Posts from the ‘research’ category

Home-Based Hypertension Program Produces ‘Striking’ Results

Naomi Fisher headshot

Naomi Fisher

A pilot study conducted by Brigham investigators found that an innovative care-delivery program helped participants reduce their blood pressure in just seven weeks.

Hypertension, or high blood pressure, affects nearly half of U.S. adults, according to the American Heart Association. Despite the serious consequences that can result from hypertension—which puts patients at an increased risk for heart attacks, strokes and other cardiovascular events—elevated blood pressure often remains untreated or undertreated for years.

Seeing opportunities for improvement, a team of innovators and clinicians at the Brigham developed a new care-delivery program for home use that aims to improve hypertension control rates quickly and at a significantly lower cost than traditional, clinic-based blood pressure programs.

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The new approach, piloted with 130 participants, helped 81 percent of patients achieve blood pressure control in, on average, less than two months. The results of the pilot study were published recently in Clinical Cardiology. Patients who enrolled had uncontrolled blood pressure (greater than 140/90) and were recruited from Brigham and Women’s Primary Care Associates, Longwood, and the Watkins Cardiovascular Clinic.

“This is a striking result, especially given the very short time frame in which control was reached,” said Naomi Fisher, MD, director of the Brigham’s Hypertension Service and Hypertension Specialty Clinic. “There are a few notable health care systems that have matched or exceeded this control rate, but most clinical practices do not approach this rate of success.”

Incorporating Technology

To overcome some of the challenges that clinical practices face, Fisher and colleagues combined several innovative strategies to create their program. Participants each received a Bluetooth-enabled blood pressure device that automatically transmits blood pressure measurements—taken by patients at home—into electronic medical records.

In addition, patients had access to “patient navigators”—non-physicians trained to use a clinical algorithm developed by hypertension specialists. The program enabled rapid assessment and medication dosage adjustments for patients. Medication adjustments were made every two weeks until home blood pressure was under 135/85.

The next step will be to test the program’s effectiveness with a larger population. With this approach, the team anticipates significant cost effectiveness and cost savings, in addition to the prevention of cardiovascular events and death from treating hypertension more intensively in men and women.

“The time-honored model of treating hypertension via traditional visits to the doctor is neither effective nor sustainable,” said Fisher. “Organizations can and should develop and adopt innovative technologies to create sustainable solutions for hypertension control.”

This work was supported by an institutional Brigham Care Redesign Incubator and Startup Program (BCRISP) award.

Study: Hospitalizations for Homeless Individuals on the Rise

A homeless individual is defined as someone who lacks fixed and reliable housing, and it is estimated that more than half a million people fit that description daily in the U.S. Looking at data across three states, investigators from the Brigham and Beth Israel Deaconess Medical Center (BIDMC) recently found that a growing proportion of homeless patients are being hospitalized and for very different health concerns than the broader American population.

Rishi Wadhera

Rishi Wadhera

The retrospective cohort study examined patterns, causes and outcomes of acute hospitalizations for homeless and non-homeless patients in three populous and diverse U.S. states: California, Florida and Massachusetts. They observed a rise in acute hospital use among homeless individuals, primarily driven by mental illness and substance use disorder. The results were published in the journal Medical Care last month.

“The homeless population is aging, and the rate of hospitalizations for homeless individuals is increasing,” said lead author Rishi Wadhera, MD, cardiology fellow in the Division of Cardiovascular Medicine at the Brigham and health policy researcher at BIDMC. “Although there has been a recent push to establish better policy and public health measures to improve the health of homeless adults, few studies have examined the patterns and causes of hospitalizations in this population.”

infographic on homeless hospitalizationsTo examine these trends, hospital discharge data was acquired from Massachusetts and Florida between 2007 and 2013 and from California between 2007 and 2011. This information came from the State Inpatient Databases (SIDs) of the Healthcare Cost and Utilization Project, created by the federal Agency for Healthcare Research and Quality. This dataset includes information such as homeless status, billing, demographics and diagnoses.

Overall, the researchers analyzed over 185,000 hospitalizations for homeless individuals and more than 32 million hospitalizations for non-homeless individuals. Over the periods studied, acute hospitalizations for homeless individuals increased in all three states (see infographic at left). Homeless patients were more often white (62 percent), male (76 percent), around 46 years old and either uninsured (42 percent) or insured by Medicaid (32 percent).

The researchers found that reasons for hospitalization among homeless and non-homeless individuals differed starkly, even after accounting for differences in demographics.

More than 50 percent of hospitalizations among homeless individuals were for mental illness and substance use disorder, while these conditions accounted for less than 20 percent of hospitalizations among demographically comparable non-homeless individuals.

Homeless adults also had a longer mean length of stay, averaging 6.5 days vs. 5.9 days among non-homeless patients. However, homeless individuals had lower in-hospital mortality rates (0.9 percent vs. 1.2 percent) and lower mean costs per day ($1,535 vs. $1,834) than the comparable non-homeless control group.

“Some states, such as Massachusetts, have expanded Medicaid eligibility, which has increased rates of insurance among homeless individuals and improved access to care. This could have led to greater use of hospital services,” said Wadhera.

“The increase in hospitalizations could also reflect more concerning trends. The opioid epidemic has disproportionately impacted the homeless population, and a repercussion of this may be an increase in acute hospitalizations,” he added. “It is also possible that these patterns suggest inadequate longitudinal care for homeless individuals, and that, from a policy perspective, we need to do a better job of providing more consistent, reliable outpatient care to this population.”

Brigham Researchers Develop Smartphone-Based Ovulation Test

A prototype of the ovulation-testing tool

A prototype of the ovulation-testing tool

Capitalizing on the latest technological advancements, a team of Brigham investigators has built a low-cost smartphone tool that can predict a woman’s ovulation and aid in family planning.

Powered by microfluidic technology (in which fluids flow through microscopic channels), artificial intelligence (AI) and the ubiquity of smartphones, the tool automatically detects fern-like patterns—a marker of ovulation—in a saliva sample. The team evaluated the performance of the device using artificial saliva in the lab and validated results in human saliva samples from six subjects, observing greater than 99 percent accuracy in effectively predicting ovulation. The results are published in Lab on a Chip.

“Before we started this project, we weren’t aware that such a need existed,” said corresponding author and principal investigator Hadi Shafiee, PhD, of the Division of Engineering in Medicine and Division of Renal Medicine.

“When we published last year on a technology for analyzing sperm to detect male infertility, we were approached by those who had read about our work and were wondering if we could develop a smartphone-based system to provide ovulation testing at home. Our study indicates that an accurate, automated and low-cost test is indeed possible.”

Those three elements are key, as current methods for monitoring fertility are often costly or subjective. These methods include ovulation detection by determining a woman’s luteinizing hormone (LH) level (a clinical blood test or at-home urine “dipstick” test), rectal or basal body temperature analysis, cervical mucus characterization and salivary ferning analysis. Salivary ferning refers to the unique appearance of dried saliva from a woman who is ovulating; when collected on a glass slide, saliva takes on a crystallized structure that resembles fern leaves. While relatively inexpensive and simple, this analysis is highly subjective. When performed by a layperson, it is prone to misinterpretation.

A diagram of the tool’s various components

To overcome this challenge, Shafiee and colleagues developed an automated process for detecting ferning in a saliva sample. Their AI algorithm was pre-trained with 1.4 million images from a broad visual database and then, more precisely, retrained with more than 1,500 salivary ferning images to classify saliva images into two categories: ovulating and nonovulating samples.

he team then evaluated the system’s ability to differentiate ovulating and nonovulating human saliva samples from six subjects. The women collected and tested their samples using the smartphone tool during both ovulating and nonovulating phases of their menstrual cycle (results were confirmed using a urine test).

To perform the test, saliva was collected on a microfluidic device, smeared and left to air-dry. The sample was inserted into a 3D-printed attachment affixed to a smartphone. The software then analyzed the fern patterns, correctly identifying ovulation in 99 percent of samples and nonovulation in 100 percent of them.

“One of the biggest advantages to this method is cost—whereas nonreusable urine stick tests can add up to $210 to $240 over the course of six months, our device represents the possibility of a one-time purchase,” said co-author Manoj Kumar Kanakasabapathy, a senior research assistant in the Shafiee laboratory. “Beyond human ovulation, there are applications here as well for animal breeding and even for dry-eye disease, which can also produce fern-like patterns in samples from eye mucosa.”

Prudhvi Thirumalaraju, another co-author and a senior research assistant in Shafiee’s lab, added: “One of the biggest problems with saliva-based tests, we realized, was that users find it difficult to interpret the fern patterns. We figured that advances in AI can be put to good use here to help people get objective results on their smartphones.”

The new system is constrained by some of the same limitations as traditional ovulation tests, and it cannot detect ovulation in women with estrogen imbalance, cysts in the ovaries and those who take fertility medications. Smoking or alcohol consumption may also interfere with accurate detection. The device will require additional testing in a larger population and approval by the U.S. Federal Drug Administration before it can be brought to market.

Study Examines New Strategy for Treating Aggressive Prostate Cancer

Anthony D’Amico headshot

Anthony D’Amico

What’s the best way to prevent aggressive prostate cancer from coming back? A new multinational study of more than 600 men with an advanced form of the disease confirms surgery alone does not offer the highest chance of survival and examines outcomes for men following a new combination treatment plan.

The study, conducted by Brigham researchers, investigated how treatment with surgery plus the appropriate use of postoperative low-dose radiation and hormone therapy fared as an option for these men before cancer recurrence. The current standard of care involves a slightly different treatment combination: high-dose radiation and hormone therapy. Researchers found that less than 10 percent of men who underwent either combination therapy died within five years, compared to 22 percent of men who underwent surgery alone.

Published earlier this month in JAMA Oncology, the findings position postoperative radiation and hormone therapy, administered before cancer recurrence, as a new prostate cancer treatment option for men with a Gleason Score of 9 or 10 electing to undergo surgery. The Gleason Score is the grading system used to assess the aggressiveness of prostate cancer and determine appropriate treatment. The higher the Gleason Score, the more likely the cancer will grow and spread quickly.

“In many cases when cancer recurs, radiation and hormone therapy are recommended, but our findings indicate that the best survival outcomes may be achieved by implementing these therapies directly after surgery and not waiting for the cancer to recur,” said Anthony D’Amico, MD, PhD, chief of Genitourinary Radiation Oncology. “While more than 75 percent of men in this study had risk factors for recurrence following surgery for which radiation and hormone therapy could have been recommended, only one-third received those treatments.”

A prior study showed that the risk of death is much higher when surgery alone is performed, compared to following the current standard of care. D’Amico said clinicians are often reluctant to use radiation and hormone therapy following surgery for patients with aggressive prostate cancer due to concerns about overtreatment.

“However, overtreatment in this population with aggressive and advanced prostate cancer is very unlikely, given that prostate cancer will recur in at least 80 percent of these men within five years of surgery and require radiation or hormone therapy at that time,” he said.

Unraveling the Mysteries of Sex Differences and the Brain

Participants speak at the Interdisciplinary Neuroscience Inaugural Symposium: Sex Differences and the Brain - Implications for Research, Health and Disease.

From left: Ursula Kaiser listens as Cynthia Lemere asks a question during the first annual Women’s Brain Initiative Symposium.

In human disease biology, sex differences are as perplexing as they are pervasive. One crucial place where these differences manifest themselves is in the brain and in conditions affecting or affected by this critical organ.

There are more women than men with Alzheimer’s disease, multiple sclerosis, obesity, eating disorders, anxiety and depression, for example, while men have higher rates of Parkinson’s disease and schizophrenia. Yet the reasons for these differences remain understudied and unknown.

“Women’s health is often understood to mean reproductive health, but that’s a narrow definition for the health of half the human race,” said Charles Jennings, PhD, executive director of the Brigham’s Program for Interdisciplinary Neuroscience and Ann Romney Center for Neurologic Diseases. “We’re increasingly recognizing that many and perhaps most diseases show differences between men and women. In many cases, the effects are quite large, and if we want to understand the cause and eventual treatment of these diseases, we can’t ignore the sex differences.”

With the help of a generous philanthropic gift from Rick and Nancy Moskovitz, the Brigham-wide Women’s Brain Initiative (WBI) launched in 2017 to support research over four years into women’s brain health and the science of sex differences.

WBI-funded projects may span a range of questions from basic biology—how male and female brains became wired differently—to practical clinical questions about sex differences in disease risk and treatment responses, as well as how conditions specific to women (such as pregnancy and menopause) influence brain health. The WBI also supports community-building through an annual symposium and an ongoing Seminar Series starting Dec. 18.

“Surprisingly, there is nothing like the WBI anywhere else,” said Patti Stoll, MBA, director of the Women’s Brain Initiative. “Our goal is to attract not only investigators who are currently interested in the subject but also those who might not yet appreciate how this area could be important for their research.”

A Catalyst for Curiosity

Rosalind Lai, MD, WBI research fellow in the Department of Neurosurgery, is examining how hormones affect subarachnoid hemorrhages—which result from the rupture of an intracranial aneurysm, an abnormal dilation in a blood vessel of the brain—and why these events occur more often in women than men.

“We know that hormonal levels are altered after a head bleed, but we want to know if estrogen is a contributing factor to the rupture of an aneurysm,” said Lai. “Being a part of the WBI means being a part of a supportive community that fosters interest and curiosity about sex differences and the brain.”

Lai attended the inaugural WBI Symposium on Sept. 26 and enjoyed talks by visiting researchers. One lecture that stood out to her was given by Arthur Arnold, PhD, from the Brain Research Institute at the University of California, Los Angeles, who spoke about how chromosomal differences could affect disease risks that have previously been attributed to hormones.

“His talk made me think more about the different factors that may affect sex differences,” said Lai.

Meeting of the Minds

Another goal of the WBI is to connect researchers and clinicians at the Brigham and encourage these experts in different disease areas to think about the effects of sex differences.

Ursula Kaiser, MD, WBI-funded researcher and chief of the Division of Endocrinology, Diabetes and Hypertension, studies the effects of endocrine-disrupting chemicals, which can act similarly to estrogens, on increased risk of premature puberty in girls.

Needing guidance about how to examine the role of estrogen in Parkinson’s disease, Silke Nuber, PhD, WBI-funded researcher in the Ann Romney Center, came to Kaiser for her expertise. Kaiser invited Nuber to her lab to learn some of the techniques for examining the effects of ovarian function and estrogen levels in preclinical models.

“I think one of the wonderful things about WBI is that it brings so many multidisciplinary groups together who perhaps haven’t interacted as much in the past,” said Kaiser. “It makes all of us more aware of other research being conducted at the Brigham.”

Building on a Brigham Legacy

The WBI does not exist in isolation—it builds on and unites entities and areas of focus with a long legacy at the Brigham. One of those collaborating entities is the Mary Horrigan Connors Center for Women’s Health and Gender Biology.

Hadine Joffe, MD, MSc, executive director of the Connors Center and vice chair for psychiatry research, has encouraged researchers to join the WBI to increase funding opportunities and further advances pertaining to sex differences and the brain. One of those investigators is Katherine Burdick, PhD, of Psychiatry, whose research on predictors of cognitive impairment in postmenopausal women with major depressive disorder (MDD) has become part of the WBI’s portfolio.

“I became aware of the opportunity to apply for funding via the WBI thanks to Hadine Joffe, with whom I worked to develop the protocol for the funded study,” said Burdick. “With support from the WBI, we are trying to identify clinical and biological explanations for why some postmenopausal women with MDD develop cognitive and functional disability while others do not. This information will hopefully lead to a more personalized-medicine approach in the future.”

Brigham Health’s Strategy in Action: Discovery and Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

Investigators Present Cardiovascular Discoveries at AHA Scientific Sessions

On Nov. 10, the American Heart Association (AHA) held its annual Scientific Sessions meeting in Chicago, featuring the latest advances from major cardiovascular trials with the potential to transform clinical practice. Investigators from the Brigham led some of the most highly anticipated trials and presented their results at the conference.

Insights into Omega-3s, Vitamin D

The benefits of omega-3 fatty acids – a “good” fat largely found in fish, nuts, flax seeds and leafy greens – have been touted in recent years. But just how protective are they in cardiovascular health?

JoAnn Manson shares findings from the VITAL study.

JoAnn Manson shares findings from the VITAL study.

Deepak L. Bhatt, MD, MPH, executive director of Interventional Cardiovascular Programs in the Division of Cardiovascular Medicine, presented results and insights from the clinical trial REDUCE-IT, which tested whether icosapent ethyl (a medication derived from an omega-3 fatty acid found in fish oil) could reduce the risk of cardiovascular events in at-risk patients. Participants were defined as “at risk” if they fell into one of two categories. Either they had atherosclerosis – a disease in which plaque builds up in the arteries – or they had diabetes plus at least one other cardiovascular risk factor along with elevated triglyceride levels, despite taking statins.

Participants who took the medication saw a 25 percent risk reduction in cardiovascular events and a 20 percent reduction in death due to cardiovascular causes, a result Bhatt described as “remarkable.”

“This may be the biggest development in cardiovascular prevention since statins,” he said. “The REDUCE-IT trial sets a new standard of care for these patients.”

In another presentation, JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine, unpacked results from the VITamin D and OmegA-3 TriaL (VITAL). VITAL also examined whether omega-3 fatty acids affected a person’s risk of experiencing cardiovascular events, but Manson and colleagues studied them among a general, racially diverse population and used a lower-dose supplement that contained both of the major forms of marine omega-3s. VITAL also examined effects on cancer occurrence.

The team found that omega-3s reduced the risk of heart attacks but did not reduce stroke, major cardiovascular events or cancer. VITAL also tested the effects of taking a vitamin D supplement, which did not reduce cardiovascular or cancer outcomes except for a signal that cancer deaths were lower over time.

Diabetes Drug Lowers Heart Failure Risk

A new class of diabetes drugs known as SGLT2 inhibitors can help lower blood glucose levels in patients with diabetes. Investigators are finding mounting evidence that the inhibitors may also lower cardiovascular risk.

Stephen Wiviott, MD, of Cardiovascular Medicine, shared findings from the DECLARE–TIMI 58 trial. The multinational trial tested an SGLT2 inhibitor known as dapagliflozin. Wiviott highlighted reductions in risk of adverse heart and kidney outcomes for patients.

Separately, Elisabetta Patorno, MD, DrPH, of the Division of Pharmacoepidemiology and Pharmacoeconomics, presented initial results from the real-world EMPRISE study, which found that another SGLT2 inhibitor reduced the risk of hospitalization for heart failure in routine care.

Inflammation and Heart Disease: A Roadmap for the Future

Brigham cardiologists have been at the forefront of basic, clinical and translational research linking inflammation and heart disease for decades and presented the next chapter in the ongoing story of the inflammatory hypothesis at this year’s meeting.

Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention, delivered results from the Cardiovascular Inflammation Reduction Trial (CIRT), a large-scale trial that tested whether low-dose methotrexate – an inexpensive, generic drug widely used to treat inflammatory diseases – was effective in reducing cardiovascular risk.

Last year, the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) showed that the high-cost drug canakinumab targeted a specific inflammatory pathway and consequently lowered rates of heart attack and cardiovascular death. By contrast, the findings from CIRT showed that low-dose methotrexate neither inhibited that same pathway nor did it reduce major adverse cardiovascular event rates.

“The results from CIRT and CANTOS, when considered together, tell us something critically important: Not all inflammation is the same, and not all drugs that target inflammation are the same,” said Ridker. “While it is disappointing that an inexpensive drug like methotrexate did not have the effects we previously saw in CANTOS, the results from CIRT shed crucial light on the underlying biology that connects inflammation with cardiovascular disease. The divergent trial results provide a clear roadmap to guide our efforts going forward.”

In a separate presentation, Brendan Everett, MD, MPH, director of General Cardiology Inpatient Service, reported that the interleukin-1β inhibitor canakinumab reduced hospitalization for heart failure and heart failure-related death. These data represent the first-large scale evidence that inflammation inhibition can improve outcomes in heart failure. The results suggest that the role of inflammation reduction in improving heart failure outcomes merits further exploration.

Celebrating Innovation at Discover Brigham

The Brigham was buzzing with excitement as Discover Brigham drew hundreds of attendees to the hospital’s main campus on Nov. 7.

Through digital poster sessions, hands-on demonstrations, panel discussions, award presentations and more, the event showcased the Brigham’s expertise in several areas of science, medicine and technology. This year’s event highlighted discoveries and insights around lung disorders, sleep medicine, genomics, cancer, women’s health and opioid use disorder.

The day-long event concluded with an awards ceremony that announced the winners of the BRIght Futures Prize and Brigham Research Institute Director’s Transformative Award.

From a Harrowing Past Emerges a Brighter Future for Brigham Researcher

Morteza Mahmoudi

Morteza Mahmoudi displays the latest prototype of a novel skin patch designed to heal chronic wounds.

Morteza Mahmoudi, PhD, vividly remembers the fear and heartache he felt as a child growing up in Iran during the Iran-Iraq War in the 1980s. The armed conflict played out in the streets of his hometown of Tehran, where he says it wasn’t unusual to encounter a friend, neighbor or loved one suffering from traumatic injuries following a missile attack.

But just as clearly, Mahmoudi recalls what the voice inside him often said those days: Help people. Help heal their pain.

Now a biomedical investigator at the Center for Nanomedicine and the Department of Anesthesiology, Perioperative and Pain Medicine, Mahmoudi has spent the last three decades following that calling. It has propelled him to fulfill his life mission to ease suffering, no matter the obstacle.

“The war was a very hard period, but when I think about those days, I realize that kind of experience puts fuel in your motivational tank for the rest of your life,” he said. “From the time I entered university, I made the decision to use my past as a driving force for the future.”

As the winner of the seventh annual BRIght Futures Prize, Mahmoudi is especially hopeful about what tomorrow holds for patients around the world. The competition’s $100,000 award will support his project, “Time to Heal Chronic Wounds.”

Sponsored by the Brigham Research Institute, the BRIght Futures competition invites the Brigham community and the public to vote for one of three finalists whose innovative research is poised to transform medicine. This year’s competition garnered its largest-ever number of votes: 16,530. Mahmoudi was announced as this year’s winner during an awards ceremony at Discover Brigham on Nov. 7.

For the past 10 years, Mahmoudi has been working to develop a skin patch to heal chronic wounds that the body is unable to repair on its own, such as bedsores and diabetic wounds. There is no effective treatment for these types of wounds, which can easily become infected and sometimes lead to amputation or even death.

Mahmoudi’s patch is made from multifunctional nanofibers – fibers that are 1,000th the diameter of a single human hair – that mimic most of the skin’s characteristics. They are engineered to deliver a cocktail of healing biomolecules and immunotherapeutic nanoparticles to a wound site. These unique properties can help cells reach the site of a wound and create new blood vessels. Meanwhile, the nanoparticles detect and help fight infections while also lessening inflammation. The BRIght Futures Prize funding will help advance the project from the lab bench to clinical trials so that it can be rigorously tested in humans.

A Long Road

Once he got the idea for the patch, Mahmoudi soon realized how ambitious an endeavor creating it would be. It demanded expertise in four highly complex, distinct scientific fields: materials science and engineering, biomedical engineering, nanomedicine and cell biology. Undeterred, Mahmoudi earned a degree in each one (a bachelor’s, master’s, doctorate and post-doctorate, respectively).

“The time in which I was working on bachelor’s and master’s was extremely hard, as in addition to my university courses and research, I had to work over 70 hours per week as a high school teacher to support my family at the time,” Mahmoudi recalled. “The motivational fuel and my old friend – my internal monologue – gave me the stamina to make it through those days and continue my scientific activities while also taking care of my immediate family.”

He kicked off his research career at universities in Ireland, Switzerland and the U.S., advancing his understanding of science and medicine as he chipped away at the project’s protocols and prototypes.

“I was like a scientific nomad,” he said. “Ten years ago, the crosstalk between different experts was not great – not like today – so that’s why I had to train in different medical and engineering fields.”

Each part of the patch – its precise structure and physical, chemical and mechanical properties – took years to perfect.

“I would say that this was one of the hardest projects I’ve ever done because it took a lot of time, and I could have easily given up many times, but I kept going,” he said. “My long-term collaborators and I made a huge number of prototypes. We haven’t yet published anything on this topic, as I believe that the scientific community and patients would benefit from the A-to-Z story, rather than progressive reports. We needed to make sure our final prototype was error-free, and we are now at that stage.”

Being part of the Brigham’s highly collaborative clinical and research community has been a tremendous gift in advancing this work, Mahmoudi said.

Today, he is excited to see the project move one step closer to changing outcomes for patients with chronic wounds, thanks to the BRIght Futures Prize.

“If I can reduce the pain of one patient, even for one minute, I have done my share. But if these patches can help many lives, that would be my ultimate dream,” Mahmoudi said. “This prize opens the way to that.”

Brigham Health’s Strategy in Action: Scalable Innovation
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Study Examines Opioid Use, Overdoses Among Massachusetts Adolescents

Avik Chatterjee

Avik Chatterjee

Opioid-related overdoses and deaths remain a major public health concern in Massachusetts, yet adolescents who experience opioid-related nonfatal overdose have been rarely studied. Using public data, Brigham investigators recently unearthed several important ways in which the opioid crisis is playing out differently among young people versus adults.

Performed in collaboration with colleagues at the Boston University School of Medicine and Massachusetts Department of Public Health (DPH), the analysis examined data on Massachusetts adolescents, ages 11 to 17, who experienced an opioid-related nonfatal overdose between 2012 and 2014. In addition to understanding how prevalent these events were in young people compared to adults, researchers also found differences in how adolescents receive medication to treat opioid use disorder after experiencing a nonfatal overdose. The team’s results were recently published in Drug and Alcohol Dependence.

Among the findings were that adolescent girls were more likely to experience an opioid-related nonfatal overdose – the opposite of what has been observed in adults – although the reasons for this remain unclear. Additionally, investigators discovered these events were, overall, far less common in young people in the period studied, occurring in just under 200 adolescents versus more than 22,000 adults.

“This evidence will help guide the conversation about adolescent opioid abuse. In a lot of ways, this study raises more questions than answers, such as why more adolescent girls are overdosing than boys,” said Avik Chatterjee, MD, MPH, first author and associate epidemiologist in the Division of Global Health Equity at the Brigham. “The ability to bring attention to a population that has been understudied with regard to the opioid epidemic will help researchers and physicians explore ways to treat this epidemic in adolescence.”

‘An Opportunity to Intervene’

An opioid-related nonfatal overdose occurs when an individual uses an opioid, sometimes in conjunction with other drugs, and becomes mentally altered or sedated to the point that immediate, lifesaving treatment is necessary.

“A nonfatal overdose might be an opportunity to intervene,” said Chatterjee. “Individuals are using opioids so much that they are at risk of dying, so this could be a time when health care professionals could step in and help the person obtain treatment before a fatal overdose occurs.”

To examine the adolescent and adult rates in Massachusetts, researchers analyzed DPH data pooled from the entire state. This dataset represents 98 percent of Massachusetts residents and includes nonidentifiable medical information from hospitals, ambulance systems, substance-use systems, health insurance companies and homeless shelters.

“This analysis took advantage of a unique tool developed by the Massachusetts Department of Public Health to enable us to access linked, multiyear data for analysis of fatal and nonfatal opioid overdoses, as well as for other health priorities and trends,” said Dana Bernson, assistant director of Special Analytic Projects at the DPH. “These results highlight the importance of our partnerships with researchers from academic, nonprofit, private and government agencies in using data to respond to the opioid epidemic.”

Researchers were interested in examining whether adolescents received medication – methadone, buprenorphine or naltrexone – to treat an opioid use disorder within 12 months of experiencing a nonfatal overdose. They found that only 8 percent of adolescents were prescribed one of these medications within a year of the overdose.

The authors note that these numbers may be low because many people now have access to opioid overdose reversal drugs outside of a health care setting.

“This study demonstrates that the opioid epidemic is different in adolescents,” Chatterjee said. “This new knowledge will shape how we intervene and prevent opioid overdoses in adolescents.”

If you or someone you know would like to seek support for substance use disorder, contact the Addiction Recovery Program, an outpatient service in the Department of Psychiatry that helps patients with substance use disorder, at 617-983-7060, option 2.

B-PREP Program Aims to Stop Breast Cancer in Its Tracks

Bprep

From left: Mil Pierce reviews information about a clinical trial with Shivam Dua at the Comprehensive Breast Health Center.

As far as she can tell, Mil Pierce, 55, of Belmont has done everything right in terms of leading a healthy lifestyle. She never smoked. She goes to the gym twice a week and walks her dog nearly every day. She doesn’t drink alcohol in excess. And she’s eliminated red meat from her diet.

Pierce has made these choices with the knowledge that she has a strong family history of breast cancer. The disease has affected her mother, maternal grandmother and a maternal great aunt, among many other relatives.

Yet after Pierce underwent genetic testing to see if she had an inherited mutation in the BRCA1 or BRCA2 genes – an alteration that greatly increases a woman’s risk of breast cancer – the lab results showed she didn’t have the harmful mutation.

That’s why Pierce was stunned to learn two years ago, following a biopsy, that there were precancerous cells in her breast tissue. If left untreated, the abnormal cells could develop into breast cancer.

“When I got that diagnosis, it hit me like a brick. I thought, wow, there’s something else going on,” she said. “Genetically speaking, there’s no explanation for it.”

Today, Pierce is hopeful not only for her own continued health but also that of her two teenage daughters, thanks to the care, resources and guidance she’s receiving through the Breast Cancer Personalized Risk Assessment, Education and Prevention (B-PREP) Program at Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC).

Launched about two years ago and led by Tari King, MD, chief of Breast Surgery at DF/BWCC, the B-PREP Program develops a comprehensive, customized risk profile for every patient and a personalized plan aimed at reducing the likelihood of developing breast cancer. Upon entering the program, patients complete a survey that asks not only about their medical history but also a wide range of lifestyle factors that experts believe can contribute to breast cancer risk, including diet, physical activity, sleep, weight changes, whether they work a night shift and more.

“Assessing individual risk for breast cancer is complicated,” King said. “Breast cancer is not just one disease; it is a family of diseases, and the risk factors that can lead to the development of different types of breast cancer also vary.”

King emphasized that the program is open to all patients, including – and perhaps especially – those who don’t know their breast cancer risk.

“Many women think that if breast cancer is not in their family that they don’t have to worry about it, and that is not true. In fact, most women who come in with their first diagnosis of breast cancer don’t have a family history,” King said. “Our doors are open to anyone who wants to learn about their risk.”

Novel Trials

Another big misconception the B-PREP Program is working to dispel is that people at increased risk are at the mercy of their biology, King said. Based on what B-PREP’s multidisciplinary team learns from an assessment, each patient receives personalized recommendations and is connected to relevant resources, such as a referral to the Brigham’s Program for Weight Management or information about clinical trials currently enrolling patients.

One such novel trial is looking at how exercise affects breast cancer risk in women who have dense breast tissue and do not currently engage in regular exercise. Led by Jennifer Ligibel, MD, a medical oncologist specializing in breast cancer at DF/BWCC, the study pairs participants with a personal trainer for 12 weeks. Researchers will collect a breast tissue sample from participants before and after they complete the exercise program.

“We know that women who exercise more have a lower risk of developing breast cancer, but we don’t know why. We also know that denser breast tissue – that is, tissue containing more glandular elements to it and less fatty tissue – is linked to a higher risk, and, again, we don’t know why,” Ligibel said. “In a previous study we conducted looking at women who already had breast cancer, we saw that exercise actually changed the immune system within the cancer. Now, we’re looking at whether those same types of changes from exercise can be seen before a tumor has even emerged.”

Pierce learned about her eligibility for the study from her B-PREP providers and became one of the first patients to enroll. She appreciates how comprehensive the B-PREP Program is, including the opportunities to participate in clinical trials that explore wellness-based approaches to prevention.

“This breast density and exercise study was music to my ears,” she said. “I’m really excited about being on the cutting edge of research, especially since there’s a mystery here.”

Brigham Health’s Strategy in Action: Advanced, Expert Care
Learn more about our strategic priorities at BWHPikeNotes.org.

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Nationwide Study Finds Patients at Risk of Coverage Denial

During a medical emergency, the last thing anyone wants to worry about is their ability to pay for care. But according to a recent study by Brigham researchers, flawed insurance policies can result in denied coverage for patients visiting an emergency department (ED) based on their discharge diagnosis.

Brigham investigators analyzed a national sample of ED visits between 2011 and 2015 to determine the proportion that could be denied coverage if commercial insurers across the U.S. adopted the coverage-denial criteria of a large national insurer, Anthem, Inc., based on ED discharge diagnoses.

Shih-Chuan (Andrew) Chou

Researchers studied ED visits of more than 28,000 commercially insured adults, ages 15 to 64, and found that the insurer’s list of nonemergent diagnoses would classify coverage denial for nearly 16 percent of the visits examined. On a larger scale, that could translate to 4.6 million ED visits annually. Their findings were published this month in JAMA Network Open.

“Up to one-sixth of adult emergency department patients with private health insurance would qualify for further review and may be denied coverage under this policy,” said lead study author Shih-Chuan (Andrew) Chou, MD, MPH, of the Department of Emergency Medicine.

Researchers noted that in almost 90 percent of ED visits, the primary presenting symptoms that brought patients to the emergency department were the same presenting symptoms as those with diagnoses at risk of denial. Yet, among these patients, more than 65 percent received emergency-level services, such as imaging or multiple blood tests.

Jeremiah Schuur

Researchers concluded that it is problematic for insurance companies to retrospectively determine coverage for a visit based on diagnosis because patients decide to go to the ED based on their symptoms – a decision that may be very reasonable at that time.

“Nearly 90 percent of adult ED patients will have symptoms that could lead to a nonemergency diagnosis – and review for possible coverage denial – including symptoms such as chest pain, which is one of the most common reasons patients are hospitalized from the ED,” Chou said.

Senior author Jeremiah Schuur, MD, MHS, of Emergency Medicine, said the onus should not be on patients to determine if such symptoms warrant coverage for emergency care.

“Patients come to the ED with symptoms and not diagnoses,” he said. “After-the-fact policies that use final diagnoses to judge the appropriateness of an ED visit and further apply a financial penalty will put patients in a difficult spot where they are expected to self-determine whether there is a concerning illness. A better solution is to make it easier for patients to receive care for acute illnesses when they want to go outside the ED and access, for example, urgent care centers.”

Study: Weight Loss Drug Shows Positive Effect on Diabetes

The weight loss drug lorcaserin shows promise for reducing the risk of diabetes and aiding patients with the disease, according to a recent study by Brigham researchers.

Approved by the U.S. Food and Drug Administration in 2012 for adults with obesity – and those who are overweight and have weight-related medical problems – lorcaserin controls a patient’s appetite by triggering feelings of fullness. Investigators from the Thrombolysis in Myocardial Infarction (TIMI) Study Group led a clinical trial to test the effects of lorcaserin, manufactured by the trial’s sponsor, Eisai Inc., in 12,000 overweight or obese patients at risk for a heart attack or stroke. At the start of the trial, more than half of participants had diabetes and another third had prediabetes.

Erin Bohula

During this year’s European Association for the Study of Diabetes and in a simultaneous publication in The Lancet, the research team reported that taking lorcaserin decreased risk for diabetes, induced diabetes remission and reduced risk of diabetes complications in obese and overweight patients.

These latest findings build on a related discovery the same team of Brigham investigators reported earlier this year on the cardiovascular safety and weight loss effectiveness of lorcaserin.

“We recently presented findings showing that use of lorcaserin resulted in modest but sustained weight loss among obese and overweight patients without increasing risk of heart attack and stroke,” said co-lead author Erin Bohula, MD, DPhil, a cardiovascular medicine and critical care specialist in the Division of Cardiovascular Medicine and a staff investigator for the TIMI Study Group. “Now we report that, when added to lifestyle interventions, lorcaserin significantly reduced incidence of diabetes, increased rates of diabetes remission and reduced the risk of diabetic microvascular complications.”

Benjamin Scirica

Researchers found that lorcaserin reduced risk of diabetes by 19 percent in prediabetic participants. Among those with diabetes, 21 percent saw a reduced risk of diabetic microvascular complications, which affect small blood vessels and lead to issues in the kidney (persistent microalbuminuria), eyes (diabetic retinopathy) or nerves (diabetic neuropathy).

“Lorcaserin provides another tool, beyond diet and exercise, for patients hoping to achieve and maintain weight loss. And, happily, even relatively modest weight loss can improve the diabetes control in those with diabetes and reduce the development of diabetes in those at risk,” said co-lead author Benjamin Scirica, MD, also of Cardiovascular Medicine and a senior investigator for the TIMI Study Group.

Hypoglycemia, or dangerously low levels of blood sugar, could be a negative side effect of taking lorcaserin for patients already on medications to lower blood sugar. For example, among participants taking insulin or a sulfonylurea (a medication to treat Type 2 diabetes), researchers reported more events of severe hypoglycemia requiring hospitalization or considered to be life-threatening – recording 12 events with lorcaserin versus four events with a placebo. The authors note that this finding highlights the importance of carefully adjusting agents known to increase risk of hypoglycemia, especially while a patient is working to lose weight.

“Given the global prevalence of obesity and its association with Type 2 diabetes and complications that can cause death or greatly diminish quality of life, we need therapeutic strategies that can be added to lifestyle modification to prevent and control diabetes,” said Scirica. “This rigorous and large-scale randomized study demonstrates the potential for improving glycemic control when adding a weight loss agent to a treatment plan.”

Channing Division Celebrates 50 Years of Pioneering Discoveries

From left: Edwin Silverman, Fran Grodstein, Scott Weiss, Yukari Perrella and Meir Stampfer

When Fran Grodstein, ScD, associate director of the Channing Division of Network Medicine and director of its Chronic Disease Epidemiology Unit, reflects on the many seminal discoveries made by Channing investigators over the past 50 years, there is no shortage of groundbreaking research that comes to mind.

Underpinning all of those accomplishments – from findings about the risks associated with consuming foods containing trans fats to the role of aspirin in preventing colorectal cancer – is not just academic excellence. Equally essential has been the Channing’s longstanding culture of professional and personal support that inspires dedication to its mission, Grodstein told an audience of investigators, clinicians and staff during a recent event celebrating the Channing’s 50th anniversary.  

“It’s a true culture of kindness, generosity and support that I have absolutely no doubt is the only reason we’ve remained as successful as we have been,” said Grodstein, one of several speakers at the ceremony and symposium commemorating the Channing’s anniversary milestone in Bornstein Amphitheater on Sept. 20.

In 1968, the Channing Laboratory became an independent research entity at Boston City Hospital with its own building on Albany Street. The Channing moved to Longwood Avenue in 1977 and joined what is now the BWH Department of Medicine. In 2012, it became the Channing Division of Network Medicine. 

Now comprising 96 faculty, 39 trainees and 145 staff members, the Channing Division of Network Medicine uses an integrated, network-based, systems biology-driven approach to better understand complex diseases and to develop new treatments and preventive strategies for them. 

Edwin Silverman, MD, PhD, chief of the division, chronicled his own history with the Channing and reflected on the many opportunities it has given him to learn and grow. Joining the lab as a postdoctoral fellow in 1994, he established the Boston Early-Onset Chronic Obstructive Pulmonary Disease (COPD) Study, which sought to identify genetic factors associated with the disease in young people. 

Silverman recalled driving 40,000 miles over four years to administer questionnaires, perform breathing tests and collect blood samples in participants’ homes. A map illustrating those travels still hangs in his office as a reminder of those early days. 

Over the years, he said, it has been exciting to witness the extraordinary research contributions made by Channing scientists and staff. Numerous studies transformed the perception of COPD from a purely smoking-related to disease to one defined by both genetic and environmental risk factors. 

Silverman also highlighted several discoveries that led directly to U.S. policy changes to improve public health, including the labeling and removal of trans fats in foods after Channing researchers in the Nurses Health Study found a link between trans fats and increased risk of coronary heart disease and overall mortality. In another example, Channing-led research resulted in changes to federal environmental regulations after investigators showed that fine-particulate air pollution levels were associated with increased mortality. 

“A key principle in all of this has been the willingness and ability to integrate population-based research, laboratory research and innovative data analysis,” Silverman said. 

Looking ahead, the division will continue its multidisciplinary research studies of many diseases, while working to intensively develop research programs in three major areas of study: healthy aging, the microbiome and the study of multiple “omics” (a term referring to the group of sciences ending in the suffix “-omics,” such as genomics and metabolomics) to better understand what causes complex diseases to emerge and progress.

“I am very proud of what Channing investigators have accomplished, both historically and in the current era,” said Joseph Loscalzo, MD, PhD, chair of Medicine and physician-in-chief at BWH. “But I’m even more excited about what Channing investigators will contribute in the future as their approach to big data, systems analysis, systems dynamics and network medicine come to full fruition.”

Brigham Health President Betsy Nabel, MD, applauded the division for its remarkable work and commitment to improving public health over the past five decades.

“I want to congratulate and thank all of you, the entire Channing team – including investigators, staff and trainees – for your valuable contributions to the Brigham, to our knowledge of medicine and all that you’ve done for our patients and families,” Nabel said. 

BWH Study Finds Sleep Apnea Prevalent, Undiagnosed Among African Americans

Dayna Johnson

Sleep apnea is a common sleep disorder associated with an increased prevalence of cardiovascular disease, hypertension, diabetes and other chronic health disorders. About 80 to 90 percent of individuals with sleep apnea are undiagnosed, and a large number of them are African Americans, according to a new BWH study.

Brigham investigators determined the prevalence of sleep apnea among 852 African-American adult men and women living in Jackson, Miss., and participating in the Jackson Heart Sleep Study. Researchers explored sleep apnea predictors and estimated the proportion of undiagnosed cases. They found a high prevalence of sleep apnea among this large sample of African-American men and women, and the majority – 95 percent – were undiagnosed and untreated. Their results were published this month in the journal SLEEP.

“We discovered that only 5 percent of individuals with moderate or severe sleep apnea had been diagnosed. In other words, over 95 percent of this sample experience nightly stresses associated with periods when breathing stops and oxygen levels fall. Untreated sleep apnea can increase risk for hypertension-related diseases such as stroke, a condition disproportionately common in African Americans,” said Dayna Johnson, PhD, associate epidemiologist in the Division of Sleep and Circadian Disorders and lead author on the study. “We also learned that asking about habitual snoring and measuring neck size (a risk factor for sleep apnea) can help identify individuals at risk.”

Researchers found that 24 percent of participants had moderate or severe sleep apnea, but only 5 percent had been diagnosed by a doctor. Men had a 12-15 percent higher prevalence of the disorder compared to women. The average age of the study sample was 63 years old; 66 percent of participants were female. In addition to habitual snoring and larger neck size, higher body-mass was identified as another important marker of sleep apnea. This is the first-known study of its size to conduct objective testing for sleep apnea and administer validated questionnaires in a sample of African Americans.

Susan Redline

“There is a large burden of untreated sleep apnea in the population. Our results point to the opportunity to improve sleep apnea screening and diagnosis in the population as a means for reducing health disparities,” said Susan Redline, MD, MPH, senior author of the study.

Michael Twery, PhD, director of the National Center on Sleep Disorders Research at National Heart, Lung and Blood Institute, added: “These findings in the Jackson Heart Study reveal that sleep apnea is underdiagnosed and a potential threat to the health and safety of African Americans. Further studies are needed to develop the tools and systems required to facilitate diagnosis and treatment of sleep apnea in African Americans and other communities.”

NICU Milk Analyzer Study Aims to Personalize Pre-Term Infant Nutrition

From left: Mandy Brown Belfort and Valencia Koomson, with baby Justin

During a prenatal visit for their second child, Valencia and Jude Koomson were surprised to learn Valencia had pre-eclampsia, a form of high blood pressure that can occur during pregnancy. The diagnosis, just 28 weeks into her pregnancy, led to immediate hospitalization and, within days, the premature birth of their son.

That was the best option for the health of both Valencia and baby Justin, born 12 weeks before his due date and weighing just over 3 pounds. He would require intensive support to continue to grow and develop in the Brigham’s Neonatal Intensive Care Unit (NICU).

With breathing assistance for Justin’s developing lungs and a feeding tube to deliver human breast milk to his belly, he grew and thrived. He soon graduated from the Intensive Support area to the Growth and Development area, no longer needing oxygen support and becoming strong enough to feed on his own.

One novel technology available to him was a breast milk analyzer, a device that assesses nutritional composition of human breast milk. Justin was among the first babies enrolled in a new study at BWH to examine whether knowing the exact nutrition in individual feedings of human milk, and adding the right nutrients (also known as fortification), could aid the smallest babies.

“We know that more optimal nutrition is a predictor of better growth and neurodevelopment,” said Mandy Brown Belfort, MD, MPH, of the Department of Pediatric Newborn Medicine.

Special Nutritional Needs

Human breast milk is uniquely equipped to meet nutritional needs of full-term infants. But pre-term babies – especially those born before 35 to 36 weeks’ gestation – generally require that a fortifier containing calories, protein, calcium and micronutrients such as zinc and Vitamin A be added to a breast milk diet. This aims to replicate the nutrition the baby would receive from the mother’s placenta if still in the womb.

Typically, a premature infant’s growth is followed carefully, but the fortifier is only adjusted if the baby’s weight gain slows over several days. Belfort and her team are using the milk analyzer to avoid this lag, with the goal of delivering accurate, customized fortification with each feeding.

The milk analyzer was initially developed and used in the dairy industry. Recently adapted for human breast milk, it is approved for use in Europe and Canada. In the United States, it is currently available only for research purposes. BWH is one of a few NICUs engaged in that research.

Prior research by Belfort and others has shown surprising variations in the nutritional composition of a mother’s milk throughout a given day. Nutritional makeup also varies from one mother to the next, and it is not necessarily related to the mother’s diet. It’s also known that nutritional quality can degrade as expressed milk is handled and stored.

In Belfort’s current study, each feeding of milk is sampled and analyzed using the countertop device that sits in the NICU’s milk storage room. A tiny syringe, containing less than a teaspoon of milk, is inserted into the analyzer. A readout shows within seconds the milk’s nutritional elements. The results determine how much fortifier should be added on top of the standard fortifier to ensure that nutrient targets are met.

Study results won’t be known immediately as to whether this nutritional fine-tuning will improve growth and development in pre-term babies. The first patients began in the study in spring 2018. Belfort’s team is continuing to offer NICU families the opportunity to volunteer.

Valencia, a scientist herself, was glad to know that she was giving her baby every opportunity to grow, while contributing to newborn science.

“We are thrilled and blessed that he could participate to customize his feedings to his specific nutritional needs,” Valencia said. “Particularly for NICU mothers, there is so much anxiety and uncertainty about what your baby needs. It’s a great comfort to know he’s being fed well here. A baby needs to eat to grow.”

She also expressed her gratitude for the high-quality, compassionate care that she and her family received.

“All the people here are so consistently amazing,” Valencia said. “I want to say a big thank you to the staff at Brigham and Women’s Hospital and the NICU. At all levels of staff, there are such wonderful, caring and loving people here.”

Brigham Health’s Strategy in Action: Discovery and Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

BWH Receives First NICU Installed MRI System in the U.S.

Work crews lower the NICU’s MRI into the Connors Center.

Arriving by crane through a roof hatch in the Mary Horrigan Connors Center for Women and Newborns on Sept. 8, a new MRI system specifically designed for safe imaging of newborns will provide high-quality scans directly in the Brigham’s Neonatal Intensive Care Unit (NICU). The system, approved by the U.S. Food and Drug Administration last year, is the first NICU-dedicated MRI in the country.

“The installation of the state-of-the-art, neonatal MRI system will greatly enhance the research capabilities of BWH and elevate and expand neurocritical care for our littlest patients,” said Terrie Inder, MBCHB, chair of the Department of Pediatric Newborn Medicine. “Locating this technology within the NICU will reduce time and patient risk associated with transporting newborns to a traditional MRI and allow MRI access from the first hours of life through the challenging, sometimes life-threatening, time within the NICU.”

Babies undergoing scans will be in a temperature-controlled, self-contained incubator bed that minimizes the patient’s movement while allowing for better control of the environment and continuous monitoring of vital signs. Information gained from the MRI can inform a care team and family as to whether brain injury has occurred and, in the future, guide which treatments may assist in preventing disability.

The self-shielded, permanently magnetic system has been specifically designed for the NICU, an area that would be typically size- and risk-prohibitive for an MRI. The system is also quieter than traditional whole-body scanners to ensure the safety and comfort of infants undergoing scans.

Manufactured by Aspect Imaging, the system, known as EMBRACE, initially will be used for research purposes.

“This new MRI system, designed with a single use – scanning of the newborn – will enhance the care we provide for our NICU patients. This empowering technology will complement our existing fleet of MRI scanners and improve efficiency by offering imaging to our tiniest patients within the controlled confines of the NICU,” said Srinivasan Mukundan Jr., PhD, MD, medical director of Magnetic Resonance Imaging in the Department of Radiology.

Brigham Health’s Strategy in Action: Advanced, Expert Care
Learn more about our strategic priorities at BWHPikeNotes.org.

The Art of Diagnosis: Looking for Medical Clues in the Mona Lisa’s Portrait

Mandeep Mehra posits that several details in the Mona Lisa suggest the iconic portrait’s subject suffered from a chronic medical condition.

The source of the Mona Lisa’s mystery has been a topic of scrutiny for centuries, and one Brigham physician-scientist maintains that her captivating expression reveals important medical clues about Lisa Gherardini, the subject of Leonardo da Vinci’s iconic painting.

Previously, researchers hypothesized that Gherardini suffered from familial heart disease and a lipid disorder. This diagnosis was made by rheumatologists and endocrinologists in 2004 and is primarily based on the skin lesions visible in the portrait.

In an article in Mayo Clinic Proceedings, Mandeep R. Mehra, MD, medical director of the BWH Heart & Vascular Center, detailed a new medical interpretation of the famous portrait. He suggested that the Mona Lisa’s thinning hair, missing eyebrows, skin lesions and yellowed eye and skin color point to a different condition: hypothyroidism.

The diagnosis is based on a careful analysis of Gherardini’s face and body as well as epidemiological information about 16th-century Italy. After studying the painting, Mehra concluded that while some visual clues are consistent with a lipid disorder, the era in which Gherardini lived weakens the feasibility of premature heart disease. In the 16th century, inaccurate understandings of the human body and rudimentary medical care meant that someone with heart disease in their 20s was unlikely to live to age 63, as Gherardini reportedly did.

Iodine is critical for the function of the thyroid, but because the body does not produce this mineral, it must be consumed through food sources or supplements. Without enough iodine, the thyroid cannot produce certain hormones, resulting in hypothyroidism. This condition is associated with a variety of symptoms, including fatigue, facial swelling, hair loss and weight gain. Prior to the invention of iodized salt, hypothyroidism was common among people whose diet did not naturally contain iodine.

While the Italian Renaissance was a period of great artistic development, it was also a time in which poor nutrition and insufficient medical care were common, even among the wealthy. The diets of 16th-century Italians were lacking in iodine. Gherardini lived in Florence, a city whose inland location prevented easy access to the seafood or meat that could have prevented hypothyroidism.

Gherardini is depicted with suggestion of a swollen thyroid gland, also known as a goiter, which supports the diagnosis of hypothyroidism, Mehra said. Additionally, historical records indicate that Gherardini gave birth to her son Andrea shortly before sitting for the portrait. She likely developed peripartum hypothyroidism – a form of the disease that emerges during pregnancy – that continued to affect her as a chronic condition.

Mehra noted it is also possible that she may have had hypothyroidism with primary biliary cirrhosis, a disease that destroys the bile ducts in the liver, although living for 40 years with that condition untreated would have been unlikely.

“The enigma of the Mona Lisa can be resolved by a simple medical diagnosis of a hypothyroidism-related illness,” he said. “In many ways, it is the allure of the imperfections of disease that give this masterpiece its mysterious reality and charm.”

Study: Moderate Carbohydrate Diets Healthiest over Long Term

Don’t trade bread for bacon just yet. According to a recent study by Brigham researchers, low-carbohydrate diets may not be as healthy as popularly believed.

Upon examining the relationship between carbohydrate intake and lifespan, investigators discovered that while higher carbohydrate intake was related to greater risk of mortality, so was lower carbohydrate intake.

The team, whose findings have been published online in The Lancet Public Health, concluded that the longest life expectancy was seen among individuals whose regular consumption of carbohydrates was in the midrange – about half of total caloric intake.

Prior randomized trials of low-carbohydrate diets have suggested short-term benefits, including weight loss and cardiovascular risk factor control, but longer-term data on trial outcomes has been unavailable. Meanwhile, data from observational studies on the long-term health effects of low-carbohydrate diets had been conflicting, largely due to differences in dietary patterns between different populations in the study groups.

To get a more accurate picture, the BWH researchers, working with collaborators at Harvard T. H. Chan School of Public Health, examined data from more than 430,000 adults enrolled across eight studies and three continents.

Sara Seidelmann

“It was important to combine data from North American, European and Asian countries in order to fully understand and appreciate the relationship between carbohydrate intake and risk of earlier death that exists across the global spectrum of eating patterns,” said Sara Seidelmann, MD, PhD, a fellow in the Division of Cardiovascular Medicine.

Plant- vs. Meat-based Diets

After looking at what types of foods participants regularly ate, Seidelmann and her colleagues noted that people with low-carbohydrate diets more frequently consumed meat and other animal-based foods, compared to individuals with different levels of carbohydrate intake.

They subsequently observed that diets largely based on animal-derived protein and fat sources – from foods like lamb, beef, pork and chicken – were associated with higher mortality. Those that favored plant-derived protein and fat intake – from foods like vegetables, nuts, peanut butter and whole-grain breads – had a lower mortality rate.

“Our data suggest that animal-based low carbohydrate diets, which are more prevalent in North American and European populations, shorten life span in the long term,” Seidelmann said.

“Alternatively, if one chooses to restrict carbohydrate intake as an approach for weight loss or to improve heart health, replacement of carbohydrates with predominately plant-based fats and proteins should be strongly considered as an alternative.”

Senior author Scott Solomon, MD, of Cardiovascular Medicine and Edward D. Frohlich Distinguished Chair at BWH added: “These results help us better understand the relationship between the specific components of diet and cardiovascular health. While a randomized trial has not been performed to compare different types of diets, these data suggest that shifting towards a more plant-based diet should help attenuate cardiovascular disease.”

Brigham Health’s Strategy in Action: Discovery and Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

A Deep Look at Nasal Polyps Offers Insights into Allergic Diseases

Nasal polyps – soft, round outgrowths that can appear in the nasal passages and sinuses – can be chronic and relentless. Although noncancerous, these outgrowths can grow large enough to block the nose and sinuses, leading to discomfort, breathing problems and infections. And while they can be surgically removed, they may grow back, sometimes in a matter of days.

Although most patients are happy to be rid of their polyps, for researchers, that tissue is precious: It may hold critical clues about intense, allergic inflammation. Brigham investigators, along with collaborators from the Broad Institute and Massachusetts Institute of Technology, have used some of the most advanced sequencing technology to peer into nasal polyps – gleaning new insights into this condition and the severe form of inflammation that may lead to disorders such as asthma, allergic rhinitis and allergic eczema. Their findings were recently published online in Nature.

“For our patients, one of the most frustrating things about chronic, allergic conditions is that we have no cure. Surgery can relieve discomfort for those with nasal polyps, but in many cases the effect is only temporary,” said co-corresponding author Nora Barrett, MD, of the Division of Rheumatology, Immunology and Allergy. “My group’s goal is to understand why the inflammatory process persists once it begins and to uncover the cause of these conditions.”

Barrett and colleagues obtained samples from 12 patients with nasal polyps or other sinus conditions, collecting a total of 18,036 cells. They compared these to nasal scrapings from healthy individuals. To better understand what genes might be involved in nasal polyps, the team then used a technique called massively parallel, single-cell RNA sequencing, which allows investigators to determine which genes are “turned on” in each cell. Rather than focusing on just one kind of suspected cell, they used this approach to look at every cell type – such as blood cells, skin tissue cells and so forth – found in harvested samples.

“To a dramatic extent, inflammation had changed the basic tissue architecture at the genetic level.” —Nora Barrett, MD, Division of Rheumatology, Immunology and Allergy

What they found surprised them. One of the most striking discoveries the researchers reported was that epithelial progenitor cells – which produce the cells that line the airways – had been permanently altered in the polyp samples. In fact, even when removed from the tissue and grown in the lab, the resulting cells showed marked genetic differences.

“To a dramatic extent, inflammation had changed the basic tissue architecture at the genetic level,” Barrett said. “These lasting changes may be driving the recurrence and persistence of chronic, allergic inflammation for nasal polyps and other allergic conditions.”

The Nature publication offers a global, cellular map of inflamed tissue for what is known as type 2 inflammation – a severe form of inflammation that involves immune cells that have gone rogue, triggering a cascade of immune action. The map points to many pathways that have been altered, and Barrett and colleagues are working through these to identify which ones may be driving inflammation and which ones may be resulting from the inflammatory process.

The research team also tested an antibody that helped restore normal genetic activity – suggesting that it may be possible to develop therapies to prevent nasal polyps from returning by restoring a normal balance to cells that have been altered by inflammation.

The team also hopes to use the new information to develop a genetic signature that would allow clinicians to take a swab of nasal mucosa to test for lung conditions.

SEQaBOO Study Aims to Unlock Genetics of Hearing Loss in Newborns

From left: Linda Johnson, Yvonne Chekaluk, Cynthia Morton, Anne Giersch and Jun Shen display buttons promoting SEQaBOO.

As part of routine universal newborn screening, every baby has a hearing test before leaving the hospital. From the moment an infant is diagnosed with partial hearing loss or deafness, a clock starts ticking.

The speech and language center of the brain rapidly develops early in life, and anything that interrupts this process can have lifelong consequences. Because of this, babies with hearing loss or deafness experience the greatest benefits when interventions – such as sign language, hearing aids or cochlear implants – are begun as soon as possible.

It can be difficult, however, for clinicians and families to anticipate which intervention will be most effective. That’s because there are multiple types and causes of hearing loss, many with genetic origins. While standard newborn screening techniques are effective at detecting the absence of hearing, they don’t account for each baby’s unique genetic makeup, which may affect how well a therapy or strategy works for them.

Hoping to chart a new frontier in personalized medicine, a team of BWH researchers recently launched a first-of-its-kind study to perform whole-genome sequencing in newborns who do not pass the newborn hearing screen. The project, called SEQuencing a Baby for an Optimal Outcome, or SEQaBOO, aims to enroll annually about 100 otherwise healthy babies, including those born at BWH as well as babies born elsewhere and referred from Boston Children’s Hospital (BCH) after not passing their confirmatory hearing test.

“Infancy is a critical window in development of speech and language, and we want to ensure babies are optimally habilitated,” said medical geneticist and SEQaBOO principal investigator Cynthia Morton, PhD, of the departments of Obstetrics and Gynecology and of Pathology. “To do this, we need the most information about the underlying etiology, or causes, of the baby’s deafness right from the start. We hope that implementing genomic sequencing into newborn screening for hearing loss will reduce the timeframe for determining how to best manage care.”

More than 150 genes can contribute to hearing loss, and as many as 800 genes could ultimately play a role in hearing, Morton explained. Researchers expect that identifying such variants early in life will help clinicians refine care and avoid unnecessary testing.

For instance, while a common variation in a gene known as GJB2 is tied to deafness at birth, it doesn’t cause abnormalities in the inner ear’s structure. If an otolaryngologist (an ear, nose and throat specialist) is aware a baby has this genetic variant, they may not choose to order a CT scan, Morton said.

In other cases, knowing the genetic variant up front may reduce the incidence of hearing loss, said Yvonne Chekaluk, MSc, MB(ASCP), project manager for the study. Certain antibiotics in conjunction with specific genetic variants can cause hearing loss, and understanding which newborns might be vulnerable is important, she explained.

Collaboration at the Core

Due to its many facets, SEQaBOO has generated several multidisciplinary collaborations at the Brigham and beyond. The team includes medical geneticists Anne Giersch, PhD, and Jun Shen, PhD, and Richard Kaufman, MD, medical director of the Adult Transfusion Service, as well as members of Pathology’s Crimson Core.

They are also partnering with staff in the Audiology Program, including Lauren McGrath, AuD, CCC-A, and with those in the Department of Pediatric Newborn Medicine, including Katherine Gregory, PhD, RN. Researchers also work closely with nurses in the Mary Horrigan Connors Center for Women and Newborns for their vital role in patient education and interactions, Morton said.

Beyond the Brigham, the team works with otolaryngologists at Massachusetts Eye and Ear, where newborns enrolled in the study receive confirmatory testing and follow-up care. Whole-genome sequencing for the study is performed at the Broad Institute. In addition to the clinical component of SEQaBOO, researchers are also surveying parents about their opinions on genetic testing in collaboration with Harvard University. (Click here to learn more about SEQaBOO’s collaborators.)

The team hopes that their findings from both the clinical and survey components of the study will help chart the path for making genomics a standard part of newborn screening nationwide.

“As a scientist, it’s very important to me to make a difference,” Chekaluk said. “I love that this project has given me the opportunity to open up new doors and collaborate with so many different departments. It’s exciting and wonderful to be a pioneer in the future of personalized medicine.”

Morton added: “We look forward to Massachusetts leading the nation in this work. It’s a big project with contributions from many individuals, and BWH is an optimal setting for this endeavor.”

To learn more about SEQaBOO, visit seqaboo.bwh.harvard.edu.

Study: Women Report Greater Satisfaction, Quality of Life with ‘Flap’ Reconstruction

Andrea Pusic

When women decide to undergo breast reconstruction after a mastectomy, they’re typically presented with two options for the procedure: an implant-based reconstruction or an autologous, or “flap,” reconstruction, which uses skin, fat or muscle from elsewhere in the body to rebuild the breast.

While demand for breast reconstruction surgery is rising, there has been limited evidence-based, patient-centered data about satisfaction and quality-of-life measures after the procedure.

In a new study, Brigham researchers evaluated patient-reported satisfaction and well-being outcomes for more than 2,000 women nationwide prior to their initial reconstruction surgery and two years afterward. They found that patients who underwent flap reconstruction had greater satisfaction with their breasts, as well as greater psychosocial and sexual well-being two years after surgery, compared to those who underwent implant reconstruction.

The findings, shared last month in JAMA Surgery, built on the one-year, patient-reported outcomes of the Mastectomy Reconstruction Outcomes Consortium (MROC).

“Patient-centered data can best inform patients and clinicians about the potential risks and expected outcomes of breast reconstruction when making a decision between implant-based or autologous breast reconstruction,” said Andrea Pusic, MD, MHS, FACS, FRCSC, chief of the Division of Plastic and Reconstructive Surgery and senior author of the study. “Given the personal and intimate nature of breast reconstruction, patient-centered data are arguably the best measures of outcomes. Understanding the expectations and quality-of-life outcomes for previous patients may help new patients and their care providers in the decision-making process.”

A Closer Look: Flap vs. Implant

The study looked at patients from 11 centers, including the Brigham. Patient satisfaction with breasts, psychosocial well-being, physical well-being and sexual well-being were measured in scores on the BREAST-Q, a validated breast-surgery, patient-reported outcome questionnaire, calibrated to detect differences between specific procedure groups and patients over time.

In addition to their overall findings, Pusic and her team discovered that the differences in patient satisfaction with their breasts and their sexual well-being became greater at the two-year mark. For patients who underwent implant-based reconstruction, satisfaction rates declined over time, likely due to symmetry issues and the inability of the implant to age naturally.

After one year, no difference in the physical well-being of the chest was reported. At two years, patients who received flap reconstruction reported favorable outcomes for physical well-being of the chest compared with implant reconstruction, but the difference remained small.

Importantly, although patients reported overall high satisfaction with flap reconstruction, physical well-being of the abdomen was not fully restored, even though approximately two-thirds of the autologous patients had muscle-sparing or perforator flap procedures. The authors note that additional research and innovation is required to further minimize the negative effect of flap harvest on abdominal wall function.

Researchers said additional studies with even longer-term follow-up are warranted to determine the association of the type of reconstruction with patient-reported outcomes when radiation is required.

Study Reveals Long-Term Risks for Women with High Blood Pressure During Pregnancy

Jennifer Stuart

Jennifer Stuart

Even though women who develop preeclampsia or gestational hypertension during pregnancy see their high blood pressure return to normal after delivery, a new study indicates they are considerably more likely to develop cardiovascular disease risk factors, such as high cholesterol and Type 2 diabetes, later in life.

Previous research has shown that women with high blood pressure during pregnancy are more likely to have a heart attack or stroke compared to women who had normal blood pressure during pregnancy. What has been less clear until now is their likelihood of developing cardiovascular disease risk factors and when such conditions begin to emerge – knowledge that is critical to developing effective screening guidelines.

To help close this gap, researchers from BWH and the Harvard T.H. Chan School of Public Health measured how often and when women with preeclampsia or gestational hypertension during their first pregnancy developed high blood pressure, diabetes and high cholesterol after pregnancy.

In addition to revealing an increased risk for all three cardiovascular risk factors, the data showed that they emerged shortly after pregnancy and persisted for decades. The findings were published in Annals of Internal Medicine earlier this month.

“Many researchers believe that pregnancy acts a cardiometabolic ‘stress test’ and that pregnancy complications may help identify women who are predisposed to develop cardiovascular disease risk factors and events later in life,” said Jennifer Stuart, ScD, associate epidemiologist in the Division of Women’s Health. “Women who have had complications, such as preeclampsia or gestational hypertension, and their doctors can use this ‘early warning signal’ to improve their cardiovascular health by modifying their diet or physical activity before those risk factors emerge.”

This study was conducted among almost 60,000 women enrolled in the Nurses’ Health Study II who had given birth at least once. Participants were studied for approximately 25 to 32 years after the first pregnancy, depending on the risk factor.

Women with preeclampsia or gestational hypertension were two to three times more likely to develop high blood pressure. They also had a 70 percent higher rate of Type 2 diabetes and a 30 percent higher rate of high cholesterol, compared to women with normal blood pressure in pregnancy.

The risk factors studied also developed at younger ages and sooner after pregnancy in women who had preeclampsia or gestational hypertension. The relative risk of developing high blood pressure was strongest within five years after the first birth, and the increased risk persisted for several decades.

Women with high blood pressure during more than one pregnancy were even more likely to later develop high blood pressure, diabetes and high cholesterol.

These findings were not explained by shared risk factors such as pre-pregnancy body mass index, smoking or family history.

“As recommended by the American Heart Association, doctors should obtain a detailed history of pregnancy complications from their patients and screen women who had high blood pressure in pregnancy at regular intervals after pregnancy for cardiovascular disease risk factors,” Stuart said.

Going Above and Beyond Each Day: Pathology Labs Celebrate Successful Surveys

Cyprian Odeke

Cyprian Odeke runs quality control for the COBAS 8000 in the Chemistry Laboratory.

The Department of Pathology laboratories were recognized by surveyors from two accrediting bodies – The Joint Commission (TJC) and the American Society for Histocompatibility and Immunogenetics (ASHI) – for their extraordinary performance in quality and safety following two surveys in May.

The survey results are the latest in a long tradition of excellent marks from both entities. Particularly significant was the flawless report from the ASHI, which surveyed the Tissue Typing Histocompatibility Lab and concluded there were no findings to address – a rare outcome for an organization as large as BWH.

“Our staff’s commitment to service excellence, professionalism and team spirit came through loud and clear to the surveyors,” said Milenko Tanasijevic, MD, MBA, vice chair for Clinical Pathology and Quality. “They go above and beyond for every specimen and demonstrate their dedication to our patients every single day, regardless of whether a survey is occurring.”

During the four-day, unannounced TJC visit, which takes place every two years, surveyors evaluated compliance with laboratory standards in the labs, patient care areas, select on-site ambulatory practices and select off-site locations across BWH.

“The surveyors were so complimentary the whole time they were here. They commented on how incredibly professional and knowledgeable our staff are,” said Denise Fountain, MS, MT(ASCP)SBB, CQA(ASQ), director of Quality Assurance and Regulatory Compliance in Pathology.

Sara White

Sara White checks cell growth in a tissue culture on an inverted microscope in the Cytogenetics Tissue Culture Laboratory.

For the first time, TJC surveyors evaluated the labs using a new scoring methodology, The SAFER Matrix, which weighs instances of noncompliance by risk and magnitude. Surveyors identified a small number of findings to be addressed – fewer than most hospitals the size of BWH – and praised the staff for their professionalism, commitment and attention to detail. Since the completion of the survey, the BWH labs have addressed all findings from the report.

The ASHI survey, which also takes place every two years, praised the cutting-edge testing and highly advanced, specialized services provided by the Tissue Typing Histocompatibility Lab, Tanasijevic said.

“These successes are especially impressive given the pace of innovation in the field, and every BWHer should take pride in the outcomes of both surveys,” said Jeffrey Golden, MD, chair of Pathology.

“For example, five years ago, we rarely sequenced tumors. Now we look at the genome of most tumors to help inform how each patient should be treated,” Golden added. “When you factor in the regulatory changes that come with adoption of these new technologies, these surveys can be extremely challenging. But the remarkable commitment of our staff, no matter what challenges they face, ensure that we continue to be a high-quality, safe laboratory that provides the very best care for our patients.”

Brigham Health’s Strategy in Action: Highest-Quality, Safe Care
Learn more about our strategic priorities at BWHPikeNotes.org.

Brigham Researchers Design Fast-Acting Cholera Vaccine

Waldor Lab members, from left: Brandon Sit, Alyson Warr, Gabriel Billings, Matthew Waldor and Troy Hubbard (not pictured: Carole Kuehl)

When an outbreak of cholera unfolds, a vaccine that offers rapid protection could mean the difference between life and death for tens of thousands of people.

In a preclinical study, investigators at the Brigham are developing a new class of vaccine that can combat cholera, a highly contagious, quickly fatal diarrheal disease with a long history of causing epidemics. The vaccine is designed to act in two ways – training the immune system to detect and destroy the bacteria in the long term and protecting a person immediately from cholera’s effects. Using mathematical modeling, the research team predicts that, if successful in humans, their highly innovative approach could change the trajectory of a cholera epidemic.

This novel therapeutic, which has been tested in a preclinical model, is made from a live strain of the disease and protects against cholera-like illness less than a day after it is administered. Traditional, oral cholera vaccines are made from strains that have been killed and take effect after about 10 days.

“Our work represents a whole new concept in vaccinology – this dual-acting agent elicits a long-term immune response and confers protection almost immediately,” said Matthew Waldor, MD, PhD, of the Division of Infectious Diseases and the study’s corresponding author. “What we’ve done is something very different than what others have done before.”

Waldor and colleagues engineered the live vaccine based on the strain of cholera that caused a large epidemic in Haiti beginning in 2010. The research team engineered the strain by removing the genetic code that gives cholera its deadly properties. They also encoded within it a system that keeps out any toxin-producing genes, preventing the strain from ever regaining toxin production abilities. The team performed additional engineering to prevent other side effects, including mild diarrhea.

Researchers tested the vaccine in a preclinical model of cholera.

The vaccine, known as HaitiV, did not elicit cholera-like symptoms and caused minimal or no fluid accumulation in the intestines after being administered, even though the vaccine colonized the small intestine. When the team exposed the preclinical experimental group to cholera 24 hours later, no signs of disease were present.

The team also performed mathematical modeling to predict the public health impact the vaccine might have compared to traditional vaccines. The researchers’ simulations showed that in a population of 100,000 people, a fast-acting vaccine could prevent 20,000 infections compared to vaccines that can take the typical 10 days to build up a host’s immunity.

“The speed with which you respond to an outbreak significantly helps your ability to control it and prevent people from getting cholera,” said lead author Troy Hubbard, PhD, a graduate student in the Waldor Laboratory at the Brigham. “We are very focused on feasibility – the idea of being able to come in with a single-dose intervention that works rapidly but confers immunity over a long period.”

The team notes that evaluating the immune response that HaitiV elicits in human volunteer studies is a critical next step.

Brigham Health’s Strategy in Action: Scalable Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

BWH Experts Explore Role of Hormones and Health Outcomes in Women

Tamarra James-Todd

Hormones have a significant influence on a woman’s health and well-being throughout her lifetime. While much is known about how hormones work, the exact ways they affect health and organ systems are far less understood.

This gap is problematic because women experience sex-specific conditions, diseases and health outcomes directly linked to their hormones, according to BWH researchers who explored these complex issues during the 13th annual Women’s Health Luncheon, a fundraiser benefitting the Mary Horrigan Connors Center for Women’s Health and Gender Biology, on May 11.

The concern is part of a broader one about the underrepresentation of female study participants in medical research and scarcity of sex-specific treatments, especially as many diseases affect women in different ways or disproportionately compared to men, said Hadine Joffe, MD, MSc, executive director of the Connors Center, vice chair of research in the Department of Psychiatry and director of the Women’s Hormone and Aging Research Program at BWH.

“When the health of women is understood, valued and protected, everyone benefits,” Joffe said. “That is why the Connors Center is working actively to advance women’s health by catalyzing research, informing and advocating across the community, and transforming education for the next generation of leaders in medicine.”

Event organizers also announced the Connors Center IGNITE Awards, which will support innovative research in women’s health by providing seed funding for early-stage projects related to the development and testing of new treatments in women. This year’s luncheon raised nearly $700,000; of that total, $100,000 will fuel two IGNITE Awards.

“We will be relentless in pushing ourselves and our peers to do everything possible to understand and advance women’s health,” said Brigham Health President Betsy Nabel, MD. “We will continue down this path not just because it’s the brave thing to do, but because it’s the right thing to do.”

This year’s program, “Hot and Heavy: A Woman’s Relationship with Her Hormones,” featured presentations from three leading female BWH investigators working to advance research and care in the areas of birth control, menopause and environmental sources of hormones.

‘A Critical Health Issue’

Renowned broadcast journalist and CBS 60 Minutes correspondent Lesley Stahl delivered the event’s keynote address, reflecting on recent interviews she conducted with researchers about the science behind a grandmother’s love and the mental health benefits of caring for grandchildren.

“I used to think there were four necessities for life: food, oxygen, love and friendship,” Stahl said. “Now I know there is a fifth – purpose.”

Lydia Pace, MD, MPH, director of the Women’s Health Policy and Advocacy Program at the Connors Center, highlighted the evolution of hormonal contraceptives. She noted that while the birth control pill has been revolutionary, long-lasting alternatives such as contraceptive implants and intrauterine devices (IUDs) are more effective. However, these options remain underutilized partly due to misconceptions about their expense among patients and providers and a lack of training among primary care physicians.

Expanding access to these devices is crucial, Pace said, noting that almost half of U.S. pregnancies are unintended.

“For many women with chronic medical conditions, like many women we care for at the Brigham, being able to prevent or carefully time a pregnancy is a critical health issue,” she said.

In the next presentation, Joffe explored the science behind hot flashes, the most common peri- and post-menopausal symptom, and disruption of sleep. These sudden, intense sensations of warmth and sweating are linked to hormonal changes in these periods of a woman’s life, but their exact cause is still a mystery, Joffe said.

Still, several treatments have shown to be successful in managing these symptoms, she noted. For women who have trouble sleeping due to hot flashes, options include hormonal therapy and selective serotonin-reuptake inhibitors, a class of drugs most commonly used to treat depression. Practicing good sleep hygiene – such as avoiding the use of electronic devices in bed – is also critical to achieve good sleep, Joffe said.

Hidden Hormones

Tamarra James-Todd, PhD, MPH, an epidemiologist in the Division of Women’s Health, discussed the issue of women’s exposure to “hidden hormones” in countless consumer products. Also known as endocrine-disrupting chemicals (EDCs), these substances are found in everything from food packaging to beauty products to furniture and electronic equipment, James-Todd explained.

Women are disproportionately exposed to these chemicals, with the average American woman being exposed to 168 EDCs each day, compared to 80 for men, James-Todd said. Exposure to high concentrations of EDCs has been associated with early onset of puberty, infertility, pregnancy loss, preterm birth and gestational diabetes, among other adverse outcomes.

Hope is on the horizon, however. Two female legislators, Sens. Dianne Feinstein of California and Susan Collins of Maine, are leading efforts to strengthen the U.S. Food and Drug Administration’s authority to regulate ingredients used in personal care products. Until then, James-Todd noted there are several lifestyle changes that can reduce broader exposure to EDCs. These include using glass containers for storing and reheating food, adopting fragrance-free products and purchasing home products made from natural materials like bamboo.