Cost-Effectiveness Analysis of Breast Cancer Control Interventions in Peru

Objectives

In Peru, a country with constrained health resources, breast cancer control is characterized by late stage treatment and poor survival. To support breast cancer control in Peru, this study aims to determine the cost-effectiveness of different breast cancer control interventions relevant for the Peruvian context.

Methods

We performed a cost-effectiveness analysis (CEA) according to WHO-CHOICE guidelines, from a healthcare perspective. Different screening, early detection, palliative, and treatment interventions were evaluated using mathematical modeling. Effectiveness estimates were based on observational studies, modeling, and on information from Instituto Nacional de Enfermedades Neoplásicas (INEN). Resource utilizations and unit costs were based on estimates from INEN and observational studies. Cost-effectiveness estimates are in 2012 United States dollars (US$) per disability adjusted life year (DALY) averted.

Results

The current breast cancer program in Peru ($8,426 per DALY averted) could be improved through implementing triennial or biennial screening strategies. These strategies seem the most cost-effective in Peru, particularly when mobile mammography is applied (from $4,125 per DALY averted), or when both CBE screening and mammography screening are combined (from $4,239 per DALY averted). Triennially, these interventions costs between $63 million and $72 million per year. Late stage treatment, trastuzumab therapy and annual screening strategies are the least cost-effective.

Conclusions

Our analysis suggests that breast cancer control in Peru should be oriented towards early detection through combining fixed and mobile mammography screening (age 45-69) triennially. However, a phased introduction of triennial CBE screening (age 40-69) with upfront FNA in non-urban settings, and both CBE (age 40-49) and fixed mammography screening (age 50-69) in urban settings, seems a more feasible option and is also cost-effective. The implementation of this intervention is only meaningful if awareness raising, diagnostic, referral, treatment and basic palliative services are simultaneously improved, and if financial and organizational barriers to these services are reduced.     

Symmetric cyanine dyes for detecting nucleic acids

A novel approach to the design of sensitive fluorescent probes for nucleic acids detection is proposed. Suitable modifications of tri- and pentamethine cyanine dyes in the polymethine chain and/or in the heterocyclic residues can result in a significant decrease in unbound dye fluorescence intensity and an increase in dye emission intensity in the presence of DNA compared to the unsubstituted dye. The sharp enhancement in the fluorescence intensity upon dye interaction with double-stranded DNA permits the application of the modified tri- and pentamethine dyes as fluorescent probes in double-stranded DNA detection in homogeneous assays.     

Culicidae Community Composition and Temporal Dynamics in Guapia?u Ecological Reserve,Cachoeiras de Macacu,Rio de Janeiro,Brazil

A temporal observational study was conducted of the Culicidae fauna in a remnant area of Atlantic Forest within a private reserve (Guapiaçu Ecological Reserve-REGUA) presenting typical vegetation cover of dense rain forest, with some patches recovering a floristic composition similar to that of the original community. Research was carried out to analyze the influence of climatic factors (mean monthly temperature, rainfall, and air relative humidity) on the temporal dynamics of the mosquito communities that occur in the reserve. The completeness of the mosquito inventory was assessed with individual-based rarefaction-extrapolation curves. Differences in species composition between sites and months were tested with PERMANOVA. True diversities of orders 0, 1, and 2 (effective numbers) were estimated and compared between sites, months, and years. Multiple stepwise regressions were used to assess relationships between climatic variables, measures of diversity, and abundances of the most common species. There were significant interactive effects between year and site on measures of diversity. However, diversity estimates showed little variation among months, and these were weakly correlated with climatic variables. Abundances of the most common species were significantly related to temperature or relative humidity, but not rainfall. The presence of mosquito species known to be vectors of human diseases combined with an intermittent flow of visitors to the study area suggests there is a risk of disease transmission that warrants further monitoring.     

Mosquito fauna of the Guapiaçu Ecological Reserve,Cachoeiras de Macacu,Rio de Janeiro,Brazil, collected under the influence of different color CDC light traps

The objective of the present study was to identify mosquito fauna and to evaluate whether different light bulb colors influence the attraction of light traps in the Guapiaçu Ecological Reserve. Samples were obtained monthly during the period of February, 2012 to January, 2013. Centers for Disease Control (CDC) light traps with incandescent light bulbs and LED (ultraviolet, blue, green, and red) bulbs were utilized. In total, 8,170 specimens were captured, including 59 species. The presence of Anopheles nimbus (Theobald 1902) and Orthopodomyia fascipes Coquillet 1906 were recorded for the first time in the state of Rio de Janeiro. The green LED trap attracted the highest number of specimens and presented the highest diversity and mosquito average. The blue and green LED traps attracted the highest number of species. However, the differences between lights were not significant. The most common species were Coquillettidia juxtamansonia (Chagas 1907), Culex declarator Dyar and Knab 1906, and Culex ribeirensis Forattini and Sallum 1985.     

A comparative genomics study of genetic products potentially encoding ladderane lipid biosynthesis

Background  

The fatty acids of anaerobic ammonium oxidizing (anammox) bacteria contain linearly concatenated cyclobutane moieties, so far unique to biology. These moieties are under high ring strain and are synthesised by a presently unknown biosynthetic pathway.     

RNA Polymerase II CTD Tyrosine 1 Is Required for Efficient Termination by the Nrd1-Nab3-Sen1 Pathway

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Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine

The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4–9.9 Log₁₀TCID₅₀/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive PER.C6 cell culture platform, the stably attenuated CAVA strains may serve as an attractive low-cost and (bio)safe option for the production of a novel next generation IPV.