Does reporting of coronary artery bypass grafting from administrative databases accurately reflect actual clinical outcomes?

ObjectivesQuality assessment of coronary artery bypass grafting has traditionally been performed with data from clinical databases. Administrative databases that rely primarily on information collected for billing purposes increasingly have been used as tools for public reporting of outcomes quality. The correlation of administrative data with clinical data for clinical quality assessment has not been confirmed.MethodsWith data from a clinical database, we analyzed the outcomes of all patients who underwent coronary artery bypass grafting surgery in 1 hospital between 1999 and 2001. This information was collected before, during, and after the surgery and hospitalization by designated clinical individuals involved with the patient’s care and then entered into an audited clinical database (The Society of Thoracic Surgeons National Cardiac Database). These data were then compared with administrative data collected on the same cohort of patients for the number of procedures performed and mortality rate as reported by the federal government (Medical Provider Analysis and Review), state government (Texas Health Care Information Council), hospital system (HCA, Inc, Casemix Database), and an internet Web site (healthgrades.com). Data were analyzed on the basis of the population reported, definitions used, risk assessment algorithms, and case volumes.ResultsBy using the audited The Society of Thoracic Surgeons database as the standard and aggregating the reporting of case volumes by the inclusion criteria of various sources of administrative data, we found variances in the reported procedure volumes and mortality. Case volumes were overreported by as much as 21% in all patients and underreported by up to 16% or more in Medicare patients. Mortality in administrative data exceeded that reported in clinical data by 21%. Reasons for variances included time period reported (calendar vs fiscal year), population reported (all patients, Medicare patients, Medicare patients aged ≥ 65 years), date used for the patient record captured (date of surgery, discharge), and the definition of mortality. Different proprietary risk-adjusting algorithms used magnified variances with risk-adjusted mortality exceeding the Society of Thoracic Surgeons data by as much as 61%.ConclusionsSubstantial variability of reported outcomes is seen in administrative data sets compared with an audited clinical database in the end points of the number of procedures performed and mortality. This variability makes it challenging for the nonclinician unfamiliar with outcomes analysis to make an informed decision

OmpA: Gating and dynamics via molecular dynamics simulations

Outer membrane proteins (OMPs) of Gram-negative bacteria have a variety of functions including passive transport, active transport, catalysis, pathogenesis and signal transduction. Whilst the structures of 25 OMPs are currently known, there is relatively little known about their dynamics in different environments. The outer membrane protein, OmpA from Escherichia coli has been studied extensively in different environments both experimentally and computationally, and thus provides an ideal test case for the study of the dynamics and environmental interactions of outer membrane proteins. We review molecular dynamics simulations of OmpA and its homologues in a variety of different environments and discuss possible mechanisms of pore gating. The transmembrane domain of E. coli OmpA shows subtle differences in dynamics and interactions between a detergent micelle and a lipid bilayer environment. Simulations of the crystallographic unit cell reveal a micelle-like network of detergent molecules interacting with the protein monomers. Simulation and modelling studies emphasise the role of an electrostatic-switch mechanism in the pore-gating mechanism. Simulation studies have been extended to comparative models of OmpA homologues from Pseudomonas aeruginosa (OprF) and Pasteurella multocida (PmOmpA), the latter model including the periplasmic C-terminal domain

A multidomain outer membrane protein from Pasteurella multocida: Modelling and simulation studies of PmOmpA

PmOmpA is a two-domain outer membrane protein from Pasteurella multocida. The N-terminal domain of PmOmpA is a homologue of the transmembrane ?-barrel domain of OmpA from Escherichia coli, whilst the C-terminal domain of PmOmpA is a homologue of the extra-membrane Neisseria meningitidis RmpM C-terminal domain. This enables a model of a complete two domain PmOmpA to be constructed and its conformational dynamics explored via MD simulations of the protein embedded within two different phospholipid bilayers (DMPC and DMPE). The conformational stability of the transmembrane ?-barrel is similar to that of a homology model of OprF from Pseudomonas aeruginosa in bilayer simulations. There is a degree of water penetration into the interior of the ?-barrel, suggestive of a possible transmembrane pore. Although the PmOmpA model is stable over 20 ns simulations, retaining its secondary structure and fold integrity throughout, substantial flexibility is observed in a short linker region between the N- and the C-terminal domains. At low ionic strength, the C-terminal domain moves to interact electrostatically with the lipid bilayer headgroups. This study demonstrates that computational approaches may be applied to more complex, multi-domain outer membrane proteins, rather than just to transmembrane ?-barrels, opening the possibility of in silico proteomics approaches to such proteins