205981265
A methodological framework of preparing economic evidence for selection of medicines in the Chinese setting.
Medicines are becoming a major component of health expenditure in China. Selection of effective and cost-effective medicines represents an important effort to improve medicines use. A guideline on cost-effectiveness studies has been available in China. This guideline, however, fails to be a practical tool to prepare and critically appraise economic evidence. This article discusses, in the Chinese context, the approach to integrating economic component into the medicines selection, and elaborates the methods of producing economic evidence, including conducing economic reviews and primary economic studies.
7754587
Effect of conventional interferon-α in patients with HBeAg-positive chronic hepatitis B: a systematic review and meta-analysis.
BACKGROUND
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.


METHODS
We searched MEDLINE, Scientific Citation 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.


RESULTS
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).


CONCLUSIONS
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.
9796021
Methodological issues in cost-effectiveness studies: a brief overview.
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.
20787139
Decision-analytical modelling in health-care economic evaluations
ObjectiveDecision-analytical modelling is widely used in health-care economic evaluations, especially in situations where evaluators lack clinical trial data, and in circumstances where such evaluations factor into reimbursement pricing decisions. This paper aims to improve the understanding and use of modelling techniques in this context, with particular emphasis on Markov modelling.MethodsWe provide an overview, in this paper, of the principles and methodological details of decision-analytical modelling. We propose a common route for practicing modelling that accommodates any type of decision-analytical modelling techniques. We use the treatment of chronic hepatitis B as an example to indicate the process of development, presentation and analysis of the Markov model, and discuss the strengths, weaknesses and pitfalls of different approaches.ConclusionsGood practice of modelling requires careful planning, conduct and analysis of the model, and needs input from modellers and users.
8889473
Cannabinoid/Endocannabinoid signaling impact on early pregnancy events.
It has been known for decades that marijuana and its major psychoactive component Δ⁹-tetrahydrocannabinol (THC) alter both male and female reproductive functions in humans and laboratory animals. The discovery of cannabinoid-like molecules (endocannabinoids), anandamide (AEA) and 2-arachidonylglycerol (2AG), as well as G-protein-coupled cannabinoid/endocannabinoid receptors CB₁ and CB₂, created an opportunity to study the adverse and beneficial effects of cannabinoids/endocannabinoids on fertility using molecular, physiological and genetic approaches. In fact, studies to explore the significance of cannabinoid/endocannabinoid signaling in reproduction have revealed some intriguing physiological roles in early pregnant events. This review summarizes some aspects of these signaling molecules in preimplantation and implantation biology utilizing genetically engineered mouse models.
30147678
GRAS proteins: the versatile roles of intrinsically disordered proteins in plant signalling.
IDPs (intrinsically disordered proteins) are highly abundant in eukaryotic proteomes and important for cellular functions, especially in cell signalling and transcriptional regulation. An IDR (intrinsically disordered region) within an IDP often undergoes disorder-to-order transitions upon binding to various partners, allowing an IDP to recognize and bind different partners at various binding interfaces. Plant-specific GRAS proteins play critical and diverse roles in plant development and signalling, and act as integrators of signals from multiple plant growth regulatory and environmental inputs. Possessing an intrinsically disordered N-terminal domain, the GRAS proteins constitute the first functionally required unfoldome from the plant kingdom. Furthermore, the N-terminal domains of GRAS proteins contain MoRFs (molecular recognition features), short interaction-prone segments that are located within IDRs and are able to recognize their interacting partners by undergoing disorder-to-order transitions upon binding to these specific partners. These MoRFs represent potential protein-protein binding sites and may be acting as molecular bait in recognition events during plant development. Intrinsic disorder provides GRAS proteins with a degree of binding plasticity that may be linked to their functional versatility. As an overview of structure-function relationships for GRAS proteins, the present review covers the main biological functions of the GRAS family, the IDRs within these proteins and their implications for understanding mode-of-action.
22251514
Sonographic evaluation of para- and perirenal fat thickness is an independent predictor of early kidney damage in obese patients
PurposeTo determine whether para- and perirenal fat ultrasonographic thickness (PFUT) is related to increased urinary albumin excretion and whether PFUT is an independent indicator of early kidney damage in obese subjects.MethodSixty-seven nonhypertensive, nondiabetic obese patients and 34 age- and sex-matched normal healthy volunteers were involved in this study. Clinical characteristics, blood biochemistry, PFUT, and urinary albumin/creatinine ratio (ACR) of the subjects were measured. The intraoperator and interoperator coefficient of variation was 5.6 and 3.2 %, respectively.ResultsACR and PFUT were significantly higher in obese patients than those of normal healthy volunteers. PFUT was higher in obese patients with microalbuminuria than those with normoalbuminuria. Correlation analysis showed PFUT had a positive correlation with body mass index (BMI, r = 0.677, P < 0.01), waist circumference (WC, r = 0.686, P < 0.01), plasma free fatty acids (FFAs, r = 0.589, P < 0.01), and ACR (r = 0.610, P < 0.01). ACR had a positive correlation with BMI (r = 0.444, P < 0.01), WC (r = 0.440, P < 0.01), and plasma FFAs (r = 0.496, P < 0.01). Multivariate regression analyses showed that ACR could be predicted by PFUT.ConclusionsPFUT may be an independent predictor of early kidney damage in nonhypertensive, nondiabetic obese patients, and PFUT could be a useful tool for the assessment of visceral fat and early kidney damage in obese patients.
10054183
Uterine deletion of Gp130 or Stat3 shows implantation failure with increased estrogenic responses.
Leukemia inhibitory factor (LIF), a downstream target of estrogen, is essential for implantation in mice. LIF function is thought to be mediated by its binding to LIF receptor (LIFR) and recruitment of coreceptor GP130 (glycoprotein 130), and this receptor complex then activates signal transducer and activator of transcription (STAT)1/3. However, the importance of LIFR and GP130 acting via STAT3 in implantation remains uncertain, because constitutive inactivation of Lifr, Gp130, or Stat3 shows embryonic lethality in mice. To address this issue, we generated mice with conditional deletion of uterine Gp130 or Stat3 and show that both GP130 and STAT3 are critical for uterine receptivity and implantation. Implantation failure in these deleted mice is associated with higher uterine estrogenic responses prior to the time of implantation. These heightened estrogenic responses are not due to changes in ovarian hormone levels or expression of their nuclear receptors. In the deleted mice, estrogen-responsive gene, Lactoferrin (Ltf), and Mucin 1 protein, were up-regulated in the uterus. In addition, progesterone-responsive genes, Hoxa10 and Indian hedgehog (Ihh), were markedly down-regulated in STAT3-inactivated uteri. These changes in uteri of deleted mice were reflected by the failure of differentiation of the luminal epithelium, which is essential for blastocyst attachment.