RESUMO
INTRODUCTION: Partial thickness burns not undergoing surgical excision are treated with topical silver products including silver sulfadiazine (SSD) and Mepilex Ag. Skin allograft is a more costly alternative that acts as definitive wound coverage until autogenous epithelialization. Economic constraints and the movement toward value-based care demand cost and outcome justification prior to adopting more costly products. METHODS: A cost-utility analysis was performed comparing skin allograft to SSD and Mepilex Ag using decision tree analysis. The base case modeled a superficial partial thickness 20% total body surface area burn. Utilities were derived from expert opinion on the basis of personal experience. Costs were derived from 2019 Medicare payments. Quality adjusted life years were calculated using rollback method assuming standard life expectancies in the United States. Probabilistic sensitivity analysis was performed to asses model robustness. RESULTS: The incremental costs of skin allograft to Mepilex Ag and SSD were $907.71 and $1257.86, respectively. The incremental quality adjusted life year (QALY) gains from allograft over Mepilex Ag and SSD were 0.011 and 0.016. This yielded an incremental cost-utility ratio for allograft vs. Mepilex Ag of $84,189.29/QALY compared with an incremental cost-utility ratio of $79,684.63/QALY for allograft vs. SSD. Assuming willingness-to-pay thresholds of $100,000/QALY, probabilistic sensitivity analysis demonstrated that allograft was cost effective to Mepilex Ag in 62.1% of scenarios, and cost effective to SSD in 64.9% of simulations. CONCLUSION: Skin allograft showed greater QALYs compared with topical silver dressings at a higher cost. Depending on willingness-to-pay thresholds, skin allograft may be a considered a cost-effective treatment of partial-thickness burns.
Assuntos
Queimaduras/terapia , Análise Custo-Benefício , Medicare/economia , Anos de Vida Ajustados por Qualidade de Vida , Sulfadiazina de Prata/administração & dosagem , Sulfadiazina de Prata/economia , Transplante de Pele/economia , Administração Tópica , Idoso , Aloenxertos , Bandagens , Árvores de Decisões , Feminino , Humanos , Masculino , Estados UnidosRESUMO
The effect of tumor necrosis factor-α (TNFα) on cartilage matrix degradation is mediated by its transport and binding within the extracellular matrix (ECM) of the tissue, which mediates availability to cell receptors. Since the bioactive form of TNFα is a homotrimer of monomeric subunits, conversion between trimeric and monomeric forms during intratissue transport may affect binding to ECM and, thereby, bioactivity within cartilage. We studied the transport and binding of TNFα in cartilage, considering the quaternary structure of this cytokine. Competitive binding assays showed significant binding of TNFα in cartilage tissue, leading to an enhanced uptake. However, studies in which TNFα was cross-linked to remain in the trimeric form revealed that the binding of trimeric TNFα was negligible. Thus, binding of TNFα to ECM was associated with the monomeric form. Binding of TNFα was not disrupted by pre-treating cartilage tissue with trypsin, which removes proteoglycans and glycoproteins but leaves the collagen network intact. Therefore, proteoglycan loss during osteoarthritis should only alter the passive diffusion of TNFα but not its binding interaction with the remaining matrix. Our results suggest that matrix binding and trimer-monomer conversion of TNFα both play crucial roles in regulating the accessibility of bioactive TNFα within cartilage.
Assuntos
Cartilagem Articular/metabolismo , Estrutura Quaternária de Proteína , Fator de Necrose Tumoral alfa/química , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Animais , Sítios de Ligação , Cartilagem Articular/citologia , Bovinos , Matriz Extracelular/metabolismo , Humanos , Radioisótopos do Iodo , Cinética , Masculino , Ligação Proteica , Transporte Proteico , Receptores do Fator de Necrose Tumoral/metabolismoRESUMO
The efficacy of biological therapeutics against cartilage degradation in osteoarthritis is restricted by the limited transport of macromolecules through the dense, avascular extracellular matrix. The availability of biologics to cell surface and matrix targets is limited by steric hindrance of the matrix, and the microstructure of matrix itself can be dramatically altered by joint injury and the subsequent inflammatory response. We studied the transport into cartilage of a 48 kDa anti-IL-6 antigen binding fragment (Fab) using an in vitro model of joint injury to quantify the transport of Fab fragments into normal and mechanically injured cartilage. The anti-IL-6 Fab was able to diffuse throughout the depth of the tissue, suggesting that Fab fragments can have the desired property of achieving local delivery to targets within cartilage, unlike full-sized antibodies which are too large to penetrate beyond the cartilage surface. Uptake of the anti-IL-6 Fab was significantly increased following mechanical injury, and an additional increase in uptake was observed in response to combined treatment with TNFα and mechanical injury, a model used to mimic the inflammatory response following joint injury. These results suggest that joint trauma leading to cartilage degradation can further alter the transport of such therapeutics and similar-sized macromolecules.