Public Insurance Payment Does Not Compensate Hospital Cost for Care of Long-Bone Fractures Requiring Additional Surgery to Promote Union.

OBJECTIVES: To quantify the total hospital costs associated with the treatment of lower extremity long-bone fracture aseptic and septic unhealed fracture, to determine if insurance adequately covers these costs, and to examine whether insurance type correlates with barriers to accessing care. DESIGN: Retrospective cohort study. SETTING: Academic Level II trauma center. PATIENTS: All patients undergoing operative treatment of OTA/AO classification 31, 32, 33, 41, 42, and 43 fractures between 2012 and 2020 at a single Level II trauma center with minimum of 1-year follow-up. MAIN OUTCOME MEASURES: The primary outcome was the total cost of treatment for all hospital-based episodes of care. Distance traveled from primary residence was measured as a surrogate for barriers to care. RESULTS: One hundred seventeen patients with uncomplicated fracture healing, 82 with aseptic unhealed fracture, and 44 with septic unhealed fracture were included in the final cohort. The median cost of treatment for treatment of septic unhealed fracture was $148,318 [interquartile range(IQR) 87,241-256,928], $45,230 (IQR 31,510-68,030) for treatment of aseptic unhealed fracture, and $33,991 (IQR 25,609-54,590) for uncomplicated fracture healing. The hospital made a profit on all patients with commercial insurance, but lost money on all patients with public insurance. Among patients with unhealed fracture, those with public insurance traveled 4 times further for their care compared with patients with commercial insurance (P = 0.004). CONCLUSIONS: Septic unhealed fracture of lower extremity long-bone fractures is an outsized burden on the health care system. Public insurance for both septic and aseptic unhealed fracture does not cover hospital costs. The increased distances traveled by our Medi-Cal and Medicare population may reflect the economic disincentive for local hospitals to care for publicly insured patients with unhealed fractures. LEVEL OF EVIDENCE: Economic Level V. See Instructions for Authors for a complete description of levels of evidence.

Markov state modeling of membrane transport proteins.

The flux of ions and molecules in and out of the cell is vital for maintaining the basis of various biological processes. The permeation of substrates across the cellular membrane is mediated through the function of specialized integral membrane proteins commonly known as membrane transporters. These proteins undergo a series of structural rearrangements that allow a primary substrate binding site to be accessed from either side of the membrane at a given time. Structural insights provided by experimentally resolved structures of membrane transporters have aided in the biophysical characterization of these important molecular drug targets. However, characterizing the transitions between conformational states remains challenging to achieve both experimentally and computationally. Though molecular dynamics simulations are a powerful approach to provide atomistic resolution of protein dynamics, a recurring challenge is its ability to efficiently obtain relevant timescales of large conformational transitions as exhibited in transporters. One approach to overcome this difficulty is to adaptively guide the simulation to favor exploration of the conformational landscape, otherwise known as adaptive sampling. Furthermore, such sampling is greatly benefited by the statistical analysis of Markov state models. Historically, the use of Markov state models has been effective in quantifying slow dynamics or long timescale behaviors such as protein folding. Here, we review recent implementations of adaptive sampling and Markov state models to not only address current limitations of molecular dynamics simulations, but to also highlight how Markov state modeling can be applied to investigate the structure-function mechanisms of large, complex membrane transporters.