Browsing by Author "Obstetrics and Gynecology, School of Medicine"
Now showing 1 - 10 of 351
Results Per Page
Sort Options
Item 56656 Programmatic Enhancements to Advance Racial Equity in Indiana (IN) CTSI(Cambridge University Press, 2021) Tucker Edmonds, Brownsyne; Robb, Sheri; Hurley, Thomas; Carroll, Aaron; Obstetrics and Gynecology, School of MedicineABSTRACT IMPACT: We present new programs aimed at training, retaining and preparing a diverse cadre of scientists to lead the field in transforming population health and advancing health equity. OBJECTIVES/GOALS: To mitigate biases inherent to the R01 grant funding process, trainees from backgrounds underrepresented in medicine (URM) may benefit from enhanced mentorship and a longer ‘runway’ to funding. As such, we have deployed two synergistic programs that aim to support URM retention and advancement. METHODS/STUDY POPULATION: The URM Program for Advising in Research and Development (UPwARD) pairs URM trainees with 2 mentors: 1) an institutional leader from outside their discipline to serve as an internal advocate and 2) an external eminent scholar who will facilitate the scholar’s development and prominence within their discipline. Additionally, the KL2 Program to Launch URM Success (KL2 PLUS) offers URM trainees a third year of funding to focus on scholarship, grant writing and leadership development. Four specific training components of KL2 PLUS include: 1) PLUS II Seminar Series, 2) Faculty Success Program, 3) attendance at the AAMC Minority Faculty Leadership Conference, and 4) CTSI Committee Service. RESULTS/ANTICIPATED RESULTS: Along with measures of productivity (papers, grants, K to R transition), we will utilize social network analyses and measures of collaboration, retention, and future CTSI engagement to evaluate the programs “success’‘ as both are designed to enhance trainee scholarly development and expand their professional and social networks. UPwARD does so by supporting engagement with external mentors at professional meetings and travel to present work across institutions. PLUS writing accountability groups will enhance publication rates and grant submissions, while also building connections with other URM faculty. Trainees also serve on IN CTSI committees to groom talent for future IN CTSI leadership. DISCUSSION/SIGNIFICANCE OF FINDINGS: Systemic inequities underlie the ‘leaky pipeline’ challenge we face in cultivating a diverse cadre of senior scientists and independent investigators. With intentional programming and targeted investments, IN CTSI aims to advance more equitable funding outcomes and diverse leadership.Item 786 Neonatal outcomes in pregnant women with diagnosis of COVID-19(Elsevier, 2021) Izewski, Joanna; Boudova, Sarah; Rouse, Caroline E.; Ibrahim, Sherrine A.; Shanks, Anthony L.; Reinhardt, Jeff C.; Scifres, Christina; Haas, David M.; Peipert, Jeffrey F.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of MedicineObjective It is unclear whether infection with COVID-19 during pregnancy increases the risk of adverse neonatal outcomes. We tested the hypothesis that a diagnosis of COVID-19 during pregnancy increases the risk of neonatal respiratory morbidity and other adverse neonatal outcomes. Study Design: Retrospective analysis of prospectively collected data from two labor and delivery units with universal COVID-19 testing policy between March 1 and May 31, 2020. Pregnant women with singleton pregnancies who delivered during the study period and underwent testing for COVID-19 at any point in their pregnancy were eligible. The primary outcome was a composite of neonatal respiratory morbidity defined as the occurrence of any one of the following: respiratory distress syndrome, transient tachypnea of the newborn, and need for respiratory support. The risk of neonatal morbidity with and without a COVID-19 diagnosis were compared using univariable and multivariable analyses. Stratified analysis compared the risks of adverse neonatal outcomes in symptomatic and asymptomatic patients with COVID-19 to those without COVID-19. Results: Of 515 subjects meeting inclusion criteria, 55 (10.7%) tested positive for COVID-19; 19 (34.6%) were asymptomatic and 36 (65.4%) were symptomatic. No neonate tested positive for COVID-19. Rates of the primary outcome, composite neonatal respiratory morbidity, were not significantly different in patients with and without COVID-19 (21.8% vs 19.6%, P=0.692). There was no significant difference in the risk of neonatal respiratory morbidity in a Cox regression model accounting for time from diagnosis to delivery, and adjusting for gestational age at delivery, mode of delivery, and maternal diabetes (adjusted hazard ratio: 0.62; 95% CI 0.35, 1.09). There were no significant differences in any of the secondary outcomes in patients with COVID-19 who were asymptomatic or symptomatic (Table). Conclusion: A diagnosis of COVID-19 during pregnancy does not appear to increase the risk of neonatal morbidity. These data may be useful in counseling women diagnosed with COVID-19 during pregnancy.Item 975 ABO blood group, rhesus type and risk of COVID-19 in pregnant women(Elsevier, 2021) Ibrahim, Sherrine A.; Boudova, Sarah; Rouse, Caroline E.; Shanks, Anthony L.; Reinhardt, Jeffrey; Scifres, Christina; Haas, David M.; Peipert, Jeffrey F.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of MedicineObjective: There is controversy regarding the association of ABO blood group, Rhesus (Rh) type and risk of COVID-19. We tested the hypothesis that ABO blood group and Rh type are associated with COVID-19 diagnosis and symptoms during pregnancy. Study Design: Retrospective analysis of prospectively collected data from two labor and delivery units with universal SARS-CoV-2 testing policy between March 1 and May 31, 2020. All pregnant women tested during the study period were eligible. The primary outcome was COVID-19 diagnosis. Secondary outcomes were measures of COVID-19 severity, including symptoms, ICU admission, respiratory support and treatment for COVID-19. Outcomes were compared across ABO blood groups. Women with blood group O or Rh positive blood type were compared with non-O groups and Rh negative, respectively, using univariable and multivariable analyses. Results: Of 586 pregnant women tested, 66 (11.3%) were positive. The most common ABO blood group in the cohort was O (52.2%) and 87.4% were Rh positive. Rates of the primary outcome, COVID-19 diagnosis, were not significantly different across ABO blood groups (P=0.47). There were also no significant differences in measures of COVID-19 severity among blood groups (Table). Compared to other blood groups, the risk of COVID-19 diagnosis was not significantly different in women with group O (13.1% vs 9.3%, adjusted OR 1.43; 95% CI 0.84, 2.4). Rh positive women were at a significantly higher risk of COVID-19 diagnosis (12.3% vs 4.1%, adjusted OR 3.38; 95% CI 1.03, 11.07) and a non-significant increased risk of symptoms (6.8% vs 2.7%, adjusted OR 2.67; 95% CI 0.63, 11.32), after adjusting for ABO blood group (Figure). Conclusion: We found no association between ABO blood group and diagnosis or severity of COVID-19 in pregnant women. However, Rhesus positive women may be at a higher risk of COVID-19.Item A Comprehensive and Bias-Free Machine Learning Approach for Risk Prediction of Preeclampsia with Severe Features in a Nulliparous Study Cohort(Research Square, 2023-04-10) Lin, Yun; Mallia, Daniel; Clark-Sevilla, Andrea; Catto, Adam; Leshchenko, Alisa; Yan, Qi; Haas, David; Wapner, Ronald; Pe'er, Itsik; Raja, Anita; Salleb-Aouissi, Ansaf; Obstetrics and Gynecology, School of MedicineObjective: Preeclampsia is one of the leading causes of maternal morbidity, with consequences during and after pregnancy. Because of its diverse clinical presentation, preeclampsia is an adverse pregnancy outcome that is uniquely challenging to predict and manage. In this paper, we developed machine learning models that predict the onset of preeclampsia with severe features or eclampsia at discrete time points in a nulliparous pregnant study cohort. Materials and methods: The prospective study cohort to which we applied machine learning is the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) study, which contains information from eight clinical sites across the US. Maternal serum samples were collected for 1,857 individuals between the first and second trimesters. These patients with serum samples collected are selected as the final cohort. Results: Our prediction models achieved an AUROC of 0.72 (95% CI, 0.69-0.76), 0.75 (95% CI, 0.71-0.79), and 0.77 (95% CI, 0.74-0.80), respectively, for the three visits. Our initial models were biased toward non-Hispanic black participants with a high predictive equality ratio of 1.31. We corrected this bias and reduced this ratio to 1.14. The top features stress the importance of using several tests, particularly for biomarkers and ultrasound measurements. Placental analytes were strong predictors for screening for the early onset of preeclampsia with severe features in the first two trimesters. Conclusion: Experiments suggest that it is possible to create racial bias-free early screening models to predict the patients at risk of developing preeclampsia with severe features or eclampsia nulliparous pregnant study cohort.Item A comprehensive and bias-free machine learning approach for risk prediction of preeclampsia with severe features in a nulliparous study cohort(Springer Nature, 2024-12-24) Lin, Yun C.; Mallia, Daniel; Clark‑Sevilla, Andrea O.; Catto, Adam; Leshchenko, Alisa; Yan, Qi; Haas, David M.; Wapner, Ronald; Pe’er, Itsik; Raja, Anita; Salleb‑Aouissi, Ansaf; Obstetrics and Gynecology, School of MedicinePreeclampsia is one of the leading causes of maternal morbidity, with consequences during and after pregnancy. Because of its diverse clinical presentation, preeclampsia is an adverse pregnancy outcome that is uniquely challenging to predict and manage. In this paper, we developed racial bias-free machine learning models that predict the onset of preeclampsia with severe features or eclampsia at discrete time points in a nulliparous pregnant study cohort. To focus on those most at risk, we selected probands with severe PE (sPE). Those with mild preeclampsia, superimposed preeclampsia, and new onset hypertension were excluded.The prospective study cohort to which we applied machine learning is the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) study, which contains information from eight clinical sites across the US. Maternal serum samples were collected for 1,857 individuals between the first and second trimesters. These patients with serum samples collected are selected as the final cohort.Our prediction models achieved an AUROC of 0.72 (95% CI, 0.69-0.76), 0.75 (95% CI, 0.71-0.79), and 0.77 (95% CI, 0.74-0.80), respectively, for the three visits. Our initial models were biased toward non-Hispanic black participants with a high predictive equality ratio of 1.31. We corrected this bias and reduced this ratio to 1.14. This lowers the rate of false positives in our predictive model for the non-Hispanic black participants. The exact cause of the bias is still under investigation, but previous studies have recognized PLGF as a potential bias-inducing factor. However, since our model includes various factors that exhibit a positive correlation with PLGF, such as blood pressure measurements and BMI, we have employed an algorithmic approach to disentangle this bias from the model.The top features of our built model stress the importance of using several tests, particularly for biomarkers (BMI and blood pressure measurements) and ultrasound measurements. Placental analytes (PLGF and Endoglin) were strong predictors for screening for the early onset of preeclampsia with severe features in the first two trimesters.Item A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response(Springer Nature, 2021) Luo, Yang; Kanai, Masahiro; Choi, Wanson; Li, Xinyi; Sakaue, Saori; Yamamoto, Kenichi; Ogawa, Kotaro; Gutierrez-Arcelus, Maria; Gregersen, Peter K.; Stuart, Philip E.; Elder, James T.; Forer, Lukas; Schönherr, Sebastian; Fuchsberger, Christian; Smith, Albert V.; Fellay, Jacques; Carrington, Mary; Haas, David W.; Guo, Xiuqing; Palmer, Nicholette D.; Chen, Yii-Der Ida; Rotter, Jerome I.; Taylor, Kent D.; Rich, Stephen S.; Correa, Adolfo; Wilson, James G.; Kathiresan, Sekar; Cho, Michael H.; Metspalu, Andres; Esko, Tonu; Okada, Yukinori; Han, Buhm; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; McLaren, Paul J.; Raychaudhuri, Soumya; Obstetrics and Gynecology, School of MedicineFine-mapping to plausible causal variation may be more effective in multi-ancestry cohorts, particularly in the MHC, which has population-specific structure. To enable such studies, we constructed a large (n = 21,546) HLA reference panel spanning five global populations based on whole-genome sequences. Despite population-specific long-range haplotypes, we demonstrated accurate imputation at G-group resolution (94.2%, 93.7%, 97.8% and 93.7% in admixed African (AA), East Asian (EAS), European (EUR) and Latino (LAT) populations). Applying HLA imputation to genome-wide association study data for HIV-1 viral load in three populations (EUR, AA and LAT), we obviated effects of previously reported associations from population-specific HIV studies and discovered a novel association at position 156 in HLA-B. We pinpointed the MHC association to three amino acid positions (97, 67 and 156) marking three consecutive pockets (C, B and D) within the HLA-B peptide-binding groove, explaining 12.9% of trait variance.Item A Novel Use of Laryngoscope for Difficult Papanicolaou Smear Collection(Hindawi, 2021-09-23) Boudova, Sarah; Thomas, Caitlin; Wolfe, John; Schilder, Jeanne M.; Obstetrics and Gynecology, School of MedicineThe prevalence of cervical cancer has dropped significantly since introduction of the Papanicolaou (Pap) screen. The greatest risk factor for cervical cancer is inadequate screening. Altered pelvic anatomy can limit the ability to collect a Pap smear. In the presented case, a woman with a history of fibroids and bleeding presented for an exam under anesthesia. Traditional approaches for collecting a Pap smear failed. A GlideScope video laryngoscope was used to visualize the cervix, and a Pap smear was collected. The specimen was satisfactory, negative for intraepithelial lesion or malignancy, and HPV negative. A laryngoscope can be repurposed to visualize collection of a challenging Pap smear. Novel approaches for Pap smear collection and cervical cancer screening are needed and have the potential to save lives.Item A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium(Elsevier, 2022) Jackson, C. G.; Moore, K. N.; Cantrell, L.; Erickson, B. K.; Duska, L. R.; Richardson, D. L.; Landrum, L. M.; Holman, L. L.; Walker, J. L.; Mannel, R. S.; Moxley, K. M.; Queimado, L.; Cohoon, A.; Ding, K.; Dockery, L. E.; Obstetrics and Gynecology, School of MedicineObjective: The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer. Patients & methods: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival. Results: Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib. Conclusions: The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen.Item A role for zinc transporter gene SLC39A12 in the nervous system and beyond(Elsevier, 2021) Davis, Danielle N.; Strong, Morgan D.; Chambers, Emily; Hart, Matthew D.; Bettaieb, Ahmed; Clarke, Stephen L.; Smith, Brenda J.; Stoecker, Barbara J.; Lucas, Edralin A.; Lin, Dingbo; Chowanadisai, Winyoo; Obstetrics and Gynecology, School of MedicineThe SLC39A12 gene encodes the zinc transporter protein ZIP12, which is expressed across many tissues and is highly abundant in the vertebrate nervous system. As a zinc transporter, ZIP12 functions to transport zinc across cellular membranes, including cellular zinc influx across the plasma membrane. Genome-wide association and exome sequencing studies have shown that brain susceptibility-weighted magnetic resonance imaging (MRI) intensity is associated with ZIP12 polymorphisms and rare mutations. ZIP12 is required for neural tube closure and embryonic development in Xenopus tropicalis. Frog embryos depleted of ZIP12 by antisense morpholinos develop an anterior neural tube defect and lack viability. ZIP12 is also necessary for neurite outgrowth and mitochondrial function in mouse neural cells. ZIP12 mRNA is increased in brain regions of schizophrenic patients. Outside of the nervous system, hypoxia induces ZIP12 expression in multiple mammalian species, including humans, which leads to endothelial and smooth muscle thickening in the lung and contributes towards pulmonary hypertension. Other studies have associated ZIP12 with other diseases such as cancer. Given that ZIP12 is highly expressed in the brain and that susceptibility-weighted MRI is associated with brain metal content, ZIP12 may affect neurological diseases and psychiatric illnesses such as Parkinson's disease, Alzheimer's disease, and schizophrenia. Furthermore, the induction of ZIP12 and resultant zinc uptake under pathophysiological conditions may be a critical component of disease pathology, such as in pulmonary hypertension. Drug compounds that bind metals like zinc may be able to treat diseases associated with impaired zinc homeostasis and altered ZIP12 function.Item A Semi-Mechanistic Metabolism Model of CYP3A Substrates in Pregnancy: Predicting Changes in Midazolam and Nifedipine Pharmacokinetics(Wiley, 2012-09-26) Quinney, S. K.; Mohamed, A. N.; Hebert, M. F.; Haas, D. M.; Clark, S.; Umans, J. G.; Caritis, S. N.; Li, L.; Obstetric-fetal Pharmacology Research Unit Network; Obstetrics and Gynecology, School of MedicinePhysiological changes in pregnancy, including changes in body composition and metabolic enzyme activity, can alter drug pharmacokinetics. A semi-mechanistic metabolism model was developed to describe the pharmacokinetics of two cytochrome P450 3A (CYP3A) substrates, midazolam and nifedipine, in obstetrics patients. The model parameters were optimized to fit the data of oral midazolam pharmacokinetics in pregnant women, by increasing CYP3A-induced hepatic metabolism 1.6-fold in the model with no change in gut wall metabolism. Fetal metabolism had a negligible effect on maternal plasma drug concentrations. Validation of the model was performed by applying changes in volume of distribution and metabolism, consistent with those observed for midazolam, to the pharmacokinetics parameters of immediate-release nifedipine in healthy volunteers. The predicted steady-state areas under the concentration-time curve (AUCs) for nifedipine were within 15% of the data observed in pregnant women undergoing treatment for preterm labor. This model predicts the pharmacokinetics of two CYP3A substrates in pregnancy, and may be applicable to other CYP3A substrates as well.