Long-term results of a randomized, observation-controlled, phase III trial of adjuvant interferon Alfa-2b in hepatocellular carcinoma after curative resection.

OBJECTIVE: To investigate the clinical efficacy of adjuvant interferon alfa-2b (IFNα-2b) therapy on recurrence-free survival (RFS) of patients with postoperative viral hepatitis-related hepatocellular carcinoma (HCC). BACKGROUND: Despite most individual trials have failed to meet their primary endpoint, recent pooled-data meta-analyses suggest that adjuvant IFN therapy may significantly reduce the incidence of recurrence in curatively ablated HCC. METHODS: Patients with curative resection of viral hepatitis-related HCC were eligible, and were stratified by underlying viral etiology and randomly allocated to receive either 53 weeks of adjuvant IFNα-2b treatment or observation alone. The primary endpoint of this study was RFS. RESULTS: A total of 268 patients were enrolled with 133 in the IFNα-2b arm and 135 in the control arm. Eighty percent of them were hepatitis B surface antigen seropositive. At a median follow-up of 63.8 months, 154 (57.5%) patients had tumor recurrence and 84 (31.3%) were deceased. The cumulative 5-year recurrence-free and overall survival rates of intent-to-treat cohort were 44.2% and 73.9%, respectively. The median RFS in the IFNα-2b and control arms were 42.2 (95% confidence interval [CI], 28.1-87.1) and 48.6 (95% CI, 25.5 to infinity) months, respectively (P = 0.828, log-rank test). Adjuvant IFNα-2b treatment was associated with a significantly higher incidence of leucopenia and thrombocytopenia. Thirty-four (24.8%) of treated patients required dose reduction, and 5 (3.8%) of these patients subsequently withdrew from therapy because of excessive toxicity. Adjuvant IFNα-2b only temporarily suppressed viral replication during treatment period. CONCLUSIONS: In this study, adjuvant IFNα-2b did not reduce the postoperative recurrence of viral hepatitis-related HCC. More potent antiviral therapy deserves to be explored for this patient population. This study is registered at ClinicalTrials.gov and carries the identifier NCT00149565.

Risk indicators for early childhood caries in Taiwan.

OBJECTIVES: The purpose of this study was to investigate the prevalence, patterns, and etiological factors for caries in children. METHODS: A total of 981 children less than 6 years of age were examined using a dental mirror and explorer. A parent or a caregiver was asked to complete a questionnaire regarding information about the child, the household, and oral hygiene. The prevalence and patterns of dental caries including pit and fissure caries, facial/lingual caries, molar proximal caries, and facial/lingual molar proximal lesions, were analyzed. Each child was classified as caries free or as having one of these four caries patterns. RESULTS: Weighted mean deft was 0.14 at age 2, 2.58 at age 3, 4.41 at age 4, 6.94 at age 5, and 7.31 at age 6. Weighted mean defs was 4.71, 8.44, 16.45 and 18.64 at ages 3, 4, 5, and 6, respectively. By age 2, 5.09% of children had caries. By age 6, 89.38% of children had caries. By age 3, 30.02% of children fitted the facial and lingual pattern of caries and by age 6, 52.90% of children fit the 'facial-lingual and molar-proximal' pattern, indicating extensive smooth surface decay. The total prevalence of early childhood caries was 56%. Multivariate-adjusted odds ratios identified factors associated with the high caries experience of the young children and found caries was strongly associated with the lack of proper tooth brushing and high consumption of sweets. Higher caries scores were also associated with areas of low urbanization. CONCLUSIONS: The findings of this survey indicated a high level of untreated caries among children in Taiwan.

Optimal word sizes for dissimilarity measures and estimation of the degree of dissimilarity between DNA sequences.

MOTIVATION: Several measures of DNA sequence dissimilarity have been developed. The purpose of this paper is 3-fold. Firstly, we compare the performance of several word-based or alignment-based methods. Secondly, we give a general guideline for choosing the window size and determining the optimal word sizes for several word-based measures at different window sizes. Thirdly, we use a large-scale simulation method to simulate data from the distribution of SK-LD (symmetric Kullback-Leibler discrepancy). These simulated data can be used to estimate the degree of dissimilarity beta between any pair of DNA sequences. RESULTS: Our study shows (1) for whole sequence similiarity/dissimilarity identification the window size taken should be as large as possible, but probably not >3000, as restricted by CPU time in practice, (2) for each measure the optimal word size increases with window size, (3) when the optimal word size is used, SK-LD performance is superior in both simulation and real data analysis, (4) the estimate beta of beta based on SK-LD can be used to filter out quickly a large number of dissimilar sequences and speed alignment-based database search for similar sequences and (5) beta is also applicable in local similarity comparison situations. For example, it can help in selecting oligo probes with high specificity and, therefore, has potential in probe design for microarrays. AVAILABILITY: The algorithm SK-LD, estimate beta and simulation software are implemented in MATLAB code, and are available at http://www.stat.ncku.edu.tw/tjwu