Effect of conventional interferon-α in patients with HBeAg-positive chronic hepatitis B: a systematic review and meta-analysis.
Although a few studies have tested the effect of interferon-α on chronic hepatitis B, its treatment effect remains uncertain, and the association of treatment effect with intervention characteristics has not been thoroughly explored. This study examined the effect of IFN-α in patients with HBeAg-positive chronic hepatitis B, and investigated the characteristics associated with treatment effect.



We searched MEDLINE,  Index, Current Content Connect, Cochrane Controlled Trial Register, and Chinese Biomedical Database, all up to 15 September 2009. We included randomized trials comparing IFN-α to placebo, no treatment, or standard care (SC) in patients with HBeAg-positive chronic hepatitis B. Two reviewers assessed the risk of bias and extracted data, independently and in duplicate. We conducted meta-analyses of the included studies, and subgroup analyses to examine the association of pre-specified characteristics (eg, dose, treatment duration) with treatment effect.



A total of 31 randomized controlled trials, involving 2164 patients, were included. The risk of bias varied across studies. Compared with placebo, no treatment, or SC, IFN-α improved loss of HBeAg (OR 2.36, 95% CI 1.83 to 3.04), HBV DNA undetectability (OR 2.04, 95% CI 1.28 to 3.32), HBeAg seroconversion (OR 1.82, 95% CI 1.26 to 2.62), ALT normalization (OR 1.24, 95% CI 1.01 to 1.56), and loss of HBsAg (OR 2.45, 95% CI 1.22 to 4.91). Treatment effects differed in high versus low dose, and long versus short duration of IFN-α. The effect of high dose IFN-α (OR 3.28, 95% CI 2.31 to 4.66) is statistically larger than that of low dose IFN-α (OR 1.58, 95% CI 1.10 to 2.28) on loss of HBeAg (interaction P = 0.017), and longer IFN-α treatment durations produce greater effects (OR 3.28, 95% CI 2.16 to 5.00) than do shorter durations (OR 1.94, 95% CI 0.42 to 2.66, interaction P = 0.038). High dose IFN-α had a significant effect on HBV DNA undetectability (OR 2.80, 95% CI 2.03 to 3.86), while low dose IFN-α did not (OR 0.93, 95% CI 0.61 to 1.41, interaction P = 0.01); longer treatments significantly improved HBV DNA undetectability (OR 2.58, 95% CI 1.62 to 4.12), but shorter durations did not (OR 1.28, 95% CI 0.83 to 1.97, interaction P = 0.024).



IFN-α can improve serological, biomedical, and virological response. Higher doses and prolonged treatments appear to have larger treatment benefits than lower doses and shorter treatments. However, the increased adverse reactions and costs associated with higher doses and prolonged treatment warrant caution in applying these results.

title: Methodological issues in cost-effectiveness studies: a brief overview.
abstract: This article discussed two methodological issues around cost-effectiveness studies, including validity and transferability of results. In an economic analysis study, methods to costing, health utility measurement, and economic modeling represent three important sources that may threaten the validity. Variations in health systems and clinical practice, and differential resource use and unit prices across regions and countries may have potentially large influence on transferability. The limitations of piggybacked design may also have implications for transferability. Caution is warranted in the design, conduct, and interpretation of cost-effectiveness studies regarding their validity and transferability.

title: Endocannabinoid signaling in female reproduction.
abstract: Marijuana is a preparation of the flower, as well as the leaves and seeds, of the plant Cannabis sativa. Marijuana has been used for medicinal and recreational purposes for thousands of years due to its psychoactive effects including euphoria, sedation, and analgesia. Although it has been suspected for decades that marijuana has adverse effects on female fertility, the underlying molecular mechanism was not clear. The discovery of cannabinoid receptors and endocannabinoids has advanced studies if cannabinoid signaling. Since then, numerous studies have been published on cannabinoid signaling in female reproductive events, including preimplantation embryo development, oviductal embryo transport, embryo implantation, placentation, and parturition. This review focuses on various aspects of endocannabinoid signaling in female fertility.

title: “Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice
abstract: BackgroundTamoxifen is used in hormone therapy for estrogen-receptor (ER)-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf), a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers.MethodsIn a model of breast cancer prevention, female Balb/c mice treated with tamoxifen (5 mg/Kg) were fed an Fe-Lf supplemented diet (5 g/Kg diet) or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18) and interferon γ (IFN-γ) were analyzed.ResultsTamoxifen weakly (IC50 ~ 8 μM) inhibited the proliferation of 4T1 cells at pharmacological concentrations in vitro. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4 day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all P < 0.001), respectively, compared to untreated controls. The combination therapy was significantly (all P < 0.05) more effective than the respective monotherapies. Oral Fe-Lf attenuated the loss of body weight caused by tamoxifen and cancer cachexia. It prevented tamoxifen-induced reductions in serum levels of IL-18 and IFN-γ, and intestinal cells expressing IL-18 and IFN-γ. It increased the levels of Lf in leukocytes residing in gut-associated lymphoid tissues. B, T and Natural killer (NK) cells containing high levels of Lf were identified in 4T1 tumors, suggesting they had migrated from the intestine. Similar effects of Fe-Lf and tamoxifen on tumor cell viability were seen in the treatment of established tumors.ConclusionsThe results indicate that Fe-Lf is a potent natural adjuvant capable of augmenting the chemotherapeutic activity of tamoxifen. It could have application in delaying relapse in tamoxifen-treated breast cancer patients who are at risk of developing ER-negative tumors.

title: Characterization of Nuclear Localization and SUMOylation of the ATBF1 Transcription Factor in Epithelial Cells
abstract: ATBF1/ZFHX3 is a large transcription factor that functions in development, tumorigenesis and other biological processes. ATBF1 is normally localized in the nucleus, but is often mislocalized in the cytoplasm in cancer cells. The mechanism underlying the mislocalization of ATBF1 is unknown. In this study, we analyzed the nuclear localization of ATBF1, and found that ectopically expressed ATBF1 formed nuclear body (NB)-like dots in the nucleus, some of which indeed physically associated with promyelocytic leukemia (PML) NBs. We also defined a 3-amino acid motif, KRK2615-2617, as the nuclear localization signal (NLS) for ATBF1. Interestingly, diffusely distributed nuclear SUMO1 proteins were sequestered into ATBF1 dots, which could be related to ATBF1's physical association with PML NBs, known SUMOylation hotspots. Furthermore, ATBF1 itself was SUMOylated. ATBF1 SUMOylation occurred at more than 3 lysine residues including K2349, K2806 and K3258 and was nuclear specific. Finally, the PIAS3 SUMO1 E3 ligase, which interacts with ATBF1 directly, diminished rather than enhanced ATBF1 SUMOylation, preventing the co-localization of ATBF1 with SUMO1 in the nucleus. These findings suggest that nuclear localization and SUMOylation are important for the transcription factor function of ATBF1, and that ATBF1 could cooperate with PML NBs to regulate protein SUMOylation in different biological processes.

title: Prescribing behaviour of village doctors under China's New Cooperative Medical Scheme.
abstract: In 2003, China introduced a new community-based rural health insurance called the New Cooperative Medical Scheme (NCMS). In 2005, to assess the NCMS effects on village doctors' prescribing behaviour, we compared an NCMS county and a non-NCMS county in Shandong Province. We collected information from a representative total of 2271 patient visits in 30 village health stations (15 per county). The average number of drugs prescribed (4.6 in the NCMS county vs. 3.1 in the non-NCMS county) and use of antibiotics (72.4% vs. 59.3%) and injections (65.1% vs. 56.3%) were high in both counties, and higher in the NCMS county. Within NCMS villages, prescribing for insured vs. uninsured patients showed a similar pattern with more drugs, antibiotics and injections for those insured. Overall, for NCMS patients, the prescription excess was about equal in value to their 20% fee discount. We conclude that over-prescribing is common in villages and worse with NCMS health insurance, raising concerns for health service quality and drug-use safety. We propose that the NCMS should be redesigned with incentives for service quality improvement. A stricter regulatory environment for doctors' prescriptions is needed in rural China to counter irrational drug use.

title: Meta-analysis of randomized trials for health care interventions: one for all?
abstract: Meta-analysis of randomized trials stands at the top of the epidemiological designs to test the effect of health care interventions. Ideally, it systematically and comprehensively collects the relevant randomized trials, and pools the trials to generate a single estimate of effects. However, the rationale for meta-analysis may not always be thoughtfully considered, and overlooking underlying principles may cause illusions. This article revisits the rationale for meta-analysis, discusses how meta-analysis can be misleading, and summarizes approaches to critically and judiciously interpret and use the results of meta-analysis.