TAG: "Women’s health"

Unnecessary chemo? Many women don’t know risk of breast cancer recurrence

UCLA-led study finds that Latino women are twice as likely to have unnecessary treatment.

By Venetia Lai, UCLA

Although 90 percent of women with early-stage breast cancer said they were aware they took a genomic test that identified their level of risk for a recurrence of the disease, 1 in 5 didn’t know the results of that analysis, according to a new fact sheet by the UCLA Center for Health Policy Research.

The test, called gene expression profiling, or GEP, is used by physicians to help guide treatment decisions and can potentially help people avoid unnecessary chemotherapy. One of a number of emerging “precision medicine” genomic technologies, the GEP estimates the activity of specific genes in breast cancer cells, which can help predict whether there is a greater chance for breast cancer to return. Those with a high risk for cancer growth benefit by having chemotherapy as part of their treatment, the authors write, but chemo has no added value for those with a low risk.

The report is based on a national study of nearly 900 women younger than 65 who were diagnosed with early stage estrogen-receptor–positive, lymph-node–negative breast cancer. The Center for Health Policy Research collaborated with researchers from Harvard University’s Brigham and Women’s Hospital and Aetna.

The study also found that 15 percent of Hispanic women with a low risk for recurrence of breast cancer had unnecessary chemotherapy as part of their treatment, more than double the rate for the group as a whole (7 percent).

“No one should have to go through the stress and discomfort of chemo without understanding the personal risks and benefits,” said Ninez Ponce, the center’s associate director and senior author of the study. “At the very least, patients should know their options. Right now, some women may be making treatment decisions based on incomplete information.”

Although 9 in 10 women surveyed said they were aware that they had taken a test that would determine their risk profile, the percentage who knew about the test varied significantly by racial and ethnic group. Only 78 percent of Hispanic women and 85 percent of African-American women were aware of the test, compared with 94 percent of white women and 98 percent of Asian-American women.

Additionally, approximately 20 percent of those surveyed said they still did not know whether the test result indicated a high or low risk for recurrence of cancer — a significant information gap. Nearly 10 percent of Hispanics and 6 percent of African Americans said their doctors did not discuss the test or test results with them, compared with just 3 percent of whites and 2 percent of Asian Americans.

Among the high-risk patients, all of the Hispanic and Asian-American women and 81 percent of African-American and white women had chemotherapy, according to the report.

One in eight women will be diagnosed with breast cancer in her lifetime. The authors write that women who know they have a low risk for recurrence have the opportunity to avoid overtreatment and the side effects of chemotherapy, which include fatigue, hair loss, nausea, vomiting, diarrhea, bruising and bleeding.

The research was funded by Aetna.

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Ovarian cancer-specific markers set stage for early diagnosis

Some mRNA isoforms identified in study also could act as new therapeutic targets.

By Heather Buschman, UC San Diego

Ovarian cancer is notoriously difficult to diagnose and treat, making it an especially fatal disease. Researchers at the UC San Diego School of Medicine and Moores Cancer Center have now identified six mRNA isoforms (bits of genetic material) produced by ovarian cancer cells but not normal cells, opening up the possibility that they could be used to diagnose early-stage ovarian cancer. What’s more, several of the mRNA isoforms code for unique proteins that could be targeted with new therapeutics. The study is published the week of May 25 by the Proceedings of the National Academy of Sciences.

“We were inspired by many studies aimed at using DNA to detect cancer,” said first author Christian Barrett, Ph.D., bioinformatics expert and project scientist in the UC San Diego School of Medicine Institute for Genomic Medicine. “But we wondered if we could instead develop an ovarian cancer detection test based on tumor-specific mRNA that has disseminated from cancer cells to the cervix and can be collected during a routine Pap test.”

While DNA carries all the instructions necessary for life, its actual sequence contains much more than just the genes that code for proteins. In contrast, mRNAs are complementary copies of just the genes. They carry the recipe for every protein that the cell will produce from the nucleus to the cytoplasm, where cellular machinery can read the recipe and build the corresponding proteins. According to the authors of this study, the advantage of using cancer mRNA for diagnosis rather than DNA is sheer number — a cancer cell might harbor just one or a few copies of a DNA mutation, but mRNA variants can occur in hundreds to thousands of copies per cell.

To determine if mRNAs can be used to distinguish ovarian cancer cells from normal cells, the team developed a custom bioinformatics algorithm and used it to mine two large public databases of genetic information — The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) program, both sponsored by the National Institutes of Health. TCGA is a catalog of RNA and DNA from 500 tumors covering many cancer types, while GTEx is a database of RNA and DNA from normal tissue samples. From these, the researchers were able to analyze mRNA sequence data from 296 ovarian cancers and 1,839 normal tissue samples.

Using this bioinformatics approach, the researchers identified six mRNA isoform molecules that have the tumor specificity required for an early detection diagnostic of ovarian cancer. They also validated their digital results in the real world using RT-quantitative PCR, a gene amplifying technique, to detect the same ovarian cancer-specific mRNA molecules in lab-grown cells.

Beyond their diagnostic potential, some of the mRNA isoforms identified in this study could also act as new therapeutic targets. These mRNA isoforms are predicted to encode proteins with unique amino acid sequences, which might allow them to be specifically targeted with certain therapeutics, such as monoclonal antibodies or T-cell-based vaccines. What’s more, the ovarian cancer-specific mRNA isoforms themselves could also be targeted with new therapeutic drugs.

“Our experimental findings were made in a laboratory and were performed on ovarian cancer cells from cell lines,” said study co-author Cheryl Saenz, M.D., a clinical professor of reproductive medicine who specializes in treating gynecologic cancers. “Clinical trials will need to be conducted on women to confirm the presence of these markers in women that we know have cancer, as well as to document the absence of the markers in women that do not have ovarian cancer.”

The authors acknowledge a few limitations to their approach, including technical limitations in detecting mRNA isoforms, a shortage of normal ovarian and fallopian tube control samples and the possibility that tumor cells that disseminate to the cervix may not genetically act the same as the primary tumor.

Still, based on these promising initial results, the authors recommend expanding their process for identifying tumor-specific mRNA isoforms to the 30 additional tumor types for which sufficient amounts of RNA sequence already exist.

Iris and Matthew Strauss, San Diego-based philanthropists who helped fund the study, are also excited by the promise this finding holds. “We created the Iris and Matthew Strauss Center for Early Detection of Ovarian Cancer in memory of our daughter, Stefanie Dawn Strauss,” said Iris Lynn Strauss. “To further honor our daughter, we provided support for this study in an effort to help other women obtain early detection from this dreadful and deadly disease.”

Additional co-authors of this study include Christopher DeBoever, Kristen Jepsen, Dennis A. Carson, and Kelly A. Frazer, all of UC San Diego.

This research was also funded, in part, by the National Cancer Institute (grant P30CA023100) and Colleen’s Dream Foundation.

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Osteoporosis screening is too common for low-risk women

Screening also is too uncommon for higher-risk women, UC Davis researchers find.

By Karen Finney, UC Davis

Many of those who should get it, don’t. And many of those who shouldn’t, do. That’s the story of a common screening test for osteoporosis, according to new research from UC Davis Health System.

The study, published online today (May 19) in the Journal of General Internal Medicine, found that screening rates increased sharply among women at age 50, despite guidelines suggesting screening at age 65 unless risk factors are present. The presence of risk factors only had a modest influence on screening decisions.

Osteoporosis causes bone density to diminish and fracture risk to increase. Because gender and age are factors most associated with the disease, the U.S. Preventive Services Task Force recommends screening for women who are age 65 and older. Younger women with certain risk factors — such as a small body frame, a history of fractures or taking medication that thins the bones — should also be screened.

As part of a UC Davis research fellowship, physician Anna Lee Amarnath assessed the electronic health records of nearly 51,000 women who were between the ages of 40 and 85 and received health care in the Sacramento region. Her evaluation included osteoporosis risk factors and whether or not the women received a screening technique called dual-energy X-ray absorptiometry (DXA), which measures bone mineral density.

Over a seven-year period, more than 42 percent of eligible women between the ages of 65 and 74 years were not screened, nor were nearly 57 percent of those older than 75, despite the favorable cost-effectiveness of screening in these age groups. In turn, nearly 46 percent of low-risk women between the ages of 50 and 59 were screened, as were 59 percent of those aged 60 to 64 years without risk factors.

“DXA screening was underused in women at increased fracture risk, including women aged 65 years and older. Meanwhile, it was common among women at low fracture risk, such as younger women without osteoporosis risk factors,” Amarnath said, in summarizing the findings.

Amarnath and the study team believe they have identified a common problem, since health care providers can be uncertain or doubtful about current screening recommendations. Doctors tend to think about age-related bone loss when women enter menopause around age 50, triggering consideration of DXA without also considering overall facture risk.

Technology-based solutions could help, according to study senior author Joshua Fenton.

“Health systems should invest in developing electronic health records systems that prompt providers at the point-of-care when screening is needed and when it can be postponed,” said Fenton, a UC Davis associate professor of family and community medicine.

In addition to Amarnath and Fenton, study authors were Peter Franks, John Robbins and Guibo Xing of UC Davis. Their work was supported by grants from the National Institutes of Health to the UC Davis Clinical and Translational Science Center (UL1TR000002) and the Agency for Healthcare Research and Quality (T32HS022236).

A copy of “Underuse and Overuse of Osteoporosis Screening in a Regional Health System: a Retrospective Cohort Study” is available at http://link.springer.com/article/10.1007/s11606-015-3349-8.

More information about the Journal of General Internal Medicine, published by Springer, is at http://link.springer.com/journal/11606.

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Women with dense breasts may not need more screening

Study shows importance of assessing cancer risk when evaluating for additional screening.

By Elizabeth Fernandez, UC San Francisco

As the debate continues to swirl around the medical significance of dense breasts and whether extra screening should be done, a new study led by UC San Francisco has found that women with dense breasts may need only routine mammograms unless they are at high risk.

In their paper, the researchers said that five-year breast cancer risk is a critical component, and breast density should not be the sole factor in deciding whether supplemental screening is justified because not all women with dense breasts are at high risk of cancer.

Research has shown that women with dense breasts may be more likely to develop cancer.

The study was published today (May 18) in Annals of Internal Medicine.

The research focused on approximately 365,000 women ages 40 to 74 years old who had undergone a regular digital screening mammogram and had no history of breast implants or breast cancer.

Breast density is determined only by mammograms – having dense breasts makes it more difficult for X-rays to pass through the breast tissue and can mask tumors. Breasts are considered dense if the woman has a lot of fibrous or glandular tissue but not much fatty tissue, according to the American Cancer Society.

“Not all women with dense breasts have a high enough risk of cancer to justify supplemental screening,” said lead author, Karla Kerlikowske, M.D., a professor of medicine and epidemiology and biostatistics at UCSF and a primary care physician at the UCSF-affiliated San Francisco VA Medical Center. “We found that for the vast majority of women undergoing mammography – including those with dense breasts but low five-year breast cancer risk – the chance of developing breast cancer within 12 months of a normal mammogram was low. Women with extremely dense breasts and intermediate to high five-year breast cancer or heterogeneously dense breasts and high five-year breast cancer risk were at highest risk for developing breast cancer after a normal mammogram.”

“Our findings can help guide women and providers in discussing supplemental imaging and whether to consider extra testing,” said Kerlikowske. “This study provides a starting point to identify women who may have the most to gain from supplemental imaging or alternative imaging strategies.”

Currently, 22 states require that women be notified if they have dense breasts. The laws also encourage women to discuss supplemental screening with their medical providers. Similar legislation, which would set a minimum standard for notification and recommend that women discuss with their doctors whether further screening is necessary, is pending in Congress, which would have a considerable impact nationally, affecting tens of millions of women annually.

Digital mammography, used by the vast majority of mammography facilities, detects 81 to 87 percent of breast cancers among women 40 to 79 years old, reported the authors. But its ability to detect breast cancer in women with extremely dense breasts is lower.

As a result, supplemental imaging has been suggested for women with dense breasts to heighten their chances for tumor detection before women become symptomatic. While supplemental imaging for women with dense breasts can increase cancer detection, it also can lead to more false-positive results and more unnecessary biopsies.

In the prospective cohort study drawing upon statistics from 2002 to 2011, the researchers analyzed screening data collected by the Breast Cancer Surveillance Consortium (BCSC). Overall, nearly half the women in the study had dense breasts, and the proportion with heightened five-year risk was highest among those with extremely dense breasts.

“We found that rather than using only breast density to decide whether women with dense breasts should be considered for supplemental imaging, breast cancer risk should be taken into consideration,” said Kerlikowske, a member of the breast oncology program at the UCSF Helen Diller Family Comprehensive Cancer Center. “The BCSC risk calculator that includes age, family history of breast cancer, history of breast biopsy, breast density and race can be used to calculate five-year breast cancer risk. Determining breast cancer risk along with knowing a woman’s breast density will optimize the identification of women with high interval cancer rates who may benefit from supplemental screening.”

The authors noted that they were unable to assess the benefits of patient discussions with providers about supplemental breast imaging.

Co-authors are Weiwei Zhu, M.S., a biostatistician at the Group Health Cooperative in Seattle and the University of Washington School of Medicine; Anna N.A. Tosteson, Sc.D., a professor of medicine at The Dartmouth Institute; Brian L. Sprague, Ph.D., an assistant professor of surgery at the University of Vermont Cancer Center; Jeffrey A. Tice, M.D., a UCSF associate professor of medicine and member of the UCSF Helen Diller Family Comprehensive Cancer Center; Constance D. Lehman, M.D., Ph.D., a professor at the University of Washington School of Medicine and vice chair of radiology; and  Diana L. Miglioretti, Ph.D., a professor of biostatistics at UC Davis and co-leader of the Breast Cancer Surveillance Consortium.

The research was supported by the National Cancer Institute-funded Breast Cancer Surveillance Consortium (P01 CA154292, HHSN261201100031C and U54 CA163303). The collection of cancer data used in the study was supported in part by several state public health departments and cancer registries in the U.S.

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Maternal obesity compromises babies’ immune system at birth

Study investigates key innate and adaptive immune cells in umbilical cord blood samples.

Ilhem Messaoudi, UC Riverside

By Iqbal Pittalwala, UC Riverside

Almost 60 percent of women of childbearing age in the United States are overweight or obese. Obesity is a major public health issue, and has been linked to health problems like heart disease, cancer and hypertension. It can complicate pregnancy by increasing the mother’s risk of having gestational diabetes, preeclampsia, preterm birth or a baby with birth defects. Maternal obesity is also linked to several adverse health outcomes for the infant that can persist into adulthood, such as type-2 diabetes, heart disease and mortality.

But when exactly does the immune system of babies born to obese mothers get compromised? Very early in the baby’s life, according to a new study by a research team led by Ilhem Messaoudi of the University of California, Riverside.

The team analyzed umbilical cord blood samples of infants born to lean, overweight and obese mothers, and found that pre-pregnancy maternal weight has a significant impact on the immune system of the neonate, putting such children at risk for potential diseases such as heart disease and asthma.

The pilot study, performed on 39 mothers in Portland, Oregon, is published online in PubMed and will soon appear in the journal Pediatric Allergy and Immunology.

“A number of studies have linked maternal obesity – starting pregnancy with excess weight and gaining a lot of weight during pregnancy – to a higher incidence of cardiovascular disease and asthma in children,” said Messaoudi, an associate professor of biomedical sciences in the School of Medicine at UC Riverside. “Our study offers potential links between changes in the offspring’s immune system and the increased susceptibility and incidence of these diseases later in life.”

The researchers used established body mass index (BMI) categories to sort the mothers participating in the study, BMI being a number calculated from height and weight. A mother was considered overweight if her BMI was 25 to 29.9. A mother was considered obese if her BMI was 30 or higher.

The mothers were all non-smoking, had no diabetes and had an uncomplicated gestation at term. Each mother delivered just one baby. Eleven mothers were lean, 14 were overweight and 14 were obese. Thirty were white, three were Asian American/Pacific Islander, one was an American-Indian/Alaskan native and two were African American. The racial identity of three women was unknown.

“We found that very specific immune cells in circulation – monocytes and dendritic cells –isolated from babies born to moms with high BMI were unable to respond to bacterial antigens compared to babies born to lean moms,” Messaoudi said. “Such babies also showed a reduction in ‘CD4 T-cells.’ Both of these changes could result in compromised responses to infection and vaccination.”

Further, the researchers found that cells (eosinophils) that play a role in allergic response and asthma pathogenesis were significantly reduced in the umbilical cord blood of babies born to obese mothers. One potential explanation for these observations is that these cells have already moved into the lungs, which could explain the increased incidence of asthma observed later in life in children born to obese mothers.

The research is the first to show the link between maternal obesity during pregnancy and neonatal immune outcomes, and shows that changes in immunity are already detectable at birth and could persist for the lifetime of the child into adulthood.

“This could change how we respond to vaccination and how we respond to asthma-inducing environmental antigens,” Messaoudi said. “As we know, in the first two years of life, children typically receive plenty of vaccines. The questions that arise are: Are the responses to vaccines in infants born to obese moms also impaired in the first two years of life?  Should we change how often we vaccinate children born to obese moms? Should we change practices of how much and how often we vaccinate?”

Messaoudi sees the research paper as a launching point for further studies and a call to action.

“If you are thinking of becoming or are already pregnant, talk to your ob-gyn about weight management, weight gain and the ideal targets for weight gain,” she said. “When moms come in for prenatal visits, doctors tell them about smoking, recreational drug use and alcohol. But they should be talking also about weight and weight management. Obesity has serious repercussions for maternal health. It is associated with low fertility and success with pregnancy.  Rates of gestational diabetes, preeclampsia, placental abruption – all of these risks increase dramatically with weight gain and obesity. So it is important to talk to your doctor about ideal weight entering into pregnancy and throughout pregnancy.”

Messaoudi was joined in the study by Randall M. Wilson and Daniel R. Jeske at UCR; and Nicole E. Marshall, Jonathan Q. Purnell and Kent Thornburg at the Oregon Health & Science University, Portland, Oregon.

The research was supported by grants from the National Institutes of Health.

More information about obesity and pregnancy can be found here.

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Specific genetic mutation may increase risk for breast cancer

Study shows women with KRAS-variant also likelier to develop new cases of breast cancer.

Joanne Weidhaas, UCLA

By Reggie Kumar, UCLA

UCLA researchers have discovered that for women with a relatively common inherited genetic mutation, known as the KRAS-variant, an abrupt lowering of estrogen in the body may increase the risk for breast cancer and impact the biology of their breast cancer. Scientists also found that women with the KRAS-variant are more likely to develop a second primary breast cancer, independent of a first breast cancer.

The two-year study, led by Dr. Joanne Weidhaas, a professor of radiation oncology at the UCLA Jonsson Comprehensive Cancer Center and director of translational research at the David Geffen School of Medicine, analyzed data from more than 1,700 women with breast cancer who submitted DNA samples to be tested for the inherited KRAS-variant. The study also included a group of women with the KRAS-variant who were cancer-free, as well as biological models to scientifically confirm the clinical findings.

Weidhaas’ team found that acute estrogen withdrawal, as experienced after removal of the ovaries or when hormone replacement therapy was discontinued, and/or a low estrogen state were associated with breast cancer in women with the KRAS-variant. Acute estrogen withdrawal also triggered breast cancer formation in KRAS-variant biological models used in the study. In addition, up to 45 percent of breast cancer patients with the KRAS-variant eventually developed a second independent breast cancer — representing a 12-fold greater risk than women with breast cancer who did not have the KRAS-variant.

“Although we had evidence that the KRAS-variant was a stronger predictor of cancer risk for women than men, we did not previously have a scientific explanation for this observation,” Weidhaas said. “This study’s findings, showing that estrogen withdrawal can influence cancer risk for women with the KRAS-variant, begins to provide some answers.”

The findings are contrary to some past research suggesting that women on combination hormone replacement therapy are more likely to develop breast cancer, but the study is in agreement with follow-up studies which found that estrogen alone might actually protect women from breast cancer.

“The KRAS-variant may be a genetic difference that could actually help identify women who could benefit from continuing estrogen, or at a minimum, at least tapering it appropriately,” Weidhaas said. “We hope that there are real opportunities to personalize risk-reducing strategies for these women, through further defining the most protective estrogen management approaches, as well as by understanding the impact of different treatment alternatives at the time of a woman’s first breast cancer diagnosis.”

The study was published in the journal Cell Cycle.

The research, which was supported by the National Cancer Institute, was done in collaboration with MiraKind, a nonprofit organization.

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New clinical model proposed to improve primary care by addressing trauma

Model developed by UCSF clinical researchers and Positive Women’s Network-USA.

By Jeff Sheehy, UC San Francisco

Recognizing that patients’ experiences of childhood and adult trauma are common and have a direct impact on their health, UC San Francisco clinical researchers and Positive Women’s Network-USA have developed and are reporting a new primary care model.

“In our clinic where we treat women with HIV, we are able to deliver lifesaving anti-HIV medications, but we still lose patients far too often. Looking back over the last 10 years, only 16 percent of our patient deaths were due to HIV/AIDS. Most deaths were due to events such as depression, suicide, murder, drug overdoses and lung diseases that are directly related to adult and childhood experiences of trauma. We also realized that trauma is having a devastating impact on the health of a broad spectrum of the U.S. population, regardless of someone’s HIV status. We need a new model of care that addresses this key social determinate of health,” said the paper’s lead author, Edward L. Machtinger, M.D., director of the Women’s HIV Program at UCSF.

The paper presenting the new model will be published in Women’s Health Issues today (May 6).

Trauma can be defined as an event, series of events, or set of circumstances (e.g., childhood and adult physical, sexual and emotional abuse; neglect; loss; community violence; war; and structural violence such as racism) that is experienced by an individual as physically or emotionally harmful or threatening and that has lasting adverse effects.

Research demonstrates that trauma affects large numbers of U.S. men and women, regardless of HIV status. For example, the Centers for Disease Control and Prevention (CDC) estimates that 25 percent of women and 16 percent of men report childhood sexual abuse and that over one-third of women experience stalking, physical violence and/or rape from an intimate partner during their lifetime. The CDC also reports that childhood and adult trauma are strongly linked to the most common causes of adult illness, death and disability in the U.S.

“Understanding the link between trauma and health is an epiphany for clinicians. Many of us have spent years struggling to help our patients improve their health but did not realize that there was a missing ingredient in our model of care. Trauma affects health not only through psychological and behavioral factors, but also biologically, through neuroendocrine and inflammatory changes in response to trauma. By understanding the central role that trauma plays in illness, we can use this new model to re-engineer clinical practice around trauma-informed principles to better serve our patients and save lives,” said Machtinger.

The model represents a fundamental paradigm shift in how primary care is delivered. It is composed of four components – environment, screening, response and foundation.

“For patients who have experienced trauma, the health care environment can seem quite frightening. Some of our current healthcare practices may even trigger patients’ memories of past traumatic events. Because trauma is so common, we need to critically examine how the healthcare environment affects not only patients but also providers and staff. By adopting trauma-informed practices and policies, health care providers and staff promote increased safety, reliability, trust and empathy to create a more healing environment for everyone, said paper co-author Leigh Kimberg, M.D., UCSF professor of medicine at San Francisco Hospital and Trauma Center.

In the trauma-informed primary care model, the health care team routinely inquires about trauma, ideally in the context of an ongoing provider-patient relationship. Patients are educated about the ways that trauma affects health. Screening includes assessment for recent trauma including intimate partner violence, lifetime trauma, and/or the emotional and physical consequences of trauma such as depression, post-traumatic stress disorder (PTSD), substance use and chronic pain.

“Response to trauma disclosure should be empathetic and supportive, validate patients’ experiences, choices and autonomy, get them immediately to safety if needed, and build on their strengths. Providers need to make an effort to understand where a patient is coming from, why they engage in unhealthy behaviors and what they get out of those behaviors,” said paper co-author, Naina Khanna, executive director of Positive Women’s Network-USA.

To help patients heal from past trauma and prevent re-victimization, the researchers say clinics will need to develop onsite trauma specific programs and/or link to community organizations that provide services such as trauma-informed mental health, PTSD reduction and interventions to enhance resilience and coping mechanisms.

“In addition, it is absolutely critical to do lethality assessments of patients at risk of violence and ensure that they get to safe places,” said Khanna.

The foundation of this new primary care model begins with a reexamination of the healthcare setting, starting with the adoption of a core set of values. These values include safety, collaboration, trustworthiness, empowerment and respect for patient choice. In addition, the model includes partnership with community organizations and government agencies, genuine support for providers and staff, and ongoing monitoring and evaluation.

To develop this new paradigm, Machtinger along with other UCSF collaborators partnered with Naina Khanna and the Positive Women’s Network-USA to convene a national working group of leading policy makers, trauma experts and advocates from the government, military, academia, and community organizations. The group, the National Strategy Group to Develop a Model of Trauma-informed Primary Care for Women Living with HIV, identified evidence-based building blocks to create the model presented in the paper

Paper co-authors include Carol Dawson-Rose, R.N., Ph.D., F.A.A.N., professor and Yvette Cuca, Ph.D., M.P.H., specialist from the UCSF School of Nursing.

This work was funded by the Mose J. Firestone Administrative Trust and the California Wellness Foundation.

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Related link:
UC Irvine study links acute stress response to disaster with prior exposure to traumatic events

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Women’s health: A critical update across the lifespan

UCTV explores women’s health issues.

Women’s health needs are unique and cover a wide spectrum over the course of a woman’s life. This UCTV series explores a broad range of topics including stress management, sexual health, exercise and the athlete in each of us, osteoporosis, breast cancer in the Bay Area and fibroid treatment options. Presented by UC San Francisco faculty from the Women’s Health Center, Osher Center for Integrative Medicine and the Department of Orthopaedic Surgery (all of which are recognized internationally for their expertise in providing comprehensive care), these programs address both comprehensive and integrative approaches in women’s health.

Programs include:

Not All Roads Point to Hysterectomy: Treatment Options for Fibroids
First air date: April 27

Breast Cancer in Marin: The Myths, The Facts & The Science
First air date: April 20

Outsmarting Stress One Breath at a Time
First air date: April 13

Breast Cancer Screening and Prevention: A Clinician’s Perspective
First air date: April 6

What’s New in Management of the Menopause?
First air date: March 30

Every Patient is an Athlete: Using Exercise as Medicine
First air date: March 23

View more on UCTV

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In utero exposure to extreme morning sickness may result in neurological deficit

UCLA study suggests nutritional deficiency early in pregnancy may play a role.

By Kim Irwin, UCLA

Women who experience extreme morning sickness during pregnancy are three times more likely to have children with developmental deficits — including attention disorders and language and speech delays — than women who have “normal” nausea and vomiting, a UCLA study found.

The research was the first to look specifically at the relationship between in utero exposure to extreme morning sickness, also known as hyperemesis gravidarum or HG, and childhood neurologic developmental outcomes, said Marlena Fejzo, the study’s first author, and an associate researcher at the David Geffen School of Medicine at UCLA.

Fejzo said the correlation was especially apparent in women whose HG symptoms began very early, prior to five weeks gestation.

“These findings show that it is vital to take HG seriously so these pregnant women can get nutritional support right away,” Fejzo said. “An encouraging finding is that we did not find any association with medications to treat this disorder and neurodevelopmental delays, so I speculate that the neurodevelopmental outcomes are more likely caused by nutrient deficiency early in pregnancy rather than medication.”

The study was published online by the European Journal of Obstetrics and Gynecology and Reproductive Biology.

HG is the condition that the former Kate Middleton, Duchess of Cambridge, has experienced during both of her pregnancies. Its cause is unknown and the symptoms are intense — including continuous nausea and vomiting so violent that it can cause detached retinas, blown eardrums, cracked ribs and torn esophagi, Fejzo said. The symptoms can last for a month or two or for the entire pregnancy.

This study looked at 312 children born between 2007 and 2011 to 203 mothers with extreme morning sickness, and 169 children born to 89 mothers who did not have the disorder. Children born to women with HG had attention and sensory disorders, and learning, speech and language delays. Fejzo said the researchers do not yet know the mechanism that causes abnormal neurologic development in children of women with hyperemesis gravidarum.

The women in the study who had HG experienced nausea and vomiting so severe that they lost at least five pounds and needed intravenous fluids. Children exposed in utero to HG were 3.28 times more likely than the others to have neurodevelopmental delays, Fejzo said.

“There is an urgent need to address whether aggressive treatment that includes vitamin and nutrient supplementation in women with early symptoms of severe nausea and vomiting decreases that risk of neurodevelopmental delay,” she said.

Fejzo said HG is diagnosed in up to 2 percent of pregnant women worldwide, and it accounts for more than 285,000 hospitalizations in the U.S. every year.

Previous studies have shown that HG is associated with low birth weight babies, small size for gestational age and preterm births. Fejzo showed previously that children born to mothers who had extreme morning sickness were 3.6 times more likely to have behavioral or emotional disorders as adults.

Fejzo and her team are investigating the genetic basis of HG, and they hope to determine whether earlier treatment in women with symptoms limits or prevents the adverse outcomes identified in the study.

“A significant increase in neurodevelopmental and behavioral disorders in children exposed to
HG in utero was demonstrated which suggests HG may be linked to life-long effects on the exposed fetus,” the study states. “The cause for this is unknown, but may be due to maternal stress, abnormal hormone levels during fetal development and/or maternal-newborn bonding after birth, or malnutrition and vitamin deficiency.”

The study was conducted at UCLA and the University of Southern California, and it was funded in part by the Hyperemesis Education and Research Foundation.

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Simple dietary change may have big impact on public health

Overnight fasting may reduce breast cancer risk in women.

By Yadira Galindo, UC San Diego

A decrease in the amount of time spent eating and an increase in overnight fasting reduces glucose levels and may reduce the risk of breast cancer among women, report UC San Diego School of Medicine researchers in the journal Cancer Epidemiology, Biomarkers & Prevention.

The findings were presented at the American Association of Cancer Research’s annual meeting in Philadelphia.

“Increasing the duration of overnight fasting could be a novel strategy to reduce the risk of developing breast cancer,” said Catherine Marinac, UC San Diego doctoral candidate and first author on the paper. “This is a simple dietary change that we believe most women can understand and adopt. It may have a big impact on public health without requiring complicated counting of calories or nutrients.”

Women who fasted for longer periods of time overnight had significantly better control over blood glucose concentrations. The data show that each three-hour increase in nighttime fasting was associated with a 4 percent lower postprandial glucose level, regardless of how much women ate.

“The dietary advice for cancer prevention usually focuses on limiting consumption of red meat, alcohol and refined grains while increasing plant-based foods,” said co-author Ruth Patterson, Ph.D., UC San Diego Moores Cancer Center associate director for population sciences and program leader of the cancer prevention program. “New evidence suggests that when and how often people eat can also play a role in cancer risk.”

Women in the study reported eating five times per day with a mean nighttime fasting of 12 hours. Those who reported longer fast durations also indicated they consumed fewer calories per day, ate fewer calories after 10 p.m. and had fewer eating episodes.

Researchers recommend large-scale clinical trials to confirm that nighttime fasting results in favorable changes to biomarkers of glycemic control and breast cancer risk.

Co-authors include Loki Natarajan, Dorothy Sears and Sheri Hartman of UC San Diego; and Linda Gallo and Elva Arredondo of San Diego State University.

Funding for this research came, in part, from the National Cancer Institute-sponsored Ruth L. Kirschstein National Research Service Award (1F31CA183125-01A1), the NCI Centers for Transdisciplinary Research on Energetics and Cancer (1U54CA155435-01) and philanthropic support from Ms. Carol Vassiliadis and family.

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A mother’s genes can influence the bacteria in her baby’s gut

Research may have applications for protecting preemies from range of intestinal diseases.

Zachary Lewis (left) and David Mills, UC Davis

By Phyllis Brown, UC Davis

Researchers at UC Davis have found that a gene, which is not active in some mothers, produces a breast milk sugar that influences the development of the community of gut bacteria in their infants. The sugars produced by these mothers, called “secretors,” are not digested by the infant, but instead nourish specific bacteria that colonize their babies’ guts soon after birth.

Mothers known as “non-secretors” have a non-functional fucosyltransferase 2 (FUT2) gene, which alters the composition of their breast milk sugars and changes how the microbial community, or microbiota, of their infants’ guts develop.

The research may have applications in a clinical setting for protecting premature infants from a range of intestinal diseases including necrotizing enterocolitis (NEC), a condition that is the second most common cause of death among premature infants in the United States.

The researchers emphasized that the finding does not suggest that breast milk from mothers without an active copy of the gene is less nourishing or healthy. Rather, it conveys the subtle and elegant choreography of one part of the human microbiome: The relationships between the mothers’ genetics, the composition of her breast milk and the development of their infants’ gut microbiota. It also reveals clues for enriching desirable bacteria in populations at risk of intestinal diseases — such as preemies.

“In no way is the nonsecretor mother’s milk less healthy, and their babies are at no greater risk,” said David Mills, Peter J. Shields Endowed Chair in Dairy Food Science at UC Davis and senior study author. “What this work does show us is that the mother’s genotype matters, and that it influences the breast milk, which clearly drives the establishment of microbes in the intestines of their babies.”

The research examining the differences in infant gut microbial populations arising from differences in human milk oligosaccharides (sugars), “Maternal Fucosyltransferase 2 Status Affects the Gut Bifidobacterial Communities of Breastfed Infants,” is published online today (April 9) in the journal Microbiome, a BioMedCentral journal.

Varieties of Bifidobacterium inhabit the gastrointestinal tracts and mouths of mammals and are one of the major genera of bacteria that make up the microbial community of the infant colon. The relationship between human genetics, breast milk and Bifidobacterium appears to have developed throughout mammalian evolution.

Development of a healthy gut microbiota can have a lifelong effect on health, and early intervention in the establishment of that microbiota could have lifelong positive effects: The early establishment of bifidobacteria has been shown to be associated with improved immune response to vaccines, development of the infants’ immature immune system, and protection against pathogens.

Bifidobacterium are known to consume the 2′-fucosylated glycans (sugars) found in the breast milk of women with the fucosyltransferase 2 mammary gene. The study found that, on average, Bifidobacterium were established earlier and more frequently in infants fed by women with an active copy of the gene, the secretors, than without one, the non-secretors.

The authors found that the intestinal tracts of infants fed by non-secretor mothers are delayed in establishing a bifidobacteria-dominated microbiota. The delay, the authors said, may be due to difficulties in the infant acquiring a species of bifidobacteria that is geared toward consuming the specific milk sugar delivered by the mother.

The research was conducted using milk samples from 44 mothers in the UC Davis Foods for Health Institute Lactation Study and fecal samples from their infants at four different time points. The researchers determined the secretor status of the mothers: 12 were non-secretor and 32 were secretor mothers. They also measured the amount and type of breast milk sugars and the amount of lactate (a beneficial molecule produced by bifidobacteria) in the infant’s feces.

The researchers determined that more infants fed by secretor mothers had high levels of bifidobacteria — 60 percent of infants versus 37.5 percent at day 6 and 80 percent versus 50 percent at day 120 –- and that infants who had more bifidobacteria had lower amounts of milk sugars left over and higher amounts of lactate in their feces.

One question that remains is whether this pattern holds true in infants living in other places.

“We are beginning to observe that infants from different parts of the world have different patterns of colonization by microbes,” said lead study author Zachary T. Lewis, a postdoctoral fellow.

“The types and levels of bacteria encountered by infants in developing countries is different from the types and levels of bacteria encountered by the babies in our UC Davis cohort, and that might account for some of the differences,” he said.

Maternal secretor status is likely only one of the many factors that influence the infant gut microbiota, Lewis said. The researchers will explore this question further in future studies.

The researchers said that understanding the mechanism behind the observed secretor/non-secretor differences may prove critical to compensating for it in situations where the infants are vulnerable, such as by providing carefully chosen pre- or probiotics. For example, prebiotics and probiotics frequently are given to premature infants  to protect them against NEC, which causes portions of the bowel to necrotize, or die.

“This work significantly advances our efforts to decipher how human milk amazingly orchestrates colonization of the infant gut by helpful bacteria, which then protects and guides intestinal development in the early stages of life. Understanding this incredible sequence of events will provide examples for how to repair this process where it has been disrupted, such as in premature infants or colicky babies,” Mills said.

Other study authors include Jennifer T. Smilowitz, Evan Parker, Danielle G. Lemay and Carlito Lebrilla, all of UC Davis; Sarah M. Totten of UC Davis and Stanford University: Mina Popovic of University of Moedna and Reggio Emilia, Italy; and Maxwell Van Tassel Michael J. Miller and Young-Su Jin of the University of Illinois Urbana-Champagne.

The research was supported by the University of California Discovery Grant Program, the UC Davis Research Investments in the Sciences and Engineering (RISE) Program, the California Dairy Research Foundation, the Bill and Melinda Gates Foundation, National Institutes of Health awards R01HD059127, R01HD065122, 8R01HD061923, R21AT006180, R01AT007079 and the Peter J. Shields Endowed Chair in Dairy Food Science.

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Women, regardless of backgrounds, seek help for ‘got to go’ feeling

Study shows importance of providers discussing urinary incontinence with patients.

By Phyllis Brown, UC Davis

Regardless of their racial, ethnic, educational or socioeconomic background, women seek help for a frustrating — and ubiquitous — feature of becoming “a woman of a certain age:” the need be close to the women’s room.

Those are the findings of a large study by UC Davis of urinary incontinence in menopausal women, based on data from the Study of Women’s Health Across the Nation (SWAN), a nine-year investigation of diverse menopausal women from six sites across the United States. The study is published online today (April 7) in Obstetrics and Gynecology.

The study, of more than 3,302 study participants from such diverse locations as Oakland, Pittsburgh and Detroit, found that most women, regardless of their backgrounds, talked with their health care provider about urinary urgency incontinence — leaking with the immediate need to reach the restroom — or stress incontinence — leaking with “coughing, laughing or sneezing” — over the nine years they were followed.

All of the participants were transitioning through menopause. Some 68 percent of women reported monthly or more frequent urinary incontinence, either leakage with urgency or with coughing, sneezing or exercising.

Earlier studies have suggested that African-American women and women of lower socioeconomic backgrounds were less likely to seek treatment.

“Our study results do not support previous findings that black women or women with lower socioeconomic circumstances are either less likely to seek care only at a higher level of bother of urinary incontinence frequency than white women or women of higher socioeconomic resources,” said Elaine Waetjen, UC Davis professor in the Department of Obstetrics and Gynecology and lead study author.

Rather, Waetjen said, the strongest associations with seeking care were worsening and persistence of symptoms. That is important, Waetjen said, because urinary incontinence is readily treatable.

“By discussing their urinary incontinence with a health care provider, women can learn about the variety of treatment options available to them, from behavioral changes to medications and surgery,” she said.

Other study authors include Guibo Xing, Joy Melnikow and Ellen Gold, all of UC Davis and Wesley O. Johnson of UC Irvine.

The study was funded by the National Institutes of Health, including the Institute of Diabetes and Digestive and Kidney Disease, Office of Research on Women’s Health, Institute on Aging, and Institute of Nursing Research, including grants number DK092864, U01NR004061, U01AG012505, U012535, U01AG02531, U01AG02531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495.

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