High versus standard doses interferon-alpha in the treatment of naïve chronic hepatitis C patients in Taiwan: a 10-year cohort study

BACKGROUND: Interferon-alpha monotherapy is effective in less than one-third patients with chronic hepatitis C. The dose-effect, tolerability and durability of interferon-alpha treatment and its long-term effect on the prevention of cirrhosis and hepatocellular carcinoma in naïve Taiwanese patients with chronic hepatitis C have not been well investigated. We conducted the present cohort study treated with high and standard interferon-alpha to illustrate the issues. METHODS: We performed a long-term virologic and histological follow-up of 214 chronic hepatitis C patients treated with interferon-alpha, 3 million units (3-MU, n = 80) or 6-MU (n = 134) thrice weekly for 24 weeks, in Taiwan between 1992 and 2001. RESULTS: There was no difference in the incidence of discontinuation between 3-MU and 6-MU groups (4/80, 5.0% versus 10/134. 7.5%). The 6-MU group had similar incidence of adverse events with the 3-MU group, except that 6-MU group had significantly higher incidence of psychological manifestations, mainly presented as irritability. The rates of sustained virological response (SVR) were significantly higher in 6-MU regimen (37.1%) than in 3-MU regimen (23.7%, p < 0.05) in per protocol analysis. Based on multivariate analysis, baseline viral load was strongly associated with SVR, followed by hepatitis C virus genotype, interferon-alpha regimen, and liver fibrosis. A histological improvement in necroinflammatory activity, but not in fibrosis was observed in the follow-up biopsy performed 0.5–5.5 years (mean: 1.9 years, n = 51) after end-of-treatment. Among patients without SVR, there was more activity improvement in 6-MU group. The durability of SVR was 100% (18/18) and 97.8% (45/46) for 3-MU and 6-MU group, respectively, in a mean follow-up period of 6.81 years (5.25–9.18 years). For 163 baseline non-cirrhotic patients, 9 of 84 (10.7%) non-responders and 3 of 79 (3.8%) sustained responders progressed to cirrhosis during a mean follow-up period of 5.52 and 5.74 years, respectively (p = 0.067, Kaplan-Meier survival analysis, log-rank test). For all 200 patients, hepatocellular carcinoma was detected in 12 of 113 (10.6%) non-responders and one of 87 (1.1%) sustained responders during a mean follow-up period of 5.67 and 5.73 years, respectively (p < 0.01, Kaplan-Meier survival analysis, log-rank test). CONCLUSION: We confirm the dose effect of interferon-alpha in chronic hepatitis C. Six-MU regimen had better efficacy than 3-MU regimen in virologic and histological responses. Both regimens had good tolerability and durability in Taiwan. Sustained response could reduce the incidence of cirrhotic change and hepatocarcinogenesis

Enhancing energy and glucose metabolism by disrupting triglyceride synthesis: Lessons from mice lacking DGAT1

Although the ability to make triglycerides is essential for normal physiology, excess accumulation of triglycerides results in obesity and is associated with insulin resistance. Inhibition of triglyceride synthesis, therefore, may represent a feasible strategy for the treatment of obesity and type 2 diabetes. Acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) is one of two DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 have increased energy expenditure and insulin sensitivity and are protected against diet-induced obesity and glucose intolerance. These metabolic effects of DGAT1 deficiency result in part from the altered secretion of adipocyte-derived factors. Studies of DGAT1-deficient mice have helped to provide insights into the mechanisms by which cellular lipid metabolism modulates systemic carbohydrate and insulin metabolism, and a better understanding of how DGAT1 deficiency enhances energy expenditure and insulin sensitivity may identify additional targets or strategies for the treatment of obesity and type 2 diabetes

Twisted fallopian tube in pregnancy: a case report

BACKGROUND: Isolated twisted fallopian tube is an uncommon event, isolated twisted fallopian tube in pregnancy is also very rare. The diagnosis is often difficult and established during the operation. The right fallopian tube is most common affected. CASE PRESENTATION: We report an uncommon twisted left fallopian tube in pregnancy. A 34-year-old G(3)P(2) 28 weeks pregnant woman presented with acute left lower abdominal pain. The clinical and ultrasonographic findings led to diagnosis of twisted left ovarian cyst. Emergency exploratory laparotomy was performed. A twisted left fallopian tube and paratubal cyst was noted and left salpingectomy was performed. The postoperative course was uneventful and the pregnancy continued until term without complication. CONCLUSIONS: Although isolated twisted fallopian tube during pregnancy is very rare, it should be included in the differential diagnosis of acute abdomen in pregnancy. Early surgical intervention will decrease obstetric morbidity and may allow preservation of the fallopian tube

Environmental Health Disparities: A Framework Integrating Psychosocial and Environmental Concepts

Although it is often acknowledged that social and environmental factors interact to produce racial and ethnic environmental health disparities, it is still unclear how this occurs. Despite continued controversy, the environmental justice movement has provided some insight by suggesting that disadvantaged communities face greater likelihood of exposure to ambient hazards. The exposure–disease paradigm has long suggested that differential “vulnerability” may modify the effects of toxicants on biological systems. However, relatively little work has been done to specify whether racial and ethnic minorities may have greater vulnerability than do majority populations and, further, what these vulnerabilities may be. We suggest that psychosocial stress may be the vulnerability factor that links social conditions with environmental hazards. Psychosocial stress can lead to acute and chronic changes in the functioning of body systems (e.g., immune) and also lead directly to illness. In this article we present a multidisciplinary framework integrating these ideas. We also argue that residential segregation leads to differential experiences of community stress, exposure to pollutants, and access to community resources. When not counterbalanced by resources, stressors may lead to heightened vulnerability to environmental hazards

Single nucleotide polymorphisms of the APC gene and colorectal cancer risk: a case-control study in Taiwan

BACKGROUND: Colorectal cancer (CRC), which has become especially prevalent in developed countries, is currently the third highest cause of cancer mortality in Taiwan. Mutation of the adenomatous polyposis coli (APC) gene, a tumour suppressor, is thought to be an early event in colorectal tumourigenesis. To date, however, no large-scale screening for APC gene variants in Chinese subjects has been performed. The present study was undertaken to identify APC gene variants that are significantly associated with the occurrence of CRC in Taiwanese subjects. METHODS: In order to compare the genotype distribution of variant sites, the full-length APC genes of 74 healthy individuals and 80 CRC patients were sequenced. RESULTS: Among the 154 Taiwanese subjects examined in this study, three new mutations, but no previously reported mutations, were found. One deletion at codon 460 leading to a frameshift and two missense mutations resulting in p.V1125A and p.S1126R substitutions were identified. Additionally, three high risk genotypes associated with three single nucleotide polymorphisms and one low risk genotype at codon 1822 were identified. CONCLUSION: The findings of this case-control study are consistent with the proposal that Taiwanese subjects differ from other subjects with respect to phenotypic presentation of APC and CRC risk

IL28B SNP rs12979860 Is a Critical Predictor for On-Treatment and Sustained Virologic Response in Patients with Hepatitis C Virus Genotype-1 Infection

Single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) have received considerable interest for their association with sustained virological response (SVR) when treating patients of genotype-1 hepatitis C virus (GT1-HCV) chronic infection with pegylated interferon and ribavirin (PegIFN/RBV). This study was to investigate the predictive power of IL28B SNPs for on-treatment responses and SVR in treatment-naïve patients with GT1-HCV chronic infection.We analyzed ten SNPs of IL28B in 191 treatment-naïve patients with GT1-HCV chronic infection who received PegIFN/RBV. In these patients, rapid virological response (RVR), early virological response (EVR) and SVR were achieved in 69.6%, 95.8% and 68.6% of the patients, respectively. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated age (0.96; 0.93-0.99; 0.012), low baseline viral load (4.65; 2.23-9.66; <0.001) and CC genotype of rs12979860 (7.74; 2.55-23.53; <0.001) but no other SNPs were independent predictors for SVR. In addition, none of the ten SNPs examined were associated with baseline viral load and stages of liver fibrosis. Regarding RVR, low baseline viral load (2.83; 1.40-5.73; 0.004) and CC genotype of rs12979860 (10.52; 3.45-32.04; <0.001) were two critical predictors. As for EVR, only CC genotype of rs12979860 (36.21; 6.68-196.38; <0.001) was the predictor. Similarly, for end of treatment response (ETR), CC genotype of rs12979860 (15.42; 4.62-51.18; <0.001) was the only predictor. For patients with RVR, only low baseline viral load (3.90; 1.57-9.68; 0.003) could predict the SVR. For patients without RVR, only rs12979860 (4.60; 1.13-18.65; 0.033) was the predictor for SVR.rs12979860 is the critical predictor for RVR, EVR, ETR and SVR in treatment-naïve patients of GT1-HCV chronic infection. Furthermore, this SNP is the only predictor for SVR in patients without RVR. These results have provided evidence that rs12979860 is the ideal IL28B SNP for genetic testing in treating patients of GT1-HCV chronic infection

Comparison of alternative risk adjustment measures for predictive modeling: high risk patient case finding using Taiwan's National Health Insurance claims

<p>Abstract</p> <p>Background</p> <p>Predictive modeling presents an opportunity to contain the expansion of medical expenditures by focusing on very few people. Evaluation of how risk adjustment models perform in predictive modeling in Taiwan or Asia has been rare. The aims of this study were to evaluate the performance of different risk adjustment models (the ACG risk adjustment system and prior expenditures) in predictive modeling, using Taiwan's National Health Insurance (NHI) claims data, and to compare characteristics of potentially high-expenditure subjects identified through different models.</p> <p>Methods</p> <p>A random sample of NHI enrollees continuously enrolled in 2002 and 2003 (n = 164,562) was selected. Health status measures and total expenditures derived from 2002 NHI claims data were used to predict the possibility of becoming 2003 top users. Statistics-based indicators (C-statistics, sensitivity, & Predictive Positive Value) and characteristics of identified top groups by different models (expenditures and prevalence of manageable diseases) were presented.</p> <p>Results</p> <p>Both diagnosis-based and prior expenditures models performed much better than the demographic model. Diagnosis-based models were better in identifying top users with manageable diseases; prior expenditures models were better in statistics-based indicators and identifying people with higher average expenditures. Prior expenditures status could correctly identify more actual top users than diagnosis-based or demographic models. The proportions of actual top users that could be identified by diagnosis-based models alone were much lower than that identified by prior expenditures status.</p> <p>Conclusions</p> <p>Predicted top users identified by different models have different characteristics and there is little agreement between modes regarding which groups would be potentially top users; therefore, which model to use should depend on the purpose of predictive modeling. Prior expenditures are a more powerful tool than diagnosis-based risk adjusters in terms of correctly identifying more actual high expenditures users. There is still much room left for improvement of diagnosis-based models in predictive modeling.</p

Clinical and laboratory findings associated with severe scrub typhus

<p>Abstract</p> <p>Background</p> <p>Scrub typhus is a mite-borne bacterial infection of humans caused by <it>Orientia tsutsugamushi </it>that causes a generalized vasculitis that may involve the tissues of any organ system. The aim of this study was to identify factors associated to severe complications from scrub typhus.</p> <p>Methods</p> <p>We conducted this prospective, case-control study on scrub typhus patients who presented to the Department of Internal Medicine at Chosun University Hospital between September, 2004 and December, 2006. Cases were 89 scrub typhus patients with severe complications and controls were 119 scrub typhus patients without severe complications.</p> <p>Results</p> <p>There were significant differences in the absence of eschar, white blood cell (WBC) counts, hemoglobin, albumin, serum creatinine, fibrinogen, C-reactive protein (CRP), and active partial thromboplastin time (aPTT) between the two groups. Multivariate analysis demonstrated that only the following four factors were significantly associated with the severe complications of scrub typhus: (1) age ≥ 60 years (odd ratio [OR] = 3.13, <it>P </it>= 0.002, confidence interval [CI] = 1.53-6.41), (2) the absence of eschar (OR = 6.62, <it>P </it>= 0.03, CI = 1.22-35.8, (3) WBC counts > 10, 000/mm3 (OR = 3.6, <it>P </it>= 0.001, CI = 1.65-7.89), and (4) albumin ≤ 3.0 g/dL (OR = 5.01, <it>P </it>= 0.004, CI = 1.69-14.86).</p> <p>Conclusions</p> <p>Our results suggest that clinicians should be aware of the potential for complications, when scrub typhus patients are older (≥ 60 years), presents without eschar, or laboratory findings such as WBC counts > 10, 000/mm3, and serum albumin level ≤ 3.0 g/dL. Close observation and intensive care for scrub typhus patients with the potential for complications may prevent serious complications with subsequent reduction in its mortality rate.</p