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Drossman Gastroenterology

A Leader in Advanced Techniques and Understanding for Better Outcomes

T H E M A G A Z I N E F O R H E A LT H C A R E P R O F E S S I O N A L S

Also in This Issue Play Nice or Else! Communication Barriers

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COVER STORY

Drossman Gastroenterology A Leader in Advanced Techniques and Understanding for Better Outcomes

j u ly 2 0 15

FEATURES

Vol. 6, Issue 6

DEPARTMENTS 13 Duke Research News

Physician Advocacy

Think Again: Ten Questions to Ask Before Selling Practice to a Hospital Marni Jameson takes offense at a practice ac-

Less Is More Using Poliovirus

14 Duke Research News Use of Defibrillator Implants in Older Heart Patients Is Low

15 Duke Research News

MRI Technology Reveals Deep-Brain Pathways in Unprecedented Detail

quisition article that suggests physicians â&#x20AC;&#x153;play niceâ&#x20AC;? to get ahead.

16 UNC Research News

Practice Management

The Art of Communication, Part II

ClinGen Consortium to Pinpoint Disease-Causing Genetic Variants

18 UNC Research News

Largest Study to Date Maps Genetic Mutations in Cutaneous Melanoma

19 WakeMed News

Managed Care Partnership Expands Benefits of Care that Rewards Quality

Margie Satinsky concludes series with best practices for improved practice intercom-

20 NEWS

munications.

The Triangle Physician

Welcome to the Area

From the Editor

Listen! T H E M A G A Z I N E F O R H E A LT H C A R E P R O F E S S I O N A L S

Medical professionals across the patient care spectrum are familiar with the challenges of treating gastrointestinal disorders. It can be a frustrating experience for patients and physicians, alike. Our cover story this month is on gastroenterologist Douglas Drossman, M.D., whose successful practice is grounded in understanding the mind-body interplay and effective physician-patient dialogue. Readers of The Triangle Physician are familiar with Dr. Drossman, who is a regular contributor. This month, Dr. Drossman gives a thorough overview of strategies for improved communication and treatment of GI disorders. Desired outcomes depend on patient understanding of their condition, how medical therapy will help and what improvements can be realistically expected. Most of all he reminds readers that their greatest assets in a two-way conversation are your ears. Complementing our cover story is the column by practice management consultant Margie Satinsky. She urges thoughtful communication and suggests a four-step process for improved communication, with Step 1 being: Open your ears. Marni Jameson, a professional advocate for independent physicians, provides a counterpoint to a Medical Group Management Association article that proposes

Editor Heidi Ketler, APR heidi@trianglephysician.com Contributing Editors Douglas A. Drossman, M.D. Marni Jameson Margie Satinsky, M.B.A. Creative Director Joseph Dally jdally@newdallydesign.com

Advertising Sales info@trianglephysiciancom News and Columns Please send to info@trianglephysician.com

The Triangle Physician is published by: New Dally Design Subscription Rates: $48.00 per year $6.95 per issue Advertising rates on request Bulk rate postage paid Greensboro, NC 27401

thought-provoking questions for careful physician consideration before agreeing to a hospital acquisition. She represents an important perspective in an ongoing national dialogue. Most health systems, organizations and related businesses welcome opportunities to increase interactions with new partners, patients and clients. So, listen up! The Triangle Physician makes reaching the more than 9,000 professionals within the Triangle medical community easy. Simply send your medical news and insight submissions and your advertising inquiries to info@trianglephysician.com. Weâ&#x20AC;&#x2122;d love to hear from you! Respectfully,

Heidi Ketler Editor

The Triangle Physician

Every precaution is taken to insure the accuracy of the articles published. The Triangle Physician can not be held responsible for the opinions expressed or facts supplied by its authors. Opinions expressed or facts supplied by its authors are not the responsibility of The Triangle Physician. The Triangle Physician makes no warrant to the accuracy or reliability of this information. All advertiser and manufacturer supplied photography will receive no compensation for the use of submitted photography. Any copyrights are waived by the advertiser. No part of this publication can be reproduced or transmitted in any form or by any means without the written permission from The Triangle Physician.

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Cover Story

Drossman Gastroenterology

A Leader in Advanced Techniques and Understanding for Better Outcomes By Douglas Drossman, M.D.

Understanding the complex mind-body

The greatest problems that emerge with

With the assistance of my physician assis-

aspects of gastrointestinal illness, particu-

decreasing amounts of time that clinicians

tant, Kellie Bunn, PA-C, Drossman Gastro-

larly functional gastrointestinal disorders

spend with patients include the inability to:

enterology is a well-established specialty

(FGIDs), and helping in the management of patients affected by these disorders are the fascinating aspects of clinical care.

1) Obtain sufficient high-quality information about the illness; and 2) Have quality time to establish an ef-

practice in FGIDs. We are most pleased that we receive referrals both locally and from around the world.

fective patient-provider relationship. Nevertheless, there have always been chal-

This can result in inaccurate diagnoses

Many patients with FGID and motility disor-

lenges to accomplishing this, particularly

and treatments as well as reduced patient

ders, like irritable bowel syndrome (IBS),

poor reimbursement for:

and physician satisfaction with each other

are referred to us after having received

and the very process of care.

treatment at high-quality practices, but

1) Spending the time needed to understand these disorders and

their disabling symptoms and poor qual-

establish the necessary relationshipcentered care; 2) Helping patients ignore dualistic biomedical dogma that leads to stigmatization; 3) Helping patients understand their conditions as â&#x20AC;&#x153;realâ&#x20AC;? and manageable; and 4) Helping to educate the referring physicians about ways to successfully continue in their patient care. In the current health care environment, this challenge is made even more difficult with the harsh reality that the doctor-patient relationship suffers due to time constraints. And this isnâ&#x20AC;&#x2122;t likely to improve, since doctors in training are spending less time with patients than ever before.

The Triangle Physician

Douglas Drossman, MD, reviews patient referrals with office administrator Dena Barbee.

Dr. Drossman and physician assistant Kellie Bunn (left) work closely on patient treatment and care and typically meet together with patients in clinic.

ity of life persist. On occasion we come

age their symptoms. A vicious cycle then

they don’t bother me as much.” That’s why

up with new diagnoses and treatments;

ensues: without feeling able to understand

a biopsychosocial approach is effective in

however, most often we attend to the edu-

or control a condition that has great impact

treating patients with IBS and other func-

cational and management aspects of con-

on one’s life, the patient becomes anxious

tional GI disorders.

ditions that have already been diagnosed.

and distressed and that, in turn, leads to more symptoms. And so it continues.

It’s important that we understand functional GI disorders – not in terms of structural

Even in the latter case, patients may say, “No one has told me what I have,” which

Specialty Practice Breaks

abnormalities diagnosed by a specific test

I interpret as a failure in communication.

Vicious Cycle

or treated by a magic medication – but as

They say, “Nothing has worked for me.”

At our clinic, we work with our patients

disorders of improper functioning of the

to get to know the illness – its impact and

gastrointestinal system that are measured

So it is important for us to understand what

their psychosocial and coping resources

and understood in terms of the patient

was prescribed and for how long, whether

– to find the ways to break the vicious

experience of illness. As such the patient

it was taken or not and to what degree the

cycle. In addition to using state-of-the-art

very much needs to be a part of the plan

patient was given the opportunity to be-

diagnostic and treatment methods when

of care.

come involved in his or her care.

needed, we also help patients regain their sense of control over their illness and their

I’ve been fortunate to have trained both in

Since functional GI disorders, like IBS,

life. We make the effort to provide a clear

gastroenterology and psychosomatic or

are diagnosed by their symptom features

physiological explanation as to why they

biopsychosocial medicine, and so my fo-

(Rome III symptom-based criteria) rather

are having symptoms and offer rationale

cus tends to be on the interaction of the

than through laboratory studies, X-ray or

for treatment based on this understanding.

brain and gut. My practice often involves working with the most complex functional

endoscopy, the patients often feel that something else is being missed, or that

A major effort is to focus on helping pa-

GI disorders, where the GI system is “out

without any of these findings their symp-

tients become “empowered,” so they can

of sync” with regard to how the intestinal

toms are psychosomatic, or “in my head.”

feel in control enough to manage their

muscles function, how the nerves are work-

As a result, patients need to understand

symptoms. Since these are chronic GI dis-

ing and how the brain is failing to regulate

that these are real diagnoses.

orders, we explain that while “cure” may

these systems. Therefore, these disorders

not occur, they can still regain their daily

must be understood from a biopsychoso-

Furthermore, because there is no single

function and improve their quality of life.

cial approach in order to integrate the role

treatment (treatment is individualized to the

It’s not unusual for a patient with years of

of biological, psychological and social fac-

patient’s particular symptom profile), they

disability to come back feeling much better

tors in understanding the illness for clinical

may feel “out of control” and unable to man-

saying: “The symptoms are still there, but

care and research.

july 2015

Advanced Training for Hard-to-Treat GI Disorders So what makes my practice so different? First, my career in gastroenterology has led to the care of patients having very difficultto-understand and –manage, painful GI disorders. This is the group where the usual GI medications have ceased to work. My interest in mind-body (or mind-gut) interactions has led me to provide very modern methods of pharmacological and behavioral treatments to improve these disorders. Enhanced Physician-Patient Communication Second, anyone having these disorders is affected personally. This person may feel stigmatized and is told simply that “it’s stress” and to “learn to relax.” The individual may also get over-studied, with more and

Drossman Gastroenterology staff members are (from left): Dena Barbee, office administrator; Tyler Westall, assistant; Dr. Drossman; Kellie Bunn, physician assistant; Susan Morris, Dr. Drossman’s assistant; and Ceciel Rooker, business manager.

more procedures that end up with negative test results. This is a very difficult situation

ganizations, including industry, who are in-

once or twice) with telephone or Skype

(and potentially dangerous) for the health

terested in core training on communication

consultations. We encourage the option of

care providers and their patients, since

skills. This is accomplished through a vari-

involving your local physician, so we can

there seems to be no way out. I try to make

ety of formats, such as “observerships” in

coordinate the care.

it clear that their symptoms are not only real

my clinical practice, onsite workshops and

but very much understood because of mod-

comprehensive programs to address larger

For more information and to set up a visit,

ern science.

groups. The more comprehensive programs

call the clinic at (919) 929-7990. We require

include lectures, small-group sessions, role

that the referring physician send a letter

playing and personal awareness sessions.

summarizing the care as well as adequate

So it’s no surprise that one of the greatest

documentation for review. First visits may

challenges facing physicians, especially those in training, is learning the basics of

Professional Development

good communication skills with patients so

to Advance Communication

a higher quality of information is obtained.

Techniques

We also welcome inquiries and questions

This is accomplished by communicating in

Finally, Drossman Gastroenterology in-

about Drossman Gastroenterology and

a fashion that builds and strengthens the

volves patient-centered or, more appro-

DrossmanCare and invite health care pro-

relationship and that, as we are now learn-

priately, relationship-centered care where

viders to contact us about our upcoming

ing, improves not only patient satisfaction

we work as a team to understand the prob-

workshops on the biopsychosocial model

but adherence to treatments and to improv-

lems and devise proper solutions.

of care, on improving doctor-patient com-

run as long as 90-120 minutes.

munications and on our preceptorships. I

ing even hard clinical outcomes. Physician assistant Kellie Bunn works close-

am available for telephone consultations

It’s not what you do in the amount of time

ly with me as part of the care team. She

to help clinicians navigate difficult interac-

available but how you do it that makes the

sees all patients with me and is available

tions with patients, and I also consult on

difference. That is why my educational pro-

throughout the week to handle phone calls

difficult-to-manage health issues.

gram, “DrossmanCare,” focuses on training

and emails with questions that may arise

health care providers across the country

and to provide prescriptions and the like.

you to design an educational program to

and internationally on these newer methods of care.

The staff at DrossmanCare will work with

I receive referrals from around the world,

meet your specific needs. For more infor-

so more than 50 percent of my patients are

mation on this, contact Ceciel Rooker at

DrossmanCare provides a variety of educa-

out of state. This allows us to provide some

ceciel@drossmancenter.com.

tional formats for individuals and other or-

of the care (once a patient has been seen

The Triangle Physician

Physician Advocacy

Think Again:

Ten Questions to Ask Before Selling Practice to a Hospital By Marni Jameson

A recent online issue of the Medical

tion, is your response slow? Are you guard-

Group Management Association (MGMA)

ed with data? When it comes to communi-

newsletter included a blog post titled “14

cation, what are you willing to share and

Questions to Consider Before a Hospital

when?” You get the idea.

Acquisition” (http://bit.ly/1eRp7ks ). The article left me unhinged by the insult to

Now, before practice managers – or their

physicians and practice managers, whom

medical group employers – become be-

this MGMA publication targets.

lievers and certainly before agreeing to

“…if they play nice with the hospital trying to buy their practice, they stand a better chance of employment after the acquisition” Basically, the blogger, a hospital industry insider, tries to reassure practice managers that if they play nice with the hospital trying to buy their practice, they stand a better chance of employment after the acquisition – so said the spider to the fly.

Marni Jameson is the executive director for the Association of Independent Doctors. You may reach her at (407) 865-4110 or marni@aid-us.org.

let their medical practices be bought by a hospital, I would ask them to consider these 10 questions: 1. How much do your doctors like their autonomy? Would they be content with an

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The post opens like this: “‘Practice managers with independent medical groups have more control over their futures after hospital acquisitions than they might think,’ said David Taylor, past MGMA board co-chair and vice president, regional services, CoxHealth, Springfield, Mo.” Taylor, who has 25 years of experience managing hospital-owned practices in large, integrated delivery networks, went on: “‘If you want to be an administrator

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here, you need to consider whether you are seen as helpful or seen as a barrier,’ Taylor explained. During negotiations, health systems judge practice managers on their behavior…. If the system asks for informa-

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Physician Advocacy administrator telling them which gloves

pact the community? For instance, if a

be spared are the ones willing to play

to use, for instance, or which devices to

non-profit health system is buying your

along, who don’t challenge the acqui-

implant?

medical group, all the taxes that group

sition and instead facilitate the transi-

once paid come off the tax rolls, mean-

tion. Is that in the best interest of your

ing budgets for incidentals like police

doctors?

2. How would your doctors feel if they could no longer refer to the specialists or outpatient centers they thought were the best and had to change their referral pat-

officers and teachers get cut, or taxes for other community members go up.

terns so they could funnel patients solely

10. If a hospital takes over the running of

to other hospital-employed doctors and

your doctor’s practice, what makes you

hospital-owned ancillary services?

think your job will be spared? Clearly, if

3. How would your doctors feel when their

you read between the lines in this blog

allegiance was forced to shift from their

post, the practice managers who may

patient’s interests to their employer’s,

In short, if your doctors would feel good about driving up health costs, reducing access to health care, lowering quality, compromising their doctor-patient relationships, seeing his or her staff lose their jobs and causing their communities financial harm, by all means, they should seriously

whom they now must please or risk unemployment? 4. How would your doctors feel about having to meet their hospital employer’s quotas for patient admissions, procedures performed and referrals to other employed physicians? 5. How will your doctors feel when their contract is not renewed, because they did not meet the quotas? 6. How would your doctors feel when their patients were charged five to 10 times more for the same procedures because hospitals would be adding their facility fees to bills and charging consumers higher contracted rates? 7. When the hospital cites a low rate of turnover among employed-physicians (if the numbers are to be believed) how much of that is due to happy doctors and how much to the non-compete clauses doctors must sign? Many contracts require doctors to not practice in the service area for a period of time, if they cut ties with the hospital. 8. When have you ever seen consolidation in health care or in any industry improve competition or quality and lower costs? 9. Besides the loss of jobs – and yes more office personnel lose their jobs in these acquisitions than get them – how would the purchase of your medical group imWomens Wellness half vertical.indd 1

The Triangle Physician

12/21/2009 4:29:23 PM

Practice Management

The Art of Communication Part 2 By Margie Satinsky, M.B.A.

This article is part two of two-part series on communication within medical practices and between medical practices and external vendors, colleagues and organizations. Part I, which appeared in the June 2015 issue of The Triangle Physician, defined communication and provided examples of situations that needed improvement. Part II recommends ways in which medical practices can improve communication.

Follow the Old Adage: Listen,

about them and the issue they perceive

React, Think and Respond

they have before we suggest an approach.

Regardless of the method that you select for communication, avoid knee-jerk reac-

Once we’ve established a trusted consul-

tions. It makes no difference if the commu-

tant/client relationship, we use email as

nication is face to face, by telephone or by

well as telephone. We use texting for quick

email, text or social media.

tasks, like appointment confirmation but not for transmitting knowledge and provid-

The following four-step approach need not

ing coaching.

Margie Satinsky, MBA, is President of Satinsky Consulting, LLC, a Durham, NC consulting firm that specializes in medical practice management. She’s provided HIPAA compliance consultation to more than 100 Covered Entities and Business Associates. Margie is the author of numerous books and articles, including Medical Practice Management in the 21st Century. For additional information, go to www.satinskyconsulting.com.

be time-consuming; thoughtful is a better word. 1. Start by opening your ears and listening to what’s being said to you. 2. Observe your own reaction, noting if it

When it comes to social media for busi-

ings that promote employee involvement

ness communications, we think it’s too

and teamwork.

impersonal. To us, each client or potential client deserves a personalized response.

is positive, negative or neutral.

With respect to patients, telephone courtesy is essential. Regardless of how your

3. Think about ways in which you might

With respect to presentations, if the au-

practice answering system works, be help-

respond, focusing both on what you

dience is 25 or smaller, we organize our

ful and responsive, not hostile. Reduce the

want to say and how you want to say it.

thoughts in carefully constructed Power-

number of phone calls by posting on your

Point format. We hand out the material

website information that both patients and

4. Then and only then, respond.

but don’t put the information on a screen

medical colleagues need to know. Com-

Select the Appropriate Means

when we make observations and recom-

municate with patients through a secure

of Communication

mendations. In our experience, a Pow-

patient portal that meets HIPAA Privacy

The options for communication are nu-

erPoint presentation with the results of

and Security Rule requirements.

merous and growing at an exponential

a strategic business-planning process or

rate. Pick the one that’s most suitable to

Health Insurance Portability and Account-

Social media may have its place, provid-

the message you want to deliver. Here are

ability Act (HIPAA) Privacy and Security

ed that you have a specific strategy, that

some examples.

Rule training produces sleep, not audi-

your approach is HIPAA compliant and

ence interaction.

that an experienced and responsible in-

Many people learn about our consulting

dividual takes responsibility for this type

services at www.satinskyconsulting.com

Let’s talk about appropriate methods of

of communication. Our recent newsletter

and initiate an inquiry or request for ser-

communications within a medical prac-

on social media (http://www.satinskycon-

vices by email. We steer those people to

tice. Informational emails to staff are fine,

sulting.com/documents/NewsletterWin-

the telephone. We don’t know them yet,

but they don’t substitute for both regular

ter2015.pdf) provides specific suggestions.

and we want to learn as much as we can

meetings with supervisors and staff meet

july 2015

Practice Management Help the Listener/Reader

asks us as a trusted advisor to provide a so-

Understand the Background and

lution. More often than not, the stated prob-

Here are examples from two dermatology

Context of Your Message

lem is not the real problem. Reaching the

practices. One practice asked for our input

We live in a specialized world. Within ev-

heart of the matter requires detective work.

on a website written and designed by one of the practice’s employees who “liked to

ery medical practice, there are different levels of knowledge about specific issues.

Here’s an example. Several months ago a

play with websites.” Poor grammar, lack

Clinicians know the practice of medicine.

primary care practice sought our guidance

of clarity and overall disorganization cre-

Some, but not all, also have a good grasp

for strategic business planning and im-

ated the impression that not only the web-

on administrative issues and regulatory re-

provement in financial performance. Dur-

site, but perhaps the quality of the clinical

quirements. Administrative staff has vary-

ing our face-to-face meeting, we learned

services, was substandard. We fixed the

ing degrees of knowledge based both in

that the practice owner had hired his rela-

problem.

the current practice environment and past

tive as the practice manager even though

experience.

that individual had no experience in health

In a second situation, we were assisting a

care management and did not plan to

practice startup with website content. After

We get the best results when we start with

learn the ropes.. To us, hiring an unquali-

correcting the same grammatical errors

background and context, taking time to

fied manager was the problem. A different

three times, we mentioned to the physician

bring the listener up to speed before mak-

choice of manager would enable the prac-

owner the importance of correct grammar,

ing an observation or recommendation.

tice to address the other issues on its own.

only to be told that he wished his website to “sound like he spoke.” We beg to differ;

Here are examples of situations that we frequently encounter. We could talk about

Use Correct Grammar

he did not speak like an experienced physi-

HIPAA compliance in our sleep, but our

Once again, short messages are fine for

cian! Hopefully our advice will not fall on

audience is often unfamiliar with many

email and texting. With respect to other

deaf ears!

of the concepts. We always start with the

forms of communication that require

basics, encouraging questions about the

written or oral presentations, use correct

Follow Your Communication with

practice’s actual experience as we go.

grammar.

a Summary An effective way to make your point is to

With respect to revenue cycle manage-

Going back to our UNC graduate students

state the problem, make your suggestions

ment, we know the importance of manag-

that we mentioned in Part I of this series,

and summarize the ways in which the

ing denials, i.e. claims that insurers haven’t

all were intelligent, but the challenges that

suggestion will address the issue. For ex-

paid for reasons that may or may not be

some experienced in expressing them-

ample, practices that use electronic health

justifiable. Not all practices understand

selves made them sound unprofessional.

records can use the software to provide

this task, and when they don’t, we need to

Here’s our advice on the grammatical er-

each patient with a written and/or elec-

take the time to articulate the purpose and

rors that we encountered most frequently:

tronic copy of a summary of the patient

the steps to take.

• Avoid ending sentences with prepositions

visit. The summary of a clinical encounter

(e.g., Where is he, not where is he at?).

is a great model for non-clinical situations.

Still another common communication challenge involves our interactions with different managed care plans. They vary

• Use strong active verbs (e.g., develop, build, revise). • Use active, not passive voice (e.g., Say

Develop a Communication Strategy for your Practice

in their responsiveness to questions about

“Wintery weather affected our ability to

Our final suggestion is most important.

rates, credentialing and claims payment.

keep the appointment” rather than “We

Take a step back and develop a commu-

We get the best results with clear explana-

were prevented from meeting at the

nication strategy for your practice, taking

tions of what our clients perceive to be the

scheduled time by wintery weather”).

into consideration the ways in which you communicate both internally and exter-

problems and with professional respect for the individuals with whom we’re com-

Proofread Your Draft and/or En-

nally. Evaluate what you do and make ad-

municating.

gage another Reader

justments and improvements on a regular

Depending on the type of communication,

basis. Patient and physician satisfaction

Engage the Listener/Reader

proofread the first draft and/or ask some-

surveys are effective tools for seeking in-

We view practice management consulting

one else to review the message. Sloppy or

put. Ask for staff suggestions too. Take it

as meeting the client in the middle. The

grammatically incorrect information may

seriously; communication counts!

client has a real or perceived problem and

send a hidden message.

The Triangle Physician

Duke Research News

Less Is More Using Poliovirus A modified poliovirus therapy that is

tumor site increased the severity of side

better at this level, and that’s what we

showing promising results for patients

effects, including weakness and seizures.

want.”

with glioblastoma brain tumors works

Patients required prolonged steroid use

best at a low dosage, according to the

to reduce the inflammation, but this also

Study authors report that the therapy ap-

research team at Duke’s Preston Robert

dampened the immune response that the

pears to be safe, with side effects related

Tisch Brain Tumor Center, where the in-

modified poliovirus is designed to initiate.

to localized brain inflammation, including muscle weakness and paralysis, seizures,

vestigational therapy is being pioneered. The research team has settled on a dose

headaches, limb swelling and tingling,

The dosage findings for the first 20 pa-

that is actually lower than the amount

speech impairments and headaches.

tients in the Phase 1 trial were presented

first tested, which the first study patient

Twelve of the first 20 patients treated

at the American Society of Clinical Oncol-

received in May 2012. That patient is still

remain alive, with the first and second

ogy annual meeting in Chicago in May.

alive and has no regrowth of her tumor.

patients more than 31 months post-treat-

Five patients have been enrolled in the

ment.

trial at the lower dosage level, designated The median survival for glioblastoma

as minus one.

patients is 14.6 months, according to the “We are now keeping to minus one,” Dr.

American Brain Tumor Association.

Desjardins said. “Inflammation is much

cluded escalating to higher doses, which

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Annick Desjardins, MD

“The purpose of a Phase 1 trial is to identify the optimal dose to minimize toxicity,” said Annick Desjardins, MD, lead author of the presentation and director of clinical research at the brain tumor center in the Duke Cancer Institute. “Our trial design in-

Drossman Gastroenterology

“For chemotherapy, we are trained to give the largest dose possible with acceptable toxicity, because that is how the drugs work to attack tumors,” Dr. Desjardins said. “But that does not appear to be necessary with our therapy, and in fact a lower dose attacks the tumor as well and results in fewer side effects.” At the higher doses, Dr. Desjardins and colleagues report, inflammation at the

july 2015

Duke Research News

Use of Defibrillator Implants in Older Heart Patients Is Low Heart attack patients age 65 and older

with reduced heart function in the study

derstand what the exact target number

who have reduced heart function might

actually received them, according to a

should be.”

still benefit from implanted defibrilla-

press advisory. While researchers weigh age and the cost

tors, according to a Duke Medicine study published in the Journal of the American

The patients in this retrospective, obser-

of the procedure, which is a reimbursable

Medical Association. But less than one in

vational study were an average of 78 years

service under Medicare for many recipi-

10 eligible patients actually gets a defibril-

old, and 44 percent of them were more

ents, researchers also considered another

lator within a year of their heart attacks,

than 80 years old. Their data was col-

potential barrier to their effective use – a

the study found.

lected by 441 hospitals across the United

gap in care at a time when patients are

States participating in a National Cardio-

most vulnerable.

Advanced age, transitions in care between

vascular Data Registry. “The optimal timing for implanting a de-

the hospital and an outpatient clinic and a mandatory waiting period to get a defi-

Most previous clinical trials on defibril-

fibrillator is still in

brillator after a heart attack were the most

lators, which have been in use since the

question, but current

likely factors for low rates of use, accord-

1980s, have focused on patients in their

guidelines

ing to the study.

60s, according to Dr. Wang. So the ben-

mend that patients

efits of defibrillator use in older adults are

wait at least 40 days

not well established.

after their heart at-

Defibrillators shock hearts back to pumping when a patient experiences a poten-

tack,”

tially fatal sudden cardiac arrest. Prior

More than 300,000 people in the U.S. die

Pokorney,

studies have primarily shown benefits to

from sudden cardiac arrest each year,

using these devices in younger patients.

and previous research indicated that as

said

Sean

MD,

cardiology fellow at the Duke University

many as 80 percent of these patients were

School of Medicine and lead author of the

“Defibrillators are life-

eligible for but did not have a defibrillator

study. “If the patient’s heart is still having

saving therapies that

implanted before they suffered the arrest.

trouble pumping blood after 40 days, they would be eligible. But a lot can happen in

have a lot of evidence

Tracy Y. Wang, MD, MHS, MSc

Sean Pokorney, MD

recom-

that 40 days.”

supporting their use,”

“This is a big debate from a quality-of-life

said Tracy Y. Wang,

perspective,” Dr. Wang said. “The deci-

MD, MHS, MSc, an

sion about defibrillators has to be indi-

In most cases, patients will have been

associate

profes-

vidualized. For older patients who are

discharged from the hospital and transi-

sor of cardiology at

debilitated, providing a defibrillator could

tioned to an outpatient care team, Dr. Po-

the Duke University

simply extend a low quality of life.”

korney said. Patients who stay connected with their cardiologists and continue to

School of Medicine and senior author of the study. “But not

In the Duke-led study, patients who had

attend follow-up appointments are more

every older patient wants one. There is a

defibrillators implanted had a one-third

likely to get the devices.

trade-off between the risks and benefits of

lower risk of death after two years than

the device. But current data suggests that

those who didn’t have a defibrillator.

But the patient’s regular physician might not be aware of her reduced heart func-

we are grossly underutilizing this therapy.” The findings of lower death risk are prom-

tion or might think her advanced age

Clinicians and researchers continue to de-

ising, Dr. Wang said, although this may be

makes her a poor candidate a defibrilla-

bate the best use of defibrillators in older

because doctors were more likely to im-

tor.

heart patients. As a result, Duke research-

plant defibrillators in older patients who

ers expected less than 100 percent usage

were healthier overall. Still, “the rates of

“We believe that age alone should not pre-

of the devices, but were surprised at just

use across the U.S. are too low,” Dr. Wang

vent eligible people from getting devices,”

how few of the 10,318 heart attack patients

said. “More work needs to be done to un-

Dr. Pokorney said. “We should be trying

The Triangle Physician

Duke Research News to understand how to refine patient selec-

use in eligible patients and practices that

The researchers received funding for this

tion towards those who are most likely to

encourage close patient follow-up and

study from the Agency for Healthcare Re-

benefit from the device, and close any

communication.

search and Quality (U19HS021092). Both

In addition to Drs. Wang and Pokorney,

ing research support from Boston Scien-

Drs. Wang and Pokorney reported receiv-

system-level gaps that present a barrier to optimal defibrillator use.”

who are also affiliated with the Duke Clini-

tific, in addition to other pharmaceutical

The study is limited as a retrospective

cal Research Institute, study authors include

companies. A full list of disclosures is in-

observation, Dr. Pokorney said, and fur-

Amy L. Miller; Anita Y. Chen; Laine Thomas;

cluded in the manuscript.

ther research is needed to determine ev-

Gregg C. Fonarow; James A. de Lemos;

idence-based approaches to defibrillator

Sana M. Al-Khatib; and Eric D. Peterson.

MRI Technology Reveals Deep-Brain Pathways in Unprecedented Detail Scientists at Duke Medicine have produced a three-dimensional map of the human brain stem at an unprecedented level of detail using magnetic resonance imaging technology. In a study published June 3 in Human Brain Mapping, the researchers unveiled an ultra-high-resolution brain stem model that could better guide brain surgeons treating such conditions as tremors and Parkinson’s disease with deep-brain stimulation (DBS). The new three-dimensional model could eliminate risky trial and error as surgeons implant electrodes – a change akin to trad-

The X-shaped pathway of nerve fibers represents the dentatorubrothalamic tract (DRT), a pathway inside the thalamus that researchers target with deep-brain stimulation to halt uncontrolled tremors. Scientists at Duke Medicine have used ultra-high-resolution magnetic resonance imaging to produce a 3-D model of the brain stem that offers unprecedented detail of neuronal circuitry that could be used to target treatments for conditions such as Alzheimer’s and Parkinson’s diseases. Photo credit: Evan Calabrese, Ph.D.

ing an outdated paper road atlas for a realtime GPS.

nates relative to the planes of the brain to

tions from DBS can include hemorrhage,

guide them when placing electrodes into

seizure or memory problems.

“On the conventional MRI that we take

the thalamus. They are targeting a circuit

before surgery, the thalamus looks like

called the dentatorubrothalamic tract, or

“This map will potentially help us reach

a gray mass where you can see only the

DRT (depicted as an X-shaped pathway in

the optimal target the first time,” Dr. Lad

borders,” said neurosurgeon Nandan Lad,

the accompanying image), Dr. Lad said.

said. “It could eliminate trial and error and

M.D., Ph.D., director of the Duke Neuro-

make the surgery safer.”

Outcomes Center and an author of the

Surgeons must often remove and reinsert

paper. “Now we will have actual detail.

electrodes and test frequencies to find

The map was produced from a 10-day

With this map, for the first time we’re able

the spots inside the thalamus where, for

scan of a healthy donor’s postmortem

to see the thalamus and that underlying

instance, the electric current subdues the

brain stem in a 7-Tesla MRI system and

circuitry that we are modulating.”

hands of a patient with debilitating trem-

then converted into a 3-D model that can

ors. This indirect targeting is the standard

be proportionally scaled to fit a person’s

Many neurosurgeons currently rely on

of care for DBS, but comes with risk. Mov-

unique brain anatomy using a high-perfor-

lower-resolution computed tomography

ing an electrode requires another pass

mance computing cluster.

and MRI scans and geographic coordi-

through delicate tissue, and complica

july 2015

Duke Research News “These images are 1,000 times more de-

of 24 electrodes in the dozen patients, the

“We now have a guide to be able to visual-

tailed than a clinical MRI,” said G. Allan

study showed.

ize these complex neuronal connections that would otherwise be impossible to

Johnson, senior author of the paper and director of the Duke Center for In Vivo

The researchers will soon begin a pro-

see,” said Evan Calabrese, Ph.D., the lead

Microscopy, where the brain stem was

spective study using the 3-D model to

author of the paper who engineered the

scanned. “You can actually see the nerve

guide DBS surgery.

3-D model. “This will help us continue to explore applications for treatments of Al-

fibers in the brain, how they’re crossing and the subtleties of contrast between

“As time goes on, imaging will only con-

zheimer’s disease, neuropathic pain, de-

gray and white matter in the brain far be-

tinue to get better,” Dr. Lad said. “We are

pression and even obsessive compulsive

yond what a clinical scan could offer.”

well-equipped and at the cutting edge of

disorders.”

understanding how to apply this technolTo test the accuracy of the model, the

ogy and will be in an even better position

In addition to Mr. Johnson, Dr. Calabrese

researchers conducted a retrospective

to treat more patients with fewer side ef-

and Dr. Lad, study authors include Patrick

study of 12 patients who had already been

fects.”

Hickey, Christine Hulette, Jingxian Zhang and Beth Parente.

treated successfully for tremors using DBS. The researchers used the 3-D mod-

The Duke team also will pursue high-

el to predict the best placement for the

resolution imaging of other circuits in the

The researchers received funding from

electrodes in each patient. The predictive

brain, brain stem and spinal cord to devel-

the National Institutes of Health and the

computer model and the actual success-

op new treatments for other conditions.

National Institute of Biomedical Imaging and Bioengineering (P41 EB015897).

ful electrode placements correlated for 22

UNC Research News

ClinGen Consortium to Pinpoint Disease-Causing Genetic Variants Millions of genetic variants have been dis-

of Medicine Department of Genetics and

that they can go to as a way to understand

covered in the last 25 years, but interpret-

this year’s ClinGen steering committee

their patients’ genetic testing results.”

ing the clinical impact of the differences

chair. “Right now there is a certain degree

in a person’s genome remains a major

to which we can infer what those variants

Clinicians and researchers hope to use in-

bottleneck in genomic medicine.

do, but most of them remain really be-

formation about genetic variants not only

yond our understanding of how they are

to make predictions about an individual’s

In a paper published May 27 in The New

affecting human health, if at all. Through

risk of disease, but also to develop more

England Journal of Medicine, a consor-

ClinGen, we’re working to evaluate the

accurate clinical trials and better, tailored

tium that includes investigators from the

clinical relevance of genes and variants

treatments and care for patients. However,

University of North Carolina School of

and to provide a public database so that

labs and clinicians may interpret the same

Medicine and UNC Lineberger Compre-

labs and clinicians will have a resource

variant differently.

hensive Cancer Center presented ClinGen, a program launched to evaluate the

Part of ClinGen’s mission is to resolve

clinical relevance of genetic variants for

these differences. Members of ClinGen

use in precision medicine and research.

are actively working with laboratories around the world to help them share their

“Sequencing has revealed that there are

data and implement standards developed

potentially several million genetic vari-

by the American College of Medical Ge-

ants per person,” said Jonathan Berg,

netics and Genomics for interpreting genetic variants, with the goal of resolving

MD, Ph.D., a UNC Lineberger member, an assistant professor in the UNC School

The Triangle Physician

Jonathan Berg, MD, Ph.D.

interpretation differences.

UNC Research News quality,” said Heidi Rehm, Ph.D., associ-

ClinGen is funded by the National Hu-

An integral part of the ClinGen project is

ate professor of pathology at Brigham and

man Genome Research Institute, with

ClinVar: a database launched in April 2013

Women’s Hospital and director of the Lab-

additional funding from the Eunice Ken-

that currently contains more than 170,000

oratory for Molecular Medicine at Part-

nedy Shriver National Institute of Child

variant submissions from laboratories

ners HealthCare Personalized Medicine.

Health and Human Development and the

around the world. The database is public-

Investigators from Brigham and Women’s

National Cancer Institute (U41 HG006834,

ly accessible, meaning that clinicians and

Hospital and Partners HealthCare are in-

U01 HG007436, U01 HG007437, HH-

researchers as well as patients can look

volved in the ClinGen consortium.

SN261200800001E). ClinVar is supported by the Intramural Research Program of

up information to find out what is known about a specific genetic variant. The site

Known as GenomeConnect, the portal

the National Institutes of Health, National

gets an average of 5,000 hits per day. Clin-

connects researchers, clinicians and pa-

Library of Medicine.

Gen collaborators are working to enhance

tients to learn about the effects of genet-

the number and quality of submissions to

ics on human health and disease. Patients

In addition to Dr. Berg, the co-principal

the ClinVar database, Dr. Berg said.

who have had or are considering having

investigators of the grant awarded to UNC

genetic testing can share their results and

in collaboration with several partners in-

In addition, ClinGen has formed expert

take surveys to share information about

clude James P. Evans, MD, Ph.D., the UNC

working groups to interpret the strength

their health. De-identified information

School of Medicine Bryson Distinguished

of gene-disease relationships, resolve dif-

will be transferred to ClinVar and other

Professor of Genetics and Medicine and

ferences in the interpretation of variants’

ClinGen resources for advancing genomic

a UNC Lineberger member; Michael

clinical significance found in ClinVar and

knowledge, and participants will receive

Watson, Ph.D., executive director of the

move variants into the category of “expert

updates when there are opportunities

American College of Medical Genetics;

panel reviewed,” so they can be used more

to connect with other participants who

and David Ledbetter, Ph.D., executive vice

confidently in clinical decision-making.

share the same condition, gene or genetic

president and chief scientific officer of

variant.

Geisinger Health System.

Dr. Berg is a co-principal investigator on the grant awarded to UNC and its partners to support the coordination of the clinical domain working groups. He said the groups are looking at variants that could play a role in a range of diseases, including pe-

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“UNC’s main role in ClinGen is, in conjunction with several partners, to coordinate the clinical domain working groups to essentially do the work of curating genes and variants,” Dr. Berg said. Another key aspect of the project will be to develop an informatics system to help the researchers review the genetic variants, he said. One of the project goals is to develop machine-learning algorithms to improve the interpretation of the variants. “Our model works a little like Wikipedia: Anyone can submit variants and interpretations to the database to rapidly enable shared resources, but that content is later curated by an expert group to standardize

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july 2015

UNC Research News

Largest Study to Date Maps Genetic Mutations in Cutaneous Melanoma UNC Lineberger Comprehensive Cancer

ciate professor of medicine at the Univer-

tors, but more work is needed to identify

Center researchers have significantly con-

sity of North Carolina School of Medicine

responders and non-responders within this

tributed to a better understanding of the ge-

Division of Hematology/Oncology and a

new melanoma subtype, as well as to de-

netic alterations found in cutaneous mela-

member of the data analysis and manu-

termine strategies to treat (patients in the

noma, the most lethal form of skin cancer,

script committee for the TCGA melanoma

Triple Wild-type subgroup without BRAF,

as part of a multi-institution, international

project. “This work can also serve as a ref-

RAS and NF1 mutations).”

effort of The Cancer Genome Atlas.

erence map to assist in personalized prognostic and treatment decisions and future

The fourth subgroup was defined by pa-

The study refined and revealed new mo-

clinical trials for patients with cutaneous

tients who lacked BRAF, RAS or NF1 mu-

lecular sub-groups of patients who could

melanoma.”

tations. They didn’t have high-incidence mutations, but had some low-frequency

potentially benefit from targeted treatments based on their tumor genetics and helped

In the study, the researchers identified four

mutations in genes, such as cKIT, and had

clarify the immune system’s role in mela-

genomic subtypes of melanoma based on

a significantly higher number of gene copy

noma.

mutations. Two subgroups were defined by

alterations (gains or losses).

mutations that have already been shown to be common in melanoma – mutations in

Thirty percent of samples in that subgroup

the BRAF and RAS genes. But from a previ-

had ultraviolet light (UV)-type signature

ously heterogeneous group of people who

mutations, while more than 90 percent of

lacked those mutations, one potentially

samples in each of the other groups had

clinically significant subgroup emerged.

UV-type signatures. The high overall incidence of UV signatures points to the impor-

Stergios Moschos, MD

That new group was characterized by in-

tant role of sun or tanning bed exposure in

activating mutations in a gene called NF1.

this disease, Dr. Moschos said.

Patients in the NF1-mutant group – which made up about 14 percent of the entire

Overall, the researchers hope the sub-

patient population in the study – were sig-

group findings can help personalize treat-

This comprehensive characterization of

nificantly older and their cancers harbored

ment decisions and guide new targeted

the biological underpinnings of melanoma

significantly more mutations. Dr. Moschos

treatment strategies.

is the latest work by researchers involved

hopes this finding will trigger new research

in The Cancer Genome Atlas (TCGA), a Na-

into targeted treatments for patients in that

The study also helped to reveal the impor-

tional Cancer Institute and National Human

group, and perhaps into the use of treat-

tance of the body’s immune response in

Genome Research Institute-sponsored ef-

ments that are already approved by the

melanoma, Dr. Moschos said. In an analy-

fort to create an atlas of genetic and epigen-

Food and Drug Administration.

sis of RNA expression data led by Katherine Hoadley, Ph.D., a UNC Lineberger member

etic changes that drive different cancers. The researchers collected samples from

“For example, BRAF and MEK inhibitor

and research assistant professor of genet-

331 patients and used several molecular

combinations are now used to treat pa-

ics; and Xiaobei Zhao, a postdoctoral re-

methodologies to complete the study, the

tients with BRAF mutant melanomas, and

search associate at UNC Lineberger, the

largest of its kind to date for cutaneous

MEK inhibitor combinations are being

study found that 51 percent of patients had

melanoma. The findings were published

explored for RAS-mutant melanomas,”

high-expression levels of genes predomi-

on June 18 in the journal Cell.

said Ian Watson, Ph.D., an instructor of

nately expressed by immune cell subsets.

genomic medicine who was one of three

A pathologic analysis of tumors confirmed

“This study explains some longstanding

analysis co-chairs for the project from The

that genes thought to be immune-related

clinical observations that we could not en-

University of Texas MD Anderson Cancer

did come from melanoma-infiltrating im-

tirely comprehend, in particular for stage III

Center. “Pre-clinical studies have already

mune cells, suggesting an augmented im-

melanoma,” said Stergios Moschos, MD, a

demonstrated that some NF1-mutant mela-

mune response in that group. And patients

UNC Lineberger member, a clinical asso-

noma cell lines respond to MEK inhibi-

in the immune-high group with regionally

The Triangle Physician

UNC Research News metastatic disease had better overall sur-

In addition to identifying cells with a higher

Another immune-related finding was that

vival than patients of similar stage and

immune response, the RNA analysis also

a protein called PD-L1 that’s been used to

without high expression of immune genes.

identified a subgroup of patients with re-

predict responses to immune checkpoint

That finding has implications for immuno-

gionally metastatic melanoma who had

inhibitors can be overexpressed by mela-

therapy treatments that work by unlocking

a worse prognosis. That group exhibited

noma cells for genetic reasons. They found

the brakes on the body’s own immune re-

high expression of genes associated with

amplification of the PD-L1 gene in people

sponse to the disease, Dr. Moschos said.

pigmentation and keratins, which are skin-

with BRAFV600 mutations in particular.

toughening proteins usually found in epi-

The finding helps explain why the test

“Given that recent studies showed that im-

thelial skin cells. This keratin-expressing

that measures PD-L1 expression in tumors

mune checkpoint inhibitors may be more

subtype of melanoma had been previously

alone is not sufficient to predict responses

effective in patients whose tumors are al-

identified by UNC Lineberger Director Nor-

to PD1/PD-L1 targeted therapies, Dr. Mos-

ready infiltrated by immune cells, it is not

man Sharpless, MD, the Wellcome Distin-

chos said.

surprising that these immunotherapies are

guished Professor in Cancer Research, and

not effective for everybody,” he said.

collaborators, but the worse prognosis of

The study was funded by the National Insti-

this group is a new finding.

tutes of Health.

WakeMed News

Managed Care Partnership Expands Benefits of Care that Rewards Quality WakeMed Key Community Care, an ac-

to align resources, share information and

eases; staff to help patients navigate care at

countable care organization, and United-

focus on prevention, chronic conditions,

the right level, at the right time, in the right

Healthcare have signed a managed care

inpatient quality and patient satisfaction

setting; and safer, more effective care as a

agreement that will enhance health ser-

and controlling medical costs.

result of shared knowledge and best practices among health care providers.

vices and improve care coordination for Triangle-area residents.

“We’re pleased to partner with UnitedHealthcare to improve both the quality and

At least 29,000 Triangle-area residents

value of care patients receive when they

enrolled in UnitedHealthcare’s employer-

see a WKCC provider,” said John Rubino,