Why Research?

Why Research?

My Experience as an Undergraduate Pre-Med Student

Author: Phil Wozniak
Date: October 15, 2014

Deciding to pursue a career in medicine has been an evolving process for me. It was never as simple as waking up one day and "just knowing" that I was supposed to be a physician. My decision to pursue medicine developed gradually through experience and culminated in the realization that medicine fulfills a calling that no other career can satisfy. Medicine as a career was very familiar to me growing up. Some of my earliest memories are of watching my mother study for medical school on the front porch while I played at the neighborhood park across the street. As a toddler, I heard all about abstract ideas like "biochemistry" and "pharmacology" from my booster seat at the kitchen table. As I grew up, I also began to ask her the "why?" behind all things medical. Why did the Band-Aid stop the bleeding? What does my temperature tell the doctor? As I got older, those questions became what is a hemorrhage, ulcer, or hematoma? My mother is graced with a talent for explaining medical complexities in simple terms; her explanations affirmed my natural curiosity and fostered my ever-growing fascination with medicine. From elementary school through high school, I watched my mother go through residency and establish a practice. I saw firsthand how challenging, yet rewarding, a career in medicine is. I knew that I wanted a career as rewarding for me as medicine is for my mother, but being an eyewitness to the effort required, I also found the prospect of a medical career quite daunting. When I entered college, I was genuinely torn between pursuing my interest in politics and pursuing medicine. I initially declared a Politics major as a freshman, but I also enrolled in General Biology to stay on track for medical school. Ultimately, I decided that I needed to explore the medical field myself through shadowing and research. My exploration began with a friend who offered to introduce me to an oncologist and take a tour of his lab. This tour began a series of referrals that eventually led me to Dr. Pablo Sanchez, an infectious diseases specialist/neonatologist.

In May of 2012, Dr. Pablo Sanchez hired me as a clinical research assistant at the University of Texas-Southwestern Medical Center/Children's Medical Center, Dallas. For my first project in the fall of 2012, Dr. Sanchez assigned me to work with Dr. Joseph Cantey, a pediatric infectious diseases and neonatology fellow. Dr. Cantey had just begun a prospective cohort study on antimicrobial stewardship that cataloged all of the antibiotics usage in the Neonatal Intensive Care Unit (NICU) at Parkland Memorial Hospital. This study includes three phases: Phase I was nine months of recording clinical results, Phase II was a six-month analysis period of Phase I results in order to come up with changes to clinical protocol, and Phase III is ongoing, and will track changes following the implementation of Phase II. Over two years, we enrolled over 2,500 infants in our study. After exclusions, our final population for analysis included 1,607 infants. Every infant received a patient record sheet designed specifically for our study. Those sheets assigned each infant a patient number and recorded their reason for admission, birth weight, notable conditions, and whether or not the infant received any antibiotic therapy. If the patient did receive antibiotics, then they were given a supplemental packet charting which antibiotics they received and duration of their therapy. We used this therapy information to calculate an "antibiotic days" metric by which to compare every individual infant. We calculated the number of antibiotic days by multiplying the number of doses given by the dosing interval in days. We also used the calculated number of antibiotic days to compare how often each type of antibiotic therapy was prescribed. For example, Gentamicin was the most frequently prescribed and accounted for 3,451 antibiotic days; conversely, Cefotaxime accounted for only 4 antibiotic days, making it the least prescribed. I was also responsible for inputting all of the paper information into our database. Each time I went to the hospital to follow up with Dr. Cantey or round with Dr. Sanchez, I left the hospital with large stacks of paper records for this study. Upon the completion of Phase I, our results showed that out of 7,570 total antibiotic days, only 6% went to treating culture-proven infection. 89% of all antibiotics prescribed treated patients with sterile cultures. We also found that 68% of all antibiotic courses were extended beyond 48 hours, resulting in 885 unnecessary antibiotic days of therapy (12% of total). Furthermore, treatment lasting for 5 or more days for a presumed infection, despite sterile cultures, accounted for 26% of all antibiotic use. These results from Phase I allowed Dr. Cantey to formulate necessary changes to clinical care. Dr. Cantey presented Phase I of this study in a Platform Presentation at the 2013 Pediatric Academic Societies annual conference. Our manuscript, "The NICU SCOUT Study: Surveillance and Correction of Unnecessary Antibiotic Therapy," has been accepted for publication by the Pediatric Infectious Disease Journal.

This study on antimicrobial stewardship prompted us to conduct a follow-up study analyzing the treatment of early-onset pneumonia in the NICU. We looked at whether the duration of therapy (shorter [5 days] versus longer [7 or more days]) affected outcome, in order to convince physicians to treat for shorter durations to minimize side effects. This study was accepted to the '2014 Pediatric Academic Societies' annual conference as a poster entitled "The Conundrum of Pneumonia Treatment in the NICU: Can Variation Inform Antibiotic Stewardship?"

In the summer of 2013, Dr. Sanchez gave me my first independent project. Using Dr. Sanchez's extensive database, I analyzed the treatment of 881 mother/infant pairs at risk or treated for congenital syphilis by Dr. Sanchez between 1984 and 2002. This study had four objectives. First, we wanted to describe the epidemiology of congenital syphilis at Parkland Memorial Hospital (PMH) and Children's Medical Center, Dallas (CMC) in those years. Second, we analyzed the maternal characteristics, demographic features, clinical findings, and management of infants born to mothers with reactive serologic tests for syphilis. Third, we compared the number of cases of congenital syphilis at PMH and CMC using the surveillance case definition of the Center for Disease Control and Prevention (CDC) versus the number of cases diagnosed by clinical, laboratory and/or radiographic methods. Finally, we sought to identify factors that could aid in the prevention of congenital syphilis. The CDC separates its surveillance case definition for congenital syphilis into two categories: probable cases and confirmed cases. Confirmed cases require demonstration of Treponema pallidum (the bacterium causing syphilis) by darkfield microscopy or specific staining of specimens from lesions, placenta, umbilical cord, or autopsy material. Probable cases of congenital syphilis must meet one of two definitions: infants whose mothers received no treatment prior to delivery or were inadequately treated at delivery, or infants with reactive serologic test for syphilis and abnormal clinical, laboratory, or radiographic findings consistent with congenital syphilis. The infants in our study were diagnosed with congenital syphilis if they had an abnormal physical exam, laboratory findings, long bone radiographs, reactive IgM immunoblot, positive PCR, or a positive rabbit infectivity test. Learning about the various laboratory techniques Dr. Sanchez used to diagnose his patients allowed me to apply what I was learning in my biochemistry classes to my research, which I found extremely gratifying. Ultimately, we diagnosed 155 infants with congenital syphilis. 121 of them had an abnormal physical exam; the remaining 34 infants had a normal physical exam, but abnormal laboratory findings. In order to compare our results to the CDC's surveillance case definition, we divided our cohort into specific subpopulations based on maternal treatment and the infant's physical examination. We excluded serofast mothers and their infants, which brought our final patient population to 794 mother/infant pairs. Infants with an abnormal physical examination were placed in their own category for analysis. We separated infants with a normal physical examination by the maternal treatment: mothers either received no treatment, inadequate treatment (less than four weeks before delivery), or treatment during pregnancy (more than four weeks before delivery). We also looked at the population of mothers as a whole, finding that 30% used illicit drugs and 6% were concomitantly infected with HIV. Mothers of infants with congenital syphilis also had significantly fewer prenatal care visits than mothers of uninfected infants (p-value = 0.004). The majority of mothers of infected infants had no prenatal care at all. Infants with an abnormal physical examination had significantly more adverse outcomes than infants with a normal physical examination. Among these 121 infants, the mean gestational age was only 33 weeks with a standard deviation of 5 weeks. Their mean birth weight was a scant 2,042 grams with a standard deviation of 782 grams. Most shocking, however, was the mortality among infants with an abnormal physical examination. 48 of these infants died, yielding an overall mortality of 40%. Stillbirths accounted for 42 deaths; the remaining 6 deaths occurred in the neonatal period. Of the infants with an abnormal physical exam consistent with congenital syphilis, 87% had a positive IgM immunoblot. 50% had spirochetes detected in serum or blood by rabbit infectivity testing, and 43% had central nervous system invasion by T. Pallidum (also detected by rabbit infectivity testing). The 673 infants that had a normal physical examination were compared by the maternal syphilis treatment. Of these infants, 1% 6% of infants had an abnormal evaluation consisting of anemia, thrombocytopenia, reactive CSF VDRL, or abnormal bone radiographs. Among mothers with untreated syphilis at delivery, there was an overall mortality of 7%.

From this study, we demonstrated that mothers of infants with congenital syphilis had significantly fewer prenatal care visits, highlighting the importance of early prenatal care for prevention of congenital syphilis. Infants with congenital syphilis also had significantly lower gestational age and birth weights than uninfected neonates. Of the 794 infants in our study population, 581 of them met the CDC's surveillance case definition for congenital syphilis. Using the CDC's definition, our population had a 15% case-fatality rate for congenital syphilis; however, using our clinical definition, the case fatality rate was 57%, which included 89 deaths, of which 67 were stillborn. 66% of deaths occurred at a gestational age of 32 weeks or less. The CDC surveillance case definition for congenital syphilis correctly identified all infants who were diagnosed with congenital syphilis because of abnormal clinical, laboratory, or radiographic findings with 100% sensitivity, but it overestimated the number of actual cases by more than 300%. The opportunities to conduct research with Drs. Sanchez and Cantey allowed me to fully experience every stage in a research project. Not only did I see how research is actually conducted, I also saw how research is published. I wrote my own abstract for submission to the 2014 Pediatric Academic Societies' annual conference in Vancouver. When my study was accepted as a Platform Presentation, I had the privilege of delivering my results to the Neonatal Infections session on May 4, 2014.

These experiences with Dr. Sanchez gave me a vision of what I hope my own practice to be. I know myself, and I know that I have to be able to treat patients in a clinical setting. Working with Dr. Sanchez allowed me to see how clinical work can become substantive, important research. When I presented our findings at the 2014 Pediatric Academic Societies' annual conference, I was fortunate enough to talk with true experts. The dialogue and debate between these clinical researchers was fascinating. I saw how projects on antibiotics conducted in the United States sparked discussion amongst neonatologists from France about how they could consider improving their own clinics. I entered the University of Dallas without a clear vision of what I wanted my life's work to be. Gaining experience along with mentors and friends like Dr. Sanchez and Dr. Cantey not only showed me how rewarding a career in medicine can be, but it also confirmed my desire to pursue medicine. The DFW metroplex is flush with phenomenal opportunities for University of Dallas students. It is up to us to take advantage of them.



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