Improving inhaler adherence in patients with Chronic Obstructive Pulmonary Disease: a cost-effectiveness analysis

Background

The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care. This study aimed to evaluate its cost-effectiveness.

Methods

An economic analysis was performed from the Belgian healthcare payer’s perspective. A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care. Three types of costs were calculated: intervention costs, medication costs and exacerbation costs. Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year. Follow-up was 1 year in the basecase analysis. Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty.

Results

In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon. This reflects cost savings of €227 for the PHARMACOP-intervention. The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care). Results showed robust cost-savings in various sensitivity analyses.

Conclusions

Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies.     

Biologically relevant effects of mRNA amplification on gene expression profiles

Background  

Gene expression microarray technology permits the analysis of global gene expression profiles. The amount of sample needed limits the use of small excision biopsies and/or needle biopsies from human or animal tissues. Linear amplification techniques have been developed to increase the amount of sample derived cDNA. These amplified samples can be hybridised on microarrays. However, little information is available whether microarrays based on amplified and unamplified material yield comparable results.     

Chromosome phylogeny of the subfamily Pitheciinae (Platyrrhini,Primates) by classic cytogenetics and chromosome painting

Background  

The New World monkey (Platyrrhini) subfamily Pitheciinae is represented by the genera Pithecia, Chiropotes and Cacajao. In this work we studied the karyotypes of Pithecia irrorata (2n = 48) and Cacajao calvus rubicundus (2n = 45 in males and 2n = 46 in females) by G- and C-banding, NOR staining and chromosome painting using human and Saguinus oedipus whole chromosome probes. The karyotypes of both species were compared with each other and with Chiropotes utahicki (2n = 54) from the literature.     

Direct anti-metastatic efficacy by the DNA enzyme Dz13 and downregulated MMP-2, MMP-9 and MT1-MMP in tumours

The DNA enzyme Dz13, targeted against the oncogene c-Jun, is capable of inhibiting various model tumours in mice albeit in ectopic models of neoplasia. In previous studies using orthotopic models of disease, the inhibitory effects of Dz13 on secondary growth was a direct result of growth inhibition at the primary lesion site. Thus, the direct and genuine effects on metastasis were not gauged. In this study, Dz13 was able to inhibit both locoregional and distal metastasis of tumour cells in mice, in studies where the primary tumours were unaffected due to the late and clinically-mimicking nature of treatment commencement. In addition, the effect of Dz13 against tumours has now been extended to encompass breast and prostate cancer. Dz13 upregulated the matrix metalloproteinase (MMP)-2 and MMP-9, and decreased expression of MT1-MMP (MMP-14) in cultured tumour cells. However, in sections of ectopic tumours treated with Dz13, both MMP-2 and MMP-9 were downregulated. Thus, not only is Dz13 able to inhibit tumour growth at the primary site, but also able to decrease the ability of neoplastic cells to metastasise. These findings further highlight the growing potential of Dz13 as an antineoplastic agent.     

YAP‐TEAD signaling promotes basal cell carcinoma development via a c‐JUN/AP1 axis

The mammalian Hippo signaling pathway, through its effectors YAP and TAZ, coerces epithelial progenitor cell expansion for appropriate tissue development or regeneration upon damage. Its ability to drive rapid tissue growth explains why many oncogenic events frequently exploit this pathway to promote cancer phenotypes. Indeed, several tumor types including basal cell carcinoma (BCC) show genetic aberrations in the Hippo (or YAP/TAZ) regulators. Here, we uncover that while YAP is dispensable for homeostatic epidermal regeneration, it is required for BCC development. Our clonal analyses further demonstrate that the few emerging Yap‐null dysplasia have lower fitness and thus are diminished as they progress to invasive BCC. Mechanistically, YAP depletion in BCC tumors leads to effective impairment of the JNK‐JUN signaling, a well‐established tumor‐driving cascade. Importantly, in this context, YAP does not influence canonical Wnt or Hedgehog signaling. Overall, we reveal Hippo signaling as an independent promoter of BCC pathogenesis and thereby a viable target for drug‐resistant BCC.     

Efficacy of population structure analysis with breeding populations and inbred lines

The objective was to assess by simulation the efficacy of population structure analysis in plant breeding. Twelve populations and 300 inbred lines were simulated and genotyped using 100 microsatellite loci. The experimental material included populations with and without admixture, ancestry relationship and linkage disequilibrium, and with distinct levels of genetic differentiation and effective sizes. The analyses were performed using Structure software and employed all available models. For all the group number (K) tested, for both populations and inbred lines, the admixture model with correlated allelic frequencies provided the highest value for the logarithm of the marginal likelihood. Fitting appropriate model and using adequate sample size for individuals and markers, Structure was effective in identifying the correct population structure, migrants and individuals with genome from distinct populations. The linkage model did not result in an improvement in clustering relative to the admixture model with correlated allelic frequencies. The inclusion of prior information did not change the results; for some K values the analyses showed slight higher values of the marginal likelihood. The reduction in the number of individuals and markers negatively affected the results. There was a high variation in the most probable K value between the evaluated methods.     

Leaf nutrient content and host plant selection by leaf-cutter ants, Atta laevigata, in a Neotropical savanna

The selection of nutrient-rich leaves by leaf-cutter ants ( Atta spp.) is thought to be of indirect benefit to these ants by promoting the growth of their symbiotic fungus. However, relatively few studies have analyzed the influence of leaf nutrient content on host plant selection by leaf-cutter ants, and conflicting results have been found. We compared the content of eight nutritional elements plus the non-nutrient aluminum between leaves harvested by colonies of Atta laevigata (Smith) (Hymenoptera: Formicidae: Attini) and leaves collected randomly within their foraging areas. In addition, we evaluated whether leaf nutrient content explained the frequency with which these ants attacked and defoliated some of the tree species found in the study area. For 2 years, we monitored 17–26 trees from 15 species and determined the number of times each plant was attacked and the amount and type of foliage removed. Leaves harvested by A. laevigata presented significantly higher concentrations of N, P, K, Zn, and Cu than those collected randomly. This result is likely to reflect the foraging pattern presented by these ants, which were selective both in terms of the plant species and age of leaves most commonly attacked. Young leaves were the only or the main leaf type exploited in many species, and in comparison to mature leaves these presented significantly higher concentrations of P and K. Large differences in the mean number of ant attacks on the tree species studied were also observed, and those presenting more leaf N tended to be the most frequently attacked.