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2015 ; 473
(9
): 2807-13
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Preventing Heterotopic Ossification in Combat Casualties-Which Models Are Best
Suited for Clinical Use?
#MMPMID25917420
Alfieri KA
; Potter BK
; Davis TA
; Wagner MB
; Elster EA
; Forsberg JA
Clin Orthop Relat Res
2015[Sep]; 473
(9
): 2807-13
PMID25917420
show ga
BACKGROUND: To prevent symptomatic heterotopic ossification (HO) and guide
primary prophylaxis in patients with combat wounds, physicians require risk
stratification methods that can be used early in the postinjury period. There are
no validated models to help guide clinicians in the treatment for this common and
potentially disabling condition. QUESTIONS/PURPOSES: We developed three
prognostic models designed to estimate the likelihood of wound-specific HO
formation and compared them using receiver operating characteristic (ROC) curve
analysis and decision curve analysis (DCA) to determine (1) which model is most
accurate; and (2) which technique is best suited for clinical use. METHODS: We
obtained muscle biopsies from 87 combat wounds during the first débridement in
the United States, all of which were evaluated radiographically for development
of HO at a minimum of 2 months postinjury. The criterion for determining the
presence of HO was the ability to see radiographic evidence of ectopic bone
formation within the zone of injury. We then quantified relative gene expression
from 190 wound healing, osteogenic, and vascular genes. Using these data, we
developed an Artificial Neural Network, Random Forest, and a Least Absolute
Shrinkage and Selection Operator (LASSO) Logistic Regression model designed to
estimate the likelihood of eventual wound-specific HO formation. HO was defined
as any HO visible on the plain film within the zone of injury. We compared the
models accuracy using area under the ROC curve (area under the curve [AUC]) as
well as DCA to determine which model, if any, was better suited for clinical use.
In general, the AUC compares models based solely on accuracy, whereas DCA
compares their clinical utility after weighing the consequences of under- or
overtreatment of a particular disorder. RESULTS: Both the Artificial Neural
Network and the LASSO logistic regression models were relatively accurate with
AUCs of 0.78 (95% confidence interval [CI], 0.72-0.83) and 0.75 (95% CI,
0.71-0.78), respectively. The Random Forest model returned an AUC of only 0.53
(95% CI, 0.48-0.59), marginally better than chance alone. Using DCA, the
Artificial Neural Network model demonstrated the highest net benefit over the
broadest range of threshold probabilities, indicating that it is perhaps better
suited for clinical use than the LASSO logistic regression model. Specifically,
if only patients with greater than 25% risk of developing HO received
prophylaxis, for every 100 patients, use of the Artificial Network Model would
result in six fewer patients who unnecessarily receive prophylaxis compared with
using the LASSO regression model while not missing any patients who might benefit
from it. CONCLUSIONS: Our findings suggest that it is possible to risk-stratify
combat wounds with regard to eventual HO formation early in the débridement
process. Using these data, the Artificial Neural Network model may lead to better
patient selection when compared with the LASSO logistic regression approach.
Future prospective studies are necessary to validate these findings while
focusing on symptomatic HO as the endpoint of interest. LEVEL OF EVIDENCE: Level
III, prognostic study.
|*Decision Support Techniques
[MESH]
|*Military Medicine
[MESH]
|Area Under Curve
[MESH]
|Biopsy
[MESH]
|Debridement
[MESH]
|Gene Expression Profiling
[MESH]
|Gene Expression Regulation
[MESH]
|Genetic Markers
[MESH]
|Humans
[MESH]
|Logistic Models
[MESH]
|Neural Networks, Computer
[MESH]
|Ossification, Heterotopic/diagnosis/*etiology/genetics/prevention & control
[MESH]