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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 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 statement on abortion by 900 professors of Obstetrics and Gynecology after the reversal of Roe versus Wade(Elsevier, 2024-01-01) Espey, Eve; Teal, Stephanie; Peipert, Jeffrey F.; Obstetrics and Gynecology, School of MedicineIn the American Journal of Obstetrics and Gynecology in 1972 and 2013, 100 leaders in obstetrics and gynecology wrote calls to action—in 1972 in anticipation of the Roe v Wade decision and in 2013 in concern over the increasing restrictions to abortion care. In this article, 900 professors support a call to action for reinstating federal protections for abortion. Over a year ago, the Supreme Court handed down the Dobbs decision, overturning nearly 50 years of precedent in retracting the constitutionally protected right to abortion. The medical community is already seeing the harms of this decision on the lives and health of our patients and on the ability to train upcoming physicians in this medically necessary evidence-based care. Further harms are anticipated, including negative effects on maternal mortality. The 900 professors of obstetrics and gynecology whose signatures appear at the conclusion of this article stand together in support of reproductive freedom, including the right to affordable, accessible, safe, and legal abortion care.Item Abnormalities in Osteoclastogenesis and Decreased Tumorigenesis in Mice Deficient for Ovarian Cancer G Protein-Coupled Receptor 1(PLOS, 2009-05-29) Li, Hui; Wang, Dongmei; Singh, Lisam Shanjukumar; Berk, Michael; Tan, Haiyan; Zhao, Zhenwen; Steinmetz, Rosemary; Kirmani, Kashif; Wei, Gang; Xu, Yan; Obstetrics and Gynecology, School of MedicineOvarian cancer G protein-coupled receptor 1 (OGR1) has been shown to be a proton sensing receptor in vitro. We have shown that OGR1 functions as a tumor metastasis suppressor gene when it is over-expressed in human prostate cancer cells in vivo. To examine the physiological functions of OGR1, we generated conditional OGR1 deficient mice by homologous recombination. OGR1 deficient mice were viable and upon gross-inspection appeared normal. Consistent with in vitro studies showing that OGR1 is involved in osteoclastogenesis, reduced osteoclasts were detected in OGR1 deficient mice. A pH-dependent osteoclasts survival effect was also observed. However, overall abnormality in the bones of these animals was not observed. In addition, melanoma cell tumorigenesis was significantly inhibited in OGR1 deficient mice. OGR1 deficient mice in the mixed background produced significantly less peritoneal macrophages when stimulated with thioglycolate. These macrophages also showed altered extracellular signal-regulated kinases (ERK) activation and nitric oxide (NO) production in response to lipopolysaccharide. OGR1-dependent pH responses assessed by cAMP production and cell survival in macrophages or brown fat cells were not observed, presumably due to the presence of other proton sensing receptors in these cells. Our results indicate that OGR1's role in osteoclastogenesis is not strong enough to affect overall bone development and its role in tumorigenesis warrants further investigation. The mice generated can be potentially used for several disease models, including cancers or osteoclast-related diseases.Item Acceptability and feasibility of community-based provision of urine pregnancy tests to support linkages to reproductive health services in Western Kenya: a qualitative analysis(BMC, 2022-09-01) Kibel, Mia; Thorne, Julie; Kerich, Caroline; Naanyu, Violet; Yego, Faith; Christoffersen‑Deb, Astrid; Bernard, Caitlin; Obstetrics and Gynecology, School of MedicineBackground: The majority of women living in rural Kenya access antenatal care (ANC) late in pregnancy, and approximately 20% have an unmet need for family planning (FP). This study aimed to determine whether training community health volunteers (CHVs) to deliver urine pregnancy testing (UPT), post-test counselling, and referral to care was an acceptable and feasible intervention to support timely initiation of ANC and uptake of FP. Methods: We applied community-based participatory methods to design and implement the pilot intervention between July 2018 and May 2019. We conducted qualitative content analysis of 12 pre-intervention focus group discussions (FGDs) with women, men, and CHVs, and of 4 post-intervention FGDs with CHVs, each with 7-9 participants per FGD group. Using a pragmatic approach, we conducted inductive line-by-line coding to generate themes and subthemes describing factors that positively or negatively contributed to the intervention's acceptability and feasibility, in terms of participants' views and the intervention aims. Results: We found that CHV-delivered point of care UPT, post-test counselling, and referral to care was an acceptable and feasible intervention to increase uptake of ANC, FP, and other reproductive healthcare services. Factors that contributed to acceptability were: (1) CHV-delivery made UPT more accessible; (2) UPT and counselling supported women and men to build knowledge and make informed choices, although not necessarily for women with unwanted pregnancies interested in abortion; (3) CHVs were generally trusted to provide counselling, and alternative counselling providers were available according to participant preference. A factor that enhanced the feasibility of CHV delivering UPT and counselling was CHV's access to appropriate supplies (e.g. carrying bags). However, factors that detracted from the feasibility of women actually accessing referral services after UPT and counselling included (1) downstream barriers like cost of travel, and (2) some male community members' negative attitudes toward FP. Finally, improved financial, educational, and professional supports for CHVs would be needed to make the intervention acceptable and feasible in the long-term. Conclusion: Training CHVs in rural western Kenya to deliver UPT, post-test counselling, and referral to care was acceptable and feasible to men, women, and CHVs in this context, and may promote early initiation of ANC and uptake of FP. Additional qualitative work is needed to explore implementation challenges, including issues related to unwanted pregnancies and abortion, the financial burden of volunteerism on CHVs, and educational and professional supports for CHVs.Item Active Learning on Center Stage: Theater as a Tool for Medical Education(Association of American Medical Colleges, 2019-01-30) Hobson, Wendy L.; Hoffmann-Longtin, Krista; Loue, Sana; Love, Linda M.; Liu, Howard Y.; Power, Christine M.; Pollart, Susan M.; Obstetrics and Gynecology, School of MedicineIntroduction: Knowledge and skill development related to communication must incorporate both affective and behavioral components, which are often difficult to deliver in a learning activity. Using theater techniques and principles can provide medical educators with tools to teach communication concepts. Methods: This 75-minute faculty development workshop presents a variety of techniques from theater and adapts them for use in medical education. Using examples related to diversity and inclusion, this session addresses general educational and theater principles, role-play, sociodrama, applied improvisation, and practical aspects of involving theater partners. The session materials include a PowerPoint presentation with facilitator notes, interactive activities to demonstrate each modality, and an evaluation. The sessions can be extended to longer formats as needed. Results: Forty-five participants at Learn Serve Lead 2016: The AAMC Annual Meeting attended the 75-minute session. We emailed 32 participants 5 months after the conference, and eight responded. Participants reported that their confidence level in using theater techniques as a tool for medical education increased from low-to-medium confidence presession to high confidence postsession. All survey respondents who were actively teaching said they had made changes to their teaching based on the workshop. All commented that they appreciated the active learning in the session. Many indicated they would appreciate video or other follow-up resources. Discussion: Principles and techniques from theater are effective tools to convey difficult-to-teach concepts related to communication. This workshop presents tools to implement activities in teaching these difficult concepts.Item Adult Comorbidity Evaluation 27 score as a predictor of survival in endometrial cancer patients(Elsevier, 2016-12) BINDER, Pratibha S; PEIPERT, Jeffrey F; KALLOGJERI, D; BROOKS, Rebecca A; MASSAD, Leslie S; MUTCH, David G; POWELL, Matthew A; THAKER, Premal H; McCOURT, Carolyn K; Obstetrics and Gynecology, School of MedicineBACKGROUND The incidence of endometrial cancer increases with age and is associated with medical comorbidities such as obesity and diabetes. While a few cohort studies of less than 500 patients showed an association between comorbidity and survival in endometrial cancer patients, the degree of association needs to be better described. The Adult Comorbidity Evaluation 27 (ACE-27) is a validated comorbidity instrument that provides a score (0–3) based on the number and severity of medical comorbidities. OBJECTIVE This study was performed to explore the association between medical comorbidities and survival of endometrial cancer patients. STUDY DESIGN Patients diagnosed with endometrial cancer from 2000–2012 were identified from the prospectively maintained Siteman Cancer Center tumor registry. Patients undergoing primary surgical treatment for endometrioid, serous and clear cell endometrial carcinoma were included. Patients primarily treated with radiation, chemotherapy or hormone therapy were excluded. Patients with uterine sarcomas or neuroendocrine tumors were excluded. Patients with missing ACE-27 scores were also excluded from analysis. Information including patient demographics, ACE-27 score, tumor characteristics, adjuvant treatment and survival data were extracted from the database. The association of ACE-27 and overall as well as recurrence-free survival was explored in a multivariable Cox regression analysis after controlling for variables found to be significantly associated with survival in univariable analysis. RESULTS A total of 2073 patients with a median age of 61 years (range 20–94) at diagnosis were identified. ACE-27 score was 0, 1, 2 and 3 in 22%, 38%, 28% and 12% of patients, respectively. Stage distribution was I (73%), II (5%), III (15%) and IV (7%) and grade distribution was 1 (52%), 2 (23%) and 3 (25%). Most patients had endometrioid histology (87%) followed by serous (11%) and clear cell (3%). The median OS for the entire cohort was 54 months [95% confidence interval (CI) 3, 154 months] and median PFS was 50 months [95% CI 2, 154 months]., On univariable analysis, age, race, marital status, stage, grade, histology and treatment type were significantly associated with overall survival and recurrence-free survival. After adjusting for these covariates, patients with ACE-27 score of 2 had a 52% higher risk of death [95% CI 1.16, 2.00] and patients with ACE-27 score of 3 had a 2.35-fold increased risk of death [95% CI 1.73, 3.21] compared to patients with an ACE-27 score of 0. Similarly, patients with ACE-27 score of 2 had a 38% higher risk of recurrence [95% CI 1.07, 1.78] and patients with ACE-27 score of 3 had a 2.05-fold increased risk of recurrence [95% CI 1.53, 2.75] compared to patients with an ACE-27 score of 0. We found no interaction between ACE-27 score and age, stage or treatment type. CONCLUSIONS Our findings demonstrate the importance of comorbidities in estimating the prognosis of endometrial cancer patients, even after adjusting for age and known tumor-specific prognostic factors like stage, grade, histology and adjuvant treatment.Item Allies Welcomed to Advance Racial Equity (AWARE) Faculty Seminar Series: Program Design and Implementation(Sage, 2021-07-24) Tucker Edmonds, Brownsyne; Neal, Chemen; Shanks, Anthony L.; Scott, Nicole; Robertson, Sharon; Rouse, Caroline E.; Bernard, Caitlin; Sotto-Santiago, Sylk; Obstetrics and Gynecology, School of MedicineIntroduction: In the wake of George Floyd's murder, White faculty in our department began to express the desire to gain a greater understanding of structural racism and racial inequity. To facilitate this learning, support allyship, and mitigate the emotional labor and taxation that frequently falls on faculty of color to respond to these appeals, we developed AWARE (Allies Welcomed to Advance Racial Equity), a faculty seminar series primarily designed for and led by a majority White faculty to tackle the topics of structural racism, Whiteness, and Anti-racist action. Methods: We developed a 6-session seminar series, identifying 5 White faculty as lecturers and a cadre of Black and White volunteer facilitators, to lead 60-minute sessions comprised of lecture, facilitated small group reflection, and large group sharing, that reviewed key topics/texts on structural racism, Whiteness, and Anti-racism. Results: Attendance ranged from 26 to 37 participants at each session. About 80% of faculty participated in at least 1 session of the program. The majority of participants (85%) felt "more empowered to influence their current environment to be more inclusive of others" and were "better equipped to advocate for themselves or others." Most (81%) felt "more connected to their colleagues following completion of the program." Ultimately, faculty thought highly of the program upon completion with 26/27 (96%) stating they would recommend the program to a colleague. Discussion: We offer a reproducible model to improve departmental climate by engaging in the shared labor of educating our colleagues and communities about structural racism, Whiteness, and Anti-racism to create a point of entry into reflection, dialogue, and deliberate actions for change.Item Allostatic Load and Adverse Pregnancy Outcomes(Wolters Kluwer, 2022-01-12) Lueth, Amir J.; Allshouse, Amanda A.; Blue, Nathan M.; Grobman, William A.; Levine, Lisa D.; Simhan, Hyagriv N.; Kim, Jin Kyung; Johnson, Jasmine; Wilson, Fernando A.; Murtaugh, Maureen; Silver, Robert M.; National Institutes of Health (NIH); National Institute of Child Health and Human Development (NICHD); Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b); National Heart, Lung, and Blood Institute (NHLBI) nuMoM2b Heart Health Study; Obstetrics and Gynecology, School of MedicineObjective: To assess the association between allostatic load, as an estimate of chronic stress, and adverse pregnancy outcomes. Methods: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study Monitoring-to-be (nuMoM2b) study, a prospective observational cohort study. Our primary exposure was dichotomous high allostatic load in the first trimester, defined as four or more out of 12 biomarkers in the “worst” quartile. The primary outcome was a composite adverse pregnancy outcome: hypertensive disorders of pregnancy (HDP), preterm birth, small for gestational age (SGA) neonate, and stillbirth. Secondary outcomes included components of the composite. Multivariable logistic regression was used to test the association between high allostatic load and adverse pregnancy outcomes, adjusted for potential confounders. Mediation and moderation analyses were conducted to assess the role of allostatic load along the causal pathway between racial disparities and adverse pregnancy outcomes. Results: Among 4,266 individuals, 34.7% had a high allostatic load. Composite adverse pregnancy outcome occurred in 1,171 (27.5%): 14.0% HDP, 8.6% preterm birth (48.0% spontaneous and 52.2% indicated), 11.0% SGA, and 0.3% stillbirth. After adjustment for maternal age, gravidity, smoking, bleeding in the first trimester, and health insurance, high allostatic load was significantly associated with composite adverse pregnancy outcome (aOR 1.5, 95% CI: 1.3, 1.7) and HDP (2.5, 2.0–2.9), but not preterm birth and SGA. High allostatic load partially mediated the association between self-reported race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race, but not for composite adverse pregnancy outcome, preterm birth, and SGA. Conclusion: High allostatic load in the first trimester is associated with adverse pregnancy outcomes, particularly HDP. Allostatic load was a partial mediator between race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race.Item Antenatal Corticosteroids in Preterm Small-for-Gestational Age Infants: A Systematic Review and Meta-Analysis(Elsevier, 2020) Blankenship, Stephanie A.; Brown, Kristine E.; Simon, Laura E.; Stout, Molly J.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of MedicineObjective This study aimed to estimate the effect of antenatal corticosteroid administration on neonatal mortality and morbidity in preterm small-for-gestational age infants through a systematic review and meta-analysis. Data Sources A predefined, systematic search was conducted through Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trial Registry Platform, and ClinicalTrials.gov yielding 5324 articles from 1970 to 2019. Study Eligibility Criteria Eligible studies compared neonatal morbidity and mortality among small-for-gestational age infants delivered preterm who received antenatal corticosteroids with those who did not. Methods The primary outcome was neonatal mortality. Secondary outcomes were respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage and periventricular leukomalacia, bronchopulmonary dysplasia or chronic lung disease of prematurity, or neonatal sepsis. We assessed heterogeneity by means of Higgins I2 statistic and Cochran’s Q test and calculated pooled odds ratios with 95% confidence intervals using random effects models. Results A total of 16 observational cohort and case-control studies published from 1995 to 2018 met the selection criteria for the systematic review and included 8989 preterm small-for-gestational age infants. Antenatal corticosteroid administration was explicitly reported among 8376 small-for-gestational age infants; 4631 (55.3%) received antenatal corticosteroids and 3741 (44.7%) did not. Of note, 13 studies including 6387 preterm small-for-gestational age infants were then included in the meta-analysis. Neonatal mortality was significantly lower among infants who received antenatal corticosteroids than those who did not (12 studies: 12.8% vs 15.1%; pooled odds ratio, 0.63; 95% confidence interval, 0.46–0.86), with significant heterogeneity between studies (I2=55.1%; P=.011). There was no significant difference in respiratory distress syndrome (12 studies: odds ratio, 0.89; 95% confidence interval, 0.69–1.15), necrotizing enterocolitis (7 studies: odds ratio, 0.93; 95% confidence interval, 0.70–1.22), intraventricular hemorrhage and periventricular leukomalacia (10 studies: odds ratio, 0.82; 95% confidence interval, 0.56–1.20), bronchopulmonary dysplasia or chronic lung disease of prematurity (8 studies: odds ratio, 1.11; 95% confidence interval, 0.88–1.41), or neonatal sepsis (6 studies: odds ratio, 1.13; 95% confidence interval, 0.86–1.49). Conclusion These data indicate that antenatal corticosteroid administration reduces neonatal mortality in small-for-gestational age infants delivered preterm, with no apparent effect on neonatal morbidity. This supports the use of antenatal corticosteroids to reduce neonatal mortality in pregnancies with small-for-gestational age infants at risk of preterm birth.