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.

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: 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: Up-regulation of survivin by AKT and hypoxia-inducible factor 1α contributes to cisplatin resistance in gastric cancer.
abstract: This study investigated the contribution of survivin and its upstream regulators, AKT and hypoxia-inducible factor 1α (HIF-1α), to the resistance of gastric cancer cells to cisplatin (CDDP). We found that over-expression of survivin increased the resistance of SGC7901 and BGC823 gastric cancer cells to CDDP. Its over-expression abrogated CDDP-induced inhibition of cell proliferation and CDDP-induced cell apoptosis. In contrast, down-regulation of survivin expression using small hairpin RNA (shRNA) vectors and the small-molecule inhibitor YM155, or inhibition of survivin function using a recombinant cell-permeable dominant-negative survivin protein (dNSur9), promoted CDDP-induced apoptosis. CDDP-resistant sub-lines generated from the parental SGC7901 and BGC823 cells by exposure to increasing concentrations of CDDP expressed higher levels of HIF-1α and survivin in response to hypoxia, and higher levels of phosphorylated AKT (pAKT). Specific inhibition of AKT reduced the expression of HIF-1α and survivin, whereas specific inhibition or depletion of HIF-1α reduced survivin expression but had no effect on the expression of phosphorylated AKT. The expression levels of survivin affected the therapeutic efficacy of CDDP in treating gastric tumors in mice. Specific inhibition of survivin, AKT and HIF-1α enhanced the sensitivity of CDDP-resistant cells to CDDP. Specific inhibition of survivin, AKT and HIF-1α synergized with CDDP to suppress the growth of gastric tumors that had been engineered to overexpress survivin. In summary, the results provide evidence that up-regulation of survivin by AKT and HIF-1α contributes to CDDP resistance, indicating that inhibition of these pathways may be a potential strategy for overcoming CDDP resistance in the treatment of gastric cancer.

title: (R)-N-(3-Methoxyphenyl)-tert-butanesulfinamide
abstract: The title compound, C11H17NO2S, was obtained by the reaction of (R)-tert-butanesulfinamide with 3-methoxyphenyl bromide in toluene. In the crystal, molecules interact head-to-tail through N—H⋯O and C—H⋯O hydrogen bonds, forming one-dimensional chains parallel to the a axis.

title: Synthetic cannabinoids and potential reproductive consequences.
abstract: Increases in emergency room visits due to abuse of designer drugs, popularly known by the street names "K2" and "Spice," are a cause for social, judicial, and clinical concerns. The psychoactive components in these herbal drugs mainly consist of different synthetic cannabinoids, and users of these street drugs are primarily within the age group of 12 to 20years old. The abusive use of synthetic cannabinoids results in anxiety, nausea, vomiting, tachycardia, elevated blood pressure, tremors, seizures, hallucinations, and paranoid behavior, but the effects of maternal use of synthetic cannabinoids during pregnancy are ambiguous due to limited studies in humans and a relative short history of the drugs. In this review, we discuss the known and potential adverse effects of synthetic cannabinoids on human pregnancy using knowledge gathered from studies in mice and limited studies in humans. In mice, multiple sites and stages of pregnancy are potential targets of synthetic cannabinoids, including preimplantation embryo development, oviductal embryo transport, implantation, placentation, and parturition. It is anticipated that maternal use of synthetic cannabinoids would result in severely compromised female fertility and pregnancy outcome.

title: Palladium-catalyzed C-N cross coupling of sulfinamides and aryl halides.
abstract: The palladium-catalyzed C-N cross coupling of sulfinamides and aryl halides is reported. In the presence of Pd(2)(dba)(3), tBuXPhos, NaOH, and a small amount of water, the C-N cross coupling of chiral tert-butanesulfinamide and aryl halides was accomplished to give N-aryl tert-butanesulfinamide without racemization, and the coupling of racemic p-toluenesulfinamide smoothly afforded N-aryl p-toluenesulfinamides. 2-Bromopyridine was also suitable for the coupling. Addition of a small amount of water to the catalytic system was of importance to obtain high yields.