Mind the gap! A multilevel analysis of factors related to variation in published cost-effectiveness estimates within and between countries

Background. Published cost-effectiveness estimates can vary considerably, both within and between countries. Despite extensive discussion, little is known empirically about factors relating to these variations. Objectives. To use multilevel statistical modeling to integrate cost-effectiveness estimates from published economic evaluations to investigate potential causes of variation. Methods. Cost-effectiveness studies of statins for cardiovascular disease prevention were identified by systematic review. Estimates of incremental costs and effects were extracted from reported base case, sensitivity, and subgroup analyses, with estimates grouped in studies and in countries. Three bivariate models were developed: a cross-classified model to accommodate data from multinational studies, a hierarchical model with multinational data allocated to a single category at country level, and a hierarchical model excluding multinational data. Covariates at different levels were drawn from a long list of factors suggested in the literature. Results. We found 67 studies reporting 2094 cost-effectiveness estimates relating to 23 countries (6 studies reporting for more than 1 country). Data and study-level covariates included patient characteristics, intervention and comparator cost, and some study methods (e.g., discount rates and time horizon). After adjusting for these factors, the proportion of variation attributable to countries was negligible in the cross-classified model but moderate in the hierarchical models (14%−19% of total variance). Country-level variables that improved the fit of the hierarchical models included measures of income and health care finance, health care resources, and population risks. Conclusions. Our analysis suggested that variability in published cost-effectiveness estimates is related more to differences in study methods than to differences in national context. Multinational studies were associated with much lower country-level variation than single-country studies. These findings are for a single clinical question and may be atypical

Valaciclovir for Chronic Hepatitis BVirus Infection after Lung Transplantation

Abstract. : We report on a chronic asymptomatic hepatitis B surface antigen (HBsAg) carrier who developed an increase in aminotransferase and HBsAg levels 1 year after lung transplantation. During treatment for cutaneous herpes simplex virus (HSV) infection with oral valaciclovir there was a marked decrease in replicating hepatitis B virus (HBV)-DNA and aminotransferase levels, which was sustained for 9 months by continuing low-dose valaciclovir. A second rise in aminotransferase levels again responded to a valaciclovir dose increase and the HBV-DNA levels declined further. Although we cannot exclude a spontaneous variation of the serologic parameters, our observation suggests that valaciclovir may represent a valuable therapeutic option in the treatment of chronic hepatitis B after lung transplantatio

The complex morphology of the young disk MWC 758: Spirals and dust clumps around a large cavity

We present Atacama Large Millimeter Array (ALMA) observations at an angular resolution of 0.1-0.2" of the disk surrounding the young Herbig Ae star MWC 758. The data consist of images of the dust continuum emission recorded at 0.88 millimeter, as well as images of the 13CO and C18O J = 3-2 emission lines. The dust continuum emission is characterized by a large cavity of roughly 40 au in radius which might contain a mildly inner warped disk. The outer disk features two bright emission clumps at radii of about 47 and 82 au that present azimuthal extensions and form a double-ring structure. The comparison with radiative transfer models indicates that these two maxima of emission correspond to local increases in the dust surface density of about a factor 2.5 and 6.5 for the south and north clumps, respectively. The optically thick 13CO peak emission, which traces the temperature, and the dust continuum emission, which probes the disk midplane, additionally reveal two spirals previously detected in near-IR at the disk surface. The spirals seen in the dust continuum emission present, however, a slight shift of a few au towards larger radii and one of the spirals crosses the south dust clump. Finally, we present different scenarios in order to explain the complex structure of the disk.Comment: 15 pages, 11 figures. The paper has been published in ApJ. References added and typos correcte

Evaluation of Information Systems Curricula

Information systems education objectives must continually adapt to a dynamic marketplace for knowledge and skills. For faculty developing programs that better prepare students for this demanding environment, existing research and guidelines provide a foundation to develop relevant coursework. However, an examination of peer institutions indicates a significant variance in how institutions of higher learning address the requirements of local markets as they prepare their students for careers. This study reviews previous information systems curricula research, examines current guidelines for information systems education, analyzes adherence to those guidelines, and summarizes innovative approaches being used by business colleges in the U.S. to prepare students. Our findings indicate that even as the number of information systems programs decline, colleges are looking for relevant ways to serve their students and communities. For information systems education to remain connected to the marketplace, the value provided by a degree in information systems must be clear to future employers. This paper concludes by offering insights gained by an analysis of thriving programs to assist faculty working on improving their undergraduate information systems curriculum

Heterozygosity: An Inconspicuous Meiosis-Linked Intrinsic Mutagen in Mice

The impact of heterozygosity as an intrinsic mutagen in mammals is unknown. In plant models, existent heterozygosity increases the local de novo meiotic mutation rate. Mice offer study of this phenomenon given well-established genomic technologies and strains with known, diverse genomic landscapes of heterozygosity. High resolution genotyping arrays assay heterozygous single-nucleotide polymorphic (SNP) loci and copy number variants (CNVs). Using a J statistic for spatial analysis, 60.9% of autosomes from 707 publicly available array samples have nonrandom spatial associations between heterozygous SNP loci and CNVs. By crossing C57BL/6J inbred mice to DBA/2J inbred mice, heterozygous SNP loci and de novo CNVs were analyzed. Of 43 de novo CNVs in F2 mice compared to both F1 and F2 heterozygous SNP landscapes, 33 and 7 were found to co-localize with heterozygous SNP loci, respectively. Heterozygosity may be an overlooked meiosis-linked contributor to CNV mutagenesis, affecting models of disease risk prediction and evolution

Pressure tuning of structure, superconductivity and novel magnetic order in the Ce-underdoped electron-doped cuprate T'-Pr_1.3-xLa_0.7Ce_xCuO_4 (x = 0.1)

High-pressure neutron powder diffraction, muon-spin rotation and magnetization studies of the structural, magnetic and the superconducting properties of the Ce-underdoped superconducting (SC) electron-doped cuprate system T'-Pr_1.3-xLa_0.7Ce_xCuO_4 with x = 0.1 are reported. A strong reduction of the lattice constants a and c is observed under pressure. However, no indication of any pressure induced phase transition from T' to T structure is observed up to the maximum applied pressure of p = 11 GPa. Large and non-linear increase of the short-range magnetic order temperature T_so in T'-Pr_1.3-xLa_0.7Ce_xCuO_4 (x = 0.1) was observed under pressure. Simultaneously pressure causes a non-linear decrease of the SC transition temperature T_c. All these experiments establish the short-range magnetic order as an intrinsic and a new competing phase in SC T'-Pr_1.2La_0.7Ce_0.1CuO_4. The observed pressure effects may be interpreted in terms of the improved nesting conditions through the reduction of the in-plane and out-of-plane lattice constants upon hydrostatic pressure.Comment: 11 pages, 10 figure

Ganciclovir/valganciclovir prophylaxis decreases cytomegalovirus-related events and bronchiolitis obliterans syndrome after lung transplantation

BACKGROUND: Until recently, cytomegalovirus (CMV) infection represented a major threat to lung transplant recipients. Preliminary studies have shown that antiviral prophylaxis might improve the outcome for these patients. METHODS: We extended our initial pilot trial of prolonged prophylaxis with either oral ganciclovir (1 g 3 times per day) or valganciclovir (450 mg twice per day). The trial included 96 patients who were at risk for CMV-related events. RESULTS: CMV prophylaxis resulted in a significant decrease in CMV-related events (i.e., active infection and disease), from 75% in a control group and for 274 cases from the literature who did not receive prophylaxis to a cumulative incidence of 27% (P < .001). Only 11% of the prophylaxis recipients experienced CMV disease (P = .002). Moreover, at 5 years, there was a significant decrease in the rate of bronchiolitis obliterans syndrome, from 60% to 43% (P = .002), and an improved rate of survival, from 47% to 73% (P= .036), irrespective of the immunosuppressive regimen received. CMV strains with UL97 mutations were recovered from 7 of 12 analyzed cases, but the presence of this mutation had no impact on the severity of CMV disease. CONCLUSIONS: A regimen of prolonged ganciclovir or valganciclovir prophylaxis decreased the rate of active CMV infection and disease, reduced the incidence of bronchiolitis obliterans syndrome, and improved the survival rate. Drug-resistant CMV strains may occur, but such strains appeared to have no impact on the outcome of CMV-related events