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Background: Colorectal cancer (CRC) mortality rates have been decreasing for many decades in the United States, with the decrease accelerating in the most recent time period. The extent to which this decrease varies across states and its influence on the geographic patterns of rates is unknown.Methods: We analyzed the temporal trend in age-standardized CRC death rates for each state from 1990 to 2007 using joinpoint regression. We also examined the change in death rates between 1990–1994 and 2003–2007 using rate ratios with 95% confidence intervals and illustrated the change in pattern using maps. The relationship between the change in mortality rates and CRC screening rates for 2004 by state was examined using Pearson's correlation.Results: CRC mortality rates significantly decreased in all states except Mississippi between 1990 and 2007 based on the joinpoint model. The decrease in death rates between 1990–1994 and 2003–2007 ranged from 9% in Alabama to greater than 33% in Massachusetts, Rhode Island, New York, and Alaska; Mississippi and Wyoming showed no significant decrease. Generally, the northeastern states showed the largest decreases, whereas southern states showed the smallest decreases. The highest CRC mortality rates shifted from the northeastern states during 1990 to 1994 to the southern states along the Appalachian corridor during 2003 to 2007. The decrease in CRC mortality rates by state correlated strongly with uptake of screening (r = −0.65, P < 0.0001).Conclusions: Progress in reducing CRC mortality varies across states, with the Northeast showing the most progress and the South showing the least progress.Impact: These findings highlight the need for wider dissemination of CRC screening. Cancer Epidemiol Biomarkers Prev; 20(7); 1296–302. ©2011 AACR.

PDF file - 85K, Mortality rates and trends in Colorectal Cancer, by State, US, 1990-2007, Non-Hispanic Whites

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PDF file - 96K, Percent change in Colorectal Mortality and Incidence Rates, 1992-95 to 2004-07

Hispanics/Latinos are the largest and fastest growing major demographic group in the United States, accounting for 16.3% (50.5 million/310 million) of the US population in 2010. In this article, the American Cancer Society updates a previous report on cancer statistics for Hispanics using incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. In 2012, an estimated 112,800 new cases of cancer will be diagnosed and 33,200 cancer deaths will occur among Hispanics. In 2009, the most recent year for which actual data are available, cancer surpassed heart disease as the leading cause of death among Hispanics. Among US Hispanics during the past 10 years of available data (2000-2009), cancer incidence rates declined by 1.7% per year among men and 0.3% per year among women, while cancer death rates declined by 2.3% per year in men and 1.4% per year in women. Hispanics have lower incidence and death rates than non-Hispanic whites for all cancers combined and for the 4 most common cancers (breast, prostate, lung and bronchus, and colorectum). However, Hispanics have higher incidence and mortality rates for cancers of the stomach, liver, uterine cervix, and gallbladder, reflecting greater exposure to cancer-causing infectious agents, lower rates of screening for cervical cancer, differences in lifestyle and dietary patterns, and possibly genetic factors. Strategies for reducing cancer risk among Hispanics include increasing utilization of screening and available vaccines, as well as implementing effective interventions to reduce obesity, alcohol consumption, and tobacco use.

During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation.Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological change was defined as a ≥ 2-point difference in HAI or Ishak fibrosis score between biopsies.Among 657 patients who received full-dose peginterferon/ribavirin "lead-in" therapy before randomization, year-1.5 HAI improvement was associated with lead-in HCV RNA suppression in both the randomized treated (P0.0001) and control (P=0.0001) groups, even in the presence of recurrent viremia. This relationship persisted at year 3.5 in both the treated (P=0.001) and control (P=0.01) groups. Among 834 patients followed for a median of 6 years, fewer clinical outcomes occurred in patients with improved HAI at year 1.5 compared with those without such improvement in both the treated (P=0.03) and control (P=0.05) groups. Among patients with Ishak 3-4 fibrosis at baseline, those with improved HAI at year 1.5 had less fibrosis progression at year 1.5 in both the treated (P=0.0003) and control (P=0.02) groups.Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment.

BACKGROUND. The current study was undertaken to evaluate the spatiotemporal projection models applied by the American Cancer Society to predict the number of new cancer cases. METHODS. Adaptations of a model that has been used since 2007 were evaluated. Modeling is conducted in 3 steps. In step I, ecologic predictors of spatiotemporal variation are used to estimate age-specific incidence counts for every county in the country, providing an estimate even in those areas that are missing data for specific years. Step II adjusts the step I estimates for reporting delays. In step III, the delay-adjusted predictions are projected 4 years ahead to the current calendar year. Adaptations of the original model include updating covariates and evaluating alternative projection methods. Residual analysis and evaluation of 5 temporal projection methods were conducted. RESULTS. The differences between the spatiotemporal model-estimated case counts and the observed case counts for 2007 were < 1%. After delays in reporting of cases were considered, the difference was 2.5% for women and 3.3% for men. Residual analysis indicated no significant pattern that suggested the need for additional covariates. The vector autoregressive model was identified as the best temporal projection method. CONCLUSIONS. The current spatiotemporal prediction model is adequate to provide reasonable estimates of case counts. To project the estimated case counts ahead 4 years, the vector autoregressive model is recommended to be the best temporal projection method for producing estimates closest to the observed case counts. Cancer 2012;118:1100–9. V C 2012 American Cancer Society.

Background: Colorectal cancer (CRC) mortality rates have been decreasing for many decades in the United States, with the decrease accelerating in the most recent time period. The extent to which this decrease varies across states and its influence on the geographic patterns of rates is unknown. Methods: We analyzed the temporal trend in age-standardized CRC death rates for each state from 1990 to 2007 using joinpoint regression. We also examined the change in death rates between 1990–1994 and 2003–2007 using rate ratios with 95% confidence intervals and illustrated the change in pattern using maps. The relationship between the change in mortality rates and CRC screening rates for 2004 by state was examined using Pearson's correlation. Results: CRC mortality rates significantly decreased in all states except Mississippi between 1990 and 2007 based on the joinpoint model. The decrease in death rates between 1990–1994 and 2003–2007 ranged from 9% in Alabama to greater than 33% in Massachusetts, Rhode Island, New York, and Alaska; Mississippi and Wyoming showed no significant decrease. Generally, the northeastern states showed the largest decreases, whereas southern states showed the smallest decreases. The highest CRC mortality rates shifted from the northeastern states during 1990 to 1994 to the southern states along the Appalachian corridor during 2003 to 2007. The decrease in CRC mortality rates by state correlated strongly with uptake of screening (r = −0.65, P < 0.0001). Conclusions: Progress in reducing CRC mortality varies across states, with the Northeast showing the most progress and the South showing the least progress. Impact: These findings highlight the need for wider dissemination of CRC screening. Cancer Epidemiol Biomarkers Prev; 20(7); 1296–302. ©2011 AACR.

Combination treatment with pegylated-interferon-alpha (PEG IFN-α) and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in only about half of patients. Because genes involved in the interferon-alpha pathway may affect antiviral responses, we analyzed the relationship between variants in these genes and SVR among participants in the Hepatitis C Antiviral Long-Term treatment Against Cirrhosis (HALT-C) trial. Patients had advanced chronic hepatitis C that had previously failed to respond to interferon-based treatment. Participants were treated with peginterferon-α2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered nonresponders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-alpha pathway. This analysis compares genotypes for participants with an SVR to nonresponders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n = 131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVS1-22G (adjusted odds ratio, 0.57; P = 0.02); IFNAR2 Ex2-33C (adjusted odds ratio, 2.09; P = 0.02); JAK1 IVS22+112T (adjusted odds ratio, 1.66; P = 0.04); and ADAR Ex9+14A (adjusted odds ratio, 1.67; P = 0.03). For the TYK2-2256A promoter region variant, a borderline association was present among European American participants (OR, 1.51; P = 0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for TYK2 -2256 carried the A variant compared with 68 of 120 (57%) nonresponders (P = 0.006). Conclusion: Genetic polymorphisms in the interferon-α pathway may affect responses to antiviral therapy of chronic hepatitis C. (HEPATOLOGY 2009.)

Background/Aims Certain host genetic polymorphisms reportedly affect the likelihood of a sustained virological response (SVR) to interferon treatment in subjects infected with hepatitis C virus (HCV). As part of the HALT-C trial we evaluated genetic associations among patients infected with HCV genotype 1 who had failed previous interferon treatment. Methods SVR was determined 24 weeks after completing treatment with pegylated interferon alfa-2a and ribavirin. Eight single nucleotide polymorphisms (SNPs) were selected on the basis of previously reported associations with treatment response. Genotypes were assessed by polymerase chain reaction-based assays. The percentage of patients who achieved SVR was determined for each genotype and for an IL10 promoter diplotype. Results Among 637 non-Hispanic Caucasian patients there were no significant associations between genotype for any individual SNP ( IL10 −1082, IL10 −592, TNF −308, TNF −238, TGFB1 codon 25, CCL2 −2518, EPHX1 codon 113 and AGT −6) and SVR, but SVR was more common among the patients who were homozygous for the ACC IL10 promoter diplotype (adjusted odds ratio, 3.24; 95% confidence interval, 1.33–7.78; p =0.001). Conclusions Among non-Hispanic Caucasian patients treated with peginterferon and ribavirin after failing previous treatment with interferon, homozygosity for the ACC IL10 promoter diplotype was associated with SVR.

This study determined the utility of a panel of serum fibrosis markers along with routine laboratory tests in estimating the likelihood of histological cirrhosis in a cohort of prior nonresponders with chronic hepatitis C. The relationship between serum markers and quantitative hepatic collagen content was also determined. Liver biopsy samples from 513 subjects enrolled in the HALT-C trial were assigned Ishak fibrosis scores. The collagen content of 386 sirius-red stained, nonfragmented biopsy samples was quantified using computerized morphometry. Serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), amino-terminal peptide of type III procollagen (PIIINP), hyaluronic acid (HA), and YKL-40 levels were determined using commercially available assays.Sixty-two percent of patients had noncirrhotic fibrosis (Ishak stage 2-4) whereas 38% had cirrhosis (Ishak stage 5,6). Multivariate analysis identified a 3-variable model (HA, TIMP-1, and platelet count) that had an area under the receiver operating curve (AUROC) of 0.81 for estimating the presence of cirrhosis. This model was significantly better than that derived from the cirrhosis discriminant score (AUROC 0.70), the AST-to-platelet ratio (AUROC 0.73), and a prior model developed in HALT-C patients (AUROC 0.79). Multivariate analysis demonstrated that the serum fibrosis markers correlated substantially better with Ishak fibrosis scores than with the log hepatic collagen content (AUROC 0.84 versus 0.72). Conclusion: A 3-variable model consisting of serum HA, TIMP-1, and platelet count was better than other published models in identifying cirrhosis in HALT-C Trial subjects. The stronger correlation of the serum markers with Ishak scores suggests that serum fibrosis markers reflect the pattern of fibrosis more closely than the quantity of hepatic collagen. (HEPATOLOGY 2008.)

Purpose.Spillover is the effect of one role on another as working adults attempt to integrate demands from work and family. We conducted a survey to understand how worker, job, and family characteristics were related to negative work-to-family spillover and how spillover was related to fruit and vegetable consumption to inform intervention design.Design.A combined mail and telephone survey.Setting.A national random sample in the United States.Subjects.1108 (44% response) unionized construction laborers.Measures.Personal characteristics, job factors, family factors, work-to-family spillover, and fruit and vegetable consumption.Analysis.Multivariable logistic and least-squares regression.Results.A range of 20% to 50% of respondents reported negative work-to-family spillover, agreeing that work demands, time, fatigue, and stress interfered with family meals or food choices. Higher spillover was associated with job factors, being of white race/ethnicity, and having children at home. Lower fruit and vegetable consumption was associated with higher work-to-family spillover (p = .002), being of white race or ethnicity (p < .0001), and working the graveyard or day shift (p = .02).Conclusion.Negative experience of work-to-family spillover may link employment to fruit and vegetable consumption and thus to worker health. Understanding the contribution of spillover to fruit and vegetable consumption aids understanding of how work experience affects health.

Iron overload may cause or contribute to hepatic injury and fibrosis. Mutations in the HFE gene may influence development or progression of chronic liver disease by increasing iron stores or modulating immune responses. The aim of this work was to assess the influence of HFE mutations and serum and hepatic measures of iron status on baseline features and response to lead-in therapy in subjects with advanced chronic hepatitis C enrolled in the Hepatitis C Anti-viral Long-term Treatment to prevent Cirrhosis (HALT-C) Trial.Entry criteria included an Ishak fibrosis score2 and lack of iron overload (Scheuer iron grade3+) according to local study pathologists. All baseline biopsy specimens were rescored by consensus of study pathologists, and detailed assessment of stainable iron was performed. Hepatic iron concentrations were measured on portions of 144 liver biopsy specimens. A total of 1051 out of 1145 subjects agreed to HFE mutational testing (C282Y, H63D, S65C).Thirty-five percent carried at least one HFE gene mutation. There were no significant differences in the prevalence of HFE gene mutations among subjects with fibrosis (35.5%) versus cirrhosis (32.9%). Thirty-three percent of subjects had end-of-treatment and 16% sustained virologic responses. Presence of HFE mutations, in particular the H63D variation, was associated with increased end-of-treatment (40% vs 29%, P = .0078) and sustained virologic responses (20% with HFE mutation vs 14% sustained virologic response without HFE mutation; P = .009).Although HFE mutations (especially the most frequent H63D mutation) are associated with increased iron loading, they are also associated with increased sustained virologic responses in US patients with advanced chronic hepatitis C.

In patients with chronic hepatitis C, advanced fibrosis and cirrhosis are associated with lower rates of sustained virologic response (SVR) to interferon (IFN)-based therapy. In this study, we assessed virologic response to retreatment with peginterferon alfa-2a and ribavirin (RBV), as a function of the baseline fibrosis score (Ishak staging) and platelet count, in 1,046 patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All patients had failed prior treatment with IFN or peginterferon RBV and had Ishak fibrosis scores > 3. Four groups of patients with increasingly severe liver disease were compared: (A) bridging fibrosis (Ishak 3 and 4) with platelet counts >125,000/ mm 3 (n 559); (B) bridging fibrosis with platelet counts 125,000/mm 3 (n 198); and (D) cirrhosis with platelet counts

Population health research on racial discrimination is hampered by a paucity of psychometrically validated instruments that can be feasibly used in large-scale studies. We therefore sought to investigate the validity and reliability of a short self-report instrument, the "Experiences of Discrimination" (EOD) measure, based on a prior instrument used in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Study participants were drawn from a cohort of working class adults, age 25-64, based in the Greater Boston area, Massachusetts (USA). The main study analytic sample included 159 black, 249 Latino, and 208 white participants; the validation study included 98 African American and 110 Latino participants who completed a re-test survey two to four weeks after the initial survey. The main and validation survey instruments included the EOD and several single-item discrimination questions; the validation survey also included the Williams Major and Everyday discrimination measures. Key findings indicated the EOD can be validly and reliably employed. Scale reliability was high, as demonstrated by confirmatory factor analysis, Cronbach's alpha (0.74 or greater), and test-re-test reliability coefficients (0.70). Structural equation modeling demonstrated the EOD had the highest correlation (r=0.79) with an underlying discrimination construct compared to other self-report discrimination measures employed. It was significantly associated with psychological distress and tended to be associated with cigarette smoking among blacks and Latinos, and it was not associated with social desirability in either group. By contrast, single-item measures were notably less reliable and had low correlations with the multi-item measures. These results underscore the need for using validated, multi-item measures of experiences of racial discrimination and suggest the EOD may be one such measure that can be validly employed with working class African Americans and Latino Americans.

In this article, the American Cancer Society estimates the number of new cancer cases and deaths for African Americans and compiles the most recent data on cancer incidence, mortality, survival, and screening prevalence based upon incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. It is estimated that 176,620 new cases of cancer and 64,880 deaths will occur among African Americans in 2013. From 2000 to 2009, the overall cancer death rate among males declined faster among African Americans than whites (2.4% vs 1.7% per year), but among females, the rate of decline was similar (1.5% vs 1.4% per year, respectively). The decrease in cancer death rates among African American males was the largest of any racial or ethnic group. The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of nearly 200,000 deaths from cancer among African Americans. Five-year relative survival is lower for African Americans than whites for most cancers at each stage of diagnosis. The extent to which these disparities reflect unequal access to health care versus other factors remains an active area of research. Overall, progress in reducing cancer death rates has been made, although more can and should be done to accelerate this progress through ensuring equitable access to cancer prevention, early detection, and state-of-the-art treatments.

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. A total of 1,660,290 new cancer cases and 580,350 cancer deaths are projected to occur in the United States in 2013. During the most recent 5 years for which there are data (2005-2009), delay-adjusted cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.5% per year in women. Overall, cancer death rates have declined 20% from their peak in 1991 (215.1 per 100,000 population) to 2009 (173.1 per 100,000 population). Death rates continue to decline for all 4 major cancer sites (lung, colorectum, breast, and prostate). Over the past 10 years of data (2000-2009), the largest annual declines in death rates were for chronic myeloid leukemia (8.4%), cancers of the stomach (3.1%) and colorectum (3.0%), and non-Hodgkin lymphoma (3.0%). The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of approximately 1.18 million deaths from cancer, with 152,900 of these deaths averted in 2009 alone. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket and other underserved populations.

Although overall cervical cancer incidence rates have decreased in both black and white women in the U.S. since the mid 1950s due to widespread screening, rates continue to be higher among blacks than among whites. However, whether this pattern differs by age is unknown.Cervical cancer cases (1975-2009, N=36,503) were obtained from nine Surveillance, Epidemiology, and End Results (SEER) Program registries. Age-standardized incidence rates for white and black women were calculated from 1975-1979 through 2005-2009 by age group (50, 50-64, and ≥65 years). Rate ratios (RRs) and 95% confidence intervals (CIs) evaluated differences in rates for blacks vs. whites by age group and stage at diagnosis during 1975-1979 and 2005-2009.Among women aged50 years, the black-to-white disparity RR decreased from nearly two-fold (RR, 1.9; 95% CI, 1.7-2.1) during 1975-1979 to unity during 2005-2009 (RR, 0.9; 95% CI, 0.8-1.0). In contrast, rates remained significantly elevated for blacks vs. whites aged 50-64 years (RR, 2.4; 95% CI, 2.1-2.7 and 1.7; 95% CI, 1.5-2.0), and for those aged ≥65 years (RR, 3.3; 95% CI, 2.9-3.8 and 2.2; 95% CI, 1.9-2.7) during both time periods, although the disparities decreased over time. Similar disparities persisted for older black women with cervical cancer of all stages.Disparities in cervical cancer incidence rates were eliminated for younger blacks vs. whites but persisted for blacks aged 50 years and older. Additional strategies are needed to increase follow-up and treatment of precancerous lesions among middle-aged and older black women.

The objective of this study was to determine the incidence and risk factors associated with new-onset and worsening portal hypertensive gastropathy (PHG) in patients with chronic hepatitis C (CHC).A total of 831 CHC patients with bridging fibrosis or cirrhosis at the time of entry were prospectively monitored for clinical and histological liver disease progression while receiving either low-dose peginterferon α2a or no antiviral therapy in the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. Upper endoscopy with grading of PHG was performed at baseline and at year 4 of the study. The presence and severity of PHG were determined using the NIEC (New Italian Endoscopy Conference) criteria, and worsening PHG was defined as a score increase of ≥1 point.During a median follow-up of 3.85 years, 50% of 514 subjects without PHG developed new-onset PHG, whereas 26% of 317 patients with baseline PHG had worsening PHG. Independent predictors of new-onset PHG included higher alkaline phosphatase and being diabetic, whereas predictors of worsening PHG were Caucasian race, lower albumin, as well as higher serum aspartate transaminase/alanine transaminase ratio and homeostatic model assessment levels. New-onset and worsening PHG were significantly associated with clinical and histological progression. They were also associated with new-onset and worsening gastroesophageal varices.New-onset and worsening PHG develop at a rate of 12.9% per year and 6.7% per year, respectively, in non-responder CHC patients with advanced fibrosis. If confirmed in other studies, endoscopic surveillance for PHG may need to be tailored to individual patient risk factors.

Iron may influence severity and progression of non-hemochromatotic liver diseases. Our aim was to assess the relationship of iron and HFE genetic variations to progression and outcomes in the HALT-C Trial and whether PegIFN therapy influenced iron variables.Participants were randomized to receive long-term PegIFN [n = 400] or no therapy [n = 413] for 3.5 y, with follow-up for up to 8.7 y [median 6.0 y]. Associations of patient characteristics with iron variables at baseline and over time were carried out using Kaplan-Meier analyses, Cox regression models, and repeated measures analysis of covariance.Participants who developed clinical outcomes [CTP7, ascites, encephalopathy, variceal bleeding, SBP, HCC, death] had significantly higher baseline scores for stainable iron in hepatocytes and in portal tract cells than those without. There were significant direct correlations between stainable iron in portal triads and lobular and total Ishak inflammatory and fibrosis scores [P0.0001]. Iron in triads at baseline increased risk of outcomes (HR = 1.35, P = 0.02). Stainable iron in hepatocytes decreased, whereas that in portal stromal cells increased significantly [P0.0001] over time. Serum iron and TIBC fell significantly over time [P0.0001], as did serum ferritin [P = 0.0003]. Chronic PegIFN treatment did not affect stainable iron. HFE genetic variations did not correlate with outcomes, including development of hepatocellular carcinoma.Stainable iron in hepatocytes and portal tract cells is a predictor of progression and clinical and histological outcomes in advanced chronic hepatitis C. Chronic low-dose PegIFN therapy did not improve outcomes, nor iron variables.

Background & Aims The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine whether suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes. Methods Seven hundred sixty-four patients treated during the lead-in phase of HALT-C trial were randomized to either peginterferon alfa-2a (90 μg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child–Turcotte–Pugh score, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma, and mortality. Results During the lead-in, ≥4-log 10 decline in serum HCV RNA occurred in 178 patients; 82% of whom lost detectable HCV RNA and later broke through or relapsed. These patients had significantly ( P = .003) fewer clinical outcomes whether randomized to maintenance therapy or control. Following randomization, serum HCV RNA increased significantly in all 90 control patients and in 58 of 88 receiving maintenance therapy. Only 30 patients had persistent suppression of HCV RNA by ≥4 log 10 during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. Conclusions Viral suppression by ≥4 log 10 with full-dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes. Continuing low-dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes.

We aimed to identify the incidence and predictors of de novo gastroesophageal variceal formation and progression in a large cohort of patients with chronic hepatitis C and advanced fibrosis.All participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial were offered an endoscopy before treatment and again after 4 years. Patients with varices at baseline also had an endoscopy at 2 years. Baseline laboratory and clinical parameters were analyzed as predictors of de novo variceal formation and variceal progression.De novo varices developed in 157 of the 598 (26.2%) patients. Most of the new varices were small (76.4%) and only 1% of patients developed variceal hemorrhage. The likelihood of developing varices was associated with subject race (HispanicCaucasianAfrican American; P = .0005), lower baseline levels of albumin (P = .051), and higher levels of hyaluronic acid (P.001) with an area under the receiver operating characteristic curve = .70. Among 210 patients with existing gastroesophageal varices, 74 (35.2%) had variceal progression or bleeding during follow-up. Patients with higher baseline ratios of serum aspartate/alanine aminotransferase (P = .028) and lower platelet counts (P = .0002) were at greatest risk of variceal progression (area under the receiver operating characteristic = .72). Prolonged, low-dose peginterferon-alpha2a therapy and beta-blockers did not influence the risk of developing new or enlarging varices.Development of varices in patients with chronic hepatitis C is associated with patient race/ethnicity and laboratory markers of disease severity. Prolonged low-dose peginterferon-alpha2a therapy and beta-blockers do not reduce the risk of variceal development or progression.

Serum fibrosis marker levels during the lead-in treatment phase of patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial were determined.Week 0, 24, 48, and 72 serum samples were analyzed for YKL-40, tissue inhibitor of matrix metalloproteinase-1, amino-terminal peptide of type III procollagen (PIIINP), and hyaluronic acid (HA) levels. All 456 chronic hepatitis C (CHC) patients received peginterferon alfa 2a and ribavirin for 24 to 48 weeks.Mean age was 49.2 years, 71% were male, and 39% had cirrhosis. Lower pretreatment serum YKL-40, tissue inhibitor of matrix metalloproteinase-1, PIIINP, and HA levels were associated significantly with week-20 virologic response (P.0001). In multivariate analysis, non-1 CHC genotype, non-black race, prior interferon monotherapy, and lower baseline serum aspartate aminotransferase/alanine aminotransferase levels and log(10)YKL-40 levels were associated independently with week-20 virologic response. Statistically significant declines in all marker levels were observed at week 72 compared with baseline in the 81 patients with a sustained virologic response, but not in the 72 patients with breakthrough or relapse. At weeks 24 and 48, significant increases were observed in serum PIIINP and HA levels compared with baseline in virologic responders and nonresponders (P.0001).Pretreatment YKL-40 levels are an independent predictor of initial virologic response to peginterferon and ribavirin treatment. Levels of all 4 serum fibrosis markers decreased significantly in the SVR patients, consistent with reduced hepatic fibrogenesis. Measuring serum fibrosis marker levels before and after antiviral therapy may provide important prognostic information in CHC patients.

Background Most occupational studies evaluate a single exposure in relation to a particular disease. However, workers typically experience multiple exposures simultaneously. There is also increasing evidence of disparities in health by sociodemographic characteristics, mostly related to social position such as gender, race/ethnicity, immigration status, income, and education. Little information exists on the worker experience of multiple occupational exposures as they vary among social groups. The objectives of this article were to: assess the burden of exposures reported within 1 year by a socially diverse population working in a range of industries; and evaluate whether sociodemographic characteristics affected the patterns of these exposures. Methods Study participants were from 14 unionized worksites in meat processing, electrical lighting manufacturing, retail grocery stores, and school bus driving. A cross-sectional study design used a self-administered, computer-assisted questionnaire (English and Spanish) to assess sociodemographic characteristics and nine workplace exposures, within the past year. An interviewer-administered job history also was collected. Results Twelve hundred eighty-two workers (72%) completed the survey: 36% women, 23% Latino, 39% black, 24% white, and 48% born outside the US. The prevalence of high exposures ranged from 21% (chemicals) to 39% (neck strain). Forty-six percent reported three or more high exposures. Exposure reporting varied among sociodemographic groups. Some of the disparities were explained by the jobs held by different groups, but after statistically controlling for job, many disparities remained. Conclusions Sociodemographic characteristics should be considered when conducting exposure assessments using questionnaires. More research is needed to understand how social characteristics may influence exposures. Am. J. Ind. Med. 50:861–875, 2007. © 2007 Wiley-Liss, Inc.

The Syracuse AUDIT (Assessment of Urban Dwellings for Indoor Toxics) project is a birth cohort study of wheezing in the first year of life in a low-income urban setting. Such studies are important because of the documented serious risks to children's health and the lack of attention and published work on asthma development and intervention in communities of this size. We studied 103 infants of mothers with asthma, living predominantly in inner-city households. Our study combines measurements of a large panel of indoor environmental agents, in-home infant assessments, and review of all prenatal and postnatal medical records through the first year of life. We found multiple environmental pollution sources and potential health risks in study homes including high infant exposure to tobacco smoke. The prevalence of maternal smoking during pregnancy was 54%; postnatal environmental tobacco smoke (ETS) exposure was nearly 90%. The majority (73%) of homes showed signs of dampness. Participants' lives were complicated by poverty, unemployment and single-parenthood. Thirty-three percent of fathers were not involved with their children, and 62% of subjects moved at least once during the study period. These socioeconomic issues had an impact on project implementation and led to modification of study eligibility criteria. Extensive outreach, follow up, and relationship-building were required in order to recruit and retain families and resulted in considerable work overload for study staff. Our experiences implementing the project will inform further studies on this and other similar populations. Future reports on this cohort will address the role of multiple environmental variables and their effects on wheezing outcome during the first year of life.

Overall declines in human immunodeficiency virus (HIV) mortality may mask patterns for subgroups, and prior studies of disparities in mortality have used area-level vs individual-level socioeconomic status measures. The aim of this study was to examine temporal trends in HIV mortality by sex, race/ethnicity, and individual level of education (as a proxy for socioeconomic status).We examined HIV deaths among non-Hispanic white, non-Hispanic black, and Hispanic men and women aged 25 to 64 years in 26 states (1993-2007; N=91 307) reported to the National Vital Statistics System. The main outcome measures were age-standardized HIV death rates, rate differences, and rate ratios by educational attainment and between the least- and the most-educated (≤12 vs ≥16 years) individuals.Between 1993-1995 and 2005-2007, mortality declined for most men and women by race/ethnicity and educational levels, with the greatest absolute decreases for nonwhites owing to their higher baseline rates. Among men with the most education, rates per 100 000 population decreased from 117.89 (95% CI, 101.08-134.70) to 15.35 (12.08-18.62) in blacks vs from 26.42 (24.93-27.92) to 1.79 (1.50-2.08) in whites. Rates were unchanged for the least-educated black women (26.76; 95% CI, 24.30-29.23; during 2005-2007) and remained high for similarly educated black men (52.71; 48.96-56.45). Relative declines were greater with increasing levels of education (P.001), resulting in widening disparities. Among men, the disparity rate ratio (comparing the least and the most educated) increased from 1.04 (95% CI, 0.89-1.21) during 1993-1995 to 3.43 (2.74-4.30) during 2005-2007 for blacks and from 0.98 (0.91-1.05) to 2.82 (2.34-3.40) for whites.Although absolute declines in HIV mortality were greatest for nonwhites, rates remain high among blacks, especially in the lowest educated groups, underscoring the need for additional interventions.