A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

<p>Abstract</p> <p>Background</p> <p>Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power.</p> <p>Results</p> <p>We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization.</p> <p>Conclusions</p> <p>A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.</p

Targeting Interventions and Populations

The delivery of health care is undergoing dramatic changes. Important drivers for these changes include the increasing complexity of modern medicine, advancements in health information technology, and the shift in the delivery of care from the hospital to other care settings. As a result, physicians are now more specialized in the services that they provide and are more likely to focus their efforts either in a hospital, outpatient, or long-term care setting. At the same time, an increasing number of eligible older adults and an escalating average cost per beneficiary will make Medicare financially unsustainable. State Medicaid programs are also undergoing rapid changes. Many face potential increases in their financial obligations under the Patient Protection and Affordability Care Act (ACA) and an increasing population of indigent older adults in need of long-term care services. Complex geriatric care is needed to address these healthcare system changes. We will describe the most prevalent and important care models for complex patients. Additionally we will detail efforts to target these interventions to appropriate populations. Finally we will review what is currently known about the quality metrics and outcome measures that have been applied to these models