- To support the advancement and leadership of women in academic medicine
- To promote education and research in women’s health
FOCUS SUPPORT 2015-2016
- Perelman School of Medicine at the University of Pennsylvania
- Center for Clinical Epidemiology and Biostatistics
- Trustees’ Council of Penn Women
- Anastasia Lyalenko Memorial Fund
- Bertha Dagan Berman
- Grisso Endowment for the Michelle Battistini Fund
- Patricia Kind
- Edna G. Kynett Memorial Foundation
Medical Student Fellowship
Award Recipients by Funder
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(faculty mentor: Victoria P. Werth MD [Dermatology])
Fellowship term, 6 months between August 2015 and March 2016
Project: Localized Cutaneous Lupus Assessment Tool (L-CLAT)
Cutaneous lupus erythematosus is an autoimmune disease that predominately affects women. This disease is difficult to manage, uncomfortable, cosmetically disfiguring and can include problematic underlying systemic disease. It’s been shown that patients with this disease suffer from a decreased quality of life. The Cutaneous Lupus Activity and Severity Index (CLASI) is one such validated tool used to assess disease in patients with skin lupus. This tool takes into account lesions located anywhere on the body, and has been used in various research studies to assess drug efficacy and to correlate disease severity with the factors previously mentioned. However, there is no validated tool to assess disease severity and change specifically for the face. The Localized Cutaneous Lupus Assessment Tool (L-CLAT) is a recently developed measure to better assess clinically significant change in disease severity in patients with disease localized to the head and neck. Validation of this tool is warranted due to the increased burden of head and neck disease on patients. The face is essential to identity, expression, and self-image, and disease of the head and neck may greatly affect these domains. Subjects will be asked to participate in two study visits. At these visits, the measure will be filled out by two raters separately. The target number of subjects is up to 50. It is hoped that by developing and validating the L-CLAT, physicians will be better able to manage patients in clinic and researchers will be better able to determine the effects and associations of autoimmune skin disease of the head and neck.
(faculty mentor: Suneeta Senapati MD [Obstetrics and Gynecology])
Fellowship term, 6 months between August 2015 and March 2016
Project: Fertility Understanding and Attitudes towards Assisted Reproductive Technologies in Women Presenting for Oocyte Cryopreservation Consult
Recently, elective oocyte cryopreservation, or egg freezing, has become increasingly widespread, but there is limited data regarding women's understanding of the process and the factors that contribute to the decision to pursue this new technology. We intend to apply a knowledge and utilization survey regarding reproduction and assisted reproductive technologies, previously developed at the University of Pennsylvania, to women presenting for fertility preservation consultation to assess fertility understanding and factors that influence them to freeze their eggs. Data will be analyzed by indication for cryopreservation and results will be compared to a previously conducted national cross-sectional survey of reproductive age women. This study will be instrumental in filling the knowledge gap regarding what motivates women to freeze their eggs and provide important insight for counseling patients about oocyte cryopreservation in the future.
(faculty mentor(s): Mark A. Morgan MD and Ashley Haggerty MD [Obstetrics and Gynecology])
Fellowship term, 6 months: November 2015 - April 2016
Project: Physician-Patient Communication and Expectations Regarding Ovarian Cancer Prognosis
In order to provide appropriate medical care, it is of the utmost importance that physicians and patients can clearly communicate about diagnoses, prognoses, and treatments. This information is especially relevant in patients with poor prognosis diagnoses, when assessing treatment options and planning for future care has huge consequences on patient quality of life, morbidity, and mortality. Because ovarian cancer is a particularly lethal malignancy with a generally poor prognosis, it represents an opportune field for investigation into this question. My project aims to directly compare and quantify the differences in perspective that patients and physicians hold regarding epithelial ovarian cancer prognosis in terms of survival at various time points and complications arising from treatment via an easily administered survey. The survey will also directly ask patients whether their treating oncologist has counseled them on prognosis, advance directives, living wills, palliative care, and hospice services. This will provide information on whether patients and physicians’ views on prognosis and care align and, if they differ, will identify a correctable deficiency in addressing the needs of this population. Finally, a structured telephone interview will explore how patients prefer to receive prognostic information. Overall, the project aims to pinpoint opportunities for better patient-physician communication regarding ovarian cancer prognosis and end-of-life care in order to provide patients with better information to understand their disease and allow for more informed and tailored decision making.
Anh Truong Butz
(faculty mentor: Monica Mainigi, MD [Obstetrics and Gynecology])
Fellowship term, 6 months: December 2014- May 2015
Project: Effect of Plancental Methylation Differences on Early Childhood Growth
DNA methylation is an epigenetic means of regulating gene expression. In previous work,we identified in in vitro fertilization (IVF)-conceived deliveries a relationship between birth weight and placental methylation. The significance and long-term effect of this methylation is unknown; it may reflect response to the effects of IVF on intrauterine environment,and decreased birth weight in IVF-conceived pregnancies has been documented. To our knowledge, no studies have identified long-term growth and development outcomes with respect to placental methylation. In this pilot study, we will obtain follow-up growth and development data from participants in our epigenetics research program. We will compare growth outcome data between assisted reproductive technology (ART) and control cohorts to assess the impact of ART on childhood growth. We will then analyze methylation data within the ART cohort (in whom methylation array is completed)to determine whether the previously identified placental methylation patterns are associated with metabolic abnormalities or altered rates of growth in early childhood. Finally, we will look at specific growth-related genes to determine whether their methylation status can predict growth and development outcome within the ART cohort.
Megan Elizabeth Fracol
(faculty mentor: Brian Czerniecki, MD, PhD [Surgery])
Fellowship term, 6 months: October 2014-March 2015
Project: Role of HER-3 in Breast Cancer Invasion and Response to an Anti-HER-2 Dendritic Cell Vaccine
Our group has developed a novel human epidermal growth factor receptor-2 (HER-2) pulsed dendritic cell vaccine that has been shown to elicit immune and clinical responses in patients with ductal carcinoma in situ (DCIS). It has been established these patients develop CD4 and CD8 T cell responses against HER-2 peptide post-vaccination and suggested by recent assays that patients may also develop an overlapping HER-3 immune response post-vaccination. However, it is still unknown to what extent these anti-HER-2 responses correlate with clinical outcome and to what extent patients also develop an anti-HER-3 immune response post-vaccination. The goal of this study is two-fold: (1) to analyze anti-HER-2 immune responses and correlate with clinical outcome and (2) to compare anti-HER-3 immune responses between healthy, DCIS and invasive breast cancer patients as well as pre- and post-vaccination with our anti-HER-2 dendritic cell vaccine.
Eneniziaogochukwu (“Zia”) Okocha
(faculty mentor: C. Neill Epperson, MD [Psychiatry])
Fellowship term, 6 months: September-December 2014 and February-March 2015
Project: Psychotherapy Sessions during Pregnancy for Low-income, Minority Women: A Study on Pregnancy and Birth Outcomes, Healthcare Utilization, and Cost
Untreated maternal mental illness during pregnancy has been associated with increased risks to mother and neonate including prematurity and low birth weight among other complications. Psychotropic medications including SSRIs have been linked to adverse neonatal outcomes. Few studies have examined the role of psychotherapy in reducing maternal psychiatric and physiologic stress over the course of pregnancy and in improving pregnancy outcomes for both mother and child. This study will explore pregnancy and birth complications and outcomes among women who were referred to psychotherapy services following screening and evaluation at their prenatal clinic appointment. We expect to see decreased pregnancy complications and improved birth outcomes in those who attend more psychotherapy appointments, as compared to women who attend only one appointment and those who do not attend any appointments but for whom psychotherapy is recommended. Additionally, the cost of health care remains a difficult topic to understand given different rates charged by different providers to different insurers. With the aid of data obtained from the University of Pennsylvania system, Medicaid insurers in the state of Pennsylvania, and possibly the U.S. Department Veterans Affairs, this study also aims to obtain a better understanding of how costs are determined and tabulated. We also wish to uncover any cost differential present in potential discrepancies in the utilization of health care between women with psychiatric illness that undergo the intervention, those who do not but for whom it is recommended, and demographic matched controls.
(faculty mentors: Aba Barden-Maja MD, Joseph Garland MD and Charmaine Smith Wright MD MSHP [Medicine: Division of General Internal Medicine])
Fellowship term, 6 months: December 2013- May 2014
Project: Family Planning Decision-making in Refugee Women
The purpose of this study is to determine how refugee women of different cultures conceptualize family planning and contraception as well as how they make decisions regarding these topics so that we can provide culturally-competent family planning counseling and services. In order to do this, we will conduct one-on-one interviews of refugee women who are of reproductive age and have ever been sexually active. Interview questions are aimed at collecting information regarding: (1) each participant’s beliefs regarding pregnancy planning and its importance, (2) the degree of involvement subjects and their partners have in making decisions regarding pregnancy and contraception, (3) the factors participants consider when making such decisions, and (4) participant’s general knowledge of family planning services. Using this data, we hope to draw conclusions about how physicians can tailor family planning counseling and services to fit specific populations in order to increase knowledge and utilization of these services and decrease the unmet need for contraception.
Jessica Marie Traylor
(faculty mentor: Celeste Durnwald MD [Obstetrics and Gynecology])
Fellowship term, 6 months: October 2013 - April 2014
Project: Women’s Perception of Future Risk and Psychosocial Outcomes following Pregnancies Complicated by Preeclampsia
Preeclampsia affects 5-8% of all pregnancies and women who have had the condition have an increased risk of developing preeclampsia with future pregnancies. In addition to its impact on obstetrical outcomes, preeclampsia influences future cardiovascular risk. Women who have had preeclampsia also have an increased risk of cardiovascular disease later in life including hypertension, ischemic heart disease and stroke. Cardiovascular disease remains the leading cause of death in women. Few studies have investigated women’s perception of future risk following pregnancies complicated by preeclampsia. Assessment of risk perception regarding future cardiovascular disease can aid healthcare providers as they encourage and support patients’ behavior modification. The primary aim of this research is to investigate how women within an urban population perceive their future obstetrical and cardiovascular risks given a history of preeclampsia. Secondary aims include using validated surveys to assess the prevalence of postpartum depressive and posttraumatic stress symptoms in this population. Women with a history of preeclampsia who deliver at HUP will be surveyed both on the postpartum service and in the High Risk Transition Clinic 1-2 weeks after discharge. Relevant clinical data such as weight and blood pressure will be collected at both interactions. We will use a prospective study design to assess the associations between risk perceptions and current lifestyle behaviors, plans to modify behaviors, social demographics and knowledge about cardiovascular disease risk factors. This information will further elucidate the postpartum needs of this population and inform the tools used to facilitate the provision of health information to patients.
(faculty mentor: Natasha Mirza MD [Otorhinolaryngology: Head and Neck Surgery])
Fellowship term, 6 months: August 2013 - February 2014
Project: The Role of Gender and Voice-Related Quality of Life in Aging Adults
Just as the human body changes with age, so does the human voice. The older person’s voice is associated with declines in multiple vocal parameters, but there are differences in the age-related voice changes in women and men. While older men’s voices are often associated with an increased breathiness and tension as well as a higher fundamental pitch, women are found to have increase roughness and hoarseness and a lower fundamental pitch. Voice abnormalities are known to impair quality of life, but age-related vocal problems often go unrecognized and untreated. While some work has been conducted on the impact of age-related voice changes in daily life on men, little is known about how these vocal changes impact the lives of aging women. Our study seeks to explore the extent to which age-related voice changes impacts the daily life of older adults and to compare and contrast these impacts in men and women. The results of this work can ultimately improve our clinical understanding of aging and how the process and its functional outcomes differ for men and women. In this way, we can better identify important opportunities for interventions and improve patient-centered care and counseling for our older population to help them in their ability to communicate effectively throughout their lives.
(faculty mentor: Ian Moore Bennett MD PhD [Family Medicine and Community Health])
Fellowship term, 6 months:October 2012 - March 2013
Project: Parental Health Literacy and Utilization of Health Services for Young Children among Mexican Immigrant Families in Philadelphia, PA
Health literacy is the degree to which a person can obtain, process and understand basic health information and services needed to make appropriate health decisions. The 2003 National Assessment of Adult literacy found 29% of parents in the US have below basic or basic health literacy and 68% are unable to correctly enter names and birth dates on an insurance form. However, much less is known about the relationship between parental health literacy and child health outcomes or service utilization. This project focuses on the relationship between parental health literacy and utilization of services to support early childhood development. Developmental delay is an important health outcome as early intervention is critical to ensure children are able to benefit from existing developmental supports in the community. Results from the Early Childhood Longitudinal study indicate that approximately 13% of children have developmental delays that would qualify them for early intervention services. However by 24 months only 10% of those children with delays were receiving early intervention services. Within the Philadelphia area, a recent evaluation of the implementation of developmental screening in 4 urban practices found that only 50% of children screened as at risk of developmental delay were referred to early intervention services. This project will investigate the relationship between parental health literacy and utilization of services supporting early childhood development in the Mexican immigrant community. Ultimately, we hope to provide information relevant to policies and recommendations supporting early childhood development in the Mexican immigrant community.
Andrew R. Fisher
(faculty mentor: Kurt Barnhart MD MSCE [Obstetrics and Gynecology, Penn Fertility Care])
Fellowship term, 6 months: September 2012 - March 2013
Project: The Significance of Collection Timing in Using Early Serum Biomarkers to Predict Ectopic Pregnancy and Miscarriage
As more women in America and across the globe are choosing to delay primagravidy or subsequent pregnancies in order to pursue personal academic or professional goals, the awareness of infertility is becoming more prominent. While the diagnosis of infertility broadly includes both male and female conditions, woman suffering through miscarriage or ectopic pregnancies are particularly prone to morbid, and all too frequently fatal, complications. My research will investigate patterns of serum biomarker levels such as human chorionic gonadotropin (hCG) and placental mRNA in early pregnancy and develop the understanding and meaning behind these trends in order to improve their clinical utility. While many investigators have analyzed such trends in early pregnancy, these studies often used imprecise measures or protocols for obtaining the data, which led to less statistical power and more limited clinical translation and generalizability. In collaboration with Dr. Kurt Barnhart and his research team, I will review the current data on maternal serum biomarkers, determine the significance of the timing of the biomarker draws, and suggest methods for improving the precision and accuracy of biomarker testing and analysis. In doing so, I believe that maternal-fetal medicine and fertility specialists will be enabled to more accurately predict the likelihood of ectopic pregnancies and miscarriages, which will provide earlier and safer treatment options for these women. In addition, specialists may be able to avoid unnecessary and risky interventions with mothers carrying healthy pregnancies who clinically or radiographically might be at risk for possible ectopic or miscarriage diagnoses.
(faculty mentor: Carrie Kovarik MD [Dermatology])
Fellowship term, 6 months: October 2012 - April 2013
Project: Evaluation of the Impact of Teledermatology on Women Presenting with Dermatologic Conditions to Primary Care Centers in Philadelphia
Teledermatology is drawing attention across the world for its potential to offer specialty care to patients separated from dermatologists by space as well as time. These patients often live in underserved urban and rural areas. My FOCUS fellowship with Dr. Carrie Kovarik explores the application of teledermatology for underserved female patients in Philadelphia. The University of Pennsylvania, Department of Dermatology, has a volunteer teledermatology consult service with an established relationship with the Sayre Health Center and the Jonathan Lax Center. In light of the warm reception of teledermatology among primary care providers at these centers, the consult service is on the cusp of expanding into the nine city health centers operated by the Philadelphia Department of Public Health. The purpose of my fellowship is to determine the impact of this exciting new development on women. My goal is to evaluate change in patient management and access to dermatologic care. I will also collect data on clinical outcomes. Measuring diagnostic and treatment plan concordance between primary care providers and dermatologists is a key component of this research. From this data, I hope to generate a set of challenging dermatologic diagnoses and/or diagnostic categories that predominantly affect women. I would ultimately like to use this information to develop an educational initiative targeted to primary care providers caring for women in the underserved urban context. I believe that this research will provide valuable insight into teledermatology as a clinical and educational tool for improving the health status of women in Philadelphia and elsewhere.
Robert L. Dood, Jr.
(faculty mentor: Brian Strom MD MPH [Biostatistics & Epidemiology])
Fellowship term, 6 months: July 1, 2011 - January 1, 2012
Project: Comparative Risk of Endometrial Cancer from Ablation Versus Medical Management of Dysfunctional Uterine Bleeding: A Population-Based Cohort
Abnormal menstruation is one of the most common chief complaints to gynecologists and family practices. Dysfunctional uterine bleeding (DUB) is responsible for almost half of these menstrual problems. First-line treatments include medical management with hormones and other medications, and endometrial ablation procedures. Beneficial effects of first-line treatments have been shown to have few differences when compared long-term. However, a comparative effectiveness approach to adverse events, including endometrial cancer, has not been performed. This is vitally important to patient decision-making and is necessary to establish quality healthcare delivery, given that guidelines for DUB treatment are mixed or absent. Endometrial cancer is a pressing outcome for women with DUB because obesity and advancing age increases risk for both DUB and endometrial cancer. The overall objective is to optimize the care for DUB by performing a comparative effectiveness study among alternative treatments. The study will have a specific focus on endometrial cancer as the outcome. The Primary Aim assesses if endometrial ablation versus medical management carries an increased risk of endometrial cancer. The Secondary Aim investigates if cancer diagnosis is delayed in women who underwent ablation vs. medical management, which is vital to interpreting the result of the Primary Aim. A retrospective cohort study will be performed in The Health Improvement Network (THIN), a UK medical record database with over 600,000 women with a diagnosis of DUB, who received either endometrial ablation or medical management. Results from the study could profoundly influence both treatment paradigms for DUB and screening regimens for endometrial cancer.
(faculty mentor: Kurt T. Barnhart MD MSCE [Obstetrics and Gynecology])
Fellowship term, 6 months: November 2011-May 2012
Project: The Effect of Endometriosis on IVF Outcomes
Endometriosis is a common cause of infertility and in vitro fertilization (IVF) is often used to assist reproduction in this population. However, IVF outcomes in women with endometriosis appear to be inferior compared to women with other etiologies of infertility, but available data are conflicting and this remains an important area of investigation. An equally important question is the effect of IVF and endometriosis on childhood outcomes. Endometriosis is associated with chronic inflammation which is in turn associated with preterm delivery and low birth weight. Moreover, recent findings have suggested that the endometrium of women with endometriosis may be altered and the hyper-estrogenic environment during IVF may further alter this environment resulting in lower pregnancy rates. Furthermore, it has been hypothesized that the treatment protocol used to prepare the endometrium for implantation of frozen embryo transfer (ET) has a beneficial effect on IVF outcomes. These findings reinforce the belief that endometrial environment greatly impacts clinically significant pregnancy outcomes. The primary aim of this research project is to elucidate the unclear effect of endometriosis on IVF outcomes. Secondary aims include determining if women with endometriosis are at increased risk for adverse childhood outcomes and if this risk differs among women with endometriosis that conceive following frozen ET when compared to fresh ET. To accomplish our study aims, we will perform a retrospective cohort study using a large national database of IVF patients in the US. These findings would have an immediate impact, both scientifically and clinically, and would update current knowledge regarding contemporary IVF techniques.
(faculty mentor: Peter Cronholm, MD MSCE [Family Medicine and Community Health])
Fellowship term, 6 months: August 2011- February 2012
Project: Community-Based Intervention for Improving Health Literacy Among Young Adult Women within the East Parkside Community
Health literacy can be defined as the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions. Adults with limited literacy skills are less likely to manage their
chronic diseases and are more likely to be hospitalized than people with stronger literacy skills leading to poorer health outcomes and higher healthcare costs. Many studies have demonstrated this link between low health literacy and poor health outcomes as well as the
sense of shame patients may feel because of their skill level. As a result, many efforts have been undertaken to address low health literacy populations, primarily at the health system level, with goals such as increasing readability of patient education materials. However, very little research has been done to implement interventions at the community level to help increase individual health literacy capabilities as well as to empower individuals to take ownership of their health. The overall objective of this project is to develop and implement a culturally-appropriate, activity-oriented health literacy curriculum, targeted for young women, to determine
its effect on health literacy scores as well as gain an understanding of perceptions, new or old, about health issues pertaining to the Patient-Physician and/or Patient-Parent-Physician relationship. Together with efforts ensuring that health information and services can be understood and used by all individuals, a community-based approach can potentially aid in building the health literacy skills necessary among healthcare consumers for improved health outcomes and increased personal confidence within the healthcare system.
(Faculty mentor: Mary Leonard MD MSCE [Pediatrics: Division of Nephrology])
Fellowship term, 6 months: November 2010- April 2011
Project: Sex Differences in Cortical Bone and the Functional Muscle-Bone Unit: Impact of Age, Sex Hormones, and Physical Activity
Cortical volumetric bone mineral density (vBMD) and dimensions are important determinants of bone strength. Sex differences in these parameters have not been well-characterized across the adult life span. In addition, prior studies suggested that sex hormones modified the associations between muscle mass and bone mass such that women had greater bone mass relative to muscle mass (functional muscle bone unit). However, these studies failed to consider differences in body size and did not distinguish between bone density and bone geometry. This objective of this study is to use quantitative computed tomography (QCT) measures of cortical vBMD and bone dimensions in 500 healthy men and women, ages 21-78 years in order to characterize sex differences in these parameters relative to age, adjusted for bone length. The relations between these bone outcomes, pQCT measures of muscle cross-sectional area, and measures of muscle isometric strength will be compared in men and women. Additional analyses will examine the influence of physical activity, sex hormones, and vitamin D levels. This project will establish a foundation for further research into understanding the impact of various chronic diseases on bone strength and the functional muscle bone unit.
(Faculty mentor: Victoria P. Werth MD [Dermatology])
Fellowship term, 6 months: September 2010 - February 2011
Project: Characterization of Photosensitivity in Cutaneous Lupus Erythematosus
Lupus erythematosus (LE) is a chronic autoimmune disease that disproportionately affects women. Skin manifestations of LE are common and many patients have one or more types of cutaneous lupus erythematosus (CLE) with little to no systemic symptoms. Dermatologic diseases, such as CLE have profound impacts on quality of life and recent work from the dermatology autoimmune group at Penn suggests that women with lupus have a poorer quality of life compared to men. Ultraviolet radiation (UVR) is a likely contributor to the pathogenesis of lupus and patients often ascribe to photosensitivity. However, photosensitivity in lupus is ill-defined with “photosensitive” reactions ranging from induction of lupus-specific lesions (e.g. discoid lesion) to experiencing a transient tingling sensation in sun-exposed skin. Most studies on photosensitivity in lupus employ phototesting protocols to investigate the pathophysiology of UVR-induction of lupus-specific lesions. We have found, however, that a large percentage of our lupus patients experience early, transient skin-related symptoms related to sun exposure. Further, our recent work suggests that this early, transient photosensitivity is associated with increased cutaneous disease activity (worse lupus-specific skin disease) and a poor quality of life. The purpose of this study is to characterize self-reported photosensitivity, investigate the underlying pathophysiology of early, transient photosensitivity symptoms, and determine the impact of photosensitivity on quality of life.
(Faculty mentor: Julia Tchou MD PhD [Surgery: Division of Endocrine and Oncologic Surgery])
Fellowship term, 6 months: August - September 2010, January 2011, March - May 2011
Project: Demographic Disparities and Imaging Features Associated with Choice of Excisional Biopsy versus Core Biopsy among Breast Cancer Patients
A woman suspected of having breast cancer currently has two medical procedures available to her to confirm her diagnosis: excisional biopsy or percutaneous core biopsy. From a medical standpoint, core biopsy is the option that often makes more sense. It is diagnostically as effective as excisional biopsy, with the added benefits of being less invasive and less costly (both to the individual and to society overall) and often easier and faster to schedule and therefore, obtain results. It is important to note, however, that core biopsy is not always possible; for example, a woman with a posterior lesion/calcifications might be better suited for excisional biopsy. Interestingly, some evidence suggests that women are still choosing excisional biopsy in the diagnosis of breast cancer even when core biopsy is available and clinically recommended. Little is known about why women’s preferences for excisional biopsy have not kept pace with the more attractive alternative (core biopsy) first introduced more than two decades ago. The purpose of this project is to tackle the first step in understanding this conundrum. We set out to determine which women are choosing excisional biopsy over core biopsy to diagnose their breast cancer. For example, does education, age, income, or imaging abnormalities influence biopsy preference? By gaining a better understanding of which women are choosing excisional biopsy, we will be better equipped not only to understand the reasons behind this choice, but also, to adjust medical policies and practices to ensure that all women are fully informed and treated with the highest standard of care.
(faculty mentor: Gary A. Koretzky MD PhD [Pathology and Laboratory Medicine])
Fellowship term, 6 months: November 2009 – May 2010
Project: Stapled Peptide Inhibitors of the Estrogen Receptor as Potential Breast Cancer Therapeutics
Breast cancer is the 2nd most common form of cancer and the 7th leading cause of death in American women. It has been well-established that both breast and prostate cancer are hormone-responsive, and that estrogen or androgens respectively play a role in the pathogenesis and growth of these cancers. Current chemotherapeutics function by either inhibiting the receptor, blocking the production of endogenous hormones, or attempting to down-regulate the receptor. However, all current therapies have limited in the efficacy in treating breast cancer by the development of tumor resistance. The development of novel staple peptides targeting the ligand binding domain of the estrogen receptor will potentially discovery prove effective at promoting receptor internalization and degradation using physiological mechanisms and therefore address the problem of acquired resistance. In addition, these unconventional bioactive “ligands” may help promote an understanding of how the ligand binding domain works through structural and functional studies, which could allow further development of improved therapeutics targeting this deadly disease.
M. Anne Radecki
(faculty mentor: Liza Wu MD [Surgery: Plastic Surgery])
Fellowship term, 6 months: November 2009 – April 2010
Project: Disparities in Breast Cancer Reconstruction: Delayed versus Immediate Reconstruction
Breast Cancer will affect 200,000 women this year alone. In recent years, there have been increasing rates of mastectomy both for breast cancer treatment and prophylactic prevention. Breast reconstruction has been shown to be oncologically safe with high rates of long-term satisfaction and to aid in the maintenance of psychological well-being and self- image. Insurance coverage of breast reconstruction is mandated by the Women’s Health and Cancer Rights Act and is defined as non-cosmetic. However, given these benefits, rates of breast reconstruction are estimated to only be approximately twenty percent. Additionally, studies have suggested that many of the ethnic and socioeconomic disparities seen in breast cancer treatment are also seen in reconstruction; with age, ethnicity, household income, living in an urban area, level of education all affecting reconstruction. Indeed, having had breast reconstruction is associated with increased rates of survival. We hope to further elucidate these disparities by comparing women who have had immediate versus delayed reconstruction. Specifically, we hope to survey women presenting for delayed breast reconstruction and will analyze what factors may have led these women to have chosen delayed reconstruction or to have prevented them from accessing the care or resources needed for immediate reconstruction. This work will not only add to our understanding of disparities that exist in breast reconstruction, but will add to our understanding of the referral networks that bring women to tertiary care centers for multi-modality breast cancer treatment.
(faculty mentors: Vincent Lo Re MD [Medicine: Infectious Diseases and Epidemiology] and Pablo Tebas MD [Medicine: Infectious Diseases])
Fellowship term, 6 months: September 2009 – January 2010; March 2010
Project: Risk of Fractures Associated with Hepatitis C Virus Infection in HIV-seropositive and HIV-seronegative Women
Coinfection with HIV and HCV is common since both infections share similar routes of transmission. In addition to its ability to induce liver fibrosis, chronic HCV is also associated with extra-hepatic complications, particularly abnormalities in bone mineral density (BMD) and bone metabolism that may contribute to morbidity among HIV/HCV patients. This problem is particularly important to women since women represent one of the fastest growing populations infected with HIV in the United States and women, particularly post-menopausal women, have higher rates of osteoporosis and fracture than men. Factors that may increase a woman’s risk of fracture, including HIV infection and potentially HCV infection, are important to elucidate so screening and possibly interventions can be implemented. No study has specifically examined the effect of HCV infection on spine and hip fractures. The specific aim of my proposed study is to examine the incidence rate of fractures at the vertebral spine and/or femoral neck in HIV/HCV-coinfected women receiving combination antiretroviral therapy compared to: 1) HIV-monoinfected women on combination antiretroviral therapy, and 2) HCV-monoinfected women. The study will be a retrospective cohort study using Medicaid data. If women infected with HIV/HCV-coinfected women are indeed found to have a higher risk of spine and/or hip fractures compared to HIV- and HCV-monoinfected women, routine screening for low bone mass would be indicated in this group, regardless of age. Such a finding would also prompt further studies to examine the mechanisms of impaired skeletal structure in HCV-infected.
(faculty mentor: Susan Domchek MD [Medicine: Hematology/Oncology])
Fellowship term, 6 months: July 2008, October 2008 – February 2009
Project: Identification of BRCA1/2 Mutations by Point Mutation Analysis and Genomic Rearrangement Testing: Comparison to Linkage Analysis
BRCA1/2 mutation carriers are at markedly elevated risk for both breast and ovarian cancers. However, most individuals with hereditary breast cancers are not BRCA mutation carriers; evidence suggests that these BRCA mutation-negative individuals may not be at excess risk for ovarian cancer. Evidence-based guidelines recommend that BRCA mutation carriers undergo prophylactic oophorectomy upon completion of childbearing to reduce the risks of breast and ovarian cancers; as non-carriers may not be at elevated risk for ovarian cancer, prophylactic oophorectomy may not be warranted in this population. Because of the distinct recommendations for BRCA mutation carriers and non-carriers, it is particularly important to identify individuals who have these deleterious mutations. Linkage analysis is considered the gold standard in detecting BRCA1/2 mutations. Comprehensive analysis looking for point mutations is offered to individuals who are candidates for genetic testing. Individuals who are mutation-negative on comprehensive analysis may undergo additional testing with recently developed techniques to identify large genomic rearrangements. The sensitivities of comprehensive analysis and additional genomic rearrangement testing directly impact the proportion of mutation carriers who are appropriately counseled and managed. Evidence-based estimates of these sensitivities for BRCA1/2 mutation testing are lacking. The present study will use linkage analysis as a gold standard to evaluate the proportion of true mutation carriers who are identified by comprehensive analysis and the proportion of carriers who are identified by genomic rearrangement testing. By estimating the sensitivity of current genetic testing, this study will impact genetic counseling interactions that occur between patients and healthcare providers.
(faculty mentor: Carrie Kovarik MD [Dermatology: Infectious Diseases])
Fellowship term, 6 months: September 2008 - February 2009
Project: Analyzing, Expanding and Developing Educational Materials for the Teledermatology Project in Sub-Saharan Africa
African Telemedicine provides support to local physicians, dermatologists, and health care workers in hospitals and clinics throughout Africa. This support is provided through Teledermatology consultation services, discussion pertaining to diagnosis and management of patients with skin diseases, links to educational resources, and access to an educational curriculum created specifically for African sites. Teledermatology is a valuable resource to facilitate healthcare and has demonstrated high levels of concordance in diagnosis and management plans compared with consultations conducted in person. This scholarly research and clinical project will focus on health issues in Africa as addressed in telemedicine consults. The goal of the work is to identify the current extent of the teledermatology program and key issues in which improvements can be enacted in the program in order to benefit both the health care workers who are submitting the consults and the local patients. The project will include an analysis of the types of problems being addressed via the consults and most importantly identification and development of educational materials and health outreach modalities to empower the patients and their health providers. This will allow for increased understanding of the factor’s impacting these patients’ health and access to health care services as well as the implementation of these services. Additionally, I will assemble pertinent educational materials to distribute to the African health care workers in an effort to foster increased understanding and independence in clinical practice and improve clinical care.
(faculty mentor: Angela DeMichele MD [Medicine: Hematology/Oncology])
Fellowship term, 6 months: July 2008 – January 2009
Project: p27 and Cyclin D1 Expression in Breast Cancer as Biomarkers of Response to Neoadjuvant Chemotherapy
Previous studies have shown that the pathologic response of tumors to neoadjuvant chemotherapy is well correlated with survival. We are part of a larger group of investigators that are working to identify surrogate biomarkers of stage II and III breast adenocarcinomas that may exhibit response to neoadjuvant chemotherapy and are predictive of pathological responses at the time of surgical resection and thus, survival. I will specifically evaluate breast adenocarcinomas for expression of the tumor suppressor gene, p27 and the oncogene, Cyclin D1, that are involved in cell cycle regulation. We will evaluate whether p27 and Cyclin D1 can be used as biomarkers of response to neoadjuvant chemotherapy, consisting of anthracycline and taxane. p27 and Cyclin D1 expression will be correlated to residual tumor burden upon imaging and pathology at the time of surgical resection. My research will hopefully contribute to a broader body of knowledge that will allow clinicians to use biomarkers to predict women that will respond well to standard chemotherapeutic agents, tailor therapy based on initial tumor profiles, and understand the biology underlying differential responses to therapy.
(faculty mentor: Samantha Butts MD MSCE [Obstetrics & Gynecology])
Fellowship term, 6 months: August - October 2007 & January - March 2008 Research-based fellowship
Project: Failure of Conservative treatment of Ectopic Pregnancy: Investigating the Role of Race
Racial disparities in the incidence of ectopic pregnancy and its associated morbidity and mortality represent persistent public health challenges in the field of Obstetrics and Gynecology. According to the most recent estimates from the CDC, the incidence of ectopic pregnancy is nearly doubled for minority women compared to white women, and minority women suffer a four-fold increased risk of ectopic pregnancy-related mortality. This racial disparity has been largely attributed to differential healthcare access and delayed diagnosis in black women with ectopic pregnancy. Differences in response to conservative treatments for ectopic pregnancy across racial categories may also contribute to the health disparities associated with this condition. Conservative treatment of ectopic pregnancy involves therapies in which the fallopian tube is not removed. One of the most widely utilized conservative treatments for ectopic pregnancy involves the administration of methotrexate, a folic acid antagonist that inhibits cellular division. Extensive research has shown conservative therapy to be highly effective, despite a failure rate of 5-10%. Several risk factors for methotrexate failure have been described; however there is no literature that has adequately addressed the role of race in the response to this treatment. From existing gynecologic databases, hospital discharge records, and inpatient pharmacy records, I will recruit subjects with a confirmed ectopic pregnancy treated conservatively. I will compile data on race, time to ectopic resolution, and other risk factors for conservative treatment failure to determine if race is an independent risk factor for treatment failure. If an association between race and methotrexate failure emerges from this data, the role of biology in addition to reduced healthcare access could be pursued to better understand this health disparity.
Maulik S. Zaveri
(faculty mentor: Laura Balcer MD [Neurology])
Fellowship term, 6 months: Start Date: Initial planning: November 2007- May 2008
Project: Gender Specific Analysis of Self-reported Visual Dysfunction in Multiple Sclerosis
The retinal nerve fiber layer (RNFL) provides a unique model for examining pathologic changes in multiple sclerosis (MS), as axons in the RNFL lack myelin. Structural changes in the retinal nerve fiber layer represent isolated axonal damage. RNFL thickness may serve as a structural biomarker in MS. The development of new retinal imaging techniques has allowed structural changes in the retina to be associated with clinical assessments of visual function. Optical coherence tomography (OCT) is a non-invasive ocular imaging technique that relies on the reflection of near infrared light and its interaction with various ocular tissue densities, permitting analysis of specific layers of the retina in terms of thickness and volume. RNFL thickness measurements using OCT have been examined in relation to visual function in MS. Reduced RNFL thickness was associated with lower visual function scores. Patients with MS have a high degree of self- reported visual dysfunction that is often not captured by visual acuity. The purpose of this study to examine vision specific health related quality of life in a cohort of MS patients using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25) and 10-Item Neuro-Ophthalmic Supplement (NOS-10). The VFQ-25 has been evaluated as an effective measure of self-reported visual loss in MS. Previous clinical trials have highlighted the potential benefit of using an MS specific questionnaire in addition to the VFQ-25. This study is designed to examine the correlation between self-reported visual dysfunction, visual acuity, and RNFL thickness measurements by OCT in a cohort of MS patients. Gender specific analysis will highlight potential areas to improve current clinical data collection for trials and provide insight for designing a specific questionnaire for men and women with MS.
(faculty mentor: Kathryn Schmitz PhD MPH [Biostatistics & Epidemiology])
Fellowship term, 6 months: November 2007 - May 2008
Project: Lymphedema and Exercise: Gaining Use and Productivity (LEG-UP) PILOT STUDY
Lymphedema is a common long-term adverse effect after the removal of lymph nodes for cancer treatment that results in abnormal, protein rich swelling of the affected limb. Left untreated, lymphedema can result in life threatening infections, disfigurement, the loss of mobility, and total disability. Over a six-month period, I will assess the feasibility and safety of a 2-month twice-weekly strength training intervention among a population of 10 cancer survivors with leg lymphedema. My project will test the hypothesis that slowly progressive strength training will increase the physiologic capacity of the affected limb(s) so that the occasionally strenuous activities of daily life pose decreased risk of lymphatic stress.
Caroline A. Banks (faculty mentor: Lily A. Arya MD MS)
Fellowship term, 6 months: November 2006 - May 2007
Project: Pattern, Knowledge and Attitudes about Fluid Intake and Lower Urinary tract Symptoms in Adolescent Girls
Lower urinary tract symptoms are common in women, and research has shown that fluid intake patterns are related to these symptoms, which include urinary tract infections and urinary incontinence. Studies that have investigated fluid intake patterns in women have shown significant differences between the fluid intake of African American and Caucasian women, but are limited. Specifically, fluid intake behavior, knowledge, and attitudes of minority women in the community are not well documented. Therefore, because it is well known that dietary patterns in adult life are established in childhood, exploring the intake patterns and fluid intake knowledge and attitudes of adolescent minority girls will help to tie learned childhood behaviors, which are carried through adolescence, to urinary symptoms that manifest during adulthood.
The FOCUS research project will be conducted in two phases. Phase one consists of administration of questionnaires aimed at assessing drinking habits, knowledge and attitudes of fluid intake, and lower urinary tract symptoms of adolescent minority girls. Phase two will consist of development and implementation of an educational module designed to educate adolescent minority girls about the importance of healthy beverage choices, the recommended amount of fluid intake, and the health impact of both recommended and non-recommended fluid intake. Finally, a post-test will be administered to assess the impact of the teaching session on students' fluid intake and to determine whether students have begun making healthier beverage choices. The information gained from this research may ultimately aid in development of behavior modification tools used to treat urinary incontinence.
Melinda J. Morton (faculty mentor: Seema Sonnad PhD)
Fellowship term, 6 months: December 2006 - May 2007
Project: Gender and Health Care Cost Growth
Rising health care costs in the United States continue to be a source of public and academic debate. Recent surveys of employers indicate that health insurance premiums have risen at a rate of 7.3 percent for the year; this rate continues to outpace the rate of economic growth and workers' earnings (5.9 percent and 3.8 percent, respectively). Perhaps more worrisome, trends in underlying costs appear to have stabilized at a rate that well exceeds growth in incomes. Yet despite these expenditures, major health indicators in the United States continue to lag behind those of other industrialized nations.
One hypothesis for the gap between health indicators and health expenditures in the United States is the use of health care technology. Technology has been recognized as a major contributor to health care cost growth, indeed as one of the factors most amenable to influence through changes in policy and practice. However, little research has been performed regarding the differences in the use of health care technologies between genders. According to the 2005 Agency for Healthcare Research and Quality (AHRQ) Disparities Report, health disparities between race, ethnicity, and socioeconomic status persist throughout the US healthcare system; furthermore, many women's health needs are inadequately addressed. Other studies reveal a gap in appropriate management of cardiovascular disease and diabetes for women, which persist across racial and ethnic groups. Through analysis of health care expenditures in one state, this study will reveal the nature and patterns of differing use of health care technologies by men and women.
Corrie Stankiewicz (faculty mentor: Angela DeMichele MD)
Fellowship term, 6 months: November 2006 - May 2007
Project: Molecular and Genetic Determinants of Bone Loss in Breast Cancer Survivors Who Have Received Adjuvant Chemotherapy
Most women with breast cancer do not die of the disease due to advances in treatment and earlier detection through screening practices. It is estimated that over 2 million women are living in the United States alone with a history of breast cancer. Although these women have survived the diagnosis of breast cancer, many have undergone treatments that have associated late morbidities. Adjuvant chemotherapy is one treatment which has increased breast cancer survivorship but carries with it long-term sequelae. Many women treated with adjuvant chemotherapy experience premature ovarian failure and accelerated bone loss. Estrogens are considered to have a positive effect on bone mineralization and several studies have shown an association between low estradiol levels, decreased bone mineral density and increased risk of fracture. Although many studies have looked at genetic variability as a basis for differential bone density and susceptibility to osteoporosis, no studies have looked at the specific population of patients who have undergone adjuvant chemotherapy for breast cancer. The ultimate goal is to identify early those patients most at risk for bone loss so that intervention can lead to decreased morbidity. To this end, we plan to characterize genetic polymorphisms related to bone mineral metabolism in patients who received adjuvant chemotherapy for breast cancer and were premenopausal at the time of diagnosis. We will then compare bone mineral density measurements and serum markers of bone turnover (such as osteocalcin, bone specific alkaline phosphatase and N-telopeptide) in patients with and without gene polymorphisms, adjusting for menopausal status post-chemotherapy.
Sade Udoetuk (faculty mentor: Emily Conant MD)
Fellowship term, 6 months: October 2006 - March 2007
Project: Outcome of Non Mass Enhancing Breast Lesions on Magnetic Resonance Imaging
Over the past 25 years, contrast-enhanced Magnetic Resonance (MR) imaging has been an important tool in breast cancer surveillance and staging. MR is highly sensitive in detecting occult cancers and it has been shown to be more reliable than x-ray mammography in breast cancer staging. Unfortunately, benign breast tissue can also show enhancement on MR and thereby be mistaken for malignancy. These false-positive results can be distressing to patients and subject them to unnecessary hospital procedures and expenses.
Non-mass lesions present a particular challenge to clinicians. Unlike other classes of MR enhancement patterns, non-mass lesions have no criteria for interpretation and, thus, it is largely unknown whether non-mass malignant lesions appear differently than non-mass benign lesions. However, if differences do exist, creating an algorithm to determine the malignant potential of theses lesions could help to ensure effective treatment, yet minimize clinical and psychological morbidity. From a data base of over 800 women, I will examine the radiographic evidence and clinical outcomes that differentiate malignant non-mass lesions from benign non-mass lesions on MR. I will compile the clinical findings, histologic samplings and imaging results of all patients found to have non-mass lesions. Based on these findings, I will develop a schema for grouping non-mass lesion morphology and calculate their predictive values.
Jesse D. Vrecenak (faculty mentor: Alan Flake MD)
Fellowship term, 6 months: August 2006 - January 2007
Project: Fetal Gene transfer in the Prevention of BRCA1-based Breast Cancers
While familial forms of breast cancer account for only 10% of overall cases, 50-80% of women who carry a mutation in BRCA1 will develop breast cancer by age 70. The BRCA1 gene acts as a cell cycle regulator, functioning as a tumor suppressor in the breast and ovary. Though testing is currently available to identify carriers of the mutation, therapeutic options are limited to prophylactic mastectomy and oophorectomy, major surgeries that carry a heavy psychological burden. In addition, neither procedure will affect the likelihood of passing the mutation to offspring. The monogenetic nature of the mutation and its clear risk profile for breast cancer make the BRCA1 gene an ideal candidate for a gene therapy approach.
Recently, a population of mammary stem cells was identified and characterized, and I plan to use a fetal gene transfer approach to attempt BRCA1 gene transfer in a mouse conditional knockout model of BRCA1 tumorigenesis. In order to demonstrate that the techniques used for in utero injection are capable of transducing mammary stem cells, I plan to first isolate stem cells from a mouse injected in utero with a viral vector containing GFP, and transplant the GFP-positive mammary stem cells into a wild-type adult female mouse. The development of a GFP-expressing, functional mammary gland in the wild-type mice will demonstrate transduction of the mammary stem cell population, and provide the groundwork for the application of this technique to BRCA1 transduction. I plan to conduct both a longitudinal study of tumorigenesis and in vitro assays to demonstrate sustained BRCA1 activity in the knockout mice after in utero gene transfer. A positive result in these studies would provide proof-in-principle for future studies of in utero gene therapy for familial breast cancers.
Jonathan Criss (faculty mentor: Laura J. Balcer MD)
Fellowship term, 6 months: September 2005 - February 2006
Project: Experiences and Concerns Regarding Pregnancy and Family Building in Patients with Multiple Sclerosis
Multiple sclerosis is a demyelinating disease of the central nervous system that affects women twice as commonly as men, most often presenting between the ages of 20 and 40. Patients with MS often have concerns regarding pregnancy, parenthood, and reproductive decision-making. Common concerns relate to the effect of pregnancy on disease course, the need to temporarily discontinue treatment, the outcome of pregnancy, the ability to care for a child, and the risk of passing on MS to offspring.
I am undertaking a cross-sectional, questionnaire-based survey to examine: 1) specific concerns and beliefs regarding pregnancy and family building among women with multiple sclerosis (MS) who have never been pregnant or adopted a child; and 2) specific medical and social experiences of women with MS who have had previous pregnancies and/or adopted children. The results of this study will be of significant importance in meeting the counseling needs of this population and in developing hypotheses for future research on the effects of pregnancy and family building on the MS disease process.
Kristin Nielsen (faculty mentor: Dennis Durbin MD MSCE)
Fellowship term, 6 months: October 2005 - April 2006
Project: Relationship Choices of Adolescent Women: Teen Pregnancy in the Context of Relationships
Teen pregnancy is a concerning issue for health care providers because of associated adverse health outcomes for both mother and child. Out of a desire to better understand this phenomenon, many studies have investigated the characteristics of men who impregnate adolescent women. Few studies, however, have examined the characteristics of the specific relationships in which pregnancy is desired and in which pregnancy occurs. Through in-depth structured interviews with 18 and 19 year old women, I will investigate qualitatively the range of responses given about desire for pregnancy during specific relationships. Further, I will examine how these responses are associated with specific emotional, social, and financial characteristics of each relationship.
The goal of this project is to better understand the factors affecting young women's desire for pregnancy during specific relationships, and to observe how these desires are associated with subsequent behavior and health outcomes. These findings may help inform health care providers' understanding of the choices made by young women at risk for teen pregnancy and may allow for more targeted interventions in the future.
Melissa DeJesus (faculty mentor: Kyle Kampman MD)
Fellowship term, 6 months: July 2004 - December 2005
Project: An Investigation of Binge Use of Cocaine and Its Associated Rewards
Gender differences exist in many psychiatric disorders, particularly in substance abuse. For example, more men are alcohol dependent, yet women are at a greater risk for alcohol related disease. They are more likely to escalate their use in less time and become dependent sooner than their male counterparts. I will be investigating the gender differences in patterns of cocaine use. Women may be predisposed to cocaine binges and escalate their use at a faster rate than men, in addition to deriving different rewards and sensitivities to the acute effects of cocaine use. If patterns of cocaine use is gender specific, targeted therapeutic interventions could be used to specifically treat women.
Melissa Johnson (faculty mentors: Barbara Weber MD and Susan Domcheck MD)
Fellowship term, 6 months: September 2003 - March 2004
Project: Breast Cancer Research- Investigation of the genetic and non-genetic determinants of breast cancer risk in African American and Caucasian women.
First, the potential role of low penetrance susceptibility genes in the molecular pathogenesis of breast cancer will be investigated. SNP genotyping will be used to identify allelic differences between African American and Caucasian women with breast cancer, specifically in genes involved in DNA damage repair. Second, identifying differences in demographics, endogenous hormonal exposures and exogenous risk factors between all cases with breast cancer and controls, with sub-analyses for race, may highlight other non-genetic risks of developing breast cancers. If differential exposures or risk factors between cases and controls can be shown to correlate with allelic differences found in genotypic analysis, augmented disease risk to certain patient populations will also be investigated.
Kathryn Ruddy (faculty mentor: Angie DeMichele MD)
Fellowship term, 6 months: August 2002 - February 2003
Project: Investigation of the breast tissue markers p21, cyclin D1, cyclin E, and p27 for possible significance in relation to age at diagnosis, menopause status, and prognosis of breast cancer. Involvement in three different projects, all focused on this question. Currently, the first two entail gathering detailed follow-up data for a prospective study of prognosis, coordinating immunohistochemical staining of p21, cyclin D1, and cyclin E for a retrospective analysis of relationship to age. The third project is a collaborative effort to analyze and present data on increased frequency of loss of p27 expression in younger women.
Hindi Elaine Stohl (faculty mentor: Susan M. Domcheck MD )
Fellowship term, 6 months: October 2004 - April 2005
Project: Recent data suggests that for women who carry mutations in BRCA 1 or 2, the lifetime risk of developing breast cancer is 60-80% and of ovarian cancer is 10-50%. Advances in medical and surgical technology have improved clinical management of these patients, and currently patients can be offered effective prophylatctic or therapeutic interventions, depending upon their clinical status. While genetic testing for BRCA 1/2 mutations has been available since 1996, the uptake for BRCA 1/2 genetic testing remains poor. In one study, only 25% of patients referred to BRCA 1/2 genetic testing centers attended a testing program. My research will explore the barriers to genetic testing among Ashkenazi Jewish women in the Greater Philadelphia area. The prevalence of BRCA 1/2 mutations in the Ashkenazi Jewish population at large is 2.5%, a frequency which is approximately five times higher than that of the general population. Due to their increased risk of carrying a BRCA 1/2 mutation, Ashkenzi Jewish women would be expected to utilize BRCA 1/2 testing at an increased frequency. Using questionnaires to survey these at risk and potentially high risk women, I hope to assess both the actual and perceived barriers to BRCA 1/2 testing and to determine whether greater education regarding genetic testing in general as well as the specific genetics of BRCA 1/2 and its health and financial implications will positively impact the number of women who opt for BRCA 1/2 genetic testing.
Nadia L. Dowshen (faculty mentor: Sara Kinsman MD PhD)
Fellowship term, 6 months: July 2003 - December 2003
Project: Sexually transmitted Infections and Adolescent Medicine Research- A Pilot Study of Adolescent Women Presenting to the ER with Abdominal Pain
Interviewing West Philadelphia girls in clinic/ER encounter. With the current alarming prevalence of STIs among adolescents in general and particularly among young minority women it is essential to understand their interaction with the reproductive health care system. I will investigate how the prevalence of diseases such as Chlamydia and HIV among young women in West Philadelphia affects their perception of themselves, their reproductive capacities, and their attitudes about health care and STI preventive practices and behavior. I will focus more specifically on the clinic/ER encounter and how this can be improved to make young women feel more comfortable, empowered and likely to stay connected to the system. The project will involve interviewing young women, in the Emergency Department, Inpatient Adolescent Unit and Adolescent Care Clinic at CHOP, about issues including the pelvic exam and what they are told and not told about how an STI diagnosis will impact their lives. The goal of the project is to inform best practices among reproductive health care providers for these young women and to increase awareness in this patient population about accessing the reproductive health care system.
(faculty mentor: Corey McMillan PhD [Neurology])
Fellowship term, 6 months: September 2015 - March 2016
Project: Gender-Related Risk Factors of Primary Age Related Tauopathy
In 2015, approximately 5.3 million Americans have been affected by Alzheimer’s disease with women comprising about two thirds of this population. The neuropathology of Alzheimer’s disease is characterized by the accumulation of both neurofibrillary tangles (NFT) of tau protein and amyloid-β plaques. Primary age related tauopathy (PART), in contrast, is a newly developed neuropathological diagnosis that describes a condition in which NFTs accumulate in the brains of aging individuals in the absence of amyloid-β plaque deposition. Therefore PART provides a neurodegenerative model to investigate the risk factors for NFTs and protective factors for amyloid-β. Clinically, patients with PART may be normal, exhibit mild cognitive impairment (MCI) or display severe amnestic dementia. While there are genetic risk factors associated with the development of Alzheimer’s dementia such as the APOE-ε4 allele, there are no known genetic risk factors for PART. Studies have demonstrated that there are differences between women and men in the Alzheimer’s disease process and in certain risk factors for developing the disease, however there have been no studies examining gender-related risk factors or biomarkers in PART. Identifying these risk factors will be crucial to the development of appropriate screening and risk assessments to identify candidates for disease modifying therapies targeting tau. Ultimately, we envision that identifying risk factors in a rare condition like PART can inform more common conditions involving tau such as Alzheimer’s disease and frontotemporal degeneration. Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, we will examine gender-specific prevalence and gender-associated risk factors and biomarkers in the development of PART. We will also investigate the association between a potential genetic risk factor, a polymorphism of the bridging integrator 1 (BIN1) gene and hippocampal volume in individuals with PART.
Mara H. Gordon
(faculty mentor: Ian Bennett MD, PhD [Family Medicine and Community Health])
Fellowship term, 6 months: September 2014 - January 2015; March 2015
Project: Technology and Perinatal Depression: Evaluating the Role of mHealth in Pregnancy in a Low-income, Urban Population
Low-income women bear a disproportionate burden of adverse outcomes in pregnancy, including an elevated risk for perinatal depression. Yet identifying and caring for these patients is challenging, especially given higher rates of missed appointments and late arrival to prenatal care within this population. There is significant excitement in the public health community surrounding mobile technology for health, or “mHealth,” as a tool to help identify and follow high risk patients between appointments. But do patients themselves see this technology as a valuable, relevant tool that helps them stay informed, communicate with their healthcare providers, and stay healthy? I plan to carry out a study of the acceptability and feasibility of mHealth interventions in a sample of women in prenatal care at the Helen O. Dickens Center for Women’s Health. Women receiving care at Dickens have a high rate of depressive symptomatology but are not systematically identified and followed. I plan to study the role of mobile technology in improving depression screening and monitoring; Dr. Ian Bennett’s group is piloting a variety of interventions in women who present for care at the Dickens Center as part of his ongoing research projects on the use of technology in identifying and treating women with perinatal depression. I will conduct a pilot evaluation of a Google Voice-based tool that allows patients and mental health providers to communicate between visits in an attempt to better understand what role mHealth might play in prenatal care. Do women using mHealth tools feel cared for by and connected to their prenatal care providers? What aspects of mHealth resonate with a low-income, urban population? Are text-message based modalities effective tools for identifying and tracking women at high risk for perinatal depression? These insights will help explore the feasibility of future investment in mHealth for high-risk prenatal patients and to tailor existing applications to the unique needs of these groups.
(faculty mentor: Brendan Carr MD MSHP [Emergency Medicine])
Fellowship term, 6 months: September 2013 - March 2014
Project: The Role of Gender in Presentation and Re-Presentation to the Emergency Department
Since the passage of the Affordable Care Act, hospitals have focused on reducing preventable readmissions. However, little consideration has been given to emergency care re-utilization. As a common portal for hospital entry and a safety-net utilized by the both insured and uninsured patients, emergency departments (EDs) have become increasingly crowded. Crowding, in turn, has been linked to poorer quality care and worse patient outcomes. Working as part of a multi-disciplinary team of physicians, nurses and researchers seeking to characterize and reduce unnecessary ED utilization, I will describe gender-related factors associated with recurrent ED utilization, with the goal of informing targeted interventions to reduce the rate of recurrent ED utilization and preventable ED crowding. Using qualitative interviews, I will explore and characterize the unique challenges women face transitioning home following ED discharge that they feel contributed to an ED re-visit. I will also explore the ways in which women are influencing the care-seeking behavior of their partners, family, and children, and whether distinct factors drive the care decisions women make for themselves. These insights will inform the development of a modification of the nurse-led, evidence-based Transitional Care Model (TCM) to the ED population with the goal of reducing ED reutilization, with targeted consideration given to any gender-based differences in utilization identified.
Martha Brown Kole
(faculty mentor: Clarisa R. Gracia MD MSCE [Obstetrics and Gynecology])
Fellowship term, 6 months: October 2012 - April 2013
Project: Quantifying menopausal symptoms pre and post cancer treatment and describing the time course to improvement
One in 3 women will develop cancer in their lifetime, many in childhood or early adulthood. Before the age of 39, women have more than a 1 in 50 chance of developing invasive cancer. With cancer becoming increasingly prevalent, and the diagnosis and treatment of many types of cancer improving, the number of cancer survivors continues to increase at a steady rate. Today there are an estimated 13.1 million cancer survivors in the United States, by 2022 there will be an estimated 18 million. With the improved survival rate of children and pre-menopausal cancer patients, the long-term reproductive sequelae of these treatments are increasingly important. For these survivors of cancer, infertility is one of the most common and life-altering complications. Following chemotherapy, which targets destroys mature ovarian follicles, women experience a cessation of menses which may last for months, years or indefinitely. Women also experience other menopausal symptoms such as hot flashes, mood changes, vaginal dryness and difficulty with sleep. To date no study had looked at the prevalence of these symptoms post cancer treatment in young cancer survivors or described the time course to improvement. Using data from the Ovarian Reserve After Cancer: Longitudinal Effects (ORACLE) study, a multi-center prospective cohort study, we will compare the prevalence of menopausal symptoms pre and post cancer treatment in pre-menopausal women with recent diagnoses of cancer. We will also describe the time course to improvement of symptoms and determine if this correlates with the return of menses.
(faculty mentor: Jun J.Mao MD [Family Medicine & Community Health])
Fellowship term, 6 months: October 2011-March 2012
Project: Aromatase Inhibitor-Associated Arthralgia as a Predictor of Suboptimal Adherence to Adjuvant Hormonal Therapy in Breast Cancer Survivors
Aromatase inhibitors (AIs) are an important class of hormonal therapies for postmenopausal women with hormone receptor-positive breast cancer. However, despite improved survival outcomes for patients on AIs, adherence to medications is suboptimal. A known toxicity of AIs is arthralgia, or joint pain, an adverse effect experienced by up to half of women. Though the presence of AI-associated arthralgia (AIAA) is well-documented, there is no study that examines the effect of these symptoms on adherence to AI therapy. The specific aim of this study is to determine if patient-reported AIAA is predictive of suboptimal adherence to AI therapy during a two-year follow-up period while the secondary aim seeks to elucidate the reasons for suboptimal adherence to AIs. A retrospective cohort study will be performed using baseline data from the Wellness after Breast Cancer study, a self-administered survey given to 500 women at the Rena Rowan Breast Cancer Center of the University of Pennsylvania. We will perform chart abstraction to determine adherence status as well as reasons for non-adherence in the two year follow-up period. The results from this study will contribute to understanding the barriers to AI adherence in breast cancer survivors with profound implications for symptom management, patient health and well-being, and long-term survival.
(Faculty mentor: Lily Arya MD MS [Obstetrics & Gynecology: Urogynecology and Pelvic Reconstructive Surgery])
Fellowship term, 6 months: July 2010 – December 2010
Project: Determination of Neuropathic Pain and Associated Phenotypic Characterization of Women with Bladder Pain Syndrome
Pain referred from the bladder, or Bladder Pain Syndrome (BPS), is one of the most common causes of discomfort in patients with chronic pelvic pain and affects 10-15% of women. Although quite prevalent among adult women, this clinical entity continues to present physicians with both diagnostic and therapeutic challenges. Recently, however, the Bladder Pain Syndrome Committee of the International Consultation on Incontinence has defined BPS as a condition in which pain, pressure or discomfort is perceived by the patient to originate from the bladder and is associated with other urinary symptoms (frequency or urgency). This new clinical definition has better enabled physicians to identify patients with symptoms suggestive of BPS, provided guidance for further evaluation and diagnostic testing, and encouraged clinical research.
Although BPS has a significant negative impact on patient well-being and quality of life, little is known about the exact pathogenesis of this disorder. In the proposed cross-sectional study we aim to expand upon mechanisms underlying this disorder by exploring the relationship between BPS symptoms, neuropathic pain and symptoms originating from other pelvic organs. This will primarily be achieved by surveying women fulfilling the diagnostic criteria of BPS and meeting our inclusion/exclusion criteria with validated questionnaires relating to pelvic floor symptoms. We hypothesize that bladder pain syndrome symptoms will be directly correlated with neuropathic pain symptoms. Further, we expect that both of these symptom sets will be related to bowel and sexual symptoms, as well as quality of life data.
(faculty mentor: Kenneth R. Ginsburg MD [Pediatrics: Adolescent Medicine])
Fellowship term, 6 months: October 2009 – March 2010
Project: Runaway Girls: Risk factors and Treatment Programs for Homeless Adolescent Woman
The lives of homeless young women are characterized by three defining features: risk, resilience, and transformation. Sadly, it is all too obvious what threats these women face: hunger, poverty, and emotional, physical and sexual violence. As healthcare providers, we must not forget the “normal” issues: acute and chronic disease, puberty, and sexual health. Faced with these burdens, the question facing healthcare providers becomes daunting: How do we heal these patients? With the support of the FOCUS fellowship, I intend to answer this question. Serving as a youth advisor at the Covenant House Crisis Center, I will study the lives of these homeless young women, the social structures and policies that help shape their lives, and the interaction between the individual women and the larger system. I am interested in studying the interface between public policy and individual lives, with a focus on the following four concepts: health care access and need, social welfare and poverty, education, and social support. My scholarly work will be guided by two parallel methodologies: ethnography and system analysis. Through individual and group interviews, neighborhood and home visits, and extensive follow-up, I will describe these women’s lives through the frameworks of health, poverty, education, and social support. Of primary interest will be their experiences with healthcare, welfare, public education, and formal and informal social groups.
(faculty mentor: Ian Bennett MD PhD [Family Medicine and Community Health])
Fellowship term, 6 months: October 2008 - March 2009
Project: Analysis of the Delivery of Mental Health Services to Low Income Pregnant and Postpartum Women
Depression during pregnancy and postpartum has a profoundly negative impact on women, infants, and families. Prenatal depression is associated with growth retardation, and postpartum depression with impaired child cognitive development. Later on, children whose mothers have major depressive disorder (MDD) are at an increased risk of developing MDD in adulthood. Importantly, successful treatment of maternal depression is associated with significant reductions in children’s psychiatric diagnoses and symptoms. Pregnancy is a critical time to impact women’s health because it is a time of increased access to care. However, mental health care during this time period is challenging; many women with MDD discontinue their antidepressants, and switching from their primary physician to a new ob-gyn physician may complicate treatment. The barriers that low-income women encounter when accessing depression treatment are particularly important to research. While meta-analyses show only a moderately increased risk for MDD amongst low-income women as compared to middle-income women, other studies suggest rates are almost twice as high in this population. This potential increased risk is compounded by pronounced disparities in quality of care, particularly for minority women. These difficulties in attaining effective treatment occur at a time where competing medical demands and new attitudes towards one’s health may decrease adherence to treatment for depression. I will perform extensive interviews with women with MDD or at risk for depression to determine their attitudes about depression, prior treatment, the decision to stop medications, and barriers to care. I will write a scholarly review of the existing literature on the delivery of services of depression in maternal care, and a journalism article to educate readers about the topic and create an impetus for improved care for this population. My project aims to address the problem that low-income pregnant and postpartum women with depression are often not receiving effective treatment.
Sarah C. Hull
(faculty mentor: Arthur Caplan PhD [Medical Ethics])
Fellowship term, 6 months: September 2007 - February 2008
Project:The Controversy Surrounding the HPV Vaccine
The vaccine against human papilloma virus (HPV), which received regulatory approval last year, is the focus of an issue at the forefront of women's health. Some see it as a miracle drug that can prevent cervical cancer. Some see it as common-sense protection against a sexually transmitted disease. Some see it as a license for young women to be promiscuous. Interestingly, the latter was not an issue when the vaccine against hepatitis B virus (HBV) was introduced, even though HBV in this country is frequently transmitted sexually. This disparity raises many normative questions that require establishing a sense of where society stands on these issues through survey-based research. Given my concern about how sexism might be shaping the HPV debate, my focus will be on two key questions: how readily society would accept a mandate for this vaccine under different labels (for example, protection from cancer versus STD prevention), and how we might receive such a vaccine for boys (given their actual risk of contracting symptomatic HPV disease as well as in the setting of a similar hypothetical disease responsible for comparable morbidity and mortality in men). In addition, an extensive literature review is required to more precisely characterize the transmission and prevalence of HPV and its ill effects in men and women alike, along with attitudes about the vaccine as well. I intend to conduct such research under the supervision of Dr. Arthur Caplan, director of the Penn Center for Bioethics.
Marah E. Gotcsik (faculty mentor: Cynthia Mollen MD MSCE)
Fellowship term, 6 months: September 2006 - February 2007
Project: Attitudes, Opinions, and Beliefs Regarding Emergency Contraception in Adolescent Girls
Teenage pregnancy is a major public health issue, as recognized by Healthy People 2010. Currently, emergency contraception is a little known and seldom used option for pregnancy prevention in the United States, especially among adolescents. In addition, there is limited data regarding attitudes and beliefs toward emergency contraception within this demographic. It is important to address this gap in the literature before creating an educational intervention, thereby increasing the likelihood of an accepted and effective message. For the FOCUS Fellowship, I will participate in interviewing urban, minority adolescent females about their views surrounding pregnancy in general and emergency contraception specifically. The interviews will be conducted in semi-structured format, allowing the subject to define the language she uses to talk about sexual health and express her thoughts and beliefs through open-ended questions. I will then assist with coding the transcripts from the interviews, and participate in the analysis of the data. The results of this study will be an important component of subsequent research, with the ultimate goal to create an educational intervention about emergency contraception for use in the emergency department. Beyond creation of the intervention, this study will be an important addition to the literature on adolescent use of emergency contraception. The current lack of understanding has resulted in policy decisions and controversy at levels as high as the Federal Drug Administration. Thus, beyond its clear relevance, this project is also very timely.
(faculty mentor: Anne R. Cappola MD ScM [Medicine; Division of Endocrinology, Diabetes and Metabolism])
Fellowship term, 6 months between August 2015 and April 2016
Project: Cardiac Effects of LT4 and LT3 Therapy for Subclinical Hypothyroidism in the Elderly
Pathologic excess and insufficient quantities of thyroid hormone more commonly occur in women, with an incidence of thyroid dysfunction roughly ten times greater than that in men. The cardiovascular system is a major target of thyroid hormone, and hypothyroidism has long been known to increase biologic markers for cardiac risk and increase rates of cardiovascular events. The impact of thyroid hormone on cardiovascular outcomes in the geriatric population is less well understood, however, due to the increasing prevalence in this age group of subclinical thyroid dysfunction. With increasing age, there is an observed increase in thyroid stimulating hormone in individuals without evidence of thyroid disease. It is thought that this likely represents an adaptive, aging-related change as opposed to a decline in thyroid function, and as such, may not warrant treatment. However, the impact of subclinical thyroid dysfunction on numerous health outcomes, including cardiovascular parameters, metabolism, and body composition is not entirely understood. Similarly, it is unclear whether or not this dysregulation, which is more commonly observed in elderly women as opposed to men, affects the sexes differently. This study aims to better characterize the effect of treatment of subclinical hypothyroidism on cardiovascular outcomes, metabolism and quality of life in the elderly as well as any differences in the magnitude of these effects between the genders. Additionally, we will explore the difference in response to treatment of subclinical thyroid dysfunction between women and men. The results of this work can improve our clinical understanding of gender differences in both the physiology and functional outcomes of subclinical hypothyroidism in the elderly, allowing physicians to improve patient-centered counseling of the aging population.
(faculty mentor: Lisa Levine MD [Obstetrics and Gynecology])
Fellowship term, 6 months: TBA
Project: The Effect of Preeclampsia on Future Cardiovascular Disease
Preeclampsia (PEC) is the leading cause of maternal morbidity and mortality in the United States and abroad. The relationship between PEC and long-term cardiovascular morbidity has been well established; however, the mechanism of progression of disease is not understood. This study aims to analyze the cardiovascular health of women with a history of PEC ten years postpartum, using an existing study cohort from the Preeclampsia: Mechanisms and Complications (PMC) trial conducted at the University of Pennsylvania from 2005-2009. The first phase of research will involve examination of the original cohort, and analysis of the feasibility of recruiting this cohort, including identifying the best means of establishing successful longitudinal follow up for these women. This will be accompanied by simultaneous retrospective chart review of ten-year postpartum cardiovascular events, markers of cardiovascular disease, and hospitalizations for the same cohort of women. The FOCUS project will provide insight into best methods for conducting long-term follow up trials for maternal health, establish a database for extensive longitudinal research on the cardiovascular health of women with a history of PEC, and introduce valuable data contributing to an understanding of the progression of cardiovascular disease in women with PEC.
(faculty co-mentors: Angela Mills, MD [Emergency Medicine] and Francis Shofer PhD [Emergency Medicine])
Fellowship term, 6 months: October 2014 - March 2015
Project: Gender Differences in Time to STEMI Activation for Patients Presenting to a UPHS Emergency Department
Cardiovascular disease remains the largest cause of mortality for women in the United States. While the implementation of AHA guidelines have reduced in-hospital mortality for ST-elevation Myocardial Infarctions (STEMI) and NSTEMI, a gender gap still remains with excess mortality in women with STEMIs, especially those younger than 60 years old. Among patients who present with STEMI, women are often older and have more comorbidities than their male counterparts, but the adjustment for baseline characteristics is not sufficient to explain the early excess mortality of women compared to men. Women hospitalized for AMI have been found to receive less aggressive medical and invasive treatments once in the hospital, partially owing to their older age, less extensive atherosclerosis, and delayed and atypical presentations. In particular, door to needle and door to balloon time is delayed for females compared to males according to data from national registries, with subsequent worse outcomes. Our aim is to study whether gender remains an independent factor associated with a modifiable factor – delays to STEMI activation – for patients that present to the emergency department, in the hopes of identifying existing gaps in provision of guidelines-based treatments in order to improve the treatment of AMI.
(faculty mentor: Daniel Rader MD [Medicine: Division of Translational Medicine and Human Genetics])
Fellowship term, 6 months: October 2013 - April 2014
Project: The Association of Serum Androgens with a Surrogate Marker of Coronary Artery Disease in Women
The leading cause of mortality in women continues to be cardiovascular disease. Various studies have examined the relationship between androgens and heart disease in women. However, those that have are typically limited to a specific sub-population of women (e.g. those with polycystic ovarian syndrome (PCOS), or those who are post-menopausal), have contradictory results, and perhaps most importantly, use immunoassays to measure androgen levels, which are neither sensitive nor specific for measuring androgens in a female population. The aim of this study is to determine if androgens are associated with a surrogate marker of atherosclerotic disease, coronary artery calcium (CAC), in a general female population using the relatively novel, extremely sensitive and specific technique to measure androgens, liquid chromatography-mass spectrometry (LC/MS). The hypothesis is that women with higher CAC scores will have higher androgen concentrations. Study participants will be selected from existing IRB-approved studies. With this approach, we hope to gain a more reliable picture of how androgens may influence and/or characterize women with CAD.
(faculty mentor: Anuja Dokras MD PhD [Obstetrics and Gynecology])
Fellowship term, 6 months: September 2012 - March 2013
Project: Phenotyping Lipoprotein Particles in Patients with PCOS to further assess Cardiovascular Risk
Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting an estimated 7-10 million reproductive-aged American women. Further research has demonstrated the strong cardiovascular implications and risk factors for atherosclerotic disease inherent in PCOS. Since cardiovascular disease (CVD) is one of the leading causes of female morbidity and mortality in the US, PCOS may represent a significant portion of the CVD seen in women. Thus, it is imperative that the precise CVD risk in PCOS be quantified. Prior studies have shown the prevalence of subclinical markers of CVD in PCOS patients and the classical perturbations in the lipid profile, including elevated triglycerides, high LDL and low LDL. In addition, a prior study piloted by Dr. Anuja Dokras and Dr. Daniel Rader demonstrated a significantly higher ApoB/ApoA1 ratio in the cardiometabolic profile of PCOS patients. The ApoB/ApoA1 ratio is often a better measure of CVD risk than LDL and cholesterol levels alone, thus simple classical measurements may not represent the whole picture when it comes to CVD risk in PCOS patients. A further clarification of the lipoprotein phenotype, including lipoprotein particle size, particle concentration and particle function, in PCOS patients will help further clarify this unknown. We hypothesize that PCOS will be associated with a more atherogenic lipoprotein phenotype beyond traditional cardiometabolic risk factors. Specifically, that PCOS will be associated with higher LDL particle number and smaller LDL particle size as measured by Nuclear Magnetic Resonance spectroscopy and with reduced function of HDL cholesterol as measured by cholesterol efflux.
(faculty mentor: Judd Hollander MD [Emergency Medicine])
Fellowship term, 6 months: August 2011 - March 2012
Project: The Effect of Patient Gender on Clinical Decision Making for Patient Presenting to the ED for Chest Pain
For the past decade, coronary artery disease has remained the number one killer of women, and continues to affect more women than men in the United States. Research has showed us that women have lower rates of intervention for their disease, including angiography, angioplasty, and bypass grafting. Traditional explanations for these lower intervention rates include delayed presentation, atypical symptoms, and less reliable diagnostic testing for women; these explanations, however, are falling by the wayside as researchers find persistent bias even when controlling for these variables. As we continue to try to understand the gender disparity in coronary artery disease treatment, the contribution of physician bias in recommending diagnostic testing and treatment interventions for women with possible coronary artery disease needs to be investigated. This study aims to understand how the patient’s gender affects the physician’s recommendations for stress testing, percutaneous interventions, and medical therapy for women with symptoms that are concerning for coronary disease. We will enroll patients presenting to the emergency room with chest pain, and will gather data on interactions with physicians throughout their hospital stay as well as their outpatient encounters. This study will survey both the patient and physicians, including emergency room physicians, hospitalists, cardiologists, and primary care physicians to assess which tests and treatment interventions are ordered. With this study we hope to uncover discrepancies in physician recommendations that may be a barrier to getting women the treatment they need for coronary artery disease.
(Faculty mentor: Anuja Dokras MD PhD [Obstetrics & Gynecology: Reproductive Endocrinology & Infertility])
Fellowship term, 6 months, September 2010 – May 2011
Project: Cardiovascular Disease Risk Factors in Polycystic Ovary Syndrome
Polycystic ovary syndrome is the most common endocrine disorder in reproductive age women. In addition to its effects on ovulation and fertility, it is associated with hypertension, hyperlipidemia, obesity, and diabetes - conditions which are major cardiovascular risk factors and may predispose women with PCOS to coronary artery disease. These comorbidities are the most serious consequences of PCOS, and a better understanding of the cardiovascular disease risk in this group is therefore of utmost importance. Several novel biomarkers have recently been implicated in the pathophysiology of metabolic disease, however their role in PCOS is not yet clear. I plan to compare serum levels of these biomarkers in women with PCOS and in a control population and will correlate my findings with clinical characteristics and hormone measurements in the PCOS subjects, as well as with their cardiovascular risk factors. The relationship between these biomarker levels, cardiovascular risk measures, and the clinical and biochemical characteristics of PCOS will clarify the cardiovascular risk in this population and potentially identify new therapeutic targets.
Arthur Robin Williams
(faculty mentor: Daniel D. Langleben MD [Psychiatry])
Fellowship term, 6 months: July 2009 – August 2009; October 2009 - January 2010
Project: Sex Differences in the Smoker’s Brain Response to Anti-smoking Ads
Tobacco smoking is the largest single preventable cause of cardiovascular disease in the industrialized world and televised anti-smoking public service announcements (PSAs) are a mainstay of public health efforts to reduce smoking. Therefore enhancing PSA messaging is of the utmost importance for more effectively reducing tobacco consumption and improving cardiovascular risk profiles. The decade of the 1990’s is now referred to as “The decade of the brain,” owing to the rapid advances in neuroscience and imaging technology that allowed researchers to better understand the most complicated organ of the human body. Functional Magnetic Resonance Imaging (fMRI) in particular has become a powerful tool for investigating brain activity in response to structured stimuli. Working with Daniel Langleben, MD (Associate Professor, Psychiatry) on an NIH-funded study investigating the effects of anti-smoking PSAs on the brain activity of smokers, I will analyze the data set by sex to explore sex-based differences in brain response. The PSAs will be categorized along two axes based on their mean sensational value (MSV) and argument strength (AS). My study will be synergistic with the parent project and explore the sex differences in the brain response to PSAs in general and its interaction with the MSV and AS in particular. Additionally, I will review the literature on the fMRI investigations of sex differences in the brain response to audiovisual cues and implications for directing future research, building upon the findings from our experiment exposing smokers to anti-smoking PSAs.
(faculty mentor: Sean Hennessy PharmD MSCE [Biostatistics & Epidemiology and Pharmacology])
Fellowship term, 6 months: September 2008 - March 2009
Project: Effect Modification by Gender on Digoxin-Associated Mortality over Time
Interventions in cardiovascular medicine may have different safety/efficacy profiles by gender. For example, digoxin may increase mortality by approximately 20% in women but not in men, an effect most likely mediated by higher serum digoxin levels in women. This phenomenon is clinically important because digoxin is still widely used. It remains unclear whether digoxin should be used differently by gender. Maintenance of low digoxin serum concentration would likely prevent excess mortality in either gender, but it is unknown whether current clinical practice avoids causing excess mortality in women. My project uses a large observational database from the United Kingdom called The Health Improvement Network, which contains over 5 million individuals. Using a retrospective cohort design, we will assess whether the mortality risk for digoxin users varies (or ‘interacts’) with gender. We will also assess whether any interaction depends on the digoxin dose or has changed over the years. THIN provides lab values on some patients, so it should also be possible to do a subgroup analysis adjusting for serum concentration of digoxin. The clinical benefit of this study is that it will identify whether digoxin, as it is really being used, is harming women. Exploration of dose-dependency and serum concentration dependency will also give insight into whether there is a way to avoid such effects. Since concerns about digoxin use in women continue to appear in the literature, either a positive or a negative finding will help guide clinical decision making.
Andrea Goldberg (faculty mentor: Michal A. Elovitz MD)
Fellowship term, 6 months: May - August 2006 and January - April 2007
Project: Short-term Maternal Outcomes After Preeclampsia: Elucidating Why These Women Are at Increased Risk for Long-Term Cardiovascular Morbidity and Mortality
Preeclampsia is a disorder of pregnancy resulting in hypertension and proteinuria after 20 weeks gestation. It affects 5-7% of all pregnancies, and has been the second leading cause of maternal death since 1982, accounting for nearly 20% of maternal mortality in the United States (CDC data, 1991-1999). Mounting evidence suggests that gestational hypertension and preeclampsia are associated with an increased risk of future cardiovascular disease, and may themselves be an early manifestation of pre-existing cardiovascular disease. Whether pregnancy acts as a "stress test," unmasking a predisposition to hypertension and cardiovascular disease that would otherwise not have been apparent until later in life, or whether a cause-effect relationship exists between preeclampsia and the subsequent development of cardiovascular disease, remains unclear. The primary aim of this research is to determine if preeclampsia is associated with an increase in cardiovascular morbidity and/or the development of cardiovascular risk factors in women at 6, 12, and 18 months after delivery.
To shed light on the pathogenesis and adverse outcomes of preeclampsia, a prospective case-control study is currently underway at the University of Pennsylvania. For the FOCUS fellowship, I will enroll patients in this study, collect maternal and fetal DNA and maternal serum, and interview study subjects at the time of delivery. I will also conduct phone interviews with both cases and controls at 6, 12, and 18 months after delivery to assess whether preeclamptics have an increased incidence of cardiovascular risk factors and metabolic syndrome compared to controls.
Bryn E. Mumma (faculty mentor: Judd Hollander MD)
Fellowship term, 6 months: 8/1/06 - 10/1/06 & 3/1/07 - 5/25/07
Project: The Effect of Gender on Patient Preferences Regarding Cardiac Procedures
Compared to men, women with acute coronary syndromes (ACS) have longer delays to presentation, treatment, and diagnosis, as well as lower rates of coronary angiography, angioplasty, and coronary artery bypass grafting (CABG) surgery. Furthermore, these differences have been associated with a higher adjusted death rate up to age 70 years and increased rates of refractory ischemia, reinfarction, and rehospitalization in women. Previous research has investigated possible reasons for this gender bias in cardiac procedure rates, including fewer physician referrals and higher rates of refusal among women. However, women's preferences regarding cardiac procedures remain largely unexplored. The current study will examine the preferences of men and women given a choice of options for the diagnosis and treatment of coronary artery disease (CAD). Any patient who presents to the Emergency Department with a primary complaint of chest pain who is over 30 years of age and medically stable will be asked to participate in the study. Patients will not be excluded based on gender, economic status, or race. Telephone follow-up and medical record examination will be utilized to determine subjects' diagnoses, therapies, and outcomes at 30 days. Patients' preferences regarding procedures will then be compared to the rates at which procedures are actually performed in the patient population. These results will be important in discerning the underlying reasons for sex discrepancies that exist in the rates of cardiac interventions.
Jennifer Shin (faculty mentor: Darren Taichman MD, PhD)
Fellowship term, 6 months: August 2003 - February 2004
Project: Quality of Life in Women with Primary Pulmonary Hypertension (PPH)
PPH is a relatively rare disease that is characterized by an increased pulmonary arterial pressure without an identifiable cause. It is a disease found predominantly in young women with patients often presenting with shortness of breath and decreased exercise tolerance. If these patients are not treated, there is a progression to right heart failure and death. Although new therapies have been shown to improve clinical function, hemodynamic parameters, and even survival, research is still needed that focuses on the woman's determinants of her quality of life and the effects of the therapies that she is undertaking. This study aims to delineate what factors are of key importance in the quality of life in this population of women.
Tim Gustafson (faculty mentor: David Sarwer MD)
Fellowship term, 6 months: November 2003 - April 2004
Project: Obesity is one of the nation's major public health concerns as the prevalence is steadily increasing and obese patients are more likely to develop diabetes, hypercholesterolemia, and stroke as well as cardiovascular disease including hypertension, angina pectoris, myocardial infarction, coronary artery disease, and congestive heart failure. Attempts at decreasing obesity can be best made with a full understanding of the social, biological, and psychiatric context in which it presents. This project, to be conducted at the University of Pennsylvania Weight and Eating Disorders Program under the mentorship of David Sarwer, PhD, will examine the relationship between obesity and one psycho-social factor in particular, a history of past sexual abuse. It will investigate the notion that obesity may serve an adaptive function in some women with a history of sexual abuse and the extent to which past sexual abuse is likely to impact obesity treatment. The project will explore ways in which obesity treatment for patients with past sexual abuse might be varied to result in better long-term outcomes thereby reducing the occurrence of obesity-related co-morbidities.
Connie Tsao (faculty mentor: Martin G. Keane MD)
Fellowship term, 6 months: September 2002 - March 2003
Project: Cardiovascular Research- Investigation of cardiovascular mortality among African American women, specifically to examine the effect of left ventricular hypertrophy on subsequent cardiovascular events, using novel imaging techniques and epidemiologic methods to extend knowledge in this important and often overlooked area.
Christine M. Perez (faculty mentor: Anne Honebrink MD FACOG)
Fellowship term, 6 months: September 2002 - March 2003
Project: Cardiovascular Research - Hormone Replacement Therapy (HRT) and Women in Mid-Life. Working with the MID LIFE PROGRAM in the Women and Children's Health Services, Women Division, associated with Pennsylvania Hospital, development and implementation of community-based screening and educational program for cardiovascular risk factors for low-income mid-life women. The program entails screening cholesterol and blood pressure, surveying basic cardiovascular knowledge, providing appropriate education and counseling, and assessing whether the education and counseling is effective. The hope is to create a program that is specifically tailored to the needs and make-up of this population.
Aluko Akini Hope (faculty mentor: Shiriki K. Kumanyika PhD MPH)
Fellowship term, 12 months: August 2001- August 2002
Project: Research with Penn Family Care Healthy Eating and Lifestyle Program (HELP) to determine cost-effective approaches to long-term weight control for black women's cardiovascular health as part of their routine ambulatory care.
Eva Zasloff (faculty mentor: Daphne Goldberg MD and Ian Bennett MD)
Fellowship term, 6 months: August 2005 - January 2006
Project: Adolescent Prenatal Education and Support Program
Extensive literature documents increased risk in adolescents of pregnancy complications including preeclamsia, low birth weight, and prematurity, as well as parenting complications such as childhood malnutrition, abuse, and neglect. These women face a bewildering array of personal, social, and medical challenges with profound implications for the future welfare of themselves as well as their children. With the guidance of my mentors, I will develop, facilitate, and evaluate an education and support program for pregnant teens. The content of the course will combine basic prenatal education with creative activities intended to explore self-awareness, empowerment, and readiness for pregnancy, birth and motherhood. The program will be held at four sites in the Philadelphia area: South Philadelphia High School, The Covenant House, the Children's Aid Society of Pennsylvania, and the Jefferson Family Medicine Clinic. The goal of this project is not only to provide these sites with a valuable one-time program, but to give them tools in order to incorporate this educational program into their already established curricula.
Caitlin Carr (faculty mentor: Emily Conant MD)
Fellowship term, 6 months: August 2005 - February 2006
Project: Impact of Whole Body PET in the Staging of Breast Cancer
Breast cancer is the most common non-cutaneous malignancy among women in the United States, and a diagnosis of breast cancer bears tangible and intangible costs. The clinician attends to these costs by working with the patient to develop an appropriate, effective therapeutic plan based on the extent of disease, as determined by selective application of diagnostic protocols and staging modalities. Depending on primary lesion characteristics and patient presentation, the staging of breast cancer may involve sentinel node mapping, axillary lymph node dissection, chest x-ray, bone scintigraphy, and chest, abdominal, or head CT. The routine use of whole body PET scans in staging of other malignancies, including lung, lymphoma, and colorectal, has prompted some experts to advocate for the use of PET in breast cancer staging.
During the six-month project, I will access a database of more than 250 patients who have had a whole body PET scan in the setting of invasive breast cancer and obtain data about the outcomes of the lesions identified on PET imaging. I plan to compare PET evaluation of the axilla with known pathologic nodal status of these patients and then correlate the results of any additional imaging or interventional procedures needed to work up PET-detected incidental lesions. I will also analyze the cost-effectiveness of PET in breast cancer staging in terms of both economic and emotional measures.
Dina Gottesman (faculty mentor: Sara Kinsman MD PhD)
Fellowship term, 6 months: September 2004 - February 2005
Project: An Analysis of How Peer Pressure Influences High-Risk Behaviors in Adolescent Females
Several high-risk behaviors including unprotected sexual intercourse, alcohol use, and cigarette smoking are typically first experimented with during adolescence, predominantly in the presence of peers. Each of these behaviors is associated with short-term as well as long-term morbidity and mortality. Through use of the National Longitudinal Survey of Adolescent Health, my research project will focus on how peer relationships during adolescence influence adolescent females' initiation of high-risk behaviors. Specifically, I will study how popular female students' rates of initiation and intensity of participation in risk behaviors influence their peers' initiation of three risk behaviors including sexual intercourse, drinking alcohol, and smoking cigarettes. The goal of the project is to elucidate the complex relationship between popularity and high-risk behaviors so that creative and practical interventions can be developed to reduce peer related influences on risk initiation.
Adriana Izquierdo (faculty mentors: Judy Shea PhD and Steve Larson MD)
Fellowship term, 6 months: November 2004 - April 2005
Project: Needs-Assessment Health Survey for Mexican Community in South Philadelphia
A qualitative and quantitative health study with an ethnographic appoach targeting a growing population of Mexican immigrants in South Philadelphia. The principal aim of this study is: to describe the population with respect to key demographic characteristics; to assess the population's perceptions of health, health care and health needs; and to characterize the population's utilization of health services. Using the results of this study, I will formulate potential methods for improving this particular population's access to health care by addressing the future allocation of health resources and implementation of health services. The final goal of this project is to develop a sustainable community health outreach program for Mexican women, based on their identified interests and needs. The program would be designed to be carried on in the future by future Penn medical students, thereby creating an opportunity for students to strengthen their languarge and clinical skills in working with a cross-cultural population of Latinos.
Alicia Veit (faculty mentors: Rhonda Boyd MD and Guy Diamond MD)
Fellowship term, 6 months: September 2003-February 2004
Project: Role of Depression in Parents: Impact on Children; Children of Depressed Parents: Family Based Prevention of Mental Health Problems
The primary goal of involvement in these two projects is to focus on examining the transmission of psychopathology from depressed parents to their children. Both medical and psychology literature document that maternal depression has a negative impact on child development, but given the potential consequences of maternal depression there are very few studies aimed at prevention or intervention. The first project, "Role of Depression in Parents: Impact on Children" is a large, multi-center trial exploring if the treatment of depression results in prevention of adverse consequences of maternal depression on child development. This final phase of this study involves recruitment of comparison matched-families, and the screening, assessment, and data evaluation of the results of these family assessments. The second project, "Children of Depressed Parents: Family-Based Prevention of Mental Health Problems"" is in the start-up phase. The primary goal of this pilot project, which will be conducted through the Center for Family Intervention Science, is to develop, manualize, and implement a family-based preventive intervention for depressed parents and their school-aged children who are in treatment. The project will be based at two local community mental health agencies: the Community council for Mental Health and Mental Retardation, Inc, in West Philadelphia, and Intercommunity Action, Inc in the Roxborough section of the Philadelphia. The first phase of the project will involve conducting and analyzing focus group interviews with both parents and mental health professionals to better understand the nature of family and individual risks related to being a depressed parent and living with a depressed parent. This information will then be used to develop an intervention based on the inclusion of parenting and family approaches to treatment, and will result in the development of manual for the parent education and training component. The final phase will involve a pilot test of this intervention.
Michelle Klaus (faculty mentors: Stephen Gluckman MD and Pablo Tebas MD)
Fellowship term, 6 months: October 2003 - March 2004
Project: Osteoporosis and HIV-infected Females
Recent data has shown that HIV-positive patients have higher rates of osteopenia and osteoporosis then their age, race and sex-matched counterparts. To-date studies have been divergent with respect to the mechanism for the association between HIV disease and decreased bone density. As the majority of investigations have been conducted primarily or exclusively with male patients, little is known about the additive effects of HIV-dependent variables to the known risk factors associated with female sex. This study will enroll female patients from HIV clinics at the Hospital of the University of Pennsylvania, Presbyterian Hospital and the Veterans Administration Medical Center to determine the prevalence of osteopenia and osteoporosis in this patient population, and the association of HIV-dependent and HIV-independent risk factors. The study will consist of patient surveys, physical exams, chart reviews, and dual energy x-ray absortiometry (DEXA) scans. The information obtained from this project may be used to assess the appropriateness of current osteoporosis screening protocols for HIV-infected women.
Teresa M. Mangin (faculty mentor: Clyde E. Markowitz MD)
Fellowship term, 6 months: May 2003 - October 2003
Project: Experiences and Concerns Regarding Pregnancy and Family-Building in Patients with Multiple Sclerosis
Multiple sclerosis is an unpredictable disease that predominantly strikes women during their childbearing years. Consequently, concerns regarding the impact of pregnancy on the disease course, the outcome of pregnancy, and risk of passing on MS to offspring are prominent ones for many patients. In order to establish a foundation for meeting the counseling needs of this population, better characterization of patients perceptions and experiences regarding family-building is necessary. The study is a cross-sectional survey to examine the following: 1) concerns and beliefs regarding pregnancy and family-building among women with multiple sclerosis (MS) who have never been pregnant or adopted a child; 2) specific medical and social experiences of women with MS who have had previous pregnancies and/or adopted children.
Ann Davis (faculty mentor: Ian Bennet MD PhD)
Fellowship term, 6 months: May 2003 - October 2003
Project: Integrating Maternal and Child Health Education with Adult Basic Literacy Education: A Pilot Project
This project will test the hypothesis that educational materials tailored to readers with a low level of literacy can improve knowledge of contraceptive options and self efficacy regarding contraceptive use. This project aims to develop and test a curriculum of contraception education materials for women with low literacy. These materials will be used in adult basic literacy classes sponsored by the Maternal Health Literacy Project, a collaboration between the Maternity Care Coalition of Delaware County and the University of Pennsylvania School of Medicine and Graduate School of Education. The goal of this project will be to improve health literacy relating to contraception in the context of improving overall basic literacy.
Sandra L. Urtishak (faculty mentor: Stephen L. Eck MD PhD)
(portion also funded by RGK Foundation)
Fellowship term, 12 months: June 2001- June 2002
Project: Breast cancer research, the goal of which is to determine whether the expression of GA733-2 on breast cancer cells enhances their ability to evade the immune response to tumor antigens. About one third of patients with breast cancer express GA733 on their tumors and these patients have a worse prognosis. In the first stage of project, the goal has been to identify cell lines that both express and do not express GA733. The remainder of the research will focus on the immune response with and without GA733 expression.
(faculty mentor: Emile R. Mohler MD [Medicine; Division of Cardiovascular Medicine])
Fellowship term, 6 months: October 2014 - January 2015; March - April 2015
Project: Investigation of Gender Differences in the Vascular Health Profile via Cytometric Fingerprinting
The pathophysiology of cardiovascular diseases differs between men and women, leading to significant variations in disease onset. As cardiovascular diseases begin with endothelial inflammation, the investigation of gender differences in vascular physiology may provide further insight into such variations in cardiovascular events. The vascular health profile (VHP) is a characterization of cardiovascular health status in specific patient populations. Two components of the VHP are endothelial progenitor cells (EPCs), markers of endothelial repair, and microparticles (MPs), markers of cellular damage. Though the relationship between gender and EPCs has been well studied, data is lacking in the realm of MPs. Cytometric fingerprinting (CF) is a method of analyzing flow cytometric data that is able to identify relationships in data sets that would normally be difficult to obtain via conventional methods. The aim of this study is to identify a VHP unique to women compared to age-similar men. Flow cytometric data from healthy men and women as well as men and women with known cardiovascular risk factors or known vascular disease will be studied. MPs and EPCs in these patients will be analyzed via CF.The application of CF in this study will not only determine the VHP of women, but it may also uncover a correlation between MPs and gender that has been difficult to discern using conventional methods. The identification a VHP signature in women may lead to better understanding of why differences exist in cardiovascular disease onset and events.
Tyler P. Johnson
(faculty mentor: Joseph Carver MD [Medicine: Cardiovascular Medicine])
Fellowship term, 6 months: October 15, 2008 – April 15, 2009
Project: Early detection and prediction of chemotherapy induced cardiac toxicity in breast cancer patients
Approximately 30% of breast cancers express the her-2 receptor and are consequently susceptible to treatment with tastuzumab (herceptin). Unfortunately, a significant proportion of women undergoing treatment with herceptin develop cardiotoxicity. Currently, doctors screen women undergoing herceptin therapy with serial echocardiograms. Unfortunately, by the time cardiotoxicity is noticeable by standard echocardiogram, the damage is often advanced and sometimes irreversible. We propose that one of the two methods we will study may provide a more sensitive method for earlier detection of herceptin-induced cardiotoxicity. These proposed methods are: tissue doppler imaging and measurement of biomarkers such BNP and nt-pro-BNP. We will follow 25 (out of a total cohort of 100) women receiving herceptin for breast cancer over one year, monitoring them with serial tissue-doppler imaging and nt-pro-BNP measurements, and correlating the findings from those exams with the incidence of cardiotoxicicty, hoping to find a more sensitive early marker for herceptin-induced cardiomyopathy.
Sandra L. Urtishak (faculty mentor: Stephen L. Eck MD PhD)
(portion also funded by the Benjamin and Mary Siddons Measey Foundation)
Fellowship term, 12 months: June 2001- June 2002
Project: Breast cancer research, the goal of which is to determine whether the expression of GA733-2 on breast cancer cells enhances their ability to evade the immune response to tumor antigens. About one third of patients with breast cancer express GA733 on their tumors and these patients have a worse prognosis. In the first stage of project, the goal has been to identify cell lines that both express and do not express GA733. The remainder of the research will focus on the immune response with and without GA733 expression.
Marin Jessica Feldman (faculty mentor: Anne Honebrink MD FACOG)
Fellowship term, 5 months: April - August 2001
Project: Development and implementation of the new women's MID LIFE PROGRAM in the Women and Children's Health Services, Women Division, associated with Pennsylvania Hospital. Involvement in recruiting low income patients (40-65 yrs old) from community; development, utilization, and evaluation of preventative health education materials, risk assessment tools, and an effective and efficient medical record format, all tailored to the needs of this population of women. To compare differences in health concerns, symptoms and pathology present in the lower income population when compared to the better described, higher income, mid-life population.