlled soy intervention trial with 350 postmenopausal women, DE and EQ were analyzed by liquid chromatography/tandem mass spectrometry at baseline and every 6 months over 2.5 years in overnight urine, spot urine and plasma. Equol production changes and status (remaining an EQ producer or nonproducer or changing towards an EQ producer or nonproducer) were assessed. Equol status was determined most dependably by overnight urine applying as cutoff a ratio of EQ/DE≥0.018 with a DE threshold ≥2 nmol/mg creatinine: the soy and placebo groups had approximately 30% consistent EQ producers during the study, but 14% and 35%, respectively, changed EQ status (mean 1.4–1.7 times), while 27% and 17%, respectively, had antibiotic treatment (P<.01 for inverse association). No significant trend in change of EQ production or status was observed when overnight urine was limited to collections closest to before and after antibiotic treatment. Similarly, antibiotic type or class, duration, dose or time between antibiotic treatment and overnight urine collection showed no consistent influence on EQ production. Equol production can markedly change intraindividually over 2.5 years, and antibiotic treatment impacts it inconsistently. Factors other than antibiotic treatment must be considered as causes for EQ production changes. [Copyright &y& Elsevier]

In patients with chronic liver disease (CLD) with or without cirrhosis, existing studies on the outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have limited generalizability. We used the National COVID Cohort Collaborative (N3C), a harmonized electronic health record dataset of 6.4 million, to describe SARS-CoV-2 outcomes in patients with CLD and cirrhosis. We identified all patients with CLD with or without cirrhosis who had SARS-CoV-2 testing in the N3C Data Enclave as of July 1, 2021. We used survival analyses to associate SARS-CoV-2 infection, presence of cirrhosis, and clinical factors with the primary outcome of 30-day mortality. We isolated 220,727 patients with CLD and SARS-CoV-2 test status: 128,864 (58%) were noncirrhosis/negative, 29,446 (13%) were noncirrhosis/positive, 53,476 (24%) were cirrhosis/negative, and 8941 (4%) were cirrhosis/positive patients. Thirty-day all-cause mortality rates were 3.9% in cirrhosis/negative and 8.9% in cirrhosis/positive patients. Compared to cirrhosis/negative patients, cirrhosis/positive patients had 2.38 times adjusted hazard of death at 30 days. Compared to noncirrhosis/positive patients, cirrhosis/positive patients had 3.31 times adjusted hazard of death at 30 days. In stratified analyses among patients with cirrhosis with increased age, obesity, and comorbid conditions (ie, diabetes, heart failure, and pulmonary disease), SARS-CoV-2 infection was associated with increased adjusted hazard of death. In this study of approximately 221,000 nationally representative, diverse, and sex-balanced patients with CLD; we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.38 times mortality hazard, and the presence of cirrhosis among patients with CLD infected with SARS-CoV-2 was associated with 3.31 times mortality hazard. These results provide an additional impetus for increasing vaccination uptake and further research regarding immune responses to vaccines in patients with severe liver disease. In this study of 220,727 patients with liver disease, 30-day mortality was 8.9% for cirrhosis/severe acute respiratory syndrome coronavirus 2–positive patients, and severe acute respiratory syndrome coronavirus 2 infection was associated with a 2.38 times hazard of death. [ABSTRACT FROM AUTHOR]