Body

TUCSON, Ariz. – Imagine taking a pill to control your pain and, instead, the medication actually increases the pain you feel. That may be the situation for patients who take opioids, but even more so for women, according to groundbreaking research by investigators at the University of Arizona College of Medicine – Tucson in the Department of Pharmacology.

The researchers identified a mechanism that explains why women may be more vulnerable than men to develop pain in general, as well as to develop pain from opioids specifically.

The cause is a neurohormone, prolactin, known largely for promoting lactation in expectant mothers in their final months of pregnancy and after childbirth.

Frank Porreca, PhD, associate department head, a professor of Pharmacology, anesthesiology, cancer biology and neuroscience at the college, and senior author on the study, notes it always has been understood that women experience some types of pain that occur without injury (known as “functional pain syndromes”) more than men. The reasons for this never were clearly understood. A possible explanation the researchers explored was the differences in the cells and nerves that send pain signals to the brain in women and men.

The findings suggest new pain-management therapies targeting the prolactin system would greatly benefit women suffering from functional pain syndromes.

“Of all these female-prevalent pain disorders, migraines are among the most common, with about 35 million migraine patients in the United States, and three out of four of those are women. In addition, in fibromyalgia patients, as many as nine out of 10 are women; for irritable bowel syndrome, three out of four are women. When you add up all those women with pain – if you can normalize that – this would provide a huge and important impact on medical care,” Dr. Porreca says.

He points out many of these pain spells are intermittent and associated with triggering events. For instance, he and his colleagues found stress releases prolactin and unexpectedly promotes pain selectively in females.

“These triggering events can be wide-ranging. They can include things like alcohol, fatigue and sleep disruption. But stress is the most common trigger self-identified by patients. That's where we started our studies – how does stress contribute to female-specific pain or female-selective pain?”

Primary authors on the paper include: Yanxia Chen, a graduate student in Dr. Porreca’s lab; Aubin Moutal, PhD, a research assistant professor in the Department of Pharmacology, working in the lab of Rajesh Khanna, PhD, a UArizona professor of anesthesiology, pharmacology and neuroscience, who also is a co-author on the paper; and Edita Navratilova, PhD, an assistant professor of pharmacology.

Dr. Navratilova says dopamine D-2 receptor agonist drugs that limit prolactin release, such as cabergoline, commonly are used for other diseases, and are not addictive. These drugs, possibly in conjunction with other classes of medications, may help treat those pain conditions in women more effectively without the addictive properties of opioids.

“If we could just reduce the proportion of women who have migraines to the same amount as in men, that would be quite revolutionary,” Dr. Navratilova says.

In addition, since publication of their findings, Dr. Porreca has been contacted by companies interested in investigating whether an antibody previously associated with breast cancer treatment might be able to be engineered as a therapy to guard against pain in women.

AURORA, Colo. (March 4, 2020)- Newly published research by a CU School of Medicine faculty member and colleagues identifies multiple ways that health care providers and organizations can improve the quality of care provided to trafficked children.

Karen Albright, PhD, associate professor of medicine at the University of Colorado School of Medicine, has edited a special issue of Child Abuse & Neglect, a journal published by the International Society on the Prevention of Child Abuse and Neglect.

The special issue focuses on the health needs of and service provision for trafficked and exploited children. In addition to research studies, it features a number of innovative programs around the globe that use a holistic approach to address the medical and mental health needs of this population. The issue can be accessed at https://www.sciencedirect.com/journal/child-abuse-and-neglect/vol/100/suppl/C.

Albright is also lead author an article featured in the issue, a systematic review of the barriers to, facilitators of, and recommendations for improving health services to trafficked and exploited children.

The review identifies 45 facilitators and 118 barriers to high-quality health care to this population, the vast majority of which fall under the locus of control of the healthcare provider and healthcare organizations. Prominent among the barriers are lack of health professional training on human trafficking and trauma-informed care, lack of health facility protocols and guidelines on human trafficking, and lack of multidisciplinary collaboration between health providers and community service providers.

The review also identifies 52 recommendations for medical and mental health service provision to trafficked children. These recommendations provide a road map of actionable steps that can be taken at multiple levels, from individual providers to large-scale social and structural changes, to improve care.

New Rochelle, NY, March 4, 2020--Little data is available about the ability of antiviral drugs used to treat COVID-19, coronavirus, to enter breastmilk, let alone the potential adverse effects on breastfeeding infants. A new perspective article reviewing what is known about the most commonly used drugs to treat coronavirus and influenza is published in Breastfeeding Medicine, the official journal of the Academy of Breastfeeding Medicine published by Mary Ann Liebert, Inc., publishers. Click here to read the protocol free on the Breastfeeding Medicine website.

Philip Anderson, PharmD, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, is the author of "Breastfeeding and Respiratory Antivirals: Coronavirus (COVID-19) and Influenza." The short answer to questions regarding drug therapy for COVID-19 is that currently there is no antiviral agent proven to be effective against this new infection. However, one investigational drug so far, remdesivir, appears promising to treat COVID-19, and it is in phase 3 clinical trials in patients. Dr. Anderson notes: "Nothing is known about the passage of remdesivir into breastmilk."

Arthur I. Eidelman, MD, Editor-in-Chief of Breastfeeding Medicine, states: "Given the reality that mothers infected with coronavirus have probably already colonized their nursing infant, continued breastfeeding has the potential of transmitting protective maternal antibodies to the infant via the breast milk. Thus, breastfeeding should be continued with the mother carefully practicing handwashing and wearing a mask while nursing, to minimize additional viral exposure to the infant."

What The Study Did: This population-based study describes the risk of experiencing violent assault among young immigrants and refugees (ages 10 to 24) compared with nonimmigrants in an analysis of  linked health and administrative databases in Ontario, Canada. Researchers acknowledge some important factors are unknown, including the circumstances of some events.

Authors: Natasha Ruth Saunders, M.D., M.Sc., of The Hospital for Sick Children, in Ontario, Canada, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(10.1001/jamanetworkopen.2020.0375)

Editor's Note: The article includes conflict of interest and funding support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

WASHINGTON -- With today's JAMA Surgery publication of findings on how many adults see their Type 2 diabetes go away and come back following weight-loss surgery, the PCORnet Bariatric Study now provides patients and their doctors with a more complete picture about the comparative benefits and risks of the two most commonly used bariatric procedures.

The study's findings on diabetes as well as earlier findings on weight loss and health risks are now being incorporated into a decision aid to empower patients consulting with their clinicians to make personalized decisions about weight-loss surgery.

People with severe obesity contemplating weight-loss surgery face a choice between the longer-used Roux-en-Y gastric bypass procedure or a newer and somewhat simpler surgical approach, sleeve gastrectomy, which now accounts for two out of every three bariatric surgeries performed in the United States.

Funded by the Patient-Centered Outcomes Research Institute (PCORI), the PCORnet Bariatric Study is the largest to date to compare these procedures. Its prior findings on weight loss and maintenance among adult patients and rates of short-term health risks were reported in Annals of Internal Medicine. Findings on rates of long-term problems requiring reoperations and other interventions appeared in JAMA Surgery.

"Taken together, the evidence from the PCORnet Bariatric Study is vital to enabling patients and their health care providers to weigh the tradeoffs of the procedures and make personalized decisions based on what matters most to each patient," said PCORI Interim Executive Director Josephine P. Briggs, M.D. "This study is exemplary of how the comparative effectiveness research that PCORI funds can empower better-informed health care decision making."

The findings are important because obesity in U.S. adults hit a 20-year high in 2017-2018, according to new data from the Centers for Disease Control and Prevention, with 42 percent of U.S. adults considered obese and about 9% of adults classified as severely obese. In addition, sleeve gastrectomy has quickly become the most commonly performed bariatric procedure in the United States, but because it was introduced in the country less than a decade ago, less evidence has been available to compare it to bypass.

"More people with severe obesity should be having conversations about the role of bariatric surgery, which has been underused because of concerns about safety and weight regain," said the study's lead co-principal investigator David Arterburn, M.D., M.P.H., an internist and senior investigator at Kaiser Permanente Washington Health Research Institute in Seattle. "The results of the PCORnet Bariatric Study show that the overwhelming majority of patients maintain successful weight loss long term, especially after bypass. But bypass patients had a higher risk of subsequent operation and hospitalization."

"As with many health care options, no one weight-loss surgical procedure is the best choice for every patient because tradeoffs are associated with each," added co-principal investigator Kathleen McTigue, M.D., M.P.H., M.S., an associate professor of medicine and epidemiology at the University of Pittsburgh. "The choice requires personalized decision making that involves weighing the evidence about the pros and cons along with each person's individual circumstances and preferences."

For example, one person might decide it's most important to lose and keep off as much weight as possible and may be willing to accept the greater risks that come with gastric bypass. Meanwhile, a second person with very similar medical history may decide it's most important to minimize the chances of additional operations and hospitalizations that require time away from work and accept the lesser weight loss associated with sleeve gastrectomy.

To make the findings more accessible to patients and health care providers to use in decision making conversations, the research team is incorporating the findings into a decision aid as part of a PCORI-funded implementation project. This tool is part of a broader process for shared decision making between doctors and patients that the team is designing at two health systems, working with four bariatric clinics, nine surgeons and dozens of primary care providers.

The PCORnet Bariatric Study was able to provide findings from the largest sample sizes available to date through its use of tens of thousands of medical records, accessed via PCORnet®, the National Patient-Centered Clinical Research Network.

Developed with funding from PCORI, PCORnet harnesses the power of real-world data drawn from electronic health records, claims data and other sources to generate real-world evidence. The network enables researchers to access aggregated, de-identified data to conduct research on large sample sizes.

Both PCORnet and PCORI emphasize patient guidance and partnership in studies. People who have had weight-loss surgery served as co-investigators and helped to refine the study question, select outcomes to study, interpret the findings and present the results.

What The Study Did: This randomized clinical trial conducted at 60 workplaces in urban ares of China examined whether a wellness program with a hypertension management component would improve blood pressure control among employees compared to usual care.

Authors: Zengwu Wang, M.D., Ph.D., of the Peking Union Medical College & Chinese Academy of Medical Sciences in Beijing, and Chun Chang, M.D., Ph.D., of Peking University in Beijing, are the corresponding authors.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamacardio.2019.6161)

Editor's Note: The article includes funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Excessive or uncontrolled buying or shopping is a highly prevalent, disabling and growing problem, yet measuring the extent and effects of this significant psychological problem and social issue remains problematic.

Buying-Shopping Disorder has not been formally accepted as a separate diagnosis, but a research team led by Flinders University's Professor Mike Kyrios and Dr Dan Fassnacht has developed diagnostic criteria that can apply a measurable scale of excessive buying.

Professor Kyrios says this new measure, the Excessive Buying Rating Scale (EBRS), forms an essential first step in measuring the severity of Buying-Shopping Disorder with agreed diagnostic criteria.

"No measures exist to assess the severity of excessive buying or shopping that are based on proposed diagnostic criteria, and this limits ongoing research efforts," says Professor Kyrios.

The new measure demonstrated good statistical properties and helped the research team to then examine the predictors of problematic buying/shopping severity.

Dr Dan Fassnacht, Lecturer in Psychology at Flinders University and co-investigator of the research, explains that having strong beliefs about the benefits of buying were significant predictors of excessive buying severity.

"Strong beliefs that buying an object will lead to emotional security or that not purchasing the object will lead to a loss of opportunity explains to some extent why people can't control their urges to buy," says Dr Fassnacht.

"We also found a small but significant effect of gender and age; females and younger people reported higher excessive buying severity."

Professor Kyrios adds: "Buying appears to be a strategy that we use to compensate for deficiencies that we see in ourselves. Those who are more uncertain about their self worth are more likely to succumb to excessive buying or shopping and to develop relevant unhelpful beliefs."

The research group considers the findings to have important implications for the development of treatments for excessive buying.

The paper detailing the EBRS results - 'Predicting the severity of excessive buying using the Excessive Buying Rating Scale and Compulsive Buying Scale,' by Michael Kyrios, Daniel Fassnacht, Kathina Ali, Bronte Maclean and Richard Moulding - has been published in the Journal of Obsessive-Compulsive and Related Disorders

The same research group, in collaboration with colleagues from the Hannover Medical School in Germany, has also conducted a survey of experts across the world to develop a consensus view of potential extended diagnostic criteria for a disorder of excessive or uncontrolled buying or shopping.

"We are still analysing the data, but these findings will help global clinical field trials, and finesse measures of severity and in ongoing research on the causes of this disabling disorder," says Professor Kyrios.

Researchers have found that the #Fitspiration philosophy is flawed, making many women feel worse about themselves and their bodies rather than inspiring them to exercise.

Despite the positive intentions and popularity of social media images depicting women being active in exercise programs, researchers at Flinders University's College of Nursing and Health Sciences have studied whether the #fitspiration Instagram movement is having its desired inspirational effect - and found the opposite to be true.

The study of more than 100 women aged 17-25 years found that viewing #fitspiration images increased negative mood and body dissatisfaction among women, and that exposure to #fitspiration images did not lead to greater exercise behaviour.

"When considering actual exercise behaviour, there appears to be no beneficial effect," says Dr Ivanka Prichard, who is Co-Deputy Director of the SHAPE Research Centre (Sport, Health, Activity, Performance and Exercise) at Flinders University, and a members of the Caring Futures Institute at Flinders University.

"Despite their positive intentions and popularity, #fitspiration images are yet another way to make women feel worse about themselves and their bodies"

"Close to 90% of young Australians use some form of social media, such as Facebook, Instagram, YouTube or Snap-Chat. Young women's rapidly growing use of image-based platforms such as Instagram is of concern, given what we know about the impact of idealised imagery on body image."

"One of the most consistent and influential forces on young women's body image is the media's depiction of idealised and often unobtainable body types such as a thin and fit ideal."

The paper - 'The effect of Instagram #fitspiration images on young women's mood, body image, and exercise behaviour', by Ivanka Prichard, Eliza Kavanagh, Kate Mulgrew, Megan Lim and Marika Tiggemann - has been published in the journal Body Image. https://doi.org/10.1016/j.bodyim.2020.02.002

Results demonstrated that exposure to #fitspiration images led to significantly higher negative mood and body dissatisfaction when compared to the same women being exposed to travel inspiration images. Some women were then asked to exercise. Of these, women who had viewed #fitspiration images felt like they "worked harder" but did not actually travel any further on a treadmill than women who had viewed travel images.

The study also investigated if engaging in exercise after viewing #fitspiration images could reduce the negative effects from image exposure - and found improvements in mood and body image following exercise.

For women who were exposed to #fitspiration and did not exercise, their levels of mood and body image perception returned to normal following a period of quiet rest.

"These findings provide further evidence highlighting fitspiration and aspiring to a thin and fit ideal as a potentially harmful online trend.

"We now need more research to examine aspects of fitspiration, such as focusing on body functionality and body diversity, that might promote positive body image," says Dr Prichard.

Dental teams could play an integral role in identifying people at high risk of developing Type 2 diabetes as well as in the early detection of the condition in those who are undiagnosed, new research suggests.

The systematic review, led by researchers in the University of Birmingham, found that using risk assessment tools such as patient questionnaires and point of care blood testing within a dental surgery setting could lead to better outcomes for patients and improved management of the condition.

Severe periodontitis - or gum disease - is significantly linked to Type 2 diabetes, a condition that is thought to affect approximately 422 million adults globally (according to the World Health Organisation). As T2DM is asymptomatic in its early stages, many individuals can remain undiagnosed for many years. However, with established links between compromised glycaemic status and oral health, dental professionals could be vital in the identification of the condition.

Lead researcher Professor Iain Chapple, Head of the University of Birmingham's School of Dentistry said: "Our review identified positive attitudes of physicians, dental team members, patients and the public towards risk assessing and early case detection of diabetes and pre-diabetes within the dental surgery. Patients also strongly supported tests being undertaken that provided immediate results.

"Not only does this demonstrate that there may be benefit in engaging the dental workforce to identify these cases, but also shows a need for a more joined up approach to care pathways between physicians and dental practitioners."

The work builds on joint international guidance published last year on gum disease and diabetes, which recommends closer working pathways between oral health care professionals and physicians, and a commissioning standard issued in 2019 by NHS England, setting out a vision for the implementation of such joint working practices. The Birmingham team were heavily involved with both publications.

CLEVELAND, Ohio (March 4, 2020)--Women who proactively have their ovaries removed to minimize their cancer risk may face a greater risk--premature death because of heart disease. That's according to a new study that identifies an increased risk for women with a family history of premature heart disease who underwent prophylactic oophorectomies before the age of 45. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

There has been ongoing debate in the medical community as to whether the surgical removal of the ovaries when performed earlier than age 45 years, alters a woman's exposure to endogenous ovarian hormones, effectively increasing her risk of heart disease. Multiple studies have suggested that women who undergo bilateral salpingo-oophorectomy (removal of the fallopian tubes and both ovaries) before the time of natural menopause have a greater risk of cardiovascular disease than women of similar age with intact ovaries.

In this study based on data from more than 2,700 postmenopausal women, researchers specifically investigated the modifying effects of family history of premature myocardial infarction (before the age of 50 years) on the association between removal of the ovaries before the age of natural menopause and mortality attributed to heart and cardiovascular disease. Their findings showed that such family history definitely elevated the risk of heart disease mortality in women who had both ovaries removed before the age of 45.

These findings have broad, mainstream relevance as ovaries are, unfortunately, the most frequently removed healthy organ for preventive purposes. Currently, more than half of women undergoing hysterectomy for benign conditions also undergo bilateral salpingo-oophorectomy. This study underscores the importance of considering potential risks before choosing to remove normal ovaries in young women.

Study results appear in the article "Family history of premature myocardial infarction modifies the associations between bilateral oophorectomy and cardiovascular disease mortality in a US national cohort of postmenopausal women."

"This study provides additional evidence that removal of the ovaries before the natural age of menopause is associated with multiple adverse long-term health outcomes, including cardiovascular disease and early mortality and should be strongly discouraged in women who are not at increased genetic risk for ovarian cancer," says Dr. Stephanie Faubion, NAMS medical director.

New research has shown that older workers with obesity are at a higher risk of prolonged sickness absence or losing their jobs for health reasons than those of normal weight, with women affected significantly more than men.

Scientists from the University of Southampton studied the association between BMI and prolonged sickness absence, cutting down at work and health-related job loss among 2299 men and 2425 women aged between 50 and 64 years.

Obesity is a major and growing public health problem, with future projections estimating that there will be more than one billion people affected globally by 2030. Being obese or overweight is a major risk factor for non-communicable diseases including diabetes; cardiovascular diseases; musculoskeletal disorders and common mental health conditions. Although obesity is becoming more prevalent in children and adolescents, the highest prevalence is seen amongst men and women in their fifties, sixties and seventies.

The participants in the study reported their height and weight at the start of the study then provided information about their ability to work after 12 and 24 months as part of Medical Research Council's Health and Employment after Fifty (HEAF) Study.

The University of Southampton team analysed the data from this study, publishing their findings in the International Journal of Environmental Research and Public Health. The research has shown that the women with obesity or severe obesity had greater odds of prolonged sickness absence compared with women of normal weight. Those with severe obesity were also the most likely to cut down, avoid, or change what they did at work because of a health problems and were almost three times as likely to lose their job because of their health.

Amongst the men taking part in the survey, there was a slightly increased risk of prolonged sickness absence amongst those with obesity but no evidence of an association between above-average BMI and health-related job loss.

Professor Karen Walker-Bone Director of the MRC Versus Arthritis Centre for Musculoskeletal Health and Work at the University of Southampton, who led the study, said: "Our study demonstrates the link between obesity and health problems that affect people's ability to work, particularly in older female workers. As a result, the burden of obesity in an aging population can be expected to hinder attempts to encourage work to older ages. These results should give employers an incentive to introduce measures that can help their employees maintain a healthy weight."

Bottom Line: Young women with breast cancer experienced substantial financial difficulties in the wake of a breast cancer diagnosis, even if they had stable jobs with insurance benefits.

Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research

Author: Florence K.L. Tangka, PhD, MS, a health economist in the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention (CDC) in Atlanta.

Background: The majority of young women treated for breast cancer are in the early stages of building their careers and raising families, so the burden of a cancer diagnosis can be significant.

How the Study was Conducted: In this study, researchers identified women between the ages of 18 and 39 who had received a breast cancer diagnosis from January 2013 to December 2014, drawing from state cancer registries in California, Florida, Georgia, and North Carolina. They chose these states because they had relatively large numbers of young breast cancer patients across all major racial/ethnic groups, Tangka said.

The researchers developed a survey with questions on insurance status, including changes in coverage; out-of-pocket costs related to their cancer care; employment status and benefits such as sick leave and scheduling flexibility; and access to treatment and quality of care. In total, 830 women completed the survey.

Results: Almost half the women--47 percent--experienced financial decline due to costs related to their cancer care. Some key findings on their employment and financial status:

The study found that 27.7 percent of the women had spent less than $500 on out-of-pocket costs; 27.9 percent had spent $500-$2,000; 18.7 percent had spent $2,001-$5,000; and 17 percent had spent $5,001-$10,000.

In order to pay these out-of-pocket costs, 81.5 percent of the women used personal funds; 22.9 percent borrowed from family or friends; 22.7 percent left some medical bills unpaid; 21.7 percent increased credit card debt; and 18.2 percent postponed paying bills.

Women without a college degree were more likely to experience financial decline. White women were the least likely to experience financial problems, although the differences in other racial/ethnic groups were not statistically significant.

Women diagnosed at stage 3 or stage 4 were the most likely to experience financial decline.

Many women reported that their cancer diagnosis affected their jobs, with 40.4 percent saying their job performance had suffered; 12.2 percent saying they had quit their jobs; and 7.5 percent saying they had lost their jobs. Also, 23.5 percent of the women said they had avoided changing jobs in order to keep their health insurance.

Fifty-five percent of the women took paid time off during their breast cancer treatment, and 47.3 percent took unpaid time off.

Author's Comments: Tangka said the results of the study indicate that many women who are diagnosed with breast cancer in the early years of their careers try to maintain their jobs in order to keep their health insurance coverage, and despite having insurance coverage, they may still experience financial challenges through the course of treatment.

Tangka added that while employment benefits varied, programs like paid sick leave, flexible scheduling, disability leave, and telecommuting often helped women maintain their employment status. She said future research could examine additional employment modifications, such as increasing part-time options.

Tangka added that a greater understanding of the costs of cancer care could help inform some women's treatment decisions.

"A lot of women don't have a good sense of how much a cancer diagnosis will cost, including out-of- pocket costs," she said. "We feel that if they have cost information, they can develop better financial plans to cover their treatment expenses."

She said the study data could serve as a reminder to clinicians that financial concerns can be considered when discussing treatment.

"Even though patients and physicians understand the importance of having discussions about the economic burden of cancer, such conversations seldom occur," Tangka said. "Cancer patients may not have choices in all aspects of cancer care, but if they have information on the duration of treatment and how much they need to pay out of pocket, they can plan better."

Study Limitations: Tangka noted that because the study included data from four states, the results may not be generalizable nationwide. Also, she said economically disadvantaged or sicker women may have been less likely to respond to the survey.

Funding & Disclosures: This study was funded by the CDC. Tangka declares no conflicts of interest.

ROCHESTER, Minn. -- Only 1 in 13 everyday patients could have participated in a pivotal international clinical trial looking at the use of catheter ablation to treat atrial fibrillation (AFib) among people with heart failure. However, new Mayo Clinic research provides evidence supporting the benefit of ablation, and shows what the outcomes might be for everyday patients. The Mayo study will be published in Heart Rhythm Journal.

The Catheter Ablation for Atrial Fibrillation with Heart Failure (CASTLE-AF) trial compared catheter ablation versus medical therapy alone for atrial fibrillation in patients with heart failure. In early 2018, the results of that trial were announced. Although the trial was fairly small with 363 participants, it showed an impressive 38% reduction in risk of death or hospitalization for worsening heart failure.

Xiaoxi Yao, Ph.D., a Mayo Clinic health services researcher, and Peter Noseworthy, M.D., a Mayo Clinic cardiologist, wanted to see if these findings would bear out across a broader population.

"Randomized clinical trials are the gold standard for evaluating new medical treatments or procedures," says Dr. Yao. "However, often their results are not necessarily applicable across a more heterogeneous group of people. Sometimes results cannot be replicated or are simply not as striking when interventions are tested across a broader population."

Why this study?

Heart failure affects about 6.5 million adults in the U.S., according to the Centers for Disease Control and Prevention. It leads to 1 in 8 deaths, and costs the nation tens of billions of dollars each year.

"Heart failure and AFib often go hand-in-hand," says Dr. Noseworthy. "The trouble is that one problem exacerbates the other. So, patients with heart failure often get much worse when they develop AFib and patients with AFib may go on to develop severe morbidity from heart failure. We need interventions for these patients to prevent the downward spiral."

Drs. Yao and Noseworthy, and their team, were able to use the OptumLabs Data Warehouse to determine what outcomes would hold true for a larger, more diverse group of people. The OptumLabs Data Warehouse is a longitudinal, real-world data asset with de-identified administrative claims and electronic health record data.

"CASTLE-AF had very dramatic results -- a nearly 40% mortality benefit of ablation in this population. We needed to see how this played out in everyday practice," says Dr. Noseworthy.

Their team identified 289,831 patients with both heart failure and atrial fibrillation between Jan. 1, 2008, and Aug. 31, 2018. This group was nearly 800 times larger than the CASTLE-AF trial.

Of these patients, less than 8% would have been fully eligible for the trial; whereas, only 15.5% would have met exclusion criteria.

"This discrepancy is one of the pitfalls of randomized clinical trials leading to less generalizable findings," says Dr. Yao. "There are many reasons why a person might not meet inclusion criteria, including some which introduce unintended bias."

Study size strengthens evidence

The Mayo team found that although less pronounced than in the CASTLE-AF trial, ablation was associated with a lower risk of death or hospitalization due to worsening heart failure across all patients, except those who would have met exclusion criteria.

"While our study validates this concept, the results are more modest in practice," says Dr. Noseworthy.

Among those who would have been eligible to participate, the current study showed an 18% reduction -- much more modest than the results of the CASTLE-AF trial. People in the current study who received ablation and met exclusion criteria for the clinical trial did not reduce their risk of death. Rather, they showed an increased likelihood hospitalizations related to heart failure.

"Our study is especially important because it provides complementary evidence in a case where very few clinical trials have been conducted," he says. "In addition, a large observational study provides a more realistic picture of treatment effects for our everyday patients."

An antidepressant in use for decades, repurposed to fight prostate cancer, shows promise in helping patients whose disease has returned following surgery or radiation, a pilot study at USC shows.

The drug -- an MAO inhibitor called phenelzine -- represents a potential new treatment direction with fewer side effects for men with recurrent prostate cancer, researchers said.

"To our knowledge, this study is the first clinical trial of an MAO inhibitor in cancer patients," said senior author Jean Shih, a University Professor in USC's School of Pharmacy who has studied the enzyme MAO, or monoamine oxidase, for four decades.

The research appears in the journal Prostate Cancer and Prostatic Diseases.

"If our findings are confirmed, this could be part of a new avenue for patients that could avoid undesirable side effects of standard therapies," said first author Mitchell Gross, a medical oncologist and research director at the Lawrence J. Ellison Institute for Transformative Medicine of USC. Gross and Shih have been collaborating for several years to bring her research out of the lab and into the clinic.

Potential option for recurrent prostate cancer

In this study, 11 of 20 participants had a measurable decline in their PSA levels after 12 weeks of twice-a-day treatment, with the greatest decline in PSA being a 74% drop. PSA stands for prostate specific antigen; it's a biomarker for prostate cancer circulating in the blood.

Prostate cancer is the second most common cancer -- behind skin cancer -- diagnosed in men in the United States, with about 174,000 cases diagnosed each year. For most patients, prostate cancer is treated with surgery or radiation or a combination of the two.

After surgery, a patient's PSA should be close to zero. However, in about one-third of patients, the PSA level rises again, indicating the cancer has returned. Hormone therapy is a standard treatment for recurrent prostate cancer, but it comes with serious side effects that impact quality of life.

That's where MAO inhibitors may be able to help.

MAO inhibitors treat depression by readjusting levels of neurotransmitters such as serotonin and dopamine in the brain. The downside is that the medication requires dietary changes and careful avoidance of drug interactions to prevent serious side effects.

Antidepressant disrupts cancer growth pathway

In prostate cancer, MAO inhibitors disrupt androgen receptor signaling -- the main growth pathway for prostate cancer. Previous studies with animals and human prostate cancer cell lines showed that MAO inhibitors decreased the growth and spread of prostate cancer, the researchers found.

Because the MAO inhibitor phenelzine is already FDA-approved, the researchers were able to rapidly design and implement a pilot study to test the drug's ability to fight cancer.

For this study, researchers enrolled 20 participants who had been treated for prostate cancer and who had elevated PSA levels. Patients received the MAO inhibitor phenelzine twice a day for 12 weeks. Fifty-five percent of the men experienced PSA declines; five of them saw PSA level declines of 30% or more; two participants saw decreases of 50% or more.

Three patients had to drop out due to dizziness or hypertension.

The main limitations of the study include the lack of a placebo comparison group and the small sample size, researchers said. Additional studies are planned, and Shih has patented a second-generation MAO inhibitor tagged with a substance that could help doctors see where the cancer has spread.

Asthma and chronic obstructive pulmonary disease (COPD) were each associated with increased risk for developing rheumatoid arthritis in a study published in Arthritis & Rheumatology.

Inflamed airways may contribute to the development of rheumatoid arthritis, but the role of chronic airway diseases in the development of rheumatoid arthritis is unclear. In this study of 205,153 women, the researchers identified 15,148 women with asthma and 3,573 with COPD as well as 1,060 women who later developed rheumatoid arthritis over a median follow-up of approximately 24 years.

Asthma was associated with a 53% higher risk of rheumatoid arthritis, and COPD was associated with an 89% higher risk, after adjusting for factors including smoking. The association was particularly strong between COPD and the seropositive form of rheumatoid arthritis, which is characterized by elevated blood levels of antibodies thought to cause arthritis-related symptoms.

"These findings support the paradigm that chronic airway mucosal inflammation contributes to the development of rheumatoid arthritis," said first author Julia A. Ford, MD, of Brigham and Women's Hospital. "It is possible that inflamed airways may be a site of antibody production prior to the clinical onset of joint inflammation," added senior author Jeffrey A. Sparks, MD, MMSc. "Patients with asthma or COPD may be susceptible to rheumatoid arthritis, and clinicians should consider monitoring them for arthritis-related signs and symptoms."