Body

December 16, 2019 -- A new study from the University of California San Francisco (UCSF) and Columbia University Mailman School of Public Health challenges assumptions that women with the highest preference against pregnancy use more effective contraceptive methods and that women who might welcome pregnancy do not use contraception. Overall, women with a stronger preference to avoid pregnancy were far more likely to use any contraceptive method. Still, over half of the women studied who reported low preference to avoid pregnancy nevertheless used a contraceptive method. The findings are published in the journal Contraception.

Using the 14-item Desire to Avoid Pregnancy (DAP) scale, a newly developed tool by study co-author Dr. Corinne Rocca (UCSF), researchers measured the ranges of women's preferences regarding a potential future pregnancy. The scale, which captures feelings about both a potential pregnancy (within three months) and child (within a year), and allows for uncertainty and ambiguity in preferences, covers three domains: desires, emotions, and perceived consequences. This is the first study to test the rigorously developed and evaluated measure of pregnancy preferences in an ethnically and geographically diverse sample of women.

The study showed that the odds of contraceptive use increased 64 percent for each increasing point on the DAP scale. Among women who had sex in the last 30 days, 21 percent reported not using any contraceptive method, while 17 percent used IUDs or implants, 31 percent used Short Acting Reversible Contraception including the Pill, and 20 percent used condoms. About 13 percent of women with a high preference to avoid pregnancy reported no use of contraception. Pregnancy preferences were not associated with the types of contraceptive methods women used.

"We found that women across all ranges of desire to avoid pregnancy used a diversity of contraceptive methods" said Goleen Samari, PhD, Columbia Mailman School assistant professor of population and family health. "The finding tells us that women use contraception for all sorts of reasons, and contraceptive counseling shouldn't be guided by pregnancy preferences alone. Even for women with strong preferences to avoid pregnancy, overemphasizing effectiveness in contraceptive counseling may not lead to contraceptive uptake and satisfaction if other contraceptive features are not addressed."

Little is known about how women manage emotional distress during high-risk pregnancies, but Rutgers researchers learned that without psychosocial support, women struggle with fears and tears while feeling isolated and worried.

The study appears in the journal Psychology of Women Quarterly.

About 15 percent of pregnancies worldwide are high-risk, making premature delivery, low infant birth weight and other poor outcomes more likely. In the United States, 10 percent of pregnant women require hospitalization because they have hyperemesis gravidarum, pre-eclampsia, kidney infections, gestational diabetes or are at risk for imminent delivery, among other conditions.

Rutgers researchers say keeping anxiety and stress to a minimum during pregnancy is important but is especially critical for high-risk pregnancies where it is believed to be a factor in premature birth.

The researchers interviewed 16 women hospitalized during high-risk pregnancies and found that trying to manage their emotions by themselves added an additional burden to an already stressful experience. The in-depth interviews are designed to elicit rich interpersonal data. A sample of 16 is typical of the phenomenological research method they used.

The study's participants included heterosexual women ages 21 to 42 from diverse racial and ethnic groups. The researchers analyzed how they tried to manage their emotions, what rationales they used and how they interpreted advice from health care providers and family members.

"We noticed a common theme among the women we spoke to -- they were trying to force themselves to feel certain emotions like "thinking positive" while trying to perform mind tricks to get themselves there," said Judith McCoyd, lead author and associate professor at the School of Social Work. "More surprisingly, the women informed us that they did not receive explicit advice on how to cope, think positive, or calm down."

The researchers suggest that professional intervention using visualization, mindfulness, cognitive-behavioral work and/or Acceptance Commitment Therapy, a type of psychotherapy that helps you accept difficulties, may all be useful interventions to try with this vulnerable group.

Aside from anxiety or depressive symptoms, the women experienced an inherent dilemma -- needing to choose between two options and feeling that neither is good. This could include believing they must think positively to enhance fetal health despite their anxiety, sadness and their fears that this could harm the fetus; feeling responsible for housework yet being told not to do it; and needing medical treatments they feared would harm their fetus.

The women also stifled their emotional expression with their medical providers to enact being a good "mother" and to be a "good patient." To try to manage their emotions, the women expended tremendous energy, leaving themselves depleted and less able to cope.

The researchers said women considering pregnancy should think about what emotional support they might receive if they have a high-risk pregnancy. Women can speak with their obstetrician-gynecologist about receiving consistent medical and psychosocial care, and ask for a health navigator, perinatal social worker or an integrated behavioral health specialist if they require hospitalization, McCoyd said.

In 2019, nearly 2 million Americans will receive a cancer diagnosis and more than 600,000 will die of cancer. Cancer diagnoses and deaths are disproportionately high among people who live in rural counties, have a low socioeconomic status, and are members of underserved racial and ethnic groups.

The Cancer Prevention and Control Research Network (CPCRN), a collaborative national network of academic centers engaged in cancer research, has produced a supplemental issue of Preventive Medicine with 12 articles that examine stakeholder-engaged implementation science and population approaches to improve equity in cancer prevention and control. The research findings reported in the supplement investigate factors at the level of the patient, community, health care provider, health care system, and the wider socio-political context.

The supplemental issue represents a diversity of collaborative research products made possible by the research and scientific networking infrastructure enabled by CPCRN, which has been funded by the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), since 2002. CPCRN is a thematic network of the CDC’s Prevention Research Centers (PRCs) in which multiple centers collaborate on research related to the dissemination and implementation of evidence-based approaches to reduce the burden of cancer, especially in disproportionately affected populations. The University of North Carolina at Chapel Hill’s PRC, the Center for Health Promotion and Disease Prevention, hosts the network’s coordinating center.

For the 2014-2019 funding cycle, the CPCRN member centers included cancer investigators at Case Western Reserve University, Oregon Health & Science University, University of Iowa, University of Kentucky, University of North Carolina at Chapel Hill, University of Pennsylvania, University of South Carolina, and University of Washington.

“In this supplemental issue, CPCRN researchers take on two tasks that are essential to reducing disparities in cancer outcomes,” said Jennifer Leeman, a guest editor on the issue and principal investigator of the University of North Carolina CPCRN collaborating center. “First, they examine the multilevel factors that are contributing to cancer disparities, and, second, they identify strategies to speed the implementation of cancer screening interventions across the different levels where factors occur. Taken together, these articles report findings that will aid public health practitioners, policymakers, and others as they design and implement interventions to reduce the burden of cancer in underserved communities.”

The 12 articles included in the supplement illustrate the types of research that are possible within a network of geographically dispersed centers all thematically linked by a common cause — reducing cancer burden in diverse populations. The supplement begins with an article authored by CPCRN federal agency partners at the CDC and NCI that provides an overview of the network and its purpose and history. The supplement ends with an article authored by several network leaders about the potential impact of CPCRN on cancer control and prevention.

In four articles, researchers report findings from their cross-center research on factors that contribute to rural disparities in cancer outcomes and present a conceptual framework to guide future research to reduce rural disparities. In five articles, CPCRN researchers report findings related to interventions to increase colorectal cancer screening rates in underserved populations. In one of these articles, researchers report on a national survey of patient navigators and the barriers they encounter to enabling populations to receive timely colorectal, breast, and cervical cancer screening.

CPCRN facilitates and coordinates timely, high-impact research across the eight collaborating centers. Each center conducts research in its own community and region, as well as collaborates with other centers to conduct multi-state research studies in topic-oriented workgroups. The articles in this issue report on several workgroup initiatives and findings completed during the latest round of network funding between 2014 and 2019.

“Because it leverages geographically dispersed, interdisciplinary teams of investigators, CPCRN is in a unique position to study the individual, geographic, policy, and other multilevel factors that increase the risk for poor cancer outcomes,” said Stephanie Wheeler, the principal investigator for the CPCRN Coordinating Center. “The articles in this supplement highlight the diversity and strength of scientific ideas and leadership that a robust thematic research network like CPCRN can produce, where the network’s contribution to science and practice is clearly greater than the sum of its parts.”

The supplement has been published open access by Elsevier, and the full issue is available for download. Articles included in the supplement can also be individually downloaded by following the links below:

The cancer prevention and control research network: Accelerating the implementation of evidence-based cancer prevention and control interventions (Guest Editor Commentary).
Leeman J, Glanz K, Hannon P, Shannon J.

The Cancer Prevention and Control Research Network (CPCRN): Advancing public health and implementation science (Funder Commentary).
White A, Sabatino SA, Vinson C, Chambers D, White MC.

Multilevel analysis in rural cancer control: A conceptual framework and methodological implications.
Zahnd WE, McLafferty SL, Eberth JM.

Financial Hardship among Rural Cancer Survivors: An Analysis of the Medical Expenditure Panel Survey.
Odahowski CL, Zahnd WE, Zgodic A, Edward JS, Hill LN, Davis MM, Perry CK, Shannon J, Wheeler SB, Vanderpool RC, Eberth JM.

Mortality-to-incidence ratios by US Congressional District: Implications for epidemiologic, dissemination and implementation research, and public health policy.
Eberth JM, Zahnd WE, Adams SA, Friedman DB, Wheeler SB, Hébert JR.

Challenges of using nationally representative, population-based surveys to assess rural cancer disparities.
Zahnd WE, Askelson N, Vanderpool RC, Stradtman L, Edward J, Farris PE, Petermann V, Eberth JM.

Estimating the impact of insurance expansion on colorectal cancer and related costs in North Carolina: A population-level simulation analysis.
Lich KH, O’Leary MC, Nambiar S, Townsley RM, Mayorga ME, Hicklin K, Frerichs L, Shafer PR, Davis MM, Wheeler SB.

Patient navigator reported patient barriers and delivered activities in two large federally-funded cancer screening programs.
Barrington WE, DeGroff A, Melillo S, Vu T, Cole A, Escoffery C, Askelson N, Seegmiller L, Gonzalez SK, Hannon P.

Mailed FIT (fecal immunochemical test), navigation or patient reminders? Using microsimulation to inform selection of interventions to increase colorectal cancer screening in Medicaid enrollees.
Davis MM, Nambiar S, Mayorga ME, Sullivan E, Hicklin K, O’Leary MC, Dillon K, Hassmiller Lich K, Gu Y, Lind BK, Wheeler SB.

Understanding quality improvement collaboratives through an implementation science lens.
Rohweder C, Wangen M, Black M, Dolinger H, Wolf M, O’Reilly C, Brandt H, Leeman J.

Advancing the use of organization theory in implementation science.
Leeman J, Baquero B, Bender M, Choy-Brown M, Ko LK, Nilsen P, Wangen M, Birken SA.

Putting Evidence Academies into action: Prostate cancer, nutrition, and tobacco control science.
Glanz K, Green S, Avelis J, Melvin CL.

An application of the Science Impact Framework to the Cancer Prevention and Control Research Network from 2014-2018.

Ko LK, Jang SH, Friedman DB, Glanz K, Leeman J, Hannon PA, Shannon J, Cole A, Williams R, Vu T.

These publications are a product of the Prevention Research Centers Program at the Centers for Disease Control and Prevention. The findings and conclusions in these publications are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the National Institute of Health. The Cancer Prevention and Control Research Network is funded through Cooperative Agreements [3 U48 DP005013-01S1A3, 3 U48 DP005000-01S2, 3 U48 DP005053-01S1, 3 U48 DP005017-01S8, 3 U48 DP005006-01S3, 3 U48 DP005030-01S5, 3 U48 DP005021-01S4, 3 U48 DP005014-01S2] from the Centers for Disease Control and Prevention and National Cancer Institute.

Journal

Preventive Medicine

Ann Arbor, December 16, 2019 - More teens who vape are using addictive or mind-altering substances than previously believed, according to a new study in the American Journal of Preventive Medicine, published by Elsevier. The data paint a different picture than previous research because of the significantly higher proportion (75 percent) of teens who vape using nicotine, marijuana, or multiple substances and not just flavoring. These findings add to growing public health concerns about youth vaping.

"Our study provided a more nuanced view of youth e-cigarette use behaviors than earlier studies. We found that youth were more likely to report vaping nicotine and marijuana than 'just flavoring' only, and that cigarette smoking intensity was associated with an increasing proportion of students reporting vaping nicotine only," explained co-investigator Hongying Dai, PhD, Associate Professor, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA.

This study examined patterns of youth vaping nicotine, marijuana, and just flavoring in the past 30 days by analyzing data from the 2017 Monitoring the Future (MTF) cross-sectional study. Of the 14,560 teens participating in that study, 12 percent reported vaping within the prior 30 days, with 7.4 percent using nicotine and 3.6 percent, marijuana. Of that group, only 24.9 percent reported vaping just flavoring only, while a majority (75.1 percent) reported vaping nicotine, marijuana, or multiple substances.

Current cigarette smoking intensity was associated with an increased risk of reporting vaping all three substances. Compared with 8th graders, more 10th and 12th graders reported vaping nicotine, marijuana, and just flavoring during the study period. Female students were also less likely to report vaping these three substances than male students. Fewer non-Hispanic blacks reported vaping nicotine and just flavoring than non-Hispanic whites. Hispanics were also less likely to report vaping nicotine.

The prevalence of e-cigarette use among US youth increased dramatically during 2017-2019, partly due to the rising popularity of products with nicotine salt and pod-based products like JUUL, and a large number of flavors appealing to adolescents. The nationwide increases in use led the US Surgeon General to issue an advisory about the epidemic in 2018, but much more needs to be done to reverse the upward trend. Due to the recent spate of vaping-related lung injuries, calls for restrictions on flavored vaping products and e-cigarette use have become more urgent. Identifying substances vaped by youth is critical to formulating, implementing, and evaluating population-wide strategies and interventions to curb youth use of these products.

"Continuous surveillance of youth behaviors and strategies and interventions to reduce youth e-cigarette use are needed. The truth is that no form of tobacco is safe," added co-investigator Mohammad Siahpush, PhD, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA.

Every cell contains a vast number of proteins, each of which has a specific function, for example as a receptor for another molecule or an enzyme that catalyses chemical reactions. Disorders of such mechanisms can seriously affect a cell and cause diseases such as cancer, in which the sick cell functions in a fundamentally different way to a healthy cell. It is therefore very common for a drug to have a protein as its target, one that the substance either inhibits or stimulates the production or uptake of. At the same time, there are a great many approved drugs with a tried and tested effect on certain diseases but without a known protein target. For such substances, it is said that the mechanism of action is either wholly or partly unknown.

Scientists are therefore interested in developing a relatively straightforward method able to identify which proteins are affected by a certain drug. Some such methods are already available, but all have their shortcomings. Researchers at Karolinska Institutet have now made use of these methods to create a new tool that gives more reliable and precise results.

The researchers developed their method by experimenting on lung cancer cells treated with 56 different kinds of drug. For each of the drugs they first worked out the dose that kills half of the cells after 48 hours (LC50) and then used this dose for all the drugs. Once half of the cells had died, they examined each cell's proteome (i.e. which proteins are present and their abundances) to ascertain which proteins the drugs targeted. In further experiments, they tested the drugs on other cells from breast and intestinal tumours, and drew conclusions about the extent to which the drugs are specific or general in their targeting of cancer cells.

The results of these experiments are described in the searchable database that the researchers have now created (see link below), while the method itself is detailed in the article published in Nature Communications. The idea is for other researchers to be able to perform similar experiments with other drugs using the same model, and to thus expand the database with more target proteins for more substances.

"We find that the cells are killed in different ways by different drugs," says Roman Zubarev, professor of medical proteomics at Karolinska Institutet. "Not so long ago we used to think that cells could only die in three ways - necrosis, apoptosis or autophagy - but now we've observed at least thirteen different ways in which cells can die. This method can help to speed up certain parts of the process of new drug development or improve our understanding of existing drugs."

A new approach to food systems is needed to help low- and middle-income countries reduce both obesity and undernutrition, two issues that have become increasingly connected, according to the first paper in a four-paper report published in The Lancet.

"We are facing a new nutrition reality where major food system changes have led the poorest countries to have high levels of overweight and obesity along with undernutrition," says Barry M. Popkin, lead author of the first paper and W.R. Kenan Jr. Distinguished Professor of Nutrition at the University of North Carolina at Chapel Hill Gillings School of Global Public Health. "Our research shows that overweight and obesity levels of at least 20% among adults are found in all low-income countries. Furthermore, the double burden of high levels of both undernutrition and overweight occurs primarily in the lowest-income countries -- a reality that is driven by the modern food system. This system has a global reach and is preventing low- and even moderate-income countries and households from consuming safe, affordable and healthy diets in a sustainable way."

Globally, estimates suggest that almost 2.3 billion children and adults are overweight, and more than 150 million children are stunted. In low- and middle-income countries, however, these emerging issues overlap in individuals, families and communities. The first paper explores the trends behind this intersection, known as the double burden of malnutrition, as well as the societal and food system changes that may be causing it, its biological explanation and effects, and policy measures that may help address malnutrition in all its forms.

Popkin and his co-authors used survey data from low- and middle-income countries in the 1990s and 2010s to estimate which countries faced a double burden of malnutrition, meaning that, in the population, more than 15% of people had wasting, more than 30% were stunted, more than 20% of women had thinness and more than 20% of people were overweight.

Results showed that more than a third of low- and middle-income countries had overlapping forms of malnutrition, 45 of 123 countries in the 1990s and 48 of 126 countries in the 2010s. The problem was particularly common in sub-Saharan Africa, south Asia, and east Asia and the Pacific, where 29, seven and nine countries were affected, respectively.

In the 2010s, 14 countries with some of the lowest incomes in the world had newly developed a double burden of malnutrition compared with the 1990s. However, fewer low- and middle-income countries with the highest incomes, relative to others in that category, were affected. The authors say this reflects the increasing prevalence of people being overweight in the poorest countries, even as segments of the population still face stunting, wasting and thinness.

"Emerging malnutrition issues are a stark indicator of the people who are not protected from the factors that drive poor diets," Popkin says. "The poorest low- and middle-income countries are seeing a rapid transformation in the way people eat, drink and move at work, home, in transport and in leisure. The new nutrition reality is driven by changes to the food system, which have increased the global availability of ultra-processed foods that are linked to weight gain while also adversely affecting infant and preschooler diets. These changes include disappearing fresh food markets, increasing numbers of supermarkets, and the control of the food chain by supermarkets and global food, catering and agriculture companies in many countries."

The other three papers in The Lancet series build on Popkin and his team's work, exploring the physiological impacts of the double burden of malnutrition and recommending "double-duty" interventions that simultaneously reduce the risk of nutritional deficiencies while preventing obesity and related diseases.

To create the systemic changes needed to end malnutrition in all its forms, the series' authors call on governments, the United Nations, civil society, academics, the media, donors, the private sector and economic platforms to address the double burden of malnutrition and bring in new actors, such as grassroots organizations, farmers and their unions, faith-based leaders, advocates for planetary health, innovators, political leaders, consumer associations, and investors who are financing fair and green companies.

SAN ANTONIO, TX - Results from NRG Oncology's BR005 study show that breast-conserving treatment without surgery cannot be recommended, based on the study criteria of clinical complete response, radiological complete response (rCR)/near rCR, and negative tumor bed biopsies. These findings were presented at the 2019 San Antonio Breast Cancer Symposium, held December 10-14.

This phase II study, which opened in June 2017, was designed as a two-stage trial to assess the accuracy of tumor bed biopsies in predicting pathologic response in patients with clinical complete and radiological complete/near complete response after neoadjuvant chemotherapy to determine if they could avoid surgery. All patients had received chemotherapy for their breast cancer, but had not yet had surgery. All underwent an image-guided biopsy after receiving chemotherapy. A total of 105 patients were enrolled from August 2017 through June 2019, with 98 being evaluable for analysis. Accrual was temporarily closed for futility analysis on June 26, 2019, because 36 of the evaluable patients had residual disease at surgery, which actually met the numbers for the primary analysis. The negative predictive value of the biopsy was 77.5% (95%CI: 66.8% to 86.1%) which did not meet the pre-specified threshold of >90% required to support the feasibility of initiating a study in which surgery could be omitted.

"Further analysis including central review of tri-modality imaging and assessment of an imaging algorithm with and without the addition of biopsy are underway. Once these are combined with information on biologic subtypes, a new prediction model will be defined," according to Mark Basik, MD, from Jewish General Hospital, and lead investigator of the study.

(SACRAMENTO) -- Allison Brashear, Dean of the UC Davis School of Medicine, is working to save the future workforce of neurology and to reduce the gender gap in the medical specialty.

More trained neurologists are needed to meet the demand for care in the U.S. More trained neurologists are needed to meet the demand for care in the U.S.

In an editorial published Dec. 3 in the journal Neurology, Brashear and colleague Nina Schor call for meaningful changes in the culture of the field - ones that aren't portrayed as concessions to accommodate women's shortcomings or special needs. Schor is deputy director at the National Institute of Neurological Disorders and Stroke.

"Burnout among all physicians and the persistent predominance of men in the neurology workforce are widening the gender gap, at a critical time when the demand for neurologists is only expected to increase," Brashear said.

In the U.S. alone, the number of trained neurologists is expected to increase by only 7% by 2025, while the projected demand for services places the increased need at 16%.

"As women increasingly make up medical school classes, choose medical fields in which they can earn the same salaries as their male colleagues, seek positions that provide flexibility in workload and work hours, and retire before 65 years of age, the specialty needs to evolve to both meet these needs and prevent the burnout that may result in early retirement and part-time status," Schor said.

Reducing the gender gap in neurology means addressing a variety of factors, from burnout and women leaving the field, to the difference in pay between male and female neurologists - a gap which is one of the largest in any medical specialty.

"In many fields and on six continents, women physicians, nurses, physician assistants and residents deal with larger clinical workloads, longer clinical hours, lower salaries and more personal caregiving and homemaking duties than their male counterparts," Brashear said. "There are also fewer women in leadership positions to advocate for change. Only 14 of 113 neurology department chairs are women."

The authors believe identifying and mitigating these factors may help narrow the gender gap and increase the supply of neurologists to better meet future patient needs. They suggest structuring positions to give more time to complete administrative tasks, offering more flexible work hours, providing daycare at the workplace, setting salaries at a level that encourages hiring help for daily tasks and chores in the home, and making it routine for all early career neurologists (men and women) to have mentors for personal and career support.

HAMILTON, ON, Dec. 13, 2019 - A team of researchers at McMaster University has developed a self-cleaning surface that can repel all forms of bacteria, preventing the transfer of antibiotic-resistant superbugs and other dangerous bacteria in settings ranging from hospitals to kitchens.

The new plastic surface - a treated form of conventional transparent wrap - can be shrink-wrapped onto door handles, railings, IV stands and other surfaces that can be magnets for bacteria such as MRSA and C. difficile.

The treated material is also ideal for food packaging, where it could stop the accidental transfer of bacteria such as E. coli, Salmonella and listeria from raw chicken, meat and other foods, as described in a paper published today by the journal ACS Nano.

The research was led by engineers Leyla Soleymani and Tohid Didar, who collaborated with colleagues from McMaster's Institute for Infectious Disease Research and the McMaster-based Canadian Centre for Electron Microscopy.

Inspired by the water-repellent lotus leaf, the new surface works through a combination of nano-scale surface engineering and chemistry. The surface is textured with microscopic wrinkles that exclude all external molecules. A drop of water or blood, for example, simply bounces away when it lands on the surface. The same is true for bacteria.

"We're structurally tuning that plastic," says Soleymani, an engineering physicist. "This material gives us something that can be applied to all kinds of things."

The surface is also treated chemically to further enhance its repellent properties, resulting in a barrier that is flexible, durable and inexpensive to reproduce.

"We can see this technology being used in all kinds of institutional and domestic settings," Didar says. "As the world confronts the crisis of anti-microbial resistance, we hope it will become an important part of the anti-bacterial toolbox."

The researchers tested the material using two of the most troubling forms of antibiotic-resistant bacteria: MRSA and Pseudomonas, with the collaboration of Eric Brown of McMaster's Institute for Infectious Disease Research.

Engineer Kathryn Grandfield helped the team verify the effectiveness of the surface by capturing electron microscope images showing that virtually no bacteria could transfer to the new surface.

The researchers are hoping to work with a commercial partner to develop commercial applications for the wrap.

Microbes living in the rectum could make a difference to the effectiveness of experimental HIV vaccines, according to researchers at the University of California, Davis. The work is published Dec. 11 in the journal mSphere.

Evidence from human and animal studies with other vaccines suggests that Lactobacillus supplements can boost production of antibodies, while treatment with antibiotics can hamper beneficial immune responses, said Smita Iyer, assistant professor at the UC Davis Center for Immunology and Infectious Diseases and School of Veterinary Medicine.

Iyer, graduate student Sonny Elizaldi and colleagues wanted to know if microbes living in the rectum and vagina - sites of HIV transmission - interacted with an experimental HIV vaccine similar to the HVTN 111 vaccine currently in early stage clinical trials in humans.

HVTN 111 includes two doses of HIV DNA snippets and a final boost with an HIV protein, all given through the skin. A vaccine that produces antibodies at the mucosal membranes where infection takes place is thought to be important in preventing HIV infection, Iyer said.

The team studied vaginal and rectal microbes from Rhesus macaques before and after they were vaccinated. They found that vaginal microbes did not show much difference before and after vaccination. However, rectal microbes did show changes, with Bacteroidetes-type bacteria, especially Prevotella, decreasing after vaccination.

Lactobacillus bacteria and better immune response

The common gut bacteria Lactobacillus and Clostridia did not change with vaccination, but the amounts of these microbes in the rectum did correlate with the immune response. Animals with high levels of either Lactobacillus or Clostridia made more antibodies to the HIV proteins gp120 and gp140, the researchers found. Prevotella bacteria showed the opposite pattern: High levels of Prevotella were correlated with weaker immune responses.

It's not clear what the mechanism could be for some bacteria to boost local immune responses in a specific site in the body, Iyer said. However, targeting these bacteria could be important to get the best possible performance out of vaccines that do not induce a particularly strong immune response, as is the case with HIV.

The microbiome could also be an important but overlooked factor to consider when evaluating vaccines in humans or animals, she said.

TAMPA, Fla. - Precision medicine with targeted therapies has led to improved treatment options and patient outcomes. These approaches were developed by studying tumors grown in laboratories and patient samples obtained before and during their treatment. However, there is often a limited supply of patient samples to adequately study, and the samples that exist do not always tell the complete genetic story of how the patient responded to specific drugs and the reasons why they failed treatment. Researchers need a better way to determine how tumors respond to therapies and evolve to resist drug treatment.

In an article published in Cancer Medicine, Moffitt Cancer Center scientists describe a community-based program called the Rapid Tissue Donation (RTD) protocol. It enables patients to consent to donating tumor tissue and blood samples for research purposes after their death. The samples provided by patients postmortem enable researchers to study the genetic and molecular makeup of primary and metastatic tumors after the patient failed treatment, and to compare those finding with what was known about the patient during earlier phases of their therapy.

There were several challenges that the Moffitt team had to overcome before embarking on this program, including ethical considerations and logistical challenges, communication with hospice care facilities, locating autopsy facilities in the community and identifying tumors in postmortem specimens.

During a two-year span from Nov. 2015 to Nov. 2017, Moffitt researchers were able to gain consent from 21 lung cancer patients from Hillsborough, Pinellas and Pasco counties to participate in the RTD study. They collected 180 tumor tissue and blood specimens from nine deceased patients, while the remaining 12 patients were still alive at the time of the article publication.

One of the logistical challenges the researchers faced was the need to preserve the specimens as quickly as possible after death to ensure that the tissue and molecular material remained intact. The average time to collect the specimens for all nine patients was 15.8 hours. Samples were collected within 20 hours of death for eight donors, and by 41 hours from death for one donor due to unavoidable logistic complexities.

Analysis of the specimens found that most of the DNA samples taken from the primary and metastatic tumors of the same patient were similar and contained the same DNA mutations. The researchers also discovered an AGK-BRAF fusion in one patient with a known EML4-ALK fusion and resistance to ALK inhibitor therapy. Activated BRAF can promote tumor growth. "This is a compelling finding because, had the AGK-BRAF fusion been detected during treatment, physicians could have adapted therapy to include a BRAF-targeted agent," said Eric Haura, M.D., medical oncologist and director of Moffitt's Lung Cancer Center of Excellence.

Analysis of tumor tissue samples for protein biomarkers showed that expression of the protein PD-L1 varied up to 55% among samples taken from the primary tumor and metastatic tumors from the same patient. Levels of PD-L1 are used as a diagnostic assay for lung cancer patients to determine if they should receive certain drugs.

"Twenty to sixty percent of individuals in this study would have a different PD-L1 result if different tumor sites were tested," said Haura. "This illustrates the importance of interpreting PD-L1 results with caution because a large number of patients might not be eligible for immunotherapy based on testing of one tumor site but would be eligible based on testing of a tumor in a different location."

Haura is pleased with the progress the RTD program has made and is excited for what is to come. He hopes that it can be expanded into other tumor types and even developed in partnership with other institutions.

Pooled analysis of three phase 1 and 2 clinical trials published online ahead of print in the journal Lancet Oncology show that the drug entrectinib is effective and well-tolerated against advanced ROS1 and NTRK fusion-positive non-small cell lung cancers (NSCLC). Results of the trials STARTRK-1 (NCT02097810), STARTRK-2 (NCT02568267), and ALKA, show 77 percent response rate to entrectinib in 53 patients with ROS1+ NSCLC, with a median progression-free survival of 19 months and a median duration of response of 24.6 months. In 54 patients with NTRK+ NSCLC, 57 percent responded to entrectinib, with a median progression-free survival of 11.2 months and a median duration of response of 10.4 months. Based on the early promise of these trials, in August 2019 the U.S. Food and Drug Administration granted entrectinib accelerated approval for the treatment of metastatic ROS1+ NSCLC and for advanced tumors across cancer types defined by NTRK fusion. The current journal articles update these findings that led to approval.

"For a drug to get simultaneous approval for use against two different targets is somewhat unique. I don't know of this ever happening before," says Robert C. Doebele, MD, PhD, director of the University of Colorado Cancer Center Thoracic Oncology Research Initiative, senior author on the ROS1 study, and first author on the NTRK study.

About 2 percent of lung cancers are driven by the improper fusion of the gene ROS1 with one of a handful of possible genetic partners, resulting in a cancer-causing ROS1 fusion gene. About 1 percent of all solid tumors, including but not limited to lung cancers, are similarly caused by NTRK fusion genes. The FDA-approved drug crizotinib can silence the action of ROS1 fusion genes in some cases, but can't reach cancers that have metastasized to the brain. And, unfortunately, 36 percent of patients with ROS1+ NSCLC already have brain metastases at the time of advanced disease diagnosis, and many more will go on to develop brain metastases during the course of care.

"For ROS1+ lung cancer, entrectinib represents a new and better standard of care due to entrectinib's effectiveness against ROS1 in the body and especially due to its activity against ROS1+ brain metastases," Doebele says. "For NTRK cancers, the picture is a little more complex and I think it depends on an NTRK+ cancer's chance of developing brain metastases. Personally, if I were a patient and felt there was any chance of me getting brain mets, I would want this brain-penetrating drug."

Included in these phase 1 or 2 studies were adults with locally advanced or metastatic ROS1+ or NTRK+ NSCLC who had received previous treatment not including other ROS1 inhibitors. Patients received entrectinib at a dose of at least 600 mg orally once per day, with at least 12 months follow-up. Doebele describes the drug as "well tolerated with a manageable safety profile," with side effects including weight increase (8%) and neutropenia (4%). Eleven percent of patients had serious treatment-related adverse events, the most common of which were nervous system disorders (3%) and cardiac disorders (2%). No treatment-related deaths occurred.

"The genes ROS1 and NTRK are on a growing list of known genetic drivers of non-small cell lung cancer. In addition to showing the benefit of entrectinib against cancers caused by these fusion genes, these results highlight the importance of genetic testing in NSCLC, especially when patients are diagnosed with the condition in the absence of other risk factors," Doebele says. "Only by testing for genes like ROS1 and NTRK can we match these genetic drivers of cancer with drugs like entrectinib."

If you want to predict which breast cancer patients will most likely stop taking aromatase inhibitors, check out their own responses to the health questions patients commonly answer in cancer clinical trials, according to research findings to be presented Friday, Dec. 13 at the San Antonio Breast Cancer Symposium.

Known as patient-reported outcomes, these surveys are used in trials to provide a patient perspective on a treatment and its impact on quality of life. Was the drug easy to take? What are your symptoms? Are you in pain? Are you able to work? Are you getting family support?

Answers can predict who is likely to stop taking aromatase inhibitors (AIs), pills taken by tens of thousands of postmenopausal women each year to treat their hormone-sensitive breast cancers, according to new research led by SWOG Cancer Research Network Vice Chair Dawn Hershman, MD. Women taking AIs who reported a poorer quality of life than their peers on the trial, and higher levels of both pain and endocrine symptoms, Hershman found, are more likely to stop taking their medication. So are women with negative beliefs about whether medication works - and whether they need it to keep their cancer from returning.

"We found a clear association between women who started the trial who were struggling with pain, poor quality of life, and endocrine symptoms - as well as beliefs that the medicine isn't helping - and those not taking the medication 36 months later," said Hershman, director of the Breast Cancer Program at NewYork-Presbyterian and Columbia University Irving Medical Center's Herbert Irving Comprehensive Cancer Center. "In this way, patient-reported outcomes can act like biomarkers. They can predict an outcome - and be used to personalize treatments."

The work will be presented the morning of Friday, Dec. 13 in a Spotlight Session highlighting notable poster presentations at the San Antonio Breast Cancer Symposium, the world's largest breast cancer research conference, with 7,500 attendees from more than 90 countries expected this year. The study was supported by SWOG, an international cancer clinical trials network funded by the National Cancer Institute (NCI) through the National Institutes of Health.

AIs are one of the most common treatments for breast cancer. The pills stop the production of estrogen in postmenopausal women, essentially starving hormone receptor-positive breast cancer cells. Many women must take AIs for a long as five years. About half report bone pain, and many have side effects that include headaches, nausea, and hot flashes. Quitting treatment can be dangerous. Women who do are at increased risk for their breast cancer returning.

Hershman and colleagues at SWOG have studied AIs intensely, searching for better ways for patients to manage AI associated pain, like acupuncture and depression drugs, and otherwise improve quality of life for women taking the pills. At the annual meeting of the American Society of Clinical Oncology (ASCO) in June, Hershman presented results of S1105, a SWOG randomized trial testing the effectiveness of text message reminders to improve AI adherence. Women on S1105 were taking AI pills for at least 30 days. The team found no difference in adherence rates between women who did and did not receive the texts. S1105 was the first long-term, prospective study to evaluate an intervention to improve cancer drug adherence.

To conduct this current study, Hershman and her team analyzed data from S1105. They reviewed information about 702 patients randomized into two groups - one that received a text twice a week for 36 months and one that did not. To see if they could find factors connected to non-adherence, researchers noted which patients quit taking the drugs, based on negative urine tests. They also studied patient-reported outcome (PRO) responses at baseline, or the start of the trial, and also at the end of the trial.

PROs included questions about:

Joint pain levels on a 1-10 scale

Endocrine symptoms, such as hot flashes, hot or cold sweats, and weight gain

Quality of life, such as mood, sleep, and walking ability

Beliefs about medications, such as confidence in effectiveness

The team divided patient responses into two groups - those with low scores on each PRO measure (0-50 percent) and those with high scores on each PRO measure (50-100 percent). The association was clear. Those who were less satisfied with medications, and didn't see their usefulness, and those who had higher reports of pain, side effects, and poor quality of life, were more likely to stop taking AIs in the long-term.

"This means we can look at baseline PRO data and identify - early on - which patients are at risk of non-adherence," Hershman said. "Consistently taking a medication over time isn't as simple as being given a reminder. There are a host of factors that affect why patients may stop. We can use PROs data to tailor interventions so they're more likely to continue taking these potentially life-saving medications. That's good to know."

A retrospective study of nearly 9800 women with breast cancer who participated in randomized clinical trials was presented today at the 2019 San Antonio Breast Cancer Symposium. The study found that women with government insurance (Medicaid or Medicare) were much less likely to participate in a clinical trial compared to their privately insured counterparts. The few women with government insurance who did participate in the trials were more likely to stop treatment early and had lower survival. The study was conducted by researchers in the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) with funding from the National Cancer Institute, part of the National Institutes of Health.

"Having insurance in and of itself was not enough to ensure access to a clinical trial or a good clinical outcome," said lead researcher Samilia Obeng-Gyasi, MD, a breast surgical oncologist at The Ohio State University who studies social determinants of cancer care.

Dr. Obeng-Gyasi and colleagues looked at data from women who participated in two large ECOG-ACRIN trials testing chemotherapy treatments. Study E1199 enrolled participants from 1999 to 2002 and study E5103 enrolled participants between 2007 and 2011. In the current analysis, Dr. Obeng-Gyasi and colleagues evaluated each participant's insurance coverage and neighborhood socioeconomic status at the time they entered the trial, to determine if either status affected the women's clinical outcomes later on.

Insurance status was either private, government (Medicaid, Medicare), or self-pay. Only about 13% of participants in each of the two trials had government insurance. The majority of patients had private insurance (85.6% in E1199 and 82% in E5103).

Patients with government insurance were less likely to complete treatment compared to their privately insured counterparts. One out of every four government insured patients did not complete treatment in E1199 versus one out of every seven privately insured women. In E5103, approximately one out of every two government insured patients did not complete therapy compared to one out of every three privately insured patients. Completion of the trial and survival outcomes were each controlled for disease severity, age, and other patient characteristics that could influence the participant's outcomes.

The government insured patients also had a higher risk of dying compared to their privately insured counterparts. In E1199, the risk of death increased by one half. For those in E5103, the risk increased by one-third.

The researchers determined the neighborhood socioeconomic status of each participant by linking their zip code to county-level data on occupation, income, poverty, wealth, education, and crowding.

There was no association between neighborhood socioeconomic status and trial completion or survival.

"Insurance appears to be a powerful determinant of clinical trial outcomes," said Dr. Obeng-Gyasi. "With continued changes to insurance at the federal and state levels, physicians and policy-makers would benefit from having more data such as what we produced in our study. Right now, most clinical trials do not collect data on social determinants of health. If they did, the information could lead us to better understand the interaction of insurance status and many other factors on the clinical outcomes of clinical trial participants."

Abstract PD10-09: Impact of insurance and socioeconomic status on clinical outcomes in therapeutic clinical trials for breast cancer. Category: Disparities and Barriers to Care. First author: Samilia Obeng-Gyasi. PD10 Spotlight Session: Toxicity, Tolerability & Cost (Friday, December 13, 7:00 AM.)

Incidence rates for hormone receptor positive (HR+) breast cancers are considerably higher in black men than white men, in stark contrast to lower incidence rates of those cancer subtypes in black versus white women. That's according to a new American Cancer Society study that used nationwide data to provide the first report on differences in subtype-specific breast cancer incidence rates between black men and white men. The study appears in JNCI Cancer Spectrum.

Incidence rates of breast cancer in men are higher in blacks than in whites in the United States, in contrast to rates for women, among whom breast cancer incidence rates remain slightly higher in whites than in blacks. There are considerable racial differences in breast cancer rates by subtype in women, with black women having about twice the rate of triple-negative breast cancer and lower rates of HR-positive cancers. This difference has significant implications for patient outcomes.

However, it is unknown whether similar subtype-specific differences in breast cancer incidence rates occur between black men and white men. To find out, researchers led by Hyuna Sung, Ph.D. examined subtype specific breast cancer incidence rates in black and white men in the U.S. using a contemporary nationwide database.

They found that rates for all subtypes were higher among black than white men, with rates for HR+/HER- breast cancers about 41% higher among black men compared to white men; about 65% higher for HR+/HER2+, more than 2.5 times higher for HR-/HER2+, and 2.27 times higher for triple-negative breast cancer. Conversely, among women, rates in blacks were 21% lower for HR+/HER2- and comparable for HR+/HER2+, but 29% and 93% higher for HR-/HER2+ and triple-negative subtypes, respectively.

"Reasons for the elevated risk of breast cancer in black men are largely unknown but may involve multitude of risk factors including genetic and non-genetic factors," write the authors. Racial differences in the prevalence of mammography and menopausal hormone supplements are thought to have contributed to the historically higher incidence rate of HR+ cancers in white women, but these are not factors in breast cancer in men.

Well-known risk factors for male breast cancer include family history of breast and/or ovarian cancers, pathogenic mutations in BRCA2, radiation exposure, and conditions that alter hormonal balance such as Klinefelter syndrome and gynecomastia, and potentially obesity and diabetes. Moreover, previous studies have found higher level of estradiol was found to be associated with increased risk of male breast cancer after controlling for body mass index, suggesting a presence of estrogen-mediated carcinogenesis in male breast cancer. However, whether associations of these risk factors vary by tumor subtypes remains unknown and should be considered in future etiologic studies.

The authors conclude that black-white patterns in subtype-specific breast cancer incidence rates differ between men and women, especially for HR+ disease, and that this may have implications for the etiology of breast cancer. Future studies, they write, should identify factors contributing to these patterns to further inform prevention strategies.