Societal cost of cancer in Norway –Results of taking a broader cost perspective

BackgroundThe broader cost consequences of diseases may be of interest for a wide range of stakeholders. We aimed to estimate all relevant societal costs of cancer and to provide insight into the relative magnitude of the different cost categories.MethodWe used data from eight different health and work-related registries in Norway. Direct, indirect, and intangible costs (value of lost life years) were estimated over a period of one year with a combination of a top-down and a bottom-up costing approach.ResultsThe indirect costs (EUR 1,997 million per year) are almost as high as direct costs (EUR 2,154 million), and the value of lost life years and quality of life represents the greatest cost related to cancer (EUR 18,200 million). In addition, cancer is associated with other costs which are commonly omitted from cost-of-illness analyses, including informal nursing (EUR 306 million), patient time costs (EUR 85 million), and excess costs of using public funds (EUR 439 million). Breast and cervical cancer had relatively high work absenteeism costs, while pancreatic and lung cancer had relatively high production costs due to premature deaths.DiscussionDirect health care costs represent small proportions of the total societal costs of cancer. Costs commonly omitted in cost-of-illness analyses represent a significant cost and should be measured and valued in these analyses.     

Can Parent Training Alter Parent Practice and Reduce Conduct Problems in Ethnic Minority Children? A Randomized Controlled Trial

A randomized prevention study for ethnic minority mothers assessed the intervention effects of Parent Management Training—Oregon Model (PMTO) on maternal parent practices and child behavior. Ninety-six mothers from Somalia and Pakistan and their children aged 3 to 9 years were randomized to PMTO or a wait-list condition (WLC). Assessments were carried out at the baseline and post-intervention, using standardized measures and a multi-agent approach. All analyses were based on the intention-to-treat principle. Analysis of covariance (ANCOVA) showed that PMTO was effective in enhancing parent practices, with a decrease in harsh discipline and an increase in positive parenting. Moreover, PMTO produced reductions in motherreported child conduct problems. The largest effect sizes were found among mothers who attended more than 50 % of the PMTO group sessions. Teacher reports showed, however, that there were no significant intervention effects on conduct problems and social competence in kindergarten or school. The results emphasize the importance and feasibility of offering PMTO to ethnic minority families.     

The necessary distinction between methodology and philosophical assumptions in healthcare research

Methodological discussions within healthcare research have traditionally described a methodological dichotomy between qualitative and quantitative methods. The aim of this article is to demonstrate that such a dichotomy presents unnecessary obstacles for good research design and is methodologically and philosophically unsustainable. The issue of incommensurability is not a question of method but rather a question of the philosophical premises underpinning a given method. Thus, transparency on the philosophical level is important for validity and consistency as well as for attempts to integrate or establish an interface to other research. I argue that it is necessary to make a distinction between methodology and philosophical assumptions and to ensure consistency in these correlations. Furthermore, I argue that the question of incommensurability is best answered at this basic philosophical level. The complexity of health care calls for methodological pluralism and creativity that utilises the strength of both qualitative and quantitative approaches. Transparency and consistency on the philosophical level can facilitate new mixed methods research designs that may be promising methodological assets for healthcare research. I believe we are ill served by fortified positions that continue to uphold old battle lines. Empirical research begins in the field of practice and requires a certain amount of pragmatism. However, this pragmatism must be philosophically informed.     

Dynamic path analysis – a useful tool to investigate mediation processes in clinical survival trials

When it comes to clinical survival trials, regulatory restrictions usually require the application of methods that solely utilize baseline covariates and the intention‐to‐treat principle. Thereby, much potentially useful information is lost, as collection of time‐to‐event data often goes hand in hand with collection of information on biomarkers and other internal time‐dependent covariates. However, there are tools to incorporate information from repeated measurements in a useful manner that can help to shed more light on the underlying treatment mechanisms. We consider dynamic path analysis, a model for mediation analysis in the presence of a time‐to‐event outcome and time‐dependent covariates to investigate direct and indirect effects in a study of different lipid‐lowering treatments in patients with previous myocardial infarctions. Further, we address the question whether survival in itself may produce associations between the treatment and the mediator in dynamic path analysis and give an argument that because of linearity of the assumed additive hazard model, this is not the case. We further elaborate on our view that, when studying mediation, we are actually dealing with underlying processes rather than single variables measured only once during the study period. This becomes apparent in results from various models applied to the study of lipid‐lowering treatments as well as our additionally conducted simulation study, where we clearly observe that discarding information on repeated measurements can lead to potentially erroneous conclusions. Copyright © 2015 John Wiley & Sons, Ltd.     

Nisoldipine tablets once daily versus nifedipine capsules three times daily in patients with stable effort angina pectoris pretreated with atenolol

Summary Treatment with nisoldipine (2×10 mg tablets once daily) and nifedipine (2×10 mg capsules three times daily) in patients with severe, but stable effort angina pretreated with atenolol (100 mg once daily in 19 patients and 50 mg once daily in one patient) were compared for their effects on bicycle exercise tolerance and their adverse effects in a randomized 2×4 week, double-blind, double-dummy crossover study. All patients had multivessel disease, 16 patients had occlusion of at least one vessel, and eight patients had a history of myocardial infarction. Two patients left the study during the initial nisoldipine period, one because of aggravation of the angina and the other because of suspected allergic reaction. Addition of nifedipine to atenolol treatment significantly improved the variables measured for severity of angina, such as time of exercise until 1 mm and 2 mm ST-segment depression, total exercise time and total workload. In contrast, no such improvement was noted after the addition of nisoldipine to atenolol. However, nisoldipine resulted in a significant prolongation of the time to the initiation of chest discomfort, the maximum heart rate, and the double product.In atenolol-treated patients with severe effort angina pectoris, nifedipine 20 mg tid improved exercise capacity, while nisoldipine 20 mg once daily did not have a similar effect.     

Comparative analysis of mammalian Y chromosomes illuminates ancestral structure and lineage-specific evolution

Although more than thirty mammalian genomes have been sequenced to draft quality, very few of these include the Y chromosome. This has limited our understanding of the evolutionary dynamics of gene persistence and loss, our ability to identify conserved regulatory elements, as well our knowledge of the extent to which different types of selection act to maintain genes within this unique genomic environment. Here, we present the first MSY (male-specific region of the Y chromosome) sequences from two carnivores, the domestic dog and cat. By combining these with other available MSY data, our multiordinal comparison allows for the first accounting of levels of selection constraining the evolution of eutherian Y chromosomes. Despite gene gain and loss across the phylogeny, we show the eutherian ancestor retained a core set of 17 MSY genes, most being constrained by negative selection for nearly 100 million years. The X-degenerate and ampliconic gene classes are partitioned into distinct chromosomal domains in most mammals, but were radically restructured on the human lineage. We identified multiple conserved noncoding elements that potentially regulate eutherian MSY genes. The acquisition of novel ampliconic gene families was accompanied by signatures of positive selection and has differentially impacted the degeneration and expansion of MSY gene repertoires in different species.Y chromosomes have arisen independently in divergent evolutionary lineages across the eukaryotic tree of life (Rice 1996; Marin and Baker 1998; Liu et al. 2004; Graves 2006; Koerich et al. 2008; Carvalho et al. 2009; Kaiser and Bachtrog 2010). While many genes are known to be Y-linked, the actual number of Y chromosomes that have been sequenced is extremely small (Skaletsky et al. 2003; Hughes et al. 2005; Kuroki et al. 2006; Clark et al. 2007; Koerich et al. 2008; Carvalho et al. 2009; Hughes et al. 2010, 2012) in relation to the rapid rate at which whole genomes are presently being sequenced. This reduced emphasis on sequencing Y chromosomes can be primarily attributed to their presumed low gene content and large amounts of repetitive DNA, that is often arrayed into long stretches of nearly identical sequence which precludes the use of shotgun sequencing approaches to assemble Y chromosome sequence into large, contiguous scaffolds. These assembly problems are further exacerbated when applying short-read next-generation sequence methods (Alkan et al. 2011).The most completely sequenced and annotated Y chromosomes are from three recently diverged catarrhine primates: human, chimpanzee, and rhesus macaque (Skaletsky et al. 2003; Hughes et al. 2005, 2010, 2012; Kuroki et al. 2006 ). Comparisons between these species offer an important glimpse into the immense structural variation and complexity that can emerge on the Y within a very short period of evolutionary time. However, these three primate species last shared a common ancestor ∼21 million years ago (Mya) (Meredith et al. 2011) and thus offer limited comparative breadth to discriminate characteristics present across most mammalian Y chromosomes from idiosyncratic features reflective of a small evolutionary sample. This lack of phylogenetic scope has (1) hampered identification of the ancestral properties of eutherian Y chromosomes, (2) obscured broader patterns of evolutionary constraint and selection in a nonrecombining environment, and (3) hidden the frequency with which novel genes arise and/or acquire new functions in species with diverse phenotypes and reproductive strategies.To expand our knowledge of eutherian Y chromosome structure and gene function, we generated the first extensive MSY (male-specific Y chromosome) sequence from two members of the Carnivora: the domestic cat, Felis silvestris catus, and domestic dog, Canis lupus familiaris. These two carnivore genomes provide a phylogenetically distinct vantage point with which to interpret the evolutionary patterns observed in the primate MSY comparisons, diverging from each other ∼55 Mya, and from primates ∼92 Mya (Meredith et al. 2011). Our combined analysis of two carnivore and three primate MSY sequences, together with physical mapping and functional sequence data from the mouse MSY, represent the first multiordinal comparison assessing deeper levels of evolutionary constraint. We also present a complete analysis of patterns of negative and positive selection to assess their effects on MSY degeneration and expansion.