Analytical Techniques to Support Hospital Case Mix Planning

This article introduces analytical techniques and a decision support tool to support capacity assessment and case mix planning (CMP) approaches previously created for hospitals. First, an optimization model is proposed to analyse the impact of making a change to an existing case mix. This model identifies how other patient types should be altered proportionately to the changing levels of hospital resource availability. Then we propose multi-objective decision-making techniques to compare and critique competing case mix solutions obtained. The proposed techniques are embedded seamlessly within an Excel Visual Basic for Applications (VBA) personal decision support tool (PDST), for performing informative quantitative assessments of hospital capacity. The PDST reports informative metrics of difference and reports the impact of case mix modifications on the other types of patient present. The techniques developed in this article provide a bridge between theory and practice that is currently missing and provides further situational awareness around hospital capacity.Comment: 20 pages, 11 tables, 6 figure

Developing A Personal Decision Support Tool for Hospital Capacity Assessment and Querying

This article showcases a personal decision support tool (PDST) called HOPLITE, for performing insightful and actionable quantitative assessments of hospital capacity, to support hospital planners and health care managers. The tool is user-friendly and intuitive, automates tasks, provides instant reporting, and is extensible. It has been developed as an Excel Visual Basic for Applications (VBA) due to its perceived ease of deployment, ease of use, Office's vast installed userbase, and extensive legacy in business. The methodology developed in this article bridges the gap between mathematical theory and practice, which our inference suggests, has restricted the uptake and or development of advanced hospital planning tools and software. To the best of our knowledge, no personal decision support tool (PDST) has yet been created and installed within any existing hospital IT systems, to perform the aforementioned tasks. This article demonstrates that the development of a PDST for hospitals is viable and that optimization methods can be embedded quite simply at no cost. The results of extensive development and testing indicate that HOPLITE can automate many nuanced tasks. Furthermore, there are few limitations and only minor scalability issues with the application of free to use optimization software. The functionality that HOPLITE provides may make it easier to calibrate hospitals strategically and/or tactically to demands. It may give hospitals more control over their case-mix and their resources, helping them to operate more proactively and more efficiently.Comment: 33 pages, 11 tables, 17 figure

Biological Channeling of a Reactive Intermediate in the Bifunctional Enzyme DmpFG

It has been hypothesized that the bifunctional enzyme DmpFG channels its intermediate, acetaldehyde, from one active site to the next using a buried intermolecular channel identified in the crystal structure. This channel appears to switch between an open and a closed conformation depending on whether the coenzyme NAD(+) is present or absent. Here, we applied molecular dynamics and metadynamics to investigate channeling within DmpFG in both the presence and absence of NAD(+). We found that substrate channeling within this enzyme is energetically feasible in the presence of NAD(+) but was less likely in its absence. Tyr-291, a proposed control point at the channel's entry, does not appear to function as a molecular gate. Instead, it is thought to orientate the substrate 4-hydroxy-2-ketovalerate in DmpG before reaction occurs, and may function as a proton shuttle for the DmpG reaction. Three hydrophobic residues at the channel's exit appear to have an important role in controlling the entry of acetaldehyde into the DmpF active site

Biological Channeling of a Reactive Intermediate in the Bifunctional Enzyme DmpFG

AbstractIt has been hypothesized that the bifunctional enzyme DmpFG channels its intermediate, acetaldehyde, from one active site to the next using a buried intermolecular channel identified in the crystal structure. This channel appears to switch between an open and a closed conformation depending on whether the coenzyme NAD+ is present or absent. Here, we applied molecular dynamics and metadynamics to investigate channeling within DmpFG in both the presence and absence of NAD+. We found that substrate channeling within this enzyme is energetically feasible in the presence of NAD+ but was less likely in its absence. Tyr-291, a proposed control point at the channel's entry, does not appear to function as a molecular gate. Instead, it is thought to orientate the substrate 4-hydroxy-2-ketovalerate in DmpG before reaction occurs, and may function as a proton shuttle for the DmpG reaction. Three hydrophobic residues at the channel's exit appear to have an important role in controlling the entry of acetaldehyde into the DmpF active site

The Efficacy of Utility Functions for Multicriteria Hospital Case-Mix Planning

A new approach to perform hospital case-mix planning (CMP) is introduced in this article. Our multi-criteria approach utilises utility functions (UF) to articulate the preferences and standpoint of independent decision makers regarding outputs. The primary aim of this article is to test whether a utility functions method (UFM) based upon the scalarization of aforesaid UF is an appropriate quantitative technique to, i) distribute hospital resources to different operating units, and ii) provide a better capacity allocation and case mix. Our approach is motivated by the need to provide a method able to evaluate the trade-off between different stakeholders and objectives of hospitals. To the best of our knowledge, no such approach has been considered before in the literature. As we will later show, this idea addresses various technical limitations, weaknesses, and flaws in current CMP. The efficacy of the aforesaid approach is tested on a case study of a large tertiary hospital. Currently UF are not used by hospital managers, and real functions are unavailable, hence, 14 rational options are tested. Our exploratory analysis has provided important guidelines for the application of these UF. It indicates that these UF provide a valuable starting point for planners, managers, and executives of hospitals to impose their goals and aspirations. In conclusion, our approach may be better at identifying case mix that users want to treat and seems more capable of modelling the varying importance of different levels of output. Apart from finding desirable case mixes to consider, the approach can provide important insights via a sensitivity analysis of the parameters of each UF.Comment: 35 pages, 6 tables, 29 figure

Multicriteria Optimization Techniques for Understanding the Case Mix Landscape of a Hospital

Various medical and surgical units operate in a typical hospital and to treat their patients these units compete for infrastructure like operating rooms (OR) and ward beds. How that competition is regulated affects the capacity and output of a hospital. This article considers the impact of treating different patient case mix (PCM) in a hospital. As each case mix has an economic consequence and a unique profile of hospital resource usage, this consideration is important. To better understand the case mix landscape and to identify those which are optimal from a capacity utilisation perspective, an improved multicriteria optimization (MCO) approach is proposed. As there are many patient types in a typical hospital, the task of generating an archive of non-dominated (i.e., Pareto optimal) case mix is computationally challenging. To generate a better archive, an improved parallelised epsilon constraint method (ECM) is introduced. Our parallel random corrective approach is significantly faster than prior methods and is not restricted to evaluating points on a structured uniform mesh. As such we can generate more solutions. The application of KD-Trees is another new contribution. We use them to perform proximity testing and to store the high dimensional Pareto frontier (PF). For generating, viewing, navigating, and querying an archive, the development of a suitable decision support tool (DST) is proposed and demonstrated.Comment: 38 pages, 17 figures, 11 table

An improved open-channel structure of MscL determined from FRET confocal microscopy and simulation

Mechanosensitive channels act as molecular transducers of mechanical force exerted on the membrane of living cells by opening in response to membrane bilayer deformations occurring in physiological processes such as touch, hearing, blood pressure regulation, and osmoregulation. Here, we determine the likely structure of the open state of the mechanosensitive channel of large conductance using a combination of patch clamp, fluorescence resonance energy transfer (FRET) spectroscopy, data from previous electron paramagnetic resonance experiments, and molecular and Brownian dynamics simulations. We show that structural rearrangements of the protein can be measured in similar conditions as patch clamp recordings while controlling the state of the pore in its natural lipid environment by modifying the lateral pressure distribution via the lipid bilayer. Transition to the open state is less dramatic than previously proposed, while the N terminus remains anchored at the surface of the membrane where it can either guide the tilt of or directly translate membrane tension to the conformation of the pore-lining helix. Combining FRET data obtained in physiological conditions with simulations is likely to be of great value for studying conformational changes in a range of multimeric membrane proteins

Model Channel Ion Currents in NaCl - SPC/E Solution with Applied-Field Molecular Dynamics

Using periodic boundary conditions and a constant applied field, we have simulated current flow through an 8.125 Angstrom internal diameter, rigid, atomistic channel with polar walls in a rigid membrane using explicit ions and SPC/E water. Channel and bath currents were computed from ten 10-ns trajectories for each of 10 different conditions of concentration and applied voltage. An electric field was applied uniformly throughout the system to all mobile atoms. On average, the resultant net electric field falls primarily across the membrane channel, as expected for two conductive baths separated by a membrane capacitance. The channel is rarely occupied by more than one ion. Current-voltage relations are concentration-dependent and superlinear at high concentrations.Comment: Accepted for publication in Biophysical Journa