Refractory hepatic hydrothorax is associated with increased mortality with death occurring at lower MELD-Na compared to cirrhosis and refractory ascites.

BACKGROUND AND AIMS: Although refractory hepatic hydrothorax (RH) is a serious complication of cirrhosis, waitlisted patients do not receive standardized Model for End-stage Liver Disease (MELD) exemption because of inadequate evidence suggesting mortality above biochemical MELD. This study aimed to examine liver-related death (LRD) associated with RH compared to refractory ascites (RA). APPROACH AND RESULTS: This was a retrospective cohort study of Veterans with cirrhosis. Eligibility criteria included participants with RH or RA, followed from their first therapeutic thoracentesis/second paracentesis until death or transplantation. The primary outcome was LRD with non-LRD or transplantation as competing risk. Of 2552 patients with cirrhosis who underwent therapeutic thoracentesis/paracentesis, 177 met criteria for RH and 422 for RA. RH was associated with a significantly higher risk of LRD (adjusted HR [aHR] 4.63, 95% CI 3.31-6.48) than RA overall and within all MELD-sodium (MELD-Na) strata (<10 aHR 4.08, 95% CI 2.30-7.24, 10-14.9 aHR 5.68, 95% CI 2.63-12.28, 15-24.9 aHR 4.14, 95% CI 2.34-7.34, ≥25 aHR 7.75, 95% CI 2.99-20.12). LRD was higher among participants requiring 1 (aHR 3.54, 95% CI 2.29-5.48), 2-3 (aHR 4.39, 95% CI 2.91-6.63), and ≥4 (aHR 7.89, 95% CI 4.82-12.93) thoracenteses relative to RA. Although participants with RH and RA had similar baseline MELD-Na, LRD occurred in RH versus RA at a lower MELD-Na (16.5 vs. 21.82, p =0.002) but higher MELD 3.0 (27.85 vs. 22.48, p <0.0001). CONCLUSIONS: RH was associated with higher risk of LRD than RA at equivalent MELD-Na. By contrast, MELD 3.0 may better predict risk of LRD in RH.

Liver Stiffness Measurement and Risk Prediction of Hepatocellular Carcinoma After HCV Eradication in Veterans With Cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis secondary to chronic hepatitis C virus (HCV) are at risk for hepatocellular carcinoma (HCC) despite a sustained virological response (SVR). We examined whether post-SVR liver stiffness measurement (LSM) could be used to stratify HCC risk. METHODS: This was a retrospective cohort study of 1850 participants identified from the Veterans Health Administration, with HCV cirrhosis and SVR, followed up over 5099 person-years, from the time of post-SVR elastography until death, HCC, or the end of the study. RESULTS: The risk of HCC increased by 3% with every 1-kPa increase in LSM (adjusted hazard ratio [aHR], 1.03, 95% confidence interval [CI], 1.01-1.04; P < .001) and decreased with the number of years from SVR (aHR, 0.79; 95% CI, 0.70-0.90; P = .0003). The adjusted annual risk of HCC was 2.03% among participants with post-SVR LSM <10 kPa, 2.48% in LSM 10-14.9 kPa (aHR, 1.71; 95% CI, 1.01-2.88; P = .046), 3.22% for LSM 15-19.9 kPa (aHR, 1.59; 95% CI, 0.78-3.20; P = .20), 5.07% among LSM 20-24.9 kPa (aHR, 2.55; 95% CI, 1.30-5.01; P = .01), and 5.44% in LSM ≥25 kPa (aHR, 3.03; 95% CI, 1.74-5.26; P < .0001). The adjusted annual risk of HCC was < 0.4% in participants with LSM <5 kPa and without diabetes mellitus. CONCLUSIONS: LSM predicts rates of HCC in patients with HCV cirrhosis after SVR at multiple cutoff levels and offers a single test to predict portal hypertension-related complications and HCC. Patients with LSM <5 kPa in the absence of diabetes mellitus had a low risk of HCC in which surveillance could be discontinued.

Comparison of infection-induced and vaccine-induced immunity against COVID-19 in patients with cirrhosis.

BACKGROUND AND AIMS: Immunity to SARS-CoV-2 can be infection or vaccine-induced. Cirrhosis is associated with vaccine hyporesponsiveness, but whether there is decreased immunity after SARS-CoV-2 infection in unvaccinated patients with cirrhosis is unknown.The objective of our study was to compare infection-induced and vaccine-induced immunity against COVID-19 among patients with cirrhosis. METHODS: This was a retrospective cohort study among US Veterans with cirrhosis between November 27, 2020, and November 16, 2021, comparing a vaccine-induced immunity group, defined as participants without a documented SARS-CoV-2 infection but fully vaccinated with two doses of an mRNA vaccine, and infection-associated immunity group, defined as unvaccinated participants who had a positive SARS-CoV-2 polymerase chain reaction (PCR). Both groups were propensity score matched for observed characteristics, including location, and the date of the immunity acquiring event, to control for the community prevalence of COVID-19 variants. The outcome was a positive SARS-CoV-2 PCR more than 60 days after previous infection in the infection-induced, or after full vaccination in the vaccine-induced immunity group. RESULTS: We compared 634 participants in the infection-induced immunity group with 27,131 participants in the vaccine-induced immunity group using inverse propensity of treatment weighting. Vaccine-induced immunity was associated with a reduced odds of developing SARS-CoV-2 infection (adjusted hazard ratio [aHR], 0.18; 95% confidence interval [CI], 0.16-0.20, p < 0.0001). On multivariable logistic regression, vaccine-induced immunity was associated with reduced odds of developing symptomatic (adjusted odds ratio [aOR], 0.36; 95% CI, 0.33-0.41, p < 0.0001), moderate/severe/critical (aOR, 0.27; 95% CI, 0.22-0.31, p < 0.0001), and severe or critical COVID-19 (aOR, 0.20; 95% CI, 0.16-0.26, p < 0.001), compared with infection-induced immunity. CONCLUSIONS: In participants with cirrhosis, vaccine-induced immunity is associated with reduced risk of developing COVID-19, compared with infection-induced immunity.

Tobacco exposures are associated with health care utilization (HCU) and health care costs in pregnant persons and their newborn babies.

INTRODUCTION: Identifying health care utilization and costs associated with active and passive smoking during pregnancy could help improve health management strategies. METHODS: Data are from the Newborn Epigenetics STudy (NEST), a birth cohort enrolled from 2005-2011 in Durham and adjacent counties in North Carolina, United States. Participants included those for whom prenatal serum samples were assayed and for whom administrative data were obtainable (N=1,045). Zero-inflated Poisson (ZIP) regression models were used to assess associations between cotinine, adjusted for covariates (e.g., race and ethnicity, age at delivery, cohabitation status, education), and health care utilization outcomes. Generalized linear regression models were used to estimate average total charges. Simulation models were conducted to determine the economic benefits of reducing SHS and smoking during pregnancy. RESULTS: Increasing levels of cotinine were positively associated with parent's number of ED visits (coefficient(b)=0.0012, standard error (SE)=0.0002; P<.001), the number of ICU hours (b=0.0079, SE=0.0025; P=.002)), time spent in the ICU (b=0.0238, SE=0.0020, P<.001), and the number of OP visits (b=0.0003, SE=0.0001; P<.001). For infants, higher cotinine levels were associated with higher number of ED (b=0.0012, SE=0.0004; P=.005), ICU (b=0.0050, SE=0.001; P<.001), and OP (b=0.0006, SE=0.0002; P<.001) visits and longer time spent in the ED (b=0.0025, SE=0.0003; P<.001), ICU (b=0.0005, SE=0.0001; P<.001), and IP (b=0.0020, SE=0.0002; P<.001). Simulation results showed that a 5% reduction in smoking would correspond to a potential median cost savings of $150,533 from ED visits of parents and infants. CONCLUSION: Our findings highlight the importance of smoke exposure cessation during pregnancy to reduce health care utilization and costs for both parents and infants. IMPLICATIONS: This study reinforces the importance of reducing smoking and secondhand smoke exposure during pregnancy. Focusing on expanding cessation services to this group could help reduce morbidities observed within this population. Furthermore, there is the potential for health care costs savings to health care systems, especially to those with high delivery numbers. These cost savings are represented by potential reductions in ED, OP, and ICU hours and visits.

Ursodeoxycholic acid is associated with a reduction in SARS-CoV-2 infection and reduced severity of COVID-19 in patients with cirrhosis.

BACKGROUND AND AIMS: Studies have demonstrated that reducing farnesoid X receptor activity with ursodeoxycholic acid (UDCA) downregulates angiotensin-converting enzyme in human lung, intestinal and cholangiocytes organoids in vitro, in human lungs and livers perfused ex situ, reducing internalization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell. This offers a potential novel target against coronavirus disease 2019 (COVID-19). The objective of our study was to compare the association between UDCA exposure and SARS-CoV-2 infection, as well as varying severities of COVID-19, in a large national cohort of participants with cirrhosis. METHODS: In this retrospective cohort study among participants with cirrhosis in the Veterans Outcomes and Costs Associated with Liver cohort, we compared participants with exposure to UDCA, with a propensity score (PS) matched group of participants without UDCA exposure, matched for clinical characteristics, and vaccination status. The outcomes included SARS-CoV-2 infection, symptomatic, at least moderate, severe, or critical COVID-19, and COVID-19-related death. RESULTS: We compared 1607 participants with cirrhosis who were on UDCA, with 1607 PS-matched controls. On multivariable logistic regression, UDCA exposure was associated with reduced odds of developing SARS-CoV-2 infection (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.41-0.71, p < 0.0001). Among patients who developed COVID-19, UDCA use was associated with reduced disease severity, including symptomatic COVID-19 (aOR 0.54, 95% CI 0.39-0.73, p < 0.0001), at least moderate COVID-19 (aOR 0.51, 95% CI 0.32-0.81, p = 0.005), and severe or critical COVID-19 (aOR 0.48, 95% CI 0.25-0.94, p = 0.03). CONCLUSIONS: In participants with cirrhosis, UDCA exposure was associated with both a decrease in SARS-CoV-2 infection, and reduction in symptomatic, at least moderate, and severe/critical COVID-19.

Postvaccination COVID-19 infection is associated with reduced mortality in patients with cirrhosis.

BACKGROUND AND AIMS: Patients develop breakthrough COVID-19 infection despite vaccination. The aim of this study was to identify outcomes in patients with cirrhosis who developed postvaccination COVID-19. METHODS: We performed a retrospective cohort study among US veterans with cirrhosis and postvaccination or unvaccinated COVID-19. Patients were considered fully vaccinated if COVID-19 was diagnosed 14 days after the second dose of either the Pfizer BNT162b2, the Moderna 1273-mRNA, or the single-dose Janssen Ad.26.COV2.S vaccines and partially vaccinated if COVID-19 was diagnosed 7 days after the first dose of any vaccine but prior to full vaccination. We investigated the association of postvaccination COVID-19 with mortality. RESULTS: We identified 3242 unvaccinated and 254 postvaccination COVID-19 patients with cirrhosis (82 after full and 172 after partial vaccination). In a multivariable analysis of a 1:2 propensity-matched cohort including vaccinated (n = 254) and unvaccinated (n = 508) participants, postvaccination COVID-19 was associated with reduced risk of death (adjusted HR [aHR], 0.21; 95% CI, 0.11-0.42). The reduction was observed after both full (aHR, 0.22; 95% CI, 0.08-0.63) and partial (aHR, 0.19; 95% CI, 0.07-0.54) vaccination, following the 1273-mRNA (aHR, 0.12; 95% CI 0.04-0.37) and BNT162b2 (aHR, 0.27; 95% CI, 0.10-0.71) vaccines and among patients with compensated (aHR, 0.19; 95% CI, 0.08-0.45) and decompensated (aHR, 0.27; 95% CI, 0.08-0.90) cirrhosis. Findings were consistent in a sensitivity analysis restricted to participants who developed COVID-19 after vaccine availability. CONCLUSIONS: Though patients with cirrhosis can develop breakthrough COVID-19 after full or partial vaccination, these infections are associated with reduced mortality.

Urban-rural disparities in geographic accessibility to care for people living with HIV.

In the United States, people living with HIV (PLWH) in rural areas fare worse along the HIV care continuum than their urban counterparts; this may be due in part to limited geographic access to care. We estimated drive time to care for PLWH, focusing on urban-rural differences. Adult Medicaid enrollees living with HIV and their usual care clinicians were identified using administrative claims data from 14 states (Medicaid Analytic eXtract, 2009-2012). We used geographic network analysis to calculate one-way drive time from the enrollee's ZIP code tabulation area centroid to their clinician's practice address, then examined urban-rural differences using bivariate statistics. Additional analyses included altering the definition of rurality; examining subsamples based on the state of residence, services received, and clinician specialty; and adjusting for individual and county characteristics. Across n = 49,596 PLWH, median drive time to care was 12.8 min (interquartile range 26.3). Median drive time for rural enrollees (43.6 (82.0)) was nearly four times longer than for urban enrollees (11.9 (20.6) minutes, p < 0.0001), and drive times exceeded one hour for 38% of rural enrollees (versus 12% of urban, p < 0.0001). Urban-rural disparities remained in all additional analyses. Sustained efforts to circumvent limited geographic access to care are critical for rural areas.

Surveillance Mammography Behaviors in Black and White Breast Cancer Survivors: Behavioral Risk Factors and Surveillance System, 2016.

BACKGROUND: Surveillance mammography is recommended annually for early detection of disease relapse among breast cancer survivors; yet Black women have poorer national rates of surveillance mammography compared to White women. Factors that influence racial disparities in surveillance mammography rates are poorly understood. The purpose of this study is to evaluate the contribution of health care access, socioeconomic status, and perceived health status on adherence to surveillance mammography among breast cancer survivors. METHODS: This is a secondary analysis of a cross-sectional survey among Black and White women ≥ 18 years, who reported a breast cancer diagnosis and completed breast surgery and adjuvant treatment from the 2016 Behavioral Risk Factor Surveillance System National Survey (BRFSS). Bivariate associations (chi-squared, t-test) for independent variables (e.g., health insurance, marital status) were analyzed with adherence to nationally recommended surveillance guidelines defined as two levels: adherent (received a mammogram in the last 12 months), vs. non- adherent ("received a mammogram in the last 2-5 years, 5 or more years or unsure). Multivariable logistic regression models were used to evaluate the relationship between study variables with adherence, while adjusting for potential confounders. RESULTS: Of 963 breast cancer survivors, 91.7% were White women with an average age of 65. 71.7% reported a surveillance mammogram in the last 12 months, while 28.2% did not. Diagnosed > 5 years (p < 0.001); not having a routine checkup visit within 12 months (p = 0.045); and not seeing a doctor when needed due to cost (p = 0.026), were significantly related to survivor's non-adherence to surveillance mammography guidelines. A significant interaction was found between race and residential area (p < 0.001). Compared to White women, Black women living in metropolitan/suburban residential areas were more likely to receive surveillance guidelines (OR:3.77;95% CI: 1.32-10.81); however Black women living in non-metropolitan areas were less likely to receive a surveillance mammogram compared to White women living in non-metropolitan areas (OR: 0.04; 95% CI: 0.00-0.50). CONCLUSION: Findings from our study further explain the impact of socioeconomic disparities on racial differences in the use of surveillance mammography among breast cancer survivors. Black women living in non-metropolitan counties are an important subgroup for future research and screening and navigation interventions.

Third dose of COVID-19 mRNA vaccine appears to overcome vaccine hyporesponsiveness in patients with cirrhosis.

BACKGROUND & AIMS: Cirrhosis is associated with immune dysregulation and hyporesponsiveness to several vaccines including those against COVID-19. Our aim was to compare outcomes between patients with cirrhosis who received 3 doses of either the Pfizer BNT162b2 mRNA or Moderna mRNA-1273 vaccines to a propensity-matched control group of patients at similar risk of infection who received 2 doses. METHODS: This was a retrospective cohort study of patients with cirrhosis who received 2 or 3 doses of a COVID-19 mRNA vaccine at the Veterans Health Administration. Participants who received 3 doses of the vaccine (n = 13,041) were propensity score matched with 13,041 controls who received 2 doses, and studied between July 18, 2021 and February 11, 2022, when B.1.617.2 (delta) and B.1.1.529 (omicron) were the predominant variants. Outcomes were aggregated as all cases with COVID-19, symptomatic COVD-19, with at least moderate COVID-19, or severe or critical COVID-19. RESULTS: Receipt of the third dose of a COVID-19 mRNA vaccine was associated with an 80.7% reduction in COVID-19 (95% CI 39.2-89.1, p <0.001), an 80.4% reduction in symptomatic COVID-19, an 80% reduction in moderate, severe or critical COVID-19, (95% CI 34.5-87.6%, p = 0.005), a 100% reduction in severe or critical COVID-19 (95% CI 99.2-100.0, p = 0.01), and a 100% reduction in COVID-19-related death (95% CI 99.8-100.0, p = 0.007). The magnitude of reduction in COVID-19 was greater with the third dose of BNT 162b2 than mRNA-1273 and among participants with compensated rather than decompensated cirrhosis. CONCLUSIONS: Administration of a third dose of a COVID-19 mRNA vaccine was associated with a more significant reduction in COVID-19 in patients with cirrhosis than in the general population, suggesting that the third dose can overcome vaccine hyporesponsiveness in this population. LAY SUMMARY: Cirrhosis is associated with decreased responsiveness to several vaccines, including those against COVID-19. In this study of 26,082 participants with cirrhosis during the delta and omicron surge, receipt of the third dose of the vaccine was associated with an 80% reduction in COVID-19, a 100% reduction in severe/critical COVID-19, and a 100% reduction in COVID-19-related death. These findings support the importance of a third dose of mRNA vaccine among patients with cirrhosis.

Male Sex Is Associated With Higher Rates of Liver-Related Mortality in Primary Biliary Cholangitis and Cirrhosis.

BACKGROUND AND AIMS: The impact of sex on the postcirrhosis progression of primary biliary cholangitis (PBC) has not been well defined. Prior studies have suggested that men have worse outcomes but present at more advanced stages of fibrosis than women. This observation, however, has been limited by small numbers of men and even fewer patients with cirrhosis. APPROACH AND RESULTS: We investigated the association of sex with the development of all-cause and liver-related mortality or transplantation, decompensation, and hepatocellular carcinoma (HCC), using competing-risk time-updating Cox proportional hazards models in a large cohort of predominantly male patients with PBC cirrhosis assembled from the Veterans Health Administration. In a cohort of 532 participants (418 male) with PBC-related cirrhosis with a total follow-up of 3,231.6 person-years (PY) from diagnosis of compensated cirrhosis, male participants had a higher unadjusted rates of death or transplantation (8.5 vs. 3.8 per 100 PY; P < 0.0001), liver-related death or transplantation (5.5 vs. 2.7 per 100 PY; P < 0.0001), decompensation (5.5 vs. 4.0 per 100 PY; P = 0.002), and HCC (0.9 vs. 0.3 per 100 PY; P < 0.0001). After adjusting for confounders, male sex was associated with a higher risk of death or transplantation (adjusted hazard ratio, 1.80; 95% CI, 1.01-3.19; P = 0.046), and liver-related death or transplantation (subhazard ratio, 2.17; 95% CI, 1.15-4.08; P = 0.02). A sensitivity analysis that defined ursodeoxycholic acid response as normalization of alkaline phosphatase and total bilirubin revealed similar findings. CONCLUSIONS: In patients with PBC and well-compensated cirrhosis, male sex is associated with a higher risk of both death and liver-related death or transplantation.

Rates of decompensation, hepatocellular carcinoma and mortality in AMA-negative primary biliary cholangitis cirrhosis.

BACKGROUND: The natural history of patients with anti-mitochondrial antibody (AMA)-negative Primary Biliary Cholangitis (PBC) cirrhosis has not been well defined, with prior studies showing discordant results. Furthermore, most studies of AMA-negative PBC have limited numbers of patients with cirrhosis and liver-related outcomes. METHODS: We investigated the association of AMA-negative PBC and the development of death, liver-related death, decompensation and hepatocellular carcinoma (HCC), in a large cohort of predominantly male patients with PBC cirrhosis assembled from the Veterans Health Administration. RESULTS: In a cohort of 521 patients with PBC cirrhosis (65 AMA-negative) with a total follow-up of 2504.3 person-years (PY) from cirrhosis diagnosis, patients with AMA-negative PBC were younger and more likely to be black but had similar rates of UDCA response. AMA-negative PBC cirrhosis was associated with similar unadjusted rates of liver-related death (4.6 vs 5.9 per 100 PY, P = .44), overall death (7.7 vs 9.6 per 100 PY, P = .31), decompensation (7.3 vs 5.1 per 100 PY, P = .12) and HCC (0.6 vs 1.0 per 100 PY, P = .63) to AMA-positive PBC. After adjusting for confounders, AMA-negative PBC cirrhosis was associated with similar rates of liver-related death (sub-Hazard Ratio [sHR] 1.27, 95% CI 0.71-2.28, P = .42, death [sHR] 1.24, 95% CI 0.81-1.90, P = .32), decompensation (sHR 1.05, 95% CI 0.56-1.98, P = .87) and HCC (sHR 0.48, 95% CI 0.11-2.10, P = .33) to AMA-positive patients. CONCLUSION: In a cohort of predominantly male patients, AMA-negative PBC cirrhosis was associated with similar rates of overall or liver-related death, HCC or decompensation compared with AMA-positive disease.

Influential factors in Black and White breast cancer survivors' beliefs about breast cancer.

PURPOSE: Breast cancer beliefs are widely studied to improve preventative screening behaviors in women without cancer; however, limited research has examined breast cancer beliefs among breast cancer survivors. To fill this gap in research we investigated racial differences and the predicting role of influential factors (e.g., stage) in survivors' beliefs about their breast cancer. METHODS: This study is a secondary analysis of data from the Narrowing Gap in Adjuvant Therapy Study (2006-2011), where Black (N = 210) and White women (N = 149) were interviewed within 20 weeks following their breast cancer diagnosis and primary surgery in Washington DC and Detroit, MI. Outcomes of this analysis were perceived susceptibility to a breast cancer recurrence and perceived severity of breast cancer. Bivariate analyses were conducted to assess racial differences in sample characteristics, and on the study outcomes. Adjusted multiple regression models examined correlates between independent variables (e.g., sociodemographic/clinical) and women's breast cancer beliefs about susceptibility of a recurrence and disease severity. RESULTS: Most of the sample were Black women (58%), had breast-conserving surgery (64%), and were privately insured (67%). Black women reported higher perceived disease severity beliefs than White women (p = 0.004). Other associated factors with greater perceived severity beliefs included lower education (p = 0.008), public health insurance (p = 0.021) and greater levels of medical mistrust (p = 0.016). In our adjusted multiple regression models' women with lower satisfaction regarding financial aspects of their healthcare were more likely to have higher perceived severity beliefs (p = 0.007); women with stage II cancer compared to stage I had greater susceptibility beliefs to a cancer recurrence (p = 0.001). CONCLUSION: We found racial differences in women's perceived severity beliefs, and identified theory-based clinical and psychosocial correlates in survivor's breast cancer beliefs by race. Specifically, women diagnosed at stage (II) compared to stage (I) reported greater perceived susceptibility to a recurrence. Survivors diagnosed at stage (I) and (III) cancers may serve as important target groups to monitor their surveillance and follow-up behaviors. This study contributes salient predictors in survivors' beliefs about their BC and informs navigation strategies to improve cancer survivorship recommendations in the context of psycho-oncology and follow-up cancer care.

Tobacco Retail Outlets, Neighborhood Deprivation and the Risk of Prenatal Smoke Exposure.

INTRODUCTION: Smoking and smoke exposure among pregnant women remain persistent public health issues. Recent estimates suggest that approximately one out of four nonsmokers have measurable levels of cotinine, a marker indicating regular exposure to secondhand smoke. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy. However, most of these studies have relied upon self-reported measures of smoking. AIMS AND METHODS: To more accurately assess smoke exposure resulting from both smoking and secondhand exposure in mothers during pregnancy, we used Bayesian regression models to estimate the association of cotinine levels with tobacco retail outlet (TRO) exposure and a neighborhood deprivation index (NDI) in six counties in North Carolina centered on Durham County. RESULTS: Results showed a significant positive association between TRO exposure (ß = 0.008, 95% credible interval (CI) = [0.003, 0.013]) and log cotinine after adjusting for individual covariates (eg, age, race/ethnicity, education, marital status). TRO exposure was not significant after including the NDI, which was significantly associated with log cotinine (ß = 0.143, 95% CI = [0.030, 0.267]). However, in a low cotinine stratum (indicating secondhand smoke exposure), TRO exposure was significantly associated with log cotinine (ß = 0.005, 95% CI = [0.001, 0.009]), while in a high cotinine stratum (indicating active smoking), the NDI was significantly associated with log cotinine (ß = 0.176, 95% CI = [0.005, 0.372]). CONCLUSIONS: In summary, our findings add to the evidence that contextual factors are important for active smoking during pregnancy. IMPLICATIONS: In this study, we found several significant associations that suggest a more nuanced understanding of the potential influence of environmental- and individual-level factors for levels of prenatal smoke exposure. Results suggested a significant positive association between TRO exposure and cotinine levels, after adjusting for the individual factors such as race, education, and marital status. Individually, NDI was similarly positively associated with cotinine levels as well. However, when combining TRO exposure alongside NDI in the same model, TROs were no longer significantly associated with overall cotinine levels.

Neighborhood Deprivation is Associated with Increased Risk of Prenatal Smoke Exposure.

Despite years of advisories against the behavior, smoking among pregnant women remains a persistent public health issue in the USA. Recent estimates suggest that 9.4% of women smoke before pregnancy and 7.1% during pregnancy in the USA. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy, including educational attainment, employment status, housing conditions, poverty, and racial demographics. However, most of these studies have relied upon self-reported measures of smoking, which are subject to reporting bias. To more accurately and objectively assess smoke exposure in mothers during pregnancy, we used Bayesian index models to estimate a neighborhood deprivation index (NDI) for block groups in Durham County, North Carolina, and its association with cotinine, a marker of smoke exposure, in pregnant mothers (n = 887 enrolled 2005-2011). Results showed a significant positive association between NDI and log cotinine (beta = 0.20, 95% credible interval = [0.11, 0.29]) after adjusting for individual covariates (e.g., race/ethnicity and education). The two most important variables in the NDI according to the estimated index weights were percent females without a high school degree and percent Black population. At the individual level, Hispanic and other race/ethnicity were associated with lowered cotinine compared with non-Hispanic Whites. Higher education levels were also associated with lowered cotinine. In summary, our findings provide stronger evidence that the socio-geographic variables of educational attainment and neighborhood racial composition are important factors for smoking and secondhand smoke exposure during pregnancy and can be used to target intervention efforts.

Human Immunodeficiency Virus-Experienced Clinician Workforce Capacity: Urban-Rural Disparities in the Southern United States.

BACKGROUND: Human immunodeficiency virus (HIV)-experienced clinicians are critical for positive outcomes along the HIV care continuum. However, access to HIV-experienced clinicians may be limited, particularly in nonmetropolitan areas, where HIV is increasing. We examined HIV clinician workforce capacity, focusing on HIV experience and urban-rural differences, in the Southern United States. METHODS: We used Medicaid claims and clinician characteristics (Medicaid Analytic eXtract [MAX] and MAX Provider Characteristics, 2009-2011), county-level rurality (National Center for Health Statistics, 2013), and diagnosed HIV cases (AIDSVu, 2014) to assess HIV clinician capacity in 14 states. We assumed that clinicians accepting Medicaid approximated the region's HIV workforce, since three-quarters of clinicians accept Medicaid insurance. HIV-experienced clinicians were defined as those providing care to ≥ 10 Medicaid enrollees over 3 years. We assessed HIV workforce capacity with county-level clinician-to-population ratios, using Wilcoxon-Mann-Whitney tests to compare urban-rural differences. RESULTS: We identified 5012 clinicians providing routine HIV management, of whom 28% were HIV-experienced. HIV-experienced clinicians were more likely to specialize in infectious diseases (48% vs 6%, P < .001) and practice in urban areas (96% vs 83%, P < .001) compared to non-HIV-experienced clinicians. The median clinician-to-population ratio for all HIV clinicians was 13.3 (interquartile range, 38.0), with no significant urban-rural differences. When considering HIV experience, 81% of counties had no HIV-experienced clinicians, and rural counties generally had fewer HIV-experienced clinicians per 1000 diagnosed HIV cases (P < .001). CONCLUSIONS: Significant urban-rural disparities exist in HIV-experienced workforce capacity for communities in the Southern United States. Policies to improve equity in access to HIV-experienced clinical care for both urban and rural communities are urgently needed.

Ursodeoxycholic Acid Response Is Associated With Reduced Mortality in Primary Biliary Cholangitis With Compensated Cirrhosis.

INTRODUCTION: Patients with cirrhosis and men have been under-represented in most studies examining the clinical benefit of response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC). The aim of this study was to study the association of UDCA response and liver-related death or transplantation, hepatic decompensation, and hepatocellular carcinoma (HCC) in patients with PBC cirrhosis. METHODS: We conducted a retrospective cohort study of veterans, predominantly men, with PBC and compensated cirrhosis to assess the association of UDCA response with the development of all-cause and liver-related mortality or transplantation, hepatic decompensation, and HCC using competing risk time-updating Cox proportional hazards models. RESULTS: We identified 501 subjects with PBC and compensated cirrhosis, including 287 UDCA responders (1,692.8 patient-years [PY] of follow-up) and 214 partial responders (838.9 PY of follow-up). The unadjusted rates of hepatic decompensation (3.8 vs 7.9 per 100 PY, P < 0.0001) and liver-related death or transplantation (3.7 vs 6.2 per 100 PY, P < 0.0001) were lower in UDCA responders compared with partial responders. UDCA response was associated with a lower risk of hepatic decompensation (subhazard ratio [sHR] 0.54, 95% confidence interval [CI] 0.31-0.95, P = 0.03), death from any cause or transplantation (adjusted hazard ratio 0.49, 95% CI 0.33-0.72, P = 0.0002), and liver-related death or transplantation (sHR 0.40, 95% CI 0.24-0.67, P = 0.0004), but not HCC (sHR 0.39, 95% CI 0.60-2.55, P = 0.32). In a sensitivity analysis, the presence of portal hypertension was associated with the highest UDCA-associated effect. DISCUSSION: UDCA response is associated with a reduction in decompensation, all-cause, and liver-related death or transplantation in a cohort of predominantly male patients with cirrhosis, with the highest benefit in patients with portal hypertension.

Changes in initiation of adjuvant endocrine therapy for breast cancer after state health reform.

BACKGROUND: Socioeconomic differences in receipt of adjuvant treatment contribute to persistent disparities in breast cancer (BCA) outcomes, including survival. Adjuvant endocrine therapy (AET) substantially reduces recurrence risk and is recommended by clinical guidelines for nearly all women with hormone receptor-positive non-metastatic BCA. However, AET use among uninsured or underinsured populations has been understudied. The health reform implemented by the US state of Massachusetts in 2006 expanded health insurance coverage and increased the scope of benefits for many with coverage. This study examines changes in the initiation of AET among BCA patients in Massachusetts after the health reform. METHODS: We used Massachusetts Cancer Registry data from 2004 to 2013 for a sample of estrogen receptor (ER)-positive BCA surgical patients aged 20-64 years. We estimated multivariable regression models to assess differential changes in the likelihood initiating AET after Massachusetts health reform by area-level income, comparing women from lower- and higher-income ZIP codes in Massachusetts. RESULTS: There was a 5-percentage point (p-value< 0.001) relative increase in the likelihood of initiating AET among BCA patients aged 20-64 years in low-income areas, compared to higher-income areas, after the reform. The increase was more pronounced among younger patients aged 20-49 years (7.1-percentage point increase). CONCLUSIONS: The expansion of health insurance in Massachusetts was associated with a significant relative increase in the likelihood of AET initiation among women in low-income areas compared with those in high-income areas. Our results suggest that expansions of health insurance coverage and improved access to care can increase the number of eligible patients initiating AET and may ameliorate socioeconomic disparities in BCA outcomes.

Use of Telehealth Expedites Evaluation and Listing of Patients Referred for Liver Transplantation.

BACKGROUND & AIMS: Liver transplantation is the only treatment that increases survival times of patients with decompensated cirrhosis. Patients who live farther away from a transplant center are disadvantaged. Health care delivery via telehealth is an effective way to manage patients with decompensated cirrhosis remotely. We investigated the effects of telehealth on the liver transplant evaluation process. METHODS: We performed a retrospective study of 465 patients who underwent evaluation for liver transplantation at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Of these, 232 patients were evaluated via telehealth, and 233 via in-person evaluation. Using regression models, we evaluated the differential effects of telehealth vs usual care on placement on the liver transplant waitlist. We also investigated the effects of telehealth on time from referral to initial evaluation by a transplant hepatologist, liver transplantation, and mortality. RESULTS: Patients in the telehealth group were evaluated significantly faster than patients evaluated in person, without or with adjustment for potential confounders (21.7 vs 79.5 d; P < .01). Telehealth also was associated with a significantly shorter time on the liver transplant waitlist (138.8 vs 249 d; P < .01). After propensity-matched analysis, telehealth was associated with a reduction in the time from referral to evaluation (hazard ratio, 0.15; 95% CI, 0.09-0.21; P < .01) and listing (hazard ratio, 0.26; 95% CI, 0.12-0.40; P < .01), but not to transplantation. In the intent-to-treat analysis of all referred patients, we found no significant difference in pretransplant mortality between patients evaluated via telehealth vs in-person. There was statistically significant interaction between model for end-stage liver disease (MELD)-Na scores and time to evaluation (P = .009) and placement on the transplant waitlist (P = .002), with telehealth offering greater benefits to patients with low MELD-Na scores. CONCLUSIONS: Use of telehealth is associated with a substantial reduction in time from referral to initial evaluation by a hepatologist and placement on the liver transplant waitlist, especially for patients with low MELD scores, with no changes in time to transplantation or pretransplant mortality. More studies are needed, particularly outside of the Veterans Administration Health System, to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.

Addition of [18 F]Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography to Cross-Sectional Imaging Improves Staging and Alters Management in Hepatocellular Carcinoma.

In this work, we characterize the value of positron emission tomography (PET) with computed tomography (CT) in combination with cross-sectional imaging for staging and prognostication of hepatocellular carcinoma (HCC) patients. In this retrospective cohort study, HCC patients underwent PET-CT after initial staging with contrast-enhanced CT or magnetic resonance imaging (MRI). The benefit of PET-CT was measured by the identification of new HCC lesions, and potential harm was quantified by the number of false positives and subsequent diagnostic evaluation. We used multivariate Cox regression analysis to evaluate the association between the highest grade on PET-CT with the risk of extrahepatic metastasis, progression-free, and overall survival. Among 148 patients, PET-CT detected additional extrahepatic metastasis in 11.9% of treatment-naïve and 13.8% of treatment-experienced patients. PET-CT changed the Barcelona Clinic Liver Cancer (BCLC) staging in 5.9% of treatment-naïve and 18.8% of treatment-experienced patients compared with CT/MRI alone, changing HCC management in 9.9% and 21.3% of patients, respectively. Of the patients, 5% (n = 8) experienced severe physical harm requiring additional procedures to evaluate extrahepatic findings. High tumor grade on PET-CT was independently associated with a higher likelihood of extrahepatic metastasis (hazard ratio [HR], 17.1; 95% confidence interval [CI], 3.6-81.5) and worse overall survival (HR, 2.4; 95% CI, 1.4-4.3). Treatment-experienced patients (versus treatment-naïve patients; HR, 9.7; 95% CI, 1.9-49.4) and BCLC stage A (HR, 8.2; 95% CI, 1.5-45.9; P < 0.01) and BCLC stage B (HR, 20.6; 95% CI, 1.5-282.2; P < 0.05) were more likely to have an upstaging with PET-CT compared with BCLC stage C (reference). PET-CT provides prognostic information and improves tumor staging beyond CT/MRI alone, with subsequent changes in management for patients with HCC.

The Impact of Massachusetts Health Reform on Colorectal and Breast Cancer Stage at Diagnosis.

BACKGROUND: This study examines the expansion of health insurance coverage in Massachusetts under state health reform as a natural experiment to investigate whether expanded insurance coverage reduced the likelihood of advanced stage colorectal cancer (CRC) and breast cancer (BCA) diagnosis. METHODS: Our study populations include CRC or BCA patients aged 50-64 years observed in the Massachusetts Cancer Registry and Surveillance Epidemiology and End Results (SEER) registries for 2001-2013. We use difference-in-differences regression models to estimate changes in the likelihood of advanced stage diagnosis after Massachusetts health reform, relative to comparison states without expanded coverage (Connecticut, New Jersey, Georgia, Kentucky, and Michigan). RESULTS: We find some suggestive evidence of a decline in the proportion of advanced stage CRC cases. Approximately half of the CRC patients in Massachusetts and control states were diagnosed at advanced stages pre reform; there was a 2 percentage-point increase in this proportion across control states and slight decline in Massachusetts post reform. Adjusted difference-in-difference estimates suggest a 3.4 percentage-point (P=0.005) or 7% decline, relative to Massachusetts baseline, in the likelihood of advanced stage diagnosis after the reform in Massachusetts, though this result is sensitive to years included in the analysis. We did not find a significant effect of reform on BCA stage at diagnosis. CONCLUSIONS: The decline in the likelihood of advanced stage CRC diagnosis after Massachusetts health reform may suggest improvements in access to health care and CRC screening. Similar declines were not observed for BCA, perhaps due to established BCA-specific safety-net programs.