Implementation of an evidence-based tobacco control intervention for school teachers in India: Evaluating the effects of a capacity-building strategy.

Background: Tobacco-Free Teachers, Tobacco-Free Society (TFT-TFS) is an evidence-based intervention that promotes tobacco use cessation among teachers and tobacco control policies among schools in India. This study tested an implementation model to build Bihar Department of Education (DOE) capacity to support and deliver TFT-TFS within schools, leveraging DOE training infrastructure. Method: We used a training-of-trainers (TOT) "cascade" implementation strategy to embed the TFT-TFS program into the Bihar DOE infrastructure. We trained 46 Cluster Coordinators to train and support Headmasters to implement TFT-TFS in their schools over one academic year. We selected three school districts, representing approximately 46 clusters and 219 schools. We used the RE-AIM framework to assess program adoption (Headmaster participation in at least one of six TFT-TFS trainings), implementation (of four core program components), and reach (teachers' participation in three or more group discussions). Using a non-inferiority design, we hypothesized that program adoption, implementation, and reach would not be inferior to the high standards demonstrated when TFT-TFS was originally tested in the Bihar School Teachers Study. We used self-reported checklists to measure outcomes and SPSS Version 25 to analyze data. Results: For adoption, 94% of Headmasters attended the first training, although participation declined by the sixth training. Among the 112 schools out of 219 with complete Headmaster checklist data, all met our minimum criteria for implementing TFT-TFS. Over 99% of schools posted a school tobacco control policy and distributed quit booklets. However, only 69% of schools met our criteria for program reach. Conclusions: This study outlines the processes for taking a tobacco control intervention to scale and implementing it through the Bihar DOE infrastructure. These findings provide a foundation for other Indian states and low- and middle-income countries to implement tobacco control and other health programs for schoolteachers. Trial registration: NCT05346991. Plain Language Summary: Each year in India, more than 1.2 million people die from tobacco-related causes, and India has the world's highest oral cancer burden. The world needs more evidence on how to bring cost-effective tobacco control interventions to scale, especially in low- and middle-income countries (LMICs). To address this gap, from 2017 to 2021, we examined the process of scaling up Tobacco-Free Teachers, Tobacco-Free Society (TFT-TFS), an evidence-based intervention promoting tobacco use cessation among teachers and tobacco control policies in schools. Our study tested an implementation model aimed at building the Bihar State Department of Education (DOE) capacity to support and deliver TFT-TFS. We used a training-of-trainers model to embed TFT-TFS into Bihar DOE infrastructure, training 46 Cluster Coordinators to in turn train and support Headmasters to implement TFT-TFS over one academic year. We hypothesized that program adoption, implementation, and reach would not be inferior to the high standards demonstrated when we originally tested TFT-TFS through the Bihar School Teachers Study (2013-2017). For adoption, 94% of Headmasters attended the first training, although participation declined by the sixth training. Of 112 schools (out of 219 with complete Headmaster checklist data), all met our minimum criteria for implementing TFT-TFS. Over 99% of schools posted a school tobacco control policy and distributed quit booklets. However, only 69% of schools met our criteria for program reach. Study findings offer other Indian states and LMICs lessons to implement tobacco control and other health programs for schoolteachers within educational systems.

Effects of a worksite tobacco control intervention in India: the Mumbai worksite tobacco control study, a cluster-randomised trial.

OBJECTIVES: We assessed a worksite intervention designed to promote tobacco control among workers in the manufacturing sector in Greater Mumbai, India. METHODS: We used a cluster-randomised design to test an integrated health promotion/health protection intervention, the Healthy, Safe, and Tobacco-free Worksites programme. Between July 2012 and July 2013, we recruited 20 worksites on a rolling basis and randomly assigned them to intervention or delayed-intervention control conditions. The follow-up survey was conducted between December 2013 and November 2014. RESULTS: The difference in 30-day quit rates between intervention and control conditions was statistically significant for production workers (OR=2.25, p=0.03), although not for the overall sample (OR=1.70; p=0.12). The intervention resulted in a doubling of the 6-month cessation rates among workers in the intervention worksites compared to those in the control, for production workers (OR=2.29; p=0.07) and for the overall sample (OR=1.81; p=0.13), but the difference did not reach statistical significance. CONCLUSIONS: These findings demonstrate the potential impact of a tobacco control intervention that combined tobacco control and health protection programming within Indian manufacturing worksites. TRIAL REGISTRATION NUMBER: NCT01841879.

Management of recurrent stress urinary incontinence after burch and sling procedures.

AIMS: To examine treatment options selected for recurrent stress urinary incontinence (rSUI) in follow-up after Burch, autologous fascial and synthetic midurethral sling (MUS) procedures. METHODS: We performed a secondary analysis of the SISTER and ToMUS trials of participants who underwent primary stress urinary incontinence (SUI) treatment (without prior SUI surgery or concomitant procedures). Using Kaplan-Meier analysis, retreatment-free survival rates by initial surgical procedure were compared. Mean MESA (Medical Epidemiologic and Social Aspects of Aging) stress index was also compared between those retreated for rSUI compared to those not retreated. RESULTS: Half of the women in the SISTEr trial met inclusion criteria for this analysis (329/655, 174 Burch and 155 fascial sling), as did 444/597 (74%) of subjects in ToMUS (221 transobturator midurethral sling (TMUS), and 223 retropubic midurethral sling (RMUS). Types of surgical retreatment included autologous fascial sling (19), synthetic sling (1), and bulking agent (18). Five-year retreatment free survival rates (and standard errors) were 87% (3%), 96% (2%), 97% (1%), and 99% (0.7%) for Burch, autologous fascial sling, TMUS, and RMUS groups respectively (P < 0.0001). For all index surgery groups, the mean MESA stress index at last visit prior to retreatment for those retreated (n = 23) was significantly higher than mean MESA stress index at last visit for those not retreated (n = 645) (P < 0.0001). CONCLUSION: In these cohorts, 6% of women after standard anti-incontinence procedures were retreated within 5 years, mostly with injection therapy or autologous fascial sling. Not all women with rSUI chose surgical retreatment.

Social contextual factors and tobacco use among Indian teachers: insights from the Bihar School Teachers' Study.

OBJECTIVE: Tobacco use within India has significant effects on the global burden of tobacco-related disease. As role models and opinion leaders, teachers are at the forefront of tobacco control efforts, yet little is known about their own tobacco use. This study examines the association between factors in the social environment and tobacco use among teachers in Bihar, India. METHODS: The study was based on the Bihar School Teachers' Study baseline survey. Seventy-two Bihar government schools (grades 8-10) were randomly selected for the study and all school personnel were invited to complete the survey in June/July in 2009 and 2010. We assessed the relation between social contextual factors and current smoking/smokeless tobacco use by fitting a series of logistic regression models. RESULTS: After controlling for clustering of teachers in schools and other covariates, our results showed teachers with one or more coworkers who used tobacco were twice as likely to be smokeless tobacco users as teachers with no co-workers who used tobacco. Teachers who reported rules prohibiting smoking at home were significantly less likely to smoke than teachers without such rules. Older male teachers also had significantly greater odds of smoking/using smokeless tobacco. CONCLUSION: These findings provide direction for future interventions targeting the social context.

Pathways between acculturation and health behaviors among residents of low-income housing: the mediating role of social and contextual factors.

Acculturation may influence health behaviors, yet mechanisms underlying its effect are not well understood. In this study, we describe relationships between acculturation and health behaviors among low-income housing residents, and examine whether these relationships are mediated by social and contextual factors. Residents of 20 low-income housing sites in the Boston metropolitan area completed surveys that assessed acculturative characteristics, social/contextual factors, and health behaviors. A composite acculturation scale was developed using latent class analysis, resulting in four distinct acculturative groups. Path analysis was used to examine interrelationships between acculturation, health behaviors, and social/contextual factors, specifically self-reported social ties, social support, stress, material hardship, and discrimination. Of the 828 respondents, 69% were born outside of the U.S. Less acculturated groups exhibited healthier dietary practices and were less likely to smoke than more acculturated groups. Acculturation had a direct effect on diet and smoking, but not physical activity. Acculturation also showed an indirect effect on diet through its relationship with material hardship. Our finding that material hardship mediated the relationship between acculturation and diet suggests the need to explicate the significant role of financial resources in interventions seeking to promote healthy diets among low-income immigrant groups. Future research should examine these social and contextual mediators using larger, population-based samples, preferably with longitudinal data.

Analysis of Ordinal Outcomes with Longitudinal Covariates Subject to Missingness.

We propose a mixture model for data with an ordinal outcome and a longitudinal covariate that is subject to missingness. Data from a tailored telephone delivered, smoking cessation intervention for construction laborers are used to illustrate the method, which considers as an outcome a categorical measure of smoking cessation, and evaluates the effectiveness of the motivational telephone interviews on this outcome. We propose two model structures for the longitudinal covariate, for the case when the missing data are missing at random, and when the missing data mechanism is non-ignorable. A generalized EM algorithm is used to obtain maximum likelihood estimates.

Inflammatory and tissue remodeling urinary biomarkers before and after mid urethral sling surgery for stress urinary incontinence.

PURPOSE: Urinary biomarkers were measured in women at baseline and 1 year after surgery for stress urinary incontinence, and associations with clinicodemographic covariates and outcomes were analyzed. MATERIALS AND METHODS: Preoperative and postoperative urine specimens from 150 women were assayed for inflammatory biomarkers (tumor necrosis factor-α, interferon-γ, interleukin-1ß, interleukin-6, interleukin-10, interleukin-12p70, interleukin-17 and nerve growth factor) and tissue remodeling biomarkers (collagenase activity, matrix metalloproteinases-1, 2, 9 and 13, and NTx [N-telopeptide cross-linked collagen], epidermal growth factor and heparin-binding epidermal growth factor-like growth factor). Paired t-tests were used to compare changes in biomarkers during 1 year (significance p <0.05). Linear regression models correlated baseline and changes in biomarker levels with covariates (significance p ≤ 0.001). Logistic regression models, controlling for age, were used to analyze associations of baseline and changes in biomarker levels with surgical failure (significance p <0.05). RESULTS: During 1 year interleukin-12p70 decreased (mean ± SD 0.53 ± 1.4 to 0.28 ± 0.62 pg/mg creatinine, p = 0.04) and nerve growth factor increased (0.034 ± 0.046 to 0.044 ± 0.060 pg/ml/mOsm, p = 0.03). Baseline NTx level per mg creatinine was positively associated with age and postmenopausal status (p = 0.001), and negatively associated with current estrogen use (p = 0.0001). Baseline collagenase activity per mg creatinine was positively associated with age (p = 0.001). Epidermal growth factor per mOsm, NTx per mOsm and interferon-γ per mOsm were negatively correlated with age, current estrogen use and UDI (Urogenital Distress Inventory)-irritative subscale score, respectively (p ≤ 0.001). Subjects with lower baseline NTx per mg creatinine were less likely to experience surgical failure (OR 0.49, 95% CI 0.26-0.93, p = 0.03). Changes in biomarker levels were not associated with any covariates or surgical failure. CONCLUSIONS: Stress urinary incontinence surgery was significantly less likely to fail in women with lower baseline NTx levels. Studies are needed to validate NTx as a possible independent biomarker for stress urinary incontinence surgery outcomes.

Patterns and predictors of health behaviors among racially/ethnically diverse residents of low-income housing developments.

PURPOSE: To examine behavioral patterns and sociodemographic predictors of diet, inactivity, and tobacco use among a diverse sample of residents from low-income housing developments. DESIGN: In this cross-sectional survey study, households and residents were randomly selected using multistage cluster sampling. Setting . The study was conducted in 20 low-income housing developments in the Boston, Massachusetts, metropolitan area. SUBJECTS: Subjects were 828 residents who completed the survey (response rate = 49.3%). Forty-one percent of participants were Hispanic and 38% were non-Hispanic Black. Measures . Outcomes measured were diet, inactivity, and tobacco use. Predictors measured were age, race/ethnicity, gender, education, country in which the subject was born, language spoken, and financial hardship. Analysis . Logistic regression analyses were conducted to examine the association of three health behaviors with sociodemographic factors. RESULTS: Age, gender, language spoken, and financial hardship showed significant relationships with all three behaviors. For example, those who reported less financial hardship (odds ratio [OR] = 1.75) were more likely to eat healthier. Residents who spoke no English, or at least one language in addition to English, were significantly more likely to report healthier eating (OR = 2.78 and 3.30, respectively) than those who spoke English only. Men were significantly more likely to report less healthy eating (OR = 0.65) than were women. Similar trends emerged for inactivity and tobacco use. CONCLUSION: Effective health promotion interventions in low-income housing developments that leverage protective factors while addressing risk factors have the potential to reduce income-related health disparities in these concentrated resource-deprived neighborhoods.

Effects of a tobacco control intervention for teachers in India: results of the Bihar school teachers study.

OBJECTIVES: We assessed a school-based intervention designed to promote tobacco control among teachers in the Indian state of Bihar. METHODS: We used a cluster-randomized design to test the intervention, which comprised educational efforts, tobacco control policies, and cessation support and was tailored to the local social context. In 2009 to 2011, we randomly selected 72 schools from participating school districts and randomly assigned them in blocks (rural or urban) to intervention or delayed-intervention control conditions. RESULTS: Immediately after the intervention, the 30-day quit rate was 50% in the intervention and 15% in the control group (P = .001). At the 9-month postintervention survey, the adjusted 6-month quit rate was 19% in the intervention and 7% in the control group (P = .06). Among teachers employed for the entire academic year of the intervention, the adjusted 6-month abstinence rates were 20% and 5%, respectively, for the intervention and control groups (P = .04). CONCLUSIONS: These findings demonstrate the potent impact of an intervention that took advantage of social resources among teachers, who can serve as role models for tobacco control in their communities.

Patient satisfaction after midurethral sling surgery for stress urinary incontinence.

OBJECTIVE: To identify factors that may contribute to patient satisfaction with outcome in women who received retropubic and transobturator midurethral slings. METHODS: Satisfaction was assessed 12 months postsurgery as a planned analysis in 597 participants from a multicenter randomized trial comparing retropubic with transobturator midurethral slings using the Incontinence Surgery Satisfaction Questionnaire. Significantly related variables associated with satisfaction in univariable analyses were entered into multivariable logistic regression models to test their independent association with satisfaction. RESULTS: One year after surgery, 264 (88.6%) in the retropubic group and 263 (88.0%) in the transobturator group completed satisfaction questionnaires. Both treatment groups demonstrated a high level of satisfaction with respect to urine leakage (retropubic 85.9% compared with transobturator 90.0%; P=.52), urgency to urinate, frequency of urination, capability of physical activity, social activity, ability to engage in sexual activity, and from an emotional standpoint. Baseline characteristics associated with reduced satisfaction were higher Medical, Epidemiologic, and Social Aspects of Aging Questionnaire urgency subscale scores, detrusor overactivity, and diabetes mellitus. The severity of both objective (frequency of incontinence episodes, pad test weight) and subjective (Incontinence Impact Questionnaire and Urogenital Distress Inventory score) measures of incontinence at baseline and the patients' perceptions of preoperative severity of incontinence and expectations of achieving postoperative cure or improvement were not statistically different between satisfied and unsatisfied patients. In the final multivariable model, satisfaction was associated with overall treatment success (odds ratio [OR] 2.57, 95% confidence interval [CI] 1.29-5.13], greater reduction in Urogenital Distress Inventory (OR 0.97, 95% CI 0.96-0.98) and Incontinence Impact Questionnaire scores (OR 0.99, 95% CI 0.98-0.99), and fewer complications (OR 0.55, 95% CI 0.30-0.99). CONCLUSION: The high level of satisfaction seen after midurethral sling procedures is associated with greater objective and patient-perceived improvement of stress incontinence and fewer complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00325039. LEVEL OF EVIDENCE: II.

Intention to quit smoking and concerns about household environmental risks: findings from the Health in Common Study in low-income housing.

PURPOSE: To assess the association between intention to quit smoking and perceptions of household environmental risks among racially/ethnically diverse residents of low-income housing. METHODS: Baseline data were collected from 2007 to 2009 for the Health in Common Study, which assessed social and physical determinants of cancer risk-related behaviors among residents of 20 low-income housing developments in the Greater Boston metropolitan area. Participants were surveyed about their tobacco use and concerns about household exposures. Household environmental inspections were also conducted to identify conditions associated with increased risk of exposure to indoor environmental agents, including pesticides, mold, and cleaning products. RESULTS: Intention to quit smoking was associated with a greater degree of concern about exposures in the home, yet not with the actual presence of household hazards, as identified by home inspections and survey findings. CONCLUSIONS: An ecological approach targeting multiple levels of influence may help to highlight the importance of both quitting tobacco and reducing potential household environmental exposures as part of comprehensive efforts to promote individual and household health.

Financial hardship and self-rated health among low-income housing residents.

BACKGROUND: Self-rated health (SRH) has been shown to be predictive of morbidity and mortality. Evidence also shows that SRH is socioeconomically patterned, although this association differs depending on the indicator of socioeconomic status used. The purpose of this study was to determine the association between SRH and financial hardship among residents of low-income housing. METHODS: We analyzed cross-sectional data from the Health in Common Study (N = 828), an observational study to investigate social and physical determinants of cancer risk-related behaviors among residents of low-income housing in three cities in the Boston metropolitan area. Modified Poisson regression models were used to obtain the relative risk of low SRH (fair or poor), adjusting for demographic and socioeconomic characteristics. RESULTS: Unadjusted models revealed that the respondents reporting financial hardship were 53% more likely to report low SRH compared with those not reporting financial hardship. After controlling for demographic characteristics, socioeconomic characteristics, and psychological distress, the results showed that those reporting financial hardship were 44% more likely to report low SRH. CONCLUSION: Our results suggest that financial hardship is a robust predictor of SRH; and over and above the influence of demographic and traditional socioeconomic indicators, and even psychological distress, financial hardship remains strongly associated with low SRH. Additional research needs to be conducted to further elucidate this pathway and to better understand the determinants of variability in financial hardship among low-income housing residents to ensure the most appropriate policy levers (e.g., housing-related policy, food-related policy) are chosen to improve health outcomes in this population.

Correlates of fruit and vegetable consumption among construction laborers and motor freight workers.

PURPOSE: The aim of this study was to compare and contrast correlates of fruit and vegetable consumption in two blue-collar populations: construction laborers and motor freight workers. METHODS: Cross-sectional data were collected from two groups of male workers: (1) construction laborers (n = 1,013; response rate = 44 %) randomly selected from a national sample, as part of a diet and smoking cessation study; and (2) motor freight workers (n = 542; response rate = 78 %) employed in eight trucking terminals, as part of a tobacco cessation and weight management study. Data were analyzed using linear regression modeling methods. RESULTS: For both groups, higher income and believing it was important to eat right because of work were positively associated with fruit and vegetable consumption; conversely, being white was associated with lower intake. Construction laborers who reported eating junk food due to workplace stress and fatigue had lower fruit and vegetable intake. For motor freight workers, perceiving fast food to be the only choice at work and lack of time to eat right were associated with lower consumption. CONCLUSION: Comparing occupational groups illustrates how work experiences may be related to fruit and vegetable consumption in different ways as well as facilitates the development of interventions that can be used across groups.

Condition-specific quality of life 24 months after retropubic and transobturator sling surgery for stress urinary incontinence.

AIMS: To compare quality of life (QoL) and factors associated with QoL change after retropubic (RMUS) and transobturator midurethral slings (TMUS) using the Incontinence Impact Questionnaire (IIQ) and the International Consultation on Incontinence Questionnaire (ICIQ). METHODS: Five hundred ninety-seven women in a multicenter randomized trial of RMUS versus TMUS were examined. The IIQ and the ICIQ were obtained at baseline and at 12 and 24 months. Repeated-measures analysis of variance tested for differences by treatment group over time. Multivariable analysis identified factors associated with QoL change at 12 months postoperative, controlling for treatment group and baseline QoL. RESULTS: Improvement in IIQ was associated with the following: treatment success, younger age, improvement in stress urinary incontinence (SUI) symptom severity, and bother (all P < 0.05). Improvement in ICIQ was associated with treatment success, younger age, improvement in SUI symptom severity and bother, lower body mass index, and no reoperation (all P < 0.05). Improvement of the IIQ was stable over time (P = 0.35) for both treatment groups (P = 0.66), whereas the ICIQ showed a small but clinically insignificant decline (P = 0.03) in both treatment groups (P = 0.51). CONCLUSIONS: Postoperative QoL was improved after RMUS and TMUS. Measures of QoL functioned similarly, although more surgically modifiable urinary incontinence factors predicted improvement with the IIQ.

Sexual activity and function in women more than 2 years after midurethral sling placement.

OBJECTIVE: The purpose of this study was to assess prospectively the effects of midurethral sling surgery on sexual function and activity. STUDY DESIGN: Sexual activity and function was assessed in 597 women with stress urinary incontinence who were enrolled in a randomized equivalence trial of retropubic compared with transobturator midurethral slings. Repeated measures analysis of variance was used to assess changes in Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire scores over a 2-year period. RESULTS: Significant, similar improvements in sexual function were seen in both midurethral sling groups. Mean Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire scores increased from 32.8 at baseline to 37.6 at 6 months and 37.3 at 24 months (P < .0001). Dyspareunia, incontinence during sex, and fear of incontinence during sex each significantly improved after surgery. Preoperative urge incontinence was associated with abstinence after surgery (P = .02); postoperative urge incontinence negatively impacted sexual function (P = .047). CONCLUSION: Midurethral sling surgery for stress urinary incontinence significantly improves sexual function, although coexistent urge incontinence has a negative impact.

Patient related factors associated with long-term urinary continence after Burch colposuspension and pubovaginal fascial sling surgeries.

PURPOSE: We examined preoperative and postoperative patient related factors associated with continence status up to 7 years after surgery for stress urinary incontinence. MATERIALS AND METHODS: Women randomized to Burch colposuspension or fascial sling surgery and assessed for the primary outcome of urinary continence 2 years after surgery were eligible to enroll in a prospective observational study. Survival analysis was used to investigate baseline and postoperative factors in the subsequent risk of stress urinary incontinence, defined as self-report of stress urinary incontinence symptoms, incontinence episodes on a 3-day diary or surgical re-treatment. RESULTS: Of the women who participated in the randomized trial 74% (482 of 655) were enrolled in the followup study. Urinary continence rates decreased during a period of 2 to 7 years postoperatively from 42% to 13% in the Burch group and from 52% to 27% in the sling group, respectively. Among the baseline factors included in the first multivariable model age (p = 0.03), prior stress urinary incontinence surgery (p = 0.02), menopausal status (0.005), urge index (0.006), assigned surgery (p = 0.01) and recruiting site (p = 0.02) were independently associated with increased risk of incontinence. In the final multivariable model including baseline and postoperative factors, Burch surgery (p = 0.01), baseline variables of prior urinary incontinence surgery (p = 0.04), menopausal status (p = 0.03) and postoperative urge index (p <0.001) were each significantly associated with a greater risk of recurrent urinary incontinence. CONCLUSIONS: Preoperative and postoperative urgency incontinence symptoms, Burch urethropexy, prior stress urinary incontinence surgery and menopausal status were negatively associated with long-term continence rates. More effective treatment of urgency urinary incontinence in patients who undergo stress urinary incontinence surgery may improve long-term overall continence status.

Rate of progression of hepatic fibrosis in patients with chronic hepatitis C: results from the HALT-C Trial.

BACKGROUND & AIMS: The gradual accumulation of hepatic fibrosis in chronic liver disease results in clinical complications. The rate of hepatic fibrosis score progression (RFSP) in predicting clinical outcomes was assessed by extending the 4-year Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial to include preenrollment liver biopsies. METHODS: The RFSP was calculated from the linear regression slope of Ishak fibrosis score vs time in 457 patients with liver biopsies (≥10-mm length) prior to the HALT-C Trial (575 biopsies) plus 1101 on-study biopsies (total 1676 biopsies). Individual slopes were calculated if duration from first to last biopsy was > 4 years. RESULTS: The RFSP as average fibrosis score vs average time in intervals (0-3 and >3 years prestudy, screening, month 24 and 48 on-study) in 455 patients in cohorts of baseline Ishak score ranged from 0.005 with Ishak score 2 to 0.124 with Ishak 6. The RFSP in individual patients (-0.35 to +0.97 Ishak units/year) had a mean of 0.12 ± 0.23 in 344 patients with prestudy and on-study biopsies (group A) and only 0.17 ± 0.22 in 169 with prestudy and screening biopsies (group B). Group A patients with RFSP slope ≥ 0.2 (95 patients, 27.6%) had higher 7-year cumulative rates of non-hepatocellular carcinoma outcomes (46% vs 8%, respectively) and with a hepatocellular carcinoma (10% vs 3%, respectively) than RFSP slope < 02 (249 patients, 72.4%) (P < .0001). RFSP and screening Ishak score correlated independently (P <.0001) with clinical outcomes in multivariate analysis. CONCLUSIONS: Rapid RFSP (>0.2), which occurred in 26.7% of HALT-C Trial patients, correlated strongly with clinical outcomes.

Excess mortality in patients with advanced chronic hepatitis C treated with long-term peginterferon.

UNLABELLED: Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis is to describe the frequency and causes of death among this cohort of patients. Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or nonliver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%), of which 76 were considered liver-related (62%) and 46 nonliver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, P = 0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, P = 0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to nonliver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality and only one death was suspected to be a direct complication of peginterferon. CONCLUSION: Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to nonliver-related causes among patients with bridging fibrosis.

A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C.

UNLABELLED: The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. Six hundred seventy-nine clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) (P<0.0001). Child-Turcotte-Pugh (CTP) score≥7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score≥7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow-up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis. CONCLUSION: Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7.

Iron levels in hepatocytes and portal tract cells predict progression and outcomes of patients with advanced chronic hepatitis C.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: Participants who developed clinical outcomes [CTP > 7, 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 [P < 0.0001]. 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 [P < 0.0001] over time. Serum iron and TIBC fell significantly over time [P < 0.0001], 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. CONCLUSIONS: 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.