ABSTRACT
BACKGROUND: The U.S. Veterans Health Administration (VHA) provides depression treatment to veterans with Traumatic Brain Injury (TBI). VHA costs of comorbid TBI-depression were estimated by Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) status over 14 years. METHODS: VHA-USING veterans with TBI DIAGNOSED IN 2000-2010 were followed through FY2014. TBI severity was determined using the Department of Defense criteria. Depression was identified by the Elixhauser algorithm. Generalized linear and seemingly unrelated regression models were used to estimate the impact of depression on annual per veteran and total VHA inpatient, outpatient, and pharmaceutical costs, by OEF/OIF status. RESULTS: A total of 66.57% of pre-OEF/OIF and 87.46% of OEF/OIF veterans had depression. Depression was estimated to increase annual total ($1,847), outpatient ($1,558), and pharmaceutical ($287) costs for pre-OEF/OIF, and $1,228, $1,685, and $191 for OEF/OIF veterans. However, depression was estimated to lower annual inpatient costs by $648 per OEF/OIF veteran. The annual VHA cost for all veterans with comorbid TBI-depression was estimated at $1,101,329,953. CONCLUSIONS: The estimated annual cost for Veterans with comorbid TBI-depression was more than $1 billion. TBI and depression screening/treatment may result in reduced inpatient VHA costs in OEF/OIF veterans exposed to TBI. VHA policymakers should consider screening for TBI and depression in pre-OEF/OIF veterans.
ABSTRACT
The common approach to modeling healthcare cost data is to use aggregated total cost from multiple categories or sources (e.g. inpatient, outpatient, prescriptions, etc.) as the dependent variable. However, this approach could hide the differential impact of covariates on the different cost categories. An alternative is to model each cost category separately. This could also lead to wrong conclusions due to failure to account for the interdependence among the multiple cost outcomes. Therefore, we propose a multivariate generalized linear mixed model (mGLMM) that allows for joint modeling of longitudinal cost data from multiple sources. We assessed four different approaches, (1) shared random intercept, (2) shared random intercept and slope, (3) separate random intercepts from a joint multivariate distribution, and (4) separate random intercepts and slopes from a joint multivariate distribution. Each of these approaches differs in the way they account for the correlation among the multiple cost outcomes. Comparison was made via goodness of fit measures and residual plots. Longitudinal cost data from a national cohort of 740,195 veterans with diabetes (followed from 2002-2006) was used to demonstrate joint modeling. Among examined models, the separate random intercept approach exhibited the lowest AIC/BIC in both log-normal and gamma GLMMs. However, for our data example, the shared random intercept approach seemed to be sufficient as the more complex models did not lead to qualitatively different conclusions.
ABSTRACT
To obtain information about the evolution of the cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the vertebrates, we investigated the cholinesterase (ChE) activity of the cephalochordate amphioxus (Branchiostoma floridae and Branchiostoma lanceolatum). On the basis of evidence from enzymology, pharmacology, and molecular biology, we conclude that amphioxus possesses two ChE activities and two ChE genes. Two covalent inhibitors of cholinesterases were able to pharmacologically isolate the two activities as drug-sensitive ChE and drug-resistant ChE. Kinetically, in terms of substrate specificity, the drug-sensitive ChE resembles vertebrate AChE, and the drug-resistant ChE resembles the BuChE of cartilaginous and bony fish or the intermediate ChE of protostome invertebrates. We also used the polymerase chain reaction with degenerate oligonucleotide primers and genomic DNA to obtain clones of 1,574 and 1,011 bp corresponding to two cholinesterase genes from amphioxus, which we designated as ChE1 and ChE2. ChE2 codes for an enzyme with an acyl-binding pocket sequence, a portion of the protein that plays an important role in determining substrate specificity, typical of invertebrate ChE. ChE1, which contains a 503-bp intron, encodes a protein with a novel acyl binding site. Phylogenetic analysis of the sequences suggests that the two genes are a result of a duplication event in the lineage leading to amphioxus. We discuss the relevance of our results to the evolution of the cholinesterases in the chordates. Previously, we reported that amphioxus contained a single cholinesterase activity with properties intermediate to AChE and BuChE (Pezzementi et al. [1991] In: Cholinesterases: Structure, Function, Mechanism, Genetics and Cell Biology. J. Massoulié et al., eds. ACS: Washington, D.C., pp. 24-31).
