A gatekeeping procedure to test a primary and a secondary endpoint in a group sequential design with multiple interim looks.

Glimm et al. (2010) and Tamhane et al. (2010) studied the problem of testing a primary and a secondary endpoint, subject to a gatekeeping constraint, using a group sequential design (GSD) with K=2 looks.

HCV genome-wide genetic analyses in context of disease progression and hepatocellular carcinoma.

Hepatitis C virus (HCV) is a major cause of hepatitis and hepatocellular carcinoma (HCC) world-wide. Most HCV patients have relatively stable disease, but approximately 25% have progressive disease that often terminates in liver failure or HCC. HCV is highly variable genetically, with seven genotypes and multiple subtypes per genotype.

Processes to manage analyses and publications in a phase III multicenter randomized clinical trial.

Background: The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial.

Reproductive history and progression of lower urinary tract symptoms in women: results from a population-based cohort study.

Objective: To examine whether reproductive history and related conditions are associated with the development and persistence of lower urinary tract symptoms (LUTS) other than urinary incontinence in a racially and/or ethnically diverse population-based sample of women.

Materials And Methods: The Boston Area Community Health Survey enrolled 3201 women aged 30-79 years of black, Hispanic, or white race and/or ethnicity. Baseline and 5-year follow-up interviews were completed by 2534 women (conditional response rate, 83.

Associations between supplemental or dietary intake of vitamin C and severity of lower urinary tract symptoms.

Objective: To examine the association between long-term dietary vitamin C intake and recent use of vitamin C supplements with the progression and severity of lower urinary tract symptoms (LUTS).

Participants And Methods: Baseline and 5-year follow-up interviews were completed by 2825 black, Hispanic or white men and women aged 30-79 years in the Boston Area Community Health survey. Dietary and supplemental vitamin C intake was assessed using a validated food frequency questionnaire.

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-1β, 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.

Intake of caffeinated, carbonated, or citrus beverage types and development of lower urinary tract symptoms in men and women.

Evidence to substantiate recommendations for restriction of caffeinated or acidic beverages as self-management for lower urinary tract symptoms (LUTS) is limited. We examined longitudinal and acute associations between beverage intake and LUTS in the Boston Area Community Health (BACH) cohort (n = 4,144) between 2002 and 2010. Multivariable models tested associations between baseline intakes and progression of LUTS at 5-year follow-up, between follow-up intakes and International Prostate Symptom Scores at follow-up, and between 5-year intake changes and LUTS progression.

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.

Contributors to self-reported health in a racially and ethnically diverse population: focus on Hispanics.

Purpose: To understand if Hispanics report health differently than other racial and ethnic groups after controlling for demographics and risk factors for poor health.

Methods: The sample (N = 5502) included 3201 women, 1767 black, 1859 white, and 1876 Hispanic subjects from the Boston Area Community Health Survey, a population-based survey of English- and Spanish-speaking residents of Boston, Massachusetts, United States, aged 30-79 years in 2002-2005. Multiple logistic regression models were used to examine the association between race/ethnicity (including interview language for Hispanics) and fair/poor self-reported health (F/P SRH) adjusting for gender, age, socioeconomic status, depression, nativity, and comorbidities.

Characteristics of persons with overactive bladder of presumed neurologic origin: results from the Boston Area Community Health (BACH) survey.

Aims: To compare the descriptive epidemiology of overactive bladder (OAB) of presumed neurologic origin (NOAB) to OAB of non-neurologic origin (N-NOAB).

Methods: Five thousand five hundred three community-dwelling persons aged 30-79 were interviewed regarding urologic symptoms (2002-2005). NOAB was defined as symptoms of urgency and/or urgency incontinence among those with a self-reported history of healthcare provider diagnosed stroke (N = 98), multiple sclerosis (N = 21), or Parkinson's disease (N = 7).

Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: results from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial.

Unlabelled: Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C virus (HCV). We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred and twenty-seven participants in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.

Predicting cirrhosis and clinical outcomes in patients with advanced chronic hepatitis C with a panel of genetic markers (CRS7).

Objectives: Genetic factors may play a role in fibrosis progression in patients with chronic hepatitis C (CHC). A cirrhosis risk score (CRS7) with seven single nucleotide polymorphisms was previously shown to correlate with cirrhosis in patients with CHC. This study aimed to assess the validity of CRS7 as a marker of fibrosis progression and cirrhosis and as a predictor of clinical outcomes in patients with CHC.

Coffee consumption is associated with response to peginterferon and ribavirin therapy in patients with chronic hepatitis C.

Background & Aims: High-level coffee consumption has been associated with reduced progression of pre-existing liver diseases and lower risk of hepatocellular carcinoma. However, its relationship with therapy for hepatitis C virus infection has not been evaluated.

Methods: Patients (n=885) from the lead-in phase of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial recorded coffee intake before retreatment with peginterferon α-2a (180 μg/wk) and ribavirin (1000-1200 mg/day).

Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial.

Background & Aims: Although percutaneous liver biopsy is a standard diagnostic procedure, it has drawbacks, including risk of serious complications. It is not known whether persons with advanced chronic liver disease have a greater risk of complications from liver biopsy than patients with more mild, chronic liver disease. The safety and complications of liver biopsy were examined in patients with hepatitis C-related bridging fibrosis or cirrhosis who were enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial.

Predicting clinical and histologic outcomes based on standard laboratory tests in advanced chronic hepatitis C.

Background & Aims: Predictors of clinical outcomes and histologic progression among patients with chronic hepatitis C and advanced fibrosis are poorly defined. We developed statistical models to predict clinical and histologic outcomes in such patients.

Methods: Baseline demographic, clinical, and histologic data from Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial participants were subjected to multivariate analyses to determine their ability to predict clinical outcomes (ascites, spontaneous bacterial peritonitis, Child-Turcotte-Pugh score >or=7 on 2 consecutive visits, variceal bleeding, hepatic encephalopathy, and liver-related death) and histologic outcome (>or=2-point increase in Ishak fibrosis stage) during the 3.

Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C.

Unlabelled: Higher coffee consumption has been associated inversely with the incidence of chronic liver disease in population studies. We examined the relationship of coffee consumption with liver disease progression in individuals with advanced hepatitis C-related liver disease. Baseline coffee and tea intake were assessed in 766 participants of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had hepatitis C-related bridging fibrosis or cirrhosis on liver biopsy and failed to achieve a sustained virological response to peginterferon plus ribavirin treatment.

Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease.

Background & Aims: Although the incidence of hepatocellular carcinoma (HCC) is increasing in the United States, data from large prospective studies are limited. We evaluated the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) cohort for the incidence of HCC and associated risk factors.

Methods: Hepatitis C virus-positive patients with bridging fibrosis or cirrhosis who did not respond to peginterferon and ribavirin were randomized to groups that were given maintenance peginterferon for 3.

Interpretation of positive transcription-mediated amplification test results from polymerase chain reaction-negative samples obtained after treatment of chronic hepatitis C.

Unlabelled: The Siemens VERSANT transcription-mediated amplification (TMA) assay is extremely sensitive for the detection of hepatitis C virus (HCV) RNA in serum. Eleven of 180 subjects in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial who achieved polymerase chain reaction (PCR)-defined sustained virological response (SVR) at week 72 also had TMA-positive results from the same blood draw; six were positive on repeat testing. We report the follow-up on these 11 patients, and the reproducibility of TMA test results from PCR-negative samples in relationship to antiviral treatment outcome.

Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial.

Herbal products, used for centuries in Far Eastern countries, are gaining popularity in western countries. Surveys indicate that persons with chronic hepatitis C (CHC) often use herbals, especially silymarin (milk thistle extract), hoping to improve the modest response to antiviral therapy and reduce side effects. The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial, involving persons with advanced CHC, nonresponders to prior antiviral therapy but still willing to participate in long-term pegylated interferon treatment, offered the opportunity to examine the use and potential effects of silymarin.