Modeling the impact of bedaquiline treatment strategies on the multidrug-resistant tuberculosis burden in India.

SETTING: Bedaquiline (BDQ) has been approved in India for the treatment of multidrug-resistant tuberculosis (MDR-TB), but is currently recommended for MDR-TB patients who have failed initial treatment with standard regimens. While some have argued that such deferred BDQ use allows a second line of defense with a potent drug, this strategy may not be optimal. OBJECTIVE: To compare several distinct scenarios of BDQ access and use, and their potential impact on the MDR-TB disease burden and the associated net economic benefit in India. METHOD: We used a state-transition model to carry out this evaluation. The scenarios differed in the timing and breadth of BDQ access. RESULTS: The simulations showed that a strategy reliant on reserving the use of BDQ for those who have failed other MDR-TB regimens is likely to result in worse treatment outcomes for patients and in inferior public health outcomes for communities, leading to reduced net monetary benefit. CONCLUSION: Our study suggests that deferring patient access to new drugs such as BDQ until front-line regimens have failed, in order to 'save' these drugs for later use, could be detrimental to patients and to public health, and could reduce the economic benefit of treating MDR-TB.

Emollient molecule effects on the drying stresses in human stratum corneum.

BACKGROUND: Emollient molecules are widely used in skin care formulations to improve skin sensory properties and to alleviate dry skin but little is understood regarding their effects on skin biomechanical properties. OBJECTIVES: To investigate the effects of emollient molecules on drying stresses in human stratum corneum (SC) and how these stresses are related to SC components and moisture content. METHODS: The substrate curvature method was used to measure the drying stresses in isolated SC following exposure to selected emollient molecules. While SC stresses measured using this method have the same biaxial in vivo stress state and moisture exchange with the environment, a limitation of the method is that moisture cannot be replenished by the underlying skin layers. This provides an opportunity to study the direct effects of emollient treatments on the moisture content and the components of the SC. Attenuated total reflectance Fourier transform infrared spectroscopy was used to determine the effects of emollient molecules on SC lipid extraction and conformation. Results Emollient molecules resulted in a complex SC drying stress profile where stresses increased rapidly to peak values and then gradually decreased to significantly lower values compared with the control. The partially occlusive treatments also penetrated into the SC where they caused extraction and changes in lipid conformation. These effects together with their effects on SC moisture content are used to rationalize the drying stress profiles. CONCLUSIONS: Emollient molecules have dramatic effects on SC drying stresses that are related to their effects on intercellular lipids and SC moisture content.