Introduction

Cost-utility analysis (CUA)-a method to evaluate intervention cost-effectiveness-transforms benefits of alternatives into a measure of quantity and quality of life, such as quality-adjusted life year (QALY), to enable comparison across heterogeneous programs. Measurement challenges prevent directly estimating utilities and calculating QALYs for caries in primary dentition. Proxy disease QALYs are often used as a substitute; however, there lacks quantitative evidence that these proxy diseases are comparable to caries.

Objective

To employ a discrete choice experiment (DCE) to quantitatively determine the most comparable proxy disease for different levels of caries in primary dentition.

Methods

A cross-sectional DCE survey was administered to respondents (N = 461) who resided in California, were aged ≥18 y, and were primary caretakers for ≥1 child aged 3 to 12 y. Four attributes were included: pain level, disease duration, treatment cost, and family life impacts. Mixed effects logistic regression and conditional logistic regression were used to analyze the survey data.

Results

Respondents from the overall sample preferred no pain over mild (odds ratio [OR] = 0.50, P < 0.05), moderate (OR = 0.57, P < 0.05), and severe pain (OR = 0.48, P < 0.05). Acute gastritis (OR = 0.44, P < 0.05), chronic gastritis (OR = 0.31, P < 0.01), and cold sore (OR = 0.38, P < 0.05) were less preferred than stage 1 caries. Acute tonsilitis (OR = 0.43, P < 0.05), acute gastritis (OR = 0.38, P < 0.05), chronic gastritis (OR = 0.26, P < 0.01), and cold sore (OR = 0.33, P < 0.01) were less preferred than stage 2 caries. Chronic gastritis (OR = 0.42,P < 0.05) was less preferred than stage 4 caries.

Conclusions

Parents viewed the characteristics of many diseases with similar QALYs differently. Findings suggest that otitis media and its QALY-as commonly used in CUAs-may be a suitable proxy disease and substitute. However, other disease states with slightly different QALYs may be suitable. As such, the recommendation is to consider a range of proxy diseases and their QALYs when conducting a CUA for child caries interventions.

Knowledge transfer statement

This study reviews and systematically compares pediatric diseases that are comparable to caries in primary dentition. The findings may inform future research using cost-utility analysis to examine the incremental cost-effectiveness ratio of interventions to prevent and treat caries as compared with an alternative.

Acute psychological stress (PS) mobilizes metabolic responses that are of immediate benefit to the host, but the current medical paradigm holds that PS exacerbates systemic and cutaneous inflammatory disorders. Although the adverse consequences of PS are usually attributed to neuroimmune mechanisms, PS also stimulates an increase in endogenous glucocorticoids (GCs) that compromises permeability barrier homeostasis, stratum corneum cohesion, wound healing, and epidermal innate immunity in normal skin. Yet, if such PS-induced increases in GC were uniformly harmful, natural selection should have eliminated this component of the stress response. Hence, we hypothesized here instead that stress-induced elevations in endogenous GC could benefit, rather than aggravate, cutaneous function and reduce inflammation in three immunologically diverse mouse models of inflammatory diseases. Indeed, superimposed exogenous (motion-restricted) stress reduced, rather than aggravated inflammation and improved epidermal function in all three models, even normalizing serum IgE levels in the atopic dermatitis model. Elevations in endogenous GC accounted for these apparent benefits, because coadministration of mifepristone prevented stress-induced disease amelioration. Thus, exogenous stress can benefit rather than aggravate cutaneous inflammatory dermatoses through the anti-inflammatory activity of increased endogenous GC.

Humans with darkly pigmented skin display superior permeability barrier function in comparison with humans with lightly pigmented skin. The reduced pH of the stratum corneum (SC) of darkly pigmented skin could account for enhanced function, because acidifying lightly pigmented human SC resets barrier function to darkly pigmented levels. In SKH1 (nonpigmented) versus SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J versus SKH1 mice, correlating with a reduced pH in the lower SC that colocalizes with the extrusion of melanin granules. Darkly pigmented human epidermis also shows substantial melanin extrusion in the outer epidermis. Both acute barrier disruption and topical basic pH challenges accelerate reacidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion. SKH2/J mice also display enhanced expression of the SC acidifying enzyme, secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice could be attributed to enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, β-glucocerebrosidase and acidic sphingomyelinase, leading to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures of darkly pigmented human keratinocytes display enhanced barrier function in comparison with lightly pigmented cultures. Together, these results suggest that the superior barrier function of pigmented epidermis can be largely attributed to the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f expression. © 2014 The Society for Investigative Dermatology.