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Jonathan L. Slaughter, MD

Award Name KL2

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Laparotomy versus Drain Placement in Premature Infants with Necrotizing Enterocolitis (NEC)

Jonathan L. Slaughter, MD, was awarded a KL2 Career Development Grant in January 2011 for his research on the comparative effectiveness of laparotomy versus drain placement in premature infants with Necrotizing Enterocolitis (NEC).

NEC is an inflammatory bowel disease that kills many premature infants. Smaller and premature babies have a higher chance of developing NEC. When NEC is detected in the early stages, doctors give infants antibiotics, which can sometimes be effective in killing the disease. However, if the disease remains, or if the infant has a more severe case, surgery is needed. In severe cases, infant’s bowels begin to rot and can rupture.

There are two surgical treatment methods that are widely-used in severe cases of NEC. One is a laparotomy, an incision into the abdomen to cut out dead bowel tissue. The other is inserting a peritoneal drain into the infant’s stomach to drain out the toxic contents that have ruptured into the stomach from the intestines. Slaughter hopes to find which operation yields better results.

His first step is to complete a meta-analysis of three studies that have been conducted on the effectiveness of the two surgeries, in which he takes data from them and combines it into one, bigger result. These studies are randomized control trials and cannot be completely generalizable.

Slaughter’s next step is to perform an observational study using the Pediatric Health Information System (PHIS). PHIS is a database of billing information on real life patients from 43 U.S. hospitals. Although slightly limited, the PHIS provides information on mortality, length of stay, gender, cost, re-admission rates and birth weight. This information is not as controlled as the information from the randomized control trials, but because the data comes from all types of patients, there are more sectors of the population that can be included in the final result. The overall goal of comparative effectiveness research is to know which outcome is better for all patients, not just the patients involved in the trials.

Slaughter will eventually take the results from his meta-analysis and observational study and try to reduce all the biases using the Bayesian hierarchical method, the statistical technique of taking prior evidence and adding new data in with it.

“With this method you can take all other diseases and risk factors that the baby might have and put them into the model so that the answer you get is controlled for,” Slaughter said.

His final step will be to use the cross-design synthesis method to determine which operation is most effective. He will blend the results from the randomized control trials with the observational study of the PHIS database and extract their weaknesses to find the best possible results.

“My long term career goal is to improve outcomes for preterm infants as a neonatal clinical scientist,” Slaughter said. “Specifically, I want to perform rigorous comparative effectiveness research that will result in more rapid improvement of neonatal care.”

Part of Slaughter’s training grant is being used to better understand Bayesian biostatistics as well as other techniques to enhance his research skills. He meets weekly with his mentors that are experts in neonatal clinical research and comparative effectiveness research. His mentors include Leif Nelin, MD; William Gardner, PhD; Kelly Kelleher, MD, MPH; and Eloise Kaizar, PhD. Kaizar and Kelleher did a Bayesian meta-analysis in 2006 of clinical trials on antidepressants causing suicidal thoughts in teens and are using data from that research to help Slaughter.

As Slaughter tries to perfect the method of cross-design synthesis, he is hopeful that it will someday be applied to diseases outside of neonatal care.

By Jessica Henry, February 28, 2011

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