<p><em>Background:</em> There is a shifting culture toward evidence-based plastic surgery. The use of high-quality evidence in patient decision-making is essential. To help achieve this goal the best evidence in the field needs to be identified, and the validity of this evidence verified.</p> <p><em>Objective:</em> This systematic review was designed to evaluate the plastic surgery literature by focusing on the prevalence of, and examining key components of quality of, Randomized Controlled Trials (RCTs) comparing surgical interventions.</p> <p><em>Methods: </em>An electronic search of the pertinent plastic surgery literature identified all RCTs published from 2000 to 2013 that compared one surgical intervention to another surgical intervention. Working in teams of two investigators independently, and in duplicate, assessed each manuscript for potential relevance and performed data extraction. Descriptive statistics, theory-driven multinomial regression, and independent samples t-test were used for data analysis.</p> <p><em>Results:</em> Of the 1664 hits obtained, 173 RCTs were included. These RCTs demonstrated the following data: 35% of RCTs performed and reported randomization properly, and 12% of RCTs reported proper allocation concealment methods. Outcome assessors were blinded in 48 (34%) RCTs, and patients blinded in 45 (26%) RCTs. Multinomial regression demonstrated that trials reporting an a <em>priori</em> sample size are significantly more likely to have a low risk of bias. One-third of trials did not state a primary outcome. The mean and median sample sizes were 73 and 43 patients respectively. Funding and conflict of interest reporting improved over time.</p> <p><em>Conclusions:</em> This systematic review establishes a baseline of the quality of evidence that currently guides practice for surgical interventions in plastic and reconstructive surgery. For the readers of plastic surgery literature to have confidence in the literature, risks of bias should be minimized and transparently reported. This will encourage plastic surgeons to apply the results and findings from published RCTs in their practice, providing patients them with the best possible treatments.</p> / Master of Science (MSc)

Preterm birth is defined as delivery prior to 37 weeks’ completed gestation. It affects an average of 11% of pregnancies worldwide and is the leading cause of death in children under age 5. Many studies have identified associations between pregnancy lipid levels and increased risk for preterm birth. This thesis investigates the role of genetic variability associated with lipids and its relationship with preterm birth, and the relationship between pre-pregnancy dyslipidemia and risk for preterm birth. Genetic variability in the form of single-nucleotide polymorphisms, previously identified by genome-wide association studies for association with lipid levels, was analyzed for association with risk for preterm birth. The study population included 992 women in California with banked 2nd trimester serum samples. Serum lipid levels and DNA were used. Genetic risk scores were constructed for each subject using published SNPs associated with lipid levels as an indicator of genetic burden. These genetic risk scores were then analyzed for association with risk for preterm birth. The GRS were not associated with the overall risk for preterm birth. However, a higher HDL-C GRS was associated with increased risk for spontaneous preterm birth. Higher triglyceride and total cholesterol GRS were associated with decreased risk for spontaneous preterm birth. The relationship between pre-pregnancy dyslipidemia and risk for preterm birth was assessed in a cohort of 2,962,434 women giving birth in the state of California from 2007-2012. Dyslipidemia, as defined by medical diagnostic codes, was associated with a 1.5-fold increase in risk for preterm birth. This association was consistent across race/ethnicity, body mass index, type of dyslipidemia, and type of preterm birth. This thesis identified counter-intuitive associations between lipid GRS and spontaneous preterm birth, while also identifying a strong relationship between pre-pregnancy dyslipidemia and all types of preterm birth including spontaneous. Together, these findings suggest that the previously reported associations between lipids and preterm birth may be reflecting unidentified dyslipidemias. One possible interpretation of the counter-intuitive genetic findings is that while extreme dyslipidemia predisposes to preterm birth a genetic predisposition to low total cholesterol also confers increased risk for spontaneous preterm birth. An alternative explanation is that these results are simply an artefact of the data and additional genetic loci and lifestyle factors confer stronger effects on risk for spontaneous PTB than the effects of the genetic loci included in this thesis.

Babesiosis is a disease caused by parasites of Babesia species that is spread through ticks. Babesiosis can affect humans and many other mammals all over the world. In the United States, babesiosis is mainly caused by Babesia microti with additional species of Babesia infecting dogs. Dogs have long been known to be a good indicator species for human tick-borne infection due to the shared spaces they have with humans and their tendency to explore and pick up diseases in the environment. This study used a group of hunting dogs to determine the presence of Babesia infection. The goal was to determine a predictive model for human infection. Infection was defined as having a positive antibody test or molecular test for Babesia species in blood samples. Blood samples were taken at two time points, tested, and compared. Statistical methods were used to analyze the results of the tests and compare them with variables such as region, gender, age, and other diseases the dogs were exposed to. Of 214 dogs, 56 had Babesia infections, with a prevalence rate of 26.2%. At the first time point the model showed age and infection with Anaplasma platys as being significant. At the 2nd time point, 29 dogs were lost to follow up, leaving a total of 185 dogs sampled with 63 testing positive for Babesia spp. The rate for the 2nd time point was 34.1%. No variables were found to be significant in the model for the 2nd time point. Despite differences in Babesia that infect humans and dogs, the hunting dog cohort reflects a model that validates the environmental exposures, coinfections, and demographic variables that affect transmission of the pathogen. Furthermore, findings of this study cast doubt on the ability of Ixodes scapularis to act as capable vector for canine-infecting Babesia species.

Depression during the perinatal time period is the most common medical condition related to pregnancy and childbirth. Based on previous research, this condition can have negative sequelae for mothers, their offspring, families and the community. Therefore, studies are needed to better understand risk factors and health outcomes among women with depression and the health outcomes among children born to mothers with depression. We examined rurality as a risk factor for depression during the perinatal time period using data from the 2016 Pregnancy Risk Assessment Monitoring Survey (aim one). We found women who resided in rural communities, as defined by their individual states, had an increase in the odds of depression during the perinatal period by 21% (OR: 1.21; 95% CI 1.05,1.41) when compared to women who resided in urban communities. Based on the results from this study, future studies are warranted to examine mediators of this relationship to develop effective public health and clinical interventions. Next, we examined the association between perinatal mental health conditions and postpartum prescription opioid use using private insurance claims data of women who delivered a baby in the state of Iowa 2005 to 2016 (aim two). Overall 38.63% of the women in our study filled at least one opioid prescription and 5.88% filled at least two prescriptions in the first 90 days postpartum. A significant interaction of having a perinatal mental health condition and delivery mode was observed for at least one (p=.04) and at least two opioid fills (<.0001). The presence of a mental health condition among women who delivered vaginally increased their odds of filling at least one opioid fill by nearly 50% (OR: 1.48 95% CI 1.35, 1.63) and by almost 20% (OR: 1.19 95% CI: 1.00, 1.43) among women with a cesarean delivery. A mental health condition significantly increased the odds of filling at least two opioid prescriptions among women with a vaginal or cesarean delivery by 2.78 (95% CI: 2.32-3.33) and 1.66 (95% CI: 1.40,1.98). Based on findings from this study, more research is needed to improve our understanding of the relationship between perinatal mental health and prescription opioid use. Finally, the association between perinatal depression and attention deficit hyperactivity disorder (ADHD) use was examined using private insurance claims data from mother-child pairs from the state of Iowa (aim three). Children were born during years 2004 through 2015. In our study children born to mothers with perinatal depression were at an increased odds of ADHD diagnosis by 170% (OR: 2.70; 95% CI 2.06, 3.55). We also evaluated how timing of depression (during pregnancy vs. postpartum) influenced the odds of ADHD diagnosis. While we found children born to mothers with depression during pregnancy and postpartum had an increased risk of ADHD diagnosis, we observed children exposed to depression during fetal development had the greatest risk overall. Research is needed to better understand the mechanisms of risk between perinatal depression and ADHD risk in offspring. Additionally, due to low power we were not able to evaluate how treatment of depression during pregnancy or postpartum may influence childhood outcomes, therefore more studies are needed in this area. Overall, findings from each study illustrate the importance of maternal mental health and how a mental health condition during the perinatal period can influence maternal and child health outcomes. Future prospective population-based studies are needed to better understand the etiologies of perinatal mental health conditions and how such conditions can influence outcomes for maternal and child health. Results from future studies have the potential to shift clinical practice to improve prevention and intervention in turn improving overall maternal and child health outcomes.

Choanal atresia is a well-defined congenital malformation; however, little is known about its prevalence and risk factors. Data from the Iowa Registry for Congenital and Inherited Disorders were used to examine prevalence, infant, and maternal characteristics of choanal artesia. Data from the National Birth Defects Prevention Study (NBDPS) were used to examine selected risk factors for choanal atresia. Overall prevalence was estimated as number of choanal atresia cases per 10,000 live births with 95% confidence intervals (CI)s. Crude and adjusted odds ratios (OR)s and 95% CIs were estimated to investigate selected risk factors. The overall prevalence of choanal atresia among live born deliveries in Iowa from January, 1998 through December, 2005 was 0.46 (95% CI=0.27, 0.78) per 10,000 live births. Using data from the NBDPS, choanal atresia cases were compared to unaffected control infants for births from October 1997 through December 2005. Overall, case infants compared to control infants were more likely to be female, preterm, and a multiple birth. For all choanal atresia cases combined, odds of high maternal zinc (OR=2.1; 95% CI=1.2, 3.9) and vitamin B-12 (OR=2.4; 95% CI=1.4, 4.3) intake in the year prior to pregnancy, and maternal periconceptional (one month before through three months after conception) exposure to anti-infective urinary tract medications (OR=3.3; 95% CI=1.3, 8.4) were significantly elevated among case compared to control mothers. For isolated choanal atresia cases (those with no additional major malformations), odds of maternal periconceptional exposure to passive cigarette smoke (OR=2.3; 95% CI=1.0, 5.3) as well as maternal intake of 3 or more cups of coffee per day one-year prior to pregnancy were increased (OR=2.9; 95% CI=1.3, 6.4) for case compared to control mothers. The reverse was found for low maternal intake of pantothenic acid (OR=0.4; 95% CI=0.2,0.9) and vitamin A (OR=0.3; 95% CI=0.1, 0.8) one-year prior to pregnancy. The current study provided support for potential associations between maternal health behaviors before and during pregnancy and choanal atresia; however, the findings were based on a modest number of cases. The study needs to be replicated in a larger case sample, also examining the role of genetics in choanal atresia.

A retrospective mortality and cancer incidence study of former nuclear weapons assemblers from the Iowa Army Ammunitions Plant was conducted. This study examined whether or not workers at the plant exhibited higher rates of mortality or cancer as a result of their work-related activities. Potential exposures included radiation, beryllium, asbestos, and solvents. Cancer incidence was determined by calculating standardized incidence ratios (SIR) and using the Iowa population as reference. SIRs were calculated on 3,889 workers from1969-2005. Overall and cause-specific mortality was determined by calculating standardized mortality ratios (SMR) and using the U.S. and Iowa populations as reference. SMRs were calculated on 5,743 workers from 1947-2005. The SIR results showed that overall cancer incidence was lower than the Iowa population. Using the Iowa population as reference, the SMR analyses for men demonstrated excesses for all cancers (SMR 1.09, 95% CI 1.02-1.17), lung cancer (SMR 1.38, 95% CI 1.24-1.54), diseases of the respiratory system (SMR 1.15, 95% CI 1.03-1.46), mesothelioma (SMR 6.20, 95 % 1.28-18.1), asbestosis (SMR 9.28, 95% CI 1.12-33.5) and COPD (SMR 1.27, 95% CI 1.10-1.46). Significantly lower SMRs were observed stomach cancer and ischemic heart disease. For women excesses were observed for all cancers (SMR 1.41, 95% CI 1.17-1.69), lung cancer (SMR 2.47, 95% CI 1.72-3.44), ischemic heart disease (SMR 1.32, 95% CI 1.09-1.58), respiratory diseases (SMR 1.59, 95% CI 1.14-2.16), and COPD (SMR 2.47, 95% CI 1.60-3.65). Using the U.S. population, men experienced lower overall mortality while women had significantly higher overall mortality. In conclusion, the SIR portion of the study showed overall lower cancer incidence for both men and women. This may be due to the Healthy Worker Effect and the limited dates of study. There are no cancer registry data before 1969 thus missing cancers with short induction periods. Workers may have also moved out of the Iowa and had a cancer diagnosis in another state. Compared to Iowa population, there was an excess of respiratory disease deaths and deaths from lung cancer in both men and women. Considering the significant respiratory exposures workers may have experienced, further study with a nested case-control design is suggested.

Objective: In 2010, motor vehicle crashes were the leading cause of death among 13 – 19 year-old males and females in the United States (National Center for Injury Prevention and Control, 2014). The overall goal of this research is to differentiate between measures associated with crashes for young teen drivers, age fourteen to fifteen years on urban and rural roads. Methods: A retrospective study of motor vehicle crashes among 14 and 15-year old drivers in the state of Iowa was conducted using crash information obtained from the Iowa Department of Transportation for the years of 2001 to 2013. Crash rates were calculated by rurality using Urban Influence Codes (UIC). The total number of crashes and crashes resulting in injury were divided by the population of young teen drivers aggregated at the UIC level. Crash and driver characteristics were analyzed for measures of association to the main outcome, injury using logistic regression. Crash and driver characteristics that were associated with injury at the p ≤ 0.20 level were eligible for model inclusion. Results: For every 1,000 young teen drivers age fourteen to fifteen years, nearly 8 were involved in a crash statewide from 2001 - 2013. Half of all crashes in the dataset occurred in an urban area (n = 4327, 51%), while 7% occurred in a suburban area, 29% in a town and 13% in a remote rural area. Results show, for all crashes and crashes resulting in injury, that as the level of rurality increases, rates of crash also increase. Remote rural crashes have the highest crash rate ratio (RR = 1.15, 95% CI: 1.08, 1.22), relative to urban crashes. The presence of multiple teen passengers in the vehicle increased the odds of having a crash that resulted in injury 10.73 times, compared to no passengers being present (95% CI: 7.10, 16.22). Characteristics with the strongest association with injury were single vehicle collisions, crashes that occurred on rural roads, crashes were the driver lost control and crashes were multiple teen passengers were present. Conclusions: Results from this study highlight the dangerous circumstances that young teen drivers face, especially when driving on rural roads. In order to protect young teen drivers from crashes, there is a need for more restrictions on the number of passengers and the development of prevention methods to make young teen drivers safer.

Pediatric acute respiratory tract infections (ARTIs) are a leading cause of morbidity and mortality. The objectives of this study were to describe the epidemiology of polymicrobial ARTI in a hospital-based pediatric population and to investigate the association of polymicrobial infection and severity of illness. We conducted a retrospective study of 559 archived respiratory specimens from 421 children under the age of 10 years collected from March 28, 2008 through June 30, 2009 and stored by the University of Iowa Hospital and Clinics Clinical Microbiology Laboratory. Specimens were tested by immunofluorescence assay and/or viral culture at the time of collection (influenza A and B, parainfluenza [PIV] 1-3, respiratory syncytial virus [RSV], adenovirus [Ad]) and uniformly by RT-PCR (human metapneumovirus [hMPV], rhinovirus [HRV], human bocavirus [HBoV]) and PCR (Ad) for the current study. Demographic and clinical data were abstracted from electronic medical records. Results from this study suggest that polymicrobial respiratory tract infections are common in this population. A virus was identified in 61.3% of 349 respiratory specimens from children with confirmed or suspected ARTI. HRV (27.5%), RSV (18.9%), HBoV (8.3%), hMPV (7.7%), and PIV (6.6%) were the most common viruses detected. A viral coinfection was identified in 21.5% of the 214 virus-positive specimens and was most often detected for Ad (53.3% of 15 Ad-positive specimens), HBoV (51.7% of 29 HBoV-positive specimens), PIV (43.5% of 23 PIV-positive specimens), HRV (35.4% of 96 HRV-positive specimens), and RSV (34.8% of 66 RSV-positive specimens). Among the 46 specimens with dual or triple viral coinfections detected, the most frequent virus-virus combination was HRV-RSV (n=12). We hypothesized that certain host-specific risk factors were associated with the likelihood of viral coinfection. While none of the covariates in the final model were significant, the results were suggestive. Male gender (OR 1.70, 95% CI 0.83-3.46), age between 6 months to 1 year (as compared to children less than 6 months old, OR 2.15, 95% CI 0.75-6.19), and history of any chronic condition that may result in immunosuppression (OR 2.05, 95% CI 0.99-4.23) were each associated with increased odds of viral coinfection (p > 0.05). We also hypothesized that children with coinfections would be more likely to have severe ARTI. Children with viral-bacterial coinfection, as compared to children with viral mono-infection, were more likely to be admitted to an intensive care unit (OR 6.00, 95% CI 2.51-14.33) even after controlling for age, history of prematurity, urban/rural residence, and leukocytosis. This study will inform medical and public health professionals with regard to the epidemiology of polymicrobial infections and their potential importance as a cause of severe acute respiratory tract infection in children. Furthermore, results of this study may contribute to the ongoing discussion of the importance of diagnostic ability to reliably detect multiple concurrent pathogens in a single individual.

Background: Antiretroviral drug resistance is steadily growing in populations of HIV treatment-naive individuals due to person-to-person transmission. However, Iowa-specific data for transmitted antiretroviral drug resistance-associated mutations prevalence has not been previously reported. We postulate that the prevalence of drug resistance in Iowa does not differ significantly between HIV risk groups. Methods: Data were collected from electronic medical records and an HIV Program database between 2006 and 2011. Information included age, gender, risk exposure group, viral load, CD4 count, CD4%, and other HIV risk factors and behaviors. Results: Transmitted drug resistance mutations (TDRM) were not associated with many risk factors, but rapid plasma reagin (RPR) screening for syphilis was significant (p=0.02) and used as a proxy for highest level of sexual risk behavior. RPR was used with minor NRTI and NNRTI along with intravenous drug use in logistic regression to model the likelihood of acquiring TDRM. Conclusion: Some question the practicality of implementing genotypic ARV resistance testing guidelines because of uncertainty about the prevalence of ARV drug resistance among treatment-naïve patients but harboring resistance mutations puts patients at high risk of failing effective, first-line therapies. Hence, genotypic resistance testing at HIV diagnoses can not only improve disease management but also assist in surveillance.

Glaucoma is the second leading cause of blindness affecting over 60 million people worldwide. The objectives of this study were to expand the existing methods of trend analysis in visual field time series data testing to aid in the early and accurate detection of glaucoma progression. Visual field data including 54 locations for each of 140 eyes (one per participant among 96 cases and 44 controls) were evaluated using the Humphrey Field Analyzer II program 24-2 Swedish interactive thresholding algorithm (SITA) standard test strategy and Goldmann size III stimuli. One eye was randomly selected for the study and data were collected between 2003 and 2009. Two visual field examinations were conducted at baseline and at eight additional time points of visual field exams taken every six months for four years. Demographic, clinical, structural and other health data in the VIP study were collected from the electronic medical record and health questionnaires. A variety of pointwise linear regression (PLR) criteria have been proposed for determining glaucomatous visual field progression. However, alternative PLR criteria have only been assessed on a limited basis. The first aim of this glaucoma progression detection study thoroughly examined PLR cut-point criteria to maximize the sensitivity and specificity of this standard tool in visual field analysis. The pointwise linear regression A2 (PLRA2) method was used to analyze the data, and Ocular Hypertension Treatment Study (OHTS) data were used to validate the decision rule. Results showed that visual field trend analysis using PLR can be refined by adjusting the standard slope-based and significance level-based criteria. By considering more restrictive declines in visual field data (e.g., < -1.2dB/y, which is approximately 12 times the normal rate of age-related decay) and relaxing the significance level criterion of the PLR slope to p < 0.04 a high specificity can be maintained, while increasing the hit rate, i.e., the proportion of glaucoma cases in which progression was detected by PLR. This work serves to improve a familiar and commonly used method of time series visual field trend analysis that can be implemented quickly to improve early detection of glaucoma progression. The second aim of this project was to investigate the performance of the nonlinear exponential and tobit regression models relative to the normal regression model in the analysis of visual field decay. The goodness-of-fit, as measured by Akaike Information Criteria (AIC), and rates of progression obtained by fitting three alternative regression models to longitudinal visual field data were compared at the location level. The results showed that visual field trend analysis using the tobit regression model results in a better model fit to visual field data, increased precision in the estimation of the rate of progression, and provides a specific advantage in modeling data from cases with advanced glaucoma. The third, and final, aim of this glaucoma progression research project sought to determine if demographic, clinical and health factors, including intraocular pressure, retinal nerve fiber layer thickness, hypertension and diabetes, differ in participants whose visual field data are best fit overall by one statistical model compared to another. This was the first study to examine person-level factors that may affect the fit of proposed analysis models for visual field data, and to utilize bivariable and multivariable methods to understand patient-level predictors of visual field model fit. In the majority of eyes, the tobit model provided either a significantly better fit or there was no difference among models. Significant differences in patient characteristics included baseline MD and previous ocular surgery. This indicates that the tobit model may fit visual field time series data at least as well as the normal and nonlinear exponential models in all cases and controls; and in some advanced cases, it may provide a significantly improved fit. This research overcame critical barriers in visual field trend analysis by increasing the sensitivity of PLR methods and further developing methods using alternative distributions to determine significant loss of function within each visual field test location. Furthermore, results of this study will contribute to the ongoing improvement of visual field trend analysis and the early detection and treatment of glaucoma progression.