Discoveries magazine Fall 2014 by Cedars-Sinai Discoveries magazine

Cedars-Sinai • Fall 2014

BED, BENCH, AND BEYOND FROM THE BARBERSHOP TO THE DELIVERY ROOM, CLINICAL RESEARCH IS BREAKING OUT OF THE BENCH-TO-BEDSIDE PARADIGM AND TAKING UP A NEW LAB: THE WORLD. PLUS: THE SCIENCE BEHIND PATIENT SATISFACTION, SAFETY, AND EFFICIENCY, PAGE 20

Contents

Cedars-Sinai

Senior Vice PreSident and dean of Medical faculty Shlomo Melmed, MD Senior Vice PreSident and chief deVeloPMent officer Arthur J. Ochoa, Esq.

In This Issue

Vice PreSident, MarKetinG and coMMunicationS Richard Elbaum director of deVeloPMent coMMunicationS Ken Ross

Fall 2014, Vol. 9, No. 2

46 Generation C

Senior editor Laura Grunberger ManaGinG editor Susan L. Wampler editorial coordinator Amanda Busick deSiGn B&G Design Studios, www.bgdesignstudios.com coVer Photo Clint Blowers

At 28, Nicolas Isley was trying to start a career, live independently, meet new friends, date a nice girl. Then cancer interrupted everything.

cedarS-Sinai diScoVerieS

© 2014 by Cedars-Sinai Medical Center. All rights reserved. Reproduction or use in whole or in part without written permission is prohibited. Cedars-Sinai Discoveries is a semiannual magazine produced by the Community Relations and Development Department of Cedars-Sinai Medical Center. Please email questions, comments, or requests for more information to: groupeditorial@cshs.org. Mail:

Senior Editor Cedars-Sinai Discoveries 8700 Beverly Blvd., #2416 Los Angeles, CA 90048 Phone: 323-866-6749 eMail: groupeditorial@cshs.org To subscribe to Discoveries magazine, visit discoveriesmagazine.org. For more information about Cedars-Sinai Medical Center, visit cedars-sinai.edu. This publication is for informational purposes only and should not be relied upon as medical advice. It has not been designed to replace a physician’s medical assessment and medical judgment. Always consult first with your physician regarding anything related to your personal health.

the Medical center MaintainS the

at cedarS-Sinai

followinG GoalS for BioMedical

Cedars-Sinai is one of the largest nonprofit academic medical centers in the western United States. For more than 20 years, Cedars-Sinai has been named Los Angeles’ “most preferred hospital for all health needs” in an independent survey of area residents. Cedars-Sinai is internationally renowned for our diagnostic and treatment capabilities and our broad spectrum of programs and services as well as breakthroughs in biomedical research and superlative medical education. The Medical Center ranks among the top 10 independent hospitals in the nation for our research activities. Biomedical research is an integral component of Cedars-Sinai’s mission.

reSearch ProGraMS:

to effectiVely iMPleMent our MiSSion, cedarS-Sinai recoGnizeS the need to:

• Provide modern facilities and expert faculty support to encourage and stimulate new and ongoing meritorious research programs • Encourage philanthropy and community support for such services, as well as community education programs

• Sustain a program of outstanding biomedical research, healthcare services, and nursing research by fostering basic and clinical investigation in the prevention and causes of medical illnesses, their pathologic mechanisms and diagnoses, and the development of cures for the ailments that afflict our society • Translate research discoveries appropriately to a clinical setting • Provide research training opportunities for graduate students and our professional teaching programs • Foster the transition of biomedical discoveries to the realms of product development, patient care application, and marketing • Provide cross-fertilization and interdependent synergy between the Medical Center and the biotechnology industry • Protect the rights of human and animal subjects

With your help, We’ll be here for her grandchildren, too.

Cedars-Sinai Medical Center has been fully accredited by the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP) for assuring protection for our human subjects during research. Cedars-Sinai was the first institution in California to receive this designation. AAHRPP is a Washington, D.C.-based nonprofit organization that uses a voluntary, peer-driven educational model to accredit institutions engaged in research involving human subjects.

For more than a century, people from around the globe have turned to Cedars-Sinai for world-class medical treatment and research.

Cedars-Sinai Health System does not discriminate against any person on the basis of race, color, national origin, disability, age, or sex in admission, treatment, or participation in its programs, services and activities, or in employment. For further information about this policy, contact the vice president, Corporate Integrity Program, at 323-866-7875.

You can help to ensure that this legacy will be available for generations to come by including Cedars-Sinai in your estate plan. A bequest does not impact resources during your lifetime and helps Cedars-Sinai continue to deliver high-quality patient care and conduct research that is vital to our Southern California community — and to the world. Max Gerber

aBout reSearch ProGraMS

To learn how you can create your own legacy at Cedars-Sinai, please contact allan carp, Certified Specialist in Planned Giving, at (323) 866-6745 or Allan.Carp@cshs.org, or visit the planned giving section of our website at csmc.edu/giving.

Contents

Cedars-Sinai

Senior Vice PreSident and dean of Medical faculty Shlomo Melmed, MD Senior Vice PreSident and chief deVeloPMent officer Arthur J. Ochoa, Esq.

In This Issue

Vice PreSident, MarKetinG and coMMunicationS Richard Elbaum director of deVeloPMent coMMunicationS Ken Ross

Fall 2014, Vol. 9, No. 2

46 Generation C

Senior editor Laura Grunberger ManaGinG editor Susan L. Wampler editorial coordinator Amanda Busick deSiGn B&G Design Studios, www.bgdesignstudios.com coVer Photo Clint Blowers

At 28, Nicolas Isley was trying to start a career, live independently, meet new friends, date a nice girl. Then cancer interrupted everything.

cedarS-Sinai diScoVerieS

the Medical center MaintainS the

at cedarS-Sinai

followinG GoalS for BioMedical

reSearch ProGraMS:

to effectiVely iMPleMent our MiSSion, cedarS-Sinai recoGnizeS the need to:

With your help, We’ll be here for her grandchildren, too.

For more than a century, people from around the globe have turned to Cedars-Sinai for world-class medical treatment and research.

aBout reSearch ProGraMS

Contents

From the Dean of Faculty

Features

We are in a new era of medical discovery, one in which getting the right medication to the right patient at the right time maximizes its impact and is as important as the development of the drug in the first place.

hen I was a medical resident in the 1960s, hand hygiene was barely discussed as an imperative. We were taught to wash our hands before seeing patients, but we rarely saw this behavior modeled by senior physicians. Today, medical institutions from the World Health Organization to the smallest clinic are acutely aware that hand hygiene is the most efficient way to reduce the spread of harmful bacteria. The evolution in hand-washing protocols is a microcosm of what is happening as a result of the expanding field of health services research. Forty years ago, researchers focused almost exclusively on the causes and mechanisms of disease, with the goal of developing advanced treatments, devices, and medications. These efforts were enormously successful. Decades later, we are in a new era of medical discovery, one in which getting the right medication to the right patient at the right time maximizes its impact and is as important as the development of the drug in the first place. The quest to push healthcare delivery toward improved quality and efficiency must be approached with as much scientific rigor and insistence on evidence as any other form of research. Cedars-Sinai is at the forefront of a major endeavor to discover new paths to quality health services, as you will see in the cover story of this issue of Discoveries. We have recruited world-class faculty like Brennan Spiegel, MD, director of Health Services Research, and Teryl Nuckols, MD, the incoming director of General Internal Medicine. These experts, in collaboration with our existing visionary team, bring a new perspective to original discovery for delivering optimal healthcare in a modern medical setting. Health services research focuses on developing new avenues to prioritize value — in delivering the highest quality of care and in ensuring efficiency and cost-effectiveness. Both physicians and patients have a vested interest in improving healthcare value. Inexpensive interventions — like installing hand sanitizers outside patient rooms, as we have done at Cedars-Sinai — can have an enormous impact on patient wellbeing and outcomes. Over the last 40 years, Cedars-Sinai has risen to a position of leadership in cutting-edge brain, heart, cancer, and surgical health innovations. Given our substantial research and clinical resources to enable new discoveries, we are committed to providing high-quality, high-value care to our community. We now are poised to drive the burgeoning field of health services research further forward as a model for our nation.

Shlomo Melmed, MD 2

| Discoveriesmagazine.org

20 The Science of Caring These days, the scientific approach to medicine extends far beyond disease prevention and treatment: It’s guiding all aspects of patient care — from measuring satisfaction to improving safety and efficiency. How health services research is transforming medicine and the patient experience.

26 Beyond the Bench Clinical research is breaking out of the benchto-bedside paradigm and taking up a new lab: the world. From labor and delivery rooms to barbershop chairs, eight studies that break the traditional research mold.

36 On Diabetes If you could change one thing to improve diabetes treatment or reduce diabetes and obesity rates in the U.S., what would it be? From big ideas to small steps, 11 surprising answers from our experts.

40 The Sound of Musing Researchers listen in on the brain’s deepest internal dialogues to illuminate the biology of memory. Discover the new frontier of neurology: recording and analyzing the activity of a single neuron.

SLIDESHOW video Audio LEARN MORE

On the Web Go online for exclusive extras, including more experts’ ideas for defusing the diabetes time bomb; Dr. Rutishauser explains what happens when a neuron fires; addressing fertility issues with young cancer patients; more myths and misconceptions on clinical trials; and a chance to see Cedars-Sinai’s 3-D printer in action.

Departments 5 NEWS & NOTES

6 STATS

18 Q&A

Vision changes may help detect Alzheimer’s disease boosting nutrition in breast milk to improve preemies’ chances BRCA gene turns 20 why fertility treatments lead to high-risk pregnancies discovery of new proteins that help regulate heartbeat a novel device to contain tumor cells liver transplants: CedarsSinai ranks first how protein patterns can help predict treatment response scorpion venom to guide brain cancer surgery new hope for kidney cancer patients

Education and training numbers that count

Linda Burnes Bolton on frontier nursing, leadership, and the profession’s role in the future of healthcare

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12 IMAGING ALL THE PEOPLE 3-D glasses may enhance your moviegoing experience, but the new blockbusters in medicine are 4-D and 3-D printing.

14 TRUE/FALSE Debunking myths and half-truths about clinical trials

16 WHAT’S INSIDE Pluripotent stem cells need food to grow from a blank slate to an adult cell. The food is called “red growth media,” and what you find inside it may surprise you.

53 FACULTY NEWS New PhD class in Biomedical Sciences and Translational Medicine urged to build “world of hope”; awards, grants, and recruitment news

56 OPINION Medical libraries are much more than a repository for books or a place of study: They are the invaluable backbone of an institution’s research enterprise.

ON THE COVER From barbershops to patients’ homes, labor and delivery rooms to operating rooms, clinical research is taking up a new lab: the world.

Fall 2014 | Discoveries |

Contents

From the Dean of Faculty

Features

Shlomo Melmed, MD 2

| Discoveriesmagazine.org

SLIDESHOW video Audio LEARN MORE

Departments 5 NEWS & NOTES

6 STATS

18 Q&A

Education and training numbers that count

Linda Burnes Bolton on frontier nursing, leadership, and the profession’s role in the future of healthcare

• ••

•

12 IMAGING ALL THE PEOPLE 3-D glasses may enhance your moviegoing experience, but the new blockbusters in medicine are 4-D and 3-D printing.

14 TRUE/FALSE Debunking myths and half-truths about clinical trials

16 WHAT’S INSIDE Pluripotent stem cells need food to grow from a blank slate to an adult cell. The food is called “red growth media,” and what you find inside it may surprise you.

53 FACULTY NEWS New PhD class in Biomedical Sciences and Translational Medicine urged to build “world of hope”; awards, grants, and recruitment news

56 OPINION Medical libraries are much more than a repository for books or a place of study: They are the invaluable backbone of an institution’s research enterprise.

ON THE COVER From barbershops to patients’ homes, labor and delivery rooms to operating rooms, clinical research is taking up a new lab: the world.

Fall 2014 | Discoveries |

News & Notes Fall

2014

6 STATS | 12 IMAGING ALL THE PEOPLE | 14 TRUE/FALSE | 16 WHAT’S INSIDE | 18 Q&A

SAVE OUR STORY Come celebrate the more than 100-year history of Cedars-Sinai by visiting the newly launched Historical Conservancy Exhibit, located adjacent to the Medical Library on the Plaza Level. You can help safeguard our proud heritage by donating your keepsake, commemorative items, or any medical treasure to the Historical Conservancy. For more information, contact Leo Gordon, MD, at historicalconservancy@cshs.org or 323-866-2925.

The Eyes Have It The eye may be a window to the soul, but when it comes to scientific inquiry, it’s proving to be a very useful window to the brain. Researchers at Cedars-Sinai’s Board of Governors Regenerative Medicine Institute have discovered eye abnormalities that may help reveal features of early-stage Alzheimer’s disease.

Using high-resolution imaging techniques on animal models, they correlated variations of the eye structure to identify initial indicators of the disease. Though additional research is needed to investigate the mechanisms of these changes in the eye in relation to changes in the brain, this area of inquiry could

ultimately make the early diagnosis of Alzheimer’s disease a reality. Cedars-Sinai has been at the cutting edge of studies on the eye and Alzheimer’s disease with a hallmark study showing that amyloid plaques, a key sign of the neurodegenerative disease, also build up in the eye.

fall 2014 | Discoveries |

News & Notes Fall

2014

6 STATS | 12 IMAGING ALL THE PEOPLE | 14 TRUE/FALSE | 16 WHAT’S INSIDE | 18 Q&A

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STATS: Education and Training

500 Number of medical residents and fellows trained at Cedars-Sinai in fiscal year 2014

Number of surgery residents who began their training last June at CedarsSinai

Milk Made Just Right For preterm babies, getting the most nutrition possible from their mother’s milk can mean the difference between healthy growth and serious, long-term developmental issues. Unfortunately, not all breast milk is created equal. The solution may lie in an innovative approach to personalized medicine: breast milk that is individually enriched for optimal nutrition. That’s the goal of a pilot study launched at the Neonatal Intensive Care Unit (NICU) at Cedars-Sinai’s Maxine Dunitz Children’s Health Center. The study examines the nutrient levels in breast milk fed to premature infants. Currently, malnourishment can only be gauged by monitoring growth rate. If infants’ growth rates lag behind the norm, it is likely they are not receiving the nourishment they need, according to Charles F. Simmons Jr., MD, chair of the CedarsSinai Department of Pediatrics and director of the Division of Neonatology. “The preterm babies

BRCA Turns 20

who are the most challenged with weight gain are often the babies who are delayed in the development of neurological functions,” he explains. Milk fortifiers are often added to increase the nutritional density of human milk, but the fortifiers are the same for everyone — even though milk varies greatly from mother to mother. “It’s a onesize-fits-all approach,” notes Dr. Simmons, the Ruth and Harry Roman Chair in Neonatology. In the pilot study underway, researchers are focusing on babies weighing less than 3.3 pounds. A sample of the mother’s breast milk is placed in a device that thoroughly analyzes each nutrient and then shows a precise breakdown of the milk’s composition of proteins, fat, and carbohydrates. The analysis indicates which specific supplements should be added to the milk. According to Dr. Simmons, future studies of the individualized dosing could lead to more rapid weight gain and a quicker release from the NICU.

April 2014 marked the 20th anniversary of the identification of the BRCA1 gene by American geneticist Mary-Claire King, PhD. At the time of Dr. King’s discovery, the idea that cancer could be caused by faulty genes was controversial. The breakthrough revolutionized genetics and cancer treatment. Simple genetic tests can now reveal whether a woman has mutations in her BRCA genes that increase the risk of breast and ovarian cancer. The Cedars-Sinai Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute is conducting several research studies for women with the BRCA1 or BRCA2 gene mutations through the Gilda Radner Hereditary Cancer Program. Since the program’s inception in 1991, more than 1,600 women have participated, contributing valuable data to the understanding of ovarian cancer in high-risk women, particularly biomarker data, genetic predisposition, and factors related to familial risk.

4,000 Number of student nurses who have received clinical education and mentorship services since Cedars-Sinai created the Geri and Richard Brawerman Nursing Institute in 2000

100

Anna Parini

Number of postdoctoral researchers who receive advanced training and conduct investigations at Cedars-Sinai

| Discoveriesmagazine.org

A Study in Fertility Women who conceive with the help of fertility treatments are at higher risk of various complications, including birth defects, low birth weight, and even infant mortality. Margareta D. Pisarska, MD, director of the Fertility and Reproductive Medicine Center at Cedars-Sinai, is leading an investigation to determine why. Her five-year study examines how the environment — both in the womb and in the hospital where the baby is born — affects the newborn and the mother. According to Dr. Pisarska — who is also director of the Division of Reproductive Endocrinology and Infertility in the Department of Obstetrics and Gynecology — the study looks “at the earliest point in human pregnancy, when the fertilized egg implants, to determine if the adverse outcomes are the result of the same genetic problems that made it difficult for the parents to conceive, or if the infertility treatments are to blame.”

The effort is the first of its kind in humans and is supported by a $4 million grant from the National Institutes of Health. Investigators also will study how the environment influences pregnancy. “We will be able to look at genes that get switched on right at the start of a pregnancy and compare that to genes that are switched on at the end of pregnancy to give us a snapshot of what’s happening in utero,” says Dr. Pisarska. She also hopes to learn more about how normal pregnancies develop and about the fetal origins of adult diseases by investigating the intrauterine environment’s effect on overall health. According to the Centers for Disease Control and Prevention, nearly 11 percent of U.S. women 15–44 have an impaired ability to get pregnant or carry a baby to term, while the number of infants conceived using assisted reproductive technologies has doubled over the past decade. fall 2014 | Discoveries |

N&N

STATS: Education and Training

500 Number of medical residents and fellows trained at Cedars-Sinai in fiscal year 2014

Number of surgery residents who began their training last June at CedarsSinai

BRCA Turns 20

4,000 Number of student nurses who have received clinical education and mentorship services since Cedars-Sinai created the Geri and Richard Brawerman Nursing Institute in 2000

100

Anna Parini

Number of postdoctoral researchers who receive advanced training and conduct investigations at Cedars-Sinai

| Discoveriesmagazine.org

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Tumor Grabber vs. Traveling Cells

Synchronized Pumping

Can a hospital gift shop actually help support the healing process? At Cedars-Sinai, we think so. Our Helping Hand Gift Shop offers a wide range of thoughtful gifts for patients, families and medical center employees. Browse through our vast selection of quality gifts, from fresh flowers and cuddly teddy bears to fashionable jewelry and clothing. And best of all, proceeds from Helping Hand Gift Shop

Helping Hand Gift Shop Plaza Level at Cedars-Sinai Medical Center 310-423-5241 cedars-sinai.edu/giftshop

Greg Clarke

benefit the Cedars-Sinai Department of Obstetrics and Gynecology.

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GIFTS TO SOOTHE. GIFTS TO CELEBRATE.

Cedars-Sinai Heart Institute investigators have discovered five new proteins that help regulate heartbeats and that could be used to limit the size of heart attacks and strokes — and even impact cancer. The proteins are smaller fragments of a larger protein that coordinates billions of heart cells per heartbeat. Until now, only one protein, Connexin 43, was known to be involved in cell-to-cell communication. The researchers found that a molecular trick known as alternative translation produces five smaller versions of the protein. These additional proteins regulate the movement of the larger protein, ensuring rapid flow of electrical communication signals that coordinate heart cells to produce a stable heartbeat. The findings advance our understanding of the cell-to-cell communication that drives healthy heart function. With less

cell communication, chances are greater of disturbances in heart rhythm that can result in disability or death. Other functions associated with Connexin 43 — such as reducing the scope of heart attacks and strokes, and preventing cancer cells from dividing — perplexed scientists, who could not see how the larger protein could play such a diverse role. Discovery of the smaller fragments answers this mystery. The researchers also concluded that a class of drugs known as “mTOR inhibitors,” currently used for immunosuppression in organ transplants, can increase the formation of the smaller proteins in cardiac cells, improving electrical coordination in the heart. The findings suggest that mTOR inhibitors could be used to prevent erratic and sometimes fatal heart rhythms, and could be used to fight other diseases.

Circulating tumor cells (CTCs) are cancerous cells that break away from malignancies and enter the blood, often spreading the cancer to other parts of the body. For prostate cancer patients, these traveling cells can increase the aggressiveness and severity of the disease. To combat such invasions, a team of scientists in the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai has enhanced a new device, a chip that identifies and “grabs” CTCs, acting like Velcro to prevent cancer from spreading. This innovative technology could enable doctors to access and identify cancerous cells in the bloodstream, which would provide the diagnostic information needed to create individually tailored treatments for patients with prostate cancer.

Best in L.A. for Liver Transplant In the latest national report on organ transplant outcomes, patients who received a new liver at the Cedars-Sinai Comprehensive Transplant Center had the best one-year survival outcomes of those treated at all hospitals in the Los Angeles region, with 90 percent of liver transplant patients surviving beyond that important milestone. Patients receiving new kidneys at the medical center also fared extremely well, with 97 percent surpassing the one-year benchmark.

fall 2014 | Discoveries |

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Tumor Grabber vs. Traveling Cells

Synchronized Pumping

Helping Hand Gift Shop Plaza Level at Cedars-Sinai Medical Center 310-423-5241 cedars-sinai.edu/giftshop

Greg Clarke

benefit the Cedars-Sinai Department of Obstetrics and Gynecology.

B:10.5”

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GIFTS TO SOOTHE. GIFTS TO CELEBRATE.

fall 2014 | Discoveries |

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Fountain of Life Proteins are life’s workhorse molecules, taking part in every cell function, from division and metabolism to the transfer of genetic information. They act as powerful biomarkers for disease progression and patient response to treatment. Within the Advanced Clinical Biosystems Research Institute at CedarsSinai, under the direction of Jennifer

Paul Garland

1-800-CEDARS-1

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The fact is heart disease kills more women than men. But, for the past 50 years, most heart research has been focused on men. That’s why the Barbra Streisand Women’s Heart Center in the Cedars-Sinai Heart Institute is committed to ending that disparity through state-of-the-art screening, diagnosis and care tailored to women. And, with the support of The Streisand Foundation, we will continue to save women’s lives.

Van Eyk, PhD — the Erika J. Glazer Chair in Women’s Heart Health — the patterns of these busy macromolecules reveal new ways to understand and target women’s heart disease. The fast-emerging field of clinical proteomics — her area of expertise — uses sophisticated robotics and powerful data processing to identify and quantify proteins

at a rate and level of precision previously unimaginable. The results are essential to predicting how a specific patient will respond to different treatments — just as gene mapping can help predict the likeliness of developing a disease. The research conducted by Dr. Van Eyk and her peers heralds a day when proteins will routinely

provide quantitative measures to aid in clinical decisions, and treatments will be precisely tailored to each patient or patient group. One such group is women with cardiovascular disease. For decades, doctors have measured a single level of the protein troponin as the sign of a heart attack in men and women. New evidence suggests the

threshold is a moving target, and that women register lower troponin levels during a heart attack than do men. An initial study suggests the threshold misses 20 percent of heart attacks in women. “We’re at the very beginning of understanding that men and women experience different symptoms and causes of heart disease,” explains C. Noel Bairey Merz, MD, medical director of the Cedars-Sinai Barbra Streisand Women’s Heart Center and the Women’s Guild Chair in Women’s Health. “Those differences begin at the molecular level,” she adds, “so that is where Dr. Van Eyk will lead us.” “The question we want to answer is, ‘Why is the troponin threshold different?’” says Dr. Van Eyk. “Now we have the opportunity to find out.” Patterns are emerging, as investigators use proteomics to hunt down other proteins that may provide a more sensitive reading of a heart attack before troponin kicks in.

fall 2014 | Discoveries |

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Paul Garland

1-800-CEDARS-1

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fall 2014 | Discoveries |

N & N imaging ALL THE PEOPLE Dr. Evan Zahn and his team used this 3-D replica of a young boy’s pulmonary artery to devise the optimal way to insert a transcatheter valve — in advance of the procedure.

A New 3-D Experience

3-D PRINTING Congenital heart defects affect eight out of every 1,000 newborns. Although many do not require immediate treatment, most cases will require a surgical or catheterbased intervention during their lifetime. Young patients suffering from pulmonary valve stenosis or leaking pulmonary valve have few treatment options. The only available transcatheter valve repair — the Melody valve — is suitable for only 15 percent of cases. For the remaining 85 percent, open-heart surgery has typically been the only option. Now, Evan Zahn, MD, and Alistair

Phillips, MD — codirectors of the Guerin Family Congenital Heart Program — are harnessing 3-D-printing technology to make the less invasive transcatheter valve technology available to more patients. Two-dimensional images from MRIs or CT scans are sent to a 3-D printer housed in the Women’s Guild Simulation Center for Advanced Clinical Skills. After about three hours’ processing, the printer turns out a model of the patient’s heart. The printer works a bit like an inkjet, but instead of ink, it emits layer upon layer of a thin, clear plastic material. Using the precise specifications of the

| Discoveriesmagazine.org

limited to diagnostics. Employed in the operating room, it radically improves surgical precision and safety. The technology can be equally useful in prevention, providing patients with such clear images of their condition that they might be more likely to take the necessary steps to regain or maintain their health. In addition, the new world of 3-D printing is leading scientists down avenues unimaginable even to their relatively recent forefathers. At Cedars-Sinai, researchers are making groundbreaking strides using three- and now four-dimensional imaging as well as 3-D printing to obtain better diagnoses and highly effective, targeted treatments for optimal outcomes. data, it yields a perfectly reconstructed model of the patient’s heart, with all of its unique features and irregularities. It also provides Zahn, Phillips, and their team with critical spatial information. “We can work with the model at our desks to figure out exactly how to place a transcatheter valve in patients previously thought to not be candidates for this minimally invasive treatment option,” says Dr. Zahn. “We can literally work out where gaps need be filled and where we might need to use stents and other devices to create an ideal ‘landing zone’ for the valve in these

complex patients. “We are so used to making decisions with our eyes, on a screen or on paper,” he adds. “There’s a change that’s hard to describe when you can take something like the heart and hold it in your hands and feel it. You can conceptualize the entire procedure. And doing so in a simulated way allows us to figure out the most intricate details before we actually perform the procedure.” Results are more predictable, allowing new minimally invasive technologies such as transcatheter valve therapy to be extended to a greater

pictures

number of patients than ever before, says Dr. Zahn.

THE FOURTH DIMENSION The next big thing in imaging will capture the fourth dimension: time.

See functional imaging and our 3-D printer in action at discoveriesmagazine.org

Rachael Porter

f hearing “3-D” conjures up images of summer movie blockbusters, strange glasses, and Godzilla leaping from the screen, think again. Three-dimensional technology is revolutionizing medical science, with pictures just as dramatic and the stakes much higher. Until recently, medical imaging could only represent the standard two dimensions, with MRIs and CT scans capturing a projected image of their target, whether an organ, a muscle, or a limb. However, new technology involves not only recording the three spatial dimensions, but also changes that occur as the target moves. The resulting image actually yields a fourth dimension: time. Multidimensional imaging is not

“We’re currently working on ways to improve our view of the heart, an organ that moves constantly,” says Debiao Li, PhD, director of the Biomedical Imaging Research Institute at Cedars-Sinai. “Angiograms are currently used for clinical diagnosis of

coronary artery disease, but are limited because you can’t gauge exactly how much blood flow has been reduced to the heart, how much of the heart muscle appears to be dead, and how much cardiac function has been affected,” he adds. “To evaluate both heart/

coronary artery anatomy and function, we need to capture the entire heart over the entire heart-beating cycle. MRI is also noninvasive, unlike angiograms. With MRI we don’t need to insert a catheter.” Dr. Li and his colleagues are among the world leaders in

developing this advanced 4-D imaging technology and conducting clinical trials in this field. The functional information the technology yields is thanks to improvements in the fields of hardware, computer science, electrical engineering, and superconducting.

“We are exploring many different advances in technology that can make imaging a central piece of modern medicine for diagnosis and treatment decisions, and to evaluate the effectiveness of a therapy.”

fall 2014 | Discoveries |

A New 3-D Experience

| Discoveriesmagazine.org

pictures

number of patients than ever before, says Dr. Zahn.

THE FOURTH DIMENSION The next big thing in imaging will capture the fourth dimension: time.

See functional imaging and our 3-D printer in action at discoveriesmagazine.org

Rachael Porter

fall 2014 | Discoveries |

N & N true/false

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Trials and Misconceptions Myths and half-truths about clinical studies are pervasive and entrenched. That may account for why so few participate, even though trials lead to dramatic advances in patient care. Stephen W. Lim, MD, chair of the Institutional Review Board overseeing human subject research at Cedars-Sinai, debunks the most common misconceptions.

Clinical trials are risky. While it is true that some clinical research carries risks, institutional review boards (IRBs) — the ethical oversight committees that review such research — ensure that risks to participants are minimized and that safety is monitored throughout. “The IRB must find a favorable benefit/risk ratio before approving any clinical

trial,” explains Dr. Lim. “A description of all foreseeable risks must also be included in the informed consent form that each participant signs. If new risks come up during the study, volunteers are alerted and can withdraw.” Although Phase I trials usually test investigational therapies for toxicity, many clinical studies are merely observational or pose very low risk. “One thing is

certain,” says Dr. Lim. “The welfare and rights of participants are always more important than the study’s success.”

Informed consent primarily protects the legal interests of researchers. Informed consent is how researchers provide information to potential participants and those already enrolled. “The process

is there to protect them,” says Dr. Lim, “and should provide enough information to explain the risks, potential benefits, and alternatives to the study. It is by no means a partial or biased document or a contract.” Participants may withdraw at any time, even if the study is still in progress, and be treated without ramifications.

My privacy will not be protected. “Researchers go to great lengths to protect the privacy of research subjects,” says Dr. Lim. “The confidentiality of medical information is protected under federal regulations,” such as the Health Insurance Portability and Accountability Act (HIPAA). Data is generally coded with a unique identification number and not directly associated with the participant’s name.

Plenty of volunteers have signed up. I don’t need to participate. “One reason drug development takes so long is that enrollment in clinical trials is much lower and slower than ideal,” says Dr. Lim. According to the National Cancer Institute, only about 3 percent of cancer

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| Discoveriesmagazine.org

patients enroll in clinical trials, although a much larger number are eligible. Approximately 40 percent of cancer trials cannot enroll enough patients. “It’s a huge problem,” he says. “We’ve gained unprecedented knowledge about numerous diseases, and we’re on the cusp of finding cures for many of them, but low trial enrollment really hampers our progress.”

A Punch to Kidney Cancer

If a clinical trial could help me, my doctor will tell me about it. Cedars-Sinai is a hub for biomedical research, with one of the largest state-of-the-art clinical research trial facilities of any private hospital — attracting exceptional physician-scientists who wish to both conduct research and treat patients. “Because so many of our clinicians lead active studies,” says Dr. Lim, “patients are likely to be made aware of clinical trial options. However, this is not the case everywhere.” To find an ongoing or upcoming clinical trial at CedarsSinai, or for answers to frequently asked questions, visit cedars-sinai.edu and click on “search clinical trials,” or visit clinicaltrials.gov, a national resource for such studies.

Placebos, coverage, and other myths about clinical trials debunked at discoveriesmagazine.org

Lights, Camera, Venom! Researchers at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute and Department of Neurosurgery have developed a unique, compact, relatively inexpensive imaging device to “light up” malignant brain tumors, such as gliomas, and other cancers. The naked eye cannot discern where the tumor stops and normal brain tissue starts, and current imaging systems do not provide a definitive view. Gliomas also have tentacles that invade normal tissue. Taking out too much normal tissue can have catastrophic consequences, but not removing the glioma entirely gives remaining cancer cells a head start on growing back. New technology such as fluorescence-guided surgery, which can provide neurosurgeons with a clear distinction between diseased tissue and normal brain — in real time — could save lives. The experimental imaging system deploys a dye

that bonds only to cancer cells. The dye contains a special peptide — a synthetic, manmade version of a small protein found in the venom of the Israeli yellow scorpion, also known as the deathstalker scorpion. Despite this fearsome name, the artificial peptide is completely harmless. When stimulated by a laser, the venom emits a glow invisible to the naked eye that can be captured by a camera designed and developed in the laboratory of Pramod Butte, PhD, a research scientist in Cedars-Sinai’s Department of Neurosurgery. The resulting image shows brain cancer cells awash in a fluorescent “paint.” In animal studies, the new experimental device clearly distinguished tumor from normal tissue. And with near-infrared light’s ability to penetrate deep into the tissue, the system identified tumors that had migrated from the main tumor and would have evaded detection.

Survival outcomes for patients with renal cell carcinoma, the most common kidney cancer, have improved significantly due to advances that target an individual’s genetic makeup. Investigators are now seeking to use a patient’s own immune system to fight disease. The Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute has launched a Phase III clinical trial aimed at providing patients with long-term control of their disease. According to Robert Figlin, MD, deputy director of the Samuel Oschin Comprehensive Cancer Institute and global principal investigator of the Phase III trial, combining targeted therapies with a vaccine-based approach may revolutionize the treatment of renal cell carcinoma during the next decade. Dr. Figlin, who is also the Steven Spielberg Family Chair in Hematology Oncology at CedarsSinai, is optimistic: “With innovative thinking and treatment approaches, and building on past progress, we’re paving the way for promising research breakthroughs and improved patient care.”

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certain,” says Dr. Lim. “The welfare and rights of participants are always more important than the study’s success.”

Informed consent primarily protects the legal interests of researchers. Informed consent is how researchers provide information to potential participants and those already enrolled. “The process

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A Punch to Kidney Cancer

Placebos, coverage, and other myths about clinical trials debunked at discoveriesmagazine.org

fall 2014 | Discoveries |

| Discoveriesmagazine.org

Sodium Bicarbonate Yes, the same type of baking soda found in your pancake batter or toothpaste can be used as a buffer to improve the pH control of

L-Ascorbic Acid It can protect you from scurvy, but L-ascorbic acid — aka Vitamin C — also plays a role in iPSC production, helping cells actively divide and proliferate. Because of their antioxidant properties, ascorbic acid molecules enhance cellular reprogramming and help reduce the level of harmful intercellular oxygen reactions.

Selenium (sodium selenite) If you remember your periodic table, then you may recognize selenium (Se34), stuck between sulfur and tellurium. The chemical element rarely occurs in nature or in pure form, and is mostly used in glassmaking and as a pigment. In our red growth solution, it protects cells from oxidative stress by allowing proper function of certain antioxidant enzymes such as glutathione peroxidase or thioredoxin reductase, which are important for sustained cell culture and expansion.

Insulin In your body, insulin is a hormone produced by beta cells inside the pancreas and is central to regulating carbohydrate and fat metabolism. In iPSC development, insulin serves as a growth factor that helps cells use the glucose and amino acids (building blocks of a protein) in the red growth media.

ingredients

nduced pluripotent stem cells (iPSCs) are adult skin or blood cells that have been reprogrammed to an embryonic stem-cell-like state. This is achieved through complex genetic manipulations that force the cells to “go back in time.” The process essentially turns the cells into blank slates that can be grown into a wide variety of mature cells — nervous system, blood, bones, or heart, for example. The technology provides unprecedented opportunities for groundbreaking research. Experts can create diseased cells to not only study a disease’s genetic and molecular makeup, but also to test potential treatments in the laboratory without any risk to human subjects. This

Transforming Growth Factor Transforming growth factor (TGF) is a protein known to increase the level of activity of another protein, Nanog, which plays a very important role in sustaining the pluripotent state. TGF leads to robust stem cell division into billions of iPSCs and ensures the long-term stability of a stem cell culture.

Holotransferrin Holotransferrin is a beta-globulin protein synthesized in the liver and secreted into the blood, where it plays a central role in transporting iron throughout the circulatory system. In the red growth media, it attaches to the cell and allows the FGF-2 protein to do its job by providing iron that helps cells maintain homeostasis (balance), regulating the amount of iron uptake. This allows for higher efficiency in making iPSCs.

Fibroblast growth factor-2 Fibroblast growth factor-2 (FGF-2) is a protein that kick-starts and blocks a host of signaling cascades inside the cells (picture a subway network with its intricate signaling system for getting a train to its destination while preventing collisions with other trains on the same tracks). It allows the formerly “old” adult cells to remain in pluripotency and survive in their young state.

the red growth media; it also provides carbonate ions that are essential for the metabolic functions of cells during the maintenance and reprogramming of iPSCs.

“disease-in-a-dish” approach was unattainable prior to the development of iPSC technology. Inside the David and Janet Polak Foundation Stem Cell Core Laboratory in Cedars-Sinai’s Board of Governors Regenerative Medicine Institute, cells are reprogrammed and maintained in embryonic-like arrested development in a clear, pinkish feeding solution called “red growth media.” When it’s time for them to begin their second life as a differentiated human cell, the careful addition of a specific protein to the mix is all it takes for these dormant pluripotent cells to grow and expand into millions or trillions of new brain, eye, or liver cells.

Inside Stem Cell Food N & N what’s inside

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| Discoveriesmagazine.org

Sodium Bicarbonate Yes, the same type of baking soda found in your pancake batter or toothpaste can be used as a buffer to improve the pH control of

ingredients

the red growth media; it also provides carbonate ions that are essential for the metabolic functions of cells during the maintenance and reprogramming of iPSCs.

Inside Stem Cell Food N & N what’s inside

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Q A &

Frontier Nursing By Sarah Spivack LaRosa

Linda Burnes Bolton — national influencer on health policy, vice president for nursing, chief nursing officer, and director of Nursing Research at Cedars-Sinai — talks about her true north, leadership, and how nurses can help light a path through the shifting topography of American healthcare.

Q. What inspired you to become a nurse? A: I was ill as a child, and in and out of the hospital with respiratory ail-

ments; the individuals who were the kindest to me, besides my family, were the nurses. That launched my lifelong commitment to caring for human beings. For me, that means using my knowledge and expertise to embrace the whole individual and to promote the wellbeing of my community. That idea has driven me throughout my life — it’s my true north. Q: The landscape of healthcare is changing. How is nursing responding? A: Florence Nightingale was one of the best scientists of her time. She

asked questions like, “What if we group together patients who have these symptoms? What if we move the latrines over here?” “What if ?”: That’s the basis of scientific inquiry. Nurses are doing that now, asking questions like, “How can we help patients better understand their medications, thereby

John Livzey

Linda Burnes Bolton, DrPH, RN, FAAN

| Discoveriesmagazine.org

EARLY LEADER

FIRSTS

KUDOS

The eldest of 12, raised in South Tucson, Arizona, she was given the task of preparing her siblings for school each day. She assigned each younger child to an older child who was responsible for bathing and dressing the little one before either could have breakfast.

The first in her family to go to college, and the only AfricanAmerican nurse to graduate from Arizona State University in 1970. “When you grow up in poverty you can either allow statistics to deprive you of hope or you can decide to look at the glass half-full and to stretch yourself.”

Named among the top 25 women in healthcare by Modern Healthcare in 2011. Presidentelect of the American Organization of Nurse Executives board. Past president, American Academy of Nursing, and the National Black Nurses Association.

decreasing dangerous errors? What makes them stop taking their medications?” To understand such patterns, you have to go where people live and work to gather evidence. We’ve been doing this community-based participatory research for years, but it’s finally gaining ground elsewhere. Q: Do you have a model for engaging nurses in healthcare and the community? A: I call it frontier nursing. Frontier nurses rode

into communities and conducted surveillance to figure out what was needed. Today, we need to explore and educate the community so people understand how to stay well. Nurses are trusted professionals and the right people to form partnerships. Over the next five years, one of our great challenges will be to transform the nursing workforce. Today, 65 percent of U.S. nurses work in acute care. At the Geri and Richard Brawerman Nursing Institute at Cedars-Sinai, we teach students that the bedside is only one element of their work. We prepare them to collaborate with pharmacists, social workers, and physicians to form a caring community. Q: Can nurses influence healthcare policy? A: Healthcare policy is about assessing the

resources necessary to promote improvement in the human condition. Nurses have deep knowledge about this and can be the best advocates. One good example is our work to ensure all Los Angeles public schools have access to a nurse. Our mobile units provide that access in underserved communities. But real change will come when we get nurses on those school boards to say, “It is not okay for you to have children under age 12 here without someone who can provide immediate health services.” Q: What makes a good leader? A: Grounding in the basic science of nursing and

nursing’s core mission of compassionate, quality care is number one. Number two is the ancient art of calling in diverse forces to examine an issue that would affect the neighborhood, community, or society. Leadership is not just about diversity but also inclusivity. fall 2014 | Discoveries |

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Q A &

Frontier Nursing By Sarah Spivack LaRosa

Q. What inspired you to become a nurse? A: I was ill as a child, and in and out of the hospital with respiratory ail-

John Livzey

Linda Burnes Bolton, DrPH, RN, FAAN

| Discoveriesmagazine.org

EARLY LEADER

FIRSTS

KUDOS

The Science of

Caring Clinical research is no longer limited to finding the next wonder drug, developing a new device, or discovering a genetic mutation. More than ever before, caregivers are engaged in the scientific study of healthcare itself: measuring patient satisfaction, exploring efficiency, and investigating how to improve safety. It’s called health services research, and it is transforming medicine.

t was a perfectly routine exam: Internist Daniel Stone, MD, was finishing up with his 68-year-old patient when she asked for a refill of her antianxiety medication. Five years earlier, Dr. Stone might simply have asked how the drug was working for her, scribbled out the prescription refill, and thought no more of it. On that day, however, he entered the order into Cedars-Sinai’s electronic medical records system and an alert popped up: Recent research indicated that benzodiazepines — a class of drugs that includes remedies for anxiety and insomnia — increased the risk of falling, hip fracture, and hospitalization in older patients and were no longer recommended. “When you’re seeing a lot of patients every day, it’s easy to gloss over something simple like a refill,” says Dr. Stone, medical director of Cedars-Sinai Medical Group.

“This tool is a catalyst for smarter care.” The tool in question is a clinical support platform called Choosing Wisely, an initiative of the American Board of Internal Medicine Foundation. Much like blind-spot monitors in sophisticated cars, Choosing Wisely offers timely cautions and guidance to caregivers as they navigate through patient visits and procedures. With the support of Consumer Reports, the information is available in easy-to-understand materials. Review of this information helps the patient and his or her physician determine appropriate treatment based on trusted data. It also helps them assess whether certain tests and procedures may be ineffective, unnecessary, or needlessly risky, given the circumstances. At CedarsSinai, the reduction in benzodiazepine use alone is projected to lead to 22 fewer fall-related injuries, three fewer hospitalizations, and two fewer deaths from falls this year.

By Sarah Spivack LaRosa • Photography by clint blowers

| Discoveriesmagazine.org

At Cedars-Sinai, the reduction in benzodiazepine prescriptions for older adults is projected to lead to 22 fewer fall-related injuries, three fewer hospitalizations, and two fewer deaths from falls this year.

summer 2013 | Discoveries |

The Science of

By Sarah Spivack LaRosa • Photography by clint blowers

| Discoveriesmagazine.org

summer 2013 | Discoveries |

After considering the alert on his screen, Dr. Stone explained the potential dangers of benzodiazepines to his patient. “Some patients will accept these risks and decide to keep using their medication, while others will ask for alternatives,” he says. This particular patient was happy to stop taking it and grateful for the extra, personalized attention. Choosing Wisely exemplifies a trend that has shaken up traditional models of medical research and clinical care in the U.S. The timeworn image of biomedical research as just involving lone investigators hunched over collections of tissue samples and beakers has been superseded. No longer confined to the laboratory, scientific methodology now sees researchers bringing studies to kitchen tables and birthing rooms, trauma bays, and barbershops (see Beyond the Bench, page 26). These days, the science of healthcare extends far beyond the realms of disease prevention and treatment. Patient satisfaction is measured minutely. Surgical efficiency and rates of cesarean sections are studied as closely as traditional evaluations like medication side effects and survival rates. And hospitals such as Cedars-Sinai are leveraging new methodologies to ensure the best possible care is provided to as many segments of the community as possible. The appropriate use of scientific analysis in all aspects of patient care has a positive impact on safety and also helps to lower costs and improve efficiency — vital considerations at a time when the American healthcare system is shifting toward greater affordability. But this advance adds up to much more than dollars and cents. It’s leading to something priceless to patients: the individualized application of data and knowledge, and a novel brand of medicine that prioritizes experience as well as biology. As

| Discoveriesmagazine.org

research moves past the confines of the lab, so does medicine’s capacity for innovation — auguring the dawn of a new kind of care that is more precise, patient-focused, and personalized.

sea change has swept the field of medical research during recent years with the publication of several landmark papers. One major report by the Institute of Medicine revealed that medical errors cause a startling 44,000–98,000 deaths per year. “That study had a huge impact because this was not a bunch of renegade doctors but one of the most prestigious medical organizations on the planet saying there was a real opportunity to improve care and reduce patient mortality,” says Scott Weingarten, MD, senior vice president and chief clinical transformation officer at Cedars-Sinai. The revelation raised an alarm among physicians and healthcare industry leaders. Two other key papers in The New England Journal of Medicine showed that patients received treatment in line with the latest and best scientific evidence only about half the time. Why was this happening? One reason is the sheer volume of medical research publications: Some 800,000 new scientific articles are added to the Library of Congress each year. “That’s a paper published every 26 seconds, plus thousands of practice guidelines,” Dr. Weingarten points out. PubMed, the

go-to source for biomedical literature, adds 500,000 new records annually. PubMed comprises a whopping 24 million citations, and its collection doubles every 13 years. As Dr. Weingarten says, “It is not humanly possible for any physician, no matter how good, to keep up.” This means that even if a physician is a deeply caring genius who devotes endless hours to reading scientific papers, it is still possible that, at some point, the patient might not get the right care at the right time. Practices had to change, and that shift came in the form of evidencebased medicine (EBM), which integrates clinical expertise with the most up-to-date medical research findings to make conscientious, judicious decisions for the care of individual patients. The use of systematic analysis is not confined to science — the approach also drives countless decisions in marketing and advertising, product design, and even sports. The bestselling book and feature film Moneyball celebrates Billy Beane, the Oakland Athletics manager who employed rigorous statistical analysis instead of the conventional wisdom most teams used to run their game. He adopted a new set of metrics for baseball that were better predictors of success and transformed one of the most revenue-challenged clubs into one of the most competitive, cost-effective teams in the sport. On the face of it, EBM sounds like what good doctors have been doing all along: studying evidence to come up

The appropriate use of scientific analysis in all aspects of patient care has a positive impact on safety and also helps lower costs and improve efficiency.

with the right answer for a patient. In fact it upends an age-old tradition that relies heavily on a single physician’s judgment and training, just like a talent scout for a baseball team would traditionally base his assessment of a young player on a narrow set of observations. Evidence-based practice filters and assesses swaths of clinical and scientific data, allowing doctors to reach decisions using a combination of the most powerful research to date, their expert intuition, and a particular patient’s idiosyncrasies and symptoms. The methodology has been around since the 1990s but has gained prominence with the growing gap between the amount of information available and the time demands of clinical practice. “The human element remains vitally important,” says Dr. Weingarten, who led the implementation of Choosing Wisely at Cedars-Sinai. “In that program, for example, the alert is used to prompt an informed discussion between doctor and patient, not make the decision.” A financial catalyst also spurred the use of this approach in healthcare. Annual health costs for a typical family of four covered by an average employersponsored health plan will top $23,000 this year. The Affordable Care Act and Medicare are pushing all health systems to be more efficient in an effort to stem ballooning costs. The Oakland A’s do-more-with-less-approach to baseball now applies to a new, value-based healthcare model that pursues quality at affordable rates. While reducing errors and inefficiencies does lower costs, Dr. Weingarten notes, “We never take a money-first approach. Our efforts focus on achieving the best possible clinical outcomes and quality of care for all of our patients.” Bradley Rosen, MD, who deals with budgets on a daily basis as CedarsSinai’s director of care transitions and

Genevieve McNamara @generationam 27m Took some codeine for my neck pain, now I feel both hungry and sick. What kind of side effect combination is that?!? #overshare Patricia Sherwood @pattywoodsy 8/18/14 Having some serious itching as a side effect of the hydrocodone. Thought I was going crazy, but it’s a thing. Tom Fitzgerald @LifesofFitzy 5/9/14 @DScottFrom I can’t take it! Hydrocodone causes night terrors for me. It’s a weird side effect a lot of people get. #painkillers

Jade Arnoldi @jarnold82 1/23/14 Has anyone else taken #codeine for a length of time? It’s making me feel utterly depressed and I don’t know if it’s just me or if it’s a side effect.

Dr. Brennan Spiegel is using Twitter to conduct a comprehensive study on how opioid pain medications affect individuals. His team filtered that mass of messages down to about 10,000 relevant to their research on the gastrointestinal side effects of such drugs.

Fall 2014 | Discoveries |

| Discoveriesmagazine.org

research moves past the confines of the lab, so does medicine’s capacity for innovation — auguring the dawn of a new kind of care that is more precise, patient-focused, and personalized.

The appropriate use of scientific analysis in all aspects of patient care has a positive impact on safety and also helps lower costs and improve efficiency.

Jade Arnoldi @jarnold82 1/23/14 Has anyone else taken #codeine for a length of time? It’s making me feel utterly depressed and I don’t know if it’s just me or if it’s a side effect.

Fall 2014 | Discoveries |

complex medical management, adds: “It’s important to remember that quality outcomes and saving money are not mutually exclusive. If we keep people healthy, it costs less and overall value increases.” The result is that today, think tanks, hospitals, and public health organizations are all focusing on efficiencies, safety, and the process of healthcare delivery. “Many have recognized that innovations in the delivery of medical care can save as many or more lives as the discovery of various new drugs, devices, or genes,” says Dr. Weingarten. Furthermore he believes that “future Nobel prizes will likely be awarded for innovative discoveries that save lives, reduce illness in communities, and improve quality of life — all while lowering healthcare costs.” The idea of using algorithms to improve medical decisions and patient satisfaction may leave a lot of people scratching their heads. But the model has the same humble goal that good medicine has always had: to find better ways to care for patients and cure diseases. “We do this to deliver the right care to the right people in the right place at the right time,” says Cedars-Sinai Vice President and Chief Nursing Officer Linda Burnes Bolton, DrPH, RN, FAAN.

hen patient experience is a priority, the questions asked during scientific inquiry are no longer confined to the realm of “Is this antibiotic working?” They include queries such as “Does this new mother’s birth plan include immediate skin-to-skin contact?” and “Who is going to make sure this elderly man, who lives alone, remembers to take his medication?” (see Beyond the Bench, p. 26). “There are things that no one else can say about your healthcare,” says Robin

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Weinick, PhD, associate director and senior social scientist at RAND Health. “How closely do you follow your physician’s advice? How often does your doctor return your calls? Do you refill your medications?” To answer these questions, providers and investigators need to know how patients are faring in their homes, both before they get sick and after they leave the hospital. “Ninety-nine percent of an individual’s experience with illness or injury happens nowhere near a physician,” says Brennan Spiegel, MD, director of Health Services Research at Cedars-Sinai. “To capture the true nature of disease and find solutions, we have to reach patients where they live.” Dr. Spiegel’s team of investigators is transforming the way patients, doctors, and hospitals communicate through innovations such as wearable biosensors that track patients’ vital signs at home and transmit their data to electronic medical records. The researchers also have developed a computer program that allows patients to explain their medical histories online. The platform is “smart,” asking relevant follow-up questions and drawing out information that leads to a robust dialogue between doctor and patient. Dr. Weinick, whose own work on healthcare quality concerns the rigorous measurement of patient experiences,

says: “There’s a movement to get patients seriously involved in how research questions are asked and answered. That will lead us to better outcomes.” Along with human diversity comes great complexity, because each individual lives at the nexus of experience, psychology, and biology. And with revolutions in fields such as genomics, every gene, protein, and bacterium involved in human health can be investigated to a degree unimaginable even a few years ago. No individual researcher, no matter how dedicated, can analyze the resultant mountains of data in the traditional way. The gap between the swelling mass of information and human computational capacity has led to more sophisticated data-dissecting tools. These tools helped map the human genome more than a decade ago and are now being used to chart the microbiome — the trillions of microorganisms that inhabit our bodies. They are also helping researchers map the human experience. Dr. Spiegel, who leads the new Center for Outcomes Research and Education at Cedars-Sinai, is using Twitter to conduct a comprehensive study assessing how opioid pain medications affect individuals. In the course of a few days, his team gathered 200,000 messages from around the globe and is

“Many have recognized that innovations in the delivery of medical care can save as many or more lives as the discovery of various new drugs, devices, or genes.” — Dr. Scott Weingarten

In the hopeful future fueled by the research revolution, medicine will address individual patients’ experiences to improve the care of their physical health, while exploiting a rich new universe of data and technology. busy categorizing them. The initial round of data included anything people were sharing about the medications on Twitter and other health-related e-forums. Dr. Spiegel’s team filtered that mass of messages down to about 10,000 that are relevant to their research on the gastrointestinal side effects of drugs. “We know from clinical trials in highly controlled environments what side effects a patient might experience,” he says, “but when we start with 200,000 bits of information, we get into the world of big data.” Mining big data allows Dr. Spiegel to identify trends. “Computer algorithms, applied correctly, can help us find otherwise undetectable signals in the noise,” he explains. “We might identify a side effect so rare that we haven’t seen it in the clinic. Or we might see how patients cope with side effects by modifying their dosage. We can use those results to form a hypothesis that ends up revealing new solutions for people struggling with opioids.” As scientists like Dr. Spiegel cast an ever-widening net, their research serves patients in the most intimate way possible. His “signals in the noise” are unique traits that are shared by small, scattered groups of individuals. As more of those traits are discovered and understood, medicine can offer personal and

precise solutions to more people. Thought leaders like Dr. Weingarten envision intensely personalized healthcare. “Your patient chart will still include your family history, medications, and all the usual information,” he says, “But down the road, we are also going to be able to go beyond that to include information related to a patient’s genomics and lifestyle to make sure that we provide cost-effective, personalized, and effective care for each patient.”

hile we all understand the need for costeffectiveness, not everyone in the medical community is on board with an emphasis on patient experience or big data. A certain amount of skepticism remains, and some physicians prefer to rely only on their years of experience and wellhoned intuition. And while big data is making an impact everywhere from marketing to medicine, the science is still in its infancy. Dr. Spiegel acknowledges that there is a backlash. “Big data is often considered to be dirty data, and that makes the scientists in us twitchy. We like data that is cultivated, clean, and whose origin we know — but unfortu-

nately that’s not reality.” He agrees with the general consensus that data alone cannot solve problems. “There is so much hype about how modern technologies can improve healthcare, but few academic hospitals are rigorously studying how to make it happen the way Cedars-Sinai is doing.” The biggest caveat of all might be that no piece of technology or novel program, no matter how brilliant, can heal every ill. “Everyone wants to live forever with the highest possible quality of life,” says Dr. Rosen. “That leads to challenges with expectation management. No one’s gotten out of life alive yet, of course. But as long as they are our patients, we will do everything we can to help them.” In the hopeful future fueled by the research revolution, medicine will address individual patients’ experiences to improve the care of their physical health, while exploiting a rich new universe of data and technology. Physician-scientists like Dr. Spiegel will continue to harness the endless river of incoming data from journals, clinical trials, social media, and electronic medical records — and strive to present it in an evocative and useful way to caregivers. “We will home in on the authentic, unique health story of each person,” he says. “How well we do for each individual will eventually determine the wellbeing of the entire population.” The change is already underway with programs such as Choosing Wisely. Dr. Stone, the physician with the 68-year-old patient and the antianxiety prescription, notes that the best alert he gets from the system is the one he never has to see. “These notifications become part of the consciousness of the physician because they transform the way you think,” he explains. “The technology, in the end, makes you a wiser doctor — and your patient walks into the world fully informed and healthier.”

Fall 2014 | Discoveries |

| Discoveriesmagazine.org

“Many have recognized that innovations in the delivery of medical care can save as many or more lives as the discovery of various new drugs, devices, or genes.” — Dr. Scott Weingarten

Fall 2014 | Discoveries |

Beyond the Bench

Intensive Care Units and the Surgical Critical Care Residency Program, Cedars-Sinai Department of Surgery

Study: OR 360, a simulation space designed to develop

rauma care is by nature chaotic. Victims of car wrecks, gunshot wounds, or cardiac arrest arrive at the Emergency Department amid a cacophony of sirens and shouts that flings surgeons and nurses into a flurry of activity. The IV tubes get tangled, the staff bumps against each other in narrow operating rooms, and someone dashes off to find an interpreter who speaks Cantonese. Cedars-Sinai’s research project OR 360 aims to curtail the chaos with a combination of 21st century technology and enlightened new practices. The medical center partnered with the U.S. military to design what has been called the “operating room of the future.” The initiative, drawing on practices from surgery, psychology, aviation, and other disciplines, addresses potential break-

| Discoveriesmagazine.org

downs in the coordination of trauma care during the “golden hour,” when prompt medical attention can mean the difference between life and death. “The quicker we get patients cared for, the better the outcomes. So our goal is to improve the efficiency and effectiveness of acute trauma care by introducing innovations in communication, technology, and workflows,” says Bruce L. Gewertz, MD, surgeon-inchief, chair of the Department of Surgery at Cedars-Sinai, and the H & S Nichols Distinguished Chair in Surgery. Military medical centers are exceptional at streamlining practices and avoiding workflow disruptions. Funded by $3.8 million in grants from the Department of Defense, members of the Cedars-Sinai team studied military surgical teams in the U.S. and Europe.

Study partner: U.S. Department of Defense

They observed their practices and interviewed surgeons, nurses, and other medical personnel. The international collaboration led OR 360 teams to rethink the way operating rooms are designed, with movable walls and equipment for more flexible use and a ceiling built like a gridded trolley system that allows the space to be endlessly reconfigurable. They identified ways to improve communication among staff and eliminate disruptions during surgery. And they designed an iPhone application that instantly conveys patient information to caregivers as they rush to the OR from far-flung parts of the hospital. As an outgrowth of the initial research, Cedars-Sinai has introduced innovations to streamline trauma care, including color-coded trauma bays that enable staffers to quickly locate supplies, whiteboards that display vital information as teams respond to shifting situations, and pre-briefings that allow doctors and staff to quickly establish their roles in complex cases. Early results are promising. The whiteboards and pre-briefings, for example, reduced the time to capture the first radiological images by more than 10 percent and the time to draw blood for the first lab tests by more than 20 percent. “This is a new way to think about the improvement and delivery of healthcare,” says Ken Catchpole, PhD, director of Surgical Safety and Human Factors Research at Cedars-Sinai. “By putting patients and clinicians at the center of the system, we can design trauma care for the 21st century that is of the highest quality possible.”

Max Gerber

In the Trauma Bay

By Sarah Spivack LaRosa

Investigator: Eric J. Ley, MD, director of Surgical

improvements in trauma and emergency care

linical research is breaking out of the lab and into the world. Investigators make house calls, study trauma bays, partner with barbershop owners and community organizations, and tap into fundamental human experiences. Meet the new faces of medical research in eight case studies that take you from L.A. to Portland, and from the barbershop to the Twittersphere.

Case Study 1:

Lab: The operating room

Beyond the Bench

Intensive Care Units and the Surgical Critical Care Residency Program, Cedars-Sinai Department of Surgery

Study: OR 360, a simulation space designed to develop

| Discoveriesmagazine.org

Study partner: U.S. Department of Defense

Max Gerber

In the Trauma Bay

By Sarah Spivack LaRosa

Investigator: Eric J. Ley, MD, director of Surgical

improvements in trauma and emergency care

Case Study 1:

Lab: The operating room

Lab: Homes, like Sylvia Lieberman’s apartment in the Westwood area of Los Angeles

Case Study 2:

Study: Path to Wellness, assessing effective ways to

By Sherry Angel

manage patients’ transitions from the hospital to the home

The House Call

Staff: Nurse practitioners like Esther Yoon, NP, MSN Subjects’ age range: 65 to 102

Max Gerber

rdinary life is filled with risk for frail, older adults home from the hospital. A fall or medication error could send them back — and trigger a steady decline. These patients are the focus of a study using a method more often associated with time-honored medicine than with breakthrough science: the house call. The study, called Path to Wellness, is testing — and looking to enhance — a model developed at the University of Pennsylvania School of Nursing, which has nurses visit patients in their homes for up to two months after they leave the hospital. The objective: improve older adult patients’ safety and quality of life while reducing costly, preventable hospital readmissions. Among the patients in the study is Sylvia Lieberman, a vibrant 97-year-old who lives in a small apartment in an assisted living facility. A leg infection brought her to Cedars-Sinai last summer. Esther Yoon, NP, MSN, visited Sylvia several times after her discharge to monitor the healing process. “Esther told me I could call her any time,” Sylvia says. “It felt good that somebody was there for me.” Led by Linda Burnes Bolton, DrPH, RN, FAAN — vice president, chief nursing officer, and director of Nursing Research at Cedars-Sinai — along with Harriet Aronow, PhD, a research scientist, and Lianna Ansryan Klemp, MSN, RN, CNS, a clinical nurse specialist, “Path to Wellness” is part of a nationwide effort to develop evidence-based models for managing transitions of care from one setting to another more effectively. “You can’t make assumptions that patients will continue to get better after they are discharged,” Dr. Aronow says. “The transitional care approach gets us into the home, where we can help ensure patients recover fully and stay in the best health possible.” Participants are recruited through Cedars-Sinai’s Frailty Project, a program funded by the Eisner Foundation. The program has led to shorter hospital stays and reduced intensive care admissions. Drs. Bolton and Aronow’s study takes the project to the next level by implementing customized care plans for patients once they return home. “We’re not the first to send nurses into the home,” says Bradley Rosen, MD, director of Care Transitions and Complex Medical Management, “but how we linked the Frailty Project with house calls is a smart deployment of resources and should prove highly effective.” Dr. Rosen, and Kelley Hart, administrative director for Cedars-Sinai’s Medical Provider Network, partner to oversee the study’s clinical visits. Although one of their most important roles is identifying medical issues early to prevent readmission, nurse practitioners (NPs) also assess patient needs and ensure care is well coordinated and the right support services are in place. These advancedpractice nurses have extensive education beyond the registered nursing degree. Those in the Path to Wellness study also have specialized training in transitional care. “This research doesn’t fit the traditional mold,” Dr. Aronow says, “but it’s hugely important because it is focused on patient needs and improving outcomes.” As for Sylvia Lieberman, her bucket list is simple: “To be able to do as much as I can for whatever time I have.” Studies like Path to Wellness help older adults do just that.

Case Study 3:

On Twitter

“G

otta take 4 of these bad boys a day… #sigh #lialda #crohns #ulcerativecolitis #crohnsdisease,” tweeted @YFAOFM July 4, 2013, from San Francisco’s East Bay. A photo shows a pill in the palm of her hand. A lot can be surmised from this tweet. The woman using the handle “YFAOFM” has inflammatory bowel disease (IBD) and a new prescription for Lialda, an ulcerative colitis medication. She is also sick of being sick (#sigh) and is looking for support via social media, hoping to connect with others who share her experience. “What we are witnessing is new: Global forums self-assemble to share intelligence in real time about everything, including healthcare,” says Brennan Spiegel, MD, director of Health Services Research at CedarsSinai. His team is using sophisticated computer algorithms to pluck thousands of communications about life with IBD from Twitter and other publicly available social media platforms. “We are describing the topography of the patient experience with IBD,” explains Dr. Spiegel. Typically, this map would be drawn using a costly focus group study that includes a small number of carefully selected patients. In Dr. Spiegel’s study, the focus group is the entire world — anybody who uses Twitter, in any language. (No privacy issues are raised with the investigation because the team scrapes data from public forums, using only people’s words — not their names — for research, and no interaction occurs between the virtual “focus group” and Dr. Spiegel’s lab.) More than 1 million people in the United States have IBD, a group of

Fall 2014 | Discoveries |

Lab: Homes, like Sylvia Lieberman’s apartment in the Westwood area of Los Angeles

Case Study 2:

Study: Path to Wellness, assessing effective ways to

By Sherry Angel

manage patients’ transitions from the hospital to the home

The House Call

Staff: Nurse practitioners like Esther Yoon, NP, MSN Subjects’ age range: 65 to 102

Max Gerber

Case Study 3:

On Twitter

“G

Fall 2014 | Discoveries |

| Discoveriesmagazine.org

Case Study 4:

In Portland

he entire population of Portland, Oregon, can consider themselves partners in the research of Sumeet S. Chugh, MD. Dr. Chugh, associate director for Genomic Cardiology at the Cedars-Sinai Heart Institute, is the driving force behind an audacious study to solve one of the heart’s deadliest mysteries. Every day, almost a thousand Americans experience an unexpected loss of heart function. Only 5 percent to 7 percent of them make it home alive. Sudden cardiac arrest usually results from an electrical disturbance in the heart that disrupts its pumping. When Dr. Chugh — now section chief of Clinical Cardiac Electrophysiology and the Pauline and Harold Price Chair in Cardiac Electrophysiology Research at Cedars-Sinai — was introduced to the problem in the 1990s, it was a “black box” of mystery that offered almost no information, he says. Most sudden cardiac arrest patients were dead on arrival, and their hearts offered no visible clues to their failure. In order to solve the puzzle, Dr. Chugh needed to study a great many patients at the very moment their hearts stopped. “You need numbers! Sudden cardiac arrest is common in the entire population, but not in 1,000 or even 10,000 people,” he explains. So he decided to use the entire Portland metro area — 1 million people — as his laboratory. Dr. Chugh successfully launched the Oregon Sudden Unexplained Death Study (Ore-SUDS) in 2002 to find clear risk factors for sudden cardiac death, such as preexisting medical conditions, genetic triggers, socioeconomic circumstances, or blood markers. He partnered with Portland’s Emergency Medical Services and the Oregon state medical examiner’s office. More than 300 ambulance paramedics who serve Multnomah County, Oregon, would become key members of the investigative team. The paramedics gather field data for the study as well as patient blood samples — all while performing the urgent work of attempting to save lives. For example, when a paramedic inserts an intravenous needle to provide medication, it’s standard to pull a little blood back to confirm the needle is positioned correctly. “Now, instead of throwing it away, we collect that blood for research,” explains Ore-SUDS research manager Ron Mariani. A retired paramedic and captain of the Portland City Fire Department, he has been instrumental in involving active paramedics in the project. Sample by tiny sample, Ore-SUDS has created a clinical database and biobank that contains medical and community-related data on nearly 5,000 people. The work is guided by the ethical, legal, and social requirements that govern this kind of research. Twelve years and 40 scientific papers later, Ore-SUDS has made significant progress. The team has identified several “hot spots” on the human genome that increase susceptibility to sudden cardiac death — and one spot that seems to offer protection. In addition, multiple novel clinical markers have been identified, and the research has revealed that African-Americans have double the odds of manifesting the condition as people of other ethnicities. Dr. Chugh’s vision is global. He helped launch a sister project in Taiwan and has been approached by colleagues from around the world. “My job is to put myself out of business,” he often says. “If each of us working on the problem shares that goal, we can end sudden cardiac death for good. I’m eternally optimistic.”—SSL

Lab: The city of Portland research manager: Ron Mariani Study: Oregon Sudden Unexplained Death Dan Root

chronic conditions including Crohn’s disease and ulcerative colitis, with symptoms ranging from mild to severe. IBD is associated with emotional distress, job anxiety, and costly medical treatments. Dr. Spiegel argues that the fullness of this “biopsychosocial illness experience” is difficult to grasp for those who treat IBD patients. “When we have 15 minutes with a patient in our office, that’s a somewhat artificial environment,” he explains. “The story patients tell may not be entirely accurate or complete.” In the laboratory of the digital world, IBD patients express themselves without constraints and, according to Dr. Spiegel, language becomes data. “It’s not structured in the ways we are accustomed to in science, but a structure can be imposed on the data provided by language, and themes arise.” Those themes include patients using coping tools such as sarcasm and humor, the side effects of drugs, and issues with adhering to diets or medications. “Even in short posts, a picture of the quality of life of IBD patients emerges,” says Dr. Spiegel. As he and his team map the universe of this disease experience, they can help caregivers connect with patients in novel ways. His group has created in-depth questionnaires to measure quality of life and has developed assessment tools to see whether interventions are making a real difference. The next phase of Dr. Spiegel’s study will actively gather real-time information on symptoms, emotions, and thoughts from patients via a smartphone application. Dr. Spiegel hopes to lift a curtain between caregivers and those living with the disease: “These technologies have the power to bring us closer to patients, even as the experiences we examine are happening farther away from us.”—SSL

Study (Ore-SUDS) to identify risk factors for sudden cardiac death

Key partners: Paramedics and firemen

summer 2013 | Discoveries |

| Discoveriesmagazine.org

Case Study 4:

In Portland

Lab: The city of Portland research manager: Ron Mariani Study: Oregon Sudden Unexplained Death Dan Root

Study (Ore-SUDS) to identify risk factors for sudden cardiac death

Key partners: Paramedics and firemen

summer 2013 | Discoveries |

Case Study 6:

Lab: Labor and delivery rooms

Case Study 5:

Investigator: Marle Shelton-Hoff, RN-C, MSN, nurse manager, Labor and Delivery and Maternal-Fetal Care units, Department of Obstetrics and Gynecology

In the Delivery Room

In Underserved Communities

Study: Rock and Roll to reduce cesarean section rates Partners: Labor and delivery nurses

Max Gerber

Key equipment: An exercise ball

hen you add rock and roll — literally — to labor, the result can be a faster delivery and a more satisfying childbirth experience. This is the outcome of a study in which Cedars-Sinai nurses helped women change positions during labor by using an exercise ball to move the birthing process along with gentle rocking and rolling. Cedars-Sinai is at the forefront of an effort to pay closer attention to what women want during this milestone. Based on research in labor and delivery rooms, and a national survey of patient preferences, innovative practices are emerging. So is the realization that improving patient satisfaction can also make childbirth safer. “Women are increasingly dissatisfied with hospital childbirth services,” says Kimberly Gregory, MD, MPH, vice chair of Women’s Healthcare Quality and Performance Improvement in Cedars-Sinai’s Department of Obstetrics and Gynecology. Rising rates of cesarean sections, falling rates of vaginal birth after a cesarean, and a decreasing ability to participate in decisionmaking are major concerns. “While observing hospital safety policies, we can also pay closer attention to patient preferences,” she adds. Dr. Gregory, also director of Maternal-Fetal Medicine, has extensively researched c-sections and helps lead a national effort to reduce such deliveries, which increase complications for both mother and newborn. She says the Rock and Roll study, led by Marle Shelton-Hoff, RN-C, MSN, nurse manager in the Labor and Delivery and Maternal-Fetal Care units, is an example of how Cedars-Sinai is getting results. In the study, a group of specially trained nurses helped first-time moms in labor shift every 30 to 40 minutes to one of nine positions. This significantly reduced c-sections as well as average hours in labor. The method was so effective, and patient reaction so positive, that all Cedars-Sinai labor and delivery nurses have since been trained in it. Another study, based on a national Internet survey, revealed a gap between women’s birth plans and outcomes. Participants’ top priorities were avoiding interventions and medications, receiving immediate skin-to-skin contact with their babies, and having a calm and supportive environment. “Cedars-Sinai is quickly translating these findings into efforts to promote greater choice while still prioritizing safety and evidence-based care,” Shelton-Hoff says. Through community outreach, she encourages women to develop birth plans and educates them about options for hospital deliveries. The medical center even offers orientations to integrate patients’ doulas into the care team. Dr. Gregory’s research shows that a mother’s anxiety and the risk of cesarean delivery are reduced when she has a trusted person at her side during childbirth. “For women with uncomplicated pregnancies, labor and delivery can be accomplished through a variety of approaches. This makes childbirth the ultimate preference-sensitive condition,” Dr. Gregory says. “This research will help us close the gap between what women want and what hospitals deliver.”—SA

hey knocked on doors in South and Central Los Angeles neighborhoods to ask new mothers questions like: What kinds of stress are you facing in your life? Do you feel safe in your neighborhood and your home? Where do you turn for support? They also monitored the women’s blood pressure, body mass index, cholesterol, and their Vitamin D and average blood sugar levels, among other things. The men and women who collected this information weren’t census takers or salespeople — they were community members trained by Cedars-Sinai researchers. The goal: to collect health data and monitor various physical health signs for a nationwide partnership called the Community Child Health Network (CCHN) study. “This is community-centric research,” says obstetrician-gynecologist Calvin J. Hobel, MD, a national expert in maternal-fetal medicine. “Researchers often go into the community and extract data, but in order to improve the health of that community, we have to work with the people living there,” explains Dr. Hobel, who has an active research laboratory at Cedars-Sinai that’s supported by three National Institutes of Health (NIH) grants. Dr. Hobel, the Helping Hand of Los Angeles-Miriam Jacobs Chair in Maternal-Fetal Medicine, is CCHN’s principal investigator at Cedars-Sinai. He partnered with local organizations such as Healthy African American Families (HAAF), the L.A. Best Babies Network, and African-American and Latino churches. These organizations turned to their member networks for

Fall 2014 | Discoveries |

Case Study 6:

Lab: Labor and delivery rooms

Case Study 5:

Investigator: Marle Shelton-Hoff, RN-C, MSN, nurse manager, Labor and Delivery and Maternal-Fetal Care units, Department of Obstetrics and Gynecology

In the Delivery Room

In Underserved Communities

Study: Rock and Roll to reduce cesarean section rates Partners: Labor and delivery nurses

Max Gerber

Key equipment: An exercise ball

Fall 2014 | Discoveries |

help, with HAAF taking the lead in coordinating community involvement. Most of the 1,600 new mothers who participated in the study are AfricanAmerican or Latina. All live in underserved communities that face significant health challenges. As data was gathered, the women received general health education and information about signs of heart disease, diabetes, depression, obesity, and other health conditions. Fathers were also interviewed to identify stress factors in their lives that could affect their family’s health. The objectives were to help women and families immediately address any health issues and take steps to protect their children’s health and improve the outcomes of future pregnancies. The process is called community-based participatory research and combines science, education, and social action to put positive change in motion even before the results of the study are in. Funded by the NIH, CCHN focused on the impact of poverty, hunger, and domestic violence, and examined how maternal allostatic load — the cumulative wear and tear on the body from chronic stress — influences health outcomes. The investigation yielded a wide range of findings about maternal and child health risk factors. For example, some young mothers who appear healthy are really at risk for diabetes and heart disease, and the first year after birth is a critical period for preventing obesity in the mother and child. Dr. Hobel also saw potential links between early cardiovascular disease and preterm birth, and signs that Vitamin D deficiency may contribute to obesity. Community members were involved in every phase of the research, from the design of the study and development of survey questions to recruitment of participants and collection and analysis of data. According to HAAF CEO Loretta Jones, a co-principal investigator of the study, this process brought

| Discoveriesmagazine.org

greater authenticity to the research. She adds that partnering in research enables neighborhood organizations to monitor health needs and do more for the people they serve on an ongoing basis. Dr. Hobel calls this sustainability. “Conducting this kind of research is a way of investing in the community that has long-term benefits,” he says.—SA

Case Study 7:

At the Kitchen Table

indy Mamelak has been assembling a lot of meals lately — boxes filled with fig bars, string cheese, pasta with meat sauce, and peanut butter and honey sandwiches. It might sound like she’s packing lunches for Meals on Wheels, but Mamelak, a bionutritionist, is actually handling a key element of an investigation into the link between obesity and a gut-dwelling microbe. The food is for 11 people enrolled in a pilot study that takes the research from the Cedars-Sinai lab to their kitchen table, and back. The study is the brainchild of Ruchi Mathur, MD, director of the Anna and Max Webb & Family Diabetes Outpatient Treatment and Education Center at Cedars-Sinai, and is funded by the American Diabetes Association. Dr. Mathur has pinpointed a microbe that, when overpopulated, makes people more prone to obesity and pre-diabetic conditions. For every one of our own cells, we host 10 others such as bacteria, fungi, and a plethora of other microscopic agents. These tiny entities form what’s called the microbiome, a relatively new frontier for researchers

who have only begun to examine how this internal ecosystem might affect the function of our bodies. Her lab is testing how efficiently people digest food with and without that microbe — which has a mouthful of a name: Methanobrevibacter smithii or M. smithii for short. “People ask me, ‘Why would gut microbes want you to gain weight?’” says Dr. Mathur. “From an evolutionary perspective, when we were cavemen, we sometimes had to club breakfast and then go three or four days without eating. Humans who could store calories better were more likely to survive.” Fast-forward several millennia and most Americans don’t go three or four hours without eating. “What was adaptive for our ancestors — having microbes that are really good at harvesting nutrition — might be maladaptive for our modern age and environment,” explains Dr. Mathur. Participants who appear to have an overabundance of M. smithii take home a three-day supply of Mamelak’s custom-made meals. “We carefully design meals that match each subject’s metabolism,” says Mamelak. Subjects then take a 10-day course of antibiotics to cull the population of M. smithii. Then the three-day diet is repeated. “We are measuring people’s digestion and metabolism before and after the antibiotic, so it’s vital that they be on a standardized diet,” says Dr. Mathur. Metabolic measurements include the use of a “smart pill” to track the speed of digestion — an electronic capsule swallowed by subjects that transmits data to a wearable device. “If the gut is emptying more slowly due to the presence of these microbes, that might encourage weight gain,” she explains. This study is shedding light, one meal at a time, on how the mass of microorganisms thriving in our gut affects our health. The findings may ultimately help inspire patient-specific antibiotics and probiotics that help people maintain a healthy metabolism.—SSL

Case Study 8:

In Barbershops

lack-owned barbershops have been community hubs for a century — incubators for everything from political activism to entrepreneurship. Now, thanks to the groundbreaking efforts of Ronald Victor, MD, Los Angeles’ barbershops also double as medical research labs to address the devastating problem of hypertension, or high blood pressure. “Uncontrolled hypertension is one of the biggest health problems facing the African-American community today,” says Dr. Victor, director of the Hypertension Center in the Cedars-Sinai Heart Institute. Among African-Americans, 43 percent of men and 45.7 percent of women have hypertension, compared to 33.9 percent of white men and 31.3 percent of white women. High blood pressure costs the nation $47.5 billion

each year. Dr. Victor, who holds the Burns and Allen Chair in Cardiology Research, has been awarded an $8.5 million grant from the National Heart, Lung, and Blood Institute to fund a clinical trial that leverages barbers’ roles as community partners. The work builds on a pioneering study he conducted in 17 Texas barbershops in which barbers offered blood pressure readings with every haircut. They advised customers with hypertension to see a doctor, and those who followed through with a physician got a free trim. Hypertensive patrons saw their blood pressure drop significantly compared to a control group. The study, published in 2011, was the first to subject newly popular barbershop-based health programs to scientific scrutiny. “Barbers can be looked at as sort of an indigenous force of community health workers,” Dr. Victor says. “They own the intervention as trusted partners.” Hypertension is a deadly condition that can cause strokes, heart attacks, and organ failure. “It’s called the silent killer because it has no symptoms. All too often, by the time a patient realizes

“Barbershops are a wonderful place to talk about health with influential peers in a uniquely personable setting. A barber’s chair is much more comfortable than a table in a cold examination room.” —Dr. Ronald Victor

he has hypertension, the heart and kidneys already have been damaged,” says Dr. Victor. The new clinical trial will include 500 African-American male patrons of 20 Los Angeles-area barbershops. All the participants will have uncontrolled hypertension and be longtime customers of the shops. Vital to the intervention’s success is the barbers’ role as agents of change. “Barbershops are a wonderful place to talk about health with influential peers in a uniquely personable setting,” says Dr. Victor. “It’s like a social club where men get the local news, gossip, and make friends.” “It’s also an easy thing to put on a blood pressure cuff monitor in there,” he adds. “A barber’s chair is much more comfortable than a table in a cold examination room.” The new study, dubbed Barbershop L.A., will test the feasibility of exporting this model to African-American communities around the country. Dr. Victor’s 2011 data concluded that, if the intervention could be rolled out at the 18,000 African-American-owned barbershops across the U.S., the first year alone would see about 800 fewer heart attacks, 550 fewer strokes, and 900 fewer deaths, saving as much as $110 million in healthcare costs. This time, clinical pharmacists will play a key role in the trial, says Dr. Victor. “Pharmacists are more accessible than doctors, are less intimidating, and are trained to develop shared goals with patients, as well as to educate them.” The study involves innovative collaborative practice agreements with pharmacists from a range of organizations, allowing them to manage the medication therapy aspect of patients’ treatment plans. Dr. Victor says, “The heart of the study’s idea is to make this something that could be sustainable and owned by the community.”—SSL

Fall 2014 | Discoveries |

| Discoveriesmagazine.org

Case Study 7:

At the Kitchen Table

Case Study 8:

In Barbershops

Fall 2014 | Discoveries |

// // On Diabetes

Driven by rising obesity levels, the Type 2 diabetes epidemic is a ticking time bomb. We asked a variety of experts — from researchers an d dietitians to surgeons and health educators — what ch anges they want to see in the care, management, or prev ention of this pernicious disease. From big ideas to small steps anyone can take, here’s how th ey answered.

Mark O. Goodarzi, MD, PhD, endocrinologist, geneticist:

Josiane Broussard, PhD, postdoctoral research scientist:

Regulate sugar like tobacco.

Get some sleep.

Obesity and diabetes arise from the interaction of our genes and our environment. “Because we can’t simply change our genes, we need to change the environmental factors in America that contribute to obesity,” says Dr. Goodarzi. “A major contributing factor of this environment is sugar. Up to 80 percent of foods sold in America have added sugar, and sugary beverages account for some 15 percent of daily caloric intake. The government needs to label sugar as unsafe and strictly limit its addition in food. Public campaigns against tobacco and trans fats have met with tremendous success. This can work with sugar, too.”

Studies suggest that people who sleep fewer than five hours per night are at higher risk for developing obesity and Type 2 diabetes. “Researchers took healthy volunteers and compared their hunger and metabolism after one week of eight hours of sleep versus a week of four hours of sleep,” Dr. Broussard says. After one week of only four hours of sleep per night, volunteers developed insulin resistance and had an increase in appetite. Their hunger-regulating hormones were also disrupted. “We need to recognize that adequate sleep is a major component of health and may reduce the risk of developing metabolic diseases,” says Dr. Broussard.

Mark O. Goodarzi, MD, PhD, is director of the Division of Endocrinol-

Josiane Broussard, PhD, is a Society in Science–Branco Weiss Fel-

ogy, Diabetes, and Metabolism at Cedars-Sinai. His research focuses

low at the Diabetes & Obesity Research Institute, where she is looking

on endocrine genetics and seeks the genetic determinants of insulin

at how sleep restriction affects the metabolic organs of the body.

resistance and related conditions such as diabetes, cardiovascular disease, and polycystic ovary syndrome.

//////////

tration by CLINT BLOWERS By Jasmine Aimaq • Photo Illus

//////

Fall 2014 | Discoveries |

// // On Diabetes

Mark O. Goodarzi, MD, PhD, endocrinologist, geneticist:

Josiane Broussard, PhD, postdoctoral research scientist:

Regulate sugar like tobacco.

Get some sleep.

Mark O. Goodarzi, MD, PhD, is director of the Division of Endocrinol-

Josiane Broussard, PhD, is a Society in Science–Branco Weiss Fel-

ogy, Diabetes, and Metabolism at Cedars-Sinai. His research focuses

low at the Diabetes & Obesity Research Institute, where she is looking

on endocrine genetics and seeks the genetic determinants of insulin

at how sleep restriction affects the metabolic organs of the body.

resistance and related conditions such as diabetes, cardiovascular disease, and polycystic ovary syndrome.

//////////

tration by CLINT BLOWERS By Jasmine Aimaq • Photo Illus

//////

Fall 2014 | Discoveries |

Ruchi Mathur, MD, endocrinologist:

Awaken your inner caveman. When our ancestors lived as hunter-gatherers, they evolved adaptive mechanisms such as insulin production and intestinal microbes that helped them harness and store calories in order to survive. “Our environment has changed faster than our genetics,” she says. “What once was adaptive is now maladaptive. We rarely go without food for three hours, let alone three days.” To combat obesity — and resulting diseases — Dr. Mathur recommends awakening your inner caveman. “Treat your body like it was meant to be treated: Fill up on vegetables, lean meats, and whole grains. Stop when you’re full, and keep your body moving.” Dr. Mathur thinks we have the power to reduce our individual burden of disease by honestly answering this simple question: How do you want to fuel your body? Ruchi Mathur, MD, is director of the Anna and Max Webb & Family Diabetes Outpatient Treatment and Education Center at CedarsSinai. Her primary clinical interests are in pre-diabetes, diabetes, and obesity, and her research focuses on the effects of gastrointestinal microbes on metabolic diseases.

says. “Patients will only need an Internet connection to verify the accuracy of the algorithms and integrity of the pump.” David H. Geller, MD, PhD, is a pediatric endocrinologist in the Department of Pediatrics at Cedars-Sinai. He has given more than 30 lectures, seminars, and presentations on endocrinology-related issues at national and international conferences and is highly active in community service, alongside his clinical practice.

fast-food restaurants, promoting a campaign to combat obesity by helping fund public parks, and advocating for better grocery stores.

Make the pharmaceutical industry pay its share.

Clinical Nutrition and Internal Medicine at the University of Texas Southwestern Medical Center. Her research examines sex differences

Miguel Burch, MD, bariatric surgeon:

In the U.S., most biomedical research is funded by the National Institutes of Health (NIH) and the majority of medical breakthroughs are born in the public sector. But private companies are allowed to mine this research and use it to develop drugs and treatments while rarely having to pay for it. Unfortunately, the NIH is in financial trouble. Less than 10 percent of proposals are now funded, so researchers are forsaking the public sector in favor of industry, where their projects won’t struggle for money. Dr. Bergman has a solution: “Some of the proceeds

in the behavior of adipose tissue and their link to Type 2 diabetes.

Trailblaze with bariatrics.

Alexander Ljubimov, PhD, ophthalmology and stem cell researcher:

Treat diabetes as more than a blood-sugar disease. Bariatric surgery can normalize blood sugar for some obese patients who suffer from Type 2 diabetes. However, it does not always reverse the risk of future complications, such as blindness and neuropathy. “It’s like the body has a metabolic memory — in some ways, the body continues to behave as if it had diabetes even after the blood sugar is normalized, because blood-sugar problems caused lasting genetic changes in the patient,” explains Dr. Ljubimov. It has become clear that diabetes is not just about insulin and glucose. “It should be treated with a combination of interventions, just like other complex diseases, such as AIDS or cancer. We need medications that prevent or treat the neuropathies that can contribute to blindness or amputation. Ultimately, we need drugs that can destroy that metabolic memory once and for all.” Alexander Ljubimov, PhD, is an internationally recognized eye re-

Carolyn Buenaflor, MPH, is associate director of Cedars-Sinai’s

searcher and the director of the Eye Program at Cedars-Sinai’s Board

Healthy Habits program. Healthy Habits helps children and families

of Governors Regenerative Medicine Institute. His research includes

learn about healthy eating and physical activity with programs reach-

studies of inhibitors of a key enzyme to block abnormal retinal vessel

from the sale of any prescription drug made by a pharmaceutical company should go directly to the NIH. The NIH would have a guaranteed source of income, and it would be fair.”

growth, gene therapy to restore corneal function in patients with diabetic retinopathy, the use of stem cells for corneal regeneration, and targeted anti-cancer nanomedicines.

Richard Bergman, PhD, the Alfred Jay Firestein Chair in Diabetes

Design a smarter implantable insulin pump.

Research at Cedars-Sinai, is director of the Diabetes & Obesity

Jan Perry, city official, diabetic:

Research Institute and the Sports Spectacular Diabetes and Obesity

Diabetic children need a better way to receive insulin and modulate blood sugars, according to pediatric endocrinologist Dr. Geller. “For them, insulin shots are especially scary, and compliance is a problem.” Pumps that continuously infuse insulin under the skin are major advancements. However, current models depend on preset instructions, receive blood glucose information from separate sensors, and cannot act independently on this data. “Fortunately, I believe we are fewer than 10 years away from a smarter pump that measures blood sugar minute-by-minute and uses personalized algorithms to deliver insulin and glucagon through separate ports,” Dr. Geller

Wellness and Research Center. The Bergman lab is elucidating why

Make government and industry work together.

| Discoveriesmagazine.org

councilmember from 2001 to 2013, helping enact restrictions on

Obesity Research Institute. She is former associate professor of

People in underserved communities are disproportionately affected by obesity and Type 2 diabetes. “There is a lot of appeal to buying and consuming cheap, high-calorie food,” says Buenaflor. “One of the things we teach is that, over the long run, that ‘big value’ meal is going to cost you a fortune in medical bills and lost productivity. We show families changes they can realistically make. There are no forbidden foods, only forbidden portion sizes. Enjoy your food. Just eat less of it.”

David Geller, MD, PhD, pediatric endocrinologist:

Jan Perry is the manager of the Economic and Workforce Development Department in Los Angeles. She served as a Los Angeles city

Richard Bergman, PhD, diabetes and obesity researcher:

Show people the true cost of “big value” meals.

children, and families in underserved communities.

their sugary products from school vending machines, an essential and encouraging development. “That trend needs to accelerate: government making public health a priority, and industry showing real leadership,” says Perry.

Deborah Clegg, PhD, is a research scientist in the Diabetes &

Carolyn Buenaflor, MPH, health educator:

ing elementary and middle school students, parents of preschool

have lower rates of diabetes than men, and research suggests it’s because they have healthier fat cells — in men, extra calories turn into lipid droplets that course through the body. After menopause, women’s fat cells shrink and their risk of diabetes becomes equal to men’s. “We need to identify what makes fat cells healthy in younger women so we can create therapies to help women as they age — as well as men in all stages of life.”

resistance to insulin predisposes people to diabetes and is developing new treatments and procedures that might reduce obesity or suppress the link between excess weight, insulin resistance, and Type 2 diabetes.

Deborah Clegg, PhD, metabolic disease specialist:

Celebrate expanding fat cells! Most people know that extra calories can be stored as fat. “That’s actually not a bad thing,” says Dr. Clegg. “It means your fat cells are healthy, expanding enough to absorb the fat and prevent it from circulating in your bloodstream. Premenopausal women

“It starts with teaching children healthy habits,” says Perry. A lifelong public servant and Type 2 diabetic, she thinks government and the private sector should work together to slow the epidemic of obesity and Type 2 diabetes. “One major goal must be to improve the food in public schools. The government simply can’t provide all the funding, although the public sector needs to do its part.” Perry notes that several Los Angeles Unified School District schools have launched healthy lunch programs, even growing their own vegetable gardens. At the same time, some private companies are voluntarily removing

For obese patients with Type 2 diabetes, bariatric surgery can lead to more than weight loss — it can also normalize blood sugar. “The welcome side effect is most reliable in patients who have had diabetes less than five years,” says Dr. Burch. “Patients with Type 2 diabetes who are at least 65 pounds overweight should probably be screened for bariatric surgery within a year or two of diagnosis, especially if their diabetes is uncontrolled and they’re gaining weight despite attempts at weight loss. Ultimately, we need to figure out why surgery normalizes glucose and develop a noninvasive way to trigger that same mechanism in diabetics who don’t need weight loss surgery.” Miguel Burch, MD, is a surgeon at the Cedars-Sinai Weight Loss Center. He is associate director of Minimally Invasive Surgery and director of the Minimally Invasive and Bariatric Surgery Fellowship. His research includes endoscopic therapies for the management of obesity and the link between bariatric surgery and diabetes resolution.

Beth Moskowitz, philanthropist, entrepreneur:

Change your traditions. When it comes to disease prevention, Moskowitz says people are getting an incomplete message. “It’s not about creating a new lifestyle — it’s about creating new traditions,” she says. For various reasons, including genetics and socioeconomic factors, Type 2 diabetes disproportionately affects certain groups, including Latinos and African-Americans. “You can’t change your genes, so change the traditions you follow and pass those on to your children,” she says. “Keep the family dinner — just change what’s on the table. Make health and a disease-free life your most important family tradition, whatever your culture.” Beth Moskowitz is executive director of Sports Spectacular, a philanthropy that allies with elite athletes and medical professionals to promote wellness through advocacy and the support of research. A valued partner of Cedars-Sinai, Sports Spectacular’s fundraising efforts have benefited a variety of programs and projects, including the Sports Spectacular Medical Genetics Institute. In 2014, Sports Spectacular pledged $10 million to establish the Sports Spectacular Diabetes and Obesity Wellness and Research Center at Cedars-Sinai.

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More experts’ answers on diabetes at discoveriesmagazine.org