Meta-analysis of randomized trials for health care interventions: one for all?
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.

title: Decision-analytical modelling in health-care economic evaluations
abstract: 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.

title: Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials
abstract: BackgroundSubgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome.MethodsWe will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes.DiscussionA clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.

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: Aspects of endocannabinoid signaling in periimplantation biology
abstract: Physiological roles of endocannabinoids, a group of endogenously produced cannabinoid-like lipid molecules that activate G protein-coupled cannabinoid receptors, are being increasingly appreciated in female reproduction. Adverse effects of cannabinoids on female fertility have been suspected for decades; however, underlying molecular and genetic bases by which they exert these effects were not clearly understood. The discovery of cannabinoid receptors (CB1 and CB2), endocannabinoid ligands (anandamide and 2-acylglycerol) as well as their key synthetic and hydrolytic pathways has helped to better understand the roles of cannabinoid/endocannabinoid signaling in preimplantation embryo development, oviductal embryo transport, embryo implantation and postimplantation embryonic growth. This review focuses on various aspects of the endocannabinoid system in female fertility based on studies that used knockout mouse models. The information generated from studies in mice is likely to shed deeper insight into fertility regulation in women.

title: A methodological framework of preparing economic evidence for selection of medicines in the Chinese setting.
abstract: 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.

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: Expression of uncoupling protein 3 is upregulated in skeletal muscle during sepsis.
abstract: Uncoupling protein 3 (UCP3) is a member of the mitochondrial transporter superfamily that is expressed primarily in skeletal muscle. UCP3 is upregulated in various conditions characterized by skeletal muscle atrophy, including hyperthyroidism, fasting, denervation, diabetes, cancer, lipopolysaccharide (LPS), and treatment with glucocorticoids (GCs). The influence of sepsis, another condition characterized by muscle cachexia, on UCP3 expression and activity is not known. We examined UCP3 gene and protein expression in skeletal muscles from rats after cecal ligation and puncture and from sham-operated control rats. Sepsis resulted in a two- to threefold increase in both mRNA and protein levels of UCP3 in skeletal muscle. Treatment of rats with the glucocorticoid receptor antagonist RU-38486 prevented the sepsis-induced increase in gene and protein expression of UCP3. The UCP3 mRNA and protein levels were increased 2.4- to 3.6-fold when incubated muscles from normal rats were treated with dexamethasone (DEX) and/or free fatty acids (FFA) ex vivo. In addition, UCP3 mRNA and protein levels were significantly increased in normal rat muscles in vivo with treatment of either DEX or FFA. The results suggest that sepsis upregulates the gene and protein expression of UCP3 in skeletal muscle, which may at least in part be mediated by GCs and FFA.