International Lessons in New Methods for Grading and Integrating Cost Effectiveness Evidence into Clinical Practice Guidelines

Economic evidence is influential in health technology assessment world-wide. Clinical Practice Guidelines (CPG) can enable economists to include economic information on health care provision. Application of economic evidence in CPGs, and its integration into clinical practice and national decision making is hampered by objections from professions, paucity of economic evidence or lack of policy commitment. The use of state-of-art economic methodologies will improve this. Economic evidence can be graded by 'checklists' to establish the best evidence for decision making given methodological rigor. New economic evaluation checklists, Multi-Criteria Decision Analyses (MCDA) and other decision criteria enable health economists to impact on decision making world-wide. We analyse the methodologies for integrating economic evidence into CPG agencies globally, including the Agency of Health Research and Quality (AHRQ) in the USA, National Health and Medical Research Council (NHMRC) and Australian political reforms. The Guidelines and Economists Network International (GENI) Board members from Australia, UK, Canada and Denmark presented the findings at the conference of the International Health Economists Association (IHEA) and we report conclusions and developments since. The Consolidated Guidelines for the Reporting of Economic Evaluations (CHEERS) 24 item check list can be used by AHRQ, NHMRC, other CPG and health organisations, in conjunction with the Drummond ten-point check list and a questionnaire that scores that checklist for grading studies, when assessing economic evidence. Cost-effectiveness Analysis (CEA) thresholds, opportunity cost and willingness-to-pay (WTP) are crucial issues for decision rules in CEA generally, including end-of-life therapies. Limitations of inter-rater reliability in checklists can be addressed by including more than one assessor to reach a consensus, especially when impacting on treatment decisions. We identify priority areas to generate economic evidence for CPGs by NHMRC, AHRQ, and other agencies. The evidence may cover demand for care issues such as involved time, logistics, innovation price, price sensitivity, substitutes and complements, WTP, absenteeism and presentism. Supply issues may include economies of scale, efficiency changes, and return on investment. Involved equity and efficiency measures may include cost-of-illness, disease burden, quality-of-life, budget impact, cost-effective ratios, net benefits and disparities in access and outcomes.. Priority setting remains essential and trade-off decisions between policy criteria can be based on MCDA, both in evidence based clinical medicine and in health planning

Cost-effectiveness of collaborative care for the treatment of major depressive disorder in primary care. A systematic review

Background. The effectiveness of collaborative care for patients with major depressive disorder in primary care has been established. Assessing its cost-effectiveness is important for deciding on implementation. This review therefore evaluates the cost-effectiveness of collaborative care for major depressive disorder in primary care. Methods. A systematic search on economic evaluations of collaborative care was conducted in Pubmed and PsychInfo. Quality of the studies was measured with the Cochrane checklist and the CHEC-list for economic evaluations. Cost-effectiveness and costs per depression-free days were reported. Results. 8 studies were found, involving 4868 patients. The quality of the cost effectiveness studies, according to the CHEC-list, could be improved. Generally, the studies did not include all relevant costs and did not perform sensitivity analysis. Only 4 out of 8 studies reported cost per QALY, 6 out of 8 reported costs per depression-free days. The highest costs per QALY reported were $49,500, the highest costs per depression-free day were$24. Conclusions. Although studies did not fulfil all criteria of the CHEC-list, collaborative care is a promising intervention and it may be cost-effective. However, to conclude on the cost-effectiveness, depression research should follow economic guidelines to improve the quality of the economic evaluations

Behavior Problems in Relation to Sustained Selective Attention Skills of Moderately Preterm Children

Attention skills may form an important developmental mechanism. A mediation model was examined in which behavioral problems of moderately preterm and term children at school age are explained by attention performance. Parents and teachers completed behavioral assessments of 348 moderately preterm children and 182 term children at 8 years of age. Children were administered a test of sustained selective attention. Preterm birth was associated with more behavioral and attention difficulties. Gestational age, prenatal maternal smoking, and gender were associated with mothers’, fathers’, and teachers’ reports of children’s problem behavior. Sustained selective attention partially mediated the relationship between birth status and problem behavior. Development of attention skills should be an important focus for future research in moderately preterm children

Diversity Arrays Technology (DArT) for Pan-Genomic Evolutionary Studies of Non-Model Organisms

Background: High-throughput tools for pan-genomic study, especially the DNA microarray platform, have sparked a remarkable increase in data production and enabled a shift in the scale at which biological investigation is possible. The use of microarrays to examine evolutionary relationships and processes, however, is predominantly restricted to model or near-model organisms. Methodology/Principal Findings: This study explores the utility of Diversity Arrays Technology (DArT) in evolutionary studies of non-model organisms. DArT is a hybridization-based genotyping method that uses microarray technology to identify and type DNA polymorphism. Theoretically applicable to any organism (even one for which no prior genetic data are available), DArT has not yet been explored in exclusively wild sample sets, nor extensively examined in a phylogenetic framework. DArT recovered 1349 markers of largely low copy-number loci in two lineages of seed-free land plants: the diploid fern Asplenium viride and the haploid moss Garovaglia elegans. Direct sequencing of 148 of these DArT markers identified 30 putative loci including four routinely sequenced for evolutionary studies in plants. Phylogenetic analyses of DArT genotypes reveal phylogeographic and substrate specificity patterns in A. viride, a lack of phylogeographic pattern in Australian G. elegans, and additive variation in hybrid or mixed samples. Conclusions/Significance: These results enable methodological recommendations including procedures for detecting and analysing DArT markers tailored specifically to evolutionary investigations and practical factors informing the decision to use DArT, and raise evolutionary hypotheses concerning substrate specificity and biogeographic patterns. Thus DArT is a demonstrably valuable addition to the set of existing molecular approaches used to infer biological phenomena such as adaptive radiations, population dynamics, hybridization, introgression, ecological differentiation and phylogeography

Effects of acute tryptophan depletion on affective processing in first-degree relatives of depressive patients and controls after exposure to uncontrollable stress

Rationale Individuals with a family history of depression may be more likely to develop depression due to an innate vulnerability of their serotonergic system. However, even though serotonergic vulnerability may constitute a risk factor in the development of depression, it does not seem to be sufficient to cause a depressive episode. Based on previous data, it is suggested that stress may be a mediating factor. Objectives This study examined the role of serotonin (5-HT) in stress coping in individuals with or without a family history of depression. Materials and methods Nineteen healthy first-degree relatives of depressive patients (FH+) and 19 healthy controls without a family history of depression (FH-) were tested in a double-blind placebo-controlled design for affective processing under acute stress exposure, following acute tryptophan depletion (ATD) or placebo. Results Significant negative effects were found of stress on affective processing in FH- and FH+. In addition, FH- responded slower to positive words after stress only following ATD, whereas FH+ responded marginally slower under stress already after placebo and before stress following ATD. Conclusion Acute stress exposure reduces positive affective bias; supporting the role of stress as an important predecessor in the development of depression. Furthermore, FH+ may be more susceptible than FH- to the negative effects of stress as well as to the negative effects of ATD. The results support the assumption that the 5-HT system is involved in stress resilience and may be more vulnerable in first-degree relatives of depression

Integrated transcriptomic and proteomic analysis of the global response of Wolbachia to doxycycline-induced stress

The bacterium Wolbachia (order Rickettsiales), representing perhaps the most abundant vertically transmitted microbe worldwide, infects arthropods and filarial nematodes. In arthropods, Wolbachia can induce reproductive alterations and interfere with the transmission of several arthropod-borne pathogens. In addition, Wolbachia is an obligate mutualist of the filarial parasites that cause lymphatic filariasis and onchocerciasis in the tropics. Targeting Wolbachia with tetracycline antibiotics leads to sterilisation and ultimately death of adult filariae. However, several weeks of treatment are required, restricting the implementation of this control strategy. To date, the response of Wolbachia to stress has not been investigated, and almost nothing is known about global regulation of gene expression in this organism. We exposed an arthropod Wolbachia strain to doxycycline in vitro, and analysed differential expression by directional RNA-seq and label-free, quantitative proteomics. We found that Wolbachia responded not only by modulating expression of the translation machinery, but also by upregulating nucleotide synthesis and energy metabolism, while downregulating outer membrane proteins. Moreover, Wolbachia increased the expression of a key component of the twin-arginine translocase (tatA) and a phosphate ABC transporter ATPase (PstB); the latter is associated with decreased susceptibility to antimicrobials in free-living bacteria. Finally, the downregulation of 6S RNA during translational inhibition suggests that this small RNA is involved in growth rate control. Despite its highly reduced genome, Wolbachia shows a surprising ability to regulate gene expression during exposure to a potent stressor. Our findings have general relevance for the chemotherapy of obligate intracellular bacteria and the mechanistic basis of persistence in the Rickettsiales